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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.

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

Psychedelics, historically celebrated for their cultural and spiritual significance, have emerged as potential breakthrough therapeutic agents due to their profound effects on consciousness, emotional processing, mood, and neural plasticity. This review explores the mechanisms underlying psychedelics' effects, focusing on their ability to modulate brain connectivity and neural circuit activity, including the default mode network (DMN), cortico-striatal thalamo-cortical (CSTC) loops, and the relaxed beliefs under psychedelics (REBUS) model. Advanced neuroimaging techniques reveal psychedelics' capacity to enhance functional connectivity between sensory cerebral areas while reducing the connections between associative brain areas, decreasing the rigidity and rendering the brain more plastic and susceptible to external changings, offering insights into their therapeutic outcome. The most relevant clinical trials of 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and lysergic acid diethylamide (LSD) demonstrate significant efficacy in treating treatment-resistant psychiatric conditions such as post-traumatic stress disorder (PTSD), depression, and anxiety, with favorable safety profiles. Despite these advancements, critical gaps remain in linking psychedelics' molecular actions to their clinical efficacy. This review highlights the need for further research to integrate mechanistic insights and optimize psychedelics as tools for both therapy and understanding human cognition. [ABSTRACT FROM AUTHOR]

Psychoactive drugs such as alcohol and stimulants are typically used in social settings such as bars, parties or small groups. Yet, relatively little is known about how social contexts affect responses to drugs, or how the drugs alter social interactions. It is possible that positive social contexts enhance the rewarding properties of drugs, perhaps increasing their potential for repeated use and abuse. In addition, drugs may enhance the rewarding effects of social interactions by increasing feelings of social closeness and connectedness. To examine these relations, we investigated the effects of several drugs (MDMA, methamphetamine, alcohol) on feelings of connection between two strangers engaged in a conversation. We also investigated feelings of connection between two participants who discussed either 'shallow' or deeper topics in two conversations, without any drugs. All four conditions: deeper conversations, MDMA, methamphetamine and alcohol significantly increased feelings of connection and closeness compared with control conditions (small talk or placebo). We postulate that these feelings of connection could contribute to the drugs' rewarding effects when the drugs are used in social contexts. [ABSTRACT FROM AUTHOR]

Background: There is ongoing research into the potential use of psychedelics and 3,4-methylenedioxy-methamphetamine (MDMA) as alternatives to commonly used medications for treating major depressive and anxiety disorders. Aims: We aimed to assess the efficacy of psychedelics and MDMA in managing depressive and anxiety symptoms and evaluate their safety profiles. Methods: We searched five databases for randomized controlled trials of psychedelics and MDMA targeting depressive and anxiety symptoms and conducted a meta-analysis using a random effects model when possible. The review protocol is registered in PROSPERO under CRD42022341325. Results: Psilocybin induced a rapid and sustained reduction in depressive and anxiety symptoms in patients with major depressive disorder and in patients with life-threatening cancer. MDMA induced a decrease in depressive symptoms in patients with life-threatening cancer, autism spectrum disorder, and post-traumatic stress disorder. MDMA's effect size was either negligible or negative in reducing generalized anxiety symptoms, but MDMA reduced social anxiety symptoms. Ayahuasca induced a reduction in depressive symptoms in individuals with treatment-resistant major depressive and personality disorders. Lysergic acid diethylamide (LSD) induced a decrease in anxiety symptoms in individuals with life-threatening cancer. Psilocybin's adverse effects were noticeable for elevated blood pressure, headaches, and panic attacks. For MDMA, elevated blood pressure, headaches, panic attacks, and feeling cold were noticeable. Conclusions: Psychedelics (psilocybin, ayahuasca, and LSD) and MDMA have the potential to induce a reduction in depressive and anxiety symptoms. Adverse effects are noticed. Rigorous randomized controlled studies with larger sample sizes utilizing instruments with better reliability and validity are warranted. [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 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.

Abstract Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression was used to identify predictors of openness to clinical use. Most participants (71.2%) were female and White (85.8%), with a mean (SD) age of 45.5 (12.7) years. Registered nurses (25.4%) and physicians (17.7%) comprised the largest professional groups. Respondents endorsed strong belief in therapeutic promise, and moderate openness to clinical use and support for legal access to both substances, with higher overall ratings for psilocybin compared to MDMA. Objective knowledge items revealed low knowledge of therapeutic uses, risks, and pharmacology. Primary concerns were lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted openness to clinical use of psilocybin and MDMA, with physicians reporting lower openness. As psychedelics continue to garner popular and scientific interest, results indicate a pressing need for additional formal training to provide balanced, evidence-based information from trusted sources.

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.

Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression was used to identify predictors of openness to clinical use. Most participants (71.2%) were female and White (85.8%), with a mean (SD) age of 45.5 (12.7) years. Registered nurses (25.4%) and physicians (17.7%) comprised the largest professional groups. Respondents endorsed strong belief in therapeutic promise, and moderate openness to clinical use and support for legal access to both substances, with higher overall ratings for psilocybin compared to MDMA. Objective knowledge items revealed low knowledge of therapeutic uses, risks, and pharmacology. Primary concerns were lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted openness to clinical use of psilocybin and MDMA, with physicians reporting lower openness. As psychedelics continue to garner popular and scientific interest, results indicate a pressing need for additional formal training to provide balanced, evidence-based information from trusted sources. [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]

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]

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]

A 64-year-old male patient who suffered from traumatic life experiences and neuropathic pain after oncological chemotherapy was treated with medium to high doses of lysergic acid diethylamide (LSD) and high doses and microdoses of methylenedioxymethamphetamine (MDMA). At the beginning of treatment, the patient did not experience any acute subjective effects of LSD at a dose of 200 µg. After increasing the LSD dose to 400 µg, he experienced subjective acute effects, and the first lasting therapeutic effects were observed. After changing from LSD to MDMA at both high doses (150-175 mg) and repeated low doses (12.5-25 mg), the patient exhibited marked improvements in neuropathic pain that were sustained even after stopping repeated MDMA treatment. MDMA mini/microdosing has not yet been broadly investigated. This case documents benefits of low doses of MDMA for the treatment of a pain disorder. Further research is needed on effects of MDMA on pain.

Although effective evidence-based trauma-focused psychotherapies for posttraumatic stress disorder (PTSD) are available, a significant proportion of patients show a suboptimal response or do not complete them. MDMA-assisted therapy (MDMA-AT) for PTSD is a promising intervention currently being evaluated in numerous studies worldwide, including investigation for potential Food and Drug Administration (FDA) approval in the United States. The concepts of set and setting are foundational in psychedelic therapy and refer to the mindset a person brings to therapy and the environment in which it takes place, respectively. Both are believed to play a critical role in the individual’s experience and efficacy of MDMA-AT. In this article, we describe the importance of set and setting in MDMA-AT for PTSD and outline the advantages and challenges of implementing this novel intervention in large healthcare settings such as the Veterans Health Administration (VHA). Mostly derived from our experience conducting clinical trials of MDMA-AT for PTSD in VHA, we present specific and practical suggestions for optimizing set and setting from both the participant’s and clinician’s perspective in a manner that both leverages the opportunities of such settings and adapts to their challenges. These recommendations are intended to inform future MDMA-AT for PTSD research and, potentially, eventual clinical implementation efforts in traditional healthcare systems.

3, 4-methylenedioxyamphetamine (MDMA) has gained significance over the years, especially at rave festivals, as a recreational drug for its noted effects in mood enhancement and autonomic stimulation. While these effects have been noted, severe adverse outcomes, and even death, following the ingestion of MDMA have been recorded.We present a 35-year-old male who ingested the drug at the Electric Daisy Carnival (EDC), the largest electronic dance music festival in North America as of 2024 [1]. Every year, many young adults are brought to local hospitals from the festival for drug overdoses, hyperthermia, and dehydration. At the festival, the patient was witnessed to have a seizure, presented with altered mental status and deemed hyperthermic at 109 degrees Fahrenheit. For these reasons, he was rapidly intubated and submerged in an ice bath at the festival’s medical tent. At the county hospital, the patient was diagnosed with multiorgan failure, cerebrovascular ischemia, and coagulopathy. He received life-saving treatment such as continuous renal replacement therapy as well as intubation for acute hypoxemic respiratory failure. MRI of the brain showed central- embolic infarcts and the patient was closely monitored in the intensive care unit (ICU) for eight days. After twenty days of inpatient treatment, the patient was discharged. He was discharged with his mental status at baseline and without gross neurologic deficits. A permacath was placed for hemodialysis to be continued outpatient.This case report highlights the importance of prompt medical management which can be crucial for patient survival following a life-threatening overdose with MDMA. It also exemplifies the need for increasing social awareness regarding the severe and detrimental outcomes an MDMA overdose can cause as this drug continues to be widely used in the setting of rave and music festivals.

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.

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.

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]

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]

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]

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 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]

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

Background: 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.

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.

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.

Although early therapeutic research on psychedelics dates back to the 1940s, this field of investigation was met with many cultural and legal challenges in the 1970s. Over the past two decades, clinical trials using psychedelics have resumed. Therefore, the goal of this study was to (1) better characterize the recent uptrend in psychedelics in clinical trials and (2) identify areas where potentially new clinical trials could be initiated to help in the treatment of widely prevalent medical disorders. A systematic search was conducted on the clinicaltrials.gov database for all registered clinical trials examining the use of psychedelic drugs and was both qualitatively and quantitatively assessed. Analysis of recent studies registered in clinicaltrials.gov was performed using Pearson's correlation coefficient testing. Statistical analysis and visualization were performed using R software. In totality, 105 clinical trials met this study's inclusion criteria. The recent uptrend in registered clinical trials studying psychedelics (p = 0.002) was similar to the uptrend in total registered clinical trials in the registry (p < 0.001). All trials took place from 2007 to 2020, with 77.1% of studies starting in 2017 or later. A majority of clinical trials were in phase 1 (53.3%) or phase 2 (25.7%). Common disorders treated include substance addiction, post-traumatic stress disorder, and major depressive disorder. Potential research gaps include studying psychedelics as a potential option for symptomatic treatment during opioid tapering. There appears to be a recent uptrend in registered clinical trials studying psychedelics, which is similar to the recent increase in overall trials registered. Potentially, more studies could be performed to evaluate the potential of psychedelics for symptomatic treatment during opioid tapering and depression refractory to selective serotonin reuptake inhibitors.

BackgroundAmong the renewed applications of psychedelic medicines in psychiatry, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder (PTSD) has demonstrated the most promise in early small-scale studies. Recent exploratory analyses from prior clinical trials of MDMA-assisted therapy for PTSD have suggested that recent use of selective serotonin reuptake inhibitors (SSRIs)-the only medication class with United States Food and Drug Administration (FDA) approval to treat PTSD-can significantly dampen the efficacy of this novel therapy. Although psychedelic medicines are not yet FDA approved, MDMA is very likely to be the first to achieve FDA approval-perhaps within the next 2 years. Given this timeline, the field would benefit from more knowledge about potential interactions between this novel therapy and our current treatments.MethodsThis brief report reviews selected literature in the basic and clinical neurosciences relevant to the interaction of SSRIs and MDMA.FindingsThe possibility that SSRI use could dampen future responses to MDMA-assisted therapy for PTSD raises many important questions about the biological mechanisms as well as ethical implications around the most appropriate way to counsel patients. In this brief report, we compare the evidence for SSRIs and MDMA-assisted therapy in the treatment of PTSD and discuss what is known about the neurobiological interactions between these 2 medicines.ConclusionsThere is strong neurobiological plausibility for the hypothesis that chronic SSRI use dampens response to MDMA-assisted therapy, although current knowledge in the field is limited and primarily relates to acute pharmacodynamic interactions. Our commentary highlights the urgent need for future work dedicated to addressing this important clinical topic.

Psychedelic science has generated hundreds of compelling published studies yet with relatively little impact on mainstream psychology. I propose that social psychologists have much to gain by incorporating psychoactive substances into their research programs. Here I use (±)-3,4-methylenedioxymethamphetamine (MDMA) as an example because of its documented ability in experiments and clinical trials to promote bonding, love, and warmth. Social connection is a fundamental human need, yet researchers still possess few tools to effectively and durably boost it. MDMA allows investigators to isolate the psychological mechanisms-as well as brain pathways-underlying felt social connection and thus reveal what should be targeted in future (nondrug) studies. Accordingly, I introduce a conceptual model that presents the proximal psychological mechanisms stimulated by MDMA (lowered fear, increased sociability, more chemistry), as well as its potential long-term impacts (improved relationships, reduced loneliness, stronger therapeutic alliances). Finally, I discuss further questions (e.g., whether using MDMA for enhancing connection can backfire) and promising research areas for building a new science of psychedelic social psychology. In sum, psychopharmacological methods can be a useful approach to illuminate commonly studied social-psychological processes, such as connectedness, prejudice, or self, as well as inform interventions to directly improve people's lives.

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: 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. [ABSTRACT FROM AUTHOR]

Introduction: Recent research suggests that psychedelics may have potential for the treatment of various substance use disorders. However, most studies to date have been limited by small sample sizes and neglecting to include non-North American and European populations. Methods: We conducted a global, cross-sectional online survey of adults (n = 5,268, 47.2%women) self-reporting past or current psychedelic use and investigated whether psychedelic use was associated with changes in use of other substances. Results: Nearly three-quarters (70.9%; n = 3,737/5,268) reported ceasing or decreasing use of one or more non-psychedelic substances after naturalistic psychedelic use. Among those with previous use, 60.6% (n = 2,634/4,344) decreased alcohol use, 55.7% (n = 1,223/2,197) decreased antidepressant use, and 54.2% (n = 767/1,415) decreased use of cocaine/crack. Over a quarter of the sample indicated that their decrease in substance use persisted for 26 weeks or more following use of a psychedelic. Factors associated with decreased use included a motivation to either decrease one's substance use or self-treat a medical condition. Importantly, 19.8% of respondents also reported increased or initiated use of one or more other substances after psychedelic use, with illicit opioids (14.7%; n = 86/584) and cannabis (13.3%; n = 540/4,064) having the highest proportions. Factors associated with increased substance use included having a higher income and residing in Canada or the US. Discussion: Although limited by cross-sectional study design, this large observational study will help inform future studies aiming to investigate the relationship between substance use patterns and psychedelic use. [ABSTRACT FROM AUTHOR]

Objective: This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Methods: The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes ("cold cognition") measured through validated neuropsychological tests. Results: A total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA's effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing. Conclusions: Small samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies. [ABSTRACT FROM AUTHOR]

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.

The research and use of psychedelic medicines to treat common mental health disorders has increased substantially in the past 2 decades. At the same time, knowledge is relatively uncommon among midwives regarding (1) the relative benefits of psychedelic-assisted therapy, (2) best practices associated with the delivery of psychedelic-assisted therapy, and (3) responsible integration of this potentially useful intervention into mental health treatment plans. The purpose of this review is to describe current applications of psychedelic medicines to treat common mental health disorders, to describe the current legal status of these medicines used in this context, and to explore the potential for midwifery practice in this area with further training. This article also addresses the disparities regarding LGBTQIA+ and BIPOC populations in relation to this topic and their historical exclusion from research and treatment access in this field.

BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with alcohol and substance use disorders (ASUD). A randomized, placebo-controlled, phase 3 trial demonstrated the safety and efficacy of MDMA-assisted therapy (MDMA-AT) for the treatment of severe PTSD. This analysis explores patterns of alcohol and substance use in patients receiving MDMA-AT compared to placebo plus therapy (Placebo+Therapy). METHODS: Adult participants with severe PTSD (n = 90) were randomized to three blinded trauma-focused therapy sessions with either MDMA-AT or Placebo+Therapy. Eligible participants met DSM-5 criteria for severe PTSD and could meet criteria for mild (current) or moderate (early remission) alcohol or cannabis use disorder; other SUDs were excluded. The current analyses examined outcomes on standardized measures of hazardous alcohol (i.e., Alcohol Use Disorder Identification Test; AUDIT) and drug (i.e., Drug Use Disorder Identification Test; DUDIT) use at baseline prior to randomization and at study termination. RESULTS: There were no treatment group differences in AUDIT or DUDIT scores at baseline. Compared to Placebo+therapy, MDMA-AT was associated with a significantly greater reduction in mean (SD) AUDIT change scores (Δ = -1.02 (3.52) as compared to placebo (Δ = 0.40 (2.70), F (80, 1) = 4.20, p = 0.0436; Hedges g= .45). Changes in DUDIT scores were not significantly different between treatment groups. CONCLUSIONS: MDMA-AT for severe PTSD may also lead to subclinical improvements in alcohol use. MDMA-AT does not appear to increase risk of illicit drug use. These data provide preliminary evidence to support the development of MDMA-AT as an integrated treatment for co-occurring PTSD and ASUD.

This article discusses the relationship between psychiatry and spirituality. It highlights the rise in deaths from suicide, drug overdoses, and alcoholism, and the impact of loneliness and isolation on mental and physical health. The article argues that psychiatry often overlooks spirituality as a need and resource for patients, despite evidence that spirituality can have both negative and positive impacts on mental illness. It suggests that recognizing and addressing spiritual needs could improve well-being and treatment outcomes. The article also explores the role of psychedelic therapy in facilitating spiritual experiences and its potential therapeutic benefits. [Extracted from the article]

INTRODUCTION: 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) has demonstrated promise in multiple clinical trials. MDMA is hypothesized to facilitate the therapeutic process, in part, by decreasing fear response during fear memory processing while increasing extinction learning. The acute administration of MDMA in healthy controls modifies recruitment of brain regions involved in the hyperactive fear response in PTSD such as the amygdala, hippocampus, and insula. However, to date there have been no neuroimaging studies aimed at directly elucidating the neural impact of MDMA-AT in PTSD patients. METHODS: We analyzed brain activity and connectivity via functional MRI during both rest and autobiographical memory (trauma and neutral) response before and two-months after MDMA-AT in nine veterans and first-responders with chronic PTSD of 6 months or more. RESULTS: We hypothesized that MDMA-AT would increase amygdala-hippocampus resting-state functional connectivity, however we only found evidence of a trend in the left amygdala-left hippocampus (t = -2.91, uncorrected p = 0.0225, corrected p = 0.0901). We also found reduced activation contrast (trauma > neutral) after MDMA-AT in the cuneus. Finally, the amount of recovery from PTSD after MDMA-AT correlated with changes in four functional connections during autobiographical memory recall: the left amygdala-left posterior cingulate cortex (PCC), left amygdala-right PCC, left amygdala-left insula, and left isthmus cingulate-left posterior hippocampus. DISCUSSION: Amygdala-insular functional connectivity is reliably implicated in PTSD and anxiety, and both regions are impacted by MDMA administration. These findings compliment previous research indicating that amygdala, hippocampus, and insula functional connectivity is a potential target of MDMA-AT, and highlights other regions of interest related to memory processes. More research is necessary to determine if these findings are specific to MDMA-AT compared to other types of treatment for PTSD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02102802, identifier NCT02102802.

After a long hiatus, psychiatry is undergoing a resurgence of interest in psychedelic drugs as therapy for a wide range of mental health disorders Accumulating clinical evidence suggests substantial potential for psychedelics used in a therapeutic context, as treatment for, among other disorders, depression, post-traumatic stress disorder (PTSD), and addictions to tobacco, opioids and alcohol. As soon as 2024, powerful new therapeutic modalities could become available for individuals with mental health problems refractory to traditional therapies. Yet research has lagged on economic considerations, such as costs and cost-effectiveness, the economic effects of widespread implementation, pricing, and economic appraisal's methodological considerations relevant to psychedelic therapies. These issues are critical if psychedelic therapies are to become widely accessible. We describe six types of economic analyses and their rationale for decisions and planning including the needs of health care payers. We also outline desirable features of this research, including scientific rigor, long horizons, equity, and a global view.

3,4-Methylenedioxymethamphetamine (MDMA), is investigated as a treatment for post-traumatic stress disorder and other anxiety-related conditions in multiple placebo-controlled and open label studies. MDMA-assisted therapy is projected for approval by the United States Food and Drug Administration (FDA) and other regulatory agencies worldwide within the next few years. MDMA is a monoamine releaser and uptake inhibitor affecting serotonin, potentially increasing the risk of serotonin syndrome (SS). No instances of SS have occurred in clinical trials. The relatively small number of patients in controlled trials warranted a survey of FDA Adverse Event Reporting System data for the occurrence of SS in a larger database. We found 20 SS cases in people exposed to MDMA, all of which had also taken one or more substances with serotonergic properties in addition to MDMA, including amphetamines, stimulants, and opioids. There were no cases of SS associated with MDMA where MDMA was the sole reported compound taken.