Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
September 1, 2022
Deepak Cyril D'Souza, Shariful A. Syed, L Taylor Flynn et al.
156 citations
A potent, rapid-onset psychedelic drug, dimethyltryptamine (DMT), was tested intravenously in a small pilot study with 7 treatment-resistant depressed individuals and 3 healthy controls. DMT was mostly safe and tolerated; no participants dropped out. Depression scores on the HAMD-17 scale dropped significantly the day after the higher dose (0.3 mg/kg), with an average decrease of 4.5 points. Side effects like increased blood pressure, heart rate, and anxiety resolved within 20-30 minutes. The findings suggest DMT may have next-day antidepressant effects in treatment-resistant depression, but more rigorous trials are needed to confirm and assess durability.
Journal of Psychopharmacology
March 20, 2023
Jordan Sloshower, Hamideh Safi-Aghdam, Surbhi Pathania et al.
153 citations
In a small exploratory study, 19 adults with moderate-to-severe major depression received placebo first, then 4 weeks later a single dose of psilocybin (0.3 mg/kg), both embedded in psychotherapy. Depression and anxiety improved after both placebo and psilocybin, with no statistically significant difference between the two conditions. However, antidepressant effect sizes were larger after psilocybin (d′ = 1.02–2.27) than after placebo (d′ = 0.65–0.99), and 66.7% of participants responded and 46.7% remitted following psilocybin. Improvements lasted about 2 months on average. The intensity of mystical-type experience during psilocybin did not correlate with antidepressant effects. The authors conclude that expectancy and therapy effects complicate interpretation but support further study of psilocybin for depression.
Journal of Psychopharmacology
June 30, 2023
Jordan Sloshower, Hamideh Safi-Aghdam, Surbhi Pathania et al.
47 citations
A single dose of psilocybin (0.3 mg/kg) doubled electroencephalographic theta power—a marker of neuroplasticity—in the auditory cortex of people with major depressive disorder two weeks later, while placebo produced no such change. Greater increases in theta power correlated with greater reductions in depression symptoms measured by the GRID-HAM-D-17 scale. These results provide evidence that psilocybin can induce sustained changes in human brain plasticity, and the theta-power increase may serve as an EEG biomarker for its antidepressant effects.
Molecular Psychiatry
July 1, 2026
Waki Nakajima, Tetsu Arisawa, Susumu Jitsuki et al.
1 citation
A novel compound, K-4, which positively modulates AMPA receptors, produced longer-lasting antidepressant-like effects in a rat model of treatment-resistant depression than ketamine alone. K-4 reduced expression of the enzyme NOX-1 in the medial prefrontal cortex. Blocking NOX-1, either with an inhibitor or by genetic knockdown, prolonged ketamine's antidepressant-like effects and reduced abnormal bursting in the lateral habenula, a brain region linked to depression. Suppressing NOX-1 may be a promising strategy for extending the benefits of ketamine in treatment-resistant depression.
Molecular Psychiatry
March 5, 2026
Waki Nakajima, Mai Hatano, Yohei Ohtani et al.
1 citation
About 30% of people with depression have treatment-resistant depression (TRD). Ketamine can help, but how it works in the human brain was unclear. Using a PET tracer that shows AMPAR density, researchers found that AMPAR density was lower in patients with more severe TRD, and its distribution differed from healthy people. After ketamine, changes in AMPAR density in certain brain areas correlated with antidepressant effects, partially restoring normal AMPAR patterns. AMPAR dynamics underlie ketamine's antidepressant effect in TRD.
Clinical EEG and Neuroscience
November 25, 2022
Shariful A. Syed, Ashley M. Schnakenberg Martin, J. Cortes-Briones et al.
Disruptions in neural oscillations, particularly in the gamma and theta frequency ranges, are a key mechanism by which THC, the primary psychoactive component of cannabis, perturbs brain function. Clinical EEG studies show that both chronic and acute cannabinoid exposure disrupts these neural oscillations in humans. The authors propose a hypothetical framework where endocannabinoids modulate neural synchrony at the network level, altering the fine tuning of oscillations and the inhibitory/excitatory balance of neural circuits. These oscillatory disruptions may relate to cannabis-induced changes in sensation, perception, and cognition, with implications for disorders such as schizophrenia.