Naunyn-Schmiedeberg's archives of pharmacology
May 1, 2024
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
31 citations
Serotonergic psychedelics like psilocin (the active metabolite of psilocybin), DOI, and TCB-2 produce antidepressant-like effects in mice by activating the 5-HT2A receptor. Twenty-four hours after a single injection, treated mice showed significantly less immobility in the forced swimming test and tail-suspension test—indicating reduced behavioral despair—compared to control mice. Blocking the 5-HT2A receptor with volinanserin eliminated these antidepressant-like effects. Psilocin's effect in the forced swimming test lasted at least three weeks. In the novelty-suppressed feeding test, psilocin reduced feeding latency (an anxiolytic-like effect), but volinanserin did not block this, and DOI and TCB-2 had no effect. None of the drugs altered spontaneous movement or head-twitch response. The findings suggest 5-HT2A activation mediates antidepressant but not anxiolytic effects of these psychedelics.
Research Square (Research Square)
July 7, 2023
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
4 citations
Serotonergic psychedelics like psilocin, DOI, and TCB-2 produce antidepressant-like effects in mice by activating the serotonin 5-HT2A receptor. Mice given a single injection of these drugs showed less immobility in the forced swimming and tail-suspension tests 24 hours later, effects blocked by a 5-HT2A antagonist. The antidepressant-like effect of psilocin lasted at least three weeks. However, only psilocin reduced anxiety-like behavior in the novelty-suppressed feeding test, and this effect was not blocked by the 5-HT2A antagonist. The drugs did not alter spontaneous movement or head-twitch responses. The findings indicate 5-HT2A mediates antidepressant but not anxiolytic effects of these psychedelics.
Folia Pharmacologica Japonica
June 30, 2024
Daisuke Ibi
1 citation
Psilocybin, the hallucinogenic compound in magic mushrooms, shows rapid and lasting antidepressant effects in patients with treatment-resistant depression, with only transient mild side effects like headache and fatigue. The U.S. FDA designated it a breakthrough therapy for major depressive disorder and treatment-resistant depression. This review presents clinical and preclinical research on psilocybin's antidepressant effects, focusing on the role of serotonin 5-HT2A receptors, and discusses the potential and challenges of psilocybin therapy.
Folia Pharmacologica Japonica
March 28, 2023
Daisuke Ibi
1 citation
Psilocybin, the psychoactive substance in magic mushrooms, shows fast-acting and long-lasting antidepressant effects in patients with major depressive disorder, including those resistant to conventional treatment. It is considered relatively harmless compared to ketamine and other similar substances. The FDA has designated psilocybin as a breakthrough therapy for major depressive disorder. Serotonergic psychedelics like psilocybin and lysergic acid diethylamide also show potential for treating depression, anxiety, and addiction. Pharmacologically, these drugs cause hallucinations by stimulating cortical serotonin 5-HT2A receptors, but whether this receptor is responsible for therapeutic effects remains unclear. This review summarizes clinical and pre-clinical studies on psychedelics for psychiatric disorders and discusses 5-HT2A as a potential therapeutic target.
Proceedings for Annual Meeting of The Japanese Pharmacological Society
January 1, 2022
Daisuke Ibi
Psilocin, the active metabolite of psilocybin, produces antidepressant effects in mice by activating serotonin 5-HT2A receptors on GABAergic neurons in the lateral septum that project to the dorsomedial hypothalamic nucleus. Selectively inhibiting this pathway eliminated the antidepressant-like effect in forced-swim and social defeat stress tests, while activating it induced antidepressant-like effects. Microinjection of bicuculline, a GABAA receptor antagonist, into the dorsomedial hypothalamic nucleus diminished psilocin's antidepressant effect. These findings suggest that this specific neural network underlies the antidepressant action of serotonergic psychedelics, separate from their hallucinatory effects mediated by the visual cortex.
Proceedings for Annual Meeting of The Japanese Pharmacological Society
January 1, 2022
Daisuke Ibi
The FDA has approved psilocybin, the psychoactive compound in magic mushrooms, as a breakthrough therapy for depression, but its detailed mechanism remains unknown. Serotonergic psychedelics like psilocybin and LSD produce hallucinatory effects by stimulating the serotonin 5-HT2A receptor. In mice, 5-HT2A agonists such as DOI and psilocin (the active metabolite of psilocybin) reduced immobility time in the forced-swim test, an effect absent when the 5-HT2A gene was knocked down in the lateral septum. Activating Gq signaling in 5-HT2A-positive neurons in the lateral septum produced antidepressant and anxiolytic effects. Most 5-HT2A-positive cells in the lateral septum are GABAergic inhibitory neurons, suggesting their activation underlies the antidepressant effect.