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Psychotomimetic Compensation and Sensitization

Ari Brouwer, Robin Carhart-Harris, Charles L. Raison

preprint DOI: 10.31234/osf.io/y8dn2 (opens in new tab)

Summary

AI-generated from the abstract

A paradox exists: drugs that can induce psychosis-like effects (psychotomimetics) also relieve symptoms that increase psychosis risk, such as attention deficits, pain, and depression. The authors introduce two concepts to explain this. Psychotomimetic compensation is a stress- or drug-induced adjustment that counteracts stress, engaging neurotransmitter systems (endocannabinoid, serotonergic, glutamatergic, dopaminergic) also activated by psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated stress or drug exposure, gradually intensifying psychotic-like experiences. Theoretical and practical implications are discussed.

Study at a glance

Characteristics Theoretical or philosophical paper
Key finding Proposes that psychotomimetic compensation and psychotomimetic sensitization can explain the paradoxical relief of psychosis-risk symptoms by psychotomimetic drugs.

Abstract

It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a stress or drug induced compensation against stress (see Fig 1) that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs (see Fig 3). Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs (Fig 3) and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.

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