Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans

Regular use of the psychedelic brew ayahuasca is associated with thinning of the posterior cingulate cortex (PCC), a key hub of the default mode network. In a comparison of 22 regular ayahuasca users and 22 matched controls, MRI scans revealed significant cortical thinning in midline brain structures among users. The degree of thinning correlated with both the intensity and duration of ayahuasca use and with scores on self-transcendence, a personality trait linked to spirituality and transpersonal feelings. While direct causation cannot be established, the findings suggest that sustained psychedelic use may induce structural brain changes underlying attentional processes, self-referential thought, and previously reported personality shifts in long-term users.

Study at a glance

Abstract

Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.