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Psychopharmacology Jun 2022± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration's phased drug development process for... (Review)
Review
RATIONALE & OBJECTIVES
± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration's phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. The current standard of care for these disorders involves treatment with psychiatric medications (e.g., selective serotonin reuptake inhibitors), so it will be important to understand drug-drug interactions between MDMA or psilocybin and psychiatric medications.
METHODS
In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the MEDLINE database via PubMed for publications of human studies in English spanning between the first synthesis of psilocybin (1958) and December 2020. We used 163 search terms containing 22 psychiatric medication classes, 135 specific psychiatric medications, and 6 terms describing MDMA or psilocybin.
RESULTS
Forty publications were included in our systematic review: 26 reporting outcomes from randomized controlled studies with healthy adults, 3 epidemiologic studies, and 11 case reports. Publications of studies describe interactions between MDMA (N = 24) or psilocybin (N = 5) and medications from several psychiatric drug classes: adrenergic agents, antipsychotics, anxiolytics, mood stabilizers, NMDA antagonists, psychostimulants, and several classes of antidepressants. We focus our results on pharmacodynamic, physiological, and subjective outcomes of drug-drug interactions.
CONCLUSIONS
As MDMA and psilocybin continue to move through the FDA drug development process, this systematic review offers a compilation of existing research on psychiatric drug-drug interactions with MDMA or psilocybin.
Topics: Adult; Drug Interactions; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Psychotherapy; Stress Disorders, Post-Traumatic
PubMed: 35253070
DOI: 10.1007/s00213-022-06083-y -
Acta Medica Portuguesa 2011Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB)... (Review)
Review
Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.
Topics: Adolescent; Flunitrazepam; Humans; Illicit Drugs; Ketamine; Lysergic Acid Diethylamide; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Sodium Oxybate; Substance-Related Disorders; Young Adult
PubMed: 22525626
DOI: No ID Found -
Psychopharmacology Mar 2022±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its... (Review)
Review
RATIONALE
±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg). Since this review comprised mostly of single-dose studies and an assortment of methodologies, an empirical dose-ranging study on this topic is warranted.
OBJECTIVES
The current study aims to evaluate the conclusion from our systematic review that 3 mg/kg may be the threshold for MDMA-induced amnesia, and to further understand the dose-effect relationship of MDMA on behavioral assays of memory, addiction, and depression.
METHODS
We systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear conditioning; behavioral sensitization, conditioned place preference, and conditioned responding; and the Porsolt forced swim test in mice.
RESULTS
High doses of MDMA (≥ 3 mg/kg) produced amnesia of fear conditioning memory, some evidence of an addictive potential, and antidepressant effects, while low doses of MDMA (≤ 1 mg/kg) had no effect on these behaviors.
CONCLUSIONS
The present dose-ranging study provides further evidence that 3 mg/kg is the threshold for MDMA-induced amnesia. These findings, in addition to our systematic review, demonstrate that careful selection of MDMA dose is critical. High doses (≥ 3 mg/kg) should likely be avoided due to evidence that they can produce amnesia and addiction. Conversely, there is little evidence to suggest that low doses, which are usually administered in clinical studies (approximately 1-2 mg/kg), will lead to these same adverse effects. Ultra-low doses (< 1 mg/kg) are likely even safer and should be investigated for therapeutic effects in future studies.
Topics: Amnesia; Animals; Conditioning, Classical; Depression; Dose-Response Relationship, Drug; Fear; Mice; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 35179622
DOI: 10.1007/s00213-022-06086-9 -
Journal of Psychopharmacology (Oxford,... Oct 2022Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered... (Review)
Review
INTRODUCTION
Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions.
OBJECTIVE
To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies.
METHODS
We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies.
RESULTS
We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies.
CONCLUSIONS
AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting.
Topics: Banisteriopsis; Hallucinogens; Headache; Humans; Lysergic Acid Diethylamide; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin
PubMed: 36017784
DOI: 10.1177/02698811221116926 -
Addictive Behaviors Jun 2024Anxiety and depression are prevalent mental health problems in people who use illicit stimulants. Improved understanding of the temporal relationship between... (Review)
Review
OBJECTIVE
Anxiety and depression are prevalent mental health problems in people who use illicit stimulants. Improved understanding of the temporal relationship between methamphetamine, ecstasy/MDMA, or cocaine use with anxiety or depression informs public health interventions and treatment options for those experiencing this co-occurrence. This narrative systematic review sought to examine associations and temporality between the use of methamphetamine, ecstasy/MDMA, or cocaine, with anxiety or depressive symptoms. Method Systematic searches of 4 electronic databases were conducted up to August 2023. Study eligibility included the measurement of anxiety and/or depressive symptoms, and frequency of illicit stimulant use (methamphetamine, cocaine, or ecstasy/MDMA) at two separate time points, with data analysis of the association between these variables. The Joanna Briggs Critical Appraisal Checklist was utilised to assess quality. Data was extracted, and a narrative synthesis incorporating an eight-criteria framework to assess associations was conducted. Results 4432 studies were screened for eligibility; 11 studies (3 RCTs and 8 prospective cohort studies) were included. Evidence for an association between depressive symptoms and methamphetamine use was demonstrated in six studies, with temporal evidence in three studies supporting methamphetamine use preceding depressive symptoms. Three studies reported an association between cocaine use and depressive symptoms. Evidence for associations with any of the illicit stimulants and anxiety symptoms was lacking.
CONCLUSIONS
There was some evidence to support a case for temporality, particularly for methamphetamine use and depressive symptoms. Investing in longitudinal studies is pivotal to understanding the dynamic and reciprocal relationship between illicit stimulant use and anxiety or depressive symptoms. A limitation of the study was the variation in the measurement and analysis of outcomes.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Methamphetamine; Depression; Prospective Studies; Anxiety; Cocaine; Central Nervous System Stimulants; Cocaine-Related Disorders
PubMed: 38394960
DOI: 10.1016/j.addbeh.2024.107988 -
Neuroscience and Biobehavioral Reviews Mar 2016MDMA ("ecstasy") is widely used as a recreational drug, although there has been some debate about its neurotoxic effects in humans. However, most studies have... (Review)
Review
MDMA ("ecstasy") is widely used as a recreational drug, although there has been some debate about its neurotoxic effects in humans. However, most studies have investigated subjects with heavy use patterns, and the effects of transient MDMA use are unclear. In this review, we therefore focus on subjects with moderate use patterns, in order to assess the evidence for harmful effects. We searched for studies applying neuroimaging techniques in man. Studies were included if they provided at least one group with an average of <50 lifetime episodes of ecstasy use or an average lifetime consumption of <100 ecstasy tablets. All studies published before July 2015 were included. Of the 250 studies identified in the database search, 19 were included. There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures. The lack of significant results was associated with high methodological heterogeneity in terms of dosages and co-consumption of other drugs, low quality of studies and small sample sizes.
Topics: Amphetamine-Related Disorders; Animals; Brain; Hallucinogens; Humans; Illicit Drugs; N-Methyl-3,4-methylenedioxyamphetamine; Neuroimaging
PubMed: 26746590
DOI: 10.1016/j.neubiorev.2015.12.010 -
Addiction (Abingdon, England) Jan 2019There is limited evidence on what shapes amphetamine-type stimulant (ATS) use trajectories. This systematic narrative review and qualitative synthesis aimed to identify...
Which individual, social and environmental influences shape key phases in the amphetamine type stimulant use trajectory? A systematic narrative review and thematic synthesis of the qualitative literature.
BACKGROUND AND AIMS
There is limited evidence on what shapes amphetamine-type stimulant (ATS) use trajectories. This systematic narrative review and qualitative synthesis aimed to identify individual, social and environmental influences shaping key phases in the ATS use trajectory: initiation, continuation, increase/relapse and decrease/abstinence.
METHODS
MEDLINE, PsycINFO, EMBASE, and PROQUEST (social science premium collection) were searched from 2000 to 2018. Studies of any qualitative design were eligible for inclusion. Extracted data were analysed according to four key phases within drug pathways, and then cross-analysed for individual, social and environmental influences.
RESULTS
Forty-four papers based on 39 unique studies were included, reporting the views of 1879 ATS users. Participants were aged 14-58 years, from varied socio-economic and demographic groups, and located in North America, Europe, Australasia and South East Asia. Reasons for initiation included: to boost performance at work and in sexual relationships, promote a sense of social 'belonging' and help manage stress. Similar reasons motivated continued use, combined with the challenge of managing withdrawal effects in long-term users. Increased tolerance and/or experiencing a critical life event contributed to an increase in use. Reasons for decrease focused on: increased awareness of the negative health impacts of long-term use, disconnecting from social networks or relationships and financial instability.
CONCLUSIONS
Amphetamine-type stimulant users are a highly diverse population, and their drug use careers are shaped by a complex dynamic of individual, social and environmental factors. Tailored, joined-up interventions are needed to address users' overlapping economic, health and social care needs in order to support long-term abstinence.
Topics: Amphetamine-Related Disorders; Disease Progression; Humans; Methamphetamine; Motivation; N-Methyl-3,4-methylenedioxyamphetamine; Peer Group; Qualitative Research; Risk Factors; Sexual Behavior; Social Behavior; Social Environment
PubMed: 30176077
DOI: 10.1111/add.14434 -
Health Technology Assessment... Jan 2009To investigate the harmful health effects of taking ecstasy (3,4-methylenedioxymethamphetamine, MDMA) for recreational purposes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To investigate the harmful health effects of taking ecstasy (3,4-methylenedioxymethamphetamine, MDMA) for recreational purposes.
DATA SOURCES
MEDLINE, EMBASE, PsycINFO and Web of Knowledge were searched. Additional information on deaths was collected from the General Mortality Register (GMR) and the Special Mortality Register collated by the National Programme on Substance Abuse Deaths (np-SAD).
REVIEW METHODS
Studies were categorised according to design, with systematic research syntheses (Level I evidence) the most valid and least open to bias. Where Level I evidence was not available, controlled observational studies (Level II evidence) were systematically reviewed. If neither Level I nor Level II evidence was available, uncontrolled case series and case reports (Level III evidence) were systematically surveyed. Data were extracted by one reviewer and a sample checked by a second. The heterogeneity of Level II evidence was addressed by undertaking stratified analyses for current and former ecstasy users and comparing them either with control groups using other illegal drugs but not ecstasy (polydrug controls) or with controls naïve to illegal drugs (drug-naïve controls). Statistical heterogeneity was minimised by using a random-effects model throughout and investigated using study-level regression analysis (metaregression).
RESULTS
Five Level I syntheses were identified; for each it was difficult to ascertain the exact methods adopted and evidence included. Small but significant deficits for ecstasy users compared to controls were reported in areas relating to attention, memory, psychomotor speed, executive systems functioning, and self-reported depressive symptoms. Data from Level II studies were directly pooled for seven individual outcomes, suggesting that ecstasy users performed worse than controls on common measures of immediate and delayed verbal recall (RAVLT, RBMT, digit span). No difference was seen in IQ (NART). The 915 outcome measures identified in Level II studies were analysed in broad domains: immediate and delayed verbal and visual memory, working memory, two measures of attention, three measures of executive function, perceptual organisation, self-rated depression, memory and anxiety, and impulsivity measured objectively and subjectively. Ecstasy users performed significantly worse than polydrug controls in 13/16 domains and significantly worse than drug-naïve controls in 7/12 domains for which sufficient data were available. The largest, most consistent exposure effects were seen in meta-analyses of memory (especially verbal and working memory, with less marked effects seen in visual memory). Former ecstasy users frequently showed deficits that matched or exceeded those seen amongst current users. At aggregate level, the effects do not appear to be dose-related, but are variably confounded by other drug use, particularly alcohol. Of Level III evidence, in the 10 years to 2006, the np-SAD and the GMR recorded an average of around 50 drug-related deaths per year involving ecstasy; it was the sole drug implicated in around 10 cases per year. Retrospective case series, based on hospital emergency department records, reported a death rate of 0-2% from emergency admissions related to ecstasy. Two major syndromes are most commonly reported as the immediate cause of death in fatal cases: hyperthermia and hyponatraemia.
CONCLUSIONS
A broad range of relatively low-quality literature suggests that recreational use of ecstasy is associated with significant deficits in neurocognitive function (particularly immediate and delayed verbal memory) and increased psychopathological symptoms. The clinical significance of the exposure effect in individual cases will be variable but, on average, deficits are likely to be relatively small. Ecstasy is associated with a range of acute harms but appears to be a rare cause of death in isolation.
Topics: Amphetamine-Related Disorders; Cognition; Databases, Bibliographic; Hallucinogens; Humans; Illicit Drugs; Memory Disorders; Mental Disorders; Mental Recall; N-Methyl-3,4-methylenedioxyamphetamine; Observation; Recreation
PubMed: 19195429
DOI: 10.3310/hta13050 -
Current Neuropharmacology 2021Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by repetitive behaviours, cognitive rigidity/inflexibility, and social-affective...
BACKGROUND
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. Unfortunately, no gold-standard treatments exist to alleviate the core socio-behavioural impairments of ASD. Meanwhile, the prosocial empathogen/entactogen 3,4-methylene-dioxy-methamphetamine (MDMA) is known to enhance sociability and empathy in both humans and animal models of psychological disorders.
OBJECTIVE
We review the evidence obtained from behavioural tests across the current literature, showing how MDMA can induce prosocial effects in animals and humans, where controlled experiments were able to be performed.
METHODS
Six electronic databases were consulted. The search strategy was tailored to each database. Only English-language papers were reviewed. Behaviours not screened in this review may have affected the core ASD behaviours studied. Molecular analogues of MDMA have not been investigated.
RESULTS
We find that the social impairments may potentially be alleviated by postnatal administration of MDMA producing prosocial behaviours in mostly the animal model.
CONCLUSION
MDMA and/or MDMA-like molecules appear to be an effective pharmacological treatment for the social impairments of autism, at least in animal models. Notably, clinical trials based on MDMA use are now in progress. Nevertheless, larger and more extended clinical studies are warranted to prove the assumption that MDMA and MDMA-like molecules have a role in the management of the social impairments of autism.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Disease Models, Animal; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Social Behavior
PubMed: 33388021
DOI: 10.2174/1570159X19666210101130258 -
Neurotoxicity Research Dec 2021Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD)...
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.
Topics: Alcohol Drinking; Animals; Drug Interactions; Humans; Hyperthermia; N-Methyl-3,4-methylenedioxyamphetamine; Risk Factors
PubMed: 34554408
DOI: 10.1007/s12640-021-00416-z