Serotonergic Psychedelics Temporarily Modify Information Transfer in Humans

Abstract

Background:Psychedelics induce intense modifications in the sensorium, the sense of “self,” and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects.Methods:Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy, a nonlinear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine.Results:The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. Transfer entropy analysis showed that frontal sources decreased their influence over central, parietal, and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced.Conclusions:These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain.

DMT Models the Near-Death Experience

“…Given strong associations between the temporal lobes and more specifically, medial temporal lobe structures, and unusual psychological experiences such as those featuring within NDEs (Carhart-Harris, 2007), we predict that the medial temporal regions may be implicated in some of the content and emotion-rich epochs that arise within the psychedelic state, such as complex imagery, entity encounters, and vivid autobiographical recollections. The relinquishment of top-down cortical control over temporal lobe activity may be an important component of this mechanism (Alonso et al, 2015; Kaelen et al, 2016; Timmermann et al, 2017). …”

Neuropharmacology of N,N-dimethyltryptamine

“…Oral dosing of DMT via ayahuasca produces both behavioral and neurochemical effects, such as decreases in motor activity (Pic-Taylor et al, 2015), impairment of cognitive function (Alonso et al, 2015; Bouso et al, 2013), sympathomimetic effects, increased prolactin and cortisol levels, and decreased lymphocytes increased natural killer cells (Dos Santos, et al, 2011). Doses of ayahuasca 15 or 30-fold higher than commonly used ritual doses increased serotonergic neurotransmission (Pic-Taylor et al, 2015).…”

The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging

“…Full-text reports of these citations were obtained for more detailed evaluation. Following detailed examination of the reports, all 27 citations were included (Alonso et al, 2015;Barbosa et al, 2005Barbosa et al, , 2009Bouso et al, 2012Bouso et al, , 2013Bouso et al, , 2015Da Silveira et al, 2005;De Araujo et al, 2012;Doering-Silveira et al, 2005a;Dos Santos et al, 2007, 2011, 2012Fábregas et al, 2010;Frecska et al, 2012;Grob et al, 1996;Halpern et al, 2008;Osório et al, 2015;Palhano-Fontes et al, 2015;Riba et al, 2001Riba et al, , 2002aRiba et al, , 2002bRiba et al, , 2003Riba et al, , 2004Riba et al, , 2006Sanches et al, 2016;Soler et al 2015;Thomas et al, 2013). Another reference was included after searching the bibliography of the selected citations (Schenberg et al, 2015).…”

“…De Araujo et al (2012) assessed the acute effects of AYA in nine frequent AYA users in an open-label neuroimaging study and reported that all subjects experienced transient increases in psychotic and mania symptoms following AYA ingestion, according to the Brief Psychiatric Ratings Scale (BPRS) and the Young Mania Rating Scale (YMRS), respectively. Alonso et al (2015) assessed the subjective acute effects of a single dose of encapsulated freeze-dried AYA (0.75 mg DMT/kg) in 10 healthy volunteers in a double-blind, randomized, crossover study. Acute AYA administration was associated with significant increases in the visionary restructuralization (Visionäre Umstrukturierung (VUS)) subscale of the Altered States of Consciousness Questionnaire (Aussergewöhnliche Psychische Zustände (APZ)), which measures illusions, hallucinations, and synesthesia.…”