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BACKGROUND: Posttraumatic Stress Disorder (PTSD) impacts both individual and relational functioning. Veteran couples are at increased risk of relationship distress due to military stressors such as deployment, family reintegration, and traumatic stress. Although both Cognitive-Behavioral Conjoint Therapy (CBCT) and its brief version (bCBCT) consistently have large effects on reducing PTSD symptoms, these treatments have more variable effects on relational outcomes. Given the impact of relationship functioning on the overall health of veterans, improving the effect of PTSD treatments on relationship functioning is an essential area of research. One promising path is the role of MDMA (3,4-methylenedioxymethamphetamine)-assisted therapy in augmenting the relational impact of established therapeutic interventions such as bCBCT. METHOD/DESIGN: This is a single site, open-label study assessing the preliminary efficacy, safety, and acceptability of MDMA-assisted therapy in combination with bCBCT in 8 veterans with PTSD and their intimate partners (N = 16). Therapy teams trained in bCBCT and MDMA-assisted therapy will deliver bCBCT combined with two MDMA sessions and two couple emotion focused integration sessions. PTSD symptom severity and relationship functioning outcomes will be evaluated. CONCLUSION: This is the first study to examine the efficacy of MDMA-assisted bCBCT for improving PTSD and relationship functioning among a sample of U.S. military veterans and their partners. This project could provide an opportunity to pilot a scalable model of treating PTSD within the Veterans Affairs healthcare system and leverage the benefits of MDMA for veterans with PTSD, as well as the downstream benefits to their partner on both individual and relationship functioning. ClinicalTrials.gov Identifier: NCT05979844.

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 drug-induced 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 injury were not measured 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.

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: The substitution of cannabis for alcohol and other drugs has been conceptualised in a harm reduction framework as where cannabis is used to reduce the negative side-effects, addiction potential, and social stigma of other drugs. There is currently mixed evidence with recent reviews suggesting cannabis co-use patterns may vary by age and ethnicity. Yet few studies have had large enough samples to examine this demographic variation in detail. Aims: To explore the co-use of cannabis with alcohol and other drugs within demographic subgroups of a large sample of people who use cannabis. Specifically: (1) whether cannabis is being substituted for other drugs, and (2), whether cannabis use leads to more, less or the same level of other drug use. Method: Online convenience survey promoted via Facebook™ completed by 23,500 New Zealand respondents. Those who had used cannabis and any of eight other substances in the same six-month period were asked if their use of cannabis had any impact on their use of each other substance ("a lot more", "little more", "no impact/same", "little less", "a lot less"). Frequency and quantity used of each other drug was compared by co-use group. Generalised logistic regression models were developed to predict co-use categories. Results: Significant proportions reported cannabis use led to "less" alcohol (60%), synthetic cannabinoid (60%), morphine (44%) and methamphetamine (40%) use. Those who reported using "less" had lower frequency and amount used of other drugs. Approximately seven-out-ten reported cannabis use had "no impact" on LSD, MDMA, and cocaine use. One-in-five reported using cannabis led to "more" tobacco use. Young adults (21–35-years) were more likely to report cannabis use led to "less" drinking and methamphetamine use. Adolescent co-users (16–20 years) reported mixed impacts. Māori were more likely to report cannabis use resulted in "less" alcohol, tobacco, methamphetamine, and LSD use. Students and those living in cities were less likely to report cannabis use lowering use of other substances. Conclusion: Cannabis and other drug co-use patterns are moderated by life stages, lifestyles, cultural perspectives, and urbanicity. Harm reduction initiatives and policy reforms should take account of these moderating factors. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusions This study explores the attitudes of psychologists towards psychedelics and psychedelic‐assisted therapy (PAT) following the world‐first regulatory changes in 2023 in Australia which permitted psilocybin and 3,4‐methylenedioxy‐methamphetamine (MDMA) to be used in clinical services.A purposive sample of 20 Australian psychologists was recruited using snowball sampling. Semi‐structured interviews were conducted which explored participants' attitudes, knowledge and concerns about PAT. Data were coded and analysed to identify and develop theme categories.Most psychologists exhibited positive attitudes towards psychedelics and their therapeutic potential, viewing them as promising for addressing chronic mental health conditions like depression. However, there was a notable concern regarding the limited evidence on efficacy and potential adverse experiences, as well as the complexity of the individualised treatment protocol. Despite enthusiasm, many psychologists had limited detailed knowledge about the interventions themselves. The need for comprehensive education and training programs, including exposure to psychedelic experiences and credible higher education institutions, was emphasised to ensure competence in administering PAT.Psychologists displayed notably positive attitudes towards PAT, likely reflecting both shifting perceptions of psychedelics and self‐selection bias within the sample. Despite this optimism, concerns were raised about psychiatric risks and the necessity for comprehensive and reputable training and supervision. The cohort showed openness to both novel treatments and innovative training methods, underscoring the importance of enhancing educational frameworks to ensure effective implementation of PAT. [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]

Objective: Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes, knowledge and readiness of both mental health consumers and the general population remain largely unknown. Methods: A cross-sectional survey was conducted among Australians, targeting individuals with mental illness as potential mental health service users. A sub-sample of individuals free of mental illness was also surveyed to assess attitudes in the general population. Participants completed the Attitudes on Psychedelics Questionnaire, the Basic Knowledge of Psychedelics Test and a questionnaire by Corrigan et al. to capture attitudes toward psychedelic therapy by mental health service users. Results: Of the 502 respondents, 64.5% self-identified as having a mental illness. A significant proportion favored legalizing psychedelics for medical use (43%) and were open to their use (52.4%), yet fewer viewed their effects positively (24%) or considered them safe (33%). Most participants reported to be psychedelic naive (61%). Participants with mental illness had significantly more experience with psychedelics than participant free of mental illness (44.1% vs 29.7%). Experience, perceived knowledge and actual knowledge significantly predicted attitudes toward legalization, effects, risks and openness to psychedelics. Conclusions: While a large proportion of Australians are in favor of legalizing psychedelics for medical purposes, concerns about safety remain. People with self-identified mental illness, those with previous recreational psychedelic experience and those with greater knowledge of psychedelics were more likely to have positive attitudes toward psychedelics and psychedelic-assisted therapy. [ABSTRACT FROM AUTHOR]

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.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.This is an expert review and synthesis of the literature.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.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]

Substance use/abuse and suicide are two closely related phenomena, mostly due to neurobiological, psychological, and social impairments. In the present narrative review, the relationship between suicidal behavior (SB) and the use and abuse of common recreational drugs, such as alcohol, cannabis, cocaine, methamphetamine, heroin, nicotine, ketamine, psilocybin, MDMA, and LSD, has been explored. Furthermore, potential mechanisms linking the two have also been examined. According to current research, all substances appear to have a deleterious effect on SB except for ketamine and psilocybin, which could potentially confer a protective effect. Further studies are needed to understand the relationship between MDMA, LSD, and suicide. [ABSTRACT FROM AUTHOR]

Key Clinical Message: MDMA and cocaine can result in acute onset rhabdomyolysis. However, delayed onset rhabdomyolysis and its pathophysiology is of concern Early therapeutic intervention improves prognosis. Such cases should be promptly referred and managed in centers equipped with critical care and renal replacement therapy. [ABSTRACT FROM AUTHOR]

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract 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 Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute (“afterglow”) window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.

Background and Aims Methods Results Conclusions Illicit drug consumption is associated with public health effects and criminal activities. This study aimed to estimate Illicit drug consumption and annual market in the Netherlands from wastewater analysis of drug residues.Residues of cocaine, amphetamine and 3,4‐methylene dioxymethamphetamine (MDMA) were measured between 2015 and 2022 in 30 Dutch wastewater treatment plants serving both rural and urban populations. These wastewater treatment plants covered 20% of the total Dutch population. The Dutch annual retail market was estimated by extrapolating consumption to the total Dutch population, back‐calculating consumption volume, correcting for drug purity and street price collected in voluntary checking services, and accounting for the correlation of consumption and urbanity.The per capita MDMA and cocaine consumption correlated positively with the urbanity of the wastewater treatment plant catchments with r2 of 31% and 64%, respectively. Amphetamine did not show a significant correlation with urbanity. The three studied drugs were conservatively estimated to cover an average annual market value of 903 (95% prediction interval 829 to 987) million Euro for the studied period. Market estimations from prevalence figures and interceptions of international trade were similar.Illicit drug consumption in the Netherlands appears to correlate positively with urban (in contrast to rural) areas. Wastewater analysis can be used to estimate the volume and monetary value of illicit drug markets as a proof of concept. [ABSTRACT FROM AUTHOR]

The present study examined ecstasy past-year use among 7th–12th grade students (N = 38,753) in Greater Cincinnati schools. The PRIDE National Drug Use survey for grades 7–12 was administered to youth in their school classrooms. Results indicated that male students, 9th–12th grade students, non-Caucasian students, and employed students were at highest risk for ecstasy use. In addition, students with low involvement in protective factors (participation in community activities, school activities and clubs, sports, faith-based institutions, and getting good grades), parent factors, teacher factors and school factors, and high involvement in risk factors (taking part in gang activity, friend's use of drugs, access to substances, and getting into trouble at school or with the law) were more likely to use this substance. These findings should be considered when developing programs to prevent ecstasy use among youth. [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]

3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative with notable psychoactive properties and emerging therapeutic potential, particularly for treating post-traumatic stress disorders (PTSD) and substance use disorders. However, its use remains controversial due to inter-individual variability influenced by both environmental and genetic factors. In this context, pharmacogenomics could play a crucial role in guiding MDMA treatment by identifying individuals with genetic predispositions affecting their response to MDMA. Tailoring treatment plans based on individual's genetic makeup may enhance therapeutic outcomes and minimize adverse effects, leading to safer and more effective use of MDMA in clinical settings. Literature analysis reveals that the influence of genetic variants within genes encoded for enzymes involved in MDMA metabolism and/or pharmacodynamics (PD) targets have been relatively under-investigated in humans. Some studies have pointed out associations between MDMA-induced effects and polymorphisms. For example, the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and cardiovascular MDMA-induced effects. Similarly, polymorphisms in the serotonin-linked promoter region (5HTTLPR) have been associated with several MDMA-induced adverse effects including mood disorders. However, despite these findings, only a few associations have been highlighted. Furthermore, some genes encoded for MDMA targets have been only poorly investigated, representing a significant research gap. These observations underscore the need for large-scale, controlled pharmacogenomics studies focusing on a broad panel of genes involved into MDMA pharmacokinetics and PD. Such studies could provide critical insights for optimizing MDMA's therapeutic use and minimizing its risks. [ABSTRACT FROM AUTHOR]

Ecstasy tablets, a type of common street drug originally consisting of 3,4‐methylenedioxymethamphetamine (MDMA), provide stimulant and hallucinogen psychoactive effects. They are frequently found in nightclubs, musical festivals or other recreational events believed to create a relaxing experience for the users. From a forensic perspective, when the drug of abuse is suspected in such scenarios, the law enforcement personnel would then require an easy‐to‐perform, quick and accurate method to detect the existence of such controlled substance prior to the seizure and subsequent forensic examination. In this study, we assessed the performance of a portable Raman spectroscopy as the primary aid in determining ecstasy tablets at the point of use. A total of 130 ecstasy tablet samples were analysed by Raman spectroscopy and characterised by gas chromatography–mass spectrometry (GC–MS). Active chemical substances and cutting agents detected by the two instrumentations were then compared. The performance of Raman spectroscopy was further assessed in terms of its accuracy, sensitivity and specificity, corresponding to the analysis results obtained from GC–MS analysis. Overall, portable Raman Spectroscopy used in this study shows an accuracy of 85.4% in analysing ecstasy tablets obtained from case samples, while the sensitivity and specificity were determined as 85.2% and 100%, respectively. No false positives for MDMA or other drugs were reported. Our results show that portable Raman spectroscopy is a suitable technique for targeted determination of the presence of ecstasy tablets, especially in forensic cases that require non‐destructive, rapid and mass screening during on‐site testing by law enforcement personnel. [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]

Research suggests that hair color, hair dyeing, and perspiration can bias hair test results regarding drug exposure, but research is needed to examine such associations in a multivariable manner. In this epidemiology study, adults were surveyed entering nightclubs and dance festivals in New York City, and 328 provided hair samples, which were analyzed using ultra‐high‐performance liquid chromatography–tandem mass spectrometry to determine the level of detection of cocaine and 3,4‐methylenedioxymethamphetamine (MDMA). Reporting use was not an inclusion criterion for analysis. We used two‐part multivariable models to delineate associations of hair color, past‐year hair dyeing, and frequency of past‐month hat wearing (which may increase perspiration) in relation to any vs. no detection of cocaine and MDMA as well as level of detection, controlling for hair length, self‐reported past‐year cocaine/ecstasy/MDMA use, and age, sex, and race/ethnicity. Those reporting having dyed their hair were at increased odds of having any level of cocaine detected (adjusted odds ratio [aOR] = 3.75, 95% CI confidence interval [CI]: 1.85–6.70), and compared to those with brown hair, those with blond(e) hair on average had lower levels of cocaine (ng/mg) detected (beta = −7.97, p = 0.025). Those reporting having dyed their hair were at increased odds of having any level of MDMA detected (aOR = 3.05, 95% CI: 1.44–6.48), and compared to those who reported never wearing a hat, those who reported wearing a hat daily or almost daily on average had lower levels of MDMA (ng/mg) detected (beta = −6.61, p = 0.025). This study demonstrates the importance of using multivariable models to delineate predictors of drug detection. [ABSTRACT FROM AUTHOR]

A portable and highly sensitive sensor was designed for the specific detection of 3,4‐methyl‐enedioxy‐methamphetamine (MDMA), in a range of field‐testing situations. The sensor can detect MDMA in street samples, even when other controlled substances drugs, or adulterants are present. In this work, we report for the first time a sensor using electroactive molecularly imprinted polymer nanoparticles computationally designed to recognize MDMA and then produced using solid phase synthesis. A composite comprising chitosan, reduced graphene oxide, and molecularly imprinted polymer nanoparticles synthesized for MDMA for the first time was immobilized on screen‐printed carbon electrodes. The sensors displayed a satisfactory sensitivity (106.8 nA × μM−1), limit of detection (1.6 nM; 0.31 ng/mL), and recoveries (92–99%). The accuracy of the results was confirmed through validation using Ultra‐High Performance Liquid Chromatography coupled with tandem Mass Spectrometry (UPLC‐MS/MS). This technology could be used in forensic analysis and make it possible to selectively detect MDMA in street samples. [ABSTRACT FROM AUTHOR]

In the past few years, psilocybin, a psychedelic compound found in “magic mushrooms” (psilocybin mushrooms), has undergone decriminalization in numerous cities across the US and has been legalized in Oregon and Colorado. Proponents of psilocybin decriminalization have emphasized its therapeutic potential in treating mental health disorders. Furthermore, psilocybin mushrooms are considered the safest psychedelic option, with lower potency and a reduced risk of overdoses and emergency hospitalizations compared to other prevalent psychedelics, such as LSD (lysergic acid diethylamide) and MDMA (3,4-methylenedioxymethamphetamine). We analyzed the impact of psilocybin reforms on public interest in psilocybin, as well as their cross-commodity effects on LSD and MDMA, utilizing extensive web-based search data. We observe a significant increase in psilocybin search volume and a notable reduction in search volume associated with LSD and MDMA. Our results are consistent nationwide across states, irrespective of their stance on psilocybin reforms. The shift in public interest toward psilocybin, which is considered the safest psychedelic, away from LSD and MDMA, carries positive implications for public health. [ABSTRACT FROM AUTHOR]

MDMA-assisted psychotherapy has shown potential as an effective treatment for post-traumatic stress disorder (PTSD). Preclinical studies involving rodents have demonstrated that MDMA can facilitate the extinction of fear memories. It has been noted that MDMA impacts oxytocin neurons and pro-inflammatory cytokines. Thus, the aim of this study was to explore the role of oxytocinergic signaling and neuroinflammatory markers in the therapeutic effects of MDMA. To achieve this, male rats were subjected to a model of PTSD involving exposure to shock and situational reminders. MDMA was microinjected into the medial prefrontal cortex (mPFC) before extinction training, followed by behavioral tests assessing activity levels, anxiety, and social function. Our findings indicate that MDMA treatment facilitated fear extinction and mitigated the shock-induced increase in freezing, as well as deficits in social behavior. Shock exposure led to altered expression of the gene coding for OXT-R and neuroinflammation in the mPFC and basolateral amygdala (BLA), which were restored by MDMA treatment. Importantly, the OXT-R antagonist L-368,899 prevented MDMA's therapeutic effects on extinction and freezing behavior. In conclusion, MDMA's therapeutic effects in the PTSD model are associated with alterations in OXT-R expression and neuroinflammation, and MDMA's effects on extinction and anxiety may be mediated by oxytocinergic signaling. [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]

MDMA (±3,4-methylenedioxymethamphetamine)-assisted therapy (MDMA-AT) was shown in previous clinical trials to have promising efficacy and safety for alleviating treatment-resistant posttraumatic stress disorder (PTSD). However, due to low ethnoracial diversity, the question remains as to whether ethnoracial minority participants would benefit similarly. Thus, a mixed-methods case study was conducted on a participant of color from an open-label trial of MDMA-AT for PTSD to provide a culturally informed lens on symptom recovery with this treatment approach. An additional aim was to elucidate mechanisms of change underlying this treatment for the participant. A case profile was provided, documenting quantitative improvement in PTSD symptoms. This was followed by an interpretative phenomenological analysis (IPA) of effects and mechanisms of action for this participant, based on integration session transcripts. Results of IPA indicated recurrent themes related to psychological mechanisms of symptom change, reduced PTSD symptoms, and additional effects (positive and negative) beyond PTSD symptom reduction. These themes were discussed and recommendations for attuning to culturally relevant material during MDMA-AT were provided. [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]

Introduction and purpose: Post-traumatic stress disorder is a psychiatric condition following an extreme event that causes a near death of an involved individual. Since conventional treatments using selective serotonin reuptake inhibitors do not consistently yield therapeutic success, alternative substances are being explored as potential solutions. This study aims to compile information regarding the outcomes of utilizing psychedelics in individuals diagnosed with PTSD. Brief description of the state of knowledge: In July 2023, after a number of clinical trials and 20-year-long efforts to overturn the impact of a prohibition, Australia became the first country to allow doctors, in clinical development and under strict control, to use the 3,4-methyl enedioxy methamphetamine (MDMA) commonly known as ecstasy, as well as psylocybin in patients with post-traumatic stress disorder or depression [1]. There is a noticeable annual growth of inquiries on PubMed involving the keywords "psychedelics" and "therapeutic", amounting to 92 in 2000 and topped by 738 searches in 2023, whereas the total number of results consists of 8415 positions. Therapeutic effects of psychedelics are becoming more recognized over time. Summary: Post-Traumatic Stress Disorder (PTSD) is a complex condition that affects both the psychological and somatic aspects of the body. Thus, a multidimensional intervention is indicated. The use of psychedelics might contribute to improvements not only in the severity of PTSD but also in depression or pain. Further research on a larger group of participants should be carried out to assess the potential role of psychedelics in conventional medicine in the future, alongside psychotherapy. [ABSTRACT FROM AUTHOR]

MDMA (3,4-methylenedioxymethamphetamine) and tramadol are central nervous system stimulants known for inducing emotional communion and socializing effects. FMRFamide, an RFamide peptide isolated from mollusks, plays diverse roles in physiological processes. This study aimed to evaluate FMRFamide's impact on testicular toxicity induced by MDMA/tramadol in Wistar rats. Thirty male Wistar rats were divided into six groups (n=5). Group A served as the control, Group B received 2 mg/kg FMRFamide for two consecutive days. Groups C, D, and E received MDMA/tramadol (20 mg/kg) for ten days, while Group F received the same dosage along with FMRFamide. Sperm analysis, biochemical, and histological assessments were conducted. The results revealed significant body weight loss, decreased sperm count and motility, increased abnormal sperm formation, and reduced serum LH, FSH, and Testosterone levels. Inducible Nitric Oxide Synthase (iNOS) expression was intensified in Groups A, B, D, and F. Notably, FMRFamide administration attenuated the adverse effects of MDMA/tramadolinduced testicular toxicity, suggesting a potential therapeutic role in safeguarding male reproductive health. These findings highlight the importance of further exploring FMRFamide's protective mechanisms and its potential application in mitigating drug-induced reproductive toxicity. [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]

Introduction and aim: It is important to understand how mental health practitioners view recent findings on psychedelic-assisted psychotherapy (PAP) as there is potential this treatment may be incorporated into clinical practice. The aim of our study was to explore how psychiatrists who are not involved in psychedelic research and who are located in the European region perceive psychedelics and PAP. Methods: We conducted online semi-structured interviews with 12 psychiatry specialists and psychiatry trainees from8 European countries. Data were analyzed using a general inductive approach informed by codebook thematic analysis. Results: Based on the interviews, we developed four main themes and 14 subthemes, including (1) Psychedelics hold potential, (2) Psychedelics are dangerous, (3) Future of psychedelics is uncertain, and (4) Psychiatry is ambivalent toward psychedelics. Discussion: Our respondents-psychiatrists acknowledged the potential of PAP but remained cautious and did not yet perceive its evidence base as robust enough. Education on psychedelics is lacking in medical and psychiatric training and should be improved to facilitate the involvement of mental health experts in decision-making on PAP. [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]

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]

Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological challenge in psychedelic AT, however, is the complexity of blinding procedures. The lack of efficacious blinding can introduce considerable response bias, reduce internal validity, and compromise participant retention. This systematic review examines design and blinding techniques in RCTs utilizing psychedelics and placebo for the treatment of psychiatric disorders. The aim of this work is to identify factors that may inform future RTC design for conducting psychedelics research. We conducted a systematic review of PubMed, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Psycinfo, Embase, and Web of Science Core Collection to examine: (1) placebo selection, (2) study design, and (3) integrity of blinding measures. Sixteen publications were identified as meeting the criteria for a systematic review. Our findings suggest that traditional placebo administration is insufficient to control for expectancy confounds. Consequently, experimental methodology that limits personnel unblinding and the use of an active placebo are important considerations when designing prospective clinical studies involving psychedelics. [ABSTRACT FROM AUTHOR]

Among several established indicators that are used to monitor the illicit drug scene, drug‐related deaths and wastewater‐based epidemiology (WBE) stand out for population‐level coverage. In this study, we aimed to compare temporal trends with respect to amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA) revealed by these indicators and explore the differences in fatal toxicity between the stimulants. All deaths in which poisoning caused by amphetamine, methamphetamine or MDMA was either the underlying or contributing cause of death in Finland in 2012, 2014, 2016, 2018 and 2020 were included in the study. Consumption of the studied drugs was measured by WBE in the same years. There was a significant correlation between poisoning and drug consumption for all three stimulants, and for amphetamine and MDMA, these figures increased over the study period. The highest fatal toxicity, as expressed by the number of deaths per million doses, was obtained for methamphetamine at an estimated dose of 50 mg, followed by MDMA (100 mg dose) and with amphetamine (50 mg dose). The fatal toxicity found here for the stimulants was close to that previously reported for many prescription opioids and tricyclic antidepressants. Our study is the first to quantitatively investigate the fatal toxicity of amphetamine‐type stimulants by comparing deaths with consumption estimates derived from WBE. It shows that amphetamine, methamphetamine and MDMA possess a quite similar capacity to cause death. This new approach adds to the earlier methods of estimating drug‐related harm. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) commonly co-occur and are associated with more severe symptomatology than either disorder alone, increased risk of suicide, and poorer response to existing treatments. A promising therapeutic intervention is the integration of 3,4-methylenedioxymethamphetamine (MDMA) and psychotherapy. The Food and Drug Administration (FDA) designated MDMA- assisted therapy (MDMA-AT) as a Breakthrough Therapy for PTSD based on results from six Phase 2 clinical trials. Case data from the first study evaluating MDMA-AT study for AUD found the treatment was well tolerated and alcohol use was significantly reduced post treatment. Methods: This manuscript reports the premise, design, and methodology of the first open-label trial of MDMA-AT for military veterans (N = 12) with PTSD and AUD. Neuroimaging and biomarker data are included to evaluate brain changes, and neuroinflammation, pre-post treatment. Conclusions: The clinical component (comorbidity) and the regulatory processes (Schedule I drug) for setting up this clinical trial are long and complex. The research community will benefit from this work to establish common clinical trial outcomes, standardized protocols, and risk assessments for FDA approval. Clinicaltrials.gov: NCT05943665.

Key Clinical Message MDMA and cocaine can result in acute onset rhabdomyolysis. However, delayed onset rhabdomyolysis and its pathophysiology is of concern Early therapeutic intervention improves prognosis. Such cases should be promptly referred and managed in centers equipped with critical care and renal replacement therapy.

Abstract 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 Background 3,4-Methylenedioxymethamphetamine (MDMA) is drug of high prevalence in Aotearoa New Zealand and is the primary drug analysed by legal drug checking services. We aimed to address the gap in literature pertaining to MDMA-related harm reduction behaviour and harm experiences within the country. Methods An online survey was used to assess the harm reduction behaviours (e.g., limiting consumption, planning use, seeking information) of people who use MDMA, in addition to their use of reagent testing and the major national drug checking and harm reduction service, KnowYourStuffNZ. Results In total, 915 people completed the survey (60.7% females, aged 18–65, median = 24, IQR = 20–28). Frequency of various MDMA-related harm reduction behaviours differed, although these were carried out relatively frequently by most participants. Those who reported experiencing harm (physical, psychological, spiritual, social) from MDMA, or another drug presumed to be MDMA, reported less frequent harm reduction behaviours than non-harmed consumers. Reagent testing of MDMA had been conducted by 42.3% of the sample. Approximately 27% of the sample had used KnowYourStuffNZ services. Of KnowYourStuffNZ clients, 95.9% reported learning about harm reduction, and 53.3% reported changing their behaviour because of the service. Reasons for not using the KnowYourStuffNZ service were primarily lack of availability in local area (32.8%) or at relevant events (51.8%), and lack of concern with substance quality (29.8%). MDMA harm was reported by 14.4% of the sample, whilst reported harm was more common from consumption of presumably non-MDMA substances, self-reported as being mistaken for MDMA. Harm was primarily physical or psychological. Potential MDMA dependence was apparent in 6.9% of the sample. Conclusions The findings highlight potential targets for harm reduction education and interventions and emphasize the need for greater availability of readily accessible drug checking services in Aotearoa New Zealand.

Introduction: The positive results of MDMA from Phase 2 and 3 clinical trials in MDMA-assisted therapy (MDMA-AT) for the treatment of post-traumatic stress disorder (PTSD) call for a critical evaluation of its regulatory status within the European mental healthcare system. This is driven by the recent submission of MDMA-AT for FDA approval in the United States. Unless coordinated efforts in the European regulatory landscape start, there may be potential divergences in national regulatory strategies. Gaining insights from researchers and clinicians involved in the application of MDMA-AT may be useful in guiding the discussion of factors involved in its implementation.Method: A comprehensive invitation-only survey was sent to researchers and clinicians involved in MDMA-AT clinical trials and contributors to the scientific literature on MDMA-AT from around the globe. This study aimed to collect opinions on clinical practices, training, and regulation worldwide, examining the global best practices and pitfalls to outline strategies for possible European implementation of MDMA-AT.Results: The survey, which included responses from 68 experts, yielded a range of opinions where a large majority endorsed the need for training and standardization, emphasizing equity and access, stressing impediments in the national approval processes, and reflecting critically on anticipated spill-over effects of MDMA-AT in clinical settings.Conclusion: The experts highlight the need for science-informed policy development, active regulatory involvement, and international cooperation to incorporate MDMA-AT into the European mental healthcare system in general and the treatment of PTSD in particular. The study emphasizes the importance of ongoing research, open professional discourse, and collaborative engagement to facilitate MDMA-AT's ethical and effective implementation.

OBJECTIVE: To compare group and individual psychedelic-assisted therapy in terms of clinician time, costs and patient access. METHODS: Using 2023 data from two group therapy trial sites, one using 3,4-Methylenedioxymethamphetamine (MDMA) to treat posttraumatic stress disorder (PTSD), and one using psilocybin to treat major depressive disorder (MDD), we compared overall variable costs, clinician costs and clinician time required by therapy protocols utilizing groups versus individual patient therapy. Using published literature, we estimated the prevalence of adults with PTSD and MDD eligible for treatment with psychedelic therapy and projected the savings in time and cost required to treat these prevalent cases. RESULTS: Group therapy saved 50.9% of clinician costs for MDMA-PTSD and 34.7% for psilocybin-MDD, or $3,467 and $981 per patient, respectively. To treat all eligible PTSD and MDD patients in the U.S. in 10 years with group therapy, 6,711 fewer full-time equivalent (FTE) clinicians for MDMA-PTSD and 1,159 fewer for FTE clinicians for psilocybin-MDD would be needed, saving up to $10.3 billion and $2.0 billion respectively, discounted at 3% annually. CONCLUSION: Adopting group therapy protocols where feasible would significantly reduce the cost of psychedelic-assisted therapies. By enhancing the number of patients served per clinician, group therapy could also ameliorate the anticipated shortage of appropriately trained clinicians, thereby accelerating access to these promising new therapies.

3,4-Methylenedioxymethamphetamine (MDMA) is currently being investigated as an adjunctive treatment to therapy for posttraumatic stress and other anxiety related disorders in clinical trials. Within the next few years MDMA-assisted therapy is projected for approval by regulatory authorities. MDMA's primary mechanism of action includes modulation of monoamine signaling by increasing release and inhibiting reuptake of serotonin, norepinephrine, and, to a lesser extent, dopamine. This pharmacology affects sympathomimetic physiology. In controlled trials, special attention has been given to cardiovascular adverse events (AEs), because transient increases in heart rate and blood pressure have been observed during the MDMA-assisted therapy sessions. Finding and quantifying the potential drivers of cardiac AEs in clinical trials is difficult since only a relatively small number of participants have been included in these studies, and a limited set of allowed concomitant drugs has been studied. In this study a more diverse set of reports from the FDA Adverse Event Reporting System was surveyed. We found 17 cases of cardiovascular AEs, in which the individuals had taken one or more substances in addition to MDMA. Interestingly, all of those concomitant medications and illicit substances, including opioids, stimulants, anticholinergics, and amphetamines, had been previously associated with cardiovascular AEs. Furthermore, in none of the reports MDMA was marked as the primary suspect.

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]

Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics' neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics. [ABSTRACT FROM AUTHOR]

Background and aims: Hallucinogens encompass a diverse range of compounds of increasing scientific and public interest. Risks associated with hallucinogen use are under‐researched and poorly understood. We aimed to compare the trends in hallucinogen‐associated health‐care use with alcohol‐ and cannabis‐associated health‐care use. Design, setting and cases: We conducted an ecological study with publicly available data on International Classification of Diseases, 10th Revision (ICD‐10) diagnosis codes associated with emergency department (ED) visits and hospitalizations from the California Department of Healthcare Access and Information (HCAI). HCAI includes primary and secondary ICD‐10 codes reported with ED or hospital discharge from every non‐federal health‐care facility licensed in California, United States, from 2016 to 2022. Measurements: ICD‐10 codes were classified as hallucinogen‐, cannabis‐ or alcohol‐associated if they were from the corresponding category in the ICD‐10 block 'mental and behavioral disorders due to psychoactive substance use'. Findings Observed hallucinogen‐associated ED visits increased by 54% between 2016 and 2022, from 2260 visits to 3476 visits, compared with a 20% decrease in alcohol‐associated ED visits and a 15% increase in cannabis‐associated ED visits. The observed hallucinogen‐associated hospitalizations increased by 55% during the same period, from 2556 to 3965 hospitalizations, compared with a 1% increase in alcohol‐associated hospitalizations and a 1% increase in cannabis‐associated hospitalizations. This rise in hallucinogenic ED visits was significantly different from the trend in cannabis‐associated (P < 0.001) and alcohol‐associated (P = 0.005) ED visits. The hallucinogen‐associated hospitalizations trend also significantly differed when compared with cannabis‐ (P < 0.001) and alcohol‐associated (P < 0.001) hospitalizations. Conclusions: Hallucinogen‐associated emergency department visits and hospitalizations in California, USA, showed a large relative but small absolute increase between 2016 and 2022. [ABSTRACT FROM AUTHOR]

Background: Recent interest in the potential therapeutic effects of psychedelics has led to investigations into their influence on molecular signaling pathways within the brain. Aims: Integrated review and analysis of different studies in this field. Methods: A systematic search was conducted across international databases including Embase, Scopus, Web of Science, and PubMed from inception to 9 July 2023. Eligibility criteria encompassed published and peer-reviewed studies evaluating changes in brain-derived neurotrophic factor (BDNF) levels after psychedelic consumption. Outcomes: A total of nine studies were included in our study. The meta-analysis demonstrated significantly higher BDNF levels in psychedelic consumers compared to healthy controls, with a pooled standardized mean difference of 0.26 (95% CI: 0.10–0.42, I 2 = 38.51%, p < 0.001). Leave-one-out analysis indicated robustness in results upon removal of individual psychedelics. No significant publication bias was observed. The results highlight the potential influence of psychedelics on neuroplasticity by altering BDNF levels. Conclusions: More precisely, the documented rise in BDNF levels indicates a neurobiological mechanism by which psychedelics could enhance synaptic plasticity and foster the growth of neurons. Given the limited data available on this topic, the conclusions remain uncertain. Consequently, we highly recommend additional research with more extensive sample sizes to yield more reliable evidence in this field. [ABSTRACT FROM AUTHOR]