World Journal of Biological Psychiatry
January 18, 2023
Shakila Meshkat, Sipan Haikazian, Joshua D. Di Vincenzo et al.
61 citations
Oral ketamine shows potential as an antidepressant for unipolar and bipolar depression, based on a systematic review of 22 studies involving 2336 patients. All included studies reported significant improvement after ketamine administration, and it was well tolerated without serious adverse events. However, the review identified important limitations, including a small number of randomized clinical trials (only four) and a high risk of bias in those trials due to analysis methods and adverse events monitoring. Ketamine dosages ranged from 0.5 to 1.25 mg/kg, with administration frequency from daily to monthly. Further research with larger samples and longer follow-up is needed to determine its antisuicidal effect and efficacy in treatment-resistant depression.
Therapeutic Advances in Psychopharmacology
January 1, 2023
Farhan Fancy, Sipan Haikazian, Danica E. Johnson et al.
23 citations
Ketamine given intravenously at subanesthetic doses (0.5–0.75 mg/kg) or as esketamine (28–84 mg) appears safe and effective as an add-on treatment for bipolar depression when combined with a mood stabilizer. Across eight studies (235 participants), 48% of those receiving ketamine achieved at least a 50% reduction in depression severity, compared with 5% on placebo. Real-world response rates were lower (30%) than in clinical trials (63%). Some studies noted reductions in suicidal ideation, though not all findings were statistically significant. Ketamine was generally well tolerated, but 2% of participants (five receiving ketamine) developed hypomanic or manic symptoms, and significant dissociative effects occurred at 40 minutes in some trials.
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.
Psychiatry Research
May 8, 2025
Noah Chisamore, Lee Phan, Roger S McIntyre et al.
7 citations
A review of pre-clinical and clinical studies on non-hallucinatory psychedelics (NHPs) for mood and anxiety disorders found five animal studies showing antidepressant-like effects, assessed via forced swim test and open field test, without the head-twitch response that indicates hallucination. One case report described a patient who inadvertently combined trazodone and psilocybin and experienced potent antidepressant effects without psychedelic effects. These preliminary findings suggest that antidepressant benefits of psychedelics may be separable from hallucinatory effects, providing impetus for rigorous clinical trials in humans.
JAMA Psychiatry
April 15, 2026
Diana Orsini, Sabrina Wong, Sara Di Luch et al.
4 citations
In randomized clinical trials of psychedelic drugs for psychiatric disorders, the drugs' strong subjective effects often reveal which treatment participants or raters think they received, a phenomenon called functional unblinding. A systematic review of 112 trials found that only 29.5% assessed whether blinding was maintained, yet 57.1% cited blinding as a limitation. Blinding failure exceeded 90% in psilocybin, LSD, and ayahuasca studies and 85% in MDMA trials with inert placebos. Ketamine trials rarely assessed blinding but fared better when midazolam was used as an active comparator. No control strategy consistently preserved ideal blinding, raising concerns about the validity of efficacy estimates.
Nature Mental Health
October 14, 2024
Danica E. Johnson, Joshua D. Rosenblat
1 citation
No Summary
Clinical Pharmacology & Therapeutics
May 28, 2026
Gia Han Le, Sabrina Wong, Danica E. Johnson et al.
The serotonin 5-HT2B receptor sits at a crossroads between potential antidepressant effects in the brain and serious heart valve risks when activated peripherally. This narrative review of preclinical and clinical literature finds that peripheral activation of 5-HT2B receptors causes valvular heart disease through cell proliferation and scarring, as seen with older drugs like fenfluramine and some dopamine agonists. In the brain, the receptor's effects are mixed: astrocytic activation may support metabolism and plasticity, while neuronal blockade can normalize dopamine and glutamate activity. Several approved antidepressant adjuncts (aripiprazole, brexpiprazole, cariprazine) antagonize this receptor without observed heart valve problems. The authors propose developing centrally selective, periphery-sparing 5-HT2B antagonists for treatment-resistant depression, with early cardiac monitoring to ensure safety.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
November 22, 2025
Shakila Meshkat, Noah Chisamore, Zoe Doyle et al.
A single dose of psilocybin was linked to small, temporary gains in processing speed and executive function in people with treatment-resistant depression. These cognitive improvements seemed unrelated to mood changes but did not consistently surpass the improvements expected from simply retaking the tests. The findings underscore the need for larger, controlled studies to determine whether psilocybin genuinely enhances cognition or if the observed changes stem from practice effects or mood shifts.