Targeting the cholinergic and endocannabinoid systems as a therapeutic intervention for core and associated phenotypes in the autism model; a systematic review

source extracted confidence: high 2026-04-09
#humans #endocannabinoids #autism-spectrum-disorder #animals

Targeting the cholinergic and endocannabinoid systems as a therapeutic intervention for core and associated phenotypes in the autism model; a systematic review

Udodi et al., 2025 | Trends Psychiatry Psychother | Systematic Review

Citation

Udodi Princewill Sopuluchukwu, Anyanwu Godson Emeka, ... Ezejindu Damian Nnabuihe. Targeting the cholinergic and endocannabinoid systems as a therapeutic intervention for core and associated phenotypes in the autism model; a systematic review. Trends Psychiatry Psychother. 2025;47:e20240791. doi:10.47626/2237-6089-2024-0791

Abstract

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has been linked to dysregulation in the cholinergic and endocannabinoid (EC) systems. This study systematically reviews the present literature on treatment strategies aimed at enhancing the activity of both systems in ASD models. METHODS: We performed a systematic evaluation of literatures that investigated the effects of different therapeutic interventions on the components of the cholinergic and EC systems in ASD models, following the guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Four databases were searched: Google Scholar, Web of science, EMBASE, and MEDLINE/PubMed, for articles published from August 2012 to February 2023. References cited in the selected research papers were also examined. Twelve papers (five on the cholinergic system, six on the EC system, and one on both) were reviewed in this study of prior work on relevant treatment strategies that impact these systems. The paper cites a total of 77 studies. RESULTS: The majority of research revealed that different therapeutic interventions downregulated cannabinoid 1 (CB1) receptors, and the system's hydrolyzing enzymes and upregulated EC, alpha 7 nicotinic acetylcholine receptor (α7-nAChR), and ACh signaling molecules. Regulation of the components of the cholinergic and EC systems by these therapies generally enhanced behaviors in ASD models. CONCLUSION: It is possible that the therapeutic interventions assessed in one or both of these systems may be effective for treating the core ASD-associated phenotype. The benefits of the therapeutic interventions reviewed in this study merit further investigation in randomized, blinded, placebo-controlled clinical trials.

Key Findings

The majority of research revealed that different therapeutic interventions downregulated cannabinoid 1 (CB1) receptors, and the system's hydrolyzing enzymes and upregulated EC, alpha 7 nicotinic acetylcholine receptor (α7-nAChR), and ACh signaling molecules. Regulation of the components of the cholinergic and EC systems by these therapies generally enhanced behaviors in ASD models.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 77
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Endocannabinoids
  • Autism Spectrum Disorder
  • Animals

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: niacin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09