# Conceptual and pragmatic clinical implications of dichotomizing psychotropics as targeting physiology—physiomodal and pathology—pathomodal

**Authors:** Michael Berk, Stephen M Stahl, Lakshmi Yatham, Janardhanan C Narayanaswamy, Seetal Dodd

PMC · DOI: 10.1093/ijnp/pyag006 · 2026-02-16

## TL;DR

This paper introduces a new way to categorize psychotropic drugs based on whether they target physiology or pathology, with implications for research and clinical practice.

## Contribution

The paper introduces the novel concepts of 'physiomodal' and 'pathomodal' drugs to classify psychotropics based on their mechanisms and effects.

## Key findings

- Drugs like antidepressants and antipsychotics are pathomodal, targeting pathophysiology with delayed effects.
- Recreational drugs repurposed as psychotropics are physiomodal, affecting physiology with immediate effects and late withdrawal risks.
- This classification impacts how clinical trials and treatment strategies are designed.

## Abstract

Conventional antidepressant, antipsychotics and mood stabilizing drugs share several characteristics. Firstly, they have a slow onset of action with benefits accruing late that is broadly mediated by long term homeostatic processes. Response generally predicts long term maintenance effects. They have little or no effect on the mental state of healthy individuals and can be conceptualized as targeting elements of pathophysiology. We can term them pathomodal. In contrast, psychotropic agents that are repurposed recreational drugs also share several effects. They have a rapid effect on mood states or perception and risk withdrawal symptoms that are generally the phenomenological mirror image of their acute effects and hence risks accrue late. Notwithstanding some heterogeneity, long term benefits are less clear than acute effects. Lastly, their effects are evident in all people who take them, and they can therefore be conceptualized as targeting elements of physiology. We can term them physiomodal. This categorization has several implications for both research design and clinical care.

## Full-text entities

- **Genes:** HTR2A (5-hydroxytryptamine receptor 2A) [NCBI Gene 3356] {aka 5-HT2A, HTR2}
- **Diseases:** mental health disorders (OMIM:603663), borderline personality disorder (MESH:D001883), hypersomnia (MESH:D006970), trauma (MESH:D014947), insomnia (MESH:D007319), withdrawal (MESH:D013375), dysphoria (MESH:D019052), lethargy (MESH:D053609), depressed mood (MESH:D003866), psychotic (MESH:D011618), fatigue (MESH:D005221), affective disorders (MESH:D019964), irritability (MESH:D001523), anxiety (MESH:D001007), suicidal ideations (MESH:D001072), ADHD (MESH:D001289)
- **Chemicals:** Psilocybin (MESH:D011562), agents (-), histamine (MESH:D006632), MDMA (MESH:D018817), lamotrigine (MESH:D000077213), Alcohol (MESH:D000438), Lithium (MESH:D008094), cannabinoids (MESH:D002186), benzodiazepine (MESH:D001569), valproate (MESH:D014635), opiates (MESH:D053610), NMDA (MESH:D016202)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12981678