In recent decades, the use of ayahuasca (AYA) – a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes – has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity.

The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging.

Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection.

The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity.

Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations.