Frontiers in Psychiatry
June 27, 2023
Irene Li, Rodney Fong, Molly M. Hagen et al.
25 citations
Medical students in Nevada hold generally positive attitudes toward psychedelics and psychedelic-assisted therapies but lack knowledge about them. In a survey of 132 students (22.7% response rate), 78.6% agreed that psychedelics have therapeutic potential, and 95.2% agreed they deserve further research. Students expressed uncertainty about neurocognitive risks. Demographic factors such as age, sex, and level of training did not significantly affect attitudes. The authors suggest that as psychedelic therapies may soon gain federal approval for psychiatric conditions, medical training should include early education on these agents to prepare future clinicians.
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.
American Journal of Therapeutics
Amna M. Aslam, Kenneth Shinozuka, Owen S. Muir et al.
5 citations
Ketamine is increasingly used for treatment-resistant depression, especially after FDA approval of esketamine, yet significant barriers to access remain. Intravenous administration is the most common method, with intramuscular and sublingual routes emerging. Patients are predominantly middle-aged (36-64 years old), and financial obstacles due to limited insurance coverage are notable. Access is limited in rural areas, and private clinics offer more flexible treatment than hospitals. The absence of long-term outcome data and variability in protocols underscore the need for standardization and further research.
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.
December 20, 2024
Amna M. Aslam, Kenneth Shinozuka, Owen S. Muir et al.
2 citations
preprint
Ketamine, particularly intravenous (IV) ketamine, is increasingly used off-label for treatment-resistant depression (TRD), despite only esketamine being FDA-approved. A scoping review of two survey-based studies found IV administration is the most common method, with intramuscular and sublingual routes used less often. Patients are predominantly middle-aged (36-64 years), and financial barriers are notable due to limited insurance coverage and out-of-pocket costs. Geographic disparities limit access in rural areas. Private clinics offer more flexible treatment approaches than hospitals. The review emphasizes the need for standardized protocols, expanded insurance coverage, and further research due to variability in practices and absence of long-term outcome data.
Frontiers in Pharmacology
June 3, 2026
Burton J. Tabaac, Robin Carhart-Harris, Teresa Yung
Three individuals with persistent symptoms after traumatic brain injury or hypoxic-ischemic brain injury completed a six-week protocol combining a participant-directed iboga-containing microdosing regimen (using whole root bark biomass with about 3.845% ibogaine content, yielding an estimated 3.8–38.5 mg/day ibogaine equivalent) with weekly Accelerated Experiential Dynamic Psychotherapy and supportive nutraceuticals. All three showed progressive neurological recovery; two reported complete symptom remission at long-term follow-up. Participants discontinued all prescription medications and reported resolution of headaches, brain fog, fatigue, irritability, and mood swings, with a return to regular activities and renewed enthusiasm. The authors note that the findings do not establish causality or iboga-specific efficacy due to the multimodal intervention and methodological limitations.
February 28, 2026
Burton J. Tabaac, Kenneth Shinozuka, Fadel et al.
preprint
Mescaline, a classic serotonergic psychedelic used ceremonially by Indigenous peoples, shows preliminary safety in healthy humans under controlled conditions, producing dose-dependent subjective effects with moderate, transient autonomic stimulation and no serious medical complications. Adverse effects are generally self-limited, and pooled safety analyses and observational data support an overall favorable safety profile in screened populations. However, there is a lack of controlled clinical trials evaluating mescaline in patient populations, so its safety in individuals with cardiovascular, metabolic, or psychiatric comorbidities remains unclear. Controlled clinical trials are needed to establish its safety and therapeutic potential.
American Journal of Therapeutics
February 20, 2026
Burton J. Tabaac, Kenneth Shinozuka, Anne Weisman et al.
5-MeO-DMT, an ultra-short-acting psychedelic, shows promise for treating depression that does not respond to other therapies, as well as other psychiatric conditions. This evidence supports the need for larger randomized controlled trials to further investigate its effectiveness.
Dialogues in Clinical Neuroscience
September 2, 2024
Shiven Chaudhry, Anne Weisman, Molly M. Hagen et al.
A two-hour team-based learning curriculum improved medical students' knowledge, comprehension, and ethical understanding of psychedelic therapies. Pre- and post-surveys from 63 and 50 students, respectively, showed significant gains in perceived knowledge and attitudes, while 48 matched pre/post-knowledge tests demonstrated enhanced comprehension. Qualitative feedback indicated greater comfort discussing psychedelics clinically, though some students expressed reservations about psychedelic-assisted therapy. The curriculum addresses an educational gap as psychedelic medicine becomes more relevant.
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
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.
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.
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.
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.
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.
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
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.