The neuropharmacological basis of psychedelic-induced visual hallucinations

Psychedelic substances such as psilocybin, LSD and DMT are known for their perceptual effects, mainly the experience of visual hallucinations that can vary from simple geometrical patterns to more complex imagery; these can happen either with open or closed eyes. It is widely accepted that these drugs exert their effects by acting as agonists on serotoninergic synapses at 5-HT2A receptor subtype, which has been proposed to be mainly sited in primary visual cortex. Although, recent studies pointed out that different types of visual hallucinations depend on the dosage ranges and that with higher doses the agonist action on 5-HT2A is seen more broadly on the brain, suggesting a top-down control during complex visual imagery. In this review previous knowledge is integrated with recent literature that includes new approaches and methods to better understand the underlying neurophysiological mechanisms that follow pharmacological interactions of selective 5-HT2A hallucinogens. These methods includes resting state fMRI, HD-EEG/MEG and the neural mechanisms investigated are: functional connectivity changes and plasticity across and within cortical networks; disinhibition, brainwave synchronization and phase-coupling.