Transl Psychiatry
November 13, 2025
Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano et al.
correction
This correction notice addresses errors in a previously published article that presented three systematic reviews and meta-analyses examining the pharmacology, neuroimaging, and phenomenology of psychedelics. The correction does not provide new findings or data but serves to amend the original publication.
December 27, 2023
Owen S. Muir, Kenneth Shinozuka, Bryce D. Beutler et al.
preprint
Psychedelic compounds may offer more potent and rapidly-acting treatments for psychiatric conditions compared to traditional small-molecule drugs, which often have limited effect sizes and adverse effects. Only one such compound, esketamine, is currently FDA-approved for depression; the others remain investigational. This article reviews six psychedelic compounds using a strengths, weaknesses, opportunities, and threats (SWOT) framework to assess their potential role in medicine.
December 26, 2023
Kirsten Cherian, Kenneth Shinozuka, Burton J. Tabaac et al.
preprint
Ibogaine, a plant-derived alkaloid used for millennia in West-Central African ceremonies, shows promise for treating opioid addiction, PTSD, depression, and traumatic brain injury. It reduces heroin and opioid cravings by over 50% for up to 24 weeks after a single dose in open-label and randomized trials. Combined with 5-MeO-DMT, it significantly lessens PTSD and depression symptoms. However, ibogaine poses serious risks, including cardiotoxicity, fatal arrhythmias, dangerous opioid interactions, and rare mania or psychosis. Rigorous double-blind, placebo-controlled research is lacking, and safer practices are needed given high trafficking rates.
December 26, 2023
Burton J. Tabaac, Kenneth Shinozuka, Alejandro Arenas et al.
preprint
Psychedelic drugs show promise for treating depression, anxiety, and other neuropsychiatric conditions that have not responded to prior interventions. While initial trials were very promising, larger studies of psilocybin with over 100 participants suggest it may not be more effective than standard antidepressants. Esketamine was approved for major depressive disorder in 2019. Two Phase III trials of MDMA for post-traumatic stress disorder found it superior to existing treatments. A Phase III trial of psilocybin is underway. The review covers LSD, DMT, ayahuasca, psilocybin, ibogaine, MDMA, and ketamine, concluding that these agents offer promise and clinicians should learn to implement them in patient-centered care.
December 26, 2023
Burton J. Tabaac, Kenneth Shinozuka, Alejandro Arenas et al.
preprint
Psilocybin, the psychoactive compound in magic mushrooms, alters consciousness by acting on the 5-HT2A receptor. Contrary to early fears of lasting mental health problems like psychosis, controlled clinical trials show it is psychologically and physiologically safe. Initial small trials reported remission rates of 42-57% for major depressive disorder and treatment-resistant depression, suggesting greater effectiveness than standard antidepressants. However, larger Phase II trials with over 100 participants found a lower remission rate of 25-29%, though a significant reduction in depressive symptoms remained. Psilocybin also shows promise for substance use disorders and end-of-life anxiety. Phase III trials are underway to confirm these findings.
American journal of therapeutics
Burton J Tabaac, Kenneth Shinozuka, Mahdi Fadel et al.
Mescaline, a classic psychedelic with a history of indigenous ceremonial use, is being reexamined for psychiatric therapy. It works primarily by activating serotonin-2A receptors. Most modern safety data come from healthy volunteers, leaving its effects in patients with cardiovascular, metabolic, or psychiatric conditions unclear. Randomized, placebo-controlled studies show mescaline produces dose-dependent subjective effects with moderate, temporary autonomic stimulation and no serious complications under controlled conditions. Adverse effects are generally self-limiting, and pooled analyses indicate a favorable safety profile in screened populations. Controlled clinical trials are needed to establish its safety and therapeutic potential in patient groups.
American journal of therapeutics
Kenneth Shinozuka, Burton J Tabaac, Alejandro Arenas et al.
MDMA, once notorious as a party drug, has shown strong promise as a treatment for PTSD. Animal studies that suggested neurotoxicity used doses far above human levels, and human samples often included recreational users taking multiple substances. Phase III clinical trials found MDMA-assisted psychotherapy has an effect size of d = 0.7–0.91, two to three times larger than existing antidepressants, with 67%–71% of patients no longer meeting PTSD diagnostic criteria within 18 weeks. Other potential applications include alcohol use disorder and social anxiety. Most trials have been sponsored by MAPS, and more research is needed comparing it to nonpharmacological treatments. FDA approval could come as soon as 2024.
Viviana D. Evans, Alejandro Arenas, Kenneth Shinozuka et al.
preprint
Ketamine, originally a dissociative anesthetic, is now used for treatment-resistant depression and major depressive disorder with suicidal ideation. A single intravenous infusion shows antidepressant effects within hours, with a large effect size on depression scores. It also reduces PTSD symptom severity and suicidal ideation in emergency settings. However, therapeutic effects often subside within weeks, requiring repeated doses. Risks include temporary or persistent memory impairment, cardiovascular issues, liver toxicity, and bladder inflammation. Ketamine's opioid-sparing effect improves postoperative pain management.
Burton J. Tabaac, Kenneth Shinozuka, Anne Weisman et al.
preprint
5-MeO-DMT, a psychedelic found in toad venom and some plants, shows rapid antidepressant effects in early clinical trials. A Phase 2b trial reported that 57.5% of participants with treatment-resistant depression achieved remission within eight days. Other Phase 2a and 2b trials suggest it may reduce depressive symptoms more effectively than existing treatments like SSRIs. The substance appears low-risk in controlled settings, though most studies are small and only two double-blind randomized controlled trials have been conducted in clinical populations. Long-term effects need further study, and its possible link to near-death experiences remains debated.
Kenneth Shinozuka, Burton J. Tabaac, Alejandro Arenas et al.
preprint
MDMA, known as a party drug in the 1980s, is emerging as a powerful treatment for PTSD. Phase III FDA trials show MDMA-assisted psychotherapy has an effect size of 0.7-0.91, two to three times larger than existing antidepressants. Within 18 weeks, 67 to 71% of patients no longer meet PTSD diagnostic criteria. The literature is biased: animal studies used doses far above human levels, and human samples often involve recreational users of multiple substances. Only six clinical trials, all by MAPS, have been conducted, but preliminary evidence suggests MDMA is much more effective than current antidepressants for PTSD.
Bryce D. Beutler, Kenneth Shinozuka, Burton J. Tabaac et al.
preprint
Lysergic acid diethylamide (LSD) shows promise for treating alcohol use disorder, anxiety, and depression, though its therapeutic potential remains incompletely understood. In clinical trials, adverse events have almost always been mild and transient, with serious events reported in none or very few participants. For anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at one year post-treatment. A meta-analysis of randomized controlled trials found that single-dose LSD significantly improves alcohol use disorder with an odds ratio of 1.96. Large-scale prospective studies are needed to explore potential clinical applications.
Kenneth Shinozuka, Burton J. Tabaac, Alejandro Arenas et al.
preprint
DMT, the psychedelic in ayahuasca, is being studied for depression. In a double-blind, placebo-controlled trial, ayahuasca led to remission in 36% of patients with treatment-resistant depression within one week. A Phase IIa trial reported that 57% of patients with major depressive disorder experienced remission 12 weeks after a single dose of DMT. DMT is naturally produced in the body, but likely at insignificant levels. The idea that DMT is released during death remains unproven. Ayahuasca can cause temporary vomiting but appears generally safe. More research is needed on DMT's therapeutic and biological roles.