Abstract

N,N-Dimethyltryptamine(DMT) is a naturally occurring psychedelic with psychoactive properties thought to be mediated via the serotonergic-pathway and serotonin 5-HT2A receptor agonism. It is associated with intense visual phenomena, perceptual changes and spiritual experiences. Visual percepts induced by DMT are characterized by a significant mismatch between physical object properties and their internal representations.

Despite current efforts, the neural correlates of these hallucinatory experiences in relation to hallucinatory pathophysiology and real visual experience remain elusive. Here we investigate the neural correlates of altered visual experiences induced by inhaled-DMT, using fMRI to measure brain activity. A within-subject study was conducted at ICNAS/CIBIT-UC with 11 healthy, DMT-experienced volunteers. 2 sessions were conducted: Active-substance (inhaled-DMT) and Control (same protocol–sham).

For the active session, DMT was self-administered by participants (~50-70mg of DMT-based extract). Percentage of DMT was quantified by high-performance liquid chromatography(HPLC-DAD), confirming an amount of 30.92%. In both sessions, pre-and post-measures of subjective experience were collected using the Vividness of Visual Imagery Questionnaire(VVIQ-RV) and the Hallucinogen Rating Scale(HRS). Contextual influence was accessed via a self-report questionnaire to address expectation factors’ contribution to subjective experience. BOLD response was measured in a 3T-MR and the fMRI task consisted of a block-design with empty-field flicker stimuli. Repeated-measures ANOVA with factors HRS x Conditions showed main effects for Condition, HRS-subscales and an interaction effect of Condition x HRS.

Direct comparison of Perception subscale scores highlight the distinct perceptual phenomenology between conditions. Specific analysis of visual domain items between conditions (visual cluster items : 57-68) supported the previous effect. Linear regression of Expectations on HRS and Visual Cluster was not significant. fMRI analysis contrasting DMTvsControl showed significant BOLD activity in extrastriate-cortex BA18,19, fusiform BA37 and parietal area BA7. These results suggest a neural basis for visual effects induced by inhaled-DMT, including associative visual cortex and parietal regions involved in imagery which can provide relevant insights for future research and therapeutic models targeting mental health conditions, as well as the study of visual consciousness.