Proceedings of the National Academy of Sciences of the United States of America
September 8, 2026
Andrian G Basargin, Andras Domokosa, Joseph J Hennessey et al.
Of the classic psychedelics, lysergic acid diethylamide (LSD) is perhaps the best-known, but its complex chemical architecture has limited synthetic investigations aimed at generating analogues with improved safety and efficacy profiles. Here, we systematically deconstruct the tetracyclic ergoline core of LSD to create 9 simplified ergoline analogues (i.e., ergologs) and evaluate them in...
Journal of Science Policy & Governance
July 2, 2026
Alaina M Jaster, Joseph J. Hennessey, Tanner L. Anderson et al.
Research on Schedule I substances in the United States remains heavily restricted by the regulatory structure imposed by the Controlled Substances Act (CSA). This regulatory system creates significant Research Harm, which can be defined as the restriction or deterrence of legitimate scientific inquiry arising from governmental actions, such as regulatory controls or criminal prohibitions that...
ACS Chem Neurosci
September 13, 2025
Emma M. Bonniwell, Rana Alabdali, Joseph J. Hennessey et al.
3 citations
The serotonin 2C receptor (5-HT 2C ) is a G protein-coupled receptor implicated in multiple physiological and psychological processes and has been investigated as a therapeutic target for neuropsychiatric conditions such as obesity, drug abuse, and depression. With renewed interest in serotonergic psychedelics for treating depression, 5-HT 2C may contribute to psychedelic-induced therapeutic...
Nature Neuroscience
September 1, 2025
Isak K Aarrestad, Lindsay P. Cameron, Ethan M Fenton et al.
Nonhallucinogenic psychoplastogens, such as tabernanthalog (TBG), are being developed as potentially safer, more scalable alternatives to psychedelics for promoting neuronal growth and treating various brain conditions. Currently, it is unclear whether 5-hydroxytryptamine 2A (5-HT2A) receptors and immediate early gene (IEG) activation have a role in the neuroplasticity-promoting effects of...
Nat Commun
December 15, 2023
Jason Wallach, Andrew B. Cao, Maggie M. Calkins et al.
153 citations
Abstract Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT 2A receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT 2A -Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT 2A -selective ligands with varying Gq efficacies, including β-arrestin-biased...
bioRxiv (Cold Spring Harbor Laboratory)
July 31, 2023
Jason Wallach, Andrew B. Cao, Maggie M. Calkins et al.
11 citations
preprint
Summary Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT 2A receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT 2A -Gq/11 and β-arrestin2 signaling, making their respective roles unclear. To elucidate this, we developed a series of 5-HT 2A -selective ligands with varying Gq efficacies, including β-arrestin-biased...
Science
February 16, 2023
Maxemiliano V. Vargas, Lee E. Dunlap, Chunyang Dong et al.
467 citations
Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently...