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Journal of Psychopharmacology

ISSN 0269-8811

223 papers in the library · 25,482 citations · publishing 1998-2026

Papers

The age of psychedelics

Journal of Psychopharmacology January 1, 2022 A. H. Young 3 citations

The field of clinical psychopharmacology has experienced shifting fortunes, particularly regarding antidepressants. After a period of celebration for drugs like SSRIs, popular opinion turned negative due to discredited analyses suggesting they were no better than placebo, though it is now recognized that antidepressants do work. Controversy continues over withdrawal and addiction claims. New treatments are emerging, including ketamine for major depressive episodes, which meta-analyses indicate is effective and practicable in routine settings. Psychedelic psychopharmacology has also reemerged, with serotonergic agents like psilocybin and MDMA showing promise for depression and PTSD, respectively. Experts recommend supplementing traditional confirmatory trials with pragmatic trials, real-world data, and digital health solutions to optimize psychedelic therapy protocols.

Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience

Journal of Psychopharmacology January 26, 2026 Jess Kerr-Gaffney, Samuel Myrtle, Famia Askari et al. 2 citations

A single dose of psilocybin, compared to an inert placebo, did not alter personality traits, psychiatric symptoms, or cognitive flexibility in healthy participants. However, both the 10 mg and 25 mg psilocybin groups reported greater changes in personal values at both short-term (day 8) and long-term follow-up (day 85). The acute psychedelic experience, particularly the feeling of oceanic boundlessness, partially explained these value changes, with auditory alterations also playing a role in one subscale. These exploratory findings are tentative and require replication in larger samples.

A novel psychedelic 5-HT 2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer

Journal of Psychopharmacology October 16, 2025 Gerard J. Marek, Soma Makai‐bölöni, Daniel Umbricht et al. 2 citations

A single intravenous dose of GM-2505, a novel 5-HT2A receptor agonist, was safe and well tolerated in 48 healthy volunteers at doses up to 20 mg. The drug produced mild, transient increases in blood pressure and pulse, no significant electrocardiograph changes, and a half-life of 40–50 minutes. Dose-dependent effects appeared on neuroendocrine hormones, neuropsychological and neurophysiological measures, subjective drug effects, and resting-state electroencephalography, with decreased theta and alpha power and increased slow and fast gamma power. These pharmacodynamic effects resembled those of other 5-HT2A agonists, but GM-2505's shorter duration of cardiovascular and subjective effects than psilocybin and longer than DMT suggests a more practical temporal profile for supervised clinical use, with an optimal dose range of 10–15 mg IV.

Substance use predictors of arrest and self-reported criminal behavior in the United States: The role of psychedelics and rarely used drugs

Journal of Psychopharmacology April 16, 2026 Jesse J. Norris 1 citation

Using data from a large US survey (2014–2023, 544,740 respondents), the study examined links between rarely used drugs and criminal behavior. Phencyclidine (PCP) use was strongly associated with arrest for serious violent offenses, assault, and sex offenses, and with attacking three or more people. Gamma-hydroxybutyrate (GHB) was linked to arrest for several offenses. Among psychedelics, psilocybin was associated with reduced odds of several offenses, while DMT/AMT/Foxy and peyote were linked to increased odds. LSD and Salvia divinorum showed mixed associations. Protective effects of psychedelics were largely absent for minors and were stronger for whites than for minorities. The mixed findings highlight the need for further research on causal connections between psychedelics and crime.

Effects of LSD, DMT and psilocybin on cognitive and psychological functions: A systematic review of the literature

Journal of Psychopharmacology February 16, 2026 Marten Kase, Karl Kristjan Kaup, Jaan Aru 1 citation

A systematic review of 32 placebo-controlled studies from 1990 to 2025 examined the acute and post-acute effects of LSD, DMT, and psilocybin on cognitive and psychological functions. Psychedelics tended to enhance emotional empathy but had no effect on cognitive empathy. Effects on memory varied by task and timing, with some impairments, enhancements, or no change. Dose-dependent impairments occurred in reaction time, attention, and inhibition tasks, though some studies found no effects. Recognition of negative stimuli was impaired under acute effects. Findings on cognitive flexibility were mixed. Many studies had small samples, and finding a reliable placebo is challenging due to psychedelics' unique subjective effects.

The effects of psilocybin on time perception in humans: A comparative analysis of subjective and objective measures

Journal of Psychopharmacology January 1, 2026 Petr Scholle, Štěpán Wenke, Tereza Nekovářová et al. 1 citation

Under psilocybin, healthy volunteers perceived time as moving more slowly and their temporal precision decreased, particularly for intervals longer than 2 seconds. In a double-blinded placebo-controlled study with 24 participants, the bisection point shifted rightward, indicating subjective time slowing, and the just noticeable difference increased, reflecting reduced accuracy. These changes were captured both by performance on the Temporal Bisection Task and by self-report scales. The findings suggest psilocybin disrupts cognitive functions such as working memory and attention, altering time perception through serotonergic system involvement.

The empathogen 3,4-methylenedioxymethamphetamine, but not methamphetamine, increases feelings of global trust

Journal of Psychopharmacology September 16, 2025 Ramona L. Martinez, Nina Radošić, Hanna Molla et al. 1 citation

MDMA increases feelings of trust in the social world beyond specific interaction partners in a lab setting. The findings align with user reports of generalized social well-being effects and suggest that MDMA may have clinical value from a social psychological perspective.

Pharmacological characterisation of psilocybin and 5-MeO-DMT discriminative cues in the rat and their translational value for identifying novel psychedelics

Journal of Psychopharmacology August 27, 2025 Guy A. Higgins, Cam Macmillan, Inés de Lannoy et al. 1 citation

Drug discrimination procedures in rats confirm that hallucinogenic effects of psychedelics like psilocybin, LSD, DMT, and 5-MeO-DMT are mediated primarily by 5-HT2A and 5-HT1A receptors. Plasma levels of psilocin required for generalization in rats (5–52 ng/mL) overlapped with human perceptual effects, while DMT and LSD needed higher exposures in rats than in humans. The duration of drug-lever generalization followed LSD > psilocybin > 5-MeO-DMT ≥ DMT, matching clinical experience. LSD showed a disconnect between plasma exposure and generalization, similar to clinical findings. These results support the translational value of drug discrimination assays for studying psychedelics.

A systematic review and narrative summary of the therapeutic potential of classic serotonergic psychedelics for smoking cessation and reduction

Journal of Psychopharmacology July 11, 2025 Diana Glenn, Seung Hee Choi, Rick S. Zimmerman 1 citation

Classic serotonergic psychedelics such as psilocybin, LSD, and ayahuasca show preliminary therapeutic potential for helping people quit or reduce smoking, but the evidence is limited. A systematic review of eight studies found that all had a serious risk of bias and weak study designs, making it difficult to draw firm conclusions. Psilocybin was the most studied compound, appearing in seven studies, followed by LSD in five, mescaline in four, ayahuasca in four, peyote in two, and N,N-dimethyltryptamine in one. The findings are promising but not yet generalizable, and stronger experimental or quasi-experimental studies with better sampling and comparison groups are needed.

Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature

Journal of Psychopharmacology December 17, 2024 G. Ingrosso, A. Cleare, M. Juruena 1 citation

A review of 16 studies involving 2,174 patients found that addiction-related problems during ketamine treatment for depression are rare. Only four patients showed clear signs of tolerance or dependence, while the vast majority did not. The studies used various forms and routes of ketamine, including intravenous, intranasal esketamine, and others. The review concludes that ketamine treatment appears relatively safe for adult depression when medically supervised, with careful dosing and monitoring. The authors note that future long-term studies using standardized scales for dependence could strengthen evidence for safe use.

Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression

Journal of Psychopharmacology July 8, 2026 Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros et al.

Inhaled DMT, combined with psychological support, is associated with reduced state anxiety up to one day after administration in both healthy individuals and patients with treatment-resistant depression. Healthy volunteers reported increased life satisfaction up to 14 days. Patients showed increased life satisfaction after 12 months and sustained improvements in quality of life over that period, including physical health, psychological health, social relationships, and environment, as well as inner peace and hope and optimism. The study is limited by an open-label design, lack of placebo control, and modest sample size.

Classical psychedelic microdosing, mood, and cognitive function: An umbrella review with narrative synthesis

Journal of Psychopharmacology June 28, 2026 Yiğit Özaydın, Buket Canlan Ozaydin

An umbrella review of systematic reviews and meta-analyses on psychedelic microdosing (repeated low doses of LSD or psilocybin) for mood and cognitive effects found that the only statistically significant pooled result was a small decrease in cognitive control, contrary to popular claims of enhancement. Self-reported mood benefits were largely not replicated under placebo-controlled conditions, suggesting expectancy effects. Short-term tolerability was acceptable, but cardiovascular signals and long-term risks remain uncharacterized. The evidence base is limited by high overlap among primary studies and methodological heterogeneity.

The purpose of the psychosocial protocol in the psychedelic-assisted therapy: A scoping review

Journal of Psychopharmacology June 26, 2026 Flavia Giaffone de Paiva Ferreira, João Ariel Bonar Fernandes, Renato Filev et al.

A scoping review categorized psychosocial protocols used in psychedelic research for mental health treatment. Seven categories were defined, reflecting distinct emphases on the substance, participant, research team, and sociocultural context. Although limited reporting and heterogeneity remain methodological challenges, the proposed parameters suggest a shared language to describe, compare, and examine psychosocial protocols across studies, reducing conceptual uncertainty. The review may facilitate research decision-making and support structured, replicable study designs while allowing flexibility for individualized and culturally responsive care. Explicitly defining the intended purpose of psychosocial protocols could improve transparent reporting and evaluation.

Blocking 5-HT2B receptors abolishes psilocybin’s efficacy in the rat forced swim test

Journal of Psychopharmacology June 23, 2026 Lenka Seillier, Alexandre Seillier, Morgan A. Zvolska et al.

Psilocybin produces rapid and sustained antidepressant-like effects in rats, as measured by reduced immobility and increased climbing in the forced swim test. Blocking the 5-HT2B receptor with the antagonist RS-127445 dose-dependently reversed these behavioral effects, indicating that 5-HT2B receptors are necessary for psilocybin's antidepressant-like activity. However, the same antagonist did not affect psilocybin-induced head-twitch responses, a proxy for psychedelic effects, suggesting that the antidepressant-like and psychedelic effects of psilocybin can be dissociated via different serotonin receptor subtypes.

From monotherapy to sequential models: An updated scoping review on ibogaine’s role in treatment for psychiatric disorders

Journal of Psychopharmacology May 12, 2026 Pravesh Sharma, Jared Kendrick, Jennifer Schram et al.

A review of human studies on ibogaine and its metabolite noribogaine found only three randomized controlled trials. In one pilot study, a single 1800 mg dose of ibogaine reduced cocaine craving versus placebo over up to 24 weeks in 20 adults. Noribogaine doses of 3-60 mg were safe in 36 healthy volunteers. In 27 opioid-dependent patients, noribogaine 60-180 mg caused dose-dependent QTc prolongation with non-significant reductions in withdrawal symptoms. Adverse effects include neurologic, psychiatric, and cardiac events, and fatalities have occurred with comorbidities. Microdosing protocols lack standardized definitions and are supported only by preliminary observational data. The authors conclude that clinical use cannot be recommended without larger, well-controlled trials due to cardiotoxicity and a narrow therapeutic margin.

Efficacy of N, N-dimethyltryptamine (DMT) psychedelic therapy for substance misuse: A systematic review and meta-analysis

Journal of Psychopharmacology April 12, 2026 L. M. Wallace, Andrea Bujor, Gustavo Sudre et al.

A systematic review and meta-analysis of studies from 1960 to 2024 found that the psychedelic agent DMT produced a large overall effect on reducing substance abuse (g = 0.94). Effects were larger for drug use (g = 1.35) than for alcohol use (g = 0.65). Studies that included psychotherapy showed significantly greater effects (g = 1.38) than those without (g = 0.60). However, the included studies had high risk of bias and high heterogeneity, so the findings should be considered preliminary rather than proof of established efficacy.

Confronting mortality: A meta-analysis and systematic review of psychedelic experiences and death anxiety

Journal of Psychopharmacology March 9, 2026 Alicia Cohorst, Petri Kajonius

A meta-analysis and systematic review found that psychedelic substances are associated with moderate-to-large reductions in death anxiety, with a significant overall effect size (Cohen's d = 0.70). Stronger effects were observed in clinically controlled settings than in the general population, and mystical experiences were positively linked to these reductions. The qualitative review identified themes of ego dissolution, emotional catharsis, and living in the present moment. The findings suggest psychedelic-assisted interventions may be effective for reducing death anxiety, especially in end-of-life care, though limitations include a small number of studies, potential publication bias, and high heterogeneity in outcome measurement.

A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression

Journal of Psychopharmacology February 27, 2026 Claire T. Roberts, Mathieu Seynaeve, Anna O. Ermakova et al.

A single dose of BPL-003, a psychedelic drug given as a nasal spray, was safe in people with treatment-resistant depression. Depression scores dropped quickly and stayed lower for 12 weeks, suggesting the drug may help this hard-to-treat condition. Larger controlled trials are needed.

Predicting and exploring ayahuasca effects: Perception, mind-wandering, and EEG oscillations

Journal of Psychopharmacology December 4, 2025 Natan Silva-Costa, Jéssica Andrade Pessoa, Kátia Cristina Andrade et al.

Ayahuasca produces profound changes in perception, cognition, and emotion, including mystical experiences and altered mind-wandering, while decreasing global alpha brain oscillations and increasing frontomedial delta and right posterior theta and beta. Lower theta during the experience is linked to stronger mystical experiences, and higher alpha is associated with less thought about nothing. Baseline brain activity before taking ayahuasca can predict some subjective effects: lower baseline theta predicts stronger bodily awareness and interoception, and lower baseline beta predicts greater positive emotionality.

Psilocybin and ketamine affect novel neuropeptides gene expression in the rat hypothalamus

Journal of Psychopharmacology April 17, 2025 Artur Pałasz, Marta Pukowiec, Katarzyna Bogus et al.

A single high dose of psilocybin (10 mg/kg) increased the gene expression of most noncanonical neuropeptides in the hypothalamus of male rats, while decreasing expression of neuromedin U. Psilocybin also raised expression of serotonin receptors 5-HT1A, 5-HT2A, and 5-HT2B, but not 5-HT2C. Ketamine had a more limited effect, increasing only NUCB2, GPR173, and POMC transcripts. These findings suggest psychedelics may alter neuropeptide signaling and serotonin transmission in the hypothalamus, contributing to understanding their brain actions.

Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

Journal of Psychopharmacology July 14, 2019 Livia Ng, Luca Pani, Anaïs Soula et al.

Claims about the positive effects of microdosing psychedelics on mood and cognition have entered public discussion, but scientific studies are scarce and no consensus on what microdosing means exists. This critique identifies questions future research must answer and offers guidelines, focusing on psilocybin due to its potential clinical approval and short-lasting effects. While anecdotal reports emphasize benefits, the paper concludes that future studies should also investigate potential risks of repeated low-dose administrations. Preclinical and clinical research examining biological measures like heart rate and receptor turnover, as well as cognitive parameters such as memory and attention, is needed to uncover possible negative consequences.