J Psychopharmacol
July 19, 2010
672 citations
In a pilot randomized controlled trial, MDMA-assisted psychotherapy reduced PTSD symptoms more than placebo therapy in people with chronic, treatment-resistant posttraumatic stress disorder. The treatment was well tolerated, with no serious adverse events. These results suggest that MDMA-assisted psychotherapy may be a safe and effective intervention for this difficult-to-treat population, warranting further investigation.
J Psychopharmacol
February 15, 2018
646 citations
Modern trials support the therapeutic potential of psychedelic drugs, but their effects are exceptionally sensitive to context—the combination of mindset and physical setting. This opinion piece highlights how classic psychedelics act through 5-HT2A receptor agonism and associated plasticity, making context crucial. It proposes a study design to test positive interactions between psychedelics and context, and presents new findings on how contextual determinants shape the quality of a psychedelic experience, which in turn predicts long-term mental health outcomes. The authors aim to inform good practice, optimize treatment models, and reduce stigma while building evidence that context minimizes harms and maximizes benefits.
J Psychopharmacol
July 11, 2019
415 citations
Emotional breakthrough—a sudden release or shift in emotion during a psychedelic experience—is a distinct and important component that predicts long-term psychological changes, separate from mystical-type experiences. A six-item Emotional Breakthrough Inventory was validated in 379 participants who completed surveys before and after a planned psychedelic experience. Emotional breakthrough scores were dose-dependent and higher when the psychedelic was taken with therapeutic intent. In a subsample of 75 participants with low baseline well-being, emotional breakthrough, mystical experience, and challenging experience scores together significantly predicted changes in well-being (r=0.45). Emotional breakthrough and mystical experience scores predicted increases in well-being, while challenging experience scores predicted smaller increases.
J Psychopharmacol
February 2, 2022
319 citations
Classic psychedelics carry minimal medical risks such as toxicity and overdose, and many persistent negative perceptions of psychological risks—including abuse liability and dependence—are unsupported by current scientific evidence when use occurs in regulated or medical contexts. Most reported adverse effects are not observed under these conditions. The review underscores the need for clinicians and therapists to maintain high safety and ethical standards and for balanced media reporting to avoid future controversies and allow continued research.
J Psychopharmacol
January 5, 2022
135 citations
A new self-report questionnaire, the Psychological Insight Scale, was developed and validated to measure the degree of psychological insight people gain from a psychedelic experience. The scale was tested in a large online sample and showed strong reliability and validity, capturing a distinct aspect of psychedelic-induced change not measured by existing tools. Higher scores on the scale were associated with greater improvements in well-being and reductions in psychological distress, suggesting that psychological insight may be a key mechanism underlying the therapeutic potential of psychedelics.
J Psychopharmacol
February 18, 2021
123 citations
In a first study of its kind, 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy was found to be safe and tolerable for patients with alcohol use disorder. The treatment did not raise serious safety concerns and was well tolerated by participants, suggesting that this combined approach warrants further investigation as a potential therapy for alcohol addiction.
J Psychopharmacol
February 28, 2019
95 citations
People who use psychedelics recreationally tend to score higher on the personality trait openness, which involves being open-minded, curious, and receptive to new experiences. This study examined whether this link might be explained by differences in the brain's serotonin system, a key chemical system affected by psychedelics. Using brain imaging, the researchers measured serotonin markers in recreational users and non-users. The findings suggest that higher openness in psychedelic users is not directly tied to these serotonin markers, indicating that other factors may underlie the personality differences.
J Psychopharmacol
August 1, 2022
73 citations
Depressive symptoms decreased two and four weeks after a psychedelic experience in a naturalistic, non-clinical setting. The study tracked a large group of people who planned to use psychedelics outside a lab or clinic, including only those with depressive symptoms at the start. A medicinal motive, prior psychedelic use, drug dose, and having an emotional breakthrough during the experience were all linked to greater symptom reductions. The authors note potential sample and attrition biases and call for further controlled and observational studies to confirm the findings.
J Psychopharmacol
February 10, 2021
73 citations
Inhaled N,N-dimethyltryptamine (DMT) in natural settings reduces alpha brainwave power (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) power. Gamma power increases correlate with reports of mystical-type experiences. DMT also raises global synchrony and metastability in the gamma band and lowers them in the alpha band. These findings align with prior lab-based psychedelic research and suggest EEG markers for mystical experiences in real-world contexts, underscoring the value of studying psychedelics in natural settings.
J Psychopharmacol
December 17, 2022
57 citations
Ketamine, an NMDA antagonist used for depression, produces rapid but transient antidepressant effects primarily through acute modulation of reward circuits and a sub-acute increase in neuroplasticity. Its dissociative and psychedelic properties arise from dose- and context-dependent disruption of large-scale functional networks: disruption of the salience network accounts for dissociation, while disruption of the default-mode network accounts for the psychedelic state. In psychedelic-assisted psychotherapy, relaxing high-level beliefs with support may allow revision of pathological self-representation models, with neuroplasticity playing a permissive role. This multi-level account suggests leveraging ketamine's psychedelic properties to enhance long-term benefits.
J Psychopharmacol
April 22, 2021
54 citations
Psychedelic therapy is experiencing a resurgence due to favorable regulations, policy changes, and positive trial results, but current confirmatory trials may not fully address safety and best practice. The authors recommend supplementing these trials with pragmatic trials, real-world data initiatives, and digital health solutions to discover optimal and personalized treatment protocols. These steps aim to develop safe, effective, and cost-efficient psychedelic therapy, which is susceptible to hype and regulatory challenges given its history.
J Psychopharmacol
March 4, 2024
51 citations
About 16% of people who used psychedelics in naturalistic settings showed a clinically meaningful decline in psychological well-being four weeks later. Those with a prior diagnosis of a personality disorder were disproportionately affected: 31% were negative responders, and multivariate regression indicated a greater than four-fold elevated risk of adverse psychological responses. The findings suggest that personality disorders may represent an elevated risk for psychedelic use, and that psychological support and a good therapeutic alliance may be especially important for this population.
J Psychopharmacol
June 15, 2020
37 citations
MDMA did not increase prosocial behavior in a controlled laboratory setting, despite raising blood levels of the drug and self-reported feelings of closeness and euphoria. In a double-blind, placebo-controlled experiment with 20 healthy volunteers, MDMA (100 mg) failed to significantly change task-based measures of empathy, trust, or cooperative behavior compared to placebo. Bayesian analyses supported the conclusion that MDMA and placebo had equivalent effects on empathy and cooperation. The drug also did not alter mood three days after administration. These findings suggest that the acute prosocial effects of MDMA observed in naturalistic or therapeutic contexts may not replicate under controlled experimental conditions.
J Psychopharmacol
June 30, 2023
33 citations
The randomized controlled trial (RCT) design assumes a drug's specific effect can be separated from nonspecific context and person effects, but ample evidence shows that physical, social, and cultural variables not only add to but also shape drug effects. Harnessing these placebo effects for patient benefit is challenging due to conceptual and normative obstacles. A new framework inspired by psychedelic science's 'set and setting' concept acknowledges that drug and nondrug factors interact synergistically, suggesting ways to reintegrate nondrug variables into biomedical practice to ethically use placebo effects for improved clinical care.
J Psychopharmacol
January 27, 2024
29 citations
A prospective survey study examined how serotonergic antidepressants affect the acute subjective experience of classic psychedelics and subsequent well-being and depressive symptoms. People taking antidepressants reported less intense mystical-type experiences and greater anxiety during psychedelic sessions compared to those not on antidepressants. Despite this blunting, both groups showed similar improvements in well-being and reductions in depressive symptoms after the session. The findings suggest that while antidepressants may dampen the acute psychedelic experience, they do not necessarily hinder long-term mental health benefits.
J Psychopharmacol
February 28, 2023
22 citations
Combining psychedelic substances with group psychotherapy may enhance group connectedness and interpersonal learning, potentially improving prosocial behavior by providing direct opportunities to practice new behavioral patterns. Challenges include a more rigid therapy structure and possible loss of patient openness, which can be mitigated by adequate therapeutic training. The article analyzes existing clinical and neurobiological literature using Yalom's 11 therapeutic factors as a framework, aiming to support clinical research on this approach.
J Psychopharmacol
December 1, 2016
19 citations
Psilocybin therapy shows promise for alleviating anxiety and depression in cancer patients, drawing on lessons from past research to guide future applications. The text reviews historical studies and outlines prospects for integrating psilocybin-assisted psychotherapy into cancer care, suggesting it may provide significant mental health relief. It emphasizes the need for careful clinical implementation and further investigation to confirm efficacy and safety.
J Psychopharmacol
December 13, 2021
18 citations
An open-label study of 14 participants found that mood remained positive during the week after receiving MDMA in a clinical setting, contrary to the 'Blue Monday' crash reported by recreational users. Self-reported sleep quality improved at 3- and 6-month follow-ups compared to baseline. No participants used or desired to use illicit MDMA, and anecdotal reports were favorable. The findings suggest that negative after-effects previously associated with MDMA may stem from confounds such as illicit drug sourcing and recreational settings, rather than the drug itself.
J Psychopharmacol
April 23, 2024
6 citations
This review examines how psychedelic-assisted therapy might help treat functional seizures, a type of functional neurological disorder. The authors explore potential underlying mechanisms, focusing on how psychedelics could affect brain networks involved in emotion, self-awareness, and body perception that are disrupted in functional seizures. They suggest that psychedelics may help by promoting neuroplasticity and altering connectivity in key brain regions, potentially allowing patients to process traumatic memories and reduce seizure frequency. The review indicates that while preliminary evidence is promising, more research is needed to establish safety and efficacy.
J Psychopharmacol
October 29, 2024
4 citations
Psychedelic-assisted therapies are gaining attention as potential treatments for mental health conditions, but their safety profile remains incompletely understood. This article maps the landscape of adverse events that can occur during such therapies, including psychological distress, physiological reactions, and challenging experiences. The authors argue that a systematic framework is needed to categorize and manage these events, drawing on clinical reports and existing literature. They emphasize that while serious adverse events appear rare, mild to moderate reactions are common and require careful protocol design and therapist training. The piece calls for standardized reporting to improve safety monitoring and clinical outcomes in this emerging field.
J Psychopharmacol
July 29, 2024
4 citations
People who use psychedelics outside of medical guidance to treat their own mental health conditions often report improvements in mental health and self-awareness, which may reduce their need for prescribed medications. An analysis of 2,552 respondents from the Global Drug Survey 2020 identified three key factors from self-reported psychedelic effects: Improved Mental Health, Improved Self-Awareness, and Neuro-Sensory Changes. Most respondents had a history of depression (80%) or anxiety (65.6%). The perceived benefits from psychedelic self-treatment were linked to a lower likelihood of currently using prescribed medication, especially for depression or combined depression and anxiety. These findings suggest that psychedelics could have therapeutic potential for mental health.
J Psychopharmacol
October 27, 2025
2 citations
Ketamine, originally developed as an anesthetic, has emerged as a promising treatment for severe depression and other psychiatric conditions, particularly in patients who have not responded to traditional therapies. The compound can provide rapid relief from depressive symptoms, often within hours, which contrasts with conventional antidepressants that may take weeks to work. This surprising discovery has opened a new frontier in mental health treatment, offering hope for those with challenging mood disorders. However, the use of ketamine in psychiatry also raises concerns about its potential for abuse and long-term side effects, necessitating careful clinical oversight.
J Psychopharmacol
June 28, 2026
In a mouse model of posttraumatic stress disorder, a single dose of psilocybin reduced fear responses to a conditioned cue measured 1, 6, and 7 days later. Psilocybin also reversed the fear conditioning-induced reductions in neuroplasticity in the hippocampus and medial prefrontal cortex, increasing dendritic branches and spine density, upregulating GluR1 and synapsin-1, enhancing brain-derived neurotrophic factor and mammalian target of rapamycin signaling, and promoting neurogenesis. These results suggest that psilocybin may have therapeutic potential for PTSD and other disorders involving fear memory by restoring neuroplasticity in these brain regions.