Rostral Anterior Cingulate Thickness Predicts the Emotional Psilocybin Experience

Abstract

Psilocybin is the psychoactive compound of mushrooms in the psilocybe species. Psilocybin directly affects a number of serotonin receptors, with highest affinity for the serotonin 2A receptor (5HT-2Ar). Generally, the effects of psilocybin, and its active metabolite psilocin, are well established and include a range of cognitive, emotional, and perceptual perturbations. Despite the generality of these effects, there is a high degree of inter-individual variability in subjective psilocybin experiences that are not well understood. Others have shown brain morphology metrics derived from magnetic resonance imaging (MRI) can predict individual drug response. Due to high expression of serotonin 2A receptors (5HT-2Ar) in the cingulate cortex, and its prior associations with psilocybin, we investigate if cortical thickness of this structure predicts the psilocybin experience in healthy adults. We hypothesized that greater cingulate thickness would predict higher subjective ratings in sub-scales of the Five-Dimensional Altered State of Consciousness (5D-ASC) with high emotionality in healthy participants (n = 55) who received oral psilocybin (either low dose: 0.160 mg/kg or high dose: 0.215 mg/kg). After controlling for sex, age, and using false discovery rate (FDR) correction, we found the rostral anterior cingulate predicted all four emotional sub-scales, whereas the caudal and posterior cingulate did not. How classic psychedelic compounds induce such large inter-individual variability in subjective states has been a long-standing question in serotonergic research. These results extend the traditional set and setting hypothesis of the psychedelic experience to include brain structure metrics.

Dose–response relationships of psilocybin-induced subjective experiences in humans

“…Further, differences in individual pharmacokinetics were reported in terms of plasma psilocin levels and 5-HT2AR occupancy, which were found to correlate with the overall subjective experience ( Brown et al, 2017 ; Hasler et al, 2004 ; Lindenblatt et al, 1998 ; Madsen et al, 2020 ). Finally, brain structure metrics have been reported to correlate with experiences, that is, a correlation of the thickness of the rostral anterior cingulate and subscales of 5D-ASC dimension Oceanic Boundlessness ( Lewis et al, 2020 ).…”

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

“…Further efforts should be devoted to identifying biological biomarkers and psychological predictors of psychedelicinduced subjective effects (such as rostral ACC thickness), as well as dissociation, negative experiences, and psychoses. This could help identify patients more likely to encounter challenging experiences (such as those with high neuroticism, emotional instability, and family history of psychosis, bipolar disorders, and childhood trauma) and implement adequate strategies to maximize therapeutic improvement while minimizing potential biological and psychological short-and longterm side effects (Barrett et al, 2017;Thal et al, 2019;Lewis et al, 2020).…”

Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

“…Moreover, the rostral ACC (rACC) sub-area of the ACC is related to emotional expression (A. Etkin et al, 2006) and-under psilocybin-has been related to subjective scores on emotional subcategories of the 5D-ASC (more on this below) (Lewis, Preller, Braden, Riecken, & Vollenweider, 2020). Magnetic resonance spectroscopy (MRS), after ingestion of ayahuasca, showed increased connectivity between the ACC and MTL regions associated with enhanced self-compassion (Sampedro et al, 2017).…”