Self-blinding citizen science to explore psychedelic microdosing.

Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a 'self-blinding' citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.

Psychedelic psychotherapy, therapy enhanced with psychedelic drugs such as LSD or psilocybin (the active ingredient of 'magic mushrooms'), has been suggested to improve psychological well-being. For this reason, trials on psychedelic therapy for the treatment of depression, addiction and other conditions are ongoing. Recently, 'microdosing' ­ a way of administering psychedelics that involves taking about 10% of a recreational dose two or three times per week ­ has gained popularity. Unlike taking large doses of psychedelics, microdosing does not induce hallucinations, but anecdotal reports suggest that it yields similar benefits as psychedelic therapy. A key feature of modern medicine are 'placebo control' studies that compare two groups of patients: one that takes a drug and another that takes inactive pills, known as placebos. Crucially, neither group knows whether they are taking drug or placebo. This control ensures that observed effects are due to the drug itself and not to unrelated psychological causes. For example, in trials of mood medicines, participants often expect to feel happier, which in itself improves their mood even when taking a placebo. This is known as the placebo effect. Restrictive drug policies make placebo-controlled studies on psychedelics difficult and expensive, in particular for microdosing, which involves taking psychedelics over a longer time period. To overcome this problem, Szigeti et al. developed a new citizen-science approach, where microdosers implemented their own placebo control based on online instructions. The advantages are the low cost and the ability to recruit participants globally. The experiment was completed by 191 microdosers, making it the largest placebo-controlled study on psychedelics to-date, for a fraction of the cost of an equivalent clinical study. The trial examined whether psychedelic microdosing can improve cognitive function and psychological well-being. The team found that microdosing significantly increased a number of psychological measures, such as well-being and life satisfaction. However, participants taking placebo also improved: there were no significant differences between the two groups. The findings confirmed positive anecdotes about microdosing improving people's moods, but at the same time show that taking empty capsules, knowing they might be microdoses, have the same benefits. This result suggests that the observed benefits are not caused by the microdose, but rather by psychological expectations. The study's innovative 'do-it-yourself' approach to placebo control may serve as a template for future citizen science studies on other popular phenomena where positive expectations and social factors could play a role, such as cannabidiol (CBD) oils, nootropics and nutrition.

Developing a new national MDMA policy: Results of a multi-decision multi-criterion decision analysis.

BACKGROUND: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) has a relatively low harm and low dependence liability but is scheduled on List I of the Dutch Opium Act ('hard drugs'). Concerns surrounding increasing MDMA-related criminality coupled with the possibly inappropriate scheduling of MDMA initiated a debate to revise the current Dutch ecstasy policy. METHODS: An interdisciplinary group of 18 experts on health, social harms and drug criminality and law enforcement reformulated the science-based Dutch MDMA policy using multi-decision multi-criterion decision analysis (MD-MCDA). The experts collectively formulated policy instruments and rated their effects on 25 outcome criteria, including health, criminality, law enforcement and financial issues, thematically grouped in six clusters. RESULTS: The experts scored the effect of 22 policy instruments, each with between two and seven different mutually exclusive options, on 25 outcome criteria. The optimal policy model was defined by the set of 22 policy instrument options which gave the highest overall score on the 25 outcome criteria. Implementation of the optimal policy model, including regulated MDMA sales, decreases health harms, MDMA-related organised crime and environmental damage, as well as increases state revenues and quality of MDMA products and user information. This model was slightly modified to increase its political feasibility. Sensitivity analyses showed that the outcomes of the current MD-MCDA are robust and independent of variability in weight values. CONCLUSION: The present results provide a feasible and realistic set of policy instrument options to revise the legislation towards a rational MDMA policy that is likely to reduce both adverse (public) health risks and MDMA-related criminal burden.

Availability of substances for use in personal vaporisers on three online cryptomarkets.

BACKGROUND: Personal vaporisers are gaining popularity as an alternative route of administration for a range of substances. Online cryptomarkets are becoming increasingly popular among people who use substances due to their perceived anonymity, ease of use, and reduced risk of violence compared to traditional face-to-face dealers. We examined the diversity of substances marketed for use in a personal vaporiser on these marketplaces. METHODS: Vaping related listings were extracted from three online cryptomarkets ('Agartha', 'Cryptonia', and 'Tochka') using The Onion Router browser. Data collection occurred between October and November 2019. RESULTS: We identified 1929 listings from 201 unique sellers. The top product on Agartha, Cryptonia, and Tochka were vape cartridges prefilled with the e-liquid (70.4 %, 39.4 %, 52.3 % respectively). The most common substance in these products was cannabis oil (96.1 %, 82.1 %, 87.8 %), followed by synthetic cannabinoids (3.7 %, 9.7 %, 9.8 %) and psychedelic substances (0.2 %, 6.4 %, 1.2 %). Vendors were primarily from the USA. Many products offered worldwide shipping (96.3 %, 42.4 %, 51.2 %). CONCLUSION: Vaping products listed on online cryptomarkets in 2019 primarily contained cannabis oils. Future studies should continue to examine cryptomarkets to identify emerging trends of substances that can be used in personal vaporisers.

Purging and the body in the therapeutic use of ayahuasca.

Ayahuasca is a psychoactive plant mixture used in ceremonial contexts throughout Western Amazonia. Its use has expanded globally in recent decades and become popular among westerners who travel to the Peruvian Amazon in increasing numbers to experience its reportedly healing effects. Through a review of relevant literature on Amazonian shamanism, combined with the authors' ethnographic data from shamanic tourism contexts of the Peruvian Amazon and neo-shamanic networks in Australia (collected between 2003 and 2015 - with a total of 227 people interviewed or surveyed, including healers and participants), we demonstrate that purging has been integral to the therapeutic use of ayahuasca across and beyond Amazonia. Therapeutic approaches to ayahuasca point to combined modulations of the gut and the mind, and the bodily and the social, that are expressed through discourse about healing and the body. Relating ethnographic evidence to recent scientific studies that connect the gut to emotional health, we do not approach the gut as merely biological ground on which cultural meanings are imposed, but rather as simultaneously physical and cultural. Based upon our analysis, we argue that ayahuasca purging should not be dismissed as a drug side effect or irrational belief but reconsidered for its potential therapeutic effects.

Crisis intervention related to the use of psychoactive substances in recreational settings--evaluating the Kosmicare Project at Boom Festival.

Kosmicare project implements crisis intervention in situations related to the use of psychoactive substances at Boom Festival (Portugal). We present evaluation research that aims to contribute to the transformation of the project into an evidence-based intervention model. It relies on harm reduction and risk minimization principles, crisis intervention models, and Grof's psychedelic psychotherapy approach for crisis intervention in situations related to unsupervised use of psychedelics. Intervention was expected to produce knowledge about the relation between substance use and mental health impact in reducing potential risk related to the use of psychoactive substances and mental illness, as well as an impact upon target population's views of themselves, their relationship to substance use, and to life events in general. Research includes data on process and outcome indicators through a mixed methods approach, collected next to a sample of n=176 participants. Sample size varied considerably, however, among different research measures. 52% of Kosmicare visitors reported LSD use. Over 40% also presented multiple drug use. Pre-post mental state evaluation showed statistically significant difference (p<.05) confirming crisis resolution. Crisis episodes that presented no resolution were more often related with mental health outburst episodes, with psychoactive substance use or not. Visitors showed high satisfaction with intervention (n=58) and according to follow-up (n=18) this perception was stable over time. Crisis intervention was experienced as very significant. We discuss limitations and implications of evaluating natural setting based interventions, and the relation between psychoactive substance use and psychopathology. Other data on visitor's profile and vulnerability to crisis showed inconclusive.

4-Bromo-2,5-dimethoxyphenethylamine (2C-B): presence in the recreational drug market in Spain, pattern of use and subjective effects.

4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive analogue of mescaline that is becoming increasingly popular as a rave and club drug. We investigated its presence in the illicit drug market in Spain, its pattern of use and profile of subjective effects. Drug material was analysed for 2C-B and information on pattern of use and subjective effects was obtained from recreational users. Scores were statistically compared with previously collected data on psychostimulants (d-amphetamine), entactogens (MDMA) and psychedelics (ayahuasca and Salvia divinorum). The percentage of samples containing 2C-B doubled between 2006 and 2009, evolved from powder to tablet form and showed low falsification rates. Respondents reported taking 2C-B orally in doses of about 20 mg. Subjective effects involved perceptual modifications analogous to those observed after ayahuasca and salvia but absent after amphetamine and MDMA. Pleasure and sociability effects did not differ from those after MDMA and incapacitation was lower than for the psychedelics used as comparators. In conclusion, we found 2C-B is consistently present in the illicit drug market in Spain. While it elicits perceptual modifications that are analogous to other psychedelics, the lower impairment and higher pleasurable effects make it comparable with entactogens.

The role of MDMA (Ecstasy) in coping with negative life situations among urban young adults.

This article examines the role of Ecstasy (MDMA or 3, 4-methylenedioxymethamphetamine) as a drug used for self-medication and coping with both short- and long-term negative life situations. We show that urban youth who do not have a specific diagnosed mental illness are more likely than those who have been diagnosed and have received treatment to use Ecstasy to cope with both situational stress and lifetime trauma. Diagnosed and treated youth sometimes self-medicate with other drugs, but do not choose Ecstasy for mediation of their psychological stress. We discuss the implications of self-medication with Ecstasy for mental health services to urban youth experiencing mental health disparities, and for the continued testing and prescription of MDMA for therapeutic use in controlled clinical settings.

Association between cannabis and psychiatric hospitalization.

OBJECTIVE: To investigate the relationship between cannabis use and mental health. METHOD: A cross-sectional analysis in a sample of 17 698 individuals with a mean age of 22 years (SD: 4.2). Participants provided information on the amount and initial age of cannabis use and history of psychiatric hospitalizations through a web-based questionnaire. To quantify Δ(9) -tetrahydrocannabinol exposure, we operationalized cannabis use as the amount of money spent on cannabis per week over the last month. The odds ratio of having a history of psychiatric hospitalizations was the primary outcome measure. RESULTS: We found a dose-response relationship between the amount of cannabis use and the odds for psychiatric hospitalization. Adjusted odds ratios for hospitalization increased with the amount of cannabis consumed from 1.6 (95% CI: 1.1-2.3) in incidental users to 6.2 (95% CI: 4.3-8.9) in heavy users (>€25/week). Our data suggested that concomitant drug use was an intermediate factor. Exposure to cannabis before the age of 12 years was found to carry a 4.8 (95% CI: 2.9-7.8) times increased odds for past psychiatric hospitalizations. CONCLUSION: We conclude that early and heavy uses of cannabis are each and independently associated with poor mental health in its users.

An in vivo microdialysis assessment of concurrent MDMA and cocaine administration in Sprague-Dawley rats.

BACKGROUND AND RATIONALE: Despite the popularity of polysubstance abuse among recreational methylendioxymethamphetamine (MDMA) users, relatively few controlled experimental studies have documented the neurobehavioral effects of MDMA in combination with other abused substances. OBJECTIVE: In this study, the combined acute effects of MDMA and cocaine were examined by conducting in vivo microdialysis in the rat nucleus accumbens while simultaneously monitoring locomotor activity. METHODS: Male Sprague-Dawley rats were administered cocaine (10 or 20 mg/kg, i.p.), MDMA (1.5 or 3.0 mg/kg, i.p.), or one of four combinations of cocaine and MDMA during microdialysis experiments. Locomotor activity was monitored, and dialysis samples were collected every 30 min for 3 h prior to injections, for one 30-min period following saline injections, and for an additional 3-h period following drug injections. Samples were analyzed for dopamine content by high-performance liquid chromatography with electrochemical detection. RESULTS: Significant differences in locomotor activity and dopamine efflux were found among treatment groups, with some MDMA/cocaine combinations producing significantly greater increases compared to single doses of cocaine or MDMA within the first 30 min after injection. CONCLUSION: Considering the popularity of polysubstance use among recreational MDMA users, the clinical implications of the current findings warrant further investigation.

[The profile of drug addicts attending the Sainte Marguerite University Hospital in Marseille analysis of the active file from 1996 to 2001]. / Données qualitatives d'une cohorte traitée par méthadone ou buprénorphine haut dosage B Marseille, entre 1996 et 2001.

OBJECTIVES: Present the evolution in the characteristics of drug addicts treated in the Addictions-Sud centre (Marseille) between 1996 and 2001, and compare the profile of patients according to the substitution therapy prescribed. METHODS: Descriptive analysis of the data collected from the inclusion questionnaire of patients seen during a hospital consultation in the centre and registered in a substitution program (n = 585 patients). RESULTS: In our active file, the use of heroin and injections has decreased since 1996, whereas the consumption of cocaine and above all amphetamines and LSD has greatly increased. When treated, 60% of the patients were administered methadone and 40% BHD. (The patients included in the methadone program (n = 348) were considerably older and frequently HIV or hepatitis C-infected than those treated with BHD (n = 229)). The proportion of patients who had previously undertaken withdrawal or substitution measures, and who continued to inject drugs, was greater in the group of patients in the methadone program. The presence of depression, psychotic disorders and anxiety was noted respectively in 46, 30 and 24% of the patients treated. DISCUSSION AND CONCLUSION: Today, it is crucial that information on the treatment of drug addicts should be reinforced, so as to measure the progression of the problems encountered, specify the indications of the two substitution products currently prescribed and understand the impact they have on the psychiatric disorders and viral pathologies frequently noted in drug addicts.

Effects of bremazocine on self-administration of smoked cocaine base and orally delivered ethanol, phencyclidine, saccharin, and food in rhesus monkeys: a behavioral economic analysis.

There is increasing evidence that kappa-opioid receptor agonists modulate cocaine-maintained behavior, and limited findings implicate the involvement of kappa-opioid receptors in ethanol-maintained behaviors. The purpose of the present study was to investigate the effects of bremazocine, a kappa-opioid agonist, on the self-administration of smoked cocaine base and oral ethanol in rhesus monkeys (Macaca mulatta). To determine the selectivity of bremazocine, the effects of bremazocine pretreatment on the oral self-administration of phencyclidine (PCP), saccharin, and food were also examined. Adult male rhesus monkeys were trained to self-administer oral ethanol, PCP, saccharin (n = 8), food (n = 6), or smoked cocaine base (n = 6) and water during daily sessions. Bremazocine (0.00032-, 0.001-, and 0.0025-mg/kg i.m.) injections were given 15 min before session. The 4 days of stable behavior before pretreatment served as baseline. Demand curves (consumption x fixed ratio; FR) were obtained for smoked cocaine base, ethanol, and PCP by varying the cost (FR) of drug deliveries and measuring consumption (deliveries). Bremazocine (0.001 mg/kg) was administered at each FR value in nonsystematic order. Results indicate that bremazocine dose dependently reduced cocaine, ethanol, PCP, and saccharin intake. Food intake was affected less by bremazocine than the other substances in five of the six monkeys. Generally, bremazocine treatment reduced the demand for cocaine, ethanol, and PCP as well as other measures of response strength. These results extend the findings that kappa-agonists reduce the self-administration of drug and nondrug reinforcers to smoked cocaine base and oral ethanol, PCP, and saccharin in rhesus monkeys.

Monitoring synthetic drug markets, trends, and public health.

The Drugs Information and Monitoring System (DIMS) in The Netherlands is a toxicoepidemiologic monitor of drug markets that was established in 1992. Its main focuses are to identify the compounds of synthetic drugs, describe prevalence and trends, and identify health risks. Here we discuss the insights gained in the Ecstasy market, based on the weekly testing of more than 100 drug samples, and key information of synthetic drug users delivering drug samples and personnel participating in the DIMS network. Pills used as Ecstasy may contain a wide variety of compounds. The percentage of samples containing MDMA increased slowly reaching almost 75% in 1996, but decreasing sharply in 1997. Amphetamines ("speed" and "ice") and experimental varieties were found in at least one third of the pills. Origins and effects of this development are discussed, as well as the risk assessment. In 1998 the percentage of MDMA pills increased more than ever before, indicating among other things that consumers prefer the conventional product. However, the use of "speed" and other drugs may also be stimulated by the decrease in 1997 of the percentage of MDMA pills. With more new types of drugs likely in the next century, a monitor such as DIMS provides important surveillance and data for public health and preventive aims.