Incilius alvarius cell-based synthesis of 5-MeO-DMT

Introduction

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is the principal psychoactive component of the parotoid gland secretion of Incilius alvarius, where it comprises an estimated 20-30% of the dry weight of the secretion. The compound acts primarily at serotonin receptors, with higher affinity for 5-HT1A than 5-HT2A, and is metabolised by CYP2D6 to bufotenine. Interest in serotonergic psychedelics has risen because preclinical and clinical work suggests they promote neuroplasticity and may have therapeutic potential for mood and anxiety disorders; 5-MeO-DMT is described as pharmacodynamically distinct from other psychedelics due to its rapid onset, short duration and particular transcriptomic effects. This study was undertaken against a backdrop of ecological concern: demand for natural toad secretion for recreational, self-medication and spiritual use places Incilius alvarius under pressure. Lerer and colleagues set out to establish a cell line derived from Incilius alvarius parotoid gland tissue and to determine whether those cells could synthesise 5-MeO-DMT in vitro, providing a potential cruelty-free and sustainable source of naturally derived 5-MeO-DMT and associated parotoid compounds (so-called entourage molecules).