Psychotomimetic compensation versus sensitization.
Pharmacology research & perspectives – August 01, 2024
Source: PubMed
Summary
Psychedelics and other psychotomimetic substances can paradoxically alleviate symptoms linked to increased risk of psychosis, such as attention deficits and depression. The concepts of psychotomimetic compensation and sensitization help explain this. In a model involving neurotransmitter systems, short-term stressors trigger temporary relief, while repeated exposure leads to intensified psychotic-like experiences. This highlights the complex relationship between substance use, stress, and schizophrenia, suggesting that while some substances may provide immediate benefits, they may also heighten vulnerability over time.
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.