JAMA
August 31, 2023
Charles L Raison, Gerard Sanacora, Joshua Woolley et al.
493 citations
A single 25-mg dose of synthetic psilocybin, administered with psychological support, produced a clinically significant and sustained reduction in depressive symptoms and functional disability over 43 days in adults with major depressive disorder. In a phase 2 trial of 104 participants, those receiving psilocybin showed a mean 12.3-point greater improvement on the Montgomery-Asberg Depression Rating Scale at day 43 compared with those receiving a niacin placebo. Psilocybin also improved daily functioning and led to more sustained response, though not remission. No serious adverse events occurred, but psilocybin was associated with more overall and severe adverse events.
ACS Omega
December 2, 2020
Alexander M. Sherwood, Romain Claveau, Rafael Lancelotta et al.
38 citations
A multigram-scale process was developed to produce 5-MeO-DMT, a psychedelic natural product from the toad Incilius alvarius, for clinical use. An optimized Fischer indole reaction yielded 5-MeO-DMT freebase, which was converted to the 1:1 succinate salt, producing 136 g of crystalline active pharmaceutical ingredient with 99.86% purity by HPLC and a net yield of 49%. The report details in-process monitoring, validated analytical methods, impurity formation and removal, and solid-state characterization essential for clinical development.
ACS Omega
February 7, 2022
Robert B. Kargbo, Alexander M. Sherwood, Poncho Meisenheimer et al.
5 citations
A thermodynamically controlled crystallization process for psilocybin, a serotonergic agonist granted breakthrough therapy status for depression, produces crystals with stronger interactions, a controlled particle size distribution, and an improved impurity profile compared to a faster, kinetically controlled process that yields smaller particles. Real-time monitoring with high-resolution inline microscopy measured particle size and metastable zone width and nucleation induction. Water recrystallization forms polymorph B (trihydrate) independently of the method, while polymorph A (anhydrate) and polymorph H (anhydrate) depend on drying: room-temperature vacuum drying yields mainly polymorph A, and heating even at low temperatures produces a mixture of polymorphs A and H.