Journal of psychopharmacology (Oxford, England)
April 6, 2026
Kirsten L Rock, Paul Rees, David Morgan et al.
MDMA is being studied as a treatment for PTSD, but many patients already take antidepressants. This retrospective case-control study used a national drug-death database to examine whether antidepressant use is linked to MDMA-related deaths. Among 1328 MDMA-positive deaths and 5312 matched controls, post-mortem detection of antidepressants was associated with lower odds of MDMA fatality compared to other drug-related deaths (adjusted odds ratio 0.595, 95% CI 0.491-0.722). However, when analyzing prescribed antidepressants, no significant association was found (adjusted odds ratio 0.838, 95% CI 0.688-1.021). The findings suggest an inverse association between antidepressant use and MDMA fatality, but the relationship is not straightforward.
Journal of psychopharmacology (Oxford, England)
March 21, 2026
J García-jiménez, D Nuñez-arias, G Carretero Merelo et al.
In a real-world clinical setting across three Spanish centers, esketamine nasal spray produced progressive improvements in depressive symptoms and functioning in adults with treatment-resistant depression. Among 50 patients, significant reductions in depression severity and disability were observed at every assessment from week 2 through discharge, with notable gains during weeks 8–16. The median time to response was 8 weeks, and to remission 16 weeks; overall response and remission rates reached 70% and 68%. Suicidal risk shifted early toward lower categories, with no suicide attempts during treatment. Higher refractoriness, measured by the Maudsley Staging Model, independently predicted lower odds of response and remission.
Journal of psychopharmacology (Oxford, England)
March 9, 2026
Caio César De Paula, Anna Beatriz Vicentini, Lorena Terene Lopes Guerra et al.
A systematic review of 16 studies found that ayahuasca has distinct short- and long-term cognitive effects. In the short term, improvements in working memory and cognitive flexibility were observed, linked to neurochemical modulation of cortical networks. Observational studies reported increased empathy and emotion recognition, while experimental studies only found reduced reaction times in social cognition tasks. Long-term studies generally found no neuropsychological deficits, with some reporting improved memory and executive function. The review notes methodological limitations including small sample sizes, varied protocols, and potential learning effects, calling for more controlled, randomized studies.
Journal of psychopharmacology (Oxford, England)
February 5, 2026
Benjamin R Lewis, Matthew J Reid, Andrew M Novick et al.
Clinical trials of classical psychedelics like psilocybin for mental health conditions face unique challenges that may persist if these treatments enter clinical practice. Four categories of challenges with trial participants are identified: treatment nonresponse, expectancy effects and functional unblinding, post-session psychological difficulties, and contagion effects. Management strategies for study teams to mitigate these risks are described. The National Network of Depression Centers and similar organizations can guide best practices to responsibly advance this promising field.
Journal of psychopharmacology (Oxford, England)
January 13, 2026
James Glazer, Hanna Molla, Royce Lee et al.
A low dose of LSD (26 micrograms) altered brain responses to reward feedback in people with mild-to-moderate depression, compared to those without depression. In depressed participants, LSD increased a brain signal called the late positive potential (LPP) when they received loss feedback, suggesting enhanced emotional processing of rewards. This change was linked to immediate positive mood and lower depressed mood two days later. Across all participants, LSD reduced other reward-related brain signals. The findings cautiously support the idea that low-dose LSD may have antidepressant effects.
Journal of psychopharmacology (Oxford, England)
January 1, 2026
Jack E Henningfield, Frederick S Barrett, Suzette M Evans et al.
Roland R. Griffiths was a highly influential scientist in behavioral and neuropsychopharmacology, known for his rigorous research on abuse liability of substances including alcohol, benzodiazepines, caffeine, tobacco, and psychedelics. This review, authored by his former mentees and collaborators, describes his methodical approach to research, his inclusive and collegial mentoring style, and his role in advancing scientific methods for abuse liability assessment, policy, and regulation. His work culminated in the establishment of the Johns Hopkins Center for Psychedelic and Consciousness Research, reflecting his curiosity-driven, humanity-serving science that continues to inspire innovation.
Journal of psychopharmacology (Oxford, England)
August 16, 2025
Dila Suay, Helena D Aicher, Berit Singer et al.
A psychedelic formulation combining DMT and harmine, but not harmine alone, impaired convergent thinking—the ability to find a single correct solution—in 30 healthy men, especially those with higher baseline reasoning. Divergent thinking, the generation of many ideas, showed no overall effect but trended toward reduced fluency and elaboration. In a real-world painting task, both DMT/HAR and harmine reduced transitions associated with incubation, and DMT/HAR uniquely decreased the shift from incubation to illumination, indicating altered pathways to insight. Subjective experiences like altered meaning and insightfulness predicted divergent but not convergent thinking. The effects of DMT/HAR on creativity are not uniform, affecting both cognitive performance and the dynamic creative process.
Journal of psychopharmacology (Oxford, England)
July 24, 2025
Mark Jeremy Hunt, Jacek Wróbel
Subanesthetic doses of ketamine produce rapid psychotomimetic and long-lasting antidepressant effects, yet its mechanisms remain unclear. Neurophysiological recordings in freely moving rodents reveal that ketamine and other NMDAR antagonists markedly enhance high-frequency oscillations (HFO, >100 Hz) across olfactory and frontostriatal brain regions. This rhythm is remarkably coherent across distinct regions, modulated by slower oscillations, and driven largely by respiration-locked olfactory bulb activity. Similar activity has been observed in other mammals. This review is the first synthesis of studies on NMDAR antagonist-enhanced HFO, identifying gaps and urging more human research.
Journal of psychopharmacology (Oxford, England)
June 19, 2025
David Weigner, Marvin Sören Meiering, Anne Weigand et al.
Ketamine infusion significantly increased functional connectivity between the pregenual anterior cingulate cortex and the dorsomedial prefrontal cortex during a working memory task, and between the pregenual anterior cingulate cortex and the left insula during rest. These effects were absent when participants were pretreated with lamotrigine, a glutamate-release inhibitor. The findings suggest that ketamine's beneficial effects on brain communication, observed in psychiatric conditions linked to chronic stress, may depend on glutamate release.
Journal of psychopharmacology (Oxford, England)
May 21, 2025
Krj Schruers, N K Leibold
Psychedelic-assisted therapy shows promise for treating mental health conditions, but systematic assessment of adverse events has been neglected. The authors recommend using the term "adverse effects" instead of "side effects" and call for comprehensive monitoring of physical parameters, behavioral outcomes, and subjective experience at baseline and throughout studies. Sex-specific differences should be considered. Several key studies addressing these issues are highlighted. More rigorous adverse effect assessment is needed to ensure safe clinical implementation.
Journal of psychopharmacology (Oxford, England)
April 4, 2025
Rebecca D Hill, Ritu A Shetty, Nathalie Sumien et al.
Three new synthetic tryptamines—5-MeO-DBT, 5-Cl-DMT, and 4-OH-MiPT—were tested in mice and rats for their effects on movement and their ability to mimic the hallucinogen DOM. All three produced depressant phases similar to DOM but were less potent. In rats trained to discriminate DOM, only 4-OH-MiPT fully substituted for DOM, suggesting it shares DOM's abuse potential, while 5-MeO-DBT and 5-Cl-DMT did not fully substitute and decreased response rates.
Journal of psychopharmacology (Oxford, England)
January 1, 2024
Otto Simonsson, Peter S Hendricks, Cecilia Ud Stenfors et al.
A longitudinal study with nearly 10,000 US and UK adults found that people who used psychedelics during a two-month period reported greater increases in unusual visual experiences compared to those who did not. The effect was strongest among first-time users. These visual experiences occurred after the acute drug effects had worn off. The findings support earlier case reports and cross-sectional studies suggesting that naturalistic psychedelic use may be linked to persistent visual phenomena, though further longitudinal research is needed to clarify cause-and-effect relationships.