The entactogen 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) as a treatment aid in psychotherapy and its safety concerns.

The phenylethylamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), is the prototypical example of an entactogen. Its original placement in highly restrictive drug usage categories in the US and UK, led to an inevitable restriction on MDMA neuroscience research and treatment. The dominant pharmacological effects of MDMA are its properties of release and inhibition of reuptake of amine neurotransmitter transporters for dopamine, norepinephrine, and serotonin. MDMA is an agonist of a wide range of receptors; its mood-altering effects are mediated via 5-HT2A receptors; this receptor may also mediate its effects on body temperature, analgesia, and anxiolytic properties. The mechanisms underlying MDMA's entactogenic properties of sociability and interpersonal closeness are not known but release and involvement of oxytocin, a peptide thought by some to be involved in social bonding, has been suggested. Adverse effects of MDMA are mostly transient; acute multiorgan adverse effects occurring during raves or crowded dance gatherings include dehydration, hyperthermia, seizures, rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. Deaths following MDMA taken by itself are rare compared to fatalities following coadministration with other drugs. A recent FDA-approved phase 3 clinical trial of MDMA for post-traumatic stress disorder (PTSD) led to the conclusion that MDMA-assisted therapy represents a potential breakthrough treatment meriting expedited clinical evaluation. Despite the ongoing deliberations by the FDA and EMA for approval of MDMA treatment of PTSD, the Australian Therapeutic Goods Administration (TGA) recently announced that after an evaluation of the therapeutic value, benefits, and risks of MDMA, it will permit its prescribing for the treatment of PTSD. Further examples of regulatory relaxation toward MDMA-assisted psychotherapy are underway. These include the FDA's recently approved clinical trial to assess MDMA's efficacy in the treatment of "asociality" in patients with schizophrenia and an open trial of MDMA treatment for alcohol-use disorder which showed decreased alcohol consumption. There are also ongoing studies on the little understood startle response, anxiety associated with life-threatening illness, and social anxiety in autistic adults.

Illicit drug consumption estimated using wastewater analysis and compared by settlement size in New Zealand.

Estimation of consumption of illicit drugs by wastewater-based epidemiology provides estimates of community drug-use patterns. This study describes monitoring data of three illicit drugs in New Zealand using wastewater-based epidemiology. Wastewater samples were collected at monthly intervals for larger (population ~ 50,000+) cities or in smaller towns where more data was required by authorities. In other smaller towns, samples were collected every 2 months. Samples were extracted and analysed for parent compounds and metabolites of methamphetamine, MDMA, cocaine, heroin and fentanyl consumption using solid-phase extraction followed by liquid chromatography coupled with tandem-mass spectrometry (LC-MS/MS) detection. Back calculations were performed to estimate the consumption of each drug in each catchment area. Methamphetamine was the drug measured with the highest estimated mean consumption rates (724 mg/1000 people per day) in New Zealand. North Island small urban settlements had the highest estimated mean methamphetamine consumption rates (1259 mg/1000 people/day). Cocaine had the lowest estimated consumption rates (9.4 mg/1000 people/day). The highest estimated mean cocaine consumption rate was in North Island major urban settlements (24.4 mg/1000 people/day). Major urban settlements had the highest estimated mean MDMA (420 mg/1000 people/day) and cocaine consumption rates (18.8 mg/1000 people/day). South Island medium urban settlements had unexpectedly high estimated mean consumption rates of MDMA (533 mg/1000 people/day) and cocaine (17.0 mg/1000 people/day). The higher-than-expected estimated cocaine consumption was from one medium urban settlement that is also a popular tourist destination in the South Island. Heroin biomarkers were not detected at any locations, and fentanyl was detected around or below the limit of reporting. This research provides information for appropriate responses for improved social and health investment to support social services associated with illicit drug consumption.

Spatio-temporal assessment of illicit drug use at large scale: evidence from 7 years of international wastewater monitoring.

BACKGROUND AND AIMS: Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population-normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011-17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data. DESIGN: Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017. SETTING AND PARTICIPANTS: Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries. MEASUREMENTS: Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of Δ9 -tetrahydrocannabinol (11-nor-9-carboxy-Δ9 -tetrahydrocannabinol) were measured in wastewater using liquid chromatography-tandem mass spectrometry. Daily mass loads (mg/day) were normalized to catchment population (mg/1000 people/day) and converted to the number of combined doses consumed per day. Spatial differences were assessed world-wide, and temporal trends were discerned at European level by comparing 2011-13 drug loads versus 2014-17 loads. FINDINGS: Benzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North-Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge. CONCLUSIONS: The analysis of wastewater to quantify drug loads provides near real-time drug use estimates that globally correspond to prevalence and seizure data.

Physical and psychosocial factors associated with psychostimulant use in a nationally representative sample of French adolescents: Specificities of cocaine, amphetamine, and ecstasy use.

PURPOSE: Patterns of psychostimulant (PST) use, psychological and physical factors, and family relationships were investigated in a nationally representative sample of adolescents. The differences between users of cocaine (Cc), ecstasy/MDMA, and amphetamine (EA) were analyzed, taking into account gender differences. METHODS: Substance use, psychological factors (lifetime suicide attempts, suicidal thoughts in the previous year, visits to a mental health professional), physical factors (health and body shape perceptions (BSP), body mass index (BMI)), and family relationships (existence of disagreements with parents, relationships with mother and father) were investigated in 26,351 17-year-old French adolescents. RESULTS: Lifetime suicidal behavior was strongly associated with EA use only. Suicidal ideation in the previous year was associated with Cc use among both boys and girls and associated with EA use among girls. Compared to Cc users, more EA users were overweight, while more Cc users were underweight compared to EA users. BSP, BMI, and EA use were related in girls only. Having a good or very good relationship with both mother and father was negatively associated with Cc use in boys and girls. Girls who had a good or very good relationship with their fathers seemed to be less prone to use EA. Boys with a good or very good relationship with their mothers seemed to be less prone to use EA. CONCLUSION: The results of the present study could serve as a basis for prevention and harm reduction strategies/programs targeting youth use and for the adaptation of these strategies/programs according to substance and gender.

Experiences of police contact among young adult recreational drug users: A qualitative study.

BACKGROUND: While young adults who engage in recreational drug use are at increased risk of contact with police, their experiences of police contact have been largely overlooked. METHOD: In-depth qualitative interviews were conducted with 70 young adult amphetamine-type stimulant (ATS; i.e., ecstasy [MDMA] and methamphetamine) users who had experienced intensive alcohol and other drug-related police contact (e.g., being arrested, charged, or raided by police). These interviews focused on perceptions of personal experiences of alcohol and other drug-related police contact and general perceptions of police and policing and were conducted as part of a larger longitudinal study of drug use among a population-based sample of young adults from South-East Queensland, Australia. RESULTS: ATS users' perceptions of their personal interactions with police and general perceptions of police and policing were influenced by a number of factors, including police behaviour, prior contact with police, friends and family members' contact with police, and perceptions of their own behaviour leading to their contact with police. While a majority of ATS users reported that their contact with police had either a neutral or negative impact on their general perceptions of police and policing, some ATS users reported that police contact had a positive impact. For 70% of ATS users, police contact was reported to have had an impact on their substance use behaviours, resulting in either modification of their substance use behaviours to avoid further police contact or reduction in their substance use. CONCLUSIONS: These findings suggest that police contact among young adult ATS users can impact on both perceptions of police and policing and substance use behaviours, emphasising the importance of the quality and nature of police contact and its potential role in harm reduction.

Using population screening for recruitment of young adults engaged in illicit drug use: methodological issues and sampling outcomes.

Social stigma, legal sanctions and the associated lack of sampling frames create barriers to the probabilistic sampling of those engaged in a variety of behaviour, including illicit drug use. We used a novel sampling approach to recruit respondents into a longitudinal study examining amphetamine-type stimulant use. A young adult population was screened for lifetime drug use to create a sampling frame of amphetamine-type stimulant users and non-users. We posted 12,118 screening questionnaires to a random selection of young adults listed on the electoral roll for Brisbane and the Gold Coast, Australia (N=107,275). Using a small pre-paid incentive and intensive telephone and postal reminders we attained a screening response rate of 49.9%. Eligible amphetamine-type stimulant users (used ecstasy or methamphetamine⩾3 times in past 12 months) and non-users (never used ecstasy or methamphetamine) were identified by screening responses. About two-thirds of each selected group took part in the longitudinal study. Comparisons with large-scale population survey data suggest the sample was broadly representative of young adult amphetamine-type stimulant users in Australia.

Young adults' trajectories of Ecstasy use: a population based study.

Young adults' Ecstasy use trajectories have important implications for individual and population-level consequences of Ecstasy use, but little relevant research has been conducted. This study prospectively examines Ecstasy trajectories in a population-based sample. Data are from the Natural History Study of Drug Use, a retrospective/prospective cohort study conducted in Australia. Population screening identified a probability sample of Ecstasy users aged 19-23 years. Complete data for 30 months of follow-up, comprising 4 time intervals, were available for 297 participants (88.4% of sample). Trajectories were derived using cluster analysis based on recent Ecstasy use at each interval. Trajectory predictors were examined using a generalized ordered logit model and included Ecstasy dependence (World Mental Health Composite International Diagnostic Instrument), psychological distress (Hospital Anxiety Depression Scale), aggression (Young Adult Self Report) and contextual factors (e.g. attendance at electronic/dance music events). Three Ecstasy trajectories were identified (low, intermediate and high use). At its peak, the high-use trajectory involved 1-2 days Ecstasy use per week. Decreasing frequency of use was observed for intermediate and high-use trajectories from 12 months, independently of market factors. Intermediate and high-use trajectory membership was predicted by past Ecstasy consumption (>70 pills) and attendance at electronic/dance music events. High-use trajectory members were unlikely to have used Ecstasy for more than 3 years and tended to report consistently positive subjective effects at baseline. Given the social context and temporal course of Ecstasy use, Ecstasy trajectories might be better understood in terms of instrumental rather than addictive drug use patterns.

Young adults' recreational social environment as a predictor of ecstasy use initiation: findings of a population-based prospective study.

AIMS: To examine prospectively the contribution of the recreational social environment to ecstasy initiation. DESIGN: Population-based retrospective/prospective cohort study. SETTING: Data from screening an Australian young adult population to obtain samples of users and non-users of ecstasy. PARTICIPANTS: A sample of 204 ecstasy-naive participants aged 19-23 years was obtained, and a 6-month follow-up identified those who initiated ecstasy use. MEASUREMENTS: We assessed a range of predictors of ecstasy initiation, including elements of participants' social environment, such as ecstasy-using social contacts and involvement in recreational settings. FINDINGS: More than 40% of ecstasy-naive young adults reported ever receiving ecstasy offers. Ecstasy initiation after 6 months was predicted independently by having, at recruitment, many ecstasy-using social contacts [adjusted relative risk (ARR) 3.15, 95% confidence interval (CI): 1.57, 6.34], attending electronic/dance music events (ARR 6.97, 95% CI: 1.99, 24.37), receiving an ecstasy offer (ARR 4.02, 95% CI: 1.23, 13.10), early cannabis use (ARR 4.04, 95% CI: 1.78, 9.17) and psychological distress (ARR 5.34, 95% CI: 2.31, 12.33). Adjusted population-attributable fractions were highest for ecstasy-using social contacts (17.7%) and event attendance (15.1%). CONCLUSIONS: In Australia, ecstasy initiation in early adulthood is associated predominantly with social environmental factors, including ecstasy-using social contacts and attendance at dance music events, and is associated less commonly with psychological distress and early cannabis use, respectively. A combination of universal and targeted education programmes may be appropriate for reducing rates of ecstasy initiation and associated harms.

The Health Effect of Psychostimulants: A Literature Review.

Prevalence of psychostimulant use is high, and raising in several countries. Nicotine is the legal stimulant causing the most important public health impact. Cocaine ranks among the most used illicit substances after cannabis. Stimulant medications are frequently misused. Psychostimulants can lead to addiction, have physical, psychological and social health consequences and can induce a great disease burden. The aim of the present article is to provide a literature review on the health effects of stimulants as potential drugs of abuse. It will cover essentially cocaine, amphetamines and its derivatives (including methamphetamines and 3-4-methylenedioxymethamphetamine, ecstasy), nicotine, caffeine and khat, and touch upon the issues of prescribed substances (anti-depressants, weight control medications, attention-deficit hyperactivity disorder medications, hypersomniac disorder). Their pharmacology, addictive potential, health consequences and treatment will be discussed. We used Medline for the literature review from 1990 to the date of this review, and mention the findings of human and animal studies (the latter only if they are of clinical relevance).