American journal of therapeutics
Burton J Tabaac, Kenneth Shinozuka, Alejandro Arenas et al.
14 citations
Psilocybin, the primary psychoactive compound in magic mushrooms, alters consciousness through the 5-HT2A receptor. This review consolidates findings on its pharmacology, safety, and clinical uses. Psilocybin is generally safe in controlled settings, with transient nausea and headache as common adverse effects. In the largest clinical trial, 7 cases of suicidal ideation occurred up to 12 weeks after a single 25 mg dose, and none of those cases responded to treatment. Selective serotonin reuptake inhibitors may blunt psilocybin's hallucinogenic effects but could enhance its antidepressant effects.
American journal of therapeutics
Kenneth Shinozuka, Burton J Tabaac, Alejandro Arenas et al.
12 citations
DMT, a serotonergic psychedelic and the main psychoactive component of ayahuasca, has been used by indigenous peoples for centuries. A double-blind, randomized controlled trial found that ayahuasca led to remission in 36% of patients with treatment-resistant depression within one week. Top-line results from a recent phase IIa trial showed that 57% of patients with major depressive disorder experienced remission 12 weeks after a single intravenous dose of DMT. DMT and ayahuasca appear physiologically and psychiatrically safe, though ayahuasca can cause transient vomiting. All clinical trials have had small sample sizes (≤34 participants). The hypothesis that endogenous DMT is released during dying remains debated.
American journal of therapeutics
Burton J Tabaac, Kenneth Shinozuka, Alejandro Arenas et al.
12 citations
Psychedelic drugs show promise for treating depression, anxiety, and other neuropsychiatric conditions, including treatment-resistant cases. Despite a mental health crisis affecting nearly one billion people worldwide, large double-blind randomized controlled trials remain scarce due to the long-standing Schedule I status of many psychedelics. Esketamine was approved for major depressive disorder in 2019. Two Phase III trials of MDMA indicate it is superior to existing treatments for post-traumatic stress disorder. However, larger trials of psilocybin (100+ participants) suggest its remission rate is 25%-29%, similar to the roughly 30% remission rate of antidepressants from the STAR*D trial. Clinicians should learn to integrate psychedelic therapy into care.
American journal of therapeutics
Bryce D Beutler, Kenneth Shinozuka, Burton J Tabaac et al.
11 citations
LSD, a hallucinogenic agent once used to augment psychoanalysis and treat alcohol use disorder, was banned in 1970 partly due to concerns it could cause or worsen mental illness. Adverse events in clinical trials are almost always mild and transient, with serious events like psychosis or suicidal ideation reported in very few or no participants. In trials for anxiety and depression linked to life-threatening illnesses, 77% of participants experience durable relief one year after treatment. A phase IIb trial (n=198) found 50% of participants remitted from generalized anxiety disorder after a single 100 μg dose. A meta-analysis of mid-20th century RCTs indicates single-dose LSD significantly improves alcohol use disorder.
American journal of therapeutics
Viviana D Evans, Alejandro Arenas, Kenneth Shinozuka et al.
10 citations
Ketamine, originally a dissociative anesthetic, is now used for treatment-resistant depression, major depressive disorder with suicidal ideation, and PTSD. A single intravenous infusion shows antidepressant effects within hours, with a weighted effect size of d = 0.96 at 24 hours (N = 518). It reduces PTSD symptom severity (Clinician-Administered PTSD Scale scores: -11.88 points) and suicidal ideation in emergency settings (Scale for Suicidal Ideation scores: -4.96 points) compared to midazolam. However, effects may subside within weeks, requiring repeated administrations. Risks include temporary cognitive impairment, cardiovascular instability, liver toxicity with prolonged use, and ketamine cystitis. Ketamine also reduces postoperative pain and opioid consumption.
American Journal of Therapeutics
March 1, 2024
Kirsten Cherian, Kenneth Shinozuka, Burton J. Tabaac et al.
9 citations
Ibogaine, a plant-derived alkaloid used for millennia in West-Central African ceremonies, shows promise for treating opioid dependence and other neuropsychiatric conditions like PTSD, depression, and anxiety. However, it poses significant safety risks, including potentially fatal cardiac arrhythmias due to QT prolongation, which co-administration with magnesium may reduce. Dangerous interactions with opiates require full opioid withdrawal before treatment. Rare mania or psychosis can occur, and transient effects include ataxia, tremors, and gastrointestinal issues. In open-label and randomized controlled trials, a single ibogaine dose reduces heroin and opioid cravings by over 50% for up to 24 weeks.
SLEEP
May 1, 2023
Afik Faerman, Lauren Anker, Kirsten Cherian et al.
5 citations
Ibogaine, an alkaloid used in traditional African ceremonies, may improve sleep and trauma symptoms in veterans with repeated blast exposure and traumatic brain injury. Thirty Special Operations Veterans who voluntarily underwent ibogaine treatment at a clinic outside the US completed sleep and PTSD assessments at baseline, immediately after treatment, and one month later. Sleep quality (Pittsburgh Sleep Quality Index) and insomnia severity (Pittsburgh Insomnia Rating Scale) significantly improved one month post-treatment, as did PTSD symptom severity (CAPS-5). However, the improvement in PTSD symptoms did not significantly predict the sleep improvements, suggesting ibogaine may affect sleep and trauma through different mechanisms. The findings indicate ibogaine's potential for treating disturbed sleep after traumatic brain injury.
American journal of therapeutics
Owen S Muir, Kenneth Shinozuka, Bryce D Beutler et al.
5 citations
This article reviews seven psychedelic compounds and their potential roles in medicine, using a SWOT (strengths, weaknesses, opportunities, threats) format to assess how they fit into the broader healthcare landscape. Historically, psychiatric conditions have been treated with small-molecule drugs that have limited effectiveness and many side effects. Psychedelic medicines may offer more potent and faster-acting treatments. However, the field is emerging: only esketamine is FDA-approved for depression, and the other compounds remain investigational, making the discussion prospective and imaginative.
Npj mental health research
January 31, 2026
Clayton Olash, Derrick Matthew Buchanan, Randi Brown et al.
1 citation
A single open-label magnesium-ibogaine treatment prompted four recurring experiential themes among 30 male U.S. Special Operations veterans with TBI and PTSD: guided replay of autobiographical memories that allowed trauma reappraisal; altered-self and mystical connectedness; emotional resolution marked by surges of forgiveness, love, and renewed purpose; and embodied healing with a vivid sense of neural repair, cognitive clarity, and somatic relief. These themes describe an accelerated, self-directed psychotherapeutic process that aligns with previously reported clinical improvements in the same cohort, suggesting mind-body mechanisms involving rapid neuroplastic change.
Journal of affective disorders
November 18, 2025
Randi Brown, Jennifer Lissemore, Kenneth Shinozuka et al.
1 citation
Among 30 male Veterans with traumatic brain injury from repeated blast/combat exposures, those who reported more intense mystical experiences during magnesium-ibogaine therapy showed larger reductions in PTSD severity both immediately and one month after treatment. Greater mystical experience intensity was also linked to larger reductions in peak alpha frequency one month later. The findings suggest that mystical experiences may contribute to improvements in PTSD following magnesium-ibogaine and may relate to persisting decreases in peak alpha frequency.
iScience
February 21, 2026
Andrew D. Geoly, John P. Coetzee, Derrick Matthew Buchanan et al.
In a small study of 22 military veterans with traumatic brain injury, a single treatment with magnesium-ibogaine was associated with changes in brain structure one month later. Brain scans showed an average reduction in predicted brain age of 1.3 years, increased thickness in 11 cortical regions, and volume expansion in 8 subcortical regions. While the authors note that the imaging technique can also reflect nonstructural changes, the overall pattern of results is consistent with neuroplastic change.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging
February 1, 2026
Malvika Sridhar, Azeezat Azeez, Andrew Geoly et al.
Meditation significantly enhances brain connectivity, with studies showing a 30% increase in functional connectivity among experienced practitioners compared to novices. Using functional magnetic resonance imaging, researchers observed notable changes in neural activity associated with consciousness and emotional regulation. In a sample of 100 participants, those who meditated regularly exhibited stronger connections between brain regions linked to attention and self-awareness. This underscores the potential of meditation as a tool for improving mental health and cognitive function, highlighting its relevance in neuroscience and psychology.
Research Square
December 17, 2025
Camarin E. Rolle, Nolan Williams, Afik Faerman et al.
A single dose of magnesium-ibogaine produced large and lasting reductions in disability, posttraumatic stress disorder, depression, and anxiety symptoms over 12 months in male U.S. Special Operations Veterans with a history of traumatic brain injury. Of 30 treated participants, 25 completed the full year of follow-up. Effect sizes at 12 months were very large (Cohen's d ≥ 2.18). The estimated probability of sustained remission at one year was 84% for PTSD, 66% for depression, and 61% for anxiety. These results suggest ibogaine may offer durable clinical benefits for TBI-related psychiatric and functional problems, though randomized controlled trials are needed to confirm the findings.
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
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.
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.
Journal of the International Neuropsychological Society
November 1, 2023
Kirsten Cherian, Afik Faerman, Lauren Anker et al.
A single ibogaine treatment was associated with improvements in processing speed, executive functions, verbal fluency, and verbal learning among U.S. Special Operations Veterans with histories of combat, blast exposure, and traumatic brain injury. Thirty participants completed neuropsychological testing before and after treatment, and 27 returned for one-month follow-up. Scores on the WAIS-IV Processing Speed Index, Delis-Kaplan Color Word test, verbal fluency, and Hopkins Verbal Learning Test improved significantly. No negative cognitive effects were observed up to one month post-treatment. The findings suggest ibogaine may have therapeutic potential for cognition after traumatic brain injury, though further research is needed.
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.
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.
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
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.