Proc Natl Acad Sci U S A
April 11, 2016
Robin L. Carhart-Harris, Suresh Muthukumaraswamy, Leor Roseman et al.
887 citations
LSD produces marked changes in brain activity that correlate with its psychological effects. Increased blood flow in the visual cortex, decreased alpha power there, and an expanded functional connectivity profile of the primary visual cortex strongly correlated with visual hallucinations, suggesting that intrinsic brain activity influences visual processing more during the psychedelic state. Decreased connectivity between the parahippocampus and retrosplenial cortex correlated strongly with ego-dissolution and altered meaning, indicating this circuit's role in maintaining the self and processing meaning. Different imaging metrics showed strong relationships, allowing firmer inferences about their functional significance.
Journal of Medicinal Chemistry
July 1, 1988
David Nichols, D. H. Lloyd, Michael P. Johnson et al.
46 citations
A new method produces pure mirror-image forms of alpha-methyltryptamines (AMTs) from substituted indoles. The key step uses reductive amination with pure enantiomers of alpha-methylbenzylamine, followed by chromatographic separation and catalytic N-debenzylation. Optical purity was confirmed by chiral HPLC. Affinities of the AMT enantiomers were measured at 5-HT2 and 5-HT1B serotonin receptor subtypes in rat frontal cortex homogenates. Enantioselectivity depended on aromatic substituents: for 5-hydroxy or 5-methoxy, the S enantiomer had higher or equal affinity compared to the R enantiomer. For 4-oxygenated AMTs, this selectivity reversed, and 4-hydroxy or 4-methoxy did not improve affinity over unsubstituted compounds. The results suggest a binding conformation where the ethylamine side chain is trans and perpendicular to the indole ring plane.
Psychedelic Med (New Rochelle)
March 13, 2023
Peter S. Hendricks, Charles D. Nichols, Kathryn A. Cunningham et al.
7 citations
A roundtable discussion among experts traces the history, current state, and future directions of psychedelic medicine. Participants review the early research era of the mid-20th century, the subsequent decades of prohibition, and the recent resurgence of clinical trials exploring psychedelics for mental health conditions. The conversation highlights therapeutic applications of substances such as psilocybin and MDMA, emphasizing their potential to treat depression, PTSD, and addiction. Experts also address challenges including regulatory hurdles, the need for trained therapists, and the importance of integrating these treatments into mainstream healthcare. The discussion concludes with cautious optimism about the field's trajectory.