Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status.
Drug metabolism and disposition: the biological fate of chemicals May 1, 2013 Xi-Ling Jiang, Hong-Wu Shen, Donald E Mager et al. 29 citations
Coadministration of the MAO-A inhibitor harmaline sharply increases systemic and brain exposure to the designer drug 5-MeO-DMT and its active metabolite bufotenine in mice. The effect is stronger in wild-type mice than in CYP2D6-humanized mice, because CYP2D6 breaks down 5-MeO-DMT into bufotenine. Surprisingly, a higher harmaline dose (15 mg/kg) reduces bufotenine levels, an effect confirmed in vitro as harmaline also inhibits CYP2D6. A unified pharmacokinetic model describing these interactions was developed and may help predict drug interactions at various doses and in different CYP2D6 genotypes.