-
The American Journal of Psychiatry May 2020The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders. (Review)
Review
OBJECTIVE
The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders.
METHODS
Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on "psilocybin," "lysergic acid diethylamide," "LSD," "ayahuasca," "-methylenedioxymethamphetamine," and "MDMA," in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms "clinical trial," "therapy," or "imaging" in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), -methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care.
RESULTS
The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as "breakthrough therapies" for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuasca is observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders.
CONCLUSIONS
Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.
Topics: Evidence-Based Practice; Hallucinogens; Humans; Lysergic Acid Diethylamide; Mental Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Psychotherapy
PubMed: 32098487
DOI: 10.1176/appi.ajp.2019.19010035 -
Experimental Neurology Jan 2022Preclinical and clinical studies indicate that 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'), in addition to having abuse potential, may elicit acute and... (Review)
Review
Preclinical and clinical studies indicate that 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'), in addition to having abuse potential, may elicit acute and persistent abnormalities of varying severity at the central level. Importantly, neurotoxic effects of MDMA have been demonstrated in experimental animals. Accordingly, central toxicity induced by MDMA may pose a serious harm for health, since MDMA is among the substances that are used for recreational purposes by young and adult people. This review provides a concise overview of recent findings from preclinical and clinical studies that evaluated the central effects of MDMA, and the mechanisms involved in the neurotoxicity induced by this amphetamine-related drug.
Topics: Animals; Brain; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Neurotoxicity Syndromes
PubMed: 34655576
DOI: 10.1016/j.expneurol.2021.113894 -
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.Nature Medicine Jun 2021Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a... (Randomized Controlled Trial)
Randomized Controlled Trial
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.
Topics: Adult; Combined Modality Therapy; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; N-Methyl-3,4-methylenedioxyamphetamine; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 33972795
DOI: 10.1038/s41591-021-01336-3 -
Dialogues in Clinical Neuroscience 2019This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA-ecstasy) in psychiatric... (Review)
Review
This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA-ecstasy) in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up to that point had looked very promising in several areas of psychiatry. In the past decade a number of groups have been working to re-evaluate the utility of these substances in medicine. So far highly promising preliminary data have been produced with psilocybin in anxiety, depression, smoking, alcoholism, and with MDMA for post-traumatic stress disorder (PTSD) and alcoholism. These findings have led to the European Medicines Agency approving psilocybin for a phase 3 study in treatment-resistant depression and the Food and Drug Administration for PTSD with MDMA. Both trials should read out in 2020, and if the results are positive we are likely to see these medicines approved for clinical practice soon afterwards. .
Topics: Hallucinogens; Humans; Ketamine; Lysergic Acid Diethylamide; Mental Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Psychiatry
PubMed: 31636488
DOI: 10.31887/DCNS.2019.21.2/dnutt -
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 -
Psychopharmacology Bulletin Jun 2021Post-traumatic stress disorder (PTSD) has become one of the most common psychiatric diagnosis in the United States specifically within the veteran population. The... (Review)
Review
Post-traumatic stress disorder (PTSD) has become one of the most common psychiatric diagnosis in the United States specifically within the veteran population. The current treatment options for this debilitating diagnosis include trauma-focused psychotherapies along with selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI). MDMA has recently been shown as a novel therapeutic agent with promisingly results in the treatment of PTSD. MDMA is a psychoactive compound traditionally categorized as a psychedelic amphetamine that deemed a Schedule I controlled substance in the 1980s. Prior to its status as a controlled substance, it was used by psychotherapists for an array of psychiatric issues. In more recent times, MDMA has resurfaced as a potential therapy for PTSD and the data produced from randomized, controlled trials back the desire for MDMA to be utilized as an effective pharmacologic therapy in conjunction with psychotherapy..
Topics: Adult; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic; Veterans
PubMed: 34421149
DOI: No ID Found -
Expert Opinion on Drug Metabolism &... May 2020: MDMA (3,4-methylenedioxymethamphetamine), a synthetic ring-substituted amphetamine, has become one of the most widely used recreational psychostimulant drugs in the... (Review)
Review
: MDMA (3,4-methylenedioxymethamphetamine), a synthetic ring-substituted amphetamine, has become one of the most widely used recreational psychostimulant drugs in the world. Among recreational ecstasy/MDMA users, polydrug use is a phenomenon whose common purpose is to experience the synergistic effect of the combined drugs, moderate MDMA effects, prevent potential toxicity, enhance a high or come down from a high from other drugs, or simply to treat existing medical conditions. Thus, MDMA-drug interactions (MDMA-DIs) lead to a higher risk of acute and life-threatening MDMA toxicity.: This article provides an overview of the MDMA-DIs with pharmaceuticals and drugs of abuse. In addition, available evidence is summarized along with clinical recommendations. Finally, the increasing importance of MDMA-DIs is highlighted.: There is a reduced number of published MDMA-DIs studies and scarce clinically significant MDMA-DIs documented in the literature. Experimental evidence points out the relevance of MDMA-DI's when MDMA is co-administered with pharmaceuticals that are metabolized by the CYP2D6 due to MDMA inhibitory action and in the case of repeated MDMA administration (MDMA-MDMAIs).
Topics: Animals; Cytochrome P-450 CYP2D6; Drug Interactions; Drug Synergism; Hallucinogens; Humans; Illicit Drugs; N-Methyl-3,4-methylenedioxyamphetamine; Pharmaceutical Preparations; Substance-Related Disorders
PubMed: 32228243
DOI: 10.1080/17425255.2020.1749262 -
Journal of Clinical Pharmacology Apr 2022This article discusses current literature on the use of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in the treatment of posttraumatic stress disorder... (Meta-Analysis)
Meta-Analysis Review
This article discusses current literature on the use of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in the treatment of posttraumatic stress disorder (PTSD). MDMA, the intended active ingredient in illicit Ecstasy or Molly products, is a psychedelic that causes an elevated mood, feeling of bonding, and increased energy. In MDMA-assisted psychotherapy, patients are subjected to 2 or 3 multihour sessions of therapy with a team of psychiatrists. The dosing of MDMA is used to allow the therapist to probe the underlying trauma without causing emotional distress. The use of MDMA-assisted psychotherapy treatment reduced patient's Clinician-Administered PTSD Scale (CAPS) scores from baseline more than control psychotherapy (-22.03; 95%CI, -38.53 to -5.52) but with high statistical heterogeneity. MDMA-assisted psychotherapy enhanced the achievement of clinically significant reductions in CAPS scores (relative risk, 3.65; 95%CI, 2.39-5.57) and CAPS score reductions sufficient to no longer meet the definition of PTSD (relative risk, 2.10; 95%CI, 1.37-3.21) with no detected statistical heterogeneity. While therapy was generally safe and well tolerated, bruxism, anxiety, jitteriness, headache, and nausea are commonly reported. While MDMA-assisted psychotherapy has been shown to be an effective therapy for patients with PTSD with a reasonable safety profile, use of unregulated MDMA or use in the absence of a strongly controlled psychotherapeutic environment has considerable risks.
Topics: Combined Modality Therapy; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 34708874
DOI: 10.1002/jcph.1995 -
Clinical Obstetrics and Gynecology Mar 2019Stimulant use, including cocaine, methamphetamines, ecstasy, and prescription stimulants, in pregnancy is increasingly common. In the United States, stimulants are the... (Review)
Review
Stimulant use, including cocaine, methamphetamines, ecstasy, and prescription stimulants, in pregnancy is increasingly common. In the United States, stimulants are the second most widely used and abused substances during pregnancy and pregnant women using stimulants in pregnancy are at increased risk of adverse perinatal, neonatal, and childhood outcomes. In this review, we describe the pharmacology, pathophysiology, and epidemiology of stimulants, summarize the maternal and neonatal effects of perinatal stimulant use, and outline treatment options for stimulant use disorders among pregnant women. Development of effective treatment strategies for stimulant use disorders identified among pregnant women are urgently needed.
Topics: Alkaloids; Central Nervous System Stimulants; Cocaine; Female; Humans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Substance-Related Disorders; Systematic Reviews as Topic; United States
PubMed: 30601144
DOI: 10.1097/GRF.0000000000000418 -
Progress in Neuro-psychopharmacology &... Jun 2018MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used... (Review)
Review
MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers. This review explores the potential role of memory reconsolidation and fear extinction during MDMA-assisted psychotherapy. MDMA enhances release of monoamines (serotonin, norepinephrine, dopamine), hormones (oxytocin, cortisol), and other downstream signaling molecules (BDNF) to dynamically modulate emotional memory circuits. By reducing activation in brain regions implicated in the expression of fear- and anxiety-related behaviors, namely the amygdala and insula, and increasing connectivity between the amygdala and hippocampus, MDMA may allow for reprocessing of traumatic memories and emotional engagement with therapeutic processes. Based on the pharmacology of MDMA and the available translational literature of memory reconsolidation, fear learning, and PTSD, this review suggests a neurobiological rationale to explain, at least in part, the large effect sizes demonstrated for MDMA in treating PTSD.
Topics: Animals; Clinical Trials as Topic; Combined Modality Therapy; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Psychotropic Drugs; Stress Disorders, Post-Traumatic
PubMed: 29524515
DOI: 10.1016/j.pnpbp.2018.03.003