The pace of psychedelic research continued its acceleration during 2021, culminating in several fascinating and groundbreaking studies. As the year comes to a close, Psychedelic Science Review is acknowledging some of the outstanding research papers of 2021.
This year, the Editor’s Choice Award for the best study on psychedelics and pharmacology goes to Dr. Adam Klein of the Department of Psychiatry at the Unversity of California San Diego and his research team, Muhammad Chatha, Lauren Laskowski, Emilie Anderson, Simon Brandt, Stephen Chapman, John McCorvy, and Adam Halberstadt. Their paper reported on the results of their work studying the SAR (structure-activity relationship) of 17 structurally related tryptamine compounds, all analogs of the magic mushroom compound psilocybin.1
The tryptamines used in the study were all 4-substituted N,N-di-alkyltryptamines. Chemically, these compounds can be further divided into two categories, 4-acetoxy (4-AcO) substituted and, 4-hydroxy (4-HO) substituted. The compounds they tested included 4-AcO-DMT (psilacetin), 4-HO-DMT (psilocin), 4-HO-DPT, and 4-HO-MiPT.
SARs are essential in medical and pharmaceutical research because they show how the chemical structure of a compound relates to its biological activity. Earlier this year, Psychedelic Science Review ran an article summarizing the findings of the Klein et al. study. Here are the highlights:
- All compounds behaved as full or partial agonists at the serotonin receptors, displaying similar potencies at 5-HT2A and 5-HT2B.
- Some compounds with bulkier N-alkyl groups (e.g., N,N-diisopropyl) had lower potency at 5-HT2C and higher 5-HT2B receptor efficacy.
- Compared to their 4-HO analogs, the 4-AcO compounds exhibited reduced in vitro 5-HT2A potency by about 10- to 20-fold.
- In contrast, the 4-AcO and 4-HO compounds exhibited similar agonist efficacy in vivo, as shown in the HTR (head-twitch response) experiments, “suggesting that O-acetylated tryptamines may be deacetylated in vivo, acting as prodrugs.”
In concluding, Dr. Klein and the research team stated, “…the tryptamine derivatives have psilocybin-like pharmacological properties, supporting their classification as psychedelic drugs.”