ACS Pharmacology & Translational Science
July 8, 2025
Miyuan Zhang, Haiyan Zhai, Liu Yang et al.
1 citation
Psilocin, the active metabolite of psilocybin, induces psychedelic-like behavior in male mice by activating neurons in the medial prefrontal cortex (mPFC). Using c-Fos immunofluorescent labeling, the mPFC was the only brain region among several tested that was specifically associated with the head twitch response (HTR), a behavioral marker of psychedelic activity. A picomolar dose of psilocin directly into the mPFC triggered significant HTR. Optogenetic activation of these neurons increased spontaneous HTR, while acute inhibition suppressed drug-induced HTR. The findings establish the mPFC as a critical regulator of psilocin's psychedelic effects, offering insights for improving the clinical safety and therapeutic use of psychedelics.
ACS Pharmacology & Translational Science
April 14, 2026
Abhishek Gupta, Tuhin Bhattacharya, Subhamoy Pratihar et al.
Iboga alkaloids can reverse drug addiction and modulate drug tolerance, but their use is limited by severe psychedelic effects and cardiotoxicity from hERG potassium channel blockade. Researchers synthesized four modified ibogaine/ibogamine analogs (C1–C4) with a benzofuran moiety replacing the indole scaffold. Among these, the Endo-iboga analogs C2 and C4 showed notable anti-inflammatory and oxidative stress-relieving activity and improved restricted locomotor activity in a formalin-induced acute pain model in mice. C4 exhibited superior cytocompatibility (IC50 = 235 μM in C2C12 cells), no significant QTc prolongation in rat ECG tests, and the lowest hERG blockade risk (IC50 = 21.25 ± 4.89 μM). C4 acted as a potent KOR agonist and MOR antagonist, with weak 5HT2A agonist and σ1 antagonist activity, suggesting potential for acute pain management without notable cardiotoxicity.
ACS Pharmacology & Translational Science
December 29, 2020
Justin C. Strickland, A. Garcia-Romeu, Matthew W. Johnson
Psilocybin, a serotonin 2A receptor agonist, shows promise as a psychiatric treatment, but little is known about how session context ("set and setting") affects outcomes. In a study on smoking cessation, ten participants received psilocybin (20–30 mg/70 kg) in two sessions, each with a different musical genre—Western classical or overtone-based—in counterbalanced order. Mystical experience scores tended to be higher during overtone-based sessions. Six of ten participants chose overtone-based music for a third session. Biologically confirmed smoking abstinence was similar between groups, with a slight benefit for those choosing overtone-based music (66.7% versus 50%). The findings question whether Western classical music typically used in psychedelic therapy is uniquely beneficial.