5-MeO-DMT

"5-MeO-DMT is a psychedelic compound with ultra-rapid onset and short duration of psychoactive effects that was first synthesized in 1936 by Japanese chemists Hoshino and Shimodaira (1936). Depending on the route of administration, 5-MeO-DMT’s acute effects may begin within 30 s and be over within 20 min (vaporization route), or begin within 3–5 min and subside within 45–60 min (insufflation, intramuscular [IM] injection route) (Ermakova et al., 2022, Reckweg et al., 2021, Reckweg et al., 2022). 5-MeO-DMT's short duration results from rapid metabolism by Monoamine Oxidase A (MAO-A) and CYP2D6 (Shen et al., 2010). This rapid onset and short duration of acute effects are viewed by some psychedelic researchers as factors that could enhance the accessibility and scalability of psychedelic-assisted treatments (Davis et al., 2019).

"In contrast to other more extensively studied psychedelics, like psilocybin, the active ingredient in psychoactive mushrooms (e.g., Psilocybe cubensis), whose main site of action in the mammal brain is the serotonin receptor subtype 2 A (5-HT2A), 5-MeO-DMT is primarily active at the 5-HT1A (Dakic et al., 2017, Krebs-Thomson et al., 2006, Szabo et al., 2014). Additionally, 5-MeO-DMT has been found to be active at the Sigma 1 receptor (sigmar-1), where it is believed to be involved in anti-inflammatory processes that may contribute to its potential therapeutic action (Dakic et al., 2017, Szabo et al., 2014).

"The phenomenology of 5-MeO-DMT has been described as distinct from other highly visual tryptamines including its closely related compound, N,N-dimethyltryptamine (DMT), but without visual effects (Ermakova et al., 2022). While 5-HT2A is abundant in the visual cortex, 5-HT1A’s low expression may explain the lack of visuals in 5-MeO-DMT experiences (Carhart-Harris & Nutt, 2017). Mechanistic studies on 5-MeO-DMT are still lacking, though research is expanding via advanced imaging techniques. Electroencephalography (EEG) studies on 5-MeO-DMT conducted in naturalistic settings (i.e., outside clinical research contexts) have recently been reported by Timmermann et al. (2025), who observed widespread reductions in alpha and posterior beta oscillatory power, patterns that align with Acosta-Urquidi’s (2015) earlier EEG recordings, also in naturalistic settings, which showed marked alpha suppression and shifts in beta and gamma activity (Acosta-Urquidi, 2015, Timmermann et al., 2025). Such reductions in organized oscillatory activity and increases in neural signal diversity have been proposed to be associated with a temporary breakdown of predictive processing in the brain (Carhart-Harris & Friston, 2019), which may underlie the profound alterations in self-experience, affect, and perception that characterize the acute subjective effects of 5-MeO-DMT (Ermakova et al., 2022).

"Consistent with these neural and theoretical accounts, the 5-MeO-DMT subjective experience is often described as transcendent, involving elements of “mystical-type” experiences, ego-dissolution and nondual awareness with an increased range of emotions from awe, love and unity to panic and terror (Delgrasso, 2024, Ermakova et al., 2022). A somatic response ranging from release in muscle tension, shaking or trembling, to primal screaming, dancing (or even running) can also accompany the experience."