BJPsych Open
December 23, 2021
Zach Walsh, Özden Merve Mollaahmetoğlu, Joseph M. Rootman et al.
180 citations
A systematic review of 83 studies found that subanesthetic doses of ketamine produce rapid, short-lived antidepressant and anti-suicidal effects. Evidence for other psychiatric conditions is less robust but suggests similarly positive but transient benefits. The conclusions are tentative due to high risk of bias across the included studies. Optimal dosing, administration methods, and best forms of adjunctive psychotherapy require further investigation.
BJPsych Open
September 1, 2022
Tommaso Barba, Sarah Buehler, Hannes Kettner et al.
57 citations
Psilocybin, but not the antidepressant escitalopram, reduced rumination and thought suppression in people with major depressive disorder six weeks after treatment. In a randomized trial of 59 participants, only those given psilocybin showed significant decreases in both maladaptive coping strategies. Among treatment responders, thought suppression decreased exclusively in psilocybin responders, while rumination decreased in both psilocybin and escitalopram responders. Reductions in rumination and thought suppression correlated with ego dissolution and psychological insight during psilocybin sessions, suggesting distinct therapeutic mechanisms for the two treatments.
BJPsych Open
July 1, 2023
Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows et al.
41 citations
A proof-of-concept randomized controlled trial will test whether combining the psychedelic psilocybin with risperidone, a drug that blocks the serotonin 2A receptor, can block psilocybin's psychedelic effects while preserving its antidepressant action in adults with treatment-resistant depression. Sixty participants will be randomly assigned to receive psilocybin plus risperidone, psilocybin alone, or placebo plus risperidone, all with 12 hours of manualized psychotherapy. Feasibility and tolerability will be assessed through recruitment, retention, and adverse events. If successful, this approach could make psilocybin therapy more acceptable and accessible by eliminating the need for a psychedelic experience and continuous monitoring.
BJPsych Open
January 18, 2022
Zach Walsh, Özden Merve Mollaahmetoğlu, Joseph Rootman et al.
28 citations
No Summary
BJPsych Open
January 1, 2021
Karen Lascelles, Lisa Marzano, Fiona Brand et al.
20 citations
Twelve fee-paying patients with treatment-resistant depression (ages 21–70, six women and six men, most reporting suicidality and some reporting self-harm) were interviewed before, during, and months after starting ketamine treatment in a routine clinic. Nearly all experienced mood improvement after initial treatments, ranging from negligible to dramatic, and eight reported reduced suicidality. Improvements were generally transitory; two patients had sustained consistent benefit and two had sustained but limited improvement. Some described hopelessness when treatment stopped working, and three experienced increased suicidal ideation. Side-effects were common and significant for two patients. Treatment cost and lack of longer-term benefit were problematic. Suggestions included closer monitoring and adjunctive therapy.
BJPsych Open
July 29, 2019
Sagar Jilka, Claire A. Murray, Ania M. Wieczorek et al.
20 citations
Patients and carers want better evidence on the long-term safety of ketamine for major depression and feel that monitoring is required, though they worry about misuse of that information. Practical barriers such as repeated travel to clinics and lack of sufficiently informed medical staff are key concerns. The study used 44 participants in 21 focus groups and an online survey, generating ten themes including monitoring, information, side-effects, recreational use, effectiveness, cost, stigma, and therapy.
BJPsych Open
June 7, 2023
Nicollette Thornton, Jason Kawalsky, Alyssa Milton et al.
11 citations
A systematic review of 119 print and online news articles from 2015 to 2020 found that media coverage of ketamine for psychiatric disorders was extremely positive (68.9% of articles). The rapid antidepressant effect was frequently emphasized (73.1% of articles), while longer-term safety and efficacy received little attention. Side-effects were reported in 80.7% of articles, mainly acute psychotomimetic effects and addiction risk, but rarely cardiovascular or bladder effects. Key opinion leaders, such as clinicians, often provided overly optimistic quotes that went beyond the existing evidence base. The authors conclude that information shaping patient expectations is being communicated through the media, and clinicians should address patients' beliefs directly.
BJPsych Open
October 13, 2023
B. Beaglehole, P. Glue, Mike Clarke et al.
9 citations
New Zealand clinicians developed practical guidelines for using ketamine to treat treatment-resistant major depressive disorder in publicly funded specialist mental health services. The guidelines offer two treatment pathways: a test of responsiveness with intramuscular ketamine followed by a 3-month course of oral ketamine, aiming to maximize short-term benefits. The guidance was created through consultation with senior leadership, clinical pharmacy, psychiatrists, nursing, service users, and Māori mental health workers.
BJPsych Open
November 1, 2024
Mourad Wahba, Caroline Hayes, Maartje Kletter et al.
6 citations
A participant in a phase 2b clinical trial of psilocybin for treatment-resistant depression experienced increased suicidal ideation and a prolonged period of severely restricted eating after administration, leading to destabilization and need for support. Despite limited improvement on depression rating scales, the participant found the experience helpful and made beneficial life changes. The case suggests psilocybin can temporarily worsen suicidal ideation and cause prolonged adverse events beyond acute effects, while paradoxically improving functional outcomes not captured by standard scales. Qualitative exploration of serious adverse events and participant accounts is needed to better understand psilocybin's varied outcomes.
BJPsych Open
October 1, 2025
Ben Beaglehole, Paul Glue, Shona Neehoff et al.
5 citations
Intramuscular ketamine shows preliminary effectiveness and is well tolerated by people with posttraumatic stress disorder in a community setting. The findings are encouraging given the known limitations of existing treatments, but more research is needed to determine the best dosing schedule and long-term role of ketamine for PTSD.
BJPsych Open
December 15, 2025
Nicole Ledwos, Jenna Baer, Muhammad Ishrat Husain et al.
2 citations
Up to 60% of people with obsessive–compulsive disorder (OCD) do not respond to standard treatments such as selective serotonin reuptake inhibitors, antipsychotic augmentation, or cognitive–behavioural therapy. This open-label pilot trial will test whether a single 25 mg dose of psilocybin combined with psychological support is feasible, tolerable, and safe for ten adults with treatment-resistant OCD. Clinical improvement will be measured with the Yale–Brown Obsessive–Compulsive Scale. Exploratory brain imaging, electroencephalogram, and transcranial magnetic stimulation-electroencephalogram measures will examine changes in dynamic connectivity and brain dynamics before, during, and up to one week after dosing. Results will inform the design of larger randomized trials and help clarify neurobiological mechanisms of psilocybin-assisted therapy.
BJPsych Open
November 1, 2025
Jonathon Marinis, Sarah Clarke, Alexandre A. Guerin et al.
2 citations
Side-effects reporting in clinical trials of psilocybin-assisted psychotherapy (PAP) for psychiatric conditions is inconsistent but improving over time. A systematic review of 24 trials published between 2005 and 2024 found that only six had high-quality side-effects reporting, while nine were low and five were very low. All nine randomized controlled trials showed high risk of bias for side-effects outcomes. There was no evidence of systematic underreporting in published articles compared with trial registers, but variability in reporting hindered comparisons. The authors conclude that existing evidence has a high risk of bias and that future trials should follow best-practice guidelines, and discussions with patients should emphasize current uncertainty about PAP side-effects.
BJPsych Open
July 1, 2023
Allan H. Young, Wiesław Jerzy Cubała, René Ernst Nielsen et al.
2 citations
Among people with treatment-resistant depression, those who had failed three or more prior treatments were more likely to achieve remission after eight weeks of esketamine nasal spray (28.0%) than after quetiapine extended release (10.9%). For those with only two prior treatment failures, remission rates were similar between the two treatments (26.5% vs. 21.8%). Esketamine also led to faster remission in both subgroups. The results suggest esketamine may be especially effective for patients with more extensive treatment histories.
BJPsych Open
February 16, 2026
Zeina Beidas, Anya Ragnhildstveit, Adam Blackman et al.
1 citation
This is a protocol for a phase II trial testing whether very low doses of psilocybin (2 mg, a microdose) can safely and effectively treat major depressive disorder. Forty adults with MDD will receive either psilocybin or a placebo once weekly for four weeks, then all will receive psilocybin for another four weeks. The trial will measure changes in depression symptoms, mood, well-being, attention, creativity, mindfulness, and pro-sociality. Results will be published regardless of outcome. The findings are expected to guide future research on dose regimens, effect sizes, and the role of expectancy bias, and to inform debates about sub-threshold versus threshold doses of psilocybin.
BJPsych Open
February 12, 2026
David A. Bender, Holly Dunn, Amanda Pekau et al.
1 citation
From 2000 to 2025, media coverage of psychedelic drugs increasingly focused on their therapeutic potential, rising from 13.3% of articles in 2000–2009 to 85.3% in 2020–2025. Overall sentiment was positive, with an average score of 78.5 out of 100. However, negative and neutral coverage has grown since 2020: the proportion of articles with sentiment scores of 65 or below rose from 3.6% in 2020 to 20.9% in 2024, and average sentiment dropped significantly in 2024 compared to 2020–2023. Artificial intelligence sentiment ratings closely matched human ratings.
BJPsych Open
July 1, 2023
Oluwatomiwa Ajayi, Arit Esangbedo, Abisola A. Lawal et al.
1 citation
Moral injury—a strong cognitive and emotional response to acts that violate one's ethical code—may precipitate a first episode of schizophrenia, according to a case report of a 22-year-old Nigerian man. His symptoms, including delusions of guilt, disorganized behavior, and beliefs of being possessed by four different people, emerged after he had intercourse for the first time, which conflicted with a conservative religious prophecy. Treatment with olanzapine led to significant improvement within two weeks. The authors suggest that cultural and religious factors can shape how moral injury manifests in psychosis, and call for further research into this association.
BJPsych Open
June 1, 2021
Amber Elyse Corrigan, Ella Burchill, Lucy Pelton et al.
1 citation
Psilocybin, the active compound in 'magic mushrooms', combined with psychotherapy is safe and effective for treatment-resistant depression (TRD), the largest contributor to global disability. Its mechanism is not fully understood, but functional neuroimaging suggests short and long-term changes in default mode network connectivity, possibly a 'reset' mechanism that restores normal function and emotional responsiveness. The drug itself, the psychotherapeutic context, and post-drug integration all play significant roles. Despite promising findings, psilocybin is a Schedule I drug, creating ethical, legal, social, and economic barriers to widespread clinical implementation. Optimizing treatment parameters and systemic legislative change are needed before this therapy can become widely available.
BJPsych Open
July 1, 2026
Alain F. Kalmar, Pascal Sienaert, Filip Bouckaert et al.
Nitrous oxide, a potent greenhouse gas, is being explored as a treatment for therapy-resistant depression, but its environmental costs are often ignored. A single one-hour treatment produces about 150 kilograms of CO2-equivalents, and a year of treatment for one patient generates roughly 7.8 metric tons of CO2-equivalents. The authors argue that these environmental externalities should be factored into assessments of the therapy's overall value.
BJPsych Open
June 18, 2026
Catherine L. Clelland
Media coverage of psychedelic therapies surged from 2000 to 2025, with positive sentiment peaking in 2020 before declining sharply from 2024. This downturn coincided with the U.S. Food and Drug Administration's decision not to approve MDMA-assisted therapy for post-traumatic stress disorder, mirroring the rise-and-fall pattern seen in the 1960s. The authors used a large-language model validated against human raters to analyze 25 years of news articles. They stress that continued progress depends on grounding therapeutic advances in scientific evidence rather than media-driven narratives.
BJPsych Open
June 1, 2026
Sunandan Banerjee
A systematic review examined whether psychedelic-assisted therapies could reduce crime-related behavior in forensic psychiatry, and what risks and practical issues would arise if such approaches were considered in UK forensic mental health services. The literature suggests potential indirect benefits through enhanced trauma processing, psychological flexibility, empathy, and reduced substance misuse—factors linked to offending and recidivism. However, substantial risks include psychosis, affective instability, behavioral disinhibition, impaired judgment, and challenges assessing capacity and criminal responsibility. No evidence supports routine clinical use in forensic populations; any future consideration would require extremely stringent patient selection, specialized non-coercive settings, and robust legal safeguards.
BJPsych Open
June 1, 2026
Sunandan Banerjee
Brain stimulation techniques such as TMS, tACS, tDCS, and DBS can induce transient changes in perception, emotion, self-experience, and cognitive flexibility that overlap with psychedelic states. Both approaches reduce default mode network dominance and increase global brain connectivity. Unlike pharmacological psychedelics, brain stimulation avoids systemic drug exposure, can be titrated or stopped in real time, and reduces risks of prolonged perceptual disturbance or psychosis. Therapeutic benefit in psychedelic research depends on psychotherapeutic processes like insight and emotional processing, not the altered state alone. Brain stimulation may similarly enhance neural flexibility, boosting psychotherapy response for depression, trauma, and addiction. Stimulation-assisted psychotherapy offers a controllable, non-pharmacological clinical model.
BJPsych Open
June 1, 2026
James Finlay
A review of studies comparing electroconvulsive therapy (ECT) and ketamine for major depression finds that ECT is more effective at reducing depressive symptoms, as measured by standard rating scales. Evidence on suicidal thoughts is limited, with no clear difference between the two treatments in the short term. Cognitive effects are mixed; ketamine may offer better short-term cognitive performance, but some studies find no difference. Side effects differ: ECT commonly causes headaches and muscle pain, while ketamine is linked to temporary dissociative and perceptual symptoms. Cost-effectiveness favors ECT, which produces more quality-adjusted life years at lower cost. Ketamine may still be useful for patients who need rapid relief or who have not responded to ECT.
BJPsych Open
June 1, 2026
Gaurav Uppal, Naima Gul, Asha Dhandapani et al.
Psychedelic-assisted therapies, particularly psilocybin-assisted psychotherapy, are more effective than control treatments (pharmacological, active placebo, and waitlist) for mood, trauma-related, and substance use disorders. A network meta-analysis of six randomized controlled trials found that psilocybin at high doses outperformed low doses, and psilocybin-assisted psychotherapy ranked highest among all treatments examined. MDMA-assisted psychotherapy and ketamine-assisted therapy also ranked higher than control conditions. The pooled summary effect favoring psychedelic-assisted therapy was large and statistically significant (−0.89, 95% CI: −1.07 to −0.72). These findings support the therapeutic potential of these treatments and highlight the need for more direct comparative trials.
BJPsych Open
June 1, 2026
Imtiaz Ahmad Dogar, Palvisha Sajid, Dua Fatima et al.
In a non-randomized trial at a tertiary care hospital in Faisalabad, Pakistan, 30 patients with treatment-resistant depression received eight intravenous ketamine infusions (0.5 mg/kg over 60 minutes) over four weeks. 22 of 30 patients (73.3%) showed a positive response, defined as a 50% or greater reduction in Hamilton Depression Rating Scale scores one hour after the first dose. Improvement persisted at two-week and one-month follow-ups. The authors conclude that subanesthetic ketamine produces rapid and substantial improvement in depressive symptoms, with a response rate consistent with global data.
BJPsych Open
May 13, 2026
Zeina Beidas, Anya Ragnhildstveit, Adam Blackman et al.
This is a correction notice for a previously published study protocol. The original protocol describes a phase II double-blind placebo-controlled randomised partial crossover trial investigating microdosing psilocybin for major depressive disorder. No new findings or data are presented.