Pharmacogenetics
August 1, 2001
Yamini Ramamoorthy, Rachel F. Tyndale, Edward M. Sellers
92 citations
The CYP2D6 enzyme metabolizes many drugs, including antidepressants and amphetamines. A common variant, CYP2D6*10, found in about 75% of Asians, has Pro34Ser and Ser486Thr substitutions. In vitro tests using a baculovirus system showed that CYP2D6.10 has much lower intrinsic clearance than the wild-type CYP2D6.1 for several substrates: for dextromethorphan, the clearance ratio was 50; for MDMA, 123; for p-hydroxylation of methamphetamine, ratios ranged from 30 to 67; for N-demethylation, from 60 to 157, showing pathway and enantiomer selectivity. Inhibition susceptibility also varied: for debrisoquine, the Ki ratio was 8.1; for fluoxetine, 16; for norfluoxetine, 30. These findings suggest that individuals with CYP2D6*10/*10 may need different drug doses and have altered risks for toxicity, interactions, and amphetamine dependence compared to those with CYP2D6*1/*1.
Frontiers in Pharmacology
February 26, 2021
Guy A. Higgins, Nicole K. Carroll, Matthew A. Brown et al.
67 citations
Low doses of the hallucinogens ketamine and psilocybin, too small to cause perceptual effects, modestly improved motivation, attention, and impulse control in low-performing male rats. In two food-rewarded tasks, acute doses of ketamine (1–3 mg/kg) and psilocybin (0.05–0.1 mg/kg) increased break point for food and improved attentional accuracy. The benefits were small and mainly seen in rats that initially performed poorly. Both drugs produced similar patterns of effect. These findings support the idea that low, sub-perceptual doses of these drugs may have therapeutic potential for depression-related symptoms like anhedonia and cognitive dysfunction, though further research is needed.
Clinical Pharmacology & Therapeutics
August 24, 2017
Edward M. Sellers, Deborah B. Leiderman
27 citations
Interest in the potential therapeutic benefits of psychedelic agents has recently increased. Besides psilocybin, many other agents with psychedelic properties have been proposed and partially tested. However, obtaining approval to market a restricted psychotomimetic agent faces formidable challenges.
Neuropharmacology
January 21, 2023
Edward M. Sellers, Myroslava K. Romach
21 citations
Developing microdoses of psychedelics could overcome many scientific and regulatory hurdles that hinder high-dose psychedelic drug development. If microdosing proves efficacious and safe for long-term use, it could be administered through the typical outpatient model for mental disorders, which would be more cost-effective than the high-dose/intense psychotherapy model. Outpatient psychotherapeutic agents have a clear approval route and would likely avoid the extensive Risk Evaluation and Mitigation Strategy required for high-dose use. The article suggests there may be different therapeutic roles for both high and low dose psychedelic agents.