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Studies of psychedelic-assisted therapy with LSD, psilocybin, MDMA, and related substances show clinical promise but inadequately assess side effects. Measuring side effects is challenging because they are not always easily differentiated from treatment effects or disease symptoms and show high heterogeneity, variable duration and impact, and sensitivity to context. A systematic questionnaire describing important characteristics of side effects of psychedelics and MDMA would greatly improve on previous methods. We aimed to create a standardized tool for recording clinically relevant side effects of psychedelics and MDMA, including their severity, duration, impact, and treatment-relatedness. We constructed the Swiss Psychedelic Side Effects Inventory (SPSI) based on insights from previous research. It was pilot tested in 145 participants from three studies. Structured feedback from an expert panel was used to improve validity and feasibility. The final SPSI contains 32 side effects and standardized follow-up questions about their severity, impact, treatment-relatedness, and duration. It is compatible with any study design and can be administered as an interview or self-report at any timepoint after treatment with psychedelics or MDMA. The SPSI omits relatively unimportant side effects for brevity's sake, though space for additional symptoms is given. Future studies are needed to confirm its validity in different contexts. The SPSI is available in English and German for collecting systematic data on side effects from psychedelics and MDMA. This information is vital for improving clinical decisions, informed consent, and patient safety. • Psychedelics and MDMA can cause a unique profile of side effects which are not well-captured by the methods used in previous studies. • Psychedelic side effects vary in their severity, duration, and subjective impact. • Using previous studies, pilot data, and expert feedback, we developed the Swiss Psychedelic Side Effects Inventory (SPSI). • The SPSI contains 32 side effects and assesses their severity, impact, duration, and treatment-relatedness. • The SPSI can be used at any timepoint after psychedelic administration in any study of psychedelics or MDMA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neurorehabilitation in military populations is complicated by higher rates of PTSD and unique characteristics of military institutions. These factors can adversely impact the patient-therapist therapeutic alliance and engagement with the rehabilitation process leading to poorer outcomes. MDMA is a non-classical psychedelic with pro-social and fear regulating properties. MDMA-assisted therapy is being explored as a novel treatment for PTSD that potentially offers rapid symptom improvement and enhances therapeutic alliance. OBJECTIVE: A review of MDMA-assisted therapy for PTSD is provided in the context of neurorehabilitation in military populations. The molecular mechanism of MDMA is outlined and a novel application of MDMA for neurorehabilitation is proposed. METHODS: This is an expert review and synthesis of the literature. RESULTS: Results from late-stage clinical trials suggest MDMA-assisted therapy for PTSD would be of particular benefit for military populations with PTSD. The unique pro-social properties of MDMA could be leveraged to enhance the therapeutic alliance and patient engagement during neurorehabilitation. CONCLUSION: The unique qualities and benefits of MDMA and MDMA-assisted therapy for PTSD suggest relevant application in military personnel undergoing neurorehabilitation. There are many similarities in patient-therapist dynamics in PTSD treatment and neurorehabilitation. The properties of MDMA which enhance therapeutic alliance, downregulate fear, and increase cognitive flexibility would potentially benefit both military personnel with and without PTSD undergoing neurorehabilitation. [ABSTRACT FROM AUTHOR]

This article reports the findings of an online survey designed to collect information about substance use (licit, illicit, or pharmaceutical) and mental health (depression or anxiety) among social workers. Among the 489 participants, Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) screenings indicated symptoms of depression and anxiety at a higher prevalence than those of the general Canadian population. There were relatively few correlations between mental health scores and substance use. PHQ-9 total score significantly predicted past-year antidepressant use and past-year sleeping medication use. GAD-7 total score significantly predicted past-year benzodiazepine use and past-year melatonin use. Effects of substances (e.g. cannabis, alcohol, benzodiazepines, cocaine, ecstasy) were predominantly beneficial or nonproblematic (e.g. enjoyment/pleasure; socializing enhanced; concentration/focus improved). Subjective experiences of social workers should be sought to understand potential relationships between mental health scores and enhancement effects of substance use. Substances are being used, at least in part, for their performance-enhancing effects to meet the expectations of day-to-day life. Interventions can shift toward root causes, with institutions held more accountable for supporting social workers and promoting "workplace care." [ABSTRACT FROM AUTHOR]

3,4-methylenedioxymethamphetamine (MDMA) assisted therapy has been shown to be a safe and effective treatment for PTSD and emerging research suggests a change in personality traits may be a factor in treatment response. Most prior research on MDMA and personality has focused on cross-sectional comparisons of MDMA users and non-users; as such, well-controlled research assessing personality and affective states change following MDMA vs placebo administration is needed. In the current pre-registered study, we investigated the impact of MDMA administration on five-factor model (FFM) traits and affective states before and 48 h after drug administration in a randomized, placebo-controlled study of healthy adults (N = 34). Statistical significance was not observed for the four a priori hypotheses; however, medium effect sizes were found between MDMA administration and trait Openness and Positive Affect 48 h following drug administration, compared to placebo (d = .79 and .51, respectively). This study provides initial results to help guide future well-powered studies with large samples and longer follow-up timepoints to continue to investigate how MDMA impacts personality and emotional experience, which may inform optimization of MDMA treatment approaches. [ABSTRACT FROM AUTHOR]

As clinical trials for psychedelics move into phase III in the USA, Europe must address its lag in integrating professional education around psychedelic-assisted therapy (PAT) and supporting psychedelic drug research. This paper evaluates the necessary frameworks for implementing PAT in Germany, emphasizing the nation's potential leadership role within the European Union. With Australia having already approved MDMA and psilocybin for mental health indications, the Ukrainian government exploring MDMA treatment for war-related PTSD, and initial clinical trials involving MDMA and LSD with patients in Switzerland which restarted the restricted medical use of these substances around 2014, the medical authorization of psychedelics in these countries establishes precedent showcasing both the promise and challenges of researching and implementing PAT in nations where the substances were formally scheduled as illicit substances. Key challenges include establishing rigorous standards for practitioner training, accessibility, and defining regulatory oversight. This paper focuses on the development of robust infrastructure in Germany, which will support the roll out of PAT, and details ethical considerations, training protocols, and governmental roles in the formulation of treatment frameworks. This approach aims not only to guide Germany in adopting PAT but also to influence broader European policy, ensuring that patients receive ethically sound and proficient care. The findings suggest pathways for Europe to reclaim its historical lead in psychiatric and therapeutic innovation. [ABSTRACT FROM AUTHOR]

Introduction: Gender and sexual minority/minoritized groups are at a higher risk of substance misuse and related harm compared to the rest of the population. However, limited research has focused on understanding the extent of these issues and the support needs of all minoritized groups within the LGBTQ + population. Methods: This qualitative cross-sectional survey sought to explore LGBTQ + individuals' perspectives on substance use and treatment experiences. Researchers used a manual thematic analysis approach to thoroughly study the data, examining each part closely to uncover themes and patterns. Co-produced with stakeholders and developed with input from LGBTQ + individuals with lived experience, the survey included 38 participants across the UK. Results: Cannabis (83% n = 20), ecstasy (68% n = 15), and cocaine (67% n = 16) were commonly used substances, while some participants (19% n = 6) reported consuming high levels of alcohol. Many respondents highlighted the role of "stigma" and peer pressure within the LGBTQ + communities as a motivator for substance use. Participants expressed a preference for informal support due to fears of "discrimination" from formal treatment services. Conclusions: The study underscores the need for research inclusive of all LGBTQ + groups and highlights the importance of tailored interventions that address the diverse needs of LGBTQ + individuals. Further exploration of peer-led interventions is necessary to assess their effectiveness. The findings emphasize the necessity of person-centered treatment approaches that recognize the heterogeneity of service users. [ABSTRACT FROM AUTHOR]

Drug use in gay men (GM) in Mexico has been explored mainly from an epidemiological perspective with little research on the impact on well-being, particularly due to consumption dynamics and the sociocultural elements that may intervene in the process. Objective: To analyze drug use and its implications for the well-being of gay men in Mexico. Methods: Three focus groups were held in May 2022 with 19 middle-class gay men from Mexico's northern, central, and southern regions through the Zoom videoconference platform. With the information collected, a content analysis was carried out investigating the following categories: types of substances consumed, frequency, causes, changes in the form of consumption, and effects on well-being. Results: The participants reported low consumption of tobacco or alcohol compared to that of other substances such as inhaled nitrites (poppers), crystal methamphetamine, ecstasy, marijuana, and cocaine. Four environments were identified based on the journey and changes in consumption patterns: the environment of initiation drugs, that of recreational drugs, that of drugs for sexual practices, and that of drugs for greater sexual pleasure. Four aspects related to the motivations for drug use were identified: the family context on drugs, homophobia, HIV diagnosis, and the COVID-19 pandemic. Finally, three main effects on well-being linked to the use of drugs for sexual practices, particularly crystal methamphetamine, are reported: security and violence, social relationships, and health. The findings are discussed within the context of the Set and Setting and Minority Stress theoretical frameworks. Conclusions: Drug use in this population needs to be approached from a multidimensional perspective, considering the sociocultural specificities determining how it is carried out. [ABSTRACT FROM AUTHOR]

Background: This paper documents changes in the prevalence and intensity of soil-transmitted helminth (STH) infections in the Geshiyaro project in the Wolaita zone of Southern Ethiopia. Methods: The Geshiyaro project comprises three intervention arms. Arm 1 is subdivided into the Arm 1 pilot (one district) and Arm 1 (four other districts), both receiving integrated community-wide mass drug administration MDA (cMDA) with intensive water, sanitation, and hygiene (WaSH) interventions. Arm 2 involves 18 districts with cMDA interventions plus the existing government-led One WaSH program, while Arm 3 serves as a control with school-based MDA (sMDA) interventions plus the existing government-led One WaSH program in three districts. The study is designed as a cohort investigation over time, with the establishment of longitudinal sentinel sites where infection levels are assessed annually. A total of 45 longitudinal parasitological surveillance sentinel sites are being used across all three intervention arms to monitor STH prevalence and intensity of infection. From each of the 45 sentinel sites, 150 individuals were randomly selected, stratified by age and gender. The t-test and analysis of variance (ANOVA) were employed to compare infection prevalence and intensity across the three study arms over time. Results: The prevalence of STH decreased significantly from 34.5% (30.6%, 38.5%) in 2019 to 10.6% (8.3%, 13.4%) in 2022/2023 (df = 1, P < 0.0001) in the Arm 1 pilot, from 27.4% (25.2%, 29.7%) in 2020 to 5.5% (4.4%, 6.7%) in 2023 (df = 1, P < 0.0001) in Arm 1, from 23% (21.3%, 24.8%) in 2020 to 4.5% (3.7%, 5.3%) in 2023 (df = 1, P < 0.001) in Arm 2, and from 49.6% (47.4%, 51.7%) in 2021 to 26.1% in 2023 (df = 1, P < 0.0001) in Arm 3. The relative reduction in the prevalence of any STH was the highest in the arms employing cMDA, namely Arm 2, with a decrease of 82.5% (79.3%, 84.2%), followed by Arm 1 with a reduction of 80.1% (75.3%, 84.6%), and then the Arm 1 pilot with a decrease of 69.4% (60.1%. 76.6%). Arm 3 employing sMDA had the lowest decrease, with a reduction of 46.9% (43.6%, 51%). The mean intensity of infection (based on Kato–Katz egg count measures) for Ascaris lumbricoides species, which was the dominant STH species present in the study area, decreased significantly in Arms 1 and 2, but only slightly in Arm 3. The prevalence of hookworm and Trichuris trichiura infections were found to be very low in all arms but also decreased significantly. Conclusions: The reduction in the prevalence and intensity of STH in Arms 1 and 2 revealed steady progress towards transmission interruption based on cMDA intervention, but additional efforts with MDA coverage and WaSH interventions are needed to achieve a prevalence threshold < 2% based on the quantitative polymerase chain reaction (qPCR) diagnostic method. [ABSTRACT FROM AUTHOR]

Science on methylenedioxymethamphetamine (MDMA) and MDMA-like substances is faced with the unique situation that this class of psychoactive agents is referred to with two basic names for its effects on the mind: empathogens and entactogens. Empathogen usually refers to the prosocial, empathetic, and openness properties of MDMA, while entactogen usually refers to the introspective and self-awareness properties of this substance. We review the origin and usage of the two terms, and also review recent findings that support that MDMA is an empathogen and an entactogen. Mostly no specified reasons can be detected whether research groups employ the term "entactogenic," "empathogenic," both, or neither, in their publications. A case is made that the use of two basic names for the effects on the mind for the same class of psychoactive substances is not warranted because a holistic principle underlies empathogenic and entactogenic properties of MDMA: an intense feeling of connection. Entactogenic characterizes being deeply connected to oneself, and empathogenic being deeply connected to others. We therefore suggest the name connectogen as the new basic name for the mind effects of MDMA and MDMA-like substances, a term having the connotation of producing a joining together/producing a connection. Thus, MDMA is basically a connectogen with at least the two major connective properties: entactogenic (intrapersonal) and empathogenic (interpersonal). Furthermore, first evidence shows that MDMA might also have further connectogenic properties such as a strong sense of connection with the here-and-now, the body, the world, and with spiritual principles. Finally, we compare connectogenic properties of MDMA with connectogenic properties of classic psychedelics, and lay out some future research in this regard. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

College students have been recognized as a risk group for substance use. Nevertheless, coherent risk factors for stimulant use remain to be elucidated. The objective of this paper is to identify risk factors associated with the recreational use of MDMA, cocaine, amphetamine and methamphetamine. An online questionnaire was distributed among colleges in Berlin. A sample of 12,914 college students participated, of which 9,382 met the inclusion criteria. Past-month prevalence was 7.0% for MDMA, 6.7% for amphetamine, 5.8% for cocaine and 0.1% for methamphetamine. Associated factors included male gender, "other" gender, homosexual and bisexual orientation, open relationship status or being single, engaging in sexual risk-taking behavior, having a psychiatric diagnosis, tobacco use, drinking alcohol and an increased number of (illicit) substances consumed in the past month and in life. Berlin college students showed a substantially higher prevalence of stimulant use compared to both the general population and college students in other cities. Certain parameters, e.g., polydrug use, were particularly high in this group. The results can be used in further development of prevention efforts. However, conclusions about causality are limited by the cross-sectional nature of this study, highlighting the necessity for longitudinal studies in this field. [ABSTRACT FROM AUTHOR]

Objectives: The Australian government recently rescheduled psilocybin and 3,4-methylenedioxymethamphetamine for limited clinical uses. This change has raised various regulatory concerns and challenges for the field of psychedelic-assisted therapy. To provide clarity, we aimed to comprehensively catalogue the matters relating to psychedelic-assisted therapy that are or could be regulated. Methods: We conducted a desktop review of the literature and current regulatory sources, semi-structured interviews with professionals who had expertise in fields relating to psychedelic-assisted therapy and a framework analysis to generate a taxonomy of relevant regulatory matters. In relation to each matter, we further identified what type of regulation (if any) currently applies to that matter, any uncertainty as to how the matter should be addressed in clinical practice in the context of current regulation and whether there are conflicting views as to how the matter could or should be further regulated. Results: The taxonomy is structured into six main regulatory domains, three of which have a substantial proportion of matters with uncertainty or conflicting views: Service Establishment, Practitioner, and Treatment Delivery. Key examples of such matters include the location of services and facilities required, which professionals are eligible to become psychedelic therapists, and with what qualifications and experience. Matters in the remaining three domains, Patient Evaluation, Drug Supply and Service Oversight, appear by comparison relatively settled, with regulation either well-established or thought unnecessary. Conclusions: The taxonomy provides a roadmap for health services establishing and implementing a psychedelic-assisted therapy program, or for government and other policymakers when determining areas that may require further regulation. [ABSTRACT FROM AUTHOR]

Ecstasy/Molly/MDMA is a widely used substance often taken in combination with other drugs in different contexts. The current study assessed ecstasy use patterns, concurrent substance use and the context of ecstasy use among an international sample of adults (N = 1,732). Participants were 87% white, 81% male, 42% college educated, 72% employed, with a mean age of 25.7 (SD = 8.3). Using the modified UNCOPE, risk for ecstasy use disorder was 22% overall, and significantly higher among younger individuals and those with greater frequency and quantity of use. Participants reporting risky ecstasy use endorsed significantly higher use of alcohol, nicotine/tobacco, cannabis, cocaine, amphetamine, benzodiazepines, and ketamine compared to those at lower risk. Great Britain (aOR = 1.86; 95% CI [1.24, 2.81]) and Nordic countries (aOR = 1.97; 95% CI [1.11, 3.47]) were approximately 2 times more likely to exhibit risk for ecstasy use disorder than the United States, Canada, Germany, and Australia/New Zealand. Taking ecstasy at home emerged as a common setting followed by electronic dance music events and music festivals. The UNCOPE may be a useful clinical tool for detecting problematic ecstasy use. Harm reduction interventions for ecstasy should target young people, substance co-administration, and context of use. [ABSTRACT FROM AUTHOR]

Introduction: People who inject drugs experience stigma across multiple settings, including when accessing health‐care services, however, comparatively little is known about experiences of stigma towards other groups of people who use illegal drugs. This paper examines experience of, and factors associated with, stigma among two samples of people who use illegal drugs when visiting both specialist alcohol and other drug (AOD) and general health‐care services. Methods: Australians who regularly (i.e., ≥monthly) inject drugs (n = 879; illicit drug reporting system [IDRS]) or use ecstasy and/or other illegal stimulants (n = 700; ecstasy and related drugs reporting system [EDRS]) were surveyed between April and July 2022 about past 6‐month experience of stigma in the above services. Multi‐variable regression analyses were performed to determine the socio‐demographic, drug use and health factors associated with stigma. Results: Experiences of stigma in general health‐care services were more common among IDRS (40%) than EDRS (24%; p < 0.001) participants, however, experiences were comparable in specialist AOD health‐care settings (22% and 20%, respectively; p = 0.687). Gender identity and experiencing high psychological distress were associated with experiencing stigma across both samples. Past‐year overdose was associated with experiencing stigma among the IDRS sample, while unstable housing and incomplete high school education were associated with experiencing stigma in the EDRS sample. Discussion and Conclusions: Experiences of stigma when accessing health‐care services are relatively common across different populations of people who use illegal drugs. Our findings highlight the multiple and intersecting dimensions of stigma and provide further support for recent calls for a universal precautions approach to stigma in health care. [ABSTRACT FROM AUTHOR]

3,4-Methylenedioxymethamphetamine (MDMA) is being investigated in controlled clinical trials for use as an adjunct medication treatment for post-traumatic stress disorder. MDMA is metabolized by N-demethylation, primarily by CYP2D6, to its main inactive metabolite, 4-hydroxy-3-methoxymethamphetamine. It is also metabolized to a lesser extent by CYP1A2, CYP2B6, and CYP3A4 to its active metabolite, 3,4-methylenedioxyamphetamine. Considering the extensive hepatic metabolism and excretion, MDMA use in psychiatry raises concerns over druginduced liver injury (DILI), a rare but dangerous event. Majority of the drugs withdrawn from the market for liver injury caused death or transplantation at frequencies under 0.01%.Unfortunately, markers for liver injurywere notmeasured in most published clinical trials. At the same time, no visible DILI-related symptoms and adverse events were observed. Idiosyncratic DILI cases are rarely registered during clinical trials due to their rare nature. In this study, we surveyed a larger, over 1,500, and a more diverse set of reports from the FDA Adverse Event Reporting System and found 23 cases of hepatic injury and hepatic failure, in which MDMA was reported to be taken in addition to one or more substances. Interestingly, 22 out of 23 cases had one or more listed drugs with a known DILI concern based on the FDA's DILIrank dataset. Furthermore, only one report had MDMA listed as the primary suspect. Considering the nearly 20 million doses of MDMA used annually, this single report is insufficient for establishing a significant association with DILI. [ABSTRACT FROM AUTHOR]

The article focuses on two psychedelic drugs, namely 3, 4-methylenedioxy-methamphetamine (MDMA) and psilocybin, that are awaiting approval from the U.S. Food and Drug Administration (FDA). Topics include history of psychedelics, uses of psychedelics as treatment for mental illness, initiatives for psychedelic reform, regulatory framework surrounding psychedelic research, calls for the FDA to provide guidance for state licensing boards and initiation of scheduling reform for MMDA and psilocybin.

Hyperthermia induced by phenethylamines, such as 3,4–methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia. [ABSTRACT FROM AUTHOR]

The 3,4‐methylenedioxymethamphetamine (MDMA) has long been used non‐medically, and it is currently under investigation for its potential therapeutic benefits. Both uses may be related to its ability to enhance empathy, sociability, emotional processing and its anxiolytic effects. However, the neural mechanisms underlying these effects, and their specificity to MDMA compared to other stimulants, are not yet fully understood. Here, using electroencephalography (EEG), we investigated the effects of MDMA and a prototypic stimulant, methamphetamine (MA), on early visual processing of socio‐emotional stimuli in an oddball emotional faces paradigm. Specifically, we examined whether MDMA or MA enhance the processing of facial expressions, compared to placebo, during the early stages of visual perception. MDMA enhanced an event‐related component that is sensitive to detecting faces (N170), specifically for happy and angry expressions compared to neutral faces. MA did not affect this measure, and neither drug altered other components of the response to emotional faces. These findings provide novel insights into the neural mechanisms underlying the effects of MDMA on socio‐emotional processing and may have implications for the therapeutic use of MDMA in the treatment of social anxiety and other psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background and aims: Adolescent polysubstance use has been associated with adverse social and health outcomes. Our aim was to measure rates and transitions to polysubstance use during adolescence and identify factors associated with initiation and discontinuation of polysubstance use. Design: Prospective cohort study. Multistate Markov modelling was used to estimate rates and identify correlates of transitions between substance use states. Setting and participants: Adolescent‐parent dyads (n = 1927; adolescents in grade 7, age ≈13 years) were recruited from Australian schools during 2010/11 (Wave 1). Adolescents were surveyed annually until 2016/17 (n = 1503; age ≈19 years; Wave 7) and parents were surveyed annually until 2014/15 (Wave 5). Measurements Alcohol, tobacco, cannabis and 3,4‐methylenedioxymethamphetamine (MDMA) use outcomes were collected at Waves 3–7. Potential confounders were collected at Waves 1–6 and consisted of sex, anxiety and depression symptoms and externalizing problems, parental monitoring, family conflict and cohesion, parental substance use and peer substance use. Covariates were age and family socioeconomic status. Findings Few adolescents engaged in polysubstance use at earlier waves (Wave 3: 5%; Wave 4: 8%), but proportions increased sharply across adolescence (Waves 5–7: 17%, 24%, 36%). Rates of transitioning to polysubstance use increased with age, with few (<9%) adolescents transitioning out. More externalizing problems (odds ratio [OR] = 1.10; 99.6% confidence interval [CI] = 1.07–1.14), parental heavy episodic drinking (OR = 1.22; 99.6% CI = 1.07–1.40), parental illicit substance use (OR = 3.56; 99.6% CI = 1.43–8.86), peer alcohol use (OR = 5.68; 99.6% CI = 1.59–20.50) and peer smoking (OR = 4.18; 99.6% CI = 1.95–8.81) were associated with transitioning to polysubstance use. Conclusions: Polysubstance use in Australia appears to be rare during early adolescence but more common in later adolescence with low rates of transitioning out. Externalizing problems and greater parental and peer substance use are risk factors for adolescent polysubstance use that may be suitable intervention targets. [ABSTRACT FROM AUTHOR]

• Less cognitive and emotional empathy and elevated social aggression in METH users. • Empathy and emotion sensitivity in MDMA users was comparable to controls. • Stronger increase in social aggression under provocation among MDMA users. • Higher MDMA or METH levels in hair both correlated with lower cognitive empathy. Methamphetamine (METH, "Crystal Meth") and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") share structural-chemical similarities but have distinct psychotropic profiles due to specific neurochemical actions. Previous research has suggested that their impact on social cognitive functions and social behaviour may differ significantly, however, direct comparisons of METH and MDMA users regarding social cognition and interaction are lacking. Performances in cognitive and emotional empathy (Multifaceted Empathy Test) and emotion sensitivity (Face Morphing Task), as well as aggressive social behaviour (Competitive Reaction Time Task) were assessed in samples of n = 40 chronic METH users, n = 39 chronic MDMA users and n = 86 stimulant-naïve controls (total N = 165). Self-reports and hair samples were used to obtain subjective and objective estimates of substance use patterns. METH users displayed diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behaviour regardless of provocation, and self-reported heightened trait anger relative to controls. MDMA users diverged from the control group only by exhibiting a distinct rise in punitive behaviour when faced with provocation. Correlation analyses indicated that both higher hair concentrations of MDMA and METH may be associated with reduced cognitive empathy. Moreover, greater lifetime MDMA use correlated with increased punitive behaviour among MDMA users. Our findings confirm elevated aggression and empathy deficits in chronic METH users, while chronic MDMA users only displayed more impulsive aggression. Dose-response correlations indicate that some of these deficits might be a consequence of use. Specifically, the dopaminergic mechanism of METH might be responsible for social-cognitive deficits. [ABSTRACT FROM AUTHOR]

Purpose of Review: On 1 July 2023, the Therapeutic Goods Administration approved 3,4‐methylenedioxymethamphetamine (MDMA)‐assisted psychotherapy for the treatment of post‐traumatic stress disorder (PTSD). Accordingly, the purpose of this review is to provide an overview of MDMA and what pharmacists should know as this treatment emerges. Sources of Information: EMBASE, MEDLINE, and CINAHL databases were searched to provide an overview narrative synthesis of the literature on MDMA, relevant to pharmacists. Key Findings: Cytochrome P450 2D6 is involved in the metabolic pathway of MDMA, an enzyme inhibited by a number of drugs used in the pharmacological management of PTSD (e.g. selective serotonin reuptake inhibitors). Co‐administration of these drugs with MDMA can lead to increases in plasma MDMA concentrations. Additionally, inhibition of the serotonin transporter can inhibit the uptake of MDMA into the presynaptic terminal, dampening the effects of MDMA and potentially, limiting the effectiveness of MDMA‐assisted psychotherapy. Accordingly, these drugs are typically withdrawn prior to treatment with MDMA. While selective serotonin reuptake inhibitor/serotonin noradrenaline reuptake inhibitor drugs with MDMA are unlikely to cause serotonin toxicity, monoamine oxidase inhibitors can. Other drugs, such as caffeine, alcohol, over‐the‐counter medicines, and complimentary/alternative medicines, can also interact with MDMA. Conclusion: With a detailed knowledge of the pharmacology of MDMA, pharmacists may play a role in MDMA‐assisted psychotherapy by collecting a detailed medication history and assisting clinicians in the withdrawal of interacting medicines. [ABSTRACT FROM AUTHOR]

The general use of cocaine is increasing in recent years, while the trend for 3,4-methylenedioxymethamphetamine (MDMA) is less clear. The relationship between blood concentrations and impairment is poorly understood, which complicates interpretation. The aims of this study were to report prevalence and blood concentrations of cocaine and MDMA in drugged drivers, and to investigate the relationship between blood concentrations and impairment. Samples of whole blood were collected from apprehended drivers in the period 2000 – 2022, and a clinical test of impairment (CTI) was simultaneously performed. The samples were initially analyzed for cocaine and MDMA using gas chromatography–mass spectrometry (until 2009 and 2012, respectively), and later using ultra-high-performance liquid chromatography–tandem mass spectrometry. Overall, cocaine was detected in 2,331 cases and MDMA in 2,569 cases. There were 377 and 85 mono cases of cocaine and MDMA, respectively. In the mono cases, the median cocaine concentration was 0.09 mg/L (range: 0.02–1.15 mg/L), and 54% of the drivers were clinically impaired. The median MDMA concentration was 0.19 mg/L (range: 0.04–1.36 mg/L), and 38% were clinically impaired. There was a statistically significant difference in the median cocaine concentration between drivers assessed as not impaired (0.07 mg/L) and drivers assessed as impaired (0.10 mg/L) (P  = 0.009). There was also a significant effect of the blood concentration of cocaine (adjusted odds ratio [aOR] = 6.42, 95% confidence interval [CI] = 1.13–36.53, P  = 0.036) and driving during the evening/night-time (aOR = 2.17, 95% CI = 1.34–3.51, P  = 0.002) on the probability of being assessed as impaired on the CTI. No significant differences were found for MDMA. Many drivers are not assessed as impaired on a CTI following cocaine or especially MDMA use. For cocaine, a relationship between blood concentrations and impairment was demonstrated, but this could not be shown for MDMA. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Long‐COVID syndrome lacks effective holistic treatment options. We present a case of a 41‐year‐old fully vaccinated female with Long‐COVID syndrome who obtained significant symptomatic relief after self‐medicating with psilocybin and MDMA. Long‐COVID, a syndrome persisting after the acute phase of coronavirus disease 2019 (COVID‐19), lacks effective holistic treatment options. We present a case of a 41‐year‐old fully vaccinated female with Long‐COVID syndrome who obtained significant symptomatic relief by self‐prescribing psilocybin and MDMA. Future research is needed to assess safety and efficacy. [ABSTRACT FROM AUTHOR]

Background: Methylenedioxymethamphetamine (MDMA) is a popular drug worldwide and use is prevalent in Aotearoa New Zealand. Although associated with some significant harms, including fatalities, MDMA is ultimately less harmful than other commonly consumed drugs. We aimed to expand the understanding of MDMA harm and harm reduction strategies from a consumer perspective so that national harm reduction efforts can be better informed. Methods: We conducted 14 semi-structured focus group discussions including 60 people (aged 18–67, median = 21) who use MDMA in the Southern region of Aotearoa New Zealand to explore their thoughts and experiences regarding MDMA associated harm and harm reduction. Reflexive thematic analysis was conducted from a critical realist perspective. Results: Five themes were generated; (1) Mindset and setting matters; (2) Looking after your body and mind, not overdoing it; (3) Other substances increase risk and harm; (4) Trusted friends and peers are protective; and (5) Valid information is key for healthy self-determination; and one subtheme 5.1) Drug checking is essential harm reduction. Conclusions: We discuss the implications for MDMA consumers and aim to inform national drug policy and the harm reduction practices of consumers and organisations, for the ultimate purpose of reducing MDMA-related harm in Aotearoa New Zealand. [ABSTRACT FROM AUTHOR]

A novel analytical method was developed for the simultaneous quantification of the R/S-enantiomers of amphetamine, methamphetamine, MDA and MDMA in hair samples using liquid chromatography-tandem mass spectrometry (LC–MS-MS). This method involved a straightforward derivatization step with dansyl chloride and the use of a chiral column, enabling the separation and quantification of all eight enantiomers in a single analysis. The method exhibited excellent linearity across a concentration range of 0.03–3.00 ng/mg for each enantiomer. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 6% and 9%, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated high sensitivity, with limits of detection (LOD) below 8 pg/mg and limits of quantification (LOQ) below 19 pg/mg for all analytes. Extraction recovery exceeded 79%, and matrix effects were minimal for all analytes. Processed sample stability evaluations revealed consistent results with deviations below 11% for all analytes. Application of the method to 32 authentic human hair samples provided valuable insights into amphetamine use patterns, allowing differentiation between medical amphetamine consumption and illicit use based on enantiomeric composition. Additionally, the method detected co-use of methamphetamine, MDA or MDMA in some samples, highlighting its applicability in drug monitoring and real-life case scenarios within a forensic institute. This innovative analytical approach offers a sensitive and selective method for enantiomeric differentiation of amphetamine, methamphetamine, MDA and MDMA in human hair samples, providing a valuable tool for forensic and clinical investigations. [ABSTRACT FROM AUTHOR]

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia--behavioral tests modeling empathy in mice--with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to measure the effectiveness of an on‐line, neuroscience‐based harm reduction intervention (The Illicit Project) on substance use, harms and knowledge over a 12‐month period. Design: We used a two‐arm cluster‐randomized controlled trial. Setting: The study was conducted at eight secondary schools across New South Wales, Australia. Participants: A total of 950 (mean age = 15.9; standard deviation = 0.68) in grades 10–12 at participating schools in 2020 took part. Intervention and comparator: The Illicit Project intervention group (schools = five, n = 681) received an on‐line, universal substance use and harm reduction programme over three classes. The active control group (schools = three, n = 269) received school‐based health education as usual. Measurements Self‐report questionnaires assessed primary [alcohol, nicotine, cannabis, 3,4‐methylenedioxymethamphetamine (MDMA), cocaine and prescription drug misuse] and secondary outcomes (alcohol‐related harms and drug literacy) at baseline and the 6‐ and 12‐month follow‐up assessment. Findings Approximately 63% (n = 595) of the sample completed the 12‐month follow‐up assessment, including 58% of the intervention group (n = 396/679) and 66% of the active control group (n = 179/271). Participants in the intervention group had slower annual increases in binge drinking [odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12–0.89], nicotine use (OR = 0.80, 95% CI = 0.52–1.23), MDMA use (OR = 0.14, 95% CI = 0.02–1.00), cocaine use (OR = 0.06, 95% CI = 0.01–0.64) and prescription drug misuse (OR = 0.07, 95% CI = 0.01–0.54) compared with the active control group. There was limited evidence of an intervention effect on cannabis use and alcohol‐related harm (P > 0.5). The secondary outcomes showed that the intervention group maintained higher levels of drug literacy knowledge (β = 3.71, 95% CI = 1.86–5.56) and harm reduction help‐seeking skills (β = 1.55, 95% CI = 0.62–2.48) compared with the active control group. Conclusion: The Illicit Project (an on‐line, neuroscience‐based substance use harm reduction intervention) was effective in slowing the uptake of risky substance use and improving drug literacy skills among late secondary school students in Australia, compared with school‐based health education as usual. [ABSTRACT FROM AUTHOR]

To provide better Quality of Service (QoS), which is expected in contemporary 6G wireless networks. We project a MDMA scheme to fulfill UE-specific QoS needs with the aid of multi-dimensional radio resource cost. This method can be successfully called Multi-Dimensional Radio Resource Allocation (MDRA). Specifically, the planned scheme incorporates two novel aspects: for each UE, the choice of user-specific nonorthogonal multiple approach mode whose cost is determined by UE-specific non-orthogonal interference cancellation; and allocating multiple dimensional radio resources for co-existing UEs in dynamic network environment. To reduce the costs of using UE-specific resources, the BS mounts UEs with diverse multidomain resources. Specific to each UE coalition by taking into consideration restrictions such as the availability of resources, the perceived quality of those resources, and the possibility for use. Every UE that is a part of the coalition has access to the radio resources that it needs, which helps to lower the costs of use while preventing resource-sharing disputes with the other nodes in the coalition. Furthermore, the allocation of multidimensional radio resources among co-existing user equipment makes it possible to solve the issue of maximizing the sum of cost-conscious utility. This is done to fulfil UE-specific quality of service needs as well as varied resource circumstances on the user equipment side. The gradient convexity with low complexity approximation and the Lagrange double decomposition approach are used in the development of the solution to this NP-hard issue. The efficacy of the system that we have presented is shown via the use of numerical simulations and a comparison of its performance with that of other methods. [ABSTRACT FROM AUTHOR]

This study extends the limited research on predictors of completion of adolescent residential drug and alcohol program. A Queensland, Australia, five-bed state-wide voluntary adolescent drug and alcohol withdrawal service collected routine clinical pre-entry data over a period of 9 years (2000–2009) on 524 subjects. Potential predictors of program completion included socio-demographic, family functioning, past mental health history, mental health problems on admission, and patterns of drug use variables. The chi-square analysis identified significant predictors with subsequent multivariate logistic regression modeling. Given the loss of data, additional multiple imputation logistic regression analysis was utilized. Initial predictors were aged 17 and over; a past history of psychiatric treatment or violence or assault; mental health problems identified on entry; absence of current alcohol use or ecstasy use. After regression and multiple imputation modeling, predictors were a history of psychiatric treatment and of violence/assault. A history of co-morbidity rather than traditional markers of good outcomes such as sex, ethnic background, income support, and housing support predicted program retention. The study reinforces the important role of non-substance psychiatry co-morbidity in the treatment of substance use disorder. [ABSTRACT FROM AUTHOR]

Adolescent substance use continues to be a global concern. Research has shown that two consistent predictors of this behavior are self-control and peer substance use. The objective of this study was to determine if these two variables interact to affect the frequency of substance use among young people. The analysis utilized three years of data from the Second International Self-Report Delinquency study (2005-2007) (ISRD-2), which gathered information from youth, ages 12-17, residing in 30 nations (n = 72,206). Illicit substance use included cannabis, ecstasy, stimulants, and other substances. A zero-inflated negative binomial model that adjusts for selection effects was estimated to predict the frequency of substance use. The results showed that adolescents with low self-control who associated with substance using peers tended to be the most frequent substance users. Yet, youth with higher levels of selfcontrol were likely to report no or low frequency use regardless of the number of their friends who used illicit substances. Self-control affects substance use among adolescents and can attenuate the influence of peer substance use. Research using longitudinal data is needed to disentangle changes in self-control, peer substance use, and one's own substance use. [ABSTRACT FROM AUTHOR]

Background: Discourses around MDMA are often predominantly concerned with identifying risk and characterizing harm. Reluctance from Australian governments to reform drug policy and implement harm reduction services has created a policy and service gap, and it is therefore pertinent to consider how people who use MDMA mediate potential harms, and how this knowledge can inform approaches to drug use and policy reform. This community-led scoping review aimed to identify Australian literature on the practices of harm reduction strategies by people who use MDMA. Methods: Seven topic-specific and multidisciplinary databases were searched in February 2023 in line with conventional scoping review methodology. Eligible articles were published from 2002 onwards, reported on the voices of people who use MDMA as primary evidence within the context of Australia, and included at least one strategy to reduce harm. Data were analyzed by drawing on conventional content analysis and thematic analysis frameworks. Results: Twenty-three peer-reviewed and gray literature sources were included. Five key themes were identified on how people mediate harms and enhance the pleasurable aspects of MDMA use: drug consumption practices, planning and preparation, testing drugs, accessing health services, and community care practices. Conclusion: The results suggest that people who use MDMA take care to identify and reduce unwanted harms. The way people who use MDMA make decisions around drugs is mediated by peer groups and online technologies, as well as broader social and cultural contexts of drug use and drug prohibition. More qualitative, participatory, and action research projects are recommended to accurately reflect the views and needs of people who use MDMA and meaningfully shape service reform. [ABSTRACT FROM AUTHOR]

Background: The prosocial compound ± 3,4-methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that has shown promise as an adjunct to psychotherapy in the treatment of post-traumatic stress disorder. MDMA increases positive responses to social images, and it has been suggested that the ability of MDMA to positively bias social perception may underlie its therapeutic efficacy as a psychotherapy adjunct. However, the effect of the compound on affective responses to positive or negative social feedback has not been tested. Aims: In this study, we aimed to test the effects of MDMA compared to placebo and the prototypical stimulant, methamphetamine (MA), on responses to positive and negative social feedback. Methods: This was a double-blind, placebo-controlled, crossover trial (NCT03790618), comparing the effects of two doses of MDMA (0.75 mg/kg, 1.5 mg/kg) to both placebo and MA (20 mg) on responses to a personalized social feedback task, similar to a dating app, in healthy adult volunteers ages 18–40 (N = 36, 18 women, 18 men). Results/Outcomes: The high dose of MDMA increased positive affective responses to social feedback. Conclusions/Interpretations: These findings suggest one process by which MDMA may facilitate social connection. Further work is needed to understand how MDMA affects responses to more generalized types of social feedback and to understand these effects in clinical populations. [ABSTRACT FROM AUTHOR]

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Australia has just rescheduled two drugs controlled under the United Nations Psychotropic Drug Conventions, psilocybin and MDMA, as treatments for treatment-resistant depression and post-traumatic stress disorder respectively. This feature explores the reasons for these developments, the opportunities and challenges they provide to psychiatry communities and how along with health systems these communities might respond to these developments. [ABSTRACT FROM AUTHOR]