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.
Biological psychiatry
April 1, 2016
Mohamed Sherif, Rajiv Radhakrishnan, Deepak Cyril D'Souza et al.
127 citations
Controlled laboratory studies in healthy humans show that cannabinoid agonists—both plant-derived and synthetic—produce positive, negative, and cognitive symptoms resembling schizophrenia. These effects are time-locked to drug administration, dose-related, and transient. The magnitude of effects is similar to ketamine but qualitatively distinct from other psychotomimetic drugs. In individuals with schizophrenia, cannabinoid agonists transiently worsen symptoms despite antipsychotic treatment, and no beneficial effects have been found, challenging the self-medication hypothesis. Genetic polymorphisms in dopamine-related genes (COMT, DAT1, AKT1) may moderate these effects. Cannabinoid-induced dopamine release does not fully account for the psychotomimetic effects; interactions among endocannabinoid, GABA, and glutamate systems affecting neural oscillations offer a plausible mechanism.
Biological psychiatry
November 15, 2012
Mohini Ranganathan, Ashley Schnakenberg, Patrick D Skosnik et al.
125 citations
Inhaled salvinorin A, the active ingredient in Salvia divinorum, produces transient psychotomimetic and perceptual alterations including dissociative and somaesthetic effects, increases plasma cortisol and prolactin, and reduces resting electroencephalogram spectral power. It does not cause euphoria, cognitive deficits, or changes in vital signs, and the effects are not dose-related. The substance is very well-tolerated without acute or delayed adverse effects, and its lack of euphoric effects suggests a low addictive potential similar to other hallucinogens.
Journal of Psychopharmacology
November 30, 2016
Benjamin Kelmendi, Philip R. Corlett, Mohini Ranganathan et al.
11 citations
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Psychopharmacology
October 1, 2024
Ardavan Mohammad Aghaei, Lia Urban Spillane, Brian Pittman et al.
9 citations
After a single 10 mg oral dose of THC, women reported a heightened subjective feeling of being 'high' compared to men, while psychotomimetic and physiological effects were similar across sexes. No sex differences appeared in verbal learning and memory. The findings suggest that women may experience a more pronounced subjective psychoactive response to THC, pointing to individual vulnerabilities that could inform tailored interventions for cannabis use disorder.
iScience
January 16, 2026
Amir Valizadeh, John D Roache, Xinyu Zhang et al.
2 citations
Post-traumatic stress disorder varies greatly in its clinical and biological features, making treatment difficult. The largest randomized trial of ketamine for PTSD found no overall benefit over placebo, highlighting the need to identify which patients might respond. Using pre-treatment blood DNA methylation profiles and clinical data from that trial, machine learning models predicted treatment response. A model based on 1,208 methylation sites outperformed models using only clinical variables, and combining both data types improved accuracy further. The methylation-derived score identified responders with 92.9% accuracy. Predictive methylation sites were near genes involved in glutamatergic signaling, immune regulation, and known PTSD risk loci, suggesting peripheral DNA methylation patterns can guide precision pharmacotherapy for PTSD.
medRxiv Preprint Server
April 10, 2020
Chadi G. Abdallah, Kyung-Heup Ahn, Lynnette A. Averill et al.
1 citation
preprint
A robust and reproducible brain connectivity fingerprint (CFP) was identified during ketamine infusion in healthy participants, characterized by reduced connectivity within primary cortices and the executive network, but increased connectivity between the executive network and the rest of the brain. This same CFP measured one week after treatment in major depressive disorder patients predicted response to eight weeks of sertraline, but not placebo. The findings suggest a brain network biomarker that links ketamine's acute effects to the mechanisms of conventional antidepressants.