Ketamine, known for its rapid-acting antidepressant effects, is often coadministered with other psychoactive drugs, including opioids and cannabinoids, in both clinical and recreational settings. We investigated whether ketamine (R-, S-, or racemic R, S-) isoforms alter the subjective effects of morphine or Δ9-tetrahydrocannabinol (THC) and whether the interoceptive effects of ketamine overlap...
Background: Psychedelics induce profound changes in perception and thinking; however, little is known about the neural mechanisms and prediction of these effects. Aims: Investigating ayahuasca-induced experiences, mind-wandering, and electroencephalogram (EEG) oscillations, beyond the prediction of subjective experiences by baseline EEG. Methods: In a randomised, double-blind,...
"Psychedelic research - Going global" is a Special Issue of the Journal of Psychopharmacology that has been compiled and published as a tribute to Dr. Roland R Griffiths in recognition of his pioneering and pivotal contribution to the field of psychedelic research. Dr. Griffiths was Professor in the Departments of Psychiatry and Neurosciences at Johns Hopkins University School of Medicine, and...
Little is known about whether 3,4-methylenedioxy-N-methamphetamine (MDMA) neurocognitive side effects improve with sustained abstinence. This study aimed to systematically review and synthesise the existing literature on the long-term neurocognitive side effects of recreational MDMA use after a minimum of 6 months of abstinence. We searched relevant databases utilising terms related to (1) MDMA...
Background: Adults over the age of 65 years are the fastest growing group of cannabis users, but there are few studies of the acute effects of cannabis in this population. Aims: In the present naturalistic study, participants were invited to smoke their preferred legal cannabis in the lab prior to tests of verbal learning and memory, executive function and information processing, and functional...
It is 60 years since ketamine was first tested in humans as an alternative but safer anaesthetic to PCP (phencyclidine) (Corssen and Domino 1966). It became widely used as the “buddy drug” for combatants in the Vietnam War: because of its great safety margin, it could be injected into wounded personnel by their buddies to relieve pain before the arrival of the medical team. Because of...
Psychedelic clinical research is expanding rapidly. This review analyses the state and trends in psychedelic clinical trial registrations. A systematic search of ClinicalTrials.Gov was conducted on 11 November 2024, to identify registered interventional trials investigating (therapeutic) effects of serotonergic psychedelics (e.g. lysergic acid diethylamide [LSD], psilocybin, [5-MeO-]DMT)....
Psychedelic research is progressing at breakneck speed and is creating new challenges for drug developers, regulatory authorities, and legislators. Most “classic” psychedelics undergoing clinical investigation are C-I controlled drugs with perceived high potential for abuse and no medical use. These and next-generation psychedelic drug-candidates require scientific and clinical assessment of...
Background: The treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. Classical psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT), which act primarily as 5-hydroxytryptamine 2A (5-HT 2A ) receptor agonists, have shown preliminary efficacy for inducing long-term remission in MDD after one or two doses....
Journal of PsychopharmacologyOctober 4, 2025Michael G. Palfreyman, Geoffrey B. Varty, Erik M. Stang et al.3 citations
The last decade represented a period of unprecedented interest in, and development of, traditional psychedelic substances for the treatment of a variety of neuropsychiatric disorders. While early clinical trials of classical psychedelics, several of the major ones being tryptamines, have demonstrated robust efficacy in patients with minimal adverse effects, many of these molecules have...
There has been an acceleration in deaths following illicit ketamine in recent years, which are increasingly featuring complex patterns of polydrug use and socio-economic vulnerability. Policy responses must extend beyond single-substance legislative controls to encompass harm reduction, treatment integration, and social support strategies.
Background: In recent years, there has been a resurgence of scientific interest in psychedelics, including psilocybin, for their potential in treating neuropsychiatric disorders. However, the reward-related effects of psilocybin and its impact on behavior remain underexplored. Aims: We aimed to evaluate the potential rewarding effects of high doses of psilocybin and its effects on rat behavior....
Our findings extend previous research by demonstrating that MDMA increases feelings of trust in the social world beyond lab-specific interaction partners. These findings are consistent with user reports of generalized social well-being effects and support the idea that MDMA may have clinical value from a social psychological perspective.
Classic psychedelics are increasingly studied as potential treatments for different psychiatric disorders. Current research protocols often require patients to discontinue antidepressants (ADs) for at least 2 weeks before psychedelic administration to decrease the risk of serotonin syndrome and limit their effect on efficacy and the acute subjective effects of psychedelics. Moreover, the...
As psychedelic clinical trials expand in scale and influence, foundational challenges in trial design have come into sharper focus. In this commentary, we examine three interrelated issues: 1) the failure of blinding in psychedelic trials, 2) the potential of alternate controls including dose-response designs as an empirical workaround, and 3) the persistent ambiguity surrounding psychosocial...
Background: Post-traumatic stress disorder (PTSD) is a debilitating condition for which there are few efficacious treatments. Psilocybin is being studied for use in treatment-resistant depression but has not yet been investigated in PTSD. Aims: The trial’s primary outcome was to investigate the safety and tolerability of single-dose psilocybin in participants with PTSD. Methods: This was a...
Background and aims: Drug discrimination procedures have made important contributions to the pre-clinical investigation of psychedelic drugs, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). One of the most important being to highlight the critical role of central 5-HT2A receptor agonism as a mediator of...
Psychiatric disorders represent a particularly challenging area of medicine to study using non-human animals. They arise from a complex interaction between genetic and environmental factors and are diagnosed using clinical interviews and diagnostic criteria based largely on self-reported symptoms and with significant heterogeneity seen within patient populations. Anxiety and major depressive...
While psychedelics are often claimed to enhance creativity, their precise effects on distinct stages of creative cognition remain poorly understood. This study investigated the acute effects of an ayahuasca-inspired formulation combining N,N-dimethyltryptamine (DMT) and harmine (DMT/HAR), as well as harmine alone (HAR), on micro-level (divergent/convergent thinking) and macro-level (creative...
Subanesthetic doses of ketamine produce complex neuropsychiatric effects, which include rapid psychotomimetic symptoms and antidepressant effects that can last several weeks. Despite over 60 years of research, the mechanism(s) of action underlying ketamine's effects in the brain remains largely mysterious. Neurophysiological field potential recordings provide a direct window into brain...
Background: Although classic psychedelic trials show therapeutic potential, the limited diversity of participants raises concerns about generalizability and safety. Aims: This study assesses the representation of race, ethnicity, and sex in interventional clinical trials of psilocybin and lysergic acid diethylamide (LSD) to evaluate disparities in participant diversity. Methods: We conducted a...
Background: Classic serotonergic psychedelics are 5-HT2A partial agonists that induce non-ordinary states of consciousness. Many have demonstrated anti-addictive properties; however, their impact on smoking behaviors remains under-researched. This review provides a synthesis of the therapeutic potential of these compounds in promoting smoking cessation and reduction. Methods: A systematic...
Background: Psilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes. Mystical experiences are considered a key aspect of the subjective effects...
Diarylethylamine drugs possess dissociative properties. These emerged as drugs of misuse, with reports of strong addictive potential, high tolerance and compulsive intake. Since one of these drugs, diphenidine, was added to the 1971 Convention on Psychotropic Substances, the United Kingdom (UK) had to consider its control. The Advisory Council on the Misuse of Drugs 2023 advice included...
Hexahydrocannabinol (HHC) recently appeared on the recreational drug market and is often sold as a legal replacement for Δ9-tetrahydrocannabinol (Δ9-THC). Users primarily consume HHC for recreational purposes, but adverse effects have been reported. Given the scant literature on HHC, additional research is needed to better understand its effects. The present study sought to determine whether...