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.