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Psychotomimetic compensation versus sensitization

Summary

This paper proposes a new way to understand why drugs that can cause psychosis-like effects (such as psilocybin, LSD, and ketamine) can also help treat depression and anxiety. The authors suggest that these drugs trigger compensatory responses in the brain that temporarily help us cope with stress, similar to how a runner’s high feels good during exercise. However, if someone uses these drugs repeatedly or experiences chronic stress, they may become sensitized and more vulnerable to developing actual psychotic symptoms over time.

Background

Psychotomimetic drugs (psychedelics, cannabis, ketamine, stimulants) paradoxically relieve symptoms associated with psychosis including attention deficits, pain, and depression. This apparent paradox requires explanation of how drugs that mimic psychosis can have therapeutic effects.

Objective

To introduce and explain two concepts—psychotomimetic compensation and psychotomimetic sensitization—to resolve the paradox of how psychotomimetic drugs can both induce psychosis-like states and provide therapeutic benefits.

Results

Psychotomimetic compensation describes short-term adaptive responses to stress mediated by neurotransmitter systems engaged by psychotomimetic drugs. Psychotomimetic sensitization explains how repeated stress or drug exposure progressively intensifies psychotic-like experiences through cross-sensitization mechanisms and feedback loops.

Conclusion

The proposed model explains therapeutic effects of psychotomimetics at short durations while accounting for increased psychosis risk with chronic or frequent use. This perspective provides theoretical grounding for understanding both the benefits and risks of psychedelic and other psychotomimetic drug use.
  • Published in:Pharmacology Research & Perspectives,
  • Study Type:Theoretical Review,
  • Source: PMID: 38923845, DOI: 10.1002/prp2.1217
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