Journal of clinical psychopharmacology
María Gómez-sousa, Daniel F Jiménez-garrido, Genís Ona et al.
24 citations
Among 40 first-time ayahuasca ceremony participants, 7 reported intense challenging psychological effects. Four of those 7 had a pre-existing psychiatric diagnosis; one month after the ceremony, two no longer met diagnostic criteria and the other two showed considerably reduced symptoms, with effects persisting at six months. Poor setting and guidance contributed to some reactions. Six of the seven did not use ayahuasca again during the study. The findings suggest that acute negative psychological reactions during ayahuasca ceremonies can sometimes be followed by positive long-term effects, highlighting the need for prospective research on safety and contextual factors.
Journal of clinical psychopharmacology
Nicole Ledwos, Joshua D Rosenblat, Daniel M Blumberger et al.
16 citations
A critical appraisal of clinical trials on serotonergic psychedelics for major depressive disorder and end-of-life distress finds that current evidence is low-level due to methodological limitations. Small randomized trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy to an active comparator, with similar preliminary positive effects for single-dose ayahuasca in treatment-resistant depression and lysergic acid diethylamide for end-of-life distress. Adverse events were mild and transient. However, small homogenous samples, expectancy bias, functional unblinding, and lack of standardized psychotherapy limit all studies. Psychedelics should remain experimental interventions used within clinical trials.
Journal of clinical psychopharmacology
Giordano Novak Rossi, Juliana Mendes Rocha, Flávia L Osório et al.
12 citations
In a small preliminary trial, ayahuasca—with or without a 600 mg dose of cannabidiol (CBD) given 90 minutes beforehand—did not produce interactive effects on emotion recognition or empathy tasks. Both groups showed faster reaction times on these tasks and reported reduced anxiety, sedation, and discomfort, but there were no differences between the group that received CBD and the one that did not. Ayahuasca was well tolerated, causing mainly nausea and gastrointestinal discomfort, with no clinically significant changes in heart or liver measures. The safety of the combination suggests that both drugs could be tested in larger trials for anxiety disorders.
Journal of clinical psychopharmacology
Lucas Silva Rodrigues, José Augusto Silva Reis, Giordano Novak Rossi et al.
8 citations
A single dose of ayahuasca, a plant hallucinogen containing N,N-dimethyltryptamine and harmine, was given with psychological support to 11 college students who drank alcohol harmfully. The treatment was well tolerated and produced strong psychoactive effects. Days of alcohol consumption per week dropped from about 2.9 to 2.1 between weeks 2 and 3, but this reduction was not statistically significant after correcting for multiple comparisons. No other measures—craving, anxiety, impulsivity, self-esteem, or social cognition—showed significant changes, except faster reaction time on an empathy task. The small sample and mild baseline drinking likely limited the findings. The study demonstrates the protocol is feasible for future larger trials.
Journal of clinical psychopharmacology
Vivian Kim, Scott M Wilson, Mary E Woesner
3 citations
Classic psychedelics, which act on serotonin receptors, show promise for treating depression and anxiety disorders according to clinical trials published since 2020. These compounds have been tested for major depressive disorder, treatment-resistant depression, bipolar II, and anxiety-spectrum disorders. However, the evidence is limited by short follow-up periods, nonstandard dosing, and study designs. Many findings come from post hoc analyses of a few parent studies. The review calls for more original research with larger, diverse samples, standardized methods including blinding, and long-term follow-up to assess benefits and adverse effects. Psychological support and the therapeutic alliance are also important considerations.
Journal of clinical psychopharmacology
July 21, 2025
Guy Ludbrook, Nathan Bryson, Beatrix Taylor et al.
2 citations
A single subcutaneous dose of RE104, a prodrug of the synthetic psychedelic 4-OH-DiPT, was generally safe and well-tolerated in 48 healthy adults with prior psychedelic experience. Doses from 5 to 40 mg produced no serious adverse events or deaths; most side effects were mild to moderate and occurred under supervision. The drug appeared rapidly in the blood, with peak levels reached in 1.0 to 1.25 hours and a half-life of 2.72 to 4.12 hours. Exposure increased proportionally with dose. Plasma levels correlated with drug effects and mystical experiences, and higher doses produced more complete mystical experiences. The psychoactive experience lasted 3 to 4 hours, shorter than psilocybin, suggesting a favorable therapeutic profile.
Journal of clinical psychopharmacology
January 12, 2026
Natia Horato, Felipe Dalvi-Garcia, Pablo E P Dutra et al.
1 citation
A systematic review of 15 studies (10 randomized double-blind controlled trials and 5 open-label trials) examined the efficacy of psychedelics for treatment-resistant depression (TRD), a severe subtype of major depressive disorder. The review suggests that both typical and atypical psychedelics can provide rapid and substantial improvement in depressive symptoms, representing an alternative and complementary therapeutic approach to traditional treatments for TRD.
Journal of clinical psychopharmacology
Chad J Reissig, Ling Chen, Srikanth C Nallani et al.
1 citation
A single dose of kratom, a plant from Southeast Asia, produced some opioid-like effects in recreational polydrug users with opioid experience. In a double-blind, placebo-controlled study with 40 participants, kratom at doses of 3 grams or more caused pupil constriction, and the 12 gram dose increased ratings of drug liking, good effects, and high. No deaths or serious adverse events occurred; the most common side effects were somnolence, vomiting, and nausea. The findings suggest kratom can produce effects associated with drugs of abuse, but results may not apply to other kratom products.
Journal of clinical psychopharmacology
Vagner Deuel de O Tavares, Kaike Thiê da Costa Gonçalves, Maria Luiza de Morais Barros et al.
1 citation
A meta-analysis of eleven studies found no significant correlation between the psychoactive (psychomimetic) effects of ketamine and clinical outcomes in mental illness, including depression. The overall correlation was r = 0.06, and for depression specifically r = 0.03, both non-significant. Sub-analyses accounting for patient disorders, intravenous administration, assessment instruments, and timing also yielded no significant findings. High heterogeneity was present. The analysis suggests that altered states of consciousness during ketamine sessions are not directly linked to clinical outcomes, but the limited number of studies and heterogeneity make this conclusion preliminary.
Journal of clinical psychopharmacology
May 1, 2026
Matteo Carminati, Mattia Tondello, Chiara Morana et al.
In a small retrospective study of 16 patients with treatment-resistant depression treated with intranasal esketamine, those who responded to treatment after 7 months had higher baseline neutrophil-to-lymphocyte ratios (NLR) than non-responders (1.81 vs. 1.23). The difference remained significant after adjusting for age. The findings suggest that a patient's inflammatory status before treatment may influence their response to esketamine, but the small sample and retrospective design limit confidence. Larger prospective studies are needed to clarify whether inflammatory markers can predict esketamine response.
Journal of clinical psychopharmacology
March 24, 2026
Riccardo Guglielmo, Emma Laura Facchinetti, Daniele Cioci et al.
Treatment-resistant depression, affecting up to one third of people with major depressive disorder, often involves lasting cognitive problems that hinder recovery. A systematic review of six studies found that esketamine does not appear to cause cognitive decline in adults aged 18 to 80. Improvements in attention and processing speed were the most frequent and robust findings, seen in both randomized trials and naturalistic studies. Memory remained stable in short-term studies but improved with longer follow-up. Executive functions improved mainly in participants with baseline impairments and in long-term assessments. Overall, esketamine appears cognitively safe and may offer selective cognitive benefits, particularly in attention and processing speed, potentially supporting functional recovery.
Journal of clinical psychopharmacology
Ewen Kervadec, Aurore Bezo, Raphaël Serreau et al.
Ibogaine, a psychedelic compound distinct from psilocybin or LSD, has attracted interest for treating substance use and psychiatric disorders, but clinical evidence remains weak. A narrative review of studies from 1990 to 2025 found 24 studies and 38 case reports. Most positive efficacy data come from uncontrolled, open-label, or retrospective studies with high risk of bias. No double-blind randomized controlled trial has shown ibogaine or its metabolite noribogaine to effectively treat opioid use disorder. One small trial reported significant effects for cocaine use disorder. Observational data suggest possible symptom relief for opioid use disorder, PTSD, or polysubstance dependence, but findings are exploratory. Serious adverse events, especially cardiotoxicity from QT prolongation, pose considerable risk given unproven efficacy. Current evidence is insufficient to support clinical use.
Journal of clinical psychopharmacology
John L Havlik, Sayana Isaac, Pralahad Raman et al.
As of late 2024, 181 ongoing clinical trials of psychogenic substances for psychiatric disorders are registered on ClinicalTrials.gov. Most are in phase 2 (51.4%) or phase 1 (18.2%), with psilocybin (35.4%) and ketamine (33.7%) the most studied compounds. Trials concentrate at a few leading academic institutions. Over 81% list their funding source as "other," and 86% of those are sponsored by universities or university-affiliated institutions. Blinding is not reported in 38.7% of trials. Major depressive disorder (51.9%), posttraumatic stress disorder (21.0%), and alcohol use disorder (11.6%) are the primary conditions targeted. The lack of clear funding disclosure indicates a need for greater transparency.