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.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
January 1, 2021
Emmanuelle A D Schindler, R Andrew Sewell, Christopher H Gottschalk et al.
138 citations
In a small exploratory double-blind, placebo-controlled, cross-over study, ten adults with migraine received a single oral dose of psilocybin (0.143 mg/kg) or placebo, with sessions two weeks apart. Over the two weeks following administration, psilocybin reduced weekly migraine days by an average of 1.65 days (95% CI: -2.53 to -0.77), significantly more than placebo, which reduced them by 0.15 days (95% CI: -1.13 to 0.83). The reduction in migraine frequency was not linked to the intensity of acute psychedelic effects. Psilocybin was well-tolerated with no serious adverse events. The findings suggest a lasting therapeutic benefit from a single dose, independent of acute psychological effects.
Neuropharmacology
July 1, 2021
Írisz Szabó, Viktória É Varga, Szabolcs Dvorácskó et al.
67 citations
Dimethyltryptamine (DMT), a natural compound that activates sigma-1 receptors, reduced spreading depolarizations—waves of electrical disruption in the brain that worsen stroke injury—in rats subjected to global forebrain ischemia. DMT also decreased the number of dying cells and supported astrocyte survival. The protective effects were shared by a selective sigma-1 receptor agonist and were blocked by a sigma-1 receptor antagonist, indicating the receptor mediates the protection. DMT remained effective even when serotonin receptors were blocked. These results suggest DMT could be an additional treatment for acute stroke.
Neuropharmacology
November 1, 2018
Landon M Klein, Nicholas V Cozzi, Paul F Daley et al.
43 citations
Most DALT derivatives bind to several serotonin receptors, sigma sites, and other targets. In mice, several compounds triggered the head-twitch response, a behavioral proxy for hallucinogen effects, with 4-acetoxy-DALT being most potent, followed by 5-fluoro-DALT, 5-methoxy-DALT, 4-hydroxy-DALT, DALT, and 5-bromo-DALT; four derivatives did not induce the response. Head-twitch potency was not linked to binding affinity at either 5-HT1A or 5-HT2A receptors alone, but a regression analysis showed that 5-HT2A receptors contribute positively and 5-HT1A receptors contribute negatively to potency, explaining 87% of the variance. These results support the role of 5-HT2A receptors in the head-twitch response and suggest that 5-HT1A activation by tryptamine hallucinogens dampens this effect.
Journal of the neurological sciences
May 15, 2024
Emmanuelle A D Schindler, R Andrew Sewell, Christopher H Gottschalk et al.
37 citations
In a blinded extension of a prior randomized trial, ten people with cluster headache received a second round of three doses of psilocybin (10 mg/70 kg, five days apart) at least six months after their first round. Attack frequency dropped significantly from a baseline of 18.4 attacks per week to 9.8 attacks per week in the three weeks after the first dose, a reduction of about 50%. This benefit occurred regardless of whether the participant had responded to psilocybin in the first round. No serious or unexpected adverse events occurred. The findings suggest that repeating a pulse of psilocybin can substantially reduce cluster headache attacks and that prior response does not predict the effect of retreatment.