Noribogaine effects on wakefulness and sleep

Noribogaine, the main metabolite of the psychedelic ibogaine, promotes wakefulness and reduces slow-wave sleep while completely blocking REM sleep in rats. These sleep-wake alterations mirror those caused by ibogaine itself, suggesting that noribogaine is responsible for the sleep-suppressing effects previously attributed to ibogaine. The findings point to serotonin reuptake inhibition as a likely mechanism underlying the wake-promoting and REM sleep-suppressing actions of both compounds.

Study at a glance

Abstract

Abstract Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects and a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine remains unknown. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep. Thus, like ibogaine, noribogaine significantly alters the sleep-wake architecture, highlighting the possible role of serotonin reuptake inhibition as a likely candidate underlying the wake-promoting and REM sleep-suppressing effects.