Journal of psychopharmacology (Oxford, England)
September 7, 2026
Torsten Passie, Michiel van Elk
Common wisdom in the psychedelic literature suggests that early controlled trials of psychedelic therapy were methodologically flawed. In this review we challenge this view and discuss 11 controlled studies that were conducted in the United States and Canada between 1965 and 1977 to evaluate psychedelic (peak) therapy for individuals suffering from alcohol and opioid use disorder and...
Journal of psychopharmacology (Oxford, England)
September 7, 2026
Sabrina Wong, Gia Han Le, Simryn Selby et al.
Extant literature indicates mitochondrial dysfunction may contribute to the pathophysiology of depressive disorders. Preclinical data indicate that anesthetic doses of ketamine are associated with deficits in mitochondrial viability and function. Ketamine and esketamine have demonstrated rapid antidepressant effects in persons with difficult-to-treat depressive disorders. Herein, we aim to...
Journal of psychopharmacology (Oxford, England)
September 3, 2026
Katelijne V Van der Heijden, Gabriel E Jacobs, Ellen H James et al.
Serotonergic psychedelics, such as N,N-dimethyltryptamine (DMT), have shown therapeutic potential in various psychiatric disorders. However, DMT demonstrates pharmacokinetic (PK) variability and a short half-life. This exploratory study investigated the PK, pharmacodynamic (PD), and safety profile of CYB004, a deuterated DMT analogue, following intravenous administration in healthy volunteers....
Journal of psychopharmacology (Oxford, England)
August 30, 2026
Tiffini N Lovell, Peter B James, Skylar L Hodgins et al.
Fentanyl is the leading cause of fatal overdoses worldwide, and repeated use may lead to substance use disorder (SUD). In SUD, drug-associated contexts can trigger reward-related behavior even in the absence of the drug. Psychedelic compounds may weaken context-drug associations, reducing reward-related behavior to fentanyl. We evaluated the effects of the psychedelic psilocin and its...
Journal of psychopharmacology (Oxford, England)
August 25, 2026
Praachi Tiwari, Bryan W Jenkins, Catherine F Moore et al.
Psychedelics have emerged as promising pharmacological agents for treating a range of neuropsychiatric disorders. While preclinical studies have provided valuable insight into the neural mechanisms underlying their effects, systematic characterization of psychedelic effects on inherent spontaneous behaviors in animal models remains limited. In the current study, male and female Sprague-Dawley...
Journal of psychopharmacology (Oxford, England)
August 17, 2026
David Eckert
The re-emergence of serotonergic psychedelics has introduced rapid-acting antidepressant effects and has been widely described as a paradigmatic shift in depression treatment. Recently, there has been intense debate about whether the acute subjective effects of psychedelics are necessary for their therapeutic efficacy or merely byproducts of underlying neuroplastic processes. Recent...
Journal of psychopharmacology (Oxford, England)
July 13, 2026
Todd D Gould, Sanjay J. Mathew, Maurizio Fava et al.
The occupancy-driven pharmacology model in psychopharmacology has guided drug discovery and development for decades, whereby the goal is stable receptor occupancy over an extended period with a direct relationship of drug exposure to pharmacodynamic and therapeutic response. Event-driven pharmacology (EDP) is a concept where the acute pharmacodynamic actions of a plastogen, a transient binding...
Journal of psychopharmacology (Oxford, England)
June 25, 2026
Joost C Van Mechelen, Tobias A Wieles, Laura Borghans et al.
Oral S-ketamine (S-KETPO) is being explored as an alternative to intravenous maintenance treatment (S-KETIV) in treatment-resistant depression (TRD). However, the first-pass effect with S-KETPO significantly alters S-ketamine's bioavailability and the systemic exposure of its active metabolites, raising potential safety and efficacy concerns. This study characterized the pharmacodynamic and...
Journal of psychopharmacology (Oxford, England)
June 25, 2026
Pavan S Brar, Rebecca B Price, Stephen Ross et al.
In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and...
Journal of psychopharmacology (Oxford, England)
June 24, 2026
Shreya Vasudeva, Gabrielle F. M. Lovell, Sabrina Wong et al.
Ketamine has emerged as a promising rapid-acting treatment for mood disorders and suicidality. Notwithstanding its replicated antidepressant efficacy, ketamine-associated risk for abuse, dependence, and misuse remain. We conducted a systematic review of clinical and preclinical studies from database inception to August 2025, including randomized and observational trials, open-label extensions,...
Journal of psychopharmacology (Oxford, England)
June 16, 2026
Alice Caulfield, Matthew Butler, Mitul A. Mehta
The therapeutic potential of psychedelics is currently being explored in a range of neuropsychiatric conditions. Nevertheless, their designation as Schedule 1 substances causes substantial regulatory and economic barriers to research. Rigorous human mechanistic studies are required to address the critical knowledge gaps surrounding the mechanisms underlying the putative treatment effects of...
Journal of psychopharmacology (Oxford, England)
June 1, 2026
Gabrielle Smith, Timothy Piatkowski, Jason Ferris et al.
1 citation
While research on novel therapeutic applications of ketamine is expanding, particularly in controlled settings, there is limited exploration of its consumption related to self-treatment of psychiatric conditions. This study investigated the characteristics of people who use ketamine and psychedelics for self-treatment of psychiatric conditions, providing insight into patterns of use within this...
Journal of psychopharmacology (Oxford, England)
May 31, 2026
Anna Beatriz Vicentini, Caio César De Paula, José Augusto Silva Reis et al.
The impact of classic psychedelics (5-HT2A receptor agonists) on personality traits has been studied for decades, and it has been hypothesized that the mechanisms underlying these changes are linked to agonism at cortical serotonergic 5-HT2A receptors. However, research results are contradictory. Therefore, the present paper aims to systematically evaluate the effects of psychedelics on...
Journal of psychopharmacology (Oxford, England)
May 29, 2026
Elliot Hampsey, Kirsty Martin, Michail Kalfas et al.
Despite renewed investigations into classical psychedelic compounds, their pharmacokinetic profiles remain incompletely understood. This systematic review collated data from healthy adult volunteers on the pharmacokinetic properties of lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), mescaline, and 5-methoxy-N,N-dimethyltryptamine (5-MEO-DMT). We identified 32 eligible...
Journal of psychopharmacology (Oxford, England)
May 29, 2026
Kristoffer Brendstrup‐brix, Brice Ozenne, Patrick M. Fisher et al.
Patients with chronic cluster headache (CCH) suffer from poor sleep, which may impact their brain microstructure and parenchymal clearance of waste products. Psilocybin has shown promise for the treatment of CCH and has been linked to increased neuroplasticity with possible influences on brain microstructure. To investigate the effects of psilocybin on sleep, brain water diffusivity, and...
Journal of psychopharmacology (Oxford, England)
May 23, 2026
Joanna Kuć, Rosalind McAlpine, Amelia Sellers et al.
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a potent, short-acting psychedelic, induces profound shifts in cognition, affect, and self-awareness. Because language explicitly expresses these domains and voice implicitly conveys them, both may serve as potential 'biomarkers' of behavioural change. This study introduces a novel framework for analysing baseline language and vocal features, pre-...
Journal of psychopharmacology (Oxford, England)
May 2, 2026
Zarmeen Zahid, Rick J. Strassman, Clifford Qualls et al.
Serotonergic psychedelics are being investigated in the treatment of various disorders and in the improvement of well-being. Evidence suggests that their subjective effects may play a role in long-term behavioral outcomes. The subjective effects are mediated by 5-HT2A receptor agonism, but the 5-HT1A receptor may also play a role in the subjective effects. This study elucidates the effects of...
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Grace Viljoen, Henrik Walter, Antonia Bendau et al.
3 citations
Psychedelic-assisted therapy (PAT) has demonstrated substantial efficacy across a range of mental disorders. However, heterogeneity between patients confers differential responsiveness. This systematic review aims to explore factors which may predict therapeutic responses to PAT. A systematic search was performed from inception through to March 2024 and studies that assessed predictors of...
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Vincent J Diehl, Abigail E. Calder, Gregor Hasler
Existing tools assess psychedelic experiences, but none specifically measure altered processing of traumatic memories-a key mechanism in trauma-focused therapies and psychotherapy in general. The helioscope effect describes how psychedelics like psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) enable revisiting challenging or traumatic experiences while remaining protected from...
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Bonnie Brusky, Katia M'Bailara, François Alla et al.
The nature and role of the psychological support provided in psychedelic-assisted treatments for psychiatric disorders are currently the object of debate. How this support is conceptualized-as a vector for therapeutic change or framework for risk minimization-has far-reaching consequences in terms of how these treatments should be regulated, delivered, and studied. To determine whether...
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Brian O'Mahony, Colm Harrington, Andrew Harkin et al.
Psychedelic drugs are increasingly under investigation as potential therapeutic agents for mental health conditions and are being increasingly used recreationally. Psychedelic use may result in an episode of intense psychological distress, commonly referred to as a "bad trip." Bad trips represent a potentially volatile, erratic, and dangerous situation, which may, in extreme cases, require...
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Guy Simon, Maya Gal-Birman, Nir Tadmor et al.
The October 7th, 2023, attack at the Nova rave represents an unprecedented scenario in trauma research: A mass casualty event in which most participants were under the influence of psychedelics. Using a mixed-methods phenomenological design, 45 survivors were interviewed. Participants were categorized by substance use: classic psychedelics (n = 24), empathogens (n = 19), and ketamine (n = 2)....
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Taylor Lyons, Joseph Marks et al.
Previous research suggests that psychedelics may, under certain conditions, decrease authoritarian attitudes, but larger and more rigorously designed studies are needed to confirm these findings. We aimed to examine the effects of psychedelic use on authoritarian attitudes. Using data from three separate studies with different designs and populations, we investigated the relationship between...
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Sunjuri Sun, Laura W. Wesseldijk et al.
While psychedelics have shown initial promise in the treatment of migraine, experimental studies have relied on small and homogenous samples, which limit the reliability and generalizability of findings. These limitations underscore the complementary value of other research designs that leverage larger and more representative samples. This cross-sectional study included three cohorts of twins...
Journal of psychopharmacology (Oxford, England)
April 24, 2026
Marco Colizzi, Elisa Morandin, Veronica Croccia et al.
Interleukin-6 (IL-6) has been implicated as a potential predictor of ketamine response in treatment-resistant depression (TRD). Esketamine, the S-enantiomer of ketamine, produces rapid antidepressant effects and offers improved safety and intranasal administration. To examine whether baseline IL-6 predicts treatment response to esketamine in individuals with TRD. Fourteen adults with TRD...