World Psychiatry
September 15, 2023
Roger S. McIntyre, Mohammad Alsuwaidan, Bernhard T. Baune et al.
712 citations
At least 30% of people with depression meet the common definition of treatment-resistant depression (TRD): inadequate response to two or more antidepressants despite adequate trials and adherence. Many cases are actually pseudo-resistant due to insufficient treatment or non-adherence. No consensus definition with proven predictive utility for clinical decisions exists, leading to varied prevalence estimates and inconsistent care. Intravenous ketamine and intranasal esketamine are effective for TRD. Some second-generation antipsychotics (e.g., aripiprazole, quetiapine XR) help as adjuncts in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation and electroconvulsive therapy are established effective interventions. Evidence for extending trials, switching, or combining antidepressants is mixed, and manual-based psychotherapies are not effective alone but help when added to antidepressants.
American Journal of Psychiatry
August 29, 2018
Nolan Williams, Boris D. Heifets, Christine Blasey et al.
510 citations
Blocking opioid receptors with naltrexone dramatically reduced the antidepressant effect of ketamine in adults with treatment-resistant depression, while leaving ketamine's dissociative effects unchanged. In a double-blind crossover trial, 12 participants received either placebo or 50 mg of naltrexone before a ketamine infusion. Seven of 12 met the response criterion (≥50% reduction in depression scores) after ketamine plus placebo, but depression score reductions were significantly smaller when naltrexone was given. The trial was halted at an interim analysis because naltrexone blocked the antidepressant effect. The findings indicate that ketamine's acute antidepressant effect requires opioid system activation, while its dissociative effects do not.
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.
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.
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.