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Rationale and objectives: Differences among psychedelic substances regarding their subjective experiences are clinically and scientifically interesting. Quantitative linguistic analysis is a powerful tool to examine such differences. This study compared five psychedelic substance report groups and a non-psychedelic report group on quantitative linguistic markers of psychological states and processes derived from recreational use-based online experience reports. Methods: Using 2947 publicly available online reports, we compared Ayahuasca and N,N-dimethyltryptamine (DMT, analyzed together), ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin (mushroom), and antidepressant drug use experiences. We examined word frequencies related to various psychological states and processes and semantic proximity to psychedelic and mystical experience scales. Results: Linguistic markers of psychological function indicated distinct effect profiles. For example, MDMA experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. In contrast, Ayahuasca and DMT experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions. LSD, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. Antidepressant reports featured more negative emotional and cognitive process-related words, fewer positive emotional and analytical thinking-related words, and were generally not similar to mystical and psychedelic language. Conclusion: This article addresses an existing research gap regarding the comparison of different psychedelic drugs on linguistic profiles of psychological states, processes, and experiences. The large sample of experience reports involving multiple psychedelic drugs provides valuable information that would otherwise be difficult to obtain. The results could inform experimental research into psychedelic drug effects in healthy populations and clinical trials for psychedelic treatments of psychiatric problems. [ABSTRACT FROM AUTHOR]

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Rationale: MDMA or Ecstasy has made a resurgence in popularity and the majority of users consist of teenagers and adolescents. Therefore, it is important to determine whether MDMA causes long‐term damage and what this damage entails. There is an ongoing debate about possible neurocognitive changes in 3,4‐methylenedioxymethamphetamine (MDMA) users related to MDMA's neurotoxic potential. Multiple neuroimaging studies have shown that Ecstasy use leads to lower serotonin transporter (SERT) availability in multiple brain regions. This may express itself in a loss of cognitive functions like memory, attention and executive function. However, there is increasing evidence reporting that MDMA's induced serotonergic adaptations are reversible over time. The question we thus address is whether the recovery of SERT function predicts a recovery of cognitive function. Objectives: This review aims to investigate MDMA's long‐term effects on SERT availability and cognitive functioning. Methods: A literature search was performed in PubMed. Studies that investigated the effects of MDMA on both SERT availability and cognitive performance were eligible for inclusion. Results: SERT availability positively correlated with time of abstinence, whereas memory performance did not show this correlation, but remained impaired in MDMA users. No significant correlation between SERT availability and memory function was found (r = 0.232, p = 0.581; r = 0.176, p = 0.677). Conclusions: The main findings of this review are that MDMA‐use leads to an acute decrease in SERT availability and causes an impairment in cognitive functions, mostly memory. However, SERT availability recovers with sustained abstinence while memory function does not. This suggests that SERT availability is not a biomarker for MDMA‐induced cognitive impairment and likely also not for MDMA‐induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Aims: To describe (i) self‐reported changes in drug use and (ii) trends in price, perceived availability, and perceived purity of illicit drugs, among people who regularly use ecstasy/ 3,4‐methylenedioxymethamphetamine (MDMA) and other illicit stimulants in Australia following COVID‐19 and associated restrictions. Design Annual interviews with cross‐sectional sentinel samples conducted face‐to‐face in 2016–19 and via video conferencing or telephone in 2020. Data were collected via an interviewer‐administered structured questionnaire. Setting: Australian capital cities. Participants: Australians aged 16 years or older who used ecstasy/MDMA and other illicit stimulants on a monthly or more frequent basis and resided in a capital city, recruited via social media and word‐of‐mouth (n ~ 800 each year). Measurements: Key outcome measures were self‐reported illicit drug market indicators (price, purity and availability) and, in 2020 only, perceived change in drug use (including alcohol and tobacco) since March 2020 and reasons for this change. Findings For most drugs, participants reported either no change or a reduction in their use since COVID‐19 restrictions were introduced. Ecstasy/MDMA was the drug most frequently cited as reduced in use (n = 552, 70% of those reporting recent use), mainly due to reduced opportunities for socialization. While market indicators were largely stable across most drugs, the odds of perceiving MDMA capsules as 'high' in purity decreased compared with 2016–19 [adjusted odds ratio (aOR) = 0.72, 95% confidence interval (CI) = 0.53–0.99], as did perceiving them as 'easy' to obtain (aOR = 0.42, CI = 0.26–0.67). The odds of perceiving cocaine and methamphetamine crystal as 'easy' to obtain also decreased (aOR = 0.67, CI = 0.46–0.96 and aOR = 0.12, CI = 0.04–0.41, respectively). Conclusions: After COVID‐19‐related restrictions were introduced in Australia, use of ecstasy/MDMA, related stimulants and other licit and illicit drugs mainly appeared to remain stable or decrease, primarily due to impediments to socialization. [ABSTRACT FROM AUTHOR]

The drug called 3,4-Methylenedioxymethamphetamine, commonly known as MDMA or Ecstasy, is proving useful for treating clients who present with posttraumatic stress disorder. The drug's current scheduling classification limits its potential use in clinical trials. Recent research shows positive trends for individuals who simultaneously undergo MDMA treatment and psychotherapy. Some cautions and limitations have been noted. Reclassification of the drug would help increase future research opportunities. [ABSTRACT FROM AUTHOR]

Background: Depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. Existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions. Aim: The aim of this study was to examine the relationships between MDMA (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (MDEs). Methods: This observational study used data from a large (N = 213,437) nationally representative sample of US adults to test the association of lifetime use of MDMA/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (LSD), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (PCP)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe MDEs. Results: Results revealed that lifetime MDMA/ecstasy use was associated with significantly lowered odds of a lifetime MDE (adjusted odds ratio (aOR) = 0.84; p < 0.001), past year MDE (aOR = 0.84; p < 0.001), and past year severe MDE (aOR = 0.82; p < 0.001). Psilocybin was associated with significantly lowered odds of a past year MDE (aOR = 0.90; p < 0.05) and past year severe MDE (aOR = 0.87; p < 0.05). All other substances either shared no relationship with a MDE or conferred increased odds of an MDE. Conclusions: These results suggest that MDMA/ecstasy and psilocybin use is associated with lower risk of depression. Experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Suicide is one of the leading causes of death worldwide and rates within the United States have risen over the past two decades. Hence, there is a critical need for novel tools to treat suicidal ideation and related mental health conditions. 3,4-Methylenedioxymethamphetamine (MDMA)/ecstasy and classic psychedelics may be two such tools. Aims: The aim of this study was to assess non-causal associations between MDMA/ecstasy and classic psychedelic use and psychological distress and suicide risk. Methods: In this study, we examined the aforementioned associations among 484,732 adult participants in the National Survey on Drug Use and Health (2008–2019). Results: Lifetime MDMA/ecstasy use was associated with reduced odds of past year suicidal thinking (10% reduced odds; odds ratio (OR) = 0.90; 95% confidence interval, CI = (0.84–0.97); p < 0.01) and past year suicidal planning (OR = 0.88; 95% CI = (0.78–0.99); p < 0.05). Furthermore, lifetime psilocybin use was associated with reduced odds of past month psychological distress (OR = 0.78; 95% CI = (0.73–0.84); p < 0.001) and past year suicidal thinking (OR = 0.90; 95% CI = (0.83–0.96); p < 0.01). Finally, lysergic acid diethylamide (LSD) was associated with increased odds of past year suicidal thinking (OR = 1.07; 95% CI = (1.00–1.15); p < 0.05). Conclusion: MDMA/ecstasy and psilocybin use are associated with reduced odds of suicidal thinking and related outcomes—though experimental studies are needed to determine whether these associations are causal. These findings call for more research into the efficacy of MDMA/ecstasy and classic psychedelics for treating psychological distress and suicidal thoughts and behaviors, and for updated drug legislation that allows for further investigation into these substances. [ABSTRACT FROM AUTHOR]

The purpose of the study is to explore how the COVID-19 situation has affected the illegal retail market and drug use patterns. Three research questions were formulated: 1) What has been the COVID-19 impact on the retail illegal drugs market? 2) How has the pandemic impacted drug use patterns? 3) Are there trends that presumably would have an impact after COVID-19? The mixed method with an explanatory sequential design was used in the analysis. At the first stage of the analysis all available quantitative data such as routine administrative data and data from regular surveys were analysed and triangulated. The results of quantitative analysis were supplemented by qualitative data, such as reports. The analysis does not suggest changes on the retail market, except for some increase in cannabis cultivation during the first wave in 2020 and a slight decrease in MDMA prevalence on the market in 2021. Drug use patterns are similar to those before the pandemic, with some exceptions that might indicate more cannabis and MDMA use among frequent users. [ABSTRACT FROM AUTHOR]

This article describes the development of an electrochemical screening strategy for 3,4‐methylenedioxymethamphetamine (MDMA), the regular psychoactive compound in ecstasy (XTC) pills. We have investigated the specific electrochemical profile of MDMA and its electro‐oxidation mechanisms at disposable graphite screen‐printed electrodes. We have proved that the formation of a radical cation and subsequent reactions are indeed responsible for the electrode surface passivation, as evidenced by using electron paramagnetic resonance spectroscopy and electrochemistry. Thereafter, pure cutting agents and MDMA as well as simulated binary mixtures of compounds with MDMA were subjected to square wave voltammetry at pH 7 to understand the characteristic electrochemical profile. An additional measurement at pH 12 was able to resolve false positives and negatives occurring at pH 7. Finally, validation of the screening strategy was done by measuring a set of ecstasy street samples. Overall, our proposed electrochemical screening strategy has been demonstrated for the rapid, sensitive, and selective detection of MDMA, resolving most of the false positives and negatives given by the traditional Marquis color tests, thus exhibiting remarkable promises for the on‐site screening of MDMA. [ABSTRACT FROM AUTHOR]

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field. [ABSTRACT FROM AUTHOR]

This article focuses on the rave subculture of St. Petersburg in the 1990s and demonstrates how new forms of psychoactive control and resistance emerged in the wake of the Soviet collapse. By staying sensitive to the material and corporeal aspects of these phenomena, it contributes to the socio-material studies of drug control and emphasizes that the physical body itself should be an important venue for drug research. In doing so, we build on existing literature that discusses bodies as information resources to detect drug use and identifies resistance strategies to increasingly technological drug control measures. We advance this discussion by suggesting that the psychoactive setting of rave in post-Soviet St. Petersburg gave rise to a highly particular yet notably elusive and difficult-to-define type of corporeality. On the one hand, this corporeality could be positively interpreted as a marker of resistance and belonging on the "inside." At the same time, it could also be employed strategically by law enforcement officers to detect and prosecute drug-consuming individuals. Moreover, we propose to view this psychoactive "rave body" as deeply embedded in its spatio-temporal context—thus accounting for the influence of time and space on the materiality of drug control and resistance. In examining these dynamics, we draw on a wide range of sources, including memoirs, press materials, early Internet archives, publicly printed interviews, photographs, and video materials. [ABSTRACT FROM AUTHOR]

Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), recreational MDMA use occasionally elicits hyperthermia and hyponatremia, sometimes with a fatal outcome. Specific risk factors for both adverse effects are profuse sweating while vigorously dancing under unfavorable conditions such as high ambient temperatures and insufficient fluid suppletion which result in dehydration. Concomitant use of MDMA and alcohol is highly prevalent, but adds to the existing risk, because alcohol facilitates the emergence of MDMA-induced adverse events, like hyperthermia, dehydration, and hyponatremia. Because of potential health-related consequences of concomitant use of MDMA and alcohol, it is important to identify the mechanisms of the interactions between alcohol and MDMA. This review summarizes the main drivers of MDMA-induced hyperthermia, dehydration, and hyponatremia and the role of concomitant alcohol use. It is shown that alcohol use has a profound negative impact by its interaction with most of these drivers, including poikilothermia, exposure to high ambient temperatures, heavy exercise (vigorous dancing), vasoconstriction, dehydration, and delayed initiation of sweating and diuresis. It is concluded that recreational and clinical MDMA-users should refrain from concomitant drinking of alcoholic beverages to reduce the risk for adverse health incidents when using MDMA. [ABSTRACT FROM AUTHOR]

3,4‐Methylenedioxymethamphetamine (MDMA) or "Ecstasy", which has been used for recreational purposes, is shown to impair memory and brain functions. Statins, beyond their efficient cholesterol-lowering impact through inhibition of HMG-COA reductase enzyme, possess multiple actions referred to as pleiotropic effects. In this regard, we aimed to investigate the neuroprotective effects of atorvastatin and rosuvastatin on MDMA-induced neurotoxicity. Adult male Wistar rats received atorvastatin (5, 10, and 20 mg/kg; orally) and rosuvastatin (5, 10, 20 mg/kg; orally) for 21 consecutive days. Then, spatial memory and learning were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally injected with MDMA (2.5, 5, and 10 mg/kg) 30 min before the first training session in 4 training days of MWM task. Afterward, rats were euthanized and their hippocampuses were dissected to evaluate reactive oxygen species (ROS) production, lipid peroxidation (LPO), and caspase-3 and -9 activities. Our findings showed that MDMA (5 and 10 mg/kg) significantly impaired spatial memory functions and dramatically increased ROS production, LPO, and caspase-3 and -9 activities compared to control. Also, atorvastatin (5, 10, and 20 mg/kg) and rosuvastatin (20 mg/kg) significantly improved memory performances and inhibited the elevation of ROS, LPO, and caspase-3 and -9 activities induced by MDMA. In conclusion, the results indicated that MDMA-induced cognitive impairment is followed by oxidative stress and activation of apoptotic pathways in the hippocampus. However, atorvastatin and rosuvastatin suppressed these deleterious consequences of MDMA and revealed protective effects against activation of pathways leading to cell damage. [ABSTRACT FROM AUTHOR]

On estime que le syndrome de stress post-traumatique (PTSD) reste chronique et sévère pour 25 à 50 % des patients malgré une prise en charge psychothérapeutique. La MDMA (« ecstasy ») possèderait des propriétés psychopharmacologiques qui renforcent l'alliance thérapeutique et permettent au patient de travailler sur le contenu traumatique sans être submergé par la peur et l'anxiété. Les résultats d'essais cliniques de phase II confirment que la MDMA améliore efficacement la prise en charge psychothérapeutique des patients atteints de PTSD sans effets secondaires sérieux. Des essais de phases III sont en cours. La Multidisciplinary Association for Psychedelic Studies (MAPS) a mis en ligne une proposition de méthode et forme des thérapeutes pour mener des psychothérapies assistées par la MDMA. La Food and Drug Administration (FDA) et l' European Medicines Agency (EMA) pourraient autoriser cet outil thérapeutique dans les prochaines années. Posttraumatic stress disorder (PTSD) is estimated to remain chronic and severe for 25–50% of patients despite psychotherapeutic treatment. Part of the reasons is that patients with PTSD can have difficulties in establishing a good therapeutical alliance with the therapist. Moreover, they often fail to re-think the content of the trauma without being overwhelmed by negative emotions and tend to rely on avoidance strategies and/or to abandon the therapy. MDMA ("ecstasy") is a drug classified as an entactogen (en "within", tactus "touch", and gen "produce"), an amphetamine with psychedelic properties that possesses psychopharmacological properties to overcome these issues. Indeed, MDMA triggers the release of oxytocin, which favors the establishment of interpersonal relationship based on kindness and trust. Moreover, MDMA diminishes the activity of the amygdale, allowing patients to work on challenging memories with less fear and anxiety. Finally, MDMA may also provide access to meaningful spiritual experiences, release of tensions and a sense of healing on a non-verbal level that are not completely understood. But are viewed as important by patients. Today, there is no evidence that the use of MDMA in a clinical setting has bad neurologic, psychological or cognitive consequences. Results of phase II trials in the United States and Europe confirm that MDMA favors psychotherapy's outcome without severe adverse effects. Phase III trials are underway. The Multidisciplinary Association for Psychedelic Studies (MAPS) has published online a method proposal and trains therapists in MDMA-assisted psychotherapy. Food and Drug Administration (FDA) and European Medicines Agency (EMA) could approve this therapeutic tool in the coming years. [ABSTRACT FROM AUTHOR]

BackgroundThe compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.MethodsIn a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level-dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.ResultsMarked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.ConclusionsThe MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug's characteristic subjective effects arise from its modulation of spontaneous brain activity.

Male rats escalate intravenous self-administration of entactogen psychostimulants, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxymethamphetamine (MDMA) under extended access conditions, as with typical psychostimulants. Here, we investigated whether female rats escalate self-administration of methylone, 3,4-methylenedioxypentedrone (pentylone), and MDMA and then studied consequences of MDMA and pentylone self-administration on GABAA receptor and kappa opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA), a brain area critically dysregulated by extended access self-administration of alcohol or cocaine. Adult female Wistar rats were trained to self-administer methylone, pentylone, MDMA (0.5 mg/kg/infusion), or saline-vehicle using a fixed-ratio 1 response contingency in 6-h sessions (long-access: LgA) followed by progressive ratio (PR) dose-response testing. The effects of pentylone-LgA, MDMA-LgA and saline on basal GABAergic transmission (miniature post-synaptic inhibitory currents, mIPSCs) and the modulatory role of KOR at CeA GABAergic synapses were determined in acute brain slices using whole-cell patch-clamp. Methylone-LgA and pentylone-LgA rats similarly escalated their drug intake (both obtained more infusions compared to MDMA-LgA rats), however, pentylone-LgA rats reached higher breakpoints in PR tests. At the cellular level, baseline CeA GABA transmission was markedly elevated in pentylone-LgA and MDMA-LgA rats compared to saline-vehicle. Specifically, pentylone-LgA was associated with increased CeA mIPSC frequency (GABA release) and amplitude (post-synaptic GABAA receptor function), while mIPSC amplitudes (but not frequency) was larger in MDMA-LgA rats compared to saline rats. In addition, pentylone-LgA and MDMA-LgA profoundly disrupted CeA KOR signaling such as both KOR agonism (1 mM U50488) and KOR antagonism (200 nM nor-binaltorphimine) decreased mIPSC frequency suggesting recruitment of non-canonical KOR signaling pathways. This study confirms escalated self-administration of entactogen psychostimulants under LgA conditions in female rats which is accompanied by increased CeA GABAergic inhibition and altered KOR signaling. Collectively, our study suggests that CeA GABA and KOR mechanisms play a critical role in entactogen self-administration like those observed with escalation of alcohol or cocaine self-administration.

Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.

Psychedelics are classed as a schedule I substance under the Controlled Substances Act of 1970 because of the potential for mind-changing effects. In vulnerable people, unsupervised use has the potential to lead to suicide. However, the management of end-of-life anxiety, severe resistant depression, resistant obsessive–compulsive disorder, and substance abuse is met with a high failure rate. The preliminary study on psychedelics has yielded promising results, prompting the Food and Drug Administration (FDA) to classify them as a breakthrough medicine. More phase 3 research, funded by pharmaceutical company, are in the works. Similar studies should be funded by national institutes and government bodies to ensure unbiased results, as the findings of such studies may need legislative changes.

MDMA's first identified potential as a therapeutic catalyst was for couple therapy. Early work in the 1970s and 1980s explored its potential amongst seasoned psychotherapists and their clients. With the completion of the first pilot trial of MDMA-assisted psychotherapy with couples for PTSD, and as the possibility of conducting MDMA-assisted psychotherapy trials expands due to new regulatory frameworks, we have an opportunity to explore and investigate how and why MDMA-assisted couples therapy works. This theoretical paper will explore the neurobiological and neurochemical effects of MDMA in a relational context, the emotional, behavioral, cognitive and somatic effects within a dyadic frame, and how empathy, communication, perception of social connection/support, non-avoidance, openness, attachment/safety, bonding/social intimacy and relationship satisfaction, are all impacted by MDMA, and can be harnessed to facilitate systems-level and interpersonal healing and growth. A model to support MDMA-assisted couple therapy is introduced, and future directions, including implications for intervention development and delivery, will be elucidated.

MDMA's first identified potential as a therapeutic catalyst was for couple therapy. Early work in the 1970s and 1980s explored its potential amongst seasoned psychotherapists and their clients. With the completion of the first pilot trial of MDMA-assisted psychotherapy with couples for PTSD, and as the possibility of conducting MDMA-assisted psychotherapy trials expands due to new regulatory frameworks, we have an opportunity to explore and investigate how and why MDMA-assisted couples therapy works. This theoretical paper will explore the neurobiological and neurochemical effects of MDMA in a relational context, the emotional, behavioral, cognitive and somatic effects within a dyadic frame, and how empathy, communication, perception of social connection/support, non-avoidance, openness, attachment/safety, bonding/social intimacy and relationship satisfaction, are all impacted by MDMA, and can be harnessed to facilitate systems-level and interpersonal healing and growth. A model to support MDMA-assisted couple therapy is introduced, and future directions, including implications for intervention development and delivery, will be elucidated. [ABSTRACT FROM AUTHOR]

Aims: To determine trends in 3,4 methylenedioxymethamphetamine (MDMA)‐related death rates across Australia, Finland, Portugal and Turkey and to analyse the toxicology and causes of death across countries. Design Analysis of MDMA‐related deaths extracted from a national coronial database in Australia (2001–19) and national forensic toxicology databases in Finland (2001–17), Portugal (2008–19) and Turkey (2007–17). Presentation of MDMA use and seizure data (market indicators). Setting: Australia, Finland, Portugal and Turkey. Cases All deaths in which MDMA was considered by the forensic pathologist to be contributory to death. Measurements Information collected on cause and circumstances of death, demographics and toxicology. Findings A total of 1400 MDMA‐related deaths were identified in Turkey, 507 in Australia, 100 in Finland and 45 in Portugal. The median age ranged from 24 to 27.5 years, and males represented between 81 and 94% of the deaths across countries. Standardized mortality rates significantly increased across all four countries from 2011 to 2017 during a period of increased purity and availability of MDMA. The underlying cause of death was predominantly due to drug toxicity in Australia (n = 309, 61%), Finland (n = 70, 70%) and Turkey (n = 840, 60%) and other causes in Portugal (n = 25, 56%). Minorities of all deaths across the countries were due to MDMA toxicity alone (13–25%). These deaths had a significantly higher blood MDMA concentration than multiple drug toxicity deaths in Australia, Finland and Turkey. Drugs other than MDMA commonly detected were stimulants (including cocaine, amphetamine and methamphetamine) (Australia 52% and Finland 61%) and alcohol (Australia 46% and Portugal 49%). In addition to MDMA toxicity, benzodiazepines (81%) and opioids (64%) were commonly identified in these deaths in Finland. In comparison, synthetic cannabinoids (15%) and cannabis (33%) were present in a minority of deaths in Turkey. Conclusions: Deaths related to 3,4 methylenedioxymethamphetamine (MDMA) increased in Australia, Finland, Portugal and Turkey between 2011 and 2017. Findings show MDMA toxicity alone can be fatal, but multiple drug toxicity remains more prevalent. [ABSTRACT FROM AUTHOR]

3,4 Methylenedioxymethamphetamine (MDMA)-assisted therapy has been recently found to be highly effective for treatment of posttraumatic stress disorder (PTSD). Previous studies have been inconclusive in elucidating potential MDMA genotoxicity. We performed three regulatory compliant studies to investigate the potential of genotoxic effects of MDMA treatment in humans: (1) an in vitro bacterial reverse mutation (Ames) assay, (2) an in vitro chromosome aberration test in Chinese hamster ovary cells, and (3) an in vivo micronucleus study in male Sprague Dawley rats. MDMA was found to not have genotoxic effects in any of the assays at or above clinically relevant concentrations. [ABSTRACT FROM AUTHOR]

La 3,4-méthylènedioxymétamphétamine (MDMA) ou ecstasy est connue comme drogue récréative illégale et connaît actuellement un regain d'intérêt dans les soirées festives auprès des jeunes. Elle est consommée pour ses effets empathogènes et entactogènes et les nouvelles tendances de consommations dans ce type de soirées l'associent fréquemment au GHB et à l'alcool. Des comprimés très colorés et de formes variées sont retrouvés sur les marchés pour être les plus attractifs possible. Et ces dernières années, on observe une nette augmentation de leurs teneurs en MDMA. Le dépistage rapide de la MDMA par méthodes immunochimiques peut être réalisé sur des automates de laboratoire ou sur des tests rapides sur les urines ou plus récemment sur des prélèvements salivaires. Une méthode de confirmation en chromatographie couplée à de la spectrométrie de masse permet d'identifier de façon spécifique la MDMA parmi les différentes et nombreuses structures amphétaminiques. Ces recherches et/ou dosages peuvent être réalisées sur de nombreuses matrices biologiques (sang, urine, salive, cheveux etc.) dans des contextes cliniques ou en médico-légal. Les tableaux d'intoxications fatales ou non fatales avec atteinte hépatique sont rapportés dans la littérature avec des concentrations très variables observées. 3,4-methylenedioxymetamphetamine (MDMA) or ecstasy is known as an illegal recreational drug and is currently experiencing renewed interest in festive evenings with young people. It is consumed for its empathetic and entactogenic effects and new consumption trends in this type of evening frequently associate it with GHB and alcohol. Very colorful tablets of various shapes are found on the markets to be the most attractive possible. And in recent years, there has been a marked increase in their MDMA content. Rapid testing of MDMA by immunochemical methods can be performed on laboratory automata or on urine rapid tests or more recently on salivary samples. À confirmation method in chromatography coupled with mass spectrometry makes it possible to identify specifically MDMA among the different amphetamine structures. This research and/or assays can be performed on many biological matrices (blood, urine, saliva, hair, etc.) in clinical or forensic cases. Fatal or non-fatal poisoning with hepatic involvement are reported in literature with variability in concentrations described. [ABSTRACT FROM AUTHOR]

The re-emergence of therapeutic uses for mind-altering, psychedelic drugs has brought the field of mental health to a new frontier in research, practice, and policymaking. In the past two decades dozens of clinical trials investigating therapeutic applications of psychedelics—including MDMA, psilocybin, and ketamine—have shown promising results in the treatment of trauma-related disorders, some forms of anxiety, and depression. These substances have also garnered preliminary support from the Food and Drug Administration, which has fast-tracked their development. As the field of psychedelic science continues to grow, a serious consideration of these novel treatments in the context of social work practice and values is imperative. This paper offers a brief overview of MDMA-, psilocybin-, and ketamine-assisted treatments, and presents an initial discussion of questions pertinent to social work practice raised by their use, including: safety, efficacy, theory of change, training needs, and social justice considerations. [ABSTRACT FROM AUTHOR]

Introduction: Calls to provide sanctioned drug‐checking (pill testing) at Australian music festivals have been met with resistance from most governments due to concerns that such services would increase use of ecstasy and other drugs. We investigated that concern and used the Theory of Planned Behaviour to examine the determinants of intention to use a drug‐checking service. Methods: Data were collected over a 3‐day period at a music festival in Western Australia. Participants (n = 247; 50% male; 52% aged 25–34 years) were presented with three hypothetical pill testing scenarios: no testing provided, onsite testing provided and fixed offsite testing provided. Results: Neither ecstasy users (n = 212) nor participants who had never used ecstasy (n = 35) reported an increased intention to use ecstasy in scenarios in which drug checking was provided. The combination of attitudes, subjective norms and perceived behavioural control predicted intention to use a fixed site drug‐checking service, while only subjective norms predicted intention to use an onsite service. Discussion and Conclusions: These data do not support the view that offering a drug‐checking service at a festival will result in ecstasy use by people who have never used ecstasy or lead to increased use among people who use ecstasy. [ABSTRACT FROM AUTHOR]

Preclinical and clinical studies indicate that synthetic psychoactive substances, in addition to having abuse potential, may elicit toxic effects of varying severity at the peripheral and central levels. Nowadays, toxicity induced by synthetic psychoactive substances poses a serious harm for health, since recreational use of these substances is on the rise among young and adult people. The present review summarizes recent findings on the peripheral and central toxicity elicited by “old” and “new” synthetic psychoactive substances in humans and experimental animals, focusing on amphetamine derivatives, hallucinogen and dissociative drugs and synthetic cannabinoids.

Abstract Background Previous reported cases on excited delirium syndrome studied on the common clinical manifestations of the syndrome. The usual forensics implication for the syndrome is that death commonly is associated with restraint procedures by law enforcement agencies; however, not many cases reported highlights the difficulties in attributing a violent scene of death to the syndrome. Case presentation We present a case of a partially naked body found in an apartment unit under suspicious circumstances with multiple injuries. The scene of death was violent, and the body was found with blood wiped all over the floor and walls. Investigators believed a violent crime had occurred, and a suspect was reprimanded. However, upon autopsy, it was found that all injuries were superficially inflicted and were unlikely to have been part of an act of commission or caused his death. Internal examination found no remarkable pathology. Toxicology revealed a presence of psychostimulants, that is, methamphetamine, MDMA, and ethyl alcohol. Reconstruction of events by the witness, who was initially suspected of the ‘murder’, revealed that the injuries and his death could likely be explained by an episode of excited delirium. Conclusion The case highlights the challenges faced when attributing excited delirium syndrome as a cause of death. The syndrome can present with injuries from aggressive or bizarre behaviour, coupled with the destruction of property, which may confuse investigators on the possible manner of death.

Background: Nowadays, one of the problems of human beings is drug addiction, which causes individual, economic and social damages. One of the most commonly used substances in parties is ecstasy pills or 3, 4-methylenedioxymethamphetamine (MDMA). This study seeks to assess the effect of curcumin in complications of ecstasy on liver tissue in rats. Methods:48 male Wistar rats in six groups were treated with curcumin (20 µ mol/kg) and MDMA (20 mg/kg) simultaneously and non-simultaneously. At the end of the experiment, blood samples were collected, lipid profile, liver enzymes were measured and morphology of liver was done. Results: MDMA consumption had adverse effect on lipid profile in comparison to the control group. Treatment of curcumin with MDMA consumption improved this effect of MDMA on lipid profile. Moreover, curcumin treatment concurrent with MDMA consumption increased liver enzymes, whereas consumption of MDMA for 15 days and curcumin treatment in the next 15 days decreased liver enzymes. Conclusion: Our findings suggest that simultaneous consumption of MDMA and curcumin have a synergistic adverse effect on liver enzymes and liver tissue. It is assumed that MDMA intestinal absorption increased by curcumin. While non-simultaneous treatment of curcumin and MDMA improved undesirable effects of MDMA on liver that is assumed by antioxidant capabilities of curcumin.

Healing from trauma occurs in a relational context, and the impacts of traumatic experiences that result in post-traumatic stress disorder (PTSD) go beyond the diagnosis itself. To fully understand a treatment for PTSD, understanding its impact on interpersonal, relational, and growth outcomes yields a more fulsome picture of the effects of the treatment. The current paper examines these secondary outcomes of a pilot trial of Cognitive Behavioral Conjoint Therapy (CBCT) for PTSD with MDMA. Six romantic dyads, where one partner had PTSD, undertook a course of treatment combining CBCT for PTSD with two MDMA psychotherapy sessions. Outcomes were assessed at mid-treatment, post-treatment, and 3- and 6-month follow-up. Both partners reported improvements in post-traumatic growth, relational support, and social intimacy. Partners reported reduced behavioral accommodation and conflict in the relationship, and patients with PTSD reported improved psychosocial functioning and empathic concern. These improvements were maintained throughout the follow-up period. These findings suggest that CBCT for PTSD with MDMA has significant effect on relational and growth outcomes in this pilot sample. Improvements in these domains is central to a holistic recovery from traumatic experiences, and lends support to the utility of treating PTSD dyadically.

Background Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g. methamphetamine [MA]) and/or entactogens (e.g. 3,4-methylenedioxymethaphetamine [MDMA])—presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates. Methods The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle. Results Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects. Conclusions These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans. [ABSTRACT FROM AUTHOR]

Psychedelics are a hallucinogenic class of psychoactive drugs with the primary effect of activating non-ordinary states of consciousness. Due to the positive preliminary findings of these drugs in the treatment of psychiatric disorders, the number of registered clinical studies has risen significantly. In this paper, clinical studies registered on clinicaltrials.gov that evaluate the treatment of any psychiatric disorder with psychedelics (excluding ketamine) are summarized and analyzed. 70 registered studies were identified from a clinicaltrials.gov search on December 3, 2020. The majority of studies aim to investigate methylenedioxymethamphetamine (MDMA) (45.7%) and psilocybin (41.4%). Studies evaluating ayahuasca, lysergic acid diethylamide (LSD), ibogaine hydrochloride, salvia divinorum, 5-MeO-DMT and DMT fumarate were less common at 1.4%, 4.2%, 2.8%, 1.4%, 1.4% and 1.4% of total registered studies, respectively. Most of the studies on MDMA, psilocybin, ayahuasca and salvia divinorum investigated their therapeutic effect on post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). LSD was investigated for MDD, anxiety, and severe somatic disorders and ibogaine hydrochloride was investigated for substance and alcohol use disorders. 5-MeO-DMT and DMT fumarate were both investigated for MDD. Only 21/70 registered studies had published results with the majority not yet completed. In view of the large number of ongoing studies investigating psychedelics, it is imperative that these studies are considered by researchers and stakeholders in deciding the most relevant research priorities for future proposed studies. • 70 registered studies investigating psychedelics for psychiatric disorders were identified. • The majority of registered studies aim to investigate MDMA (46%) and psilocybin (41%). • Other psychedelics under investigation include LSD, ayahuasca, salvia, ibogaine, 5-MeO-DMT and DMT fumarate. • Only 21/70 (30%) registered studies have published results to date. [ABSTRACT FROM AUTHOR]

The vast majority of illicit stimulants act at monoaminergic systems, causing both psychostimulant and adverse effects. Stimulants can interact as substrates or antagonists at the nerve terminal monoamine transporter that mediates the reuptake of monoamines across the nerve synaptic membrane and at the vesicular monoamine transporter (VMAT-2) that mediates storage of monoamines in vesicles. Stimulants can act directly at presynaptic or postsynaptic receptors for monoamines or have indirect monoamine-mimetic actions due to the release of monoamines. Cocaine and other stimulants can acutely increase the risk of sudden cardiac death. Stimulants, particularly MDMA, in hot conditions, such as that occurring at a "rave," have caused fatalities from the consequences of hyperthermia, often compounding cardiac adverse actions. This review examines the pharmacology of the cardiovascular and temperature adverse actions of stimulants. [ABSTRACT FROM AUTHOR]

Background: Garcinia kola (GK) has been experimentally tested for its potential usefulness against oxidative stress-related disorders in a number of body tissues, as well as a number of pathogenic and parasitic diseases. Studies investigating GK extracts' usefulness in combating nervous tissue toxicity, neuroinflammatory disorders, and neuronal degeneration are still inadequate and not yet conclusive. Purpose: To evaluate the effects of 3,4-methylenedioxymethamphetamine (MDMA)-induced neuroinflammation on the pyramidal neurons and astrocytes of the cornu ammonis 1 (CA1) region of the hippocampus and the role of GK extract (GKE) in attenuating the effects in the rat model. Methods: The study was carried out by using 60 healthy adult male Wistar rats, which were randomly assigned into six groups, A, B, C, D, E, and F (n = 10)—A (control), B (100 mg/kg body weight of GKE only), C (200 mg/kg body weight of GKE only), D (20 mg/kg body weight of MDMA only), E (100 mg/kg body weight of GKE and 20 mg/kg body weight of MDMA), and F (200 mg/kg body weight of GKE and 20 mg/kg body weight of MDMA). Treatment was given for 21 days. Following 24 hours after the last administration, five rats in each group were anesthetized with diether and perfused intracardially, and the brains were excised and fixed in 10 percent neutral buffered formalin for the histological hematoxylin and eosin (H&E) and immunohistochemical glial fibrillary acidic proteins (GFAP). A thin-slice coronal section of the brain was obtained at the level of the optic chiasma and processed via the paraffin-embedding method. Also, the remaining five brains were used to assess neurotransmitter levels (serotonin and dopamine) and cytochrome c-oxidase. The statistical analysis was done using a one-way analysis of variance (ANOVA). Results: A significant reduction (P <.05) in body weight was observed in the group that was administered with MDMA when compared with the control and the rest of the treated groups. Dopamine and serotonin levels were significantly decreased (P <.05) in the MDMA-only group when compared with the control and the rest of the treated groups. The control group and groups B, C, and F showed intact pyramidal neurons, unlike group D, which showed vacuolated and degenerating neurons. The expressions of vacuolation and degeneration in group D were less than those in group E, which received a low dose of GKE and MDMA. Hippocampal astrocytic expressions were significantly higher (P >.05) in the MDMA-only group when compared with the control and other groups. Conclusion: GKE has significant neuroprotective potential against MDMA-induced toxicity in brain tissue. This is evident in its prevention of MDMA-induced oxidative stress, pyramidal neuronal vacuolation, dispersion, and reactive astrogliosis in the CA1 region of the hippocampus. Our findings are dose-dependent, with 200 mg/kg of the extract being novel. We, however, recommend further study into the mechanism of action of GKE, on how it attenuates the astrocytic reaction caused by MDMA exposure. [ABSTRACT FROM AUTHOR]

Polydrug abuse is common among drug abusers. In particular, psychostimulants are often taken with ethanol, and the combination of 3,4-methylenedioxymethamphetamine (MDMA) and alcohol is one of the most common forms of polydrug abuse. However, the mechanism by which these drugs influence behavior remains unclear. The present study was designed to delineate the mechanisms that underlie the effects of the interaction between MDMA and ethanol on behavior in rodents. The combination of MDMA with ethanol enhanced their locomotor-increasing, rewarding, and discriminative stimulus effects without enhancing their effects on the release of dopamine from the nucleus accumbens in rodents. In addition, ethanol potently enhanced locomotor activity produced by the dopamine receptor agonist apomorphine in mice. In antagonism tests, the dopamine D1 -receptor antagonist SCH23390, but not the D2 -receptor antagonist haloperidol, completely suppressed hyperlocomotion induced by MDMA. However, hyperlocomotion induced by the co-administration of MDMA and ethanol was potently suppressed by haloperidol. These results suggest that the synergistic effects of MDMA and ethanol are mediated through dopamine transmission, especially through postsynaptical regulation of D2 -receptor-mediated functions. [ABSTRACT FROM AUTHOR]

Healing from trauma occurs in a relational context, and the impacts of traumatic experiences that result in post-traumatic stress disorder (PTSD) go beyond the diagnosis itself. To fully understand a treatment for PTSD, understanding its impact on interpersonal, relational, and growth outcomes yields a more fulsome picture of the effects of the treatment. The current paper examines these secondary outcomes of a pilot trial of Cognitive Behavioral Conjoint Therapy (CBCT) for PTSD with MDMA. Six romantic dyads, where one partner had PTSD, undertook a course of treatment combining CBCT for PTSD with two MDMA psychotherapy sessions. Outcomes were assessed at mid-treatment, post-treatment, and 3- and 6-month follow-up. Both partners reported improvements in post-traumatic growth, relational support, and social intimacy. Partners reported reduced behavioral accommodation and conflict in the relationship, and patients with PTSD reported improved psychosocial functioning and empathic concern. These improvements were maintained throughout the follow-up period. These findings suggest that CBCT for PTSD with MDMA has significant effect on relational and growth outcomes in this pilot sample. Improvements in these domains is central to a holistic recovery from traumatic experiences, and lends support to the utility of treating PTSD dyadically. [ABSTRACT FROM AUTHOR]

Methylenedioxymethamphetamine (MDMA) is an amphetamine analogue that preferentially stimulates the release of serotonin (5HT) and results in relatively small increases in synaptic dopamine (DA). The ratio of drug‐stimulated increases in synaptic DA, relative to 5HT, predicts the abuse liability; drugs with higher DA:5HT ratios are more likely to be abused. Nonetheless, MDMA is a drug that is misused. Clinical and preclinical studies have suggested that repeated MDMA exposure produces neuroadaptive responses in both 5HT and DA neurotransmission that might explain the development and maintenance of MDMA self‐administration in some laboratory animals and the development of a substance use disorder in some humans. In this paper, we describe the research that has demonstrated an inhibitory effect of 5HT on the acquisition of MDMA self‐administration and the critical role of DA in the maintenance of MDMA self‐administration in laboratory animals. We then describe the circuitry and 5HT receptors that are positioned to modulate DA activity and review the limited research on the effects of MDMA exposure on these receptor mechanisms. [ABSTRACT FROM AUTHOR]

Introduction Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Previous research has led to the designation of 3,4-methylenedioxymethamphetamine (MDMA) as a Breakthrough Therapy for treatment of post-traumatic stress disorder (PTSD) when administered as an adjunct to psychotherapy. Objectives Here we report the findings of the first randomized, double-blind, Phase 3 trial assessing the efficacy and safety of 3 sessions with a flexible dose of MDMA or placebo administered under direct observation to participants with severe PTSD (n = 100) as an adjunct to inner-directed psychotherapy. Methods Change in PTSD symptoms (CAPS-5) and functional impairment (SDS) were assessed by a central, blinded Independent Rater Pool at baseline and following each treatment session. Adverse events (AEs), concomitant medications, suicidal ideation and behavior were tracked throughout the study. Vital signs were measured during experimental sessions. The primary endpoint was 18 weeks post-randomization. Results Change in CAPS-5 and SDS, placebo-subtracted Cohen’s d effect size, and a responder analysis will be presented. There were three serious AEs of suicidal ideation or behavior reported. MDMA was well tolerated, with some treatment emergent AEs occurring at greater frequency for the MDMA group during and after experimental sessions. Conclusions If MDMA-assisted psychotherapy significantly attenuates PTSD symptomatology and associated functional impairment, these results will form the basis for marketing authorization applications worldwide, including among participants with dissociative subtype of PTSD, depression, history of alcohol and substance use disorders, and adverse childhood experiences. Disclosure No significant relationships.

Introduction Recently there has been renewal in interest of psychedelic research. Classic psychedelics such as lysergic acid diethylamide (LSD), psilocybin and mescaline act pharmacologically as agonists at the 5-HT2A receptor. The entactogens like methylenedioxymethamphetamine (MDMA), acts as a serotonin, dopamine and noradrenaline agonist. All of these drugs are potential candidates in the treatment of multiple psychiatric illnesses. Objectives The authors intend to review the literature on the clinical application of psychedelic drugs in psychiatric disorders. Methods Non-systematic review of the literature. Results In recent clinical trial the psychedelic is given with psychotherapeutic input. In a supportive setting, psychedelics produced immediate and significant anti-depressant and anxiolytic effects that were endured for several months. Randomized clinical trials support the efficace of psilocybin in the treatment of depression and those with anxiety and depression symptoms provoked by life-threatening cancer. There have also been studies showing efficacy in both alcohol and tobacco dependence. When administered safely LSD can reduce anxiety and have anti-addictive property. Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD. Psychedelics were well-tolerated, few adverse effects have been reported. The most common adverse effects were transient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure, with no persisting adverse effects. Serious adverse events, such as persistent psychosis and suicidality, have not been demonstrated. Conclusions Psychedelics appear to be effective in multiple psychiatric disorders and are well-tolerated, although further evidence is required, to better see they therapeutic potential. Disclosure No significant relationships.

Introduction Post-traumatic stress disorder (PTSD) is often a chronic condition, despite the existence of evidence-based treatment options. Psychotherapy is the designated first line treatment for PTSD, although high rates of psychiatric and medical comorbidity are observed among patients who have undergone treatment. The psychoactive properties of psychedelics may be of particular interest within a substance-assisted psychotherapy approach, offering new treatment opportunities for this debilitating disorder. Objectives Review current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD. Methods Literature review using Medline database. Results 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy appears to be a potentially safe, effective, and durable treatment for individuals with treatment-refractory PTSD. Based on a small number of studies, ketamine administration appears to result in temporary symptom relief and may, in combination with psychotherapy, lead to lasting reductions in PTSD symptoms. Although these have not yet been investigated in controlled studies, it is known that psilocybin and LSD induce psychoactive effects that could as well contribute to the psychotherapeutic treatment of PTSD. Conclusions The use of psychedelic compounds within a substance-assisted psychotherapy framework offers a novel method for pharmacotherapy-psychotherapy integration, although there is still much to learn from both a clinical and neurobiological perspective. It is necessary to generate more data regarding the safety and efficacy of psychedelics, in addition to research on cost-effectiveness, its use in mental health care infrastructure and also regarding the training of specialized therapists.

Introduction Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials. Objectives To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD. Methods Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck’s Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within seven days of intervention. Results Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75mg (MD -46.90; 95% CI -58.78, -35.02), 125mg (MD -20.98; 95% CI -34.35, -7.61) but not 100mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after seven days. Conclusions These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck’s Depression Inventory. Better powered RCTs are required to investigate further. Disclosure James Rucker has attended trial related meetings paid for by Compass Pathways Ltd.

Illicit drugs use and abuse remains an increasing challenge for worldwide authorities and, therefore, it is important to have accurate methods to detect them in seized samples, biological fluids and wastewaters. They are recently classified as the latest group of emerging pollutants as their consumption increased tremendously in recent years. Nanomaterials have gained much attention over the last decade in the development of sensors for a myriad of applications. The applicability of these nanomaterials, functionalized or not, significantly increases and it is therefore highly suitable for use in the detection of illicit drugs. We have assessed the suitability of various nanoplatforms, such as graphene (GPH), multi-walled carbon nanotubes (MWCNTs), gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs) for the electrochemical detection of illicit drugs. GPH and MWCNTs were chosen as the most suitable platforms and cocaine, 3,4-methylendioxymethamfetamine (MDMA), 3-methylmethcathinone (MMC) and α-pyrrolidinovalerophenone (PVP) were tested. Due to the hydrophobicity of the nanomaterials-based platforms which led to low signals, two strategies were followed namely, pretreatment of the electrodes in sulfuric acid by cyclic voltammetry and addition of Tween 20 to the detection buffer. Both strategies led to an increase in the oxidation signal of illicit drugs. Binary mixtures of illicit drugs with common adulterants found in street samples were also investigated. The proposed strategies allowed the sensitive detection of illicit drugs in the presence of most adulterants. The suitability of the proposed sensors for the detection of illicit drugs in spiked wastewaters was finally assessed.

Serotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SOs), a synchronized cortical network activity universally present across species. SOs are observed during anesthesia and are considered to be the default cortical activity pattern. We discovered that (±)3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine, two potent 5-HT releasers, inhibit SOs within the entorhinal cortex (EC) in anesthetized mice. Combining opto- and pharmacogenetic manipulations with in vitro electrophysiological recordings, we uncovered that somatostatin-expressing (Sst) interneurons activated by the 5-HT2A receptor (5-HT2AR) play an important role in the suppression of SOs. Since 5-HT2AR signaling is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, we propose that the newly discovered link between Sst interneurons and 5-HT will contribute to our understanding of these complex topics.

Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.