Journal of Psychopharmacology
October 3, 2024
Charles Q. Choi, Danica E. Johnson, David Chen‐li et al.
11 citations
Posttraumatic stress disorder (PTSD) can develop after a traumatic event, causing intrusive re-experiencing, mood and cognitive changes, and altered arousal. Few treatments help patients who cannot access or do not benefit from conventional psychotherapy or pharmacotherapy. This review examines the neurobiology of PTSD and psilocybin's mechanism of action, suggesting that psilocybin may be an underexplored treatment option based on pharmacodynamic and psychoanalytic principles, though further research is needed.
Journal of Psychopharmacology
September 16, 2024
Isabella A Savides, Kim Outhoff
11 citations
A semi-structured review of psilocybin microdosing—taking sub-hallucinogenic doses of the psychedelic compound found in magic mushrooms—identified major research gaps that prevent firm conclusions about its benefits. Most available evidence comes from observational studies, while clinical and non-clinical trials remain sparse and inconsistent. The review highlights the need for more randomized placebo-controlled trials, studies of dose-response relationships, psychological and personality testing, use of active placebos, diverse study populations, psilocybin-exclusive microdosing research, and refined animal models. Definitive conclusions about efficacy remain elusive.
Journal of Psychopharmacology
November 30, 2016
Benjamin Kelmendi, Philip R. Corlett, Mohini Ranganathan et al.
11 citations
No Summary
Journal of Psychopharmacology
August 29, 2025
Niall M. Mcgowan, James Rucker, Rachel Yehuda et al.
10 citations
A single 25 mg dose of psilocybin, given with psychological support, was safe and well-tolerated in 22 adults with PTSD. No serious adverse events occurred, and most side effects (headache, nausea, crying, fatigue) resolved within a day. PTSD symptoms, measured by the CAPS-5 scale, showed a clinically meaningful average decrease of nearly 30 points at 4 and 12 weeks after the dose, and this improvement was linked to the intensity of the psychedelic experience. Functional impairment and quality of life also improved. The open-label design and small sample size mean further controlled trials are needed to confirm efficacy.
Journal of Psychopharmacology
May 12, 2025
Clémentine Estric, Thomas Duron, Sarah Kabani et al.
10 citations
Psychedelics show promise for treating psychiatric disorders, but how participants are prepared (set) and the environment where the drug is taken (setting) vary widely across studies. This systematic review examined 27 articles covering 25 clinical trials with 763 participants. Participant selection and creating a safe environment were consistently reported, but other elements like monitor training (52% of studies), controlling visual distractions (64%), and ensuring a pleasant environment (68%) were less consistently described. Psilocybin was the most studied psychedelic (47% of trials). The lack of standardization in set and setting limits comparability and reproducibility, and harmonizing these aspects would improve future research.
Journal of Psychopharmacology
January 20, 2025
Joshua Liebnau, Felix Betzler, André Kerber
10 citations
Psilocybin, given in a supportive setting, may relieve depression by promoting openness, cognitive and neural flexibility, and greater acceptance of emotional experiences. A renewed sense of connectedness to self, others, and the world emerged as a key experience. Imaging studies consistently found altered brain dynamics, including reduced connectivity within and across the default mode network and increased connectivity between networks. These changes may create a vulnerable window for change, highlighting the need for a supportive environment and therapeutic guidance. The antidepressant effects appear to arise from an interplay between neurobiological mechanisms and common psychotherapeutic factors, rather than from pharmacology alone.
Journal of Psychopharmacology
August 13, 2024
Oliver Rumle Hovmand, Dea Siggaard Stenbæk, M. Madsen et al.
9 citations
The Danish translation of the Five Dimensional Altered States of Consciousness Questionnaire (5D-ASC) is a valid tool for measuring altered states of consciousness among Danish-speaking individuals. Confirmatory factor analysis showed that the 11 subscales fit the data well and better than the original five-dimensional solution, with good internal consistency. Total scores correlated positively with psilocybin dose in a recreative sample of 550 users, but no correlations were found with intention or setting. The questionnaire was also tested in 47 healthy volunteers receiving psilocybin in a lab setting.
Journal of Psychopharmacology
December 4, 2023
Maha N. Mian, Brianna R. Altman, Fiona Low et al.
8 citations
A new 32-item scale, the Protective Strategies for Psychedelics Scale (PSPS), measures strategies people use to reduce harm when taking psychedelics. Two factors emerged: long-term preparation (mood, setting, scheduling) and short-term preparation (social context, health, other substances). The scale showed excellent reliability and was strongly correlated with existing protective behavior scales for cannabis and alcohol, and moderately with lifetime psychedelic use. The authors call for further validation in diverse samples.
Journal of Psychopharmacology
September 23, 2024
B. M. Altman, Manya Magnus
7 citations
In a nationally representative sample of over 253 million U.S. adults, the relationship between hallucinogen use and psychological distress differed by sexual identity. Among heterosexual individuals, those who had used hallucinogens had 24% lower odds of experiencing severe psychological distress compared to those who had not. However, for sexual minority individuals, hallucinogen use was not significantly associated with psychological distress. The study suggests that the potential mental health benefits of psychedelics may not extend equally to all groups, and further research is needed to understand why hallucinogen use was not protective for sexual minorities, who already face higher rates of poor mental health.
Journal of Psychopharmacology
July 11, 2025
Aleksander Kwaśny, Patrycja Ciurkowska, Wiesław Jerzy Cubała et al.
6 citations
In interventional clinical trials of psilocybin and LSD, participants are overwhelmingly White, raising concerns about whether these therapies are safe and effective for diverse populations. A cross-sectional analysis of nine eligible trials (eight psilocybin, one LSD) registered on ClinicalTrials.gov through January 2025 found that among 501 psilocybin participants, 87.2% were White, 3.0% Black, and 5.0% Asian; ethnicity was reported in only four trials, with 13.4% identifying as Hispanic or Latino. The single LSD trial of 11 older adults reported no race or origin data. Participation-to-population ratios for U.S.-only trials confirmed underrepresentation of Black and Asian individuals. The authors conclude that broader recruitment and standardized reporting are essential to ensure equity and establish safety and efficacy across groups.
Journal of Psychopharmacology
October 16, 2023
Maciej Koniewski, Piotr Popik, Natalia Malikowska‐racia et al.
6 citations
Psilocybin, but not LSD, produced an immediate antidepressant-like effect in rats tested on a differential reinforcement of low-rate responding (DRL 72s) schedule, shown by increased reinforced presses and response efficiency. Neither drug showed lasting effects up to four weeks after administration. The DRL 72s test, which reliably distinguishes antidepressants from other psychoactive drugs, detected only acute changes. These results suggest that detecting sustained antidepressant-like effects in rodents may require new behavioral methods, and question whether prolonged efficacy observed in humans depends on the psychotherapy typically paired with psychedelic treatment.
Journal of Psychopharmacology
September 12, 2025
Stephan Tap, Kelan Thomas, Tomáš Páleníček et al.
5 citations
Classic psychedelics like psilocybin are being studied for psychiatric disorders. Current protocols typically require patients to stop antidepressants (ADs) for at least two weeks before psychedelic use to avoid serotonin syndrome and preserve efficacy, but discontinuation can worsen depression and increase suicidal ideation. This scoping review of 18 studies found that using ADs alongside classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, especially with psilocybin. Some studies showed significant improvements in depression and other symptoms. Although some evidence suggests a potential reduction in acute subjective psychedelic effects, this was not consistent. The authors conclude that maintaining ADs may improve patient access and avoid discontinuation risks.
Journal of Psychopharmacology
November 30, 2016
Paul Summergrad
5 citations
No Summary
Journal of Psychopharmacology
October 21, 2025
Abdo Uyar, Linda Forbrich, Ulrike Lueken et al.
4 citations
Psychedelic clinical trials have grown exponentially since 2006, with a sharp acceleration after 2019. Psilocybin is the most studied substance and closest to approval, while short-acting psychedelics like 5-MeO-DMT have recently entered trials with narrower clinical goals. Industry involvement is rising, but university-led research still dominates. Reporting of psychotherapy components increased after 2023 FDA recommendations, yet descriptions of interventions remain inconsistent. The rapid expansion across diverse indications and substances reflects growing clinical interest, though industry prioritizes scalability and approval. Incomplete reporting of psychotherapeutic elements limits cross-study comparisons and understanding of which therapeutic combinations optimize outcomes.
Journal of Psychopharmacology
October 16, 2025
David J. Heal, Jane Gosden, Sharon L. Smith
4 citations
Psychedelic research is advancing rapidly, creating new challenges for drug developers, regulators, and legislators. Most classic psychedelics under clinical investigation are Schedule I controlled substances with high abuse potential and no accepted medical use. These and next-generation psychedelic drug-candidates require scientific and clinical assessment of their abuse and dependence potential before being placed into a lower controlled drug schedule (C-II to C-V). The FDA is likely to conduct the first regulatory assessment of a classic psychedelic and has provided guidance on addressing clinical and regulatory challenges. This review builds on that foundation, discussing areas of abuse and dependence evaluation that remain unclear.
Journal of Psychopharmacology
March 31, 2025
Tomislav Majić, Timo Torsten Schmidt, Anna Gröticke et al.
4 citations
A new questionnaire called the Afterglow Inventory (AGI) reliably measures pleasant psychological effects that can occur days after a psychedelic experience, such as with psilocybin or LSD. The AGI captures five distinct dimensions: vitality, transpersonal aspects, inspiration/creativity, interpersonal relationships, and relationship to nature. In an international online survey of 1,323 people who had recently used a psychedelic and 157 controls, the AGI successfully distinguished between the two groups. Stronger and more positive acute psychedelic experiences were associated with higher afterglow scores. This tool may help researchers understand how short-term afterglow effects connect to longer-term therapeutic outcomes.
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.