People who use ayahuasca in a neo-shamanic group and a Santo Daime church in Uruguay differ in personality and acute psychological effects. Santo Daime members scored lower on Neuroticism-Anxiety, Dependence, Low Self-Esteem, Anger, and Restlessness, possibly due to the protective effects of a structured church religion or because some neo-shamanic participants were undergoing treatment. During rituals, the neo-shamanic group reported stronger somesthesia and perception, linked to their high-arousal setting. Chemical analysis found typical alkaloids with no adulterants; the neo-shamanic sample had a higher β-carbolines-to-DMT ratio, which may explain the stronger somesthetic effects. Personality and acute effects correlated only in the neo-shamanic group, suggesting a more individualistic tradition.
Ibogaine and its main metabolite noribogaine inhibit the vesicular monoamine transporter 2 (VMAT2) with submicromolar potency, as shown in cell-based assays and two-photon microscopy of mouse brain synaptic vesicle clusters. Noribogaine also induces partial serotonin release from synaptic vesicles and binds VMAT2 at a distinct site from the established inhibitor dihydrotetrabenazine. These compounds additionally inhibit plasma membrane monoamine transporters, prominently the serotonin transporter (SERT), and a novel target, organic cation transporter 2 (OCT2). Several iboga analogs display dual inhibition of VMAT2 and SERT with comparable potencies, termed "Synaptic Reuptake Inhibitors" (SynRIs). This profile explains why ibogaine and noribogaine do not induce catalepsy, unlike other VMAT2 inhibitors, and illustrates the complex "matrix pharmacology" of iboga compounds.