Journal of Clinical Psychopharmacology
December 30, 2022
Helena Rogg, Mihai Avram, Felix Müller et al.
8 citations
Ketamine treatment in patients with borderline personality disorder (BPD) may reduce symptom severity, but the evidence is preliminary and based on small samples. The review suggests that ketamine could be a potential therapeutic option for BPD, particularly for comorbid depression, though more rigorous studies are needed to confirm efficacy and safety. The authors note that existing studies have significant limitations, including lack of control groups and short follow-up periods.
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
September 25, 2025
Rachel Landrum, Amanda M. Raines, Philip D. Harvey et al.
1 citation
Maintenance intravenous racemic ketamine therapy produced significant, persistent, and broad symptom relief for treatment-resistant depression. Reductions occurred in both clinician-rated (Montgomery-Åsberg Depression Rating Scale) and patient-reported (Patient-Health Questionnaire-9) depression scores. Changes in individual symptoms were similar to prior trials: suicidal ideation and depressed mood improved most, while appetite disturbance improved least.
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 O de 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
March 12, 2026
Olga Ponomareva, Sean R. Stetson, Bruce Meltzer et al.
Chronic insomnia, common in PTSD, leads to depression, cognitive impairment, and substance abuse. Sleep abnormalities in PTSD include trauma-related nightmares, prolonged sleep latency, frequent interruptions, and disrupted sleep cycles. This review examines pharmacological treatment for nightmares, focusing on noradrenergic signaling and alpha-1 adrenergic blocking agents like prazosin. Randomized controlled trials suggest prazosin's clinical efficacy for PTSD-related nightmare disorder in subpopulations. Case studies, pilot, and open-label trials indicate possible clinical use of terazosin, tamsulosin, and doxazosin, but further RCTs are needed. Prazosin has the best evidence base; when not feasible, alternative alpha-1 blockers may be effective in a subset of patients.
Journal of Clinical Psychopharmacology
December 9, 2025
Namik Kirlic, Merve Atli, Sunil Mistry et al.
In people with treatment-resistant depression who received a single dose of 25, 10, or 1 mg of COMP360 psilocybin, the drug dose was the strongest and most consistent predictor of the subjective psychedelic experience. Some pretreatment characteristics—such as positive affect, lower generalized anxiety symptoms, higher executive functioning, and greater personality disorder symptoms—had weak effects on different aspects of the experience. These findings suggest that pretreatment clinical characteristics are not major determinants of the acute psychedelic experience; dose remains the largest driver.
Journal of Clinical Psychopharmacology
October 16, 2022
Richard Balon
No Summary
Journal of Clinical Psychopharmacology
August 1, 2018
Shaina Archer, Carson Chrenek, Jennifer Swainson
In a small group of 11 patients with treatment-resistant depression who initially responded to an acute course of ketamine infusions, ongoing maintenance infusions helped sustain the antidepressant effect for some. All patients had lower depression scores during maintenance treatment than at baseline. At the end of the observation period, 4 patients continued maintenance ketamine, 1 switched to intranasal ketamine, 4 stopped because the drug lost its effect, 1 stopped due to side effects, and for 2 the reason was unrecorded. No major adverse events occurred, and the treatment was generally well tolerated. The authors suggest maintenance ketamine may help some responders, but more research is needed on optimal duration and long-term safety.
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.
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
September 12, 2020
K. Fluegge
A letter to the editor raises concerns about using nitrous oxide (N2O) for treatment-resistant major depressive disorder (trMDD). The authors note that cobalamin dysregulation and folate deficiency are already documented in trMDD, citing evidence that cerebrospinal fluid metabolite abnormalities appear in over half of such patients, with cerebral folate deficiency most common, and that vitamin B12 levels predict deep white matter hyperintensities in MDD. They argue that N2O could worsen these effects, especially since its antidepressant effects are transitory, and call for clarifying why one-carbon metabolism dysregulation exists before considering N2O as a treatment.
Journal of Clinical Psychopharmacology
April 1, 2018
Peter Nagele, Charles F Zorumski, Charles R Conway
Nitrous oxide (laughing gas) is being studied as a fast-acting antidepressant for treatment-resistant major depression, but most psychiatrists are unfamiliar with its medical administration and regulations. This review educates psychiatrists on nitrous oxide's pharmacology and administration basics, and addresses common misconceptions about the gas.