Psilocin, LSD, mescaline, and DOB all induce broadband desynchronization of EEG and disconnection in rats with robust translational validity

Abstract

Serotonergic psychedelics are recently gaining a lot of attention as a potential treatment of several neuropsychiatric disorders. Broadband desynchronization of EEG activity and disconnection in humans have been repeatedly shown; however, translational data from animals are completely lacking. Therefore, the main aim of our study was to assess the effects of tryptamine and phenethylamine psychedelics (psilocin 4 mg/kg, LSD 0.2 mg/kg, mescaline 100 mg/kg, and DOB 5 mg/kg) on EEG in freely moving rats. A system consisting of 14 cortical EEG electrodes, co-registration of behavioral activity of animals with subsequent analysis only in segments corresponding to behavioral inactivity (resting-state-like EEG) was used in order to reach a high level of translational validity. Analyses of the mean power, topographic brain-mapping, and functional connectivity revealed that all of the psychedelics irrespective of the structural family induced overall and time-dependent global decrease/desynchronization of EEG activity and disconnection within 1–40 Hz. Major changes in activity were localized on the large areas of the frontal and sensorimotor cortex showing some subtle spatial patterns characterizing each substance. A rebound of occipital theta (4–8 Hz) activity was detected at later stages after treatment with mescaline and LSD. Connectivity analyses showed an overall decrease in global connectivity for both the components of cross-spectral and phase-lagged coherence. Since our results show almost identical effects to those known from human EEG/MEG studies, we conclude that our method has robust translational validity.

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

“…The changes in resting state EEG, which included decreased spectral power in the alpha/beta bands, accompanied by widespread increases in signal diversity, were not specific to the visual system, but also correlated with somatic and metacognitive/affective domains (343,344). Interestingly, a recent EEG study in freely moving rats showed some overlap with human studies, with a time-dependent global decrease and desynchronization of EEG activity, particularly in the frontal and sensorimotor cortex (345). Similar to the previously discussed vulnerability to adverse effects of psychedelics in people with incoherent self-concept/aberrant salience in the context of psychosis spectrum disorder, baseline dysfunction in the some of the perceptual systems may increase the risk of adverse events in psychedelic therapy.…”

Psilocybin—Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience

“…Previous studies in animal models demonstrated that 5-HT2A and 5-HT1A receptors finely tune the amplitude of gamma oscillations [ 57 ], and serotonin-boosting medications suppress gamma activity [ 58 , 59 ], possibly through 5-HT1AR [ 57 ]. Our recent study [ 14 ] showed the global desynchronization of gamma activity by tryptamines (such as psilocin) administered to rats. Thus, we expected that psilocybin would attenuate the gamma response in a similar manner, as seen in various states with disrupted E/I balance and cognition, including psychosis or during intoxication with other psychedelic substances, such as ketamine [ 25 , 26 , 54 ].…”

“…Psilocybin has been shown to negatively affect the electrophysiological markers of both early visual (P1 and N170)/auditory (N100) [ 9 , 10 , 11 , 12 ] and higher-order attentive cognitive processing (P300) [ 9 , 13 ], but the mismatch negativity (MMN), as a marker of pre-attentive cognition [ 9 , 12 ], was not attenuated. Similarly, serotoninergic psychedelics, including psilocin, the active metabolite of psilocybin, have been shown recently to decrease gamma oscillations in the animal model [ 14 ]. Although gamma activity is one of the most valuable avenues for understanding the neurobiology of cognitive processing [ 15 ], the resting state gamma oscillations are difficult to study using EEG in humans due to contamination with muscle artefacts.…”

Alternative Options for Complex, Recurrent Pain States Using Cannabinoids, Psilocybin, and Ketamine: A Narrative Review of Clinical Evidence

“…When looking at these electrophysiological changes in the brain, research groups have found that this drug administration causes broadband desynchronization and a disconnect in neurons in the sensorimotor cortex on EEG monitoring [ 16 ]. The results are an overall resetting due to decreased global activity and connectivity.…”