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.

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.

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

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.

UNASSIGNED: Recent interest in the potential therapeutic effects of psychedelics has led to investigations into their influence on molecular signaling pathways within the brain.
UNASSIGNED: Integrated review and analysis of different studies in this field.
UNASSIGNED: A systematic search was conducted across international databases including Embase, Scopus, Web of Science, and PubMed from inception to 9 July 2023. Eligibility criteria encompassed published and peer-reviewed studies evaluating changes in brain-derived neurotrophic factor (BDNF) levels after psychedelic consumption.
UNASSIGNED: A total of nine studies were included in our study. The meta-analysis demonstrated significantly higher BDNF levels in psychedelic consumers compared to healthy controls, with a pooled standardized mean difference of 0.26 (95% CI: 0.10-0.42, I2 = 38.51%, p < 0.001). Leave-one-out analysis indicated robustness in results upon removal of individual psychedelics. No significant publication bias was observed. The results highlight the potential influence of psychedelics on neuroplasticity by altering BDNF levels.
UNASSIGNED: More precisely, the documented rise in BDNF levels indicates a neurobiological mechanism by which psychedelics could enhance synaptic plasticity and foster the growth of neurons. Given the limited data available on this topic, the conclusions remain uncertain. Consequently, we highly recommend additional research with more extensive sample sizes to yield more reliable evidence in this field.

OBJECTIVE: Monoamine neurotransmitters play a role in aggression, especially when altered by illicit substances. However, some literature suggests that not all illicit substances may lead to aggression, notably psychedelics. This narrative review investigates the associations between serotonergic psychedelics and MDMA on aggressive behaviour.
METHODS: PubMed and PsycINFO were searched for original, peer-reviewed articles evaluating the effects of serotonergic psychedelics and 3,4-methylenedioxymethamphetamine (MDMA) on violent and aggressive behavior using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS: After removing duplicates, a total of 555 articles were screened, with 16 meeting the inclusion criteria. One additional article was obtained through reference screening bringing the total to 17 articles. Of these 17 articles, 14 studies focused on MDMA and three on serotonergic psychedelics. Findings were mixed, with some results demonstrating increased aggression following psychedelics and others suggesting protective effects. Limitations in the current literature include varied definitions of psychedelics, lack of standardized objective outcome measures, and failure to control for confounding.
CONCLUSIONS: As psychedelic research continues to expand, further assessment on the effects of serotonergic psychedelics and MDMA on aggressive behavior is required.

Psychedelic compounds have been utilized by humans for centuries for medicinal, religious, and tribal purposes. Clinical trial data starting from the early 2000s and continuing today indicates that psychedelics are a clinically efficacious treatment for a variety of neurological and psychiatric disorders. However, all clinical trials examining these substances have excluded any individual with a past or current history of seizures, leaving a large cohort of epilepsy and non-epilepsy chronic seizure disorder patients without anywhere to turn for psychedelic-assisted therapy. These exclusions were made despite any significant evidence that clinically supervised psychedelic use causes or exacerbates seizures in this population. To date, no clinical trial or preclinical seizure model has demonstrated that psychedelics induce seizures. This review highlights several cases of individuals experiencing seizures or seizure remission following psychedelic use, with the overall trend being that psychedelics are safe for use in a controlled, supervised clinical setting. We also suggest future research directions for this field.

Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder.
The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population.
A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE.
4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions.
While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.

Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA\'s effects on sexual responsiveness and its potential role in treating sexual dysfunction.
The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles.
We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were \"MDMA\" or \"ecstasy\" in combination with \"desire,\" \"arousal,\" \"lubrication,\" \"orgasm,\" \"pleasure,\" \"libido,\" \"erection,\" and \"ejaculation.\" Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis.
We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative.
Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.

UNASSIGNED: Cannabis use disorder (CUD) is prevalent in ~2-5% of adults in the United States and is anticipated to increase as restrictions to cannabis decrease and tetrahydrocannabinol (THC) content in cannabis products increase. No FDA-approved medications for CUD are currently available, despite trials of dozens of re-purposed and novel drugs. Psychedelics have garnered interest as a therapeutic class in other substance use disorders, and self-report surveys suggest they may result in positive outcomes for CUD. Herein, we review the existing literature pertaining to psychedelic use in persons with or at risk for CUD and consider the potential rationale underpinning psychedelics as a treatment for CUD.
UNASSIGNED: A systematic search was performed in several databases. Inclusion criteria were primary research reporting use of psychedelics or related substances and CUD for treatment in human subjects. Exclusion criteria were results including psychedelics or related substances without changes in cannabis use or risks associated with CUD.
UNASSIGNED: Three hundred and five unique results were returned. One article was identified using the non-classical psychedelic ketamine in CUD; three articles were identified as topically relevant based on their secondary data or consideration of mechanism. Additional articles were reviewed for purposes of background, review of safety considerations, and formulating rationale.
UNASSIGNED: Limited data and reporting are available on the use of psychedelics in persons with CUD, and more research is needed given the anticipated increase in CUD incidence and increasing interest in psychedelic use. While psychedelics, broadly, have a high therapeutic index with infrequent serious adverse effects, particular adverse effects at risk in the CUD population, such as psychosis and cardiovascular events, should be considered. Possible mechanisms by which psychedelics have therapeutic potential in CUD are explored.