ACS chemical neuroscience
February 1, 2023
Lindsay P Cameron, Seona D Patel, Maxemiliano V Vargas et al.
113 citations
Activation of serotonin 2A receptors (5-HT2ARs) is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. While hallucinogenic properties are generally attributed to 5-HT2AR activation, it was unclear whether these receptors also mediate antidepressant effects, especially because some nonhallucinogenic analogues show antidepressant-like properties. Using pharmacological and genetic tools, the authors demonstrate that 5-HT2AR activation is required for the antidepressant-like effects of tryptamine psychedelics, suggesting that hallucinogenic and therapeutic effects can arise through the same receptor.
Journal of neurochemistry
July 1, 2022
Hannah N Saeger, David E Olson
59 citations
Psychedelics show promise for treating depression, PTSD, and substance use disorder, potentially by reversing cortical atrophy through effects on neurotrophic factors, neuronal growth, and immune modulation. This review argues that similar approaches could benefit neurodegenerative disorders like Alzheimer's disease, where the primary psychedelic target, the 5-HT2A receptor, is dysregulated. Evidence also suggests psychedelics might help manage behavioral and psychological symptoms of dementia (BPSD). The authors call for more research in neurodegenerative models, emphasizing that the compounds' robust effects on neuroplasticity and inflammation warrant further investigation.
ACS chemical neuroscience
October 15, 2025
Cassandra J Hatzipantelis, Lindsay P Cameron, Min Liu et al.
A new genetic mouse model lacking the enzyme indolethylamine N-methyltransferase (INMT) shows that INMT is not required for the production of endogenous psychedelics, suggesting alternative biosynthetic pathways exist in rodents. INMT knockout mice had no major abnormalities in reproduction or growth but did exhibit altered behaviors across several domains. The study also describes highly sensitive mass spectrometry methods for quantifying endogenous psychedelics in mice. These findings challenge the assumption that INMT is the primary enzyme for endogenous psychedelic production and open new questions about the role of these compounds in health and disease.