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.
Scientific reports
April 17, 2024
Jordan Sloshower, Richard J Zeifman, Jeffrey Guss et al.
56 citations
Psilocybin-assisted therapy improves psychological flexibility, mindfulness, and values-congruent living in people with moderate to severe major depressive disorder, and these improvements are strongly linked to reductions in depression severity. In an exploratory placebo-controlled study, participants received placebo then psilocybin (0.3 mg/kg) four weeks later, with dosing sessions embedded in Acceptance and Commitment Therapy. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved after psilocybin and were maintained through week 16. The findings suggest that increasing psychological flexibility may be a key mechanism underlying psilocybin's therapeutic effects.