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Understanding reasons for drug use amongst young people: a functional perspective

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Annabel Boys, John Marsden, John Strang, Understanding reasons for drug use amongst young people: a functional perspective, Health Education Research , Volume 16, Issue 4, August 2001, Pages 457–469, https://doi.org/10.1093/her/16.4.457

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This study uses a functional perspective to examine the reasons young people cite for using psychoactive substances. The study sample comprised 364 young poly-drug users recruited using snowball-sampling methods. Data on lifetime and recent frequency and intensity of use for alcohol, cannabis, amphetamines, ecstasy, LSD and cocaine are presented. A majority of the participants had used at least one of these six drugs to fulfil 11 of 18 measured substance use functions. The most popular functions for use were using to: relax (96.7%), become intoxicated (96.4%), keep awake at night while socializing (95.9%), enhance an activity (88.5%) and alleviate depressed mood (86.8%). Substance use functions were found to differ by age and gender. Recognition of the functions fulfilled by substance use should help health educators and prevention strategists to make health messages about drugs more relevant and appropriate to general and specific audiences. Targeting substances that are perceived to fulfil similar functions and addressing issues concerning the substitution of one substance for another may also strengthen education and prevention efforts.

The use of illicit psychoactive substances is not a minority activity amongst young people in the UK. Results from the most recent British Crime Survey show that some 50% of young people between the ages of 16 and 24 years have used an illicit drug on at least one occasion in their lives (lifetime prevalence) ( Ramsay and Partridge, 1999 ). Amongst 16–19 and 20–24 year olds the most prevalent drug is cannabis (used by 40% of 16–19 year olds and 47% of 20–24 year olds), followed by amphetamine sulphate (18 and 24% of the two age groups respectively), LSD (10 and 13%) and ecstasy (8 and 12%). The lifetime prevalence for cocaine hydrochloride (powder cocaine) use amongst the two age groups is 3 and 9%, respectively. Collectively, these estimates are generally comparable with other European countries ( European Monitoring Centre for Drugs and Drug Addiction, 1998 ) and the US ( Johnston et al ., 1997 , 2000 ).

The widespread concern about the use of illicit drugs is reflected by its high status on health, educational and political agendas in many countries. The UK Government's 10-year national strategy on drug misuse identifies young people as a critical priority group for prevention and treatment interventions ( Tackling Drugs to Build a Better Britain 1998 ). If strategies to reduce the use of drugs and associated harms amongst the younger population are to be developed, particularly within the health education arena, it is vital that we improve our understanding of the roles that both licit and illicit substances play in the lives of young people. The tendency for educators, practitioners and policy makers to address licit drugs (such as alcohol) separately from illegal drugs may be unhelpful. This is partly because young illicit drug users frequently drink alcohol, and may have little regard for the illicit and licit distinction established by the law. To understand the roles that drug and alcohol use play in contemporary youth culture, it is necessary to examine the most frequently used psychoactive substances as a set.

It is commonplace for young drug users to use several different psychoactive substances. The terms `poly-drug' or `multiple drug' use have been used to describe this behaviour although their exact definitions vary. The term `poly-drug use' is often used to describe the use of two or more drugs during a particular time period (e.g. over the last month or year). This is the definition used within the current paper. However, poly-drug use could also characterize the use of two or more psychoactive substances so that their effects are experienced simultaneously. We have used the term `concurrent drug use' to denote this pattern of potentially more risky and harmful drug use ( Boys et al. 2000a ). Previous studies have reported that users often use drugs concurrently to improve the effects of another drug or to help manage its negative effects [e.g. ( Power et al ., 1996 ; Boys et al. 2000a ; Wibberley and Price, 2000 )].

The most recent British Crime Survey found that 5% of 16–29 year olds had used more than one drug in the last month ( Ramsay and Partridge, 1999 ). Given that 16% of this age band reported drug use in the month prior to interview, this suggests that just under a third of these individuals had used more than one illicit substance during this time period. With alcohol included, the prevalence of poly-drug use is likely to be much higher.

There is a substantial body of literature on the reasons or motivations that people cite for using alcohol, particularly amongst adult populations. For example, research on heavy drinkers suggested that alcohol use is related to multiple functions for use ( Edwards et al ., 1972 ; Sadava, 1975 ). Similarly, research with a focus on young people has sought to identify motives for illicit drug use. There is evidence that for many young people, the decision to use a drug is based on a rational appraisal process, rather than a passive reaction to the context in which a substance is available ( Boys et al. 2000a ; Wibberley and Price, 2000 ). Reported reasons vary from quite broad statements (e.g. to feel better) to more specific functions for use (e.g. to increase self-confidence). However, much of this literature focuses on `drugs' as a generic concept and makes little distinction between different types of illicit substances [e.g. ( Carman, 1979 ; Butler et al ., 1981 ; Newcomb et al ., 1988 ; Cato, 1992 ; McKay et al ., 1992 )]. Given the diverse effects that different drugs have on the user, it might be proposed that reasons for use will closely mirror these differences. Thus stimulant drugs (such as amphetamines, ecstasy or cocaine) will be used for reasons relating to increased nervous system arousal and drugs with sedative effects (such as alcohol or cannabis), with nervous system depression. The present study therefore selected a range of drugs commonly used by young people with stimulant, sedative or hallucinogenic effects to examine this issue further.

The phrase `instrumental drug use' has been used to denote drug use for reasons specifically linked to a drug's effects ( WHO, 1997 ). Examples of the instrumental use of amphetamine-type stimulants include vehicle drivers who report using to improve concentration and relieve tiredness, and people who want to lose weight (particularly young women), using these drugs to curb their appetite. However, the term `instrumental substance use' seems to be used when specific physical effects of a drug are exploited and does not encompass use for more subtle social or psychological purposes which may also be cited by users. In recent reports we have described a `drug use functions' model to help understand poly-substance use phenomenology amongst young people and how decisions are made about patterns of consumption ( Boys et al ., 1999a , b , 2000a ). The term `function' is intended to characterize the primary or multiple reasons for, or purpose served by, the use of a particular substance in terms of the actual gains that the user perceives that they will attain. In the early, 1970s Sadava suggested that functions were a useful means of understanding how personality and environmental variables impacted on patterns of drug use ( Sadava, 1975 ). This work was confined to functions for cannabis and `psychedelic drugs' amongst a sample of college students. To date there has been little research that has examined the different functions associated with the range of psychoactive substances commonly used by young poly-drug users. It is unclear if all drugs with similar physical effects are used for similar purposes, or if other more subtle social or psychological dimensions to use are influential. Work in this area will help to increase understanding of the different roles played by psychoactive substances in the lives of young people, and thus facilitate health, educational and policy responses to this issue.

Previous work has suggested that the perceived functions served by the use of a drug predict the likelihood of future consumption ( Boys et al ., 1999a ). The present study aims to develop this work further by examining the functional profiles of six substances commonly used by young people in the UK.

Patterns of cannabis, amphetamine, ecstasy, LSD, cocaine hydrochloride and alcohol use were examined amongst a sample of young poly-drug users. Tobacco use was not addressed in the present research.

Sampling and recruitment

A snowball-sampling approach was employed for recruitment of participants. Snowball sampling is an effective way of generating a large sample from a hidden population where no formal sampling frame is available ( Van Meter, 1990 ). A team of peer interviewers was trained to recruit and interview participants for the study. We have described this procedure in detail elsewhere and only essential features are described here ( Boys et al. 2000b ). Using current or ex-drug users to gather data from hidden populations of drug using adults has been found to be successful ( Griffiths et al ., 1993 ; Power, 1995 ).

Study participants

Study participants were current poly-substance users with no history of treatment for substance-related disorders. We excluded people with a treatment history on the assumption that young people who have had substance-related problems requiring treatment represent a different group from the general population of young drug users. Inclusion criteria were: aged 16–22 years and having used two or more illegal substances during the past 90 days. During data collection, the age, gender and current occupation of participants were recorded and monitored to ensure that sufficient individuals were recruited to the groups to permit subgroup analyses. If an imbalance was observed in one of these variables, the interviewers were instructed to target participants with specific characteristics (e.g. females under the age of 18) to redress this imbalance.

Study measures

Data were collected using a structured interviewer-administered questionnaire developed specifically for the study. In addition to recording lifetime substance use, questions profiled consumption patterns of six substances in detail. Data were collected between August and November 1998. Interviews were audiotaped with the interviewee's consent. This enabled research staff to verify that answers had been accurately recorded on the questionnaire and that the interview had been conducted in accordance with the research protocol. Research staff also checked for consistency across different question items (e.g. the total number of days of drug use in the past 90 days should equal or exceed the number of days of cannabis use during the same time period). On the few occasions where inconsistencies were identified that could not be corrected from the tape, the interviewer was asked to re-contact the interviewee to verify the data.

Measures of lifetime use, consumption in the past year and past 90 days were based on procedures developed by Marsden et al . ( Marsden et al ., 1998 ). Estimated intensity of consumption (amount used on a typical using day) was recorded verbatim and then translated into standardized units at the data entry stage.

Functions for substance use scale

The questionnaire included a 17-item scale designed to measure perceived functions for substance use. This scale consisted of items developed in previous work ( Boys et al ., 1999a ) in addition to functions derived from qualitative interviews ( Boys et al ., 1999b ), new literature and informal discussions with young drug users. Items were drawn from five domains (Table I ).

Participants were asked if they had ever used a particular drug in order to fulfil each specific function. Those who endorsed the item were then invited to rate how frequently they had used it for this purpose over the past year, using a five-point Likert-type scale (`never' to `always'; coded 0–4). One item differed between the function scales used for the stimulant drugs and for alcohol and cannabis. For the stimulant drugs (amphetamines, cocaine and ecstasy) the item `have you ever used [named drug] to help you to lose weight' was used, for cannabis and alcohol this item was replaced with `have you ever used [drug] to help you to sleep?'. (The items written in full as they appeared in the questionnaire are shown in Table III , together with abbreviations used in this paper.)

Statistical procedures

The internal reliability of the substance use functions scales for each of the six substances was judged using Chronbach's α coefficient. Chronbach's α is a statistic that reflects the extent to which each item in a measurement scale is associated with other items. Technically it is the average of correlations between all possible comparisons of the scale items that are divided into two halves. An α coefficient for a scale can range from 0 (no internal reliability) to 1 (complete reliability). Analyses of categorical variables were performed using χ 2 statistic. Differences in scale means were assessed using t -tests.

The sample consisted of 364 young poly-substance users (205 males; 56.3%) with a mean age of 19.3 years; 69.8% described their ethnic group as White-European, 12.6% as Black and 10.1% were Asian. Just over a quarter (27.5%) were unemployed at the time of interview; a third were in education, 28.8% were in full-time work and the remainder had part-time employment. Estimates of monthly disposable income (any money that was spare after paying for rent, bills and food) ranged from 0 to over £1000 (median = £250).

Substance use history

The drug with the highest lifetime prevalence was cannabis (96.2%). This was followed by amphetamine sulphate (51.6%), cocaine hydrochloride (50.5%) (referred to as cocaine hereafter) and ecstasy (48.6%). Twenty-five percent of the sample had used LSD and this was more common amongst male participants (χ 2 [1] = 9.68, P < 0.01). Other drugs used included crack cocaine (25.5%), heroin (12.6%), tranquillizers (21.7%) and hallucinogenic mushrooms (8.0%). On average, participants had used a total of 5.2 different psychoactive substances in their lives (out of a possible 14) (median = 4.0, mode = 3.0, range 2–14). There was no gender difference in the number of different drugs ever used.

Table II profiles use of the six target drugs over the past year, and the frequency and intensity of use in the 90 days prior to interview.

There were no gender differences in drug use over the past year or in the past 90 days with the exception of amphetamines. For this substance, females who had ever used this drug were more likely to have done so during the past 90 days than males (χ 2 [1] = 4.14, P < 0.05). The mean number of target drugs used over the past 90 days was 3.2 (median = 3.0, mode = 3.0, range 2–6). No gender differences were observed. Few differences were also observed in the frequency and intensity of use. Males reported drinking alcohol more frequently during the three months prior to interview ( t [307] = 2.48, P < 0.05) and using cannabis more intensively on a `typical using day' ( t [337] = 3.56, P < 0.001).

Perceived functions for substance use

There were few differences between the functions endorsed for use of each drug `ever' and those endorsed for use during `the year prior to interview'. This section therefore concentrates on data for the year prior to interview. We considered that in order to use a drug for a specific function, the user must have first hand knowledge of the drug's effects before making this decision. Consequently, functions reported by individuals who had only used a particular substance on one occasion in their lives (i.e. with no prior experience of the drug at the time they made the decision to take it) were excluded from the analyses. Table III summarizes the proportion of the sample who endorsed each of the functions for drugs used in the past year. Roman numerals have been used to indicate the functions with the top five average scores. Table III also shows means for the total number of different items endorsed by individual users and the internal reliability of the function scales for each substance using Chronbach's α coefficients. There were no significant gender differences in the total number of functions endorsed for any of the six substances.

The following sections summarize the top five most popular functions drug-by-drug together with any age or gender differences observed in the items endorsed.

Cannabis use ( n = 345)

Overall the most popular functions for cannabis use were to `RELAX' (endorsed by 96.8% of people who had used the drug in the last year), to become `INTOXICATED' (90.7%) and to `ENHANCE ACTIVITY' (72.8%). Cannabis was also commonly used to `DECREASE BOREDOM' (70.1%) and to `SLEEP' (69.6%) [this item was closely followed by using to help `FEEL BETTER' (69.0%)]. Nine of the 17 function items were endorsed by over half of those who had used cannabis on more than one occasion in the past year. There were no significant gender differences observed, with the exception of using to `KEEP GOING', where male participants were significantly more likely to say that they had used cannabis to fulfil this function in the past year (χ 2 [1] = 6.10, P < 0.05).

There were statistically significant age differences on four of the function variables: cannabis users who reported using this drug in the past year to help feel `ELATED/EUPHORIC' or to help `SLEEP' were significantly older than those who had not used cannabis for these purposes (19.6 versus 19.0; t [343] = 3.32, P < 0.001; 19.4 versus 19.0; t [343] = 2.01, P < 0.05). In contrast, those who had used cannabis to `INCREASE CONFIDENCE' and to `STOP WORRYING' tended to be younger than those who did not (19.0 versus 19.4; t [343] = –2.26, P < 0.05; 19.1 versus 19.5; t [343] = –1.99, P < 0.05).

Amphetamines ( n = 160)

Common functions for amphetamine use were to `KEEP GOING' (95.6%), to `STAY AWAKE' (91.3%) or to `ENHANCE ACTIVITY' (66.2%). Using to help feel `ELATED/EUPHORIC' (60.6%) and to `ENJOY COMPANY' (58.1%) were also frequently mentioned. Seven of the 17 function items were endorsed by over half of participants who had used amphetamines in the past year. As with cannabis, gender differences were uncommon: females were more likely to use amphetamines to help `LOSE WEIGHT' than male participants (χ 2 [1] = 21.67, P < 0.001).

Significant age differences were found on four function variables. Individuals who reported using amphetamines in the past year to feel `ELATED/EUPHORIC' were significantly older than those who did not (19.9 versus 19.0; t [158] = 2.87, P < 0.01). In contrast, participants who used amphetamines to `STOP WORRYING' (18.8 versus 19.8; t [158] = –2.77, P < 0.01), to `DECREASE BOREDOM' (19.2 versus 19.9; t [158] = –2.39, P < 0.05) or to `ENHANCE ACTIVITY' (19.3 versus 20.1; t [158] = –2.88, P < 0.01) were younger than those who had not.

Ecstasy ( n = 157)

The most popular five functions for using ecstasy were similar to those for amphetamines. The drug was used to `KEEP GOING' (91.1%), to `ENHANCE ACTIVITY' (79.6%), to feel `ELATED/EUPHORIC' (77.7%), to `STAY AWAKE' (72.0%) and to get `INTOXICATED' (68.2%). Seven of the 17 function items were endorsed by over half of those who had used ecstasy in the past year. Female users were more likely to use ecstasy to help `LOSE WEIGHT' than male participants (Fishers exact test, P < 0.001).

As with the other drugs discussed above, participants who reported using ecstasy to feel `ELATED/EUPHORIC' were significantly older than those who did not (19.8 versus 18.9; t [155] = 2.61, P < 0.01). In contrast, those who had used ecstasy to `FEEL BETTER' (19.3 versus 20.0; t [155] = –2.29, P < 0.05), to `INCREASE CONFIDENCE' (19.2 versus 19.9; t [155] = –2.22, P < 0.05) and to `STOP WORRYING' (19.0 versus 19.9; t [155] = –2.96, P < 0.01) tended to be younger.

LSD ( n = 58)

Of the six target substances examined in this study, LSD was associated with the least diverse range of functions for use. All but two of the function statements were endorsed by at least some users, but only five were reported by more than 50%. The most common purpose for consuming LSD was to get `INTOXICATED' (77.6%). Other popular functions included to feel `ELATED/EUPHORIC' and to `ENHANCE ACTIVITY' (both endorsed by 72.4%), and to `KEEP GOING' and to `ENJOY COMPANY' (both endorsed by 58.6%). Unlike the other substances examined, no gender or age differences were observed.

Cocaine ( n = 168)

In common with ecstasy and amphetamines, the most widely endorsed functions for cocaine use were to help `KEEP GOING' (84.5%) and to help `STAY AWAKE' (69.0%). Consuming cocaine to `INCREASE CONFIDENCE' and to get `INTOXICATED' (both endorsed by 66.1%) were also popular. However, unlike the other stimulant drugs, 61.9% of the cocaine users reported using to `FEEL BETTER'. Ten of the 17 function items were endorsed by over half of those who had used cocaine in the past year.

Gender differences were more common amongst functions for cocaine use than the other substances surveyed. More males reported using cocaine to `IMPROVE EFFECTS' of other drugs (χ 2 [1] = 4.00, P < 0.05); more females used the drug to help `STAY AWAKE' (χ 2 [1] = 12.21, P < 0.001), to `LOSE INHIBITIONS' (χ 2 [1] = 9.01, P < 0.01), to `STOP WORRYING' (χ 2 [1] = 8.11, P < 0.01) or to `ENJOY COMPANY' of friends (χ 2 [1] = 4.34, P < 0.05). All participants who endorsed using cocaine to help `LOSE WEIGHT' were female.

Those who had used cocaine to `FEEL BETTER' (18.9 versus 19.8; t [166] = –3.06, P < 0.01), to `STOP WORRYING' (18.6 versus 19.7; t [166] = –3.86, P < 0.001) or to `DECREASE BOREDOM' (18.9 versus 19.6; t [166] = –2.52, P < 0.05) were significantly younger than those who did not endorse these functions. Similar to the other drugs, participants who had used cocaine to feel `ELATED/EUPHORIC' in the past year tended to be older than those who had not (19.6 versus 18.7; t [166] = 3.16, P < 0.01).

Alcohol ( n = 312)

The functions for alcohol use were the most diverse of the six substances examined. Like LSD, the most commonly endorsed purpose for drinking was to get `INTOXICATED' (89.1%). Many used alcohol to `RELAX' (82.7%), to `ENJOY COMPANY' (74.0%), to `INCREASE CONFIDENCE' (70.2%) and to `FEEL BETTER' (69.9%). Overall, 11 of the 17 function items were endorsed by over 50% of those who had drunk alcohol in the past year. Male participants were more likely to report using alcohol in combination with other drugs either to `IMPROVE EFFECTS' of other drugs (χ 2 [1] = 4.56, P < 0.05) or to ease the `AFTER EFFECTS' of other substances (χ 2 [1] = 7.07, P < 0.01). More females than males reported that they used alcohol to `DECREASE BOREDOM' (χ 2 [1] = 4.42, P < 0.05).

T -tests revealed significant age differences on four of the function variables: those who drank to feel `ELATED/EUPHORIC' were significantly older (19.7 versus 19.0; t [310] = 3.67, P < 0.001) as were individuals who drank to help them to `LOSE INHIBITIONS' (19.6 versus 19.0; t [310] = 2.36, P < 0.05). In contrast, participants who reported using alcohol just to get `INTOXICATED' (19.2 versus 20.3; t [310] = –3.31, P < 0.001) or to `DECREASE BOREDOM' (19.2 versus 19.6; t [310] = –2.25, P < 0.05) were significantly younger than those who did not.

Combined functional drug use

The substances used by the greatest proportion of participants to `IMPROVE EFFECTS' from other drugs were cannabis (44.3%), alcohol (41.0%) and amphetamines (37.5%). It was also common to use cannabis (64.6%) and to a lesser extent alcohol (35.9%) in combination with other drugs in order to help manage `AFTER EFFECTS'. Amphetamines, ecstasy, LSD and cocaine were also used for these purposes, although to a lesser extent. Participants who endorsed the combination drug use items were asked to list the three main drugs with which they had combined the target substance for these purposes. Table IV summarizes these responses.

Overall functions for drug use

In order to examine which functions were most popular overall, a dichotomous variable was created for each different item to indicate if one or more of the six target substances had been used to fulfil this purpose during the year prior to interview. For example, if an individual reported that they had used cannabis to relax, but their use of ecstasy, amphetamines and alcohol had not fulfilled this function, then the variable for `RELAX' was scored `1'. Similarly if they had used all four of these substances to help them to relax in the past year, the variable would again be scored as `1'. A score of `0' indicates that none of the target substances had been used to fulfil a particular function. Table V summarizes the data from these new variables.

Over three-quarters of the sample had used at least one target substance in the past year for 11 out of the 18 functions listed. The five most common functions for substance use overall were to `RELAX' (96.7%); `INTOXICATED' (96.4%); `KEEP GOING' (95.9%); `ENHANCE ACTIVITY' (88.5%) and `FEEL BETTER' (86.8%). Despite the fact that `SLEEP' was only relevant to two substances (alcohol and cannabis), it was still endorsed by over 70% of the total sample. Using to `LOSE WEIGHT' was only relevant to the stimulant drugs (amphetamines, ecstasy and cocaine), yet was endorsed by 17.3% of the total sample (almost a third of all female participants). Overall, this was the least popular function for recent substance use, followed by `WORK' (32.1%). All other items were endorsed by over 60% of all participants.

Gender differences were identified in six items. Females were significantly more likely to have endorsed the following: using to `INCREASE CONFIDENCE' (χ 2 [1] = 4.41, P < 0.05); `STAY AWAKE' (χ 2 [1] = 5.36, P < 0.05), `LOSE INHIBITIONS' (χ 2 [1] = 4.48, P < 0.05), `ENHANCE SEX' (χ 2 [1] = 5.17, P < 0.05) and `LOSE WEIGHT' (χ 2 [1] = 29.6, P < 0.001). In contrast, males were more likely to use a substance to `IMPROVE EFFECTS' of another drug (χ 2 [1] = 11.18, P < 0.001).

Statistically significant age differences were identified in three of the items. Those who had used at least one of the six target substances in the last year to feel `ELATED/EUPHORIC' (19.5 versus 18.6; t [362] = 4.07, P < 0.001) or to `SLEEP' (19.4 versus 18.9; t [362] = 2.19, P < 0.05) were significantly older than those who had not used for this function. In contrast, participants who had used in order to `STOP WORRYING' tended to be younger (19.1 versus 19.7; t [362] = –2.88, P < 0.01).

This paper has examined psychoactive substance use amongst a sample of young people and focused on the perceived functions for use using a 17-item scale. In terms of the characteristics of the sample, the reported lifetime and recent substance use was directly comparable with other samples of poly-drug users recruited in the UK [e.g. ( Release, 1997 )].

Previous studies which have asked users to give reasons for their `drug use' overall instead of breaking it down by drug type [e.g. ( Carman, 1979 ; Butler et al ., 1981 ; Newcomb et al ., 1988 ; Cato, 1992 ; McKay et al ., 1992 )] may have overlooked the dynamic nature of drug-related decision making. A key finding from the study is that that with the exception of two of the functions for use scale items (using to help sleep or lose weight), all of the six drugs had been used to fulfil all of the functions measured, despite differences in their pharmacological effects. The total number of functions endorsed by individuals for use of a particular drug varied from 0 to 15 for LSD, and up to 17 for cannabis, alcohol and cocaine. The average number ranged from 5.9 (for LSD) to 9.0 (for cannabis). This indicates that substance use served multiple purposes for this sample, but that the functional profiles differed between the six target drugs.

We have previously reported ( Boys et al. 2000b ) that high scores on a cocaine functions scale are strongly predictive of high scores on a cocaine-related problems scale. The current findings support the use of similar function scales for cannabis, amphetamines, LSD and ecstasy. It remains to be seen whether similar associations with problem scores exist. Future developmental work in this area should ensure that respondents are given the opportunity to cite additional functions to those included here so that the scales can be further extended and refined.

Recent campaigns that have targeted young people have tended to assume that hallucinogen and stimulant use is primarily associated with dance events, and so motives for use will relate to this context. Our results support assumptions that these drugs are used to enhance social interactions, but other functions are also evident. For example, about a third of female interviewees had used a stimulant drug to help them to lose weight. Future education and prevention efforts should take this diversity into account when planning interventions for different target groups.

The finding that the same functions are fulfilled by use of different drugs suggests that at least some could be interchangeable. Evidence for substituting alternative drugs to fulfil a function when a preferred drug is unavailable has been found in other studies [e.g. ( Boys et al. 2000a )]. Prevention efforts should perhaps focus on the general motivations behind use rather than trying to discourage use of specific drug types in isolation. For example, it is possible that the focus over the last decade on ecstasy prevention may have contributed inadvertently to the rise in cocaine use amongst young people in the UK ( Boys et al ., 1999c ). It is important that health educators do not overlook this possibility when developing education and prevention initiatives. Considering functions that substance use can fulfil for young people could help us to understand which drugs are likely to be interchangeable. If prevention programmes were designed to target a range of substances that commonly fulfil similar functions, then perhaps this could address the likelihood that some young people will substitute other drugs if deterred from their preferred substance.

There has been considerable concern about the perceived increase in the number of young people who are using cocaine in the UK ( Tackling Drugs to Build a Better Britain 1998 ; Ramsay and Partridge, 1999 ; Boys et al. 2000b ). It has been suggested that, for a number of reasons, cocaine may be replacing ecstasy and amphetamines as the stimulant of choice for some young people ( Boys et al ., 1999c ). The results from this study suggest that motives for cocaine use are indeed similar to those for ecstasy and amphetamine use, e.g. using to `keep going' on a night out with friends, to `enhance an activity', `to help to feel elated or euphoric' or to help `stay awake'. However, in addition to these functions which were shared by all three stimulants, over 60% of cocaine users reported that they had used this drug to `help to feel more confident' in a social situation and to `feel better when down or depressed'. Another finding that sets cocaine aside from ecstasy and amphetamines was the relatively common existence of gender differences in the function items endorsed. Female cocaine users were more likely to use to help `stay awake', `lose inhibitions', `stop worrying', `enjoy company of friends' or to help `lose weight'. This could indicate that women are more inclined to admit to certain functions than their male counterparts. However, the fact that similar gender differences were not observed in the same items for the other five substances, suggests this interpretation is unlikely. Similarly, the lack of gender differences in patterns of cocaine use (both frequency and intensity) suggests that these differences are not due to heavier cocaine use amongst females. If these findings are subsequently confirmed, this could point towards an inclination for young women to use cocaine as a social support, particularly to help feel less inhibited in social situations. If so, young female cocaine users may be more vulnerable to longer-term cocaine-related problems.

Many respondents reported using alcohol or cannabis to help manage effects experienced from another drug. This has implications for the choice of health messages communicated to young people regarding the use of two or more different substances concurrently. Much of the literature aimed at young people warns them to avoid mixing drugs because the interactive effects may be dangerous [e.g. ( HIT, 1996 )]. This `Just say No' type of approach does not take into consideration the motives behind mixing drugs. In most areas, drug education and prevention work has moved on from this form of communication. A more sophisticated approach is required, which considers the functions that concurrent drug use is likely to have for young people and tries to amend messages to make them more relevant and acceptable to this population. Further research is needed to explore the motivations for mixing different combinations of drugs together.

Over three-quarters of the sample reported using at least one of the six target substances to fulfil 11 out of the 18 functions. These findings provide strong evidence that young people use psychoactive drugs for a range of distinct purposes, not purely dependent on the drug's specific effects. Overall, the top five functions were to `help relax', `get intoxicated', `keep going', `enhance activity' and `feel better'. Each of these was endorsed by over 85% of the sample. Whilst all six substances were associated to a greater or lesser degree with each of these items, there were certain drugs that were more commonly associated with each. For example, cannabis and alcohol were popular choices for relaxation or to get intoxicated. In contrast, over 90% of the amphetamine and ecstasy users reported using these drugs within the last year to `keep going'. Using to enhance an activity was a common function amongst users of all six substances, endorsed by over 70% of ecstasy, cannabis and LSD users. Finally, it was mainly alcohol and cannabis (and to a lesser extent cocaine) that were used to `feel better'.

Several gender differences were observed in the combined functions for recent substance use. These findings indicate that young females use other drugs as well as cocaine as social supports. Using for specific physical effects (weight loss, sex or wakefulness) was also more common amongst young women. In contrast, male users were significantly more likely to report using at least one of the target substances to try to improve the effects of another substance. This indicates a greater tendency for young males in this sample to mix drugs than their female counterparts. Age differences were also observed on several function items: participants who had used a drug to `feel elated or euphoric' or to `help sleep' tended to be older and those who used to `stop worrying about a problem' were younger. If future studies confirm these differences, education programmes and interventions might benefit from tailoring their strategies for specific age groups and genders. For example, a focus on stress management strategies and coping skills with a younger target audience might be appropriate.

Some limitations of the study need to be acknowledged. The sample for this study was recruited using a snowball-sampling methodology. Although it does not yield a random sample of research participants, this method has been successfully used to access hidden samples of drug users [e.g. ( Biernacki, 1986 ; Lenton et al ., 1997 )]. Amongst the distinct advantages of this approach are that it allows theories and models to be tested quantitatively on sizeable numbers of subjects who have engaged in a relatively rare behaviour.

Further research is now required to determine whether our observations may be generalized to other populations (such as dependent drug users) and drug types (such as heroin, tranquillizers or tobacco) or if additional function items need to be developed. Future studies should also examine if functions can be categorized into primary and subsidiary reasons and how these relate to changes in patterns of use and drug dependence. Recognition of the functions fulfilled by substance use could help inform education and prevention strategies and make them more relevant and acceptable to the target audiences.

Structure of functions scales

Profile of substance use over the past year and past 90 days ( n = 364)

Proportion (%) of those who have used [substance] more than once, who endorsed each functional statement for their use in the past year

Combined functional substance use reported by the sample over the past year

Percentage of participants who reported having used at least one of the target substances to fulfil each of the different functions over the past year ( n = 364)

We gratefully acknowledge research support from the Health Education Authority (HEA). The views expressed in this paper are those of the authors and do not necessarily reflect those of the HEA. We would also like to thank the anonymous referees for helpful comments and suggestions on an earlier draft of this paper.

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• Published: 11 November 2019

The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies

• Ying Han 1 ,
• Wei Yan 2 ,
• Yongbo Zheng 2 ,
• Muhammad Zahid Khan 1 ,
• Kai Yuan 2 &
• Lin Lu 2 , 3  

Translational Psychiatry volume  9 , Article number:  282 ( 2019 ) Cite this article

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• Pharmacodynamics

Fentanyl is a powerful opioid anesthetic and analgesic, the use of which has caused an increasing public health threat in the United States and elsewhere. Fentanyl was initially approved and used for the treatment of moderate to severe pain, especially cancer pain. However, recent years have seen a growing concern that fentanyl and its analogs are widely synthesized in laboratories and adulterated with illicit supplies of heroin, cocaine, methamphetamine, and counterfeit pills, contributing to the exponential growth in the number of drug-related overdose deaths. This review summarizes the recent epidemic and evolution of illicit fentanyl use, its pharmacological mechanisms and side effects, and the potential clinical management and prevention of fentanyl-related overdoses. Because social, economic, and health problems that are related to the use of fentanyl and its analogs are growing, there is an urgent need to implement large-scale safe and effective harm reduction strategies to prevent fentanyl-related overdoses.

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Introduction

Fentanyl was first developed in 1960 by Paul Janssen as a potent opioid anesthetic and analgesic. At the time, fentanyl was the fastest-acting opioid discovered to date and more powerful than morphine (50–100 times) and heroin (30–50 times) 1 , 2 . Transdermal, intravenous, and transbuccal fentanyl administration and several other drugs with chemical structures that are similar to fentanyl have been developed, approved, and used for surgical anesthesia and the management of severe cancer pain and perioperative pain, eventually becoming the most often used synthetic opioid in clinical practice 3 , 4 , 5 . Since 1979, fentanyl and its analogs have been synthesized in laboratories and sold as heroin substitutes or mixed with other illicitly sourced drugs, leading to an increase in fentanyl-related overdose deaths 6 , 7 . Postmortem studies have consistently found pulmonary edema, congestion, and needle puncture sites in these victims. Based on data from the National Vital Statistics System, 599,255 drug overdose deaths occurred from 1979 to 2016 in the United States, and the overall mortality rate has seen exponential growth. Fentanyl-related overdose deaths predominantly occurred in the northeastern United States, mostly affecting younger people (20–40 years of age), and grew sharply since 2013 8 .

Rapid death from ingesting fentanyl has become increasingly more common. Its high potency, fast onset of action, and duration of the desired effect may be particularly important contributing factors to the higher risk of overdose deaths and social consequences 9 . Fentanyl has become a major contributor to cocaine-related fatal overdoses. The rate of fentanyl-related overdose deaths increased 55% between 2015 and 2017 in New York city 10 , 11 . Synthetic opioids are also increasingly detected in illicit supplies of heroin, methamphetamine, and counterfeit pills. Analysis of a sampling of 1 million unique patients’ urine drug test (UDT) specimens showed that positivity rates for fentanyl have increased by 1850% among cocaine positive UDT results and increased by 798% among methamphetamine-positive UDT results between January 2013 and September 2018 12 . This mixture may lead to the increases in cocaine-related and methamphetamine-related overdoses. Moreover, the number of fatal overdoses from synthetic opioids, primarily fentanyl and its analogs, was 19,547 in 2016 in the United States, and this rate increased by 88% per year from 2013 to 2016 13 , 14 , 15 , 16 . The incidence of heroin-related overdose deaths stabilized in 2017, whereas deaths that involved other synthetic opioids continued to increase 17 . Given the substantial individual and public health threats of this emerging problem, the present review summarizes the epidemic and evolution of illicit fentanyl use, its pharmacological mechanism of action, its adverse consequences, and the clinical management and prevention of fentanyl-related overdoses.

Epidemic and evolution of illicit fentanyl use

Fentanyl is currently approved and commonly used to treat breakthrough pain in cancer patients and various other clinical conditions that involve noncancer pain, such as postoperative pain. However, its potential for abuse and the rise in overdose deaths pose a serious challenge to public health 18 , 19 , 20 , 21 . Deaths that were attributable to illicit fentanyl use were first reported in the early 1980s and occurred sporadically in the United States 6 , 7 , 22 . A surge in the occurrence of fentanyl-related fatalities among illicit drug users occurred in 2006. A total of 1013 deaths in six states occurred from April 4, 2005, to March 28, 2007 23 . Since then, the prevalence of opioid-related mortality has increased persistently, and the number of reported fentanyl-related deaths more than doubled (from 2628 to 5544) between 2012 and 2014 21 , 24 , 25 . The rate of fentanyl-related overdose deaths increased from <15% in 2010 to ~50% in 2017 in Marion County, Indiana 26 . Overall overdose deaths and first-responder calls increased in a community-based sample in an impoverished neighborhood in Vancouver, Canada, in 2017, and fentanyl was detected in 52% of the subjects who were prescribed opioid agonist therapy 27 . At the same time, fentanyl-related deaths also increased in Australia 28 , 29 .

The presence of fentanyl and its analogs has become a central contributor to the increase in the number of opioid-related overdose deaths. Preliminary estimates of opioid overdose deaths in the United States in 2016 revealed that fentanyl and its analogs (e.g., acetylfentanyl, furanylfentanyl, and carfentanil) have contributed to nearly half of opioid overdose deaths 16 , 30 , 31 . Moreover, the number of deaths that were attributable to illicitly manufactured fentanyl and its analogs nearly quadrupled between July 2015 and June 2017 in Montgomery County, Ohio 32 . Heroin-positive cases declined while methamphetamine-positive cases increased in these victims. Urine drug screens showed that the prevalence of recent fentanyl use in patients who received opioid agonist treatment in England was 3%, and multiple fatalities with synthetic fentanyl analogs were reported in northern England in early 2017 33 , 34 .

Fentanyl is ~30–50 times more potent than heroin, and smaller volumes of heroin and other drugs that are adulterated with fentanyl can produce powerful effects with lower production costs. Detecting fentanyl and its analogs in used syringes can reveal exposure risk 35 . The fentanyl detection rate was significantly higher among drug users who injected drugs in the past 6 months compared with non-injection drug users. The prevalence of non-fatal overdose is very high among people who inject drugs 36 , 37 , 38 . The prevalence of intravenous fentanyl use among people who inject drugs in Australia is 8%. Given the narrow range between effective and lethal doses, this population is at high risk of overdose 37 , 39 , 40 . The opioid crisis is likely attributable to illicitly manufactured fentanyl and its analogs around the world, especially when they are mixed with heroin and other drugs, and the route of administration 41 , 42 .

Many people who have survived fentanyl overdose appear to be unaware that they ever took the drug. Surveys from 17 harm reduction sites in British Columbia, Canada, revealed that the prevalence of fentanyl use was 29% (70/242; based on urine drug screen), 73% of whom report that they did not knowingly use fentanyl 43 . Urine drug screens in methadone-maintained patients in Wayne County, Michigan, showed that 38% of 368 unique patients tested positive for fentanyl, and 67.3% of 113 patients reported that they did not know anyone who sought to obtain fentanyl in a subsequent anonymous survey 44 . A high risk of overdose and deaths was found among this vulnerable population that exhibited high fentanyl exposure, thus highlighting the pressing need to develop appropriate harm-reduction strategies, such as surveillance, the development of early-warning systems, pill-testing technology about the presence of fentanyl in various drug products, naloxone training and distribution, overdose education, and urine screens 21 , 45 , 46 . The vast majority of people reported their willingness to use rapid test strips to detect the presence of fentanyl in drugs or urine at home or utilize drug-checking services at supervised injection clinics 47 , 48 . Multiplex ultrahigh-performance liquid chromatography (UHPLC–MS)/liquid chromatography tandem mass spectrometry (LC–MS–MS)/liquid chromatography–quadrupole time-of-flight–mass spectrometry (LC–QTOF–MS) analyses have also been developed and validated for the detection of fentanyl and its analogs and metabolites in blood, hair, and oral fluid, which will be helpful for informing harm reduction behaviors and combating the fentanyl crisis 49 , 50 , 51 , 52 . A newly developed lateral flow immunoassay was also evaluated for effectiveness in the detection of fentanyl analogs 53 .

Pharmacological mechanisms and side effects of fentanyl

Despite the beneficial clinical anesthetic and pain-relieving effects of fentanyl, the frequent use of fentanyl primarily affects the central nervous system (CNS) and gastrointestinal, cardiovascular, and pulmonary systems and can cause several side effects 54 . Digestive symptoms, such as nausea, vomiting, and constipation, are common in patients who repeatedly use fentanyl 55 , 56 . Immunosuppression was also shown to be precipitated by analgesic opioid drugs, including fentanyl, in preclinical and clinical studies. Such immunosuppression can be especially dangerous in the elderly and already immunocompromised patients 57 , 58 , 59 . Additionally, fentanyl and synthetic opioids have other frequently reported side effects, including migraine, dizziness, vertigo, confusion, hallucinations, and a higher risk of fractures in the elderly 59 , 60 , 61 , 62 , 63 . Fentanyl has rewarding effects and thus high abuse potential. Its repeated use leads to the development of tolerance and drug dependence 64 , 65 . Analyses of adverse-event reporting systems in the United States, Europe, and the United Kingdom have shown that cases of fentanyl-related misuse, abuse, dependence, and withdrawal steadily increased between 2004 and 2018, resulting in prolonged hospitalization or death 66 . Other mental disorders, such as depression, insomnia, and suicidality, can also occur with fentanyl abuse, contributing to relapse and a higher risk of respiratory depression or overdose death 65 , 67 . The treatment of these mental disorders may help prevent fentanyl-related fatalities and achieve abstinence.

Fentanyl is a full μ-opioid receptor agonist, but it also acts on δ- and κ-opioid receptors 68 , 69 . Fentanyl has been shown to exert its analgesic and lethal effects through different receptor populations in the CNS. It is eliminated from cerebrospinal fluid at approximately the same rate as morphine 70 , 71 . Acute naloxone administration antagonizes fentanyl-induced analgesia more than fentanyl-induced lethality. β-funaltrexamine was shown to inhibit both fentanyl-induced analgesia and lethality 71 . Overdose-related concentrations of fentanyl were shown to block human ether-a-go-go-related gene (hERG) potassium channels in ventricular myocytes that were isolated from neonatal rats, which may contribute to fentanyl-related overdose death or sudden death 72 .

Respiratory depression is the most dangerous adverse reaction to fentanyl that can result in lethality. In rats, intravenous injections of fentanyl dose-dependently decreased oxygen levels in the nucleus accumbens, basolateral amygdala, and subcutaneous space, followed by a delayed increase in glucose and fluctuations in brain temperature and metabolic brain activity 73 , 74 , 75 . Neuronal hypermetabolism that is induced by fentanyl and its analogs may damage the hippocampus and limbic system, causing an amnestic syndrome in patients who use fentanyl 76 , 77 , 78 , 79 . With regard to brain hypoxia and hypothermia, fentanyl has synergistic effects with heroin, which is consistent with the higher risk of overdose death that is associated with heroin–fentanyl mixtures 73 , 80 . Fentanyl-related respiratory depression is also dose-dependent, which reaches a peak 5 min after administration and requires 4 h to recover in humans. Such effects can lead to prolonged apnea and sudden death 74 , 81 , 82 . Epidural fentanyl infusion has been shown to cause postoperative adult respiratory distress syndrome 83 . The μ 1 -opioid receptor is involved in respiratory depression that is induced by fentanyl and its analogs but not morphine 84 . Selective α4β2 nicotinic receptor agonist A85380 reversed fentanyl-induced respiratory depression in rats without significant side effects 85 . The calcium-activated potassium channel blocker GAL021 was shown to attenuate morphine-induced respiratory depression in rats, mice, and nonhuman primates, and it produced stimulatory effects during alfentanil-induced respiratory depression, without affecting sedation in humans 86 , 87 , 88 . However, more studies are needed to confirm the efficacy and potential toxicity of A85380 and GAL021.

Many studies have reported cardiovascular symptoms after fentanyl-induced analgesia, such as myocardial ischemia, QTc interval prolongation, and bradycardia 89 , 90 , 91 . Fentanyl is commonly used during percutaneous coronary interventions, but the relative safety of its use requires further investigation because intravenous fentanyl has been reported to induce hypothermia, impair ticagrelor absorption, and cause antiplatelet effects 92 , 93 , 94 . Autopsy and toxicological analyses indicated that chronic fentanyl use may be responsible for hypertrophy, cardiac fibrosis, and atherosclerosis 54 , 95 , 96 . Neither sigma nor opioid receptors are essential for the fentanyl-induced attenuation of muscarinic coronary contraction 97 .

Fentanyl administration provides effective pain relief, but its long-term use can result in a lowering of pain thresholds 98 , 99 . This phenomenon of fentanyl-induced hyperalgesia is a challenge in the clinical management of perioperative and chronic pain. Recent studies showed that fentanyl-induced hyperalgesia was modulated by the activation of extracellular signal-regulated kinase in the laterocapsular division of the central nucleus of the amygdala (CeLC) and CaMKIIα in the CeLC–periaqueductal gray–rostral ventromedial medulla–spinal cord descending facilitative pain pathway in rats 100 , 101 .

Interventions for the management and prevention of fentanyl overdose

Similar treatments are prescribed for opioid use disorder and opioid overdose, including the Food and Drug Administration (FDA)-approved medications methadone, buprenorphine, extended-release naltrexone, and naloxone 102 . Lofexidine, a central α 2 -adrenergic receptor agonist, was the first non-opioid medication that was approved by the United States FDA for the treatment of opioid withdrawal 103 , 104 . Lofexidine has fewer prescriptive barriers and comparable efficacy and safety relative to other opioid receptor agonizts, but it is generally more expensive. Sparse data are available on the effectiveness of interventions to prevent overdoses that are caused by illicitly manufactured fentanyl (Table 1 ). Compared with other opioid-related overdoses, illicit fentanyl-related overdoses appear to be accompanied by distinct symptoms, such as body and chest rigidity, dyskinesia, and slow or irregular heart rate, which can affect overdose management, such as oxygen provisions and appropriate doses of naloxone 105 , 106 . To avoid or reduce the adverse effects of fentanyl, the FDA proposed to control the duration of use and doses of fentanyl 107 . One study showed that the majority of patients who were presumed to experience fentanyl overdose could be discharged after brief emergency room observation, thus unlikely requiring additional naloxone dosing in the emergency room 108 .

There are limited data on the efficacy of methadone or buprenorphine for the treatment of illicit fentanyl use. A retrospective study in Rhode Island showed that 6 months of methadone maintenance protected against death and promoted abstinence in fentanyl-exposed patients, but relapse rates were still high 109 . Buprenorphine is a μ-opioid receptor partial agonist and κ-opioid receptor antagonist that is commonly used to treat opioid use disorder. It also exerts antidepressant and anxiolytic activity and is a promising treatment for neonatal opioid withdrawal syndrome 110 . A retrospective cohort study showed that 6-month treatment retention rates and opioid abstinence rates were not different between individuals who were positive for fentanyl or heroin at baseline before initiating buprenorphine treatment, indicating that buprenorphine may still be beneficial for treating fentanyl exposure 111 . Repeated treatment with buprenorphine produced a greater magnitude of antinociceptive tolerance than higher-efficacy agonizts (e.g., morphine and etonitazene) in rats 112 . Studies in pigeons and rhesus monkeys showed that the amount of tolerance that develops to the reinforcing potency of opioids depends on their efficacy, and the higher-efficacy μ-opioid receptor agonist sufentanil was more difficult to antagonize than the low-efficacy μ-opioid receptor agonist morphine 113 , 114 , 115 . These data indicate that buprenorphine may have lower efficacy for the treatment of fentanyl overdose compared with heroin overdose, although no human trials have been performed to date 116 .

Naloxone is a μ-opioid receptor antagonist that is used to treat fentanyl-related overdose, regardless of the suspected route of administration. However, its efficacy is inconsistent, and safe dosing needs to be considered from the perspective of precipitating opioid withdrawal 117 , 118 , 119 . Recent studies also showed that extended-release naltrexone was equally safe and effective as a buprenorphine–naloxone combination at promoting abstinence and treatment retention once treatment was initiated, but fewer participants successfully initiated naltrexone treatment 120 , 121 . Larger or repeated doses of naloxone are speculated to be required for the treatment of fentanyl overdose because of its higher affinity for μ-opioid receptors. However, a study of a community naloxone distribution program in Allegheny County showed that the average doses of naloxone that were administered to reverse overdose did not change between 2013 and 2016, although the incidence of overdoses that were related to fentanyl and its analogs increased during the same time 122 . A retrospective study of the fentanyl epidemic in Chicago showed that doses of naloxone up to 12 mg may effectively treat fentanyl overdose 123 . Naloxone was shown to reverse transdermal fentanyl overdose-induced sedation, the reduction of body temperature, and the reduction of heart rate in dogs 124 . A systematic review found a low incidence of mortality or serious adverse events that were caused by prehospital naloxone administration in opioid overdose patients, although the source of overdose was mostly heroin and not fentanyl 125 . Additionally, seeking emergency medical help was positively associated with overdose victims who received higher doses of naloxone and rescue breathing in British Columbia, Canada 126 . A survey of 316 street-recruited people who used opioids in Baltimore showed that the majority of them perceived the high risk of fentanyl-adulterated heroin and overdose, but most of them did not often carry naloxone with them 127 . The early adoption and distribution of take-home naloxone have been reported to effectively prevent opioid overdose deaths 128 , 129 , 130 . Therefore, harm reduction strategies, such as safe injection sites, the expansion of available opioid agonist treatment, and overdose prevention training (e.g., carrying naloxone and not use drugs alone, higher dose or multiple administrations of naloxone), are needed to control the adverse effects of fentanyl and reduce overdoses 131 .

Additionally, more potent, longer-acting opioid receptor antagonists are needed to prevent fentanyl-related overdose deaths. Compared with naloxone, nalmefene has been shown to have superior efficacy in reversing the carfentanil-induced loss of righting reflex and respiratory depression in rats 132 . Nalmefene is generally well tolerated and is a recent option for patients with alcohol dependence 133 , 134 , 135 . Additionally, novel, selective, and potent μ-opioid receptor antagonists, such as 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ) and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN), have been reported to produce less opioid tolerance, dependence, and withdrawal signs. Furthermore, NAN pretreatment was shown to block the discriminative stimulus effects of fentanyl in rats. The orexin-1 receptor antagonist SB-334867 was also shown to decrease motivation and demand for fentanyl in rats 136 . Therefore, these drugs could be considered candidates for the treatment of opioid use disorder 137 . Chronic anticonvulsant carbamazepine therapy was shown to increase fentanyl clearance and decrease plasma concentrations in neurosurgical patients, which may attenuate the actions of fentanyl 138 . A case report showed that treatment with slow-release oral morphine in a near-fatal fentanyl overdose patient was successful, despite the patient’s previous failures with methadone and buprenorphine/naloxone-based opioid agonist therapies, which could be considered potential alternative treatments 139 .

Previous studies have reported the vaccine consisting of fentanyl hapten conjugated to tetanus toxoid or keyhole limpet hemocyanin carrier protein, and immunization with these vaccines reduced fentanyl biodistribution to the brain, and blunted its antinociceptive effects and respiratory depression in rodents 140 , 141 . Moreover, the conjugate vaccine stimulated the endogenous generation of antibodies with high affinity for a variety of fentanyl analogs 140 , and was shown to blunt fentanyl reinforcement 142 . A recent study screened and purified monoclonal antibodies (mAbs) from vaccinated mice, and found that the 6A4 mAb prevented the acute lethality of fentanyl, and reversed both fentanyl and carfentanil-induced antinociception as effective as naloxone 143 . These findings suggest that immunopharmacotherapies including active vaccine or its combination with passive mAb may be potential and promising treatment strategies to address the current opioid crisis. Accumulating evidence also implicate the dysbiosis of gut microbiome in the pathophysiology of drug addiction, however data regarding fentanyl use is rare 144 . Manipulating the compositions of the gut microbiome or its products may guide new adjuvant therapies for opioid addiction in the future.

A United States FDA Risk Evaluation and Mitigation Strategy (REMS) program was also implemented to assess transmucosal immediate-release fentanyls (TIRFs) and found that substantial rates of TIRFs were prescribed inappropriately 145 , 146 . With the findings of deficiencies in the structure and administration of TIRFs, the development of other REMSs is needed to ensure the safe and appropriate use of approved drugs, especially dangerous opioid drugs 147 .

In conclusion, the crisis of opioid-related overdoses, especially fentanyl and its analogs, is a major threat to both individual and public health. Respiratory depression, cardiovascular effects, and neuropsychiatric symptoms are associated with fentanyl overdose and lethality. Naloxone is the standard rescue drug for fentanyl overdose, but its efficacy is inconsistent. Further clinical research is needed to optimize individualized medication-assisted treatments in patients who overdose on fentanyl and its analogs. To address the social, economic, and health problems that are associated with fentanyl and its analogs, coordinated efforts are needed to implement large-scale harm reduction strategies (e.g., naloxone distribution, innovative studies, and the development of novel drugs).

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This work was supported in part by the National Natural Science Foundation of China (nos. 81701312 and 81521063).

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Han, Y., Yan, W., Zheng, Y. et al. The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies. Transl Psychiatry 9 , 282 (2019). https://doi.org/10.1038/s41398-019-0625-0

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Understanding the Demand for Illegal Drugs (2010)

Chapter: 1 introduction, 1 introduction.

A merica’s problem with illegal drugs seems to be declining, and it is certainly less in the news than it was 20 years ago. Surveys have shown a decline in the number of users dependent on expensive drugs (Office of National Drug Control Policy, 2001), an aging of the population in treatment (Trunzo and Henderson, 2007), and a decline in the violence related to drug markets (Pollack et al., 2010). Still, research indicates that illegal drugs remain a concern for the majority of Americans (Caulkins and Mennefee, 2009; Gallup Poll, 2009).

There is virtually no disagreement that the trafficking in and use of cocaine, heroin, and methamphetamine continue to cause great harm to the nation, particularly to vulnerable minority communities in the major cities. In contrast, there is disagreement about marijuana use, which remains a part of adolescent development for about half of the nation’s youth. The disagreement concerns the amount, source, and nature of the harms from marijuana. Some note, for example, that most of those who use marijuana use it only occasionally and neither incur nor cause harms and that marijuana dependence is a much less serious problem than dependence on alcohol or cocaine. Others emphasize the evidence of a potential for triggering psychosis (Arseneault et al., 2004) and the strengthening evidence for a gateway effect (i.e., an opening to the use of other drugs) (Fergusson et al., 2006). The uncertainty of the causal mechanism is reflected in the fact that the gateway studies cannot disentangle the effect of the drug itself from its status as an illegal good (Babor et al., 2010).

The federal government probably spends $20 billion per year on a wide array of interventions to try to reduce drug consumption in the United States, from crop eradication in Colombia to mass media prevention programs aimed at preteens and their parents. 1 State and local governments spend comparable amounts, mostly for law enforcement aimed at suppressing drug markets. 2 Yet the available evidence, reviewed in detail in this report, shows that drugs are just as cheap and available as they have ever been.

Though fewer young people are starting to use drugs than in some previous years, for each successive birth cohort that turns 21, approximately half have experimented with illegal drugs. The number of people who are dependent on cocaine, heroin, and methamphetamine is probably declining modestly, 3 and drug-related violence has appears to have declined sharply. 4 At the same time, injecting drug use is still a major vector for HIV transmission, and drug markets blight parts of many U.S. cities.

The declines in drug use that have occurred in recent years are probably mostly the natural working out of old epidemics. Policy measures— whether they involve prevention, treatment, or enforcement—have met with little success at the population level (see Chapter 4 ). Moreover, research on prevention has produced little evidence of any targeted interventions that make a substantial difference in initiation to drugs when implemented on a large scale. For treatment programs, there is a large body of evidence of effectiveness and cost-effectiveness (reviewed in Babor et al., 2010), but the supply of treatment facilities is inadequate and,

perversely, not enough of those who need treatment are persuaded to seek it (see Chapter 4 ). Efforts to raise the price of drugs through interdiction and other enforcement programs have not had the intended effects: the prices of cocaine and heroin have declined for more than 25 years, with only occasional upward blips that rarely last more than 9 months (Walsh, 2009).

STUDY PROJECT AND GOALS

Given the persistence of drug demand in the face of lengthy and expensive efforts to control the markets, the National Institute of Justice asked the National Research Council (NRC) to undertake a study of current research on the demand for drugs in order to help better focus national efforts to reduce that demand. In response to that request, the NRC formed the Committee on Understanding and Controlling the Demand for Illegal Drugs. The committee convened a workshop of leading researchers in October 2007 and held two follow-up meetings to prepare this report. The statement of task for this project is as follows:

An ad hoc committee will conduct a workshop-based study that will identify and describe what is known about the nature and scope of markets for illegal drugs and the characteristics of drug users. The study will include exploration of research issues associated with drug demand and what is needed to learn more about what drives demand in the United States. The committee will specifically address the following issues:

What is known about the nature and scope of illegal drug markets and differences in various markets for popular drugs?

What is known about the characteristics of consumers in different markets and why the market remains robust despite the risks associated with buying and selling?

What issues can be identified for future research? Possibilities include the respective roles of dependence, heavy use, and recreational use in fueling the market; responses that could be developed to address different types of users; the dynamics associated with the apparent failure of policy interventions to delay or inhibit the onset of illegal drug use for a large proportion of the population; and the effects of enforcement on demand reduction.

Drawing on commissioned papers and presentations and discussions at a public workshop that it will plan and hold, the committee will prepare a report on the nature and operations of the illegal drug market in the United States and the research issues identified as having potential for informing policies to reduce the demand for illegal drugs.

The committee drew on economic models and their supporting data, as well as other research, as one part of the evidentiary base for this

report. However, the context for and content of this report were informed as well by the general discussion and the presentations in the workshop. The committee was not able to fully address task 2 because research in that area is not strong enough to give an accurate description of consumers across different markets nor to address the questions about why markets remain robust despite the risks associated with buying and selling. The discussion at the workshop underscored the point that neither the available ethnographic research nor the limited longitudinal research on drug-seeking behavior is strong enough to inform these questions related to task 2. With regard to task 3, the committee benefitted considerably from the paper by Jody Sindelar that was presented at the workshop and its discussion by workshop participants.

This study was intended to complement Informing America’s Policy on Illegal Drugs: What We Don’t Know Keeps Hurting Us (National Research Council, 2001) by giving more attention to the sources of demand and assessing the potential of demand-side interventions to make a substantial difference to the nation’s drug problems. This report therefore refers to supply-side considerations only to the extent necessary to understand demand.

The charge to the committee was extremely broad. It could have included reviewing the literature on such topics as characteristics of substance users, etiology of initiation of use, etiology of dependence, drug use prevention programs, and drug treatments. Two considerations led to narrowing the focus of our work. The first was substantive. Each of the topics just noted involves a very large field of well-developed research, and each has been reviewed elsewhere. Moreover, each of these areas of inquiry is currently expanding as a result of new research initiatives 5 and new technologies (e.g., neuroimaging, genetics). The second consideration was practical: given the available resources, we could not undertake a complete review of the entire field.

Thus, we decided to focus our work and this report tightly on demand models in the field of economics and to evaluate the data needs for advancing this relatively undeveloped area of investigation. That is, this area has a relatively shorter history of accumulated findings than the more clinical, biological, and epidemiological areas of drug research. Yet it is arguably better situated to inform government policy at the national level. A report on economic models and supporting data seemed to us more timely than a report on drug consumers and drug interventions.

The rest of this chapter briefly lays out some concepts that provide a basis for understanding the committee’s work and the rest of the report.

Chapter 2 presents the economic framework that seems most useful for studying the phenomenon of drug demand. It emphasizes the importance of understanding the responsiveness of demand and supply to price, which is the intermediate variable targeted by the principal government programs in the United States, namely, drug law enforcement. Chapter 3 then examines changes in the consumption of drugs and assesses the various indicators that are available to measure that consumption. Chapter 4 turns to the program type that most focuses specifically on reducing drug demand, the treatment of dependent users. It considers how well these programs work and how the treatment system might be expanded to further reduce consumption. Finally, Chapter 5 presents our recommendations for how the data and research base might be built to improve understanding of the demand for drugs and policies to reduce it.

PROGRAM CONCEPTS

A standard approach to considering drug policy is to divide programs into supply side and demand side. This approach accepts that drugs, as commodities, albeit illegal ones, are sold in markets. Supply-side programs aim to reduce drug consumption by making it more expensive to purchase drugs through increasing costs to producers and distributors. Demand-side programs try to lower consumption by reducing the number of people who, at a given price, seek to buy drugs; the amount that the average user wishes to consume; or the nonmonetary costs of obtaining the drugs. This approach has value, but it also raises questions.

The value of this framework is that it allows systematic evaluation of programs. A successful supply-side program will raise the price of drugs, as well as reduce the quantity available, while a demand-side program will lower both the number of users and the quantity consumed, as well as eventually reducing the price. As noted above, this report is primarily focused on improving understanding of the sources of demand.

There are two basic objections to this approach. First, some programs have both demand- and supply-side effects. Since many dealers are themselves heavy users, drug treatment will reduce supply, just as incarceration of drug dealers lowers demand. Second, there is a collection of programs that do not attempt to reduce demand or supply; rather, their goal is to reduce the damage that drug use and drug markets cause society, which are generally referred to as “harm-reduction” programs (Iversen, 2005; National Institute on Drug Abuse, 2010). 6 Nonetheless, the classifi-

cation of interventions into demand reduction and supply reduction is a very helpful heuristic for policy purposes, as well as being written into the legislation under which the Office of National Drug Control Policy operates.

What determines the demand for drugs? Clearly, many different factors play a role: cultural, economic, and social influences are all important. At the individual level, a rich set of correlates have been explored, either in large-scale cross-sectional surveys (such as the National Survey on Drug Use and Health and the National Household Survey on Drug Abuse) or in small-scale longitudinal studies (see, e.g., Wills et al., 2005). Below we briefly summarize the complex findings of those studies.

Less has been done at the population level. It is known that rich western countries differ substantially in the extent of drug use, in ways that do not seem to reflect policy differences. For example, despite the relatively easy access to marijuana in the Netherlands, that nation has a prevalence rate that is in the middle of the pack for Europe, while Britain, despite what may be characterized as a pragmatic and relatively evidence-oriented drug policy, has Europe’s highest rates of cocaine and heroin addiction (European Monitoring Center for Drugs and Drug Addiction, 2007). There is only minimal empirical research that has attempted to explain those differences. Similarly, there is very little known about why epidemics of drug use occur at specific times. In the United States, for example, there is no known reason for the sudden spread of methamphetamine from its long-term West Coast concentration to the Midwest that began in the early 1990s. There are only the most speculative conjectures as to the proximate causes.

A DYNAMIC AND HETEROGENEOUS PROCESS

The committee’s starting point is that drug use is a dynamic phenomenon, both at the individual and community levels. In the United States there is a well-established progression of use of substances for individuals, starting with alcohol or cigarettes (or both) and proceeding through marijuana (at least until recently) possibly to more dangerous and expensive drugs (see, e.g., Golub and Johnson, 2001). Such a progression seems to be a common feature of drug use, although the exact sequence might not apply in other countries and may change over time. For example, cigarettes may lose their status as a gateway drug because of new restrictions on their use. 7 Recently, abuse of prescription drugs has emerged as a possible gateway, with high prevalence rates reported for youth aged 18-25;

however, because of limited economic research on this phenomenon, this report’s focus is on completely illegal drugs.

At the population level, there are epidemics, in which, like a fashion good, a new drug becomes popular rapidly in part because of its novelty and then, often just as rapidly, loses its appeal to those who have not tried it. For addictive substances (including marijuana but not hallucinogens, such as LSD), that leaves behind a cohort of users who experimented with the drug and then became habituated to it.

An important and underappreciated element of the demand for illegal drugs is its variation in many dimensions. For example, the demand for marijuana may be much more responsive to price changes than the demand for heroin because fewer of those who use marijuana are drug dependent (Iversen, 2005; National Institute on Drug Abuse, 2010). Users who are employed, married, and not poor may be more likely to desist than users of the same drug who are unemployed, not part of an intact household, and poor. There may be differences in the characteristics of demand associated with when the specific drug first became available in a particular community, that is, whether it is early or late in a national drug “epidemic.”

There are also unexplained long-term differences in the drug patterns in cities that are close to each other. In Washington, DC, in 1987 half of all those arrested for a criminal offense (not just for drugs) tested positive for phencyclidine, while in Baltimore, 35 miles away, the drug was almost unknown. Although the Washington rate had fallen to approximately 10 percent in 2009 (District of Columbia Pretrial Services Agency, 2009), it remains far higher than in other cities. More recently, the spread of methamphetamine has shown the same unevenness: in San Antonio only 2.3 percent of arrestees tested positive for methamphetamine in 2002; in Phoenix, the figure was 31.2 percent (National Institute of Justice, 2003). These differences had existed for more than 10 years.

The implication of this heterogeneity is that programs that work for a particular drug, user type, place, or period may be much less effective under other circumstances, which substantially complicates any research task. It is hard to know how general are findings on, say, the effectiveness of a prevention program aimed at methamphetamine use by adolescents in a city where the drug has no history. Will this program also be effective for trying to prevent cocaine use among young adults in cities that have long histories of that drug?

This report does not claim to provide the answers to such ambitious questions. It does intend, however, to equip policy officials and the public to understand what is known and what needs to be done to provide a more sound base for answering them.

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Despite efforts to reduce drug consumption in the United States over the past 35 years, drugs are just as cheap and available as they have ever been. Cocaine, heroin, and methamphetamines continue to cause great harm in the country, particularly in minority communities in the major cities. Marijuana use remains a part of adolescent development for about half of the country's young people, although there is controversy about the extent of its harm.

Given the persistence of drug demand in the face of lengthy and expensive efforts to control the markets, the National Institute of Justice asked the National Research Council to undertake a study of current research on the demand for drugs in order to help better focus national efforts to reduce that demand.

This study complements the 2003 book, Informing America's Policy on Illegal Drugs by giving more attention to the sources of demand and assessing the potential of demand-side interventions to make a substantial difference to the nation's drug problems. Understanding the Demand for Illegal Drugs therefore focuses tightly on demand models in the field of economics and evaluates the data needs for advancing this relatively undeveloped area of investigation.

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The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies

1 National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, 100191 Beijing, China

2 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 100191 Beijing, China

Yongbo Zheng

Muhammad zahid khan.

3 Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, 100871 Beijing, China

Fentanyl is a powerful opioid anesthetic and analgesic, the use of which has caused an increasing public health threat in the United States and elsewhere. Fentanyl was initially approved and used for the treatment of moderate to severe pain, especially cancer pain. However, recent years have seen a growing concern that fentanyl and its analogs are widely synthesized in laboratories and adulterated with illicit supplies of heroin, cocaine, methamphetamine, and counterfeit pills, contributing to the exponential growth in the number of drug-related overdose deaths. This review summarizes the recent epidemic and evolution of illicit fentanyl use, its pharmacological mechanisms and side effects, and the potential clinical management and prevention of fentanyl-related overdoses. Because social, economic, and health problems that are related to the use of fentanyl and its analogs are growing, there is an urgent need to implement large-scale safe and effective harm reduction strategies to prevent fentanyl-related overdoses.

Introduction

Fentanyl was first developed in 1960 by Paul Janssen as a potent opioid anesthetic and analgesic. At the time, fentanyl was the fastest-acting opioid discovered to date and more powerful than morphine (50–100 times) and heroin (30–50 times) 1 , 2 . Transdermal, intravenous, and transbuccal fentanyl administration and several other drugs with chemical structures that are similar to fentanyl have been developed, approved, and used for surgical anesthesia and the management of severe cancer pain and perioperative pain, eventually becoming the most often used synthetic opioid in clinical practice 3 – 5 . Since 1979, fentanyl and its analogs have been synthesized in laboratories and sold as heroin substitutes or mixed with other illicitly sourced drugs, leading to an increase in fentanyl-related overdose deaths 6 , 7 . Postmortem studies have consistently found pulmonary edema, congestion, and needle puncture sites in these victims. Based on data from the National Vital Statistics System, 599,255 drug overdose deaths occurred from 1979 to 2016 in the United States, and the overall mortality rate has seen exponential growth. Fentanyl-related overdose deaths predominantly occurred in the northeastern United States, mostly affecting younger people (20–40 years of age), and grew sharply since 2013 8 .

Rapid death from ingesting fentanyl has become increasingly more common. Its high potency, fast onset of action, and duration of the desired effect may be particularly important contributing factors to the higher risk of overdose deaths and social consequences 9 . Fentanyl has become a major contributor to cocaine-related fatal overdoses. The rate of fentanyl-related overdose deaths increased 55% between 2015 and 2017 in New York city 10 , 11 . Synthetic opioids are also increasingly detected in illicit supplies of heroin, methamphetamine, and counterfeit pills. Analysis of a sampling of 1 million unique patients’ urine drug test (UDT) specimens showed that positivity rates for fentanyl have increased by 1850% among cocaine positive UDT results and increased by 798% among methamphetamine-positive UDT results between January 2013 and September 2018 12 . This mixture may lead to the increases in cocaine-related and methamphetamine-related overdoses. Moreover, the number of fatal overdoses from synthetic opioids, primarily fentanyl and its analogs, was 19,547 in 2016 in the United States, and this rate increased by 88% per year from 2013 to 2016 13 – 16 . The incidence of heroin-related overdose deaths stabilized in 2017, whereas deaths that involved other synthetic opioids continued to increase 17 . Given the substantial individual and public health threats of this emerging problem, the present review summarizes the epidemic and evolution of illicit fentanyl use, its pharmacological mechanism of action, its adverse consequences, and the clinical management and prevention of fentanyl-related overdoses.

Epidemic and evolution of illicit fentanyl use

Fentanyl is currently approved and commonly used to treat breakthrough pain in cancer patients and various other clinical conditions that involve noncancer pain, such as postoperative pain. However, its potential for abuse and the rise in overdose deaths pose a serious challenge to public health 18 – 21 . Deaths that were attributable to illicit fentanyl use were first reported in the early 1980s and occurred sporadically in the United States 6 , 7 , 22 . A surge in the occurrence of fentanyl-related fatalities among illicit drug users occurred in 2006. A total of 1013 deaths in six states occurred from April 4, 2005, to March 28, 2007 23 . Since then, the prevalence of opioid-related mortality has increased persistently, and the number of reported fentanyl-related deaths more than doubled (from 2628 to 5544) between 2012 and 2014 21 , 24 , 25 . The rate of fentanyl-related overdose deaths increased from <15% in 2010 to ~50% in 2017 in Marion County, Indiana 26 . Overall overdose deaths and first-responder calls increased in a community-based sample in an impoverished neighborhood in Vancouver, Canada, in 2017, and fentanyl was detected in 52% of the subjects who were prescribed opioid agonist therapy 27 . At the same time, fentanyl-related deaths also increased in Australia 28 , 29 .

The presence of fentanyl and its analogs has become a central contributor to the increase in the number of opioid-related overdose deaths. Preliminary estimates of opioid overdose deaths in the United States in 2016 revealed that fentanyl and its analogs (e.g., acetylfentanyl, furanylfentanyl, and carfentanil) have contributed to nearly half of opioid overdose deaths 16 , 30 , 31 . Moreover, the number of deaths that were attributable to illicitly manufactured fentanyl and its analogs nearly quadrupled between July 2015 and June 2017 in Montgomery County, Ohio 32 . Heroin-positive cases declined while methamphetamine-positive cases increased in these victims. Urine drug screens showed that the prevalence of recent fentanyl use in patients who received opioid agonist treatment in England was 3%, and multiple fatalities with synthetic fentanyl analogs were reported in northern England in early 2017 33 , 34 .

Fentanyl is ~30–50 times more potent than heroin, and smaller volumes of heroin and other drugs that are adulterated with fentanyl can produce powerful effects with lower production costs. Detecting fentanyl and its analogs in used syringes can reveal exposure risk 35 . The fentanyl detection rate was significantly higher among drug users who injected drugs in the past 6 months compared with non-injection drug users. The prevalence of non-fatal overdose is very high among people who inject drugs 36 – 38 . The prevalence of intravenous fentanyl use among people who inject drugs in Australia is 8%. Given the narrow range between effective and lethal doses, this population is at high risk of overdose 37 , 39 , 40 . The opioid crisis is likely attributable to illicitly manufactured fentanyl and its analogs around the world, especially when they are mixed with heroin and other drugs, and the route of administration 41 , 42 .

Many people who have survived fentanyl overdose appear to be unaware that they ever took the drug. Surveys from 17 harm reduction sites in British Columbia, Canada, revealed that the prevalence of fentanyl use was 29% (70/242; based on urine drug screen), 73% of whom report that they did not knowingly use fentanyl 43 . Urine drug screens in methadone-maintained patients in Wayne County, Michigan, showed that 38% of 368 unique patients tested positive for fentanyl, and 67.3% of 113 patients reported that they did not know anyone who sought to obtain fentanyl in a subsequent anonymous survey 44 . A high risk of overdose and deaths was found among this vulnerable population that exhibited high fentanyl exposure, thus highlighting the pressing need to develop appropriate harm-reduction strategies, such as surveillance, the development of early-warning systems, pill-testing technology about the presence of fentanyl in various drug products, naloxone training and distribution, overdose education, and urine screens 21 , 45 , 46 . The vast majority of people reported their willingness to use rapid test strips to detect the presence of fentanyl in drugs or urine at home or utilize drug-checking services at supervised injection clinics 47 , 48 . Multiplex ultrahigh-performance liquid chromatography (UHPLC–MS)/liquid chromatography tandem mass spectrometry (LC–MS–MS)/liquid chromatography–quadrupole time-of-flight–mass spectrometry (LC–QTOF–MS) analyses have also been developed and validated for the detection of fentanyl and its analogs and metabolites in blood, hair, and oral fluid, which will be helpful for informing harm reduction behaviors and combating the fentanyl crisis 49 – 52 . A newly developed lateral flow immunoassay was also evaluated for effectiveness in the detection of fentanyl analogs 53 .

Pharmacological mechanisms and side effects of fentanyl

Despite the beneficial clinical anesthetic and pain-relieving effects of fentanyl, the frequent use of fentanyl primarily affects the central nervous system (CNS) and gastrointestinal, cardiovascular, and pulmonary systems and can cause several side effects 54 . Digestive symptoms, such as nausea, vomiting, and constipation, are common in patients who repeatedly use fentanyl 55 , 56 . Immunosuppression was also shown to be precipitated by analgesic opioid drugs, including fentanyl, in preclinical and clinical studies. Such immunosuppression can be especially dangerous in the elderly and already immunocompromised patients 57 – 59 . Additionally, fentanyl and synthetic opioids have other frequently reported side effects, including migraine, dizziness, vertigo, confusion, hallucinations, and a higher risk of fractures in the elderly 59 – 63 . Fentanyl has rewarding effects and thus high abuse potential. Its repeated use leads to the development of tolerance and drug dependence 64 , 65 . Analyses of adverse-event reporting systems in the United States, Europe, and the United Kingdom have shown that cases of fentanyl-related misuse, abuse, dependence, and withdrawal steadily increased between 2004 and 2018, resulting in prolonged hospitalization or death 66 . Other mental disorders, such as depression, insomnia, and suicidality, can also occur with fentanyl abuse, contributing to relapse and a higher risk of respiratory depression or overdose death 65 , 67 . The treatment of these mental disorders may help prevent fentanyl-related fatalities and achieve abstinence.

Fentanyl is a full μ-opioid receptor agonist, but it also acts on δ- and κ-opioid receptors 68 , 69 . Fentanyl has been shown to exert its analgesic and lethal effects through different receptor populations in the CNS. It is eliminated from cerebrospinal fluid at approximately the same rate as morphine 70 , 71 . Acute naloxone administration antagonizes fentanyl-induced analgesia more than fentanyl-induced lethality. β-funaltrexamine was shown to inhibit both fentanyl-induced analgesia and lethality 71 . Overdose-related concentrations of fentanyl were shown to block human ether-a-go-go-related gene (hERG) potassium channels in ventricular myocytes that were isolated from neonatal rats, which may contribute to fentanyl-related overdose death or sudden death 72 .

Respiratory depression is the most dangerous adverse reaction to fentanyl that can result in lethality. In rats, intravenous injections of fentanyl dose-dependently decreased oxygen levels in the nucleus accumbens, basolateral amygdala, and subcutaneous space, followed by a delayed increase in glucose and fluctuations in brain temperature and metabolic brain activity 73 – 75 . Neuronal hypermetabolism that is induced by fentanyl and its analogs may damage the hippocampus and limbic system, causing an amnestic syndrome in patients who use fentanyl 76 – 79 . With regard to brain hypoxia and hypothermia, fentanyl has synergistic effects with heroin, which is consistent with the higher risk of overdose death that is associated with heroin–fentanyl mixtures 73 , 80 . Fentanyl-related respiratory depression is also dose-dependent, which reaches a peak 5 min after administration and requires 4 h to recover in humans. Such effects can lead to prolonged apnea and sudden death 74 , 81 , 82 . Epidural fentanyl infusion has been shown to cause postoperative adult respiratory distress syndrome 83 . The μ 1 -opioid receptor is involved in respiratory depression that is induced by fentanyl and its analogs but not morphine 84 . Selective α4β2 nicotinic receptor agonist A85380 reversed fentanyl-induced respiratory depression in rats without significant side effects 85 . The calcium-activated potassium channel blocker GAL021 was shown to attenuate morphine-induced respiratory depression in rats, mice, and nonhuman primates, and it produced stimulatory effects during alfentanil-induced respiratory depression, without affecting sedation in humans 86 – 88 . However, more studies are needed to confirm the efficacy and potential toxicity of A85380 and GAL021.

Many studies have reported cardiovascular symptoms after fentanyl-induced analgesia, such as myocardial ischemia, QTc interval prolongation, and bradycardia 89 – 91 . Fentanyl is commonly used during percutaneous coronary interventions, but the relative safety of its use requires further investigation because intravenous fentanyl has been reported to induce hypothermia, impair ticagrelor absorption, and cause antiplatelet effects 92 – 94 . Autopsy and toxicological analyses indicated that chronic fentanyl use may be responsible for hypertrophy, cardiac fibrosis, and atherosclerosis 54 , 95 , 96 . Neither sigma nor opioid receptors are essential for the fentanyl-induced attenuation of muscarinic coronary contraction 97 .

Fentanyl administration provides effective pain relief, but its long-term use can result in a lowering of pain thresholds 98 , 99 . This phenomenon of fentanyl-induced hyperalgesia is a challenge in the clinical management of perioperative and chronic pain. Recent studies showed that fentanyl-induced hyperalgesia was modulated by the activation of extracellular signal-regulated kinase in the laterocapsular division of the central nucleus of the amygdala (CeLC) and CaMKIIα in the CeLC–periaqueductal gray–rostral ventromedial medulla–spinal cord descending facilitative pain pathway in rats 100 , 101 .

Interventions for the management and prevention of fentanyl overdose

Similar treatments are prescribed for opioid use disorder and opioid overdose, including the Food and Drug Administration (FDA)-approved medications methadone, buprenorphine, extended-release naltrexone, and naloxone 102 . Lofexidine, a central α 2 -adrenergic receptor agonist, was the first non-opioid medication that was approved by the United States FDA for the treatment of opioid withdrawal 103 , 104 . Lofexidine has fewer prescriptive barriers and comparable efficacy and safety relative to other opioid receptor agonizts, but it is generally more expensive. Sparse data are available on the effectiveness of interventions to prevent overdoses that are caused by illicitly manufactured fentanyl (Table ​ (Table1). 1 ). Compared with other opioid-related overdoses, illicit fentanyl-related overdoses appear to be accompanied by distinct symptoms, such as body and chest rigidity, dyskinesia, and slow or irregular heart rate, which can affect overdose management, such as oxygen provisions and appropriate doses of naloxone 105 , 106 . To avoid or reduce the adverse effects of fentanyl, the FDA proposed to control the duration of use and doses of fentanyl 107 . One study showed that the majority of patients who were presumed to experience fentanyl overdose could be discharged after brief emergency room observation, thus unlikely requiring additional naloxone dosing in the emergency room 108 .

Overview of medications for the treatment of opioid use disorder and potential implications for the treatment of fentanyl overdose

MOR μ-opioid receptor, KOR κ-opioid receptor, OU D opioid use disorder

There are limited data on the efficacy of methadone or buprenorphine for the treatment of illicit fentanyl use. A retrospective study in Rhode Island showed that 6 months of methadone maintenance protected against death and promoted abstinence in fentanyl-exposed patients, but relapse rates were still high 109 . Buprenorphine is a μ-opioid receptor partial agonist and κ-opioid receptor antagonist that is commonly used to treat opioid use disorder. It also exerts antidepressant and anxiolytic activity and is a promising treatment for neonatal opioid withdrawal syndrome 110 . A retrospective cohort study showed that 6-month treatment retention rates and opioid abstinence rates were not different between individuals who were positive for fentanyl or heroin at baseline before initiating buprenorphine treatment, indicating that buprenorphine may still be beneficial for treating fentanyl exposure 111 . Repeated treatment with buprenorphine produced a greater magnitude of antinociceptive tolerance than higher-efficacy agonizts (e.g., morphine and etonitazene) in rats 112 . Studies in pigeons and rhesus monkeys showed that the amount of tolerance that develops to the reinforcing potency of opioids depends on their efficacy, and the higher-efficacy μ-opioid receptor agonist sufentanil was more difficult to antagonize than the low-efficacy μ-opioid receptor agonist morphine 113 – 115 . These data indicate that buprenorphine may have lower efficacy for the treatment of fentanyl overdose compared with heroin overdose, although no human trials have been performed to date 116 .

Naloxone is a μ-opioid receptor antagonist that is used to treat fentanyl-related overdose, regardless of the suspected route of administration. However, its efficacy is inconsistent, and safe dosing needs to be considered from the perspective of precipitating opioid withdrawal 117 – 119 . Recent studies also showed that extended-release naltrexone was equally safe and effective as a buprenorphine–naloxone combination at promoting abstinence and treatment retention once treatment was initiated, but fewer participants successfully initiated naltrexone treatment 120 , 121 . Larger or repeated doses of naloxone are speculated to be required for the treatment of fentanyl overdose because of its higher affinity for μ-opioid receptors. However, a study of a community naloxone distribution program in Allegheny County showed that the average doses of naloxone that were administered to reverse overdose did not change between 2013 and 2016, although the incidence of overdoses that were related to fentanyl and its analogs increased during the same time 122 . A retrospective study of the fentanyl epidemic in Chicago showed that doses of naloxone up to 12 mg may effectively treat fentanyl overdose 123 . Naloxone was shown to reverse transdermal fentanyl overdose-induced sedation, the reduction of body temperature, and the reduction of heart rate in dogs 124 . A systematic review found a low incidence of mortality or serious adverse events that were caused by prehospital naloxone administration in opioid overdose patients, although the source of overdose was mostly heroin and not fentanyl 125 . Additionally, seeking emergency medical help was positively associated with overdose victims who received higher doses of naloxone and rescue breathing in British Columbia, Canada 126 . A survey of 316 street-recruited people who used opioids in Baltimore showed that the majority of them perceived the high risk of fentanyl-adulterated heroin and overdose, but most of them did not often carry naloxone with them 127 . The early adoption and distribution of take-home naloxone have been reported to effectively prevent opioid overdose deaths 128 – 130 . Therefore, harm reduction strategies, such as safe injection sites, the expansion of available opioid agonist treatment, and overdose prevention training (e.g., carrying naloxone and not use drugs alone, higher dose or multiple administrations of naloxone), are needed to control the adverse effects of fentanyl and reduce overdoses 131 .

Additionally, more potent, longer-acting opioid receptor antagonists are needed to prevent fentanyl-related overdose deaths. Compared with naloxone, nalmefene has been shown to have superior efficacy in reversing the carfentanil-induced loss of righting reflex and respiratory depression in rats 132 . Nalmefene is generally well tolerated and is a recent option for patients with alcohol dependence 133 – 135 . Additionally, novel, selective, and potent μ-opioid receptor antagonists, such as 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ) and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN), have been reported to produce less opioid tolerance, dependence, and withdrawal signs. Furthermore, NAN pretreatment was shown to block the discriminative stimulus effects of fentanyl in rats. The orexin-1 receptor antagonist SB-334867 was also shown to decrease motivation and demand for fentanyl in rats 136 . Therefore, these drugs could be considered candidates for the treatment of opioid use disorder 137 . Chronic anticonvulsant carbamazepine therapy was shown to increase fentanyl clearance and decrease plasma concentrations in neurosurgical patients, which may attenuate the actions of fentanyl 138 . A case report showed that treatment with slow-release oral morphine in a near-fatal fentanyl overdose patient was successful, despite the patient’s previous failures with methadone and buprenorphine/naloxone-based opioid agonist therapies, which could be considered potential alternative treatments 139 .

Previous studies have reported the vaccine consisting of fentanyl hapten conjugated to tetanus toxoid or keyhole limpet hemocyanin carrier protein, and immunization with these vaccines reduced fentanyl biodistribution to the brain, and blunted its antinociceptive effects and respiratory depression in rodents 140 , 141 . Moreover, the conjugate vaccine stimulated the endogenous generation of antibodies with high affinity for a variety of fentanyl analogs 140 , and was shown to blunt fentanyl reinforcement 142 . A recent study screened and purified monoclonal antibodies (mAbs) from vaccinated mice, and found that the 6A4 mAb prevented the acute lethality of fentanyl, and reversed both fentanyl and carfentanil-induced antinociception as effective as naloxone 143 . These findings suggest that immunopharmacotherapies including active vaccine or its combination with passive mAb may be potential and promising treatment strategies to address the current opioid crisis. Accumulating evidence also implicate the dysbiosis of gut microbiome in the pathophysiology of drug addiction, however data regarding fentanyl use is rare 144 . Manipulating the compositions of the gut microbiome or its products may guide new adjuvant therapies for opioid addiction in the future.

A United States FDA Risk Evaluation and Mitigation Strategy (REMS) program was also implemented to assess transmucosal immediate-release fentanyls (TIRFs) and found that substantial rates of TIRFs were prescribed inappropriately 145 , 146 . With the findings of deficiencies in the structure and administration of TIRFs, the development of other REMSs is needed to ensure the safe and appropriate use of approved drugs, especially dangerous opioid drugs 147 .

In conclusion, the crisis of opioid-related overdoses, especially fentanyl and its analogs, is a major threat to both individual and public health. Respiratory depression, cardiovascular effects, and neuropsychiatric symptoms are associated with fentanyl overdose and lethality. Naloxone is the standard rescue drug for fentanyl overdose, but its efficacy is inconsistent. Further clinical research is needed to optimize individualized medication-assisted treatments in patients who overdose on fentanyl and its analogs. To address the social, economic, and health problems that are associated with fentanyl and its analogs, coordinated efforts are needed to implement large-scale harm reduction strategies (e.g., naloxone distribution, innovative studies, and the development of novel drugs).

Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (nos. 81701312 and 81521063).

Conflict of interest

The authors declare that they have no conflict of interest.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

• Open access
• Published: 14 March 2023

Illicit drug use in university students in the UK and Ireland: a PRISMA-guided scoping review

• Maeve Boden 1 &

Substance Abuse Treatment, Prevention, and Policy volume  18 , Article number:  18 ( 2023 ) Cite this article

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Interest in the health and well-being of university students has increased in the UK and Ireland in the past two decades as their numbers have grown. Recent high-profile deaths of students after using illicit drugs have highlighted the importance of the topic for policy makers. This scoping review maps the state of the existing literature evaluating use of illicit drugs in university students in the UK and Ireland. It aims to highlight research gaps and inform policy.

We conducted a systematic search of papers related to psychoactive drug use in university students in the UK and Ireland published before August 2021. The 18 extracted study characteristics included author(s); year of publication; journal; location of data collection; study design; delivery method (e.g., online survey, in-person, postal survey); number of participants; response rate; participant course of study, year of study, degree level (i.e., undergraduate, postgraduate), gender and age; time-period assessed (e.g., lifetime, current use, past 12 months); primary aim; primary outcome; ethical approval; and funding source.

The PRISMA-guided search strategy identified 1583 papers for abstract review; of 110 papers retained for full-text review, 54 studies met criteria for inclusion for this paper. Primary outcomes were coded into five groups: prevalence and patterns of drug use; factors associated with drug use; attitudes and knowledge about, and motivation for, drug use; supply of drugs; consequences of drug use. The results show that there is no coherent body of research in this area. The prevalence of reported drug use has crept up and the range of substances reported has broadened over time, and attitudes to drugs on average have normalised. However, there are significant methodological limitations that limit the utility of these findings. There was little evidence of published work on prevention of, or intervention to reduce, drug-related harms.

The domains identified offer a framework for university administrators, researchers and policy makers to understand the potential response to drug use in university students in the UK and Ireland. Recommendations are made to fill the gaps in the research evidence base.

Illicit drugs are psychoactive substances whose non-medical use has been banned by international drug control treaties as they are believed to pose an unacceptable risk to the health of people that use them [ 1 ]. Prospective cohort studies in high-income countries consistently show that adolescence is the peak period for first illicit drug use, and levels and frequency of use begin to increase in mid-adolescence and peak in early adulthood before slowly declining with age [ 2 , 3 ]. This is consistent with the latest figures available for England and Wales, which relate to trends in drug use for the year ending March 2020 [ 4 ]. Approximately 1 in 5 (21%) young adults aged 16–24 years had taken an illicit drug in the last year (1.3 million people) compared with 1 in 11 (9.4%) adults aged 16–59 years. Furthermore, twice as many young adults had taken a drug more than once a month in the last year. Cannabis was the most common drug used by 16–24 year olds (18.7%).

Illicit drug use in young adults tends to be more experimental and opportunistic than in older age groups, but some young adults start to use drugs more frequently and a small number progress to regular use and dependence. Degenhardt and colleagues have described the epidemiology of illicit drug use in young people (defined as 10–24 years old) around the world, the harms that they cause, and the potential responses available to reduce these harms [ 2 , 5 , 6 ]. Variations in patterns of drug use initiation between countries and cultures suggests that a young person’s entry into illicit drug use may reflect their personal characteristics, illicit drug availability, and social settings that facilitate or deter drug use [ 2 ].

Illicit drug use appears to be a common but infrequent activity amongst university students. In the UK most students start university at the age of 18 or 19, and it was reported in 2017/18 that a record 50.2% of English 17- to 30-year-olds had participated in higher education. This coincides with a period often known as ‘emerging adulthood’, commonly defined as the period between the end of compulsory schooling and the onset of adult commitments such as employment, long-term sexual relationships and parenthood [ 7 ].

During this period most students live away from home for the first time and so become more financially independent and self-reliant as a consequence. New friends are made and old friends from school are left behind, as the individual begins to forge a new adult identity away from parental influence. Peer and romantic interactions become more important, and there is a need to be more self-directed in terms of time management. The university can therefore be seen as a specific ‘risk environment’ [ 8 ], where cultural and environmental factors including distance from parents and the interconnected nature of student life can accelerate trajectories from drug experimentation to more involved drug use [ 9 ]. In this transitional phase, experimentation with drugs may be seen as a normative behaviour by students that helps them to develop new social relationships, enhance new experiences or to boost academic or recreational performance [ 7 , 10 ].

A national survey of 2810 students in the UK in 2018 reported that 56% of respondents had used drugs, and 39% currently used them [ 11 ]. Cannabis was the most frequently taken drug (94% of respondents who said that they had used drugs) and was the most likely to have been used regularly. However, ecstasy, nitrous oxide and cocaine had all been used by most of the drug-using population at some point. Large scale North American surveys show that the annual prevalence of illicit substance use in university student populations has grown gradually from 34% in 2006, to 43% in 2018 [ 12 ]. The US national Monitoring the Future follow-up study reported that the annual prevalence in cannabis use in university students was at a historic high level, with a 5-year trend from 2014–2019 showing a significant 8.6% increase [ 12 ].

The 2017 Government Drug Strategy in England emphasised that Colleges and Universities had an important role to play in supporting the health and welfare of their students [ 13 ] (p9). Likewise, when the Irish Government convened a Rapid Response Group in September 2019 to address illicit drug use in higher education institutions (HEIs) it noted that HEIs “ can assist in addressing the hazards of illicit drug use by implementing actions that have the potential to reduce the number of students who decide to use drugs in the first place, or to reduce the harm experienced by those students who have chosen to use drugs ” [ 14 ]. However, there has been relatively little research on the incidence and prevalence of drug use in UK or Irish university student populations. Previous reviewers have noted methodological shortcomings, including small sample sizes and/or a narrow focus on students from a single university or even a single department [ 15 , 16 ]. It is not clear whether student attitudes to drugs differ from their non-student peers, or whether they have changed over time. There is also a lack of consensus on the extent of drug-related harms and the most effective strategies to reduce them if necessary. In early 2022 Universities UK (UUK) announced that it wished to set out a common approach to reduce harms from drug use and to better tackle supply [ 17 ]. They noted that some universities had the stated aim of a ‘drug-free campus’ whereas others had implemented harm reduction and treatment services.

A coherent body of research into illicit drug use by university students might be expected to explore the epidemiology of use, potential mechanisms of initiation, escalation and reduction in use, prevailing attitudes towards and beliefs about drugs, any potential benefits or harms resulting from use, and methods for detecting, preventing and treating problematic use. The existing evidence base in this area is built on research in North American university populations [ 18 , 19 ], but there are considerable differences between the USA and Europe in terms of the structure and funding of higher education, social and criminal justice systems, and the availability of treatment for substance use disorders. We therefore conducted a PRISMA-guided scoping review of the literature to answer the question ‘what is known from the existing literature about the use of illicit drugs by university students in the UK and Ireland?’. Scoping reviews aim to be comprehensive but with a focus on identifying gaps in the literature to inform policy. As such, they provide an overview of the research in an area of study but without an in-depth consideration of research quality [ 20 ]. The process involves identifying an initial research question, searching for and selecting relevant studies, and collating, charting, summarizing, and reporting the data [ 21 ]. This review is the first attempt to identify gaps in the evidence base to guide future research, policy and practice in identifying and reducing the potential harm of illicit psychoactive drug use in university students in the UK and Ireland.

In line with scoping review guidance, we first considered the concept (what is known about illicit drug use), target population (university students in the UK or Ireland), and. outcomes of interest (including epidemiology, mechanisms of initiation, escalation and reduction in use, attitudes and beliefs about drugs, benefits or harms of use, and methods for detecting, preventing and treating problematic use) to clarify the focus of the scoping study [ 20 , 22 ]. A search strategy was developed in line with our overarching question, and three electronic databases were searched in July 2021 to identify published papers: MEDLINE, PsycINFO and Web of Science. Search terms including ‘United Kingdom’, ‘Ireland’, ‘student’, ‘university’ and drug use’ were used (see Supplementary file 1 for a full list of search strings). The search terms were broad to be as comprehensive as possible. The reference lists of the included papers were searched and experts in the field contacted to identify any further evidence. The electronic databases EThOS and OpenGrey were used to search for unpublished evidence. Following the guidance for a systematic search created by the Canadian Agency for Drugs and Technology in Health [ 23 ], a general Google search was completed and the first 50 results were screened. There were no restrictions imposed on the date of publication, but due to time and cost restraints only English language papers were included.

Study selection

The search produced 1583 potential papers for inclusion. The inclusion and exclusion criteria were formulated as an iterative process once the breadth of the literature was understood. Systematic reviews and literature reviews were excluded but reference lists were searched. Primary studies were not excluded based on their design, and both quantitative and qualitative research was included. Theses and student dissertations were included, but other unpublished literature was assessed separately. Studies that also included non-student participants or non-UK/Ireland-based universities were only included if the results were separated by population and the relevant data could be extracted. Papers discussing drug education in the university curriculum of healthcare professionals were excluded. The full search included papers that focussed on the use of drugs prescribed by a healthcare professional (even if used illicitly e.g. those used as ‘cognitive enhancers’). However, this report focuses on illicit drugs only (see data supplement 2 for excluded papers on the latter topic). If more than one report used duplicate data, the most comprehensive or relevant paper was included.

Two independent reviewers (MB and ED) undertook the study selection process. The titles of the records found in the search were screened and the relevant abstracts independently assessed, with any disagreements between reviewers resolved through discussion. Full-text papers were then obtained and reviewed. The reviewers met frequently to discuss challenges surrounding study selection and to ensure the search strategy was suitable. Papers that assessed any aspect of the use of illicit drugs conducted in the UK or Ireland were included. Figure  1 shows the process of study selection using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework [ 24 ]. The excluded papers are listed in Supplementary file 2 , along with the reasons for exclusion.

Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart

Data extraction

An iterative model was used to determine the study characteristics extracted [ 20 ]. Both researchers independently used a data-charting tool to extract study characteristics from the first five papers included, before meeting to discuss any difficulties and refine the variables to extract. The final characteristics recorded were [ 1 ] author, [ 2 ] year of publication, [ 3 ] journal, [ 4 ] location of data collection, [ 5 ] study design, [ 6 ] delivery method (e.g., online survey, in-person, postal survey), [ 7 ] participant number, [ 8 ] response rate, [ 9 ] participant course of study, [ 10 ] participant year of study, [ 11 ] participant degree level (i.e., undergraduate, postgraduate), [ 12 ] participant gender, [ 13 ] participant age, [ 14 ] time-period assessed (e.g., lifetime, current use, past 12 months), [ 15 ] primary aim [ 16 ] primary outcome (categorized into 6 groups: prevalence and patterns of drug use, risk and protective factors, consequences of drug use, attitudes and knowledge, motivations for drug use, source of drugs), [ 17 ] ethical approval, and [ 18 ] funding source. One researcher (MB) then extracted the 18 study characteristics from each included study and the other researcher independently reviewed the completed data-charting form, with any disputes resolved with discussion. Quality was not formally assessed but ethical approval and funding were used as crude proxies in line with scoping review guidance [ 25 ].

A review of the grey literature found eleven relevant papers, all of which focussed on the prevalence of drug use among university students. One was a survey conducted by the UK National Union of Students and a national charity providing expertise on drugs and the law (Release) [ 11 ], and a second was commissioned by the UK Higher Education Policy Institute from a professional surveying organisation (YouthSight) [ 26 ]. A third reported on a national student survey in Ireland, and the remainder were student newspaper reports. The largest survey was carried out by The Tab, an online magazine covering youth culture and student issues. This had 16,000 responses from students across the UK, but no information was provided on the sampling methodology used. None of these papers reported how they recruited participants or their demographic characteristics, and so these studies are not considered further in this review but are detailed in Supplementary file 2 .

Fifty-four peer-reviewed papers were included representing unique data from 50 separate studies, and 56 papers were excluded at the full-text review stage. These results are summarised in a PRISMA flowchart in Fig.  1 .

Study characteristics

Table 1 summarises the study characteristics. Since the 1980s the number of published papers has increased with each full decade, and almost half of the papers included in this review were published within the last 10 years. All four nations of the UK (England, Wales, Scotland, Northern Ireland) and the Republic of Ireland were represented. Five papers did not report their location within the UK, and only seven papers included universities in more than one country. English (44%) and Irish (19%) universities were the best represented. The majority (63%) of papers recruited participants from just one university, and only 3 (6%) recruited participants from 10 or more universities.

The subject that participants were studying varied, with 16 (30%) papers limiting the sample to a particular course or courses (usually medical, dental or nursing studies). The academic year of study of participants was recorded in 41 (76%) of the papers, and the choice of year group was usually decided pragmatically with no particular focus on students early or late in their course of study. The gender breakdown in the 43 (80%) papers that reported it was between 30 and 89% female. The mean age of the sample was reported in 21 (39%) papers and ranged between 18.8 and 24.9 years.

Study design

A clear majority of the studies had a cross-sectional design, with only 4 reporting data from more than one time point. Forty-seven papers (87%) reported a quantitative analysis, 4 (7%) reported a qualitative analysis and 3 (6%) used mixed methods. In those that employed mixed methods, cross-sectional data was used to inform later semi-structured interviews and open questionnaires. In the 51 papers where numerical data were collected, 36 (67%) used in-person interviews, 9 (17%) on-line data collection, 6 (11%) postal data collection and 1 analysed secondary data.

Ethical approval and funding source

Under half (23, 43%) of the papers reported that they had obtained ethical approval and the remainder did not report whether approval had been sought or not. Twelve of the papers reported funding from various sources including university funds, the British Medical Association, the Wellcome Trust and the Northern Regional Health Authority. The remainder either did not report whether funding was received or specified that there was no external funding for the project.

Drugs assessed

The drugs assessed in the papers were grouped into categories: a broad definition of illicit drugs (sometimes including prescription drugs used in an illicit way) (43, 80% of papers), cannabis only (8, 15%), and ecstasy only (3, 6%). Most papers included questions about drugs alongside alcohol and tobacco. Cannabis was the most reported drug under study, but the range of substances reported increased over time.

Primary and secondary outcome domains

The outcomes of the papers were coded into five categories, with papers that reported more than one outcome coded multiple times. Forty-one of the fifty-four papers (76%) reported the prevalence or pattern of drug use, 28 (52%) factors associated with drug use, 14 (26%) student attitudes towards, knowledge about, and motivations to use drugs, 6 (11%) information about the source and supply of drugs, and 7 (13%) the consequences of drug use. The included papers are categorised by outcome in Table 2 .

Prevalence or patterns of drug use

The 41 papers examining prevalence or patterns of illicit drug use collected data through either an in-person interview (29, 71%), a postal response (4, 10%), an online survey (7, 17%) or both in-person and online methods (1, 2%). The number of participants ranged from 47 to 7855, and 39 of the 46 (85%) samples reported included a percentage response rate ranging from 6 to 100%. The response rate varied by the method used to collect data (in-person 60–100%, postal 33–97%, online 6–33%, in-person and online 41%). In terms of participants recruited the online surveys had the most participants (mean of 3382 compared with mean of 765 in the in-person surveys and 430 in the postal surveys) but the lowest response rates (mean of 15.5% compared with 82.2% in-person and 68.5% postal). A range of time periods of drug use were assessed, including lifetime (35 papers), past year [ 13 ], past 6 months [ 2 ], past 3 months [ 1 ], past 3 months [ 1 ], past 30 days [ 1 ], past month [ 1 ], past 4 weeks [ 1 ], past week [ 3 ], ‘since starting degree’ [ 1 ], ‘current academic year’ [ 1 ] and ‘current’ [ 12 ]. There was a broad trend towards students reporting more experience of a wider range of illicit substances. However, the variability in participant samples, the methods used to collect the data, and the time periods of drug use considered meant that it was not possible to formally assess trends in drug use over time.

Factors associated with drug use

Twenty-eight papers (52%) assessed factors associated with drug use, and these are summarised in Table 3 . Many papers reported more than one associated factor. Twelve papers (22%) explored demographic variables, including age, gender, ethnicity, socioeconomic status, living circumstances and international student status. Eleven (20%) measured personality factors or mental health, including instruments measuring sensation seeking and anxiety. The link between health-related behaviours, including tobacco smoking, alcohol consumption and physical activity, and drug use was assessed in 11 (20%) papers. Other associations included academic course or year of study (8, 15%), attitudes to drug use and health awareness (3, 6%), normative beliefs (2, 4%), academic performance (2, 4%) and religious beliefs (2, 4%). No clear and consistent patterns of association could be drawn from the data.

Attitudes towards, knowledge about, and motivations to use illicit drugs

Fourteen papers assessed student attitudes towards drugs and/or their knowledge about their effects. Issues covered included the morality or ethics of drug use, safety beliefs, the perceived effect of drug use and perceived motivations for use. Early studies noted that attitudes to cannabis were markedly different to those towards tobacco or alcohol [ 27 ]. People that drank alcohol perceived that people that used cannabis were ‘definitely emotionally unstable’ and ‘definitely less able to cope with life’, whereas the latter group perceived that people that used illicit drugs in general were ‘more interested’ and ‘vested with more friends’. This attitudinal separation was hypothesised to be an effective ‘barrier’ to starting cannabis use.

By the late 1990s, papers were reporting that students that regularly used illicit drugs were similar to the general population of students both in their views about the causes of drug use and their personal and social characteristics [ 28 ]. Both students that used drugs and those that did not agreed that youth culture influences and sensation-seeking were the most endorsed reasons for drug taking. The illegality of drugs had little influence on levels of consumption [ 29 ]. Some support was found to support the idea that increasingly liberal views towards drugs would appear across a student’s time at university [ 30 ]. Although attitudes towards tobacco became less positive in year 3 when compared to starting university, there was no such change for illicit drugs. By the 2010s, students were shown to rate tobacco as most harmful to physical health, alcohol most harmful with regard to injuries and social consequences, and cannabis as most harmful with regard to mental health [ 31 ]. As the legal substance alcohol was rated as more harmful than the illegal substance cannabis, the authors hypothesised that young people in the years to come may be less supportive of a traditional drug policy based on criminalization [ 31 ].

By 2018, Patton’s survey found that the top three reasons for drug consumption were for fun or pleasure, for relaxation, and to enhance an activity [ 16 ]. These reasons were thought to fit with the ‘normalization’ hypothesis [ 32 ]. Depictions of drug use in the media were widespread, and 78% felt comfortable consuming media that featured drug use. There was also further evidence of the shift from drug use as a deviant activity into mainstream cultural arrangements (59% of abstainers had one or more close friends who use drugs) [ 16 ]. These results suggest that attitudes towards drugs may have changed over time amongst the student population, but the level of acceptance is not uniform or consistent between different substances in different populations.

The supply of illicit drugs

Six papers were concerned with the supply of drugs. An early study in the 1970s in Ireland found that most students were approached to buy drugs at parties, in pubs or hotels, or at clubs. Roughly half of students obtained their first drugs from friends [ 33 ]. A study in England in the 1990s also found that drugs were usually bought from friends and were most commonly consumed in other people’s rooms or at parties [ 29 ]. The authors contrasted this with alcohol which was consumed in bars or public places. More recently, a larger survey of 7 of the 9 universities in Wales found that half of the students that used drugs obtained them solely from friends and associates, and another 25% used friends and external markets [ 34 ]. In many cases supplying drugs amounted to sharing them or giving them away, but over a third said they had sold drugs. Drugs like nitrous oxide, cannabis, synthetic cannabinoids, ecstasy and magic mushrooms were usually sourced from friends, whereas other drugs (khat, crack, steroids, heroin) more likely to be bought. Male students were more likely to buy from dealers. The authors concluded that methods used by university students to obtain and supply drugs shared features of both ‘social supply’ and ‘traditional drug markets’ [ 34 ].

Moyle and Coomber also considered the nature of the supply of drugs in students. They conducted semi-structured interviews with 60 social suppliers of recreational drugs in two studies involving both a student population ( n  = 30) and a general population sample ( n  = 30) [ 9 , 35 ]. Both samples provided evidence that supplying drugs to, and receiving them from, friends and social contacts had become increasingly normalised and seen as less than ‘real dealing’ and more like gift-giving [ 35 ]. Early experiences of social supply occurred pre-university and usually involved a ‘one off’ act of sharing cannabis. However, once at university this had increased to ‘buying cannabis in bulk and selling excess amounts to friends, and/or purchasing ‘standard’ 3.5 g bags of powders like cocaine and MDMA on behalf of a group and retaining a quantity of the substance as payment’. This behaviour rarely continued when they returned home [ 9 ].

Consequences of drug use

Seven papers reported the consequences of drug use. Two studies surveyed consequences of any illicit drug [ 36 , 37 ], four focussed on cannabis [ 38 , 39 , 40 , 41 ] and one on ecstasy [ 42 ]. Two large online surveys collected data on physical and psychological effects of drugs and drug-related crime, providing a broad overview of a range of issues. In contrast studies utilising in-depth structured interviews with qualitative analysis explored the positive and negative effects of cannabis [ 39 ] and the effects of cannabis on driving [ 41 ]. One lab-based study examined cannabis-related impairments in prospective memory by comparing people that used cannabis and people that did not on both self-reported prospective memory failures and on an objective video-based prospective memory task [ 38 ]. Two studies used objective measures to quantify the consequences of drug use on mental health e.g., the Hospital Anxiety and Depression scale [ 40 , 42 ]. Overall, the positive effects of relaxation, mood elevation and enhanced creativity were balanced by negative effects such as forgetfulness, poor concentration, and reduced productivity. Impaired mental health was a common theme, including paranoia, moodiness, anxiety, irritability, confusion and dependence. Crime-related consequences included driving under the influence, antisocial behaviour and selling drugs [ 36 , 41 ].

This scoping review was conducted at a time when increasing attention was being paid to the issue of drug use in university students, and media reports about drug-related student deaths had prompted a government response in both the UK and Ireland. Universities UK, a body representing 140 Universities across the UK, formed a ‘Task Force’ to explore the issue of drugs on campus in early 2022 [ 17 ], with the stated aim of setting out ‘ a common approach to reduce harms from drug use and to better tackle supply’ . The aim of this scoping review was to map the breadth and depth of research into illicit drug use in university students in the UK and Ireland. In this paper our focus was on illicit drugs, and we excluded a growing body of work on the illicit use of prescribed stimulant medications as aids to studying (to be analysed elsewhere). We made no attempt to assess the quality of studies included, and do not claim to draw conclusions about the findings. However, the gaps in the resulting survey of research covering a period of over 50 years may help to guide policy makers and researchers in the UUK Task Force.

The epidemiology of drug use in university student populations

Monitoring student drug (and alcohol) use over time should be critical to the development of effective evidence-based policy and intervention strategies. High quality estimates can be used to identify trends and patterns, understand the direct and indirect harms of drug use, and guide further research to understand risk and protective factors for student drug use and the effectiveness of policy or treatment interventions. This review found that the prevalence of drug use was the most studied area in terms of number of published papers. However, as has been noted by other researchers [ 16 ], the existing UK/Irish research is methodologically limited. Most published studies reported prevalence of use, but the time window of assessment and the instruments used were variable. Studies including students from more than one university were the exception, and the population under study was often drawn from a single university department. It was rare for a paper to distinguish between single use (e.g., tried once in a lifetime) and regular use (e.g., several days in the past week), and validated clinical diagnoses were never reported. Most of the published papers described cross-sectional studies, with no attempt to follow up participants. One research group based in the north-east of England has repeated studies over time [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ], but not used the same methodology or followed through one cohort for significant length of time. Little of the research moved beyond simple descriptions and correlations, and it was rare that any under-pinning theory or conceptual model was described. Finally, there was very little evidence about drug use in specific high-risk populations e.g., LGBTQ or non-white students, or students with co-existing mental health problems.

The Advisory Council on the Misuse of Drugs (ACMD) has noted that prevalence data on young people’s drug use within the UK are ‘generally limited, highly variable and of low quality’ [ 52 ]. They recommend reviewing the scope and detail of the current approaches to monitor prevalence, ensuring that outcome measures used are fit for purpose. Expertise and experience in this area can be drawn from North America, where regular national surveys using sound methodology include university-age students [ 12 ]. The authors of a Canadian report on quality standards for measuring drug use in high schools [ 53 ] noted that surveying students in school is an efficient and cost-effective means of collecting data from young people, and similar reasoning could be applied to universities. However, there is a need for standardised methodology that can be replicated over time in representative samples.

Recommendation : A national survey of student drug use that covers the whole of the UK and Northern Ireland would be helpful, particularly if it was repeated to monitor trends over time. Standardised data collection instruments tailored to young adults must be developed and tested (e.g. see [ 53 ]), and the first step towards this approach has already been taken in Ireland under government direction [ 54 ]. Alternatively, the creation of representative student ‘consumer panels’ may allow researchers to explore patterns and frequencies of drug use in nationally representative samples.

Positive and negative risk factors for drug use

Although several studies described the association of a range of demographic, psychological and social factors with drug use, methodological limitations limited the utility of these findings. Some important areas of potential study were completely absent in our findings. For example, a developing evidence base suggests that there is a positive association between adverse childhood experiences (ACEs) and the development of substance use disorder in adolescence and adulthood [ 55 ]. One potential framework for study is the life course model of substance use [ 56 ], with a focus on the role of illicit drug use in developmental role transitions. Many authors have argued that emerging adulthood (i.e. the traditional university years) is developmentally different from adolescence (school) or full adulthood [ 10 ]. Independence from parents, new social and romantic relationships with peers, increased access to drugs and alcohol, and the need for self-directed study all contribute to a unique social milieu at a developmental stage already characterised by peak levels of risk-taking and high levels of mental health problems [ 57 , 58 , 59 ]. Understanding the factors that increase or decrease substance use at university is important to develop effective responses.

Recommendation: Prospective cohort study designs are needed that include student populations to identify which factors play a role in the initiation, development and cessation of drug use. Risk and protective factors for illicit drug use in young adults may be conceptualised as contextual (e.g. availability of the drug, or social norms that are tolerant of illicit drug use), fixed markers of risk (e.g., sex, parental and sibling substance use, poverty or potential genetic factors), and individual and interpersonal risk factors (e.g., novelty and sensation seeking, conduct disorder in childhood, parenting styles, or poor quality of parent–child interaction) [ 2 , 60 ]. Affiliation with peers that use drugs is one of the strongest predictors of illicit drug use in young adults and of crucial importance in the transitional social milieu of a university campus [ 61 ]. The impact of an increasing awareness of neurodiversity in young adults should also be investigated.

The harms (and benefits) of drug use in the student population

The consequences of illicit drug use were only reported in seven of the papers included in this review, with some limited focus on mental health and criminal justice issues. There were no studies exploring the impact on university-specific outcomes such as completion of a course of study, academic achievement and progression to further study or employment. This is surprising, as these outcomes are important markers of university quality used in national league tables. Understanding the specific harms that relate to university students will help to tailor prevention and treatment responses to this population.

Recommendation : The potential harms of illicit drug use in student populations occur across several domains, including academic performance (attendance and grades), other high-risk behaviours (unprotected sex, violence, driving under the influence), exacerbation of mental health problems, or legal issues (prosecution for possession or dealing) [ 62 ]. These consequences could potentially reshape the entire trajectory of the student’s life course [ 63 ]. Therefore, it would be useful to collect, collate and track standardised data nationally from a range of university departments (e.g., student welfare, registry) as a marker of illicit drug-related harm. Such quantitative data could usefully be supplemented by detailed qualitative studies of each aspect of harm (e.g., academic, physical, mental, social, or legal).

Knowledge about, attitudes and motivation to use drugs

Levels of objective knowledge about drug use were rarely studied, and yet may form the bedrock of a harm reduction approach [ 64 ]. Likewise attitudes and motivations to use drugs were not often reported or studied, despite the existence of potentially useful underpinning theories such as the theory of planned behaviour [ 65 ]. The use of conceptual models to guide findings is important to build an effective evidence base for prevention and intervention. The 2021 UK Government Drug Strategy aims to achieve a ‘generational shift in the demand for drugs’, and one proposed strategy for achieving this is ‘ research and testing messaging through an evidence-based, targeted behaviour change initiative, initially aimed at students in further and higher education’ [ 66 ] (p49). The document further notes that communications campaigns work best when they are tailored and targeted to the audience, and a recent ACMD report on prevention of illicit drug use notes that some activities have been ineffective, such as fear arousal approaches (including ‘scared straight’ approaches) or stand-alone mass media campaigns [ 67 ].

Our results suggest that a national trend towards ‘normalisation’ of recreational drug use has been replicated on university campuses. Furthermore, this has merged with the social supply of drugs, leading to a perception amongst some students that supplying (sometimes) large amounts of drugs is routine [ 35 ]. However, the overall picture is complicated, and not all studies included students who didn’t use drugs and so their voice was often not heard. Survey work using student panels rather than open online questionnaires shows that some students believe that their university should take a tougher stance on drugs [ 26 ]. The ‘social norms’ approach is based on challenging misperceptions individuals hold about their peers. Research at eight Further Education Colleges in the UK reported a perceived norm of frequency of substance use that was higher than the reported norm, and the majority of respondents did not actively approve of tobacco, cannabis or other drug use [ 68 ]. This reflects similar findings in the university system in Canada [ 69 ]. The social norms approach may be a viable method of developing effective methods of behaviour change in UK students.

Recommendation : Studies of knowledge about, and attitudes towards, illicit drugs in representative populations of UK or Irish students would be helpful in designing strategies to educate students about illicit drug use. Theoretically-driven interventions to reduce use and prevent harm may have a significant impact later in life, and comparisons could usefully be drawn with non-student peers.

Prevention and treatment of drug-related harms

Our scoping review found little evidence of published work in UK/Irish universities on prevention of, or intervention to reduce, drug-related harms. Reviews of the North American literature on prevention and treatment have also noted a lack of published studies, but parent-based and in-person brief motivational interventions appear to be promising [ 18 , 70 ]. Our review found no such interventions published in UK or Irish student populations. This may reflect the slow response of universities to consider drug use and tackle its potential harms, and the impact of stigma and illegality on students’ help-seeking attempts. A review of psychological interventions for prevention and treatment of mental health disorders in university students [ 71 ] was also limited by the poor quality of the literature and exclusion of non-published data. It noted considerable uncertainty about the best way to provide interventions for students, and relatively few trials adapted intervention delivery to student-specific concerns. It called for further work to better understand the mechanisms underlying students’ mental health problems, perhaps using transdiagnostic, stepped care approaches. Research on both mental health and drug use should involve students in the design of interventions to increase their acceptability to this population.

The prevention of alcohol-related harm has been well studied in university populations, and several existing interventions for student drinking share theoretical and methodological underpinnings with effective interventions in drug prevention and treatment in other populations (i.e., school-based prevention, adolescent and adult drug treatment) [ 6 , 18 ]. These interventions could be adapted to target drug prevention on university campuses. As is the case in the wider community, a recovery orientated system of care is required, with a full continuum of care encompassing harm reduction through to abstinence [ 72 ]. The development of the first Collegiate Recovery Programs [ 21 ] to support abstinent students at Teesside University and the University of Birmingham [ 73 ] represents the first part of such a continuum. However, despite big strides in the development of campus-based mental health support in the past decade, the issue of addiction to drugs, alcohol or other behaviours has been largely ignored. Tackling this deficit will be important to ensure that students are able to maximise the potential benefits of a university education.

Recommendation : Several commentators have noted that the stigma of psychoactive drug use appears to be particularly prominent in universities in the UK and Ireland, with ‘zero tolerance’ approaches often limiting informed debate [ 64 ]. Working collaboratively across the Higher Education sector may be helpful in supporting universities to provide education and prevent harm whilst respecting the illegality of illicit drug use. There is also a need to develop interventions tailored to the unique needs of students who have developed a drug use disorder, and to evaluate abstinence-based recovery programs on campus.

Conclusions

This review has exposed large gaps in the research evidence base around illicit drug use in university students in the UK and Ireland. The limited evidence reviewed here suggests that more students are coming into contact with illicit drugs and many are experiencing harms. There is therefore a need to unite student unions and universities in exploring the prevalence of drug use and its impact on students, supported by high quality research. A national survey of student drug use that covers the whole of the UK and Northern Ireland would be helpful, particularly if it was repeated to monitor trends over time. Alternatively, the creation of representative student ‘consumer panels’ may allow researchers to understand attitudes of students to the use of psychoactive substances on campus and to explore methods of reducing harm. Little effort has been made to explore the views of those who do not use drugs, or to identify the motivations of university students to decrease or cease drug use. Promising areas of future research on motivations to change in relation to illicit drug use include the social contextual factors, perceptions of effects on social relationships, and actions of friends and family members to prompt contemplation of change [ 74 ]. Trials to evaluate novel theoretically-based prevention and treatment programs that take into account established risk factors for drug use and drug use disorders are also needed [ 18 , 70 ].

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Methylenedioxymethamphetamine

Higher Education Institute

Preferred Reporting of Items for Systematic Reviews and Meta-Analyses

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Additional file 1., additional file 2: table1..

Papers excluded from the study and reason for exclusion ( n =40).  Table2. Additional papers excluded because the focus was prescribed drugs used as‘cognitive enhancers’ and not illicit drugs ( n =15).  Table3. Grey Literature – all excluded as no detail about methods used.

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Boden, M., Day, E. Illicit drug use in university students in the UK and Ireland: a PRISMA-guided scoping review. Subst Abuse Treat Prev Policy 18 , 18 (2023). https://doi.org/10.1186/s13011-023-00526-1

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The Dark Web and the future of illicit drug markets

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Information and communication technologies (ICTs), particularly the internet, have transformed almost every aspect of human life. While most of the breakthroughs in this area have offered great benefits, unintended negative consequences have also resulted. One example of the latter is the surge in illicit drug trafficking using the dark web and other internet-based techniques. Two key reasons for this surge are the anonymity of offenders and the diversity of internet-based trading platforms. Recent developments have shown that cybercriminals have made considerable use of the dark web to expand illicit drug trafficking globally, which has become a source of concern. According to global surveys, a substantial percentage of participants confessed to buying illicit drugs online. Law enforcement agencies are constantly undertaking surveillance operations to track and disrupt mass criminals and prevent crime on the dark web. The closure of major online drug trafficking platforms, on the other hand, has a minimal long-term impact on drug sales on the dark web market because customers and suppliers migrate to other trade platforms and overall sales eventually recover, highlighting the importance of a technologically robust intergovernmental regulatory framework. In this context, this article seeks to address and analyze the following issues: First, we provide an overview of Bitcoin and blockchain technology. Second, we explain the methods of purchasing drugs over the dark web. Finally, the paper concludes by discussing the future of the Dark Web and will propose some solutions and recommendations to regulate drug trafficking over the dark web.

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Chawki, M. The Dark Web and the future of illicit drug markets. J Transp Secur 15 , 173–191 (2022). https://doi.org/10.1007/s12198-022-00252-y

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Illicit Drugs Use And Prevention Research Paper

Sample Illicit Drugs Use And Prevention Research Paper. Browse other research paper examples and check the list of research paper topics for more inspiration. iResearchNet offers academic assignment help for students all over the world: writing from scratch, editing, proofreading, problem solving, from essays to dissertations, from humanities to STEM. We offer full confidentiality, safe payment, originality, and money-back guarantee. Secure your academic success with our risk-free services.

For this research paper, drugs are defined psychoactive chemical agents, i.e., substances that alter cognitive processes. Within this definition two classes of illicit substances emerge. Some legal psychoactive sub-stances reside in consumer products that are widely used, normative approved, and not usually perceived as drugs at all. Examples of these are nicotine in tobacco products, ethanol in alcoholic beverages, and caffeine in coffee or tea. Norms binding consumption of these goods vary in sanctions, but keep the list of permissible users and contexts broad. The next class of legitimate drugs is medicines. They can be legally acquired and consumed but only if matching symptoms have been verified by a physician. Drugs belonging to either of the two categories are also abused, i.e., consumed in a problematic or harmful manner. A third group of psychoactive drugs has been declared illicit because of the problematic effects or consequences caused by any of its constituents.

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Illicit drugs that are widely used include central nervous system stimulants (such as crack cocaine, cocaine, and amphetamines), central nervous system inhibitors (opiates, heroin and sedative-hypnotics such as benzodiazepines or barbiturates), or hallucinogens (hemp products such as marijuana or hashish, LSD, and phenocyclidine) (AOD 1995). Some goods employed as illicit drugs have legal uses also; examples are home and office products containing solvents or propellants, the fumes of which can be inhaled. Finally, so-called designer drugs are derivatives of illicit substances that technically are not illegal, but produce comparable effects. Experimentation with illicit drugs may lead through various mechanisms involving social, psychological, and pharmacological connections to dependency and abuse (Des Jarlais and Hubbard 1997).

This research paper describes ways to combat illicit drug abuse at a national level, including equivalent products, a task that has been characterized as a failure in twentieth century health promotion (Fielding 1999). After the introduction to the situation in the United States and Europe—broadening the perspective is impossible as even authorities have only a vague conception of illicit drug use in many sites (United Nations International Drug Control Programme 1997)—attention turned towards evidence concerning the significance of prevention efforts in communities, schools, and families. Obviously, more is already known than have been put into practice—it is important to disseminate the knowledge—but nevertheless more research is needed on the results of general social policy measures, community and family interventions, and interventions directed to those already marginalized.

1. Breadth And Risk Factors Of Illicit Drug Use Abuse

Quantitative information on use exists from industrialized countries including the United Sates (Johnson et al. 1996, NIDA 1997) and most European countries (EMCDDA 1998). Having had at least one occasion of use seems to be a quite variable phenomenon in terms of type of drug, period, region, and ethnic group in the United States. Substantial geographical variability is observed in Europe also, from which a much more limited time series is available.

It is noteworthy that though the countries with statistical information available are usually classified as illicit drug consumers as opposed to producers, this labeling does not describe the situation accurately: drugs are also consumed where they are produced. Development of a global illicit drug use information system is timely.

Statistics on illicit drug use are based on self-reporting. While there are good reasons to have doubts about the accuracy of this information (Hser 1997), many experts (including Preston et al. 1997) have provided evidence about its usefulness. Only surveys are feasible and their results permit reliable comparisons of time points and cultures even though level-of-use estimates based on them are diluted.

United Nations’ experts (United Nations International Drug Control Programme 1997) contend that global illicit drug consumption is higher than ever. Surveys indicate accordingly that both experimentation with drugs and their regular use have increased substantially in industrialized countries since World War II. At present illicit drugs involve both genders in the age range from early teens to young adulthood almost equally. In the United States, tenth graders (15–16 years of age; this is the age of the average first user) reported in 1996 the following lifetime use of illicit drugs: marijuana 42 percent, inhalants 18 percent, hallucinogens 11 percent, cocaine 7 percent, crack cocaine 4 percent, heroin 2 percent, stimulants 17 percent, and steroids 2 percent. As a comparison, the daily use of marijuana was admitted by about one in every 10 lifetime users of teen age, and 30 days’ consumption of the above-mentioned drugs varied between one third and one sixth of their respective lifetime consumption among US teenagers.

In 1997, at least experimenting with hemp products was admitted by 33 percent of 15–16-year-olds in the UK, 18 percent in Denmark, but only 3 percent in Greece. The corresponding figures for solvents were 20 percent, 12 percent, and 7 percent, and for amphetamines 18 percent, 2 percent, and 4 percent, which represent high, medium, and low ranges of their respective consumption in the 14 European Union countries (EMCDDA 1998). While some calming information exists about the former socialist countries situated in Europe (EMCDDA 1998), this area must be included among those that need a better monitoring system for reliable conclusions (eesv MSDP 1998).

There are numerous risk factors for drug use (Newcomb 1994) involving cultural and structural, interpersonal, psychosocial, or biogenetic factors. Cultural and societal risks include drug use promoting social norms, economic hardships, and drug availability. Among the interpersonal influences are family use, favorable familial attitudes, family or peer conflict and economic difficulties, and connections to peers using drugs. Psychosocial determinants involve earlier persistent problem behavior, rebelliousness, poor school achievement, early experimentation, and positive drug attitudes. Among the biogenetic causes, genetic susceptibility and psycho-physiological vulnerability to drug effects must be mentioned.

2. Ways To Control Illicit Drugs

Illicit drugs are consumer goods subject to economic laws of supply and demand. Increases in world travel, opening of national borders, deregulation of trade and finance, and political instability and conflicts have led into increased supply of these drugs. To reduce the supply, countries have started to network in many ways, including cooperation in such international organizations as the United Nations and World Health Organization. The traditional goal of control politics has been the elimination of illicit drugs from the market. When in fact drug use has increased in spite of efforts to achieve the opposite, some European countries have added harm reduction as a goal for educating youth in general (Uhl and Springer 1998).

International cooperation of law-making and law-enforcing organizations is one of the instruments to control illicit substance use (Van der Stel 1998). Another vital method involves social policy directed to the prevention of marginalization of citizens. Societies form a web of complex social systems in which the role of governmental control varies. Irrespective of their position in that dimension, a few countries have already established health political programs for illicit drug prevention. They, like all health promotion programs (Green 1999), must be implemented in the basic social units, communities.

2.1 Community Programs To Influence Supply And Demand

Aguirre-Molina and Gorman (1996) described community programs in drug prevention in the United States, although few of them exist in large numbers. These are comprehensive, empowering, and developmental community-based interventions that target multiple social systems and employ manifold strategies. They aim at all factors in the environment that contribute to the risk or protective factors. Programs already tested and three decades of experience with cardiovascular community programs encourage the continued cooperation of prevention workers and researchers.

Community-based programs usually cannot affect the production and manufacture of drugs (although this may be possible), but they can influence drug availability and access. Second, community organization involves both law enforcement and the local media, and can involve broad-based community change interventions. Furthermore, high-risk groups of people or high-risk neighborhoods need to be focused upon. Third, community-based intervention programs may aim at individuals at different phases of their life cycle.

2.2 School Programs To Control Demand

Drug education can be directed to different audiences: in the most general form, it is directed to populations via the mass media in community programs. The next lower level is that of groups—most notably school classes. Finally, education may be executed on a face-to-face basis to individuals. As youth is the subpopulation most at risk and can be addressed in school programs, these have be the main focus of efforts and most of the research.

School programs have been largely developed and implemented in the United States (Tobler 1997, Kreft and Brown 1998), but they have also been applied in Europe (White and Pitts 1998, Uhl and Springer 1998). Programs properly tested involve contents such as knowledge (drug effects, social influences, actual use of drugs), emotions (self-esteem, self-awareness, values), refusal skills (drug refusal, public commitment, cognitive behavioral skills, nondrug support systems), more generic or life skills (communication, assertiveness, decision making, coping, social, goalsetting skills), safety skills (own-peer security when drugs are used), extracurricular activities (job, sports, culture, leisure time, community work), or what can be termed prosocial activities (peer counseling, homework, rewards, parent and/or community involvement). Participation of the peer group in the program implementation varies on the dimension of noninteractive vs. interactive. In the list above, the divide is between programs clarifying emotions and teaching refusal skills: programs dealing with knowledge and emotions are noninteractive, the rest are interactive.

Kreft and Brown (1998) present sharp critique directed towards the poorly conducted bulk of illicit drug education studies. Dusenbury and Falco (1997) also note that extra care must be taken when making a purchase among programs available. The review by Tobler (1997), however, enumerates studies defying that criticism and uses sound meta-analytic techniques to yield conclusions, but not, however, verifying whether multilevel modeling important for school studies where students of same class unit have a common environment has been adopted or not. White and Pitts (1998) came to essentially the same results also.

Only interactive school programs of drug education can be deemed effective. Among the interactive programs, the highest effects were observed for general life-skills programs, followed by programs having either prosocial nonschool activities or social influence as content. Second, the effects when they exist are usually modest in size. As effect size estimates are bound to be subjective, it is helpful to contend that if an effect size of interactive programs were to be observed in a study concerning effects of medicines, a recommendation for use would be made. Third, the effect includes postponing experimentation—often the interactive programs’ effects are to be seen for 3 years. Fourth, when programs were implemented in larger groups, the effectiveness attenuated, except among multicultural audiences. This may indicate either poorer administration of larger programs and or increasing methodological problems posed by larger intervention to internal validity. Fifth, sizeable effects in postponing drug experimentation have been observed in small studies using interactive delivery. Sixth, the effects seem to be equivocal for different drugs.

Educational programs have been targeted at audiences from 8 to 25 years old in a variety of settings including schools and colleges, community settings, the family, medical therapeutic settings, and mass media (White and Pitts 1998). Tobler and White and Pitts made it clear that most of the available programs are meant for school and for primary and secondary prevention. There is a serious lack of programs to be implemented in other contexts or directed at groups at special risk (White and Pitts 1998).

2.3 Family-Based Interventions To Increase Prosocial Bonding And Help With Problems

The community and schools have to be named as important contexts of the above interventions. The possible sites of impact include recreational and religious settings, work, and, importantly, the family, in which the primary socialization takes place. Because of centrality of the family in illicit drug use prevention, this contexts attracts primary interest.

Biglan and Metzler (1998) noted that drug use among young people is associated with engagement in diverse problem behaviors and certain parental practices (lack of effective monitoring, discipline, and positive involvement with children). Three types of family interventions can be discerned: universal to the general population of families, selective to families with high-risk youth, and indicated interventions to dysfunctional families with many risks (Kumpfer 1998). Of these, the most significant from the public health perspective are universal interventions (Catalano et al. 1998).

At the beginning of the twenty-first century, some promising interventions involving the social developmental model, using prosocial bonding family, school, and peers as a protection against the development of conduct problems, school misbehavior, and drug use, are in the evaluation phase. It is

hypothesized that strong prosocial bonding to others reduces the risk of substance abuse. It can be expected that the success of this undertaking is dependent on the extent to which prosocial involvement within the family is available to the child, skills necessary in participating in the family interactions, and rewards punishments provided by parent for conforming nonconforming with the family expectations and beliefs. As in the case of community research, more studies need to be reported before definite conclusions of their real worth can be arrived at.

3. Conclusion: Towards More Effective Cooperation

Illicit drug abuse prevention continues to be an important task of health promotion, both nationally and internationally. Although all undertakings in prevention may not be easily evaluated (a good example of which is international control measures), scientific rigor should always be aimed at when making the choice. Only school-based programs have been reliably evaluated so far, leading to a recommendation of adopting interactive programs relying on life or refusal skills. Both community and family interventions seem to be important to consider, although they need to be applied and then evaluated further before firm conclusions can be made. At the highest level, national policy goals need to be adapted to changing circumstances in many countries, a global information system should established, and international cooperation at all levels strengthened for the success of prevention and developing its objectives.

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Policy Considerations to Prevent Drug Shortages and Mitigate Supply Chain Vulnerabilities in the United States

Key Highlights

Drug shortages impact patients, families, caregivers, pharmacists, hospitals, nursing homes, hospices, and other individuals and entities across the health care system.

Drug shortages are a decades-old problem arising, in part, from market forces that touch stakeholders across the drug supply chain—providers and pharmacies, manufacturers, and the middlemen in the system. Key issues include a broad lack of transparency, concentration among middlemen, and prices for generic drugs that are driven to levels so low that they create insufficient incentives for redundancy or resilience-oriented manufacturing, distribution, and purchasing. These market failures lead to pharmaceutical supply chains that are brittle, disruption-prone, and too slow to recover from shortages.

Supply chain resilience involves fostering processes that are less likely to face disruptions, as well as establishing the ability to withstand and mitigate disruptions so their impact—when they occur—is limited. This resilience also comes from diversification of supply—both in redundancy of manufacturing capacity and a balance of domestic and diversified foreign sourcing—and the presence of reliable, efficient, and sustainable, robust manufacturing practices.

The Department of Health and Human Services (HHS or Department) has made significant strides in shoring up the system’s ability to respond to shortages. Nevertheless, more impactful and enduring solutions require additional statutory authorities and funding to resolve underlying causes of shortages. All supply chain participants play a part in these solutions.

This paper describes policy concepts for consideration, including collaboration with the private sector to develop and implement a Manufacturer Resiliency Assessment Program (MRAP) and a Hospital Resilient Supply Program (HRSP). As described, the combination of these programs would bring transparency into the market, link purchasing and payment decisions to supply chain resilience practices, and incentivize investments in supply chain resilience and diversification in the supply chain—including domestic manufacturing—at a scale that would drive impactful change in the market. This paper focuses on generic sterile injectable medicines used in inpatient settings, given their importance to acute inpatient care, and their relative risk of supply disruptions—though HHS recognizes that these challenges affect other products, and therefore, the solutions described here may be applicable in other markets. 

*This content is in the process of Section 508 review. If you need immediate assistance accessing this content, please submit a request to Sharon Arnold, [email protected] . Content will be updated pending the outcome of the Section 508 review.

Read our research on: Abortion | International Conflict | Election 2024

Regions & Countries

Most americans favor legalizing marijuana for medical, recreational use, legalizing recreational marijuana viewed as good for local economies; mixed views of impact on drug use, community safety.

Pew Research Center conducted this study to understand the public’s views about the legalization of marijuana in the United States. For this analysis, we surveyed 5,140 adults from Jan. 16 to Jan. 21, 2024. Everyone who took part in this survey is a member of the Center’s American Trends Panel (ATP), an online survey panel that is recruited through national, random sampling of residential addresses. This way nearly all U.S. adults have a chance of selection. The survey is weighted to be representative of the U.S. adult population by gender, race, ethnicity, partisan affiliation, education and other categories. Read more about the ATP’s methodology .

Here are the questions used for the report and its methodology .

As more states pass laws legalizing marijuana for recreational use , Americans continue to favor legalization of both medical and recreational use of the drug.

An overwhelming share of U.S. adults (88%) say marijuana should be legal for medical or recreational use.

Nearly six-in-ten Americans (57%) say that marijuana should be legal for medical and recreational purposes, while roughly a third (32%) say that marijuana should be legal for medical use only.

Just 11% of Americans say that the drug should not be legal at all.

Opinions about marijuana legalization have changed little over the past five years, according to the Pew Research Center survey, conducted Jan. 16-21, 2024, among 5,14o adults.

The impact of legalizing marijuana for recreational use

While a majority of Americans continue to say marijuana should be legal , there are varying views about the impacts of recreational legalization.

About half of Americans (52%) say that legalizing the recreational use of marijuana is good for local economies; just 17% think it is bad and 29% say it has no impact.

More adults also say legalizing marijuana for recreational use makes the criminal justice system more fair (42%) than less fair (18%); 38% say it has no impact.

However, Americans have mixed views on the impact of legalizing marijuana for recreational use on:

• Use of other drugs: About as many say it increases (29%) as say it decreases (27%) the use of other drugs, like heroin, fentanyl and cocaine (42% say it has no impact).
• Community safety: More Americans say legalizing recreational marijuana makes communities less safe (34%) than say it makes them safer (21%); 44% say it has no impact.

Partisan differences on impact of recreational use of marijuana

There are deep partisan divisions regarding the impact of marijuana legalization for recreational use.

Majorities of Democrats and Democratic-leaning independents say legalizing recreational marijuana is good for local economies (64% say this) and makes the criminal justice system fairer (58%).

Fewer Republicans and Republican leaners say legalization for recreational use has a positive effect on local economies (41%) and the criminal justice system (27%).

Republicans are more likely than Democrats to cite downsides from legalizing recreational marijuana:

• 42% of Republicans say it increases the use of other drugs, like heroin, fentanyl and cocaine, compared with just 17% of Democrats.
• 48% of Republicans say it makes communities less safe, more than double the share of Democrats (21%) who say this.

Demographic, partisan differences in views of marijuana legalization

Sizable age and partisan differences persist on the issue of marijuana legalization though small shares of adults across demographic groups are completely opposed to it.

Older adults are far less likely than younger adults to favor marijuana legalization.

This is particularly the case among adults ages 75 and older: 31% say marijuana should be legal for both medical and recreational use.

By comparison, half of adults between the ages of 65 and 74 say marijuana should be legal for medical and recreational use, and larger shares in younger age groups say the same.

Republicans continue to be less supportive than Democrats of legalizing marijuana for both legal and recreational use: 42% of Republicans favor legalizing marijuana for both purposes, compared with 72% of Democrats.

There continue to be ideological differences within each party:

• 34% of conservative Republicans say marijuana should be legal for medical and recreational use, compared with a 57% majority of moderate and liberal Republicans.
• 62% of conservative and moderate Democrats say marijuana should be legal for medical and recreational use, while an overwhelming majority of liberal Democrats (84%) say this.

Views of marijuana legalization vary by age within both parties

Along with differences by party and age, there are also age differences within each party on the issue.

A 57% majority of Republicans ages 18 to 29 favor making marijuana legal for medical and recreational use, compared with 52% among those ages 30 to 49 and much smaller shares of older Republicans.

Still, wide majorities of Republicans in all age groups favor legalizing marijuana at least for medical use. Among those ages 65 and older, just 20% say marijuana should not be legal even for medical purposes.

While majorities of Democrats across all age groups support legalizing marijuana for medical and recreational use, older Democrats are less likely to say this.

About half of Democrats ages 75 and older (53%) say marijuana should be legal for both purposes, but much larger shares of younger Democrats say the same (including 81% of Democrats ages 18 to 29). Still, only 7% of Democrats ages 65 and older think marijuana should not be legalized even for medical use, similar to the share of all other Democrats who say this.

Views of the effects of legalizing recreational marijuana among racial and ethnic groups

Substantial shares of Americans across racial and ethnic groups say when marijuana is legal for recreational use, it has a more positive than negative impact on the economy and criminal justice system.

About half of White (52%), Black (53%) and Hispanic (51%) adults say legalizing recreational marijuana is good for local economies. A slightly smaller share of Asian adults (46%) say the same.

Criminal justice

Across racial and ethnic groups, about four-in-ten say that recreational marijuana being legal makes the criminal justice system fairer, with smaller shares saying it would make it less fair.

However, there are wider racial differences on questions regarding the impact of recreational marijuana on the use of other drugs and the safety of communities.

Use of other drugs

Nearly half of Black adults (48%) say recreational marijuana legalization doesn’t have an effect on the use of drugs like heroin, fentanyl and cocaine. Another 32% in this group say it decreases the use of these drugs and 18% say it increases their use.

In contrast, Hispanic adults are slightly more likely to say legal marijuana increases the use of these other drugs (39%) than to say it decreases this use (30%); 29% say it has no impact.

Among White adults, the balance of opinion is mixed: 28% say marijuana legalization increases the use of other drugs and 25% say it decreases their use (45% say it has no impact). Views among Asian adults are also mixed, though a smaller share (31%) say legalization has no impact on the use of other drugs.

Community safety

Hispanic and Asian adults also are more likely to say marijuana’s legalization makes communities less safe: 41% of Hispanic adults and 46% of Asian adults say this, compared with 34% of White adults and 24% of Black adults.

Wide age gap on views of impact of legalizing recreational marijuana

Young Americans view the legalization of marijuana for recreational use in more positive terms compared with their older counterparts.

Clear majorities of adults under 30 say it is good for local economies (71%) and that it makes the criminal justice system fairer (59%).

By comparison, a third of Americans ages 65 and older say legalizing the recreational use of marijuana is good for local economies; about as many (32%) say it makes the criminal justice system more fair.

There also are sizable differences in opinion by age about how legalizing recreational marijuana affects the use of other drugs and the safety of communities.

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Table of contents, most americans now live in a legal marijuana state – and most have at least one dispensary in their county, 7 facts about americans and marijuana, americans overwhelmingly say marijuana should be legal for medical or recreational use, clear majorities of black americans favor marijuana legalization, easing of criminal penalties, religious americans are less likely to endorse legal marijuana for recreational use, most popular.

About Pew Research Center Pew Research Center is a nonpartisan fact tank that informs the public about the issues, attitudes and trends shaping the world. It conducts public opinion polling, demographic research, media content analysis and other empirical social science research. Pew Research Center does not take policy positions. It is a subsidiary of The Pew Charitable Trusts .