OPEN Foundation

Day: 5 January 2018

Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing—study on P300 and mismatch negativity in healthy volunteers

January 5, 2018 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By / , , , , , ,

Abstract

Rationale

Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors in information processing is less clear.

Objectives

We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/C agonistic properties, in healthy volunteers.

Methods

Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed.

Results

Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude (p = 0.009) but did not affect the MMN. Psilocybin’s disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude (p = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude (p = 0.014).

Conclusions

Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT2A receptors in altered information processing in psychosis and schizophrenia.

Bravermanová, A., Viktorinová, M., Tylš, F., Novák, T., Androvičová, R., Korčák, J., … & Vlček, P. (2018). Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing—study on P300 and mismatch negativity in healthy volunteers. Psychopharmacology, 1-13. 10.1007/s00213-017-4807-2
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A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: Results from a randomized, controlled laboratory study

January 5, 2018 / Addiction, Ketamine, Mystical experiences, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , , ,

Abstract

Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however, suggest that some of the psychoactive effects of sub-anesthetic ketamine may have therapeutic potential. Here, we assess whether a subset of these effects – the so-called mystical-type experience – mediates the effect of ketamine on craving and cocaine use in cocaine dependent research volunteers. We found that ketamine leads to significantly greater acute mystical-type effects (by Hood Mysticism Scale: HMS), dissociation (by Clinician Administered Dissociative States Scale: CADSS), and near-death experience phenomena (by the Near-Death Experience Scale: NDES), relative to the active control midazolam. HMS score, but not the CADSS or NDES score, was found to mediate the effect of ketamine on global improvement (decreased cocaine use and craving) over the post-infusion period. This is the first controlled study to show that mystical-type phenomena, long considered to have therapeutic potential, may work to impact decision-making and behavior in a sustained manner. These data suggest that an important direction for medication development is the identification of ketamine-like pharmacotherapy that is selectively psychoactive (as opposed to free of experiential effects entirely), so that mystical-type perspectival shifts are more reliably produced and factors lending to abuse or behavioral impairment are minimized. Future research can further clarify the relationship between medication-occasioned mystical-type effects and clinical benefit for different disorders.
Dakwar, E., Nunes, E. V., Hart, C. L., Hu, M. C., Foltin, R. W., & Levin, F. R. (2018). A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: Results from a randomized, controlled laboratory study. Neuropharmacology. 10.1016/j.neuropharm.2018.01.005
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30 April - Q&A with Rick Strassman

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