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Journal of Psychopharmacology

ISSN 0269-8811

266 papers in the library · 27,424 citations · publishing 1998-2026

Papers

β-carboline-independent antidepressant-like effect of the standardized extract of the barks of Mimosa tenuiflora (Willd) Poir. occurs via 5-HT2A/2C receptors in mice

Journal of Psychopharmacology June 20, 2022 Luiz Antonio Miranda de Souza Duarte Filho, Isabela Araújo E Amariz, Rodolfo Hideki Vicente Nishimura et al. 12 citations

A standardized extract of Mimosa tenuiflora (SEMT), the plant used to prepare jurema wine, shows antidepressant-like effects in mice. The extract contains 24.74 ± 0.8 mg/g of N,N-dimethyltryptamine (DMT) and also yuremamine. In the tail suspension and forced swim tests, SEMT reduced immobility, indicating antidepressant-like activity, and this effect did not require harmine, a β-carboline. A sub-dose combination with ketamine also reduced immobility. SEMT enhanced head twitch behavior induced by 5-HTP, and ketanserin blocked its antidepressant-like effect, suggesting the effect involves activation of 5-HT2A/2C receptors.

DOI: 10.1177/02698811221104050 Antidepressant Traditional medicine Pharmacology Receptor +1

Mechanisms of psilocybin on the treatment of posttraumatic stress disorder

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.

DOI: 10.1177/02698811241286771 Psilocybin Anxiety Posttraumatic stress Arousal +8

Less is more? A review of psilocybin microdosing

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.

DOI: 10.1177/02698811241278769 Psilocybin Observational study Grey literature Medicine +3

The serotonin 2A receptor agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner

Journal of Psychopharmacology February 12, 2020 Tobias Buchborn, Taylor Lyons, Chenchen Song et al. 11 citations

Activating serotonin 2A receptors with a highly selective agonist (N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine) increases heart rate and slightly elevates neck-arterial blood flow in anesthetized mice. Raising the heat-pad temperature from 37°C to 41°C enhanced the drug's effect on blood flow while counteracting the rapid heart rate. The drug also slowed breathing, which reversed at the higher temperature, and selectively increased core body temperature only under elevated pad conditions. Arterial oxygen saturation remained unchanged. These results suggest that selective serotonin 2A receptor activation links cardiovascular changes with thermoregulation, potentially influencing brain hemodynamics relevant to the psychedelic state.

DOI: 10.1177/0269881120903465 Serotonin Serotonergic Thermoregulation Agonist +11

Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial

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.

DOI: 10.1177/02698811251362390 Psilocybin Traumatic stress Tolerability Open label +6

Set and setting of psychedelics for therapeutic use in psychiatry: A systematic review

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.

DOI: 10.1177/02698811251338214 Ayahuasca LSD Dimethyltryptamine Psilocybin +9

Catalyst for change: Psilocybin’s antidepressant mechanisms—A systematic review

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.

DOI: 10.1177/02698811241312866 Psilocybin Default mode network Psychedelic therapy Neuroscience +7

Deepening our understanding of psychedelics by expanding psychedelic data collection in the United States National Survey on Drug Use and Health

Journal of Psychopharmacology September 16, 2022 Brian S. Barnett 10 citations

As regulatory and financial barriers to clinical psychedelic research recede, a clearer understanding of naturalistic psychedelic use and its epidemiology is needed, since such use is growing and will likely always exceed clinical use. Psychedelics' effects vary by setting, so research findings may differ depending on context. Improving data collection on real-world psychedelic use should be a higher public health priority. Expanding data collection in the U.S. National Survey on Drug Use and Health could address this need, ensuring high-quality information for the public, scientists, and regulators as psychedelics' role in medicine and society is reevaluated.

DOI: 10.1177/02698811221123051 Public health Naturalism Naturalistic observation Data collection +12

Altered states of consciousness in Danish healthy volunteers and recreational users of psilocybin and the possible impact of setting and intention: Danish validation of the five-dimensional altered states of consciousness questionnaire

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.

DOI: 10.1177/02698811241269669 Psilocybin Danish Altered state Consciousness +5

Development of the Protective Strategies for Psychedelics Scale: A novel inventory to assess safety strategies in the context of psychedelics

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.

DOI: 10.1177/02698811231214060 Context archaeology Psychology Scale ratio

Perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide in healthy participants within a novel intervention paradigm: Qualitative results from a proof-of-concept study

Journal of Psychopharmacology March 1, 2022 Peter S. Hendricks, Heith Copes, Neiloufar Family et al. 8 citations

In a proof-of-concept study with 31 healthy participants given 50 to 100 µg of LSD, most felt safe throughout the experiment, attributing their comfort to the study structure and support from attendants, which allowed them to let go and immerse themselves. A minority initially worried about having a challenging experience, but those concerns lessened over time. Participants reported transcendent, mystical-type experiences typical of classic psychedelics, with nearly half noting the important role of music during the drug's acute effects. They endorsed the clinical utility of LSD in controlled environments, believing it is safe and could help others. Findings suggest this scalable intervention paradigm is feasible and warrants further research with clinical populations.

DOI: 10.1177/02698811211055855 Lysergic acid diethylamide Thematic analysis Intervention counseling Qualitative research +7

Serotonergic neurotransmission in emotional processing: New evidence from long-term recreational poly-drug ecstasy use

Journal of Psychopharmacology September 6, 2016 Helle Ruff Laursen, Susanne Henningsson, Julian Macoveanu et al. 8 citations

Prolonged recreational use of MDMA (ecstasy) alters serotonin neurotransmission, similar to a depleted state. In this fMRI study, 14 ecstasy users and 12 non-users viewed faces expressing anger, disgust, fear, sadness, or no emotion while their amygdala activity was measured. Serotonin transporter binding, assessed via PET, correlated negatively with amygdala activity in users. Greater lifetime ecstasy intake was associated with increased amygdala activity during angry face processing, while longer time since last use showed a trend toward decreased activity during angry and sad face processing. The results indicate dose-dependent effects of long-term serotonin depletion on emotional face processing.

DOI: 10.1177/0269881116662633 Full text Ecstasy Serotonergic MDMA Serotonin +9

Association between lifetime hallucinogen use and psychological distress varies by sexual identity in a nationally representative sample

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.

DOI: 10.1177/02698811241278774 Clinical psychology Association psychology Hallucinogen Psychological distress +5

Associations between MDMA/ecstasy use and physical health in a U.S. population-based survey sample

Journal of Psychopharmacology October 1, 2022 Grant Jones, Jocelyn A. Ricard, Peter S. Hendricks et al. 7 citations

Lifetime use of MDMA (ecstasy) is associated with better self-reported physical health, including lower risks of overweight/obesity, heart conditions, cancer, hypertension, and diabetes, along with higher odds of reporting good overall health. These associations emerged from a large, nationally representative U.S. sample, controlling for potential confounders. The findings suggest protective links between ecstasy use and various physical health markers, but the authors call for longitudinal studies and clinical trials to confirm causality.

DOI: 10.1177/02698811221127318 Ecstasy Odds ratio Population Psychiatry +6

Unequal representation? A cross-sectional analysis of age, sex, race, and ethnicity in clinical trials of classic psychedelics

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.

DOI: 10.1177/02698811251353250 Psilocybin Ethnic group Generalizability theory Clinical trial +5

Acute but not long-lasting antidepressant-like effect of psilocybin in differential reinforcement of low-rate 72 schedule in rats

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.

DOI: 10.1177/02698811231205692 Psilocybin Antidepressant Hallucinogen Differential reinforcement +3

Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective, cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? A mega-analysis

Journal of Psychopharmacology January 9, 2021 Abigail M. Freeman, Claire Mokrysz, Chandni Hindocha et al. 6 citations

Tolerance to some acute effects of delta-9-tetrahydrocannabinol (THC) develops in a domain-specific way, with more frequent cannabis use linked to reduced intensity of subjective effects like feeling stoned and reduced psychosis-like effects. Tolerance to alertness reduction occurred more readily than tolerance to psychotomimetic effects, while tolerance to memory impairment was weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC. These findings come from a mega-analysis of 128 cannabis users across four double-blind, placebo-controlled studies.

DOI: 10.1177/0269881120959601 Full text Cannabis Psychotomimetic Delta-9-tetrahydrocannabinol Schizotypy +7

Concomitant use of antidepressants and classic psychedelics: A scoping review

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.

DOI: 10.1177/02698811251368360

Out of control: Blinding, dose response, and psychosocial controls in psychedelic trials

Journal of Psychopharmacology September 1, 2025 Sandeep M. Nayak, Zarmeen Zahid 5 citations

As psychedelic clinical trials grow, fundamental design problems become clearer. Blinding fails because participants and therapists can easily tell who received a psychedelic due to its strong subjective effects, which are themselves considered therapeutically relevant. Alternative controls, such as dose-response designs, offer a practical workaround. The role of psychotherapy in psychedelic treatment remains ambiguous and poorly defined. The authors argue that preserving traditional placebo-controlled frameworks is inadequate and instead propose graded dose comparisons and unblinded comparative efficacy studies. They also outline a plan to empirically isolate psychotherapy's contribution, calling for operational definitions, fidelity monitoring, and risk mitigation. Progress will require triangulating evidence across multiple imperfect but complementary methods.

DOI: 10.1177/02698811251368367 Blinding Psychosocial Ambiguity Nocebo +9

Landscape analysis of pre-registered clinical trials involving classical psychedelics

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.

DOI: 10.1177/02698811251371690

Mind the gap! Addressing unresolved aspects of abuse potential evaluation and scheduling of classic and novel psychedelic drugs

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.

DOI: 10.1177/02698811251382147

The Afterglow Inventory (AGI): Validation of a new instrument for measuring subacute effects of classic serotonergic psychedelics

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.

DOI: 10.1177/02698811251326937 Psilocybin Lysergic acid diethylamide Afterglow Clinical psychology +2