Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Abstract

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual's visual experiences. These visual alterations show consistent attributes despite large inter- and intra-individual variances. Many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment ("Visual Intensifications"). Environmental objects might be altered in size ("Visual illusions") or take on a modified and special meaning for the subject ("Altered self-reference"). Subjects may perceive light flashes or geometrical figures containing recurrent patterns ("Elementary imagery and hallucinations") influenced by auditory stimuli ("Audiovisual synesthesia"), or they may envision images of people, animals, or landscapes ("Complex imagery and hallucinations") without any physical stimuli supporting their percepts. This wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. Starting with mechanisms that act at the cellular level, the key role of 5-HT2A receptor activation and the subsequent increased cortical excitation will be considered. Next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hallucinations. The decrease of alpha oscillations by hallucinogens will then be introduced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. Finally, the hallucinogen-induced parallel decrease of the N170 visual evoked potential and increased medial P1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions, and intensifications.

The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

“…In contrast, serotonergic psychedelics tend to produce subtler perceptual modifications that cannot be easily classified in either category and that are frequently described as “simple” visual imagery (Nichols, 2004 , 2016 ) [however, some exceptional serotonergic psychedelics such as N,N-diisopropyltryptamine (DiPT) primarily induce auditory distortions; Shulgin and Carter, 1979 ]. The nature of simple visual imagery elicited by serotonergic psychedelics is consistent with their effect at cortical areas early in the visual hierarchy (Ermentrout and Cowan, 1979 ; Bressloff et al, 2002 ; de Araujo et al, 2012 ; Carhart-Harris et al, 2016 ; Kometer and Vollenweider, 2016 ; Roseman et al, 2016 ). In addition, changes in higher visual areas have been reported for the acute effects of serotonergic psychedelics.…”

“…The most frequent visual modifications induced by serotonergic psychedelics are elementary in nature and include color and pattern recognition enhancement (Hartman and Hollister, 1963 ; Oster, 1966 ), the presence of trails behind moving objects (Dubois and VanRullen, 2011 ), drifting of the visual field, and imagery that is predominantly geometric in nature (Klüver, 1942 ; Siegel and Jarvik, 1975 ; Kometer and Vollenweider, 2016 ; Roseman et al, 2016 ). This last feature of perceptual distortions has been explained by the form of the retino–cortical map and the architecture of the human primary visual cortex (Ermentrout and Cowan, 1979 ; Bressloff et al, 2002 ; Kometer and Vollenweider, 2016 ). These observations suggest that visual distortions elicited by typical recreational doses of serotonergic psychedelics and REM sleep dreams might differ in terms of their complexity and similarity to the visual content typical of conscious wakefulness.…”

Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1

“…Similarly, decreasing the gain of the visual input could shift the balance toward the internally generated signals, and thus result in visual hallucinations. The decrease in gain by serotonin we found here may therefore shed light onto the mechanism by which the visual cortex is involved in hallucinations caused by serotonergic hallucinogens ( Bressloff et al, 2002 ; de Araujo et al, 2012 ; Kometer et al, 2013 ; Carhart-Harris et al, 2016 ; Kometer and Vollenweider, 2016 ).…”

The Pharmacology of Visual Hallucinations in Synucleinopathies

“…The molecule exhibits complex pharmacology and modulates serotonergic, dopaminergic, and glutamatergic transmissions. The activation of the 5-HT2A receptors in the pyramidal neurons of the prefrontal and limbic cortex is now considered the most critical mechanism for the LSD-driven production of schizophrenia-like hallucinations (Passie et al, 2008;Eggers, 2013;Kometer and Vollenweider, 2018). The LSD-driven modulation of dopaminergic neurotransmission appears to have a lesser role in the production of psychedelic effects.…”