Psychotomimetic compensation versus sensitization.

Psychotomimetic drugs—such as amphetamines, cannabis, psychedelics, and dissociatives—can paradoxically relieve symptoms like attention deficits, pain, and depression, which themselves increase the risk of psychosis or co-occur with it. The authors propose two concepts to explain this paradox. Psychotomimetic compensation describes a short-term, drug-induced relief from stress, mediated by neurotransmitter systems including endocannabinoid, serotonergic, glutamatergic, and dopaminergic pathways. Psychotomimetic sensitization occurs after repeated stress or drug exposure, gradually intensifying psychotic-like experiences over time. The model has theoretical and practical implications.

Study at a glance

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 short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.