“Current treatments for autism spectrum disorders (ASD) are limited in efficacy and are often associated with substantial side effects. These medications typically ameliorate problem behaviors associated with ASD, but do not target core symptom domains. As a result, there is a significant amount of research underway for development of novel experimental therapeutics.

Endocannabinoids are arachidonic acid-derived lipid neuromodulators, which, in combination with their receptors and associated metabolic enzymes, constitute the endocannabinoid (EC) system. Cannabinoid signaling may be involved in the social impairment and repetitive behaviors observed in those with ASD. In this review, we discuss a possible role of the EC system in excitatory-inhibitory (E-I) imbalance and immune dysregulation in ASD.

Novel treatments for the core symptom domains of ASD are needed and phytocannabinoids could be useful experimental therapeutics for core symptoms and associated domains.”

https://pubmed.ncbi.nlm.nih.gov/33689997/

“Novel treatments for the core symptom domains of ASD are needed, and the endocannabinoid (EC) system could be a target for those therapies through the administration of exogenous cannabinoids.”

https://www.sciencedirect.com/science/article/abs/pii/S0022395621001266?via%3Dihub

“Healing autism spectrum disorder with cannabinoids: a neuroinflammatory story” https://pubmed.ncbi.nlm.nih.gov/33358985/

“Recent years have seen an impressive amount of research devoted to understanding the etiopathology of Autism Spectrum Disorder (ASD) and developing therapies for this syndrome. Because of the lack of biomarkers of ASD, this work has been largely based on the behavioral characterization of rodent models, based on a multitude of genetic and environmental manipulations.

Here we highlight how the endocannabinoid system (ECS) has recently emerged within this context of mouse behavioral studies as an etiopathological factor in ASD and a valid potential therapeutic target.

We summarize the most recent results showing alterations of the ECS in rodent models of ASD, and demonstrating ASD-like behaviors in mice with altered ECS, induced either by genetic or pharmacological manipulations. We also give a critical overview of the most relevant advances in designing treatments and novel mouse models for ASD targeting the ECS, highlighting the relevance of thorough and innovative behavioral approaches to investigate the mechanisms acting underneath the complex features of ASD.”

https://pubmed.ncbi.nlm.nih.gov/34813825/

“Autism Spectrum Disorder (ASD) is a complex pathology with unknown aetiology and developing therapeutic approaches.•

Recent mouse behavioural studies have highlighted the role of the endocannabinoid system (ECS) in ASD.•

Novel pharmacological treatments and new genetic mouse models for ASD can be identified and designed by targeting the ECS.”

https://www.sciencedirect.com/science/article/abs/pii/S014976342100525X?via%3Dihub

“Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD.

The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects.

ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.”

https://pubmed.ncbi.nlm.nih.gov/33805951/

https://www.mdpi.com/1420-3049/26/7/1845

“Can autism be triggered by acetaminophen activation of the endocannabinoid system? Acetaminophen use in children has been associated with increased autism risk. Recent evidence suggests that acetaminophen’s analgesic actions result from activation of the endocannabinoid system, and activation of this system can have neuromodulatory consequences during development. This investigation was performed to determine if there is evidence to support the hypothesis that acetaminophen use can trigger autism by activation of the endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/20628445/

“Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders.”

https://pubmed.ncbi.nlm.nih.gov/34556849/

“Healing autism spectrum disorder with cannabinoids: a neuroinflammatory story” https://pubmed.ncbi.nlm.nih.gov/33358985/

“Translational research made with Cannabis sativa L. and its biocompounds provides data for some targeted diseases, as also symptoms associated with Autism Spectrum Disorders (ASDs). The main compounds ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are capable of modulating the endocannabinoid system since its dysregulation interferes with the pathophysiology of ASDs there are clinical evidence for its potential use in the treatment of the disease. Conventional therapy still has limitations, as it does not always treat the central symptoms, and there are many patients who do not respond to treatment, which demands more research on new therapies. Through the analysis of published literature on this topic, it is verified that cannabinoids, in particular CBD, improves symptoms associated with common comorbidities in ASDs. Some studies also demonstrate the therapeutic potential of these compounds in the treatment of central symptoms of autism. In addition, cannabinoid therapy to ASDs is associated with low adverse effects and a reduction in concomitant medication. Although it appears to be promising, it is essential to do the translation of this data into clinical research and some of its potential and critical gaps are discussed in this review pointing to large-scale and long-term clinical trials that should include more patients and homogeneous samples.”

https://pubmed.ncbi.nlm.nih.gov/35453548/

“Autism spectrum disorder (ASD) is a group of disabilities with impairments in physical, verbal, and behavior areas. Regardless the growing frequency of autism, no medicine has been formed for the management of the ASD primary symptoms. The most frequently prescribed drugs are off-label. Therefore, there is necessity for an advance tactic for the treatment of autism. The endocannabinoid system has a central role in ruling emotion and social behaviors. Dysfunctions of the system donate to the behavioral deficits in autism. Therefore, the endocannabinoid system represents a potential target for the development of a novel autism therapy. Cannabis and associated compounds have produced substantial research attention as a capable therapy in neurobehavioral and neurological syndromes. In this review we examine the potential benefits of medical cannabis and related compounds in the treatment of ASD and concurrent disorders.”

https://pubmed.ncbi.nlm.nih.gov/35320905/