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Ketamine and Psilocybin Differentially Impact Sensory LearningDuring the Mismatch Negativity

Shona G. Allohverdi, Milad Soltanzadeh, André Schmidt, Colleen E. Charlton, Daniel J. Hauke, Povilas Karvelis, Franz X. Vollenweider, Andreea O. Diaconescu

Research Square September 26, 2024 preprint DOI: 10.21203/rs.3.rs-4492873/v1 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Placebo-controlled within-subject crossover design
Population Healthy subjects
Interventions S-ketamine psilocybin
Topics Ketamine Psilocybin Esketamine
Keywords Sensory system Cognitive psychology
Key points Ketamine and psilocybin have distinct effects on sensory learning, with ketamine reducing sensory precision more than psilocybin, while both drugs reduce belief precision.

Abstract

Abstract Ketamine and psilocybin show potential as therapies for various mental illnesses, including major depressive disorder. However, further investigation into their neural mechanisms is required to understand their effects on the brain. By combining computational modelling with electroencephalography (EEG), we examine the effects of ketamine and psilocybin on hierarchical sensory precision-weighted prediction error (pwPE) learning in the context of the auditory mismatch negativity, an event-related potential consistently shown to be reduced under psychotomimetic interventions. We employed a Bayesian framework and re-analyzed a previously acquired EEG dataset (Schmidt et al., 2012) by modelling single-trial EEG data using the Hierarchical Gaussian Filter. Using a placebo-controlled within-subject crossover design, healthy subjects were administered either S-ketamine or psilocybin during an auditory roving paradigm of pure sinusoidal tones. Our findings elucidate distinct neural impacts of ketamine and psilocybin on sensory learning: ketamine led to a larger reduction in the effect of sensory precision compared to placebo from 207 to 316 ms peaking at 277 ms in the frontal central channels, while psilocybin showed no significant effect. Both drugs reduced the expression of belief precision between 160 to 184 ms, peaking at 172 ms. For higher-level volatility pwPEs, ketamine reduced the expression while psilocybin had null effect at 312 ms. For perception of elementary imagery, ketamine had a greater effect than psilocybin on sensory and volatility precision, while psilocybin had a greater effect on volatility pwPEs. Our findings suggest hallucinogens have distinct effects on sensory learning that could inform tailored therapies for major depression.

Comparable studies

Other randomized controlled trials on psilocybin, most cited first.

Study Year Design Participants
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety 2016 Randomized controlled trial n = 51
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression 2016 Double-blind, placebo-controlled, crossover trial n = 29
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... 2006 Double-blind study n = 36
Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression 2021 Randomized controlled trial
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... 2020 Randomized controlled trial n = 24

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Ketamine Psilocybin Esketamine Depression