Journal of Psychopharmacology
February 16, 2025
Sachin Ahuja, Farida Zaher, Lena Palaniyappan
4 citations
A systematic review of studies using natural language processing to analyze speech and text after psychoactive drug use found that all studied substances—stimulants, MDMA, cannabis, ketamine, and psychedelics—alter language production. Emerging patterns include increased verbosity with stimulants, reduced lexicon with LSD, increased semantic proximity to emotional words with MDMA, increased positive sentiment with psilocybin, and altered speech acoustics with cannabis. Only one study provided externally validated support for identifying MDMA intoxication using NLP and machine learning. Meta-analysis was not possible due to heterogeneity and few studies. The authors call for standardized speech tasks and a shared language corpus to improve replicability.
Journal of Psychopharmacology
November 30, 2016
Alasdair Breckenridge, Diederick E. Grobbee
4 citations
No Summary
Journal of Psychopharmacology
November 1, 2006
Roland W. Freudenmann, Carlos Schönfeldt-lecuona, Manfred Spitzer et al.
4 citations
Depression in people who formerly used ecstasy heavily may not improve with standard antidepressants like SSRIs, possibly because long-term ecstasy use damages serotonin pathways. A patient with MDMA-induced depression who did not respond to several antidepressants, including an SNRI and an SSRI, achieved stable remission of mood and cognitive symptoms after receiving repeated bilateral electroconvulsive therapy (ECT), with improvement lasting over 1.5 years. Add-on ECT could be a treatment option for former ecstasy users with severe depression that does not respond to antidepressants, though clinical trials are needed to confirm its usefulness.
Journal of Psychopharmacology
March 13, 2026
Francisco A. Moreno, Katja Ehrmann Allen, Christopher B. Wiegand et al.
3 citations
Psilocybin, a psychedelic compound, was generally well-tolerated and reduced obsessive-compulsive disorder (OCD) symptoms in a small clinical trial. No serious adverse events, psychotic symptoms, or changes in suicide severity occurred. Psilocybin, but not placebo, significantly lowered scores on the Yale-Brown Obsessive Compulsive Scale. After eight weeks of treatment including at least four high doses, 73.3% of participants responded (at least 35% reduction in symptoms), and 40% achieved remission. Benefits diminished but remained substantial at six months. Higher cumulative doses were linked to greater symptom reduction. Larger trials are needed to confirm efficacy and refine protocols.
Journal of Psychopharmacology
January 6, 2026
Connor J. Maltby, Adam K. Klein, Enya Paschen et al.
3 citations
Psilocybin produces rapid and sustained antidepressant effects in major depressive disorder, but the underlying neurobiological mechanisms are unclear. In mice, psilocybin caused dose-dependent occupancy of the 5-HT₂A receptor in the prefrontal cortex, with an inverted-U dose-response for head twitch behavior peaking between 44% and 62% receptor occupancy. A 1.5 mg/kg dose increased time spent in open areas of the elevated zero maze, indicating reduced anxiety, while 3 mg/kg reduced immobility in the forced swim test, suggesting antidepressant-like effects. Both doses shifted α-tubulin post-translational modifications toward more dynamic microtubules and selectively increased synaptic protein expression in the prefrontal cortex, but not the amygdala. These findings indicate that psilocybin's therapeutic effects may involve dose- and region-specific enhancement of neuronal plasticity, with distinct signatures for anxiolytic-like and antidepressant-like properties.
Journal of Psychopharmacology
October 4, 2025
Michael G. Palfreyman, Geoffrey B. Varty, Erik M. Stang et al.
3 citations
Classic psychedelic tryptamines show promise for neuropsychiatric disorders, but their broad utility is limited by properties requiring complex delivery and the enigmatic role of the 'psychedelic experience' in therapeutic efficacy. Reducing their mechanism to mere 5-HT2A receptor activation raises the question of whether efficacy is achievable without psychedelic effects. These molecules also interact with other serotonin receptors (e.g., 5-HT1A, 5-HT2C) and non-serotonergic receptors, necessitating further scrutiny of their polypharmacology. This perspective reviews limitations of current non-conjugated tryptamines, explores approaches to improve them, and discusses developing next-generation psychedelic and non-psychedelic compounds, along with the pharmacology underlying these potential therapies.
Journal of Psychopharmacology
September 29, 2025
Jade Pullen, John Corkery, Rebecca Mcknight et al.
3 citations
Deaths following illicit ketamine use have accelerated in recent years, increasingly involving complex polydrug use and socio-economic vulnerability. Policy responses should extend beyond single-substance legislative controls to include harm reduction, treatment integration, and social support strategies.
Journal of Psychopharmacology
September 22, 2025
Vítor Bruno, Martha López-canul, Brandon Richardson et al.
3 citations
Psilocybin, at a dose of 10 mg/kg administered every other day, does not produce conditioned place preference (CPP) in Sprague-Dawley rats, indicating a lack of rewarding or reinforcing effects under this regimen. During conditioning, psilocybin increased head twitching, wet-dog shaking, and defecation, while decreasing grooming, body licking, and rearing compared to vehicle. However, 48 hours after the final injection, no behavioral differences remained between groups. These findings suggest that psilocybin's acute behavioral effects are transient and that it does not induce reward-related learning in the CPP paradigm, though further research is needed to assess addiction liability across different protocols.
Journal of Psychopharmacology
July 1, 2025
Ryan M Brudner, Erica Kaczmarek, Marc G Blainey et al.
3 citations
In a small sample of 31 individuals with treatment-resistant major depressive disorder or bipolar II disorder, those who reported more intense mystical experiences after their first dose of psilocybin-assisted psychotherapy showed greater reductions in depressive symptoms two weeks later. This link between mystical experiences and antidepressant benefit was not observed after the second or third psilocybin doses. The findings offer preliminary support for the idea that mystical-type experiences play a therapeutic role in psilocybin-assisted psychotherapy, extending prior work to a clinically complex population with treatment-resistant depression.
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.
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.
Journal of Psychopharmacology
December 26, 2025
Alice Caulfield, Allan H. Young, Mitul Mehta
2 citations
Psychedelics may produce lasting behavioral and clinical change by enhancing learning mechanisms. This narrative review synthesizes evidence across behavioral, neural, and computational levels, proposing that viewing psychedelic mechanisms through the lens of learning unifies context-dependent outcomes, increased environmental sensitivity, and neuroplastic change. Persistent changes in top-down and bottom-up information processing at a systems-level may account for both therapeutic and adverse effects, converging with the reopening of critical learning periods. This systems-level framework explains why outcomes vary widely and depend on context: the learning environment—including psychological support and therapeutic insights—shapes lasting effects. Understanding these mechanisms has translational relevance for psychedelic-assisted psychotherapy.
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.
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.
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.
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.
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.
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.
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.
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.
Journal of Psychopharmacology
May 3, 2023
Alain Braillon, Florian Naudet
1 citation
The text is too brief to summarize. It only indicates the intended audience is international, without providing any substantive content, finding, argument, or description.
Journal of Psychopharmacology
August 31, 2021
Isaac Cohen, Laken Barber, Tyson Paul Dubnicka et al.
1 citation
3,4-Methylenedioxymethamphetamine (MDMA)-assisted therapy is highly effective for posttraumatic stress disorder (PTSD). Previous research on MDMA's potential to damage DNA (genotoxicity) has been inconclusive. Three regulatory-compliant studies—a bacterial reverse mutation (Ames) assay, a chromosome aberration test in Chinese hamster ovary cells, and an in vivo micronucleus study in male Sprague Dawley rats—found that MDMA did not cause genotoxic effects at or above clinically relevant concentrations.
Journal of Psychopharmacology
July 16, 2026
Robert F. Dougherty, Nadav Liam Modlin, Niall M. Mcgowan et al.
In a 12-week clinical trial of 25 mg COMP360 psilocybin for 22 participants with post-traumatic stress disorder, audio recordings showed that during drug-administration sessions speech by either party was rare: silence filled 78% of the time on average, compared to 25% to 30% in non-administration sessions. Thematic analysis of post-dosing interviews revealed that support was minimally enacted but experientially salient, autonomy was promoted through the introspective state and non-directive support, and primary modes of support during altered states included reassurance and validation. The minimal verbal interaction distinguishes this monitoring and support from conventional psychotherapies and MDMA-assisted therapy.
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.
Journal of Psychopharmacology
June 28, 2026
Yiğit Özaydın, Buket Canlan Özaydın
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.