Translational psychiatry
December 4, 2024
Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano et al.
17 citations
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and may help treat depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—subjective experience, neuroimaging, and molecular pharmacology—reveals that medium and high doses of LSD produce stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences exist in receptor selectivity among the drugs. The analysis finds high heterogeneity and risk of bias, calling for standardized methods and more research.
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.
bioRxiv (Cold Spring Harbor Laboratory)
April 28, 2024
Kenneth Shinozuka, Prejaas Tewarie, Andrea I. Luppi et al.
5 citations
preprint
LSD weakens the brain's directed connectivity hierarchy by increasing the balance between senders and receivers of neural signals. This finding supports the REBUS theory, which proposes that psychedelics flatten the hierarchy of information flow in the brain. Analyzing magnetoencephalography data from 16 healthy participants given 75 micrograms of intravenous LSD, the study found that LSD diminishes the asymmetry of directed connectivity averaged over time. Machine learning classifiers distinguished LSD from placebo more accurately when trained on hierarchy metrics than on traditional functional connectivity measures.
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.
American journal of therapeutics
Amna M Aslam, Kenneth Shinozuka, Owen 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.
Human brain mapping
April 1, 2025
Clayton R Coleman, Kenneth Shinozuka, Robert Tromm et al.
4 citations
LSD alters consciousness by changing connectivity between the dorsolateral prefrontal cortex (DLPFC), thalamus, and visual areas. In healthy participants, stronger functional connectivity between the left and right DLPFC, thalamus, and fusiform face area correlated with greater ego dissolution. Emotional arousal was linked to increased connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory reverse analysis supported these findings. Magnetoencephalography data showed that LSD increased theta-band information flow from the thalamus to the DLPFC, supporting the idea that disrupted thalamic gating underlies ego dissolution. The results clarify the DLPFC's role in LSD-induced altered states.
bioRxiv Preprint Server
September 19, 2025
Kenneth Shinozuka, Winson F.z. Yang, Ruby M. Potash et al.
3 citations
preprint
Advanced meditators can enter a state called extended cessation (EC) in which they intentionally suppress consciousness and later emerge with clarity and equanimity. In the first electrophysiological study of EC, five meditators were recorded with EEG and MEG. EC markedly reduced alpha power and tended to increase neural complexity, unlike sleep, anesthesia, or disorders of consciousness. The findings indicate that the neural correlates of EC are distinct from other unconscious states and that complexity alone is not sufficient for consciousness, offering new insights into advanced meditation and human flourishing.
Electronic workshops in computing
July 1, 2021
Carl Smith, Kenneth Shinozuka, Alex Zhao et al.
3 citations
The Museum of Consciousness presents a collection of short audio samples designed by artists and consciousness explorers to cultivate expansive states of consciousness. The samples include mindfulness meditations, placebo highs, sound journeys, and novel introspection methods. Visitors rate each sample using Raph Milliere's 6D model of self-consciousness, which was inspired by psychedelics and meditation, and play a game guessing the curators' pre-assigned ratings. Feedback from visitors is incorporated into a regenerative system that shapes future exhibits.
bioRxiv (Cold Spring Harbor Laboratory)
October 7, 2023
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
2 citations
preprint
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and show therapeutic potential for depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—phenomenology, neuroimaging, and pharmacology—reveals that medium and high doses of LSD produce significantly stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences emerged in receptor selectivity among the drugs. The findings highlight high heterogeneity and risk of bias, underscoring the need for standardized methods.
bioRxiv (Cold Spring Harbor Laboratory)
March 24, 2026
Kenneth Shinozuka, Mattia Rosso, Anna Chaiken et al.
1 citation
A single dose of the atypical psychedelic ibogaine can be highly effective at treating PTSD in veterans up to twelve months later, according to an observational study of 30 veterans. Using a novel EEG analysis method, researchers found that ibogaine shifted high-beta (24 and 25 Hz) brain networks from frontal areas toward posterior regions, an effect seen both three to four days and one month after treatment. This posterior shift correlated with improvements in PTSD symptoms and was replicated in an independent dataset on ibogaine for opioid use disorder. Neural modeling suggested the shift reflects increased corticocortical, not corticothalamic, connectivity. The reconfiguration of high-beta networks may be a robust biomarker for ibogaine's therapeutic effects.
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.
bioRxiv Preprint Server
December 9, 2024
Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) alters consciousness by affecting brain connectivity, particularly in the dorsolateral prefrontal cortex (DLPFC). Using fMRI and MEG data from healthy participants, the study found that ego dissolution—a hallmark of the psychedelic experience—was positively correlated with increased functional connectivity between the left and right DLPFC, thalamus, and fusiform face area. Emotional arousal was linked to stronger connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory analysis supported these findings. MEG data showed that LSD increased directed information flow from the thalamus to the DLPFC in the theta band, suggesting disrupted thalamic gating contributes to ego dissolution. These results indicate a key role for the DLPFC in LSD-induced states of consciousness.
Research Square
June 17, 2026
Martijn Arns, Kenneth Shinozuka, Joseph Barsuglia
Ibogaine, a substance showing early promise for treating substance use disorders and PTSD in veterans, carries a risk of cardiac arrhythmia and death. A retrospective multisite study of 19,071 patients treated under safety guidelines at 11 international clinics found that all six deaths occurring within 72 hours were among patients treated for opioid use disorder (6 out of 10,382), with no deaths among 8,689 non-SUD patients. A systematic review of ibogaine-associated fatalities mirrored this pattern: 41 of 44 fatalities with known indication involved substance use disorder, predominantly opioid detoxification. The findings indicate that ibogaine-associated mortality is largely confined to opioid detoxification and rare in non-SUD indications.
Research Square
February 27, 2026
Randi Brown, Kenneth Shinozuka, Irakli Kaloiani et al.
A survey of 151 US veterans who received funding for psychedelic treatment found that after their most memorable psychedelic experience, the proportion who endorsed an active belief in God or a higher power increased significantly, while the proportion who denied such belief decreased significantly. No significant changes occurred in affiliation with spiritual or religious groups, but qualitative analysis indicated shifts in the nature of participants' relationship with spirituality. The findings suggest that psychedelic experiences can catalyze increased spiritual connection and reorientation, especially among those who previously doubted or did not believe.
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.
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
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.