Psychedelic Symphonies: Investigating LSD and Music-Induced Brain Activity Using fMRI

LSD is a psychedelic drug known for its ability to alter perception and psychological functioning by acting on the serotonin 2A receptor. Historically, LSD and other psychedelics were used in psychiatry, and there is currently a resurgence of interest in their therapeutic potential. Recent studies suggest that psychedelic therapy, often involving the patient lying down with closed eyes and listening to music, can effectively treat various psychiatric disorders. Music may play a crucial role in therapeutic outcomes by facilitating profound emotional or peak experiences. However, the neural mechanisms underlying the interaction between psychedelics and music remain poorly understood but could offer vital insights into brain functioning and therapeutic processes.In this study, we used functional magnetic resonance imaging (fMRI) to investigate the effects of LSD, music, and their interaction on brain activity, specifically focusing on music perception and emotion generation. We included 51 healthy participants from two randomised, double-blind, cross-over, placebo-controlled studies. Participants were MRI scanned approximately two hours after receiving either 100 µg of LSD or placebo. We conducted three analyses to assess the effects of LSD, music, and their interaction: (1) within- and between-network connectivity across eight canonical resting-state networks, (2) seed-based connectivity of limbic (thalamus, nucleus accumbens, amygdala, hippocampus, and parahippocampal gyrus) and cortical structures (superior temporal gyrus and Heschl’s gyrus) involved in music-induced emotion, and (3) two measures of the brain’s low-frequency oscillations, known as ALFF (amplitude of low-frequency fluctuations) and fALFF (fractional ALFF). Additionally, we aimed to replicate previously reported findings on the effects of music and psychedelics.LSD decreased within-network connectivity in the default mode and visual networks while increasing between-network connectivity across various networks. Seed-based analyses revealed that LSD altered the functional connectivity of all investigated limbic and cortical structures. Furthermore, LSD significantly decreased ALFF and fALFF in the occipital lobe and default mode network regions, with decreased ALFF correlating with participants' psychometric scores. However, our results indicate a general lack of music and interaction effects, with significant effects observed only for the auditory cortex. Additionally, we could not replicate prior findings. In conclusion, LSD impacts networks and structures involved in music processing and significantly reduces the power of cortical low-frequency oscillations. However, these effects appear to be largely unaffected by music listening.