Cannabinoids for People with ASD: A Systematic Review of Published and Ongoing Studies

Abstract

The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Also, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, has been recently approved for treatment-resistant epilepsy. Seizures represent frequent medical comorbidities of ASD and could be responsible for the onset or worsening of behavioral problems. Thus, it has been hypothesized that cannabinoids could be useful in improving some ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of KnowledgeTM, PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. Findings are promising, as cannabinoids appeared to improve problem behaviors, sleep, hyperactivity, and communication deficits, with limited cardiac and metabolic side effects. Interestingly, they generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in epileptic patients. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials need to be implemented with better characterization and homogenization of samples, and well-defined outcomes.

Autism and associated disorders: cannabis as a potential therapy

“…Oral administration of cannabidiol to ASD children has also shown improvement in ASD-associated sleep disorders [164]. CBD appears to optimize sleep and improve ASD-associated sleep problems and may have a beneficial value in autistic sleep conditions [271][272][273][274].…”

Combinatorial approaches for treating neuropsychiatric social impairment

“…Supporting therapeutic potential, clinical studies indicate that enhancement of endocannabinoid signalling may treat social anxiety and post-traumatic stress disorder (PTSD) as well as several facets of ASD, and these approaches are undergoing clinical development [142][143][144]. Findings thus far, while mixed, are promising, as cannabinoids appear to improve ASD-associated symptoms such as caregiver-rated social responsiveness and decrease polypharmacy burden [143]. Recently, administration of a selective FAAH inhibitor resulted in significant improvements in social anxiety over a placebo in a randomized control trial with 149 patients [145].…”

“…Recently, administration of a selective FAAH inhibitor resulted in significant improvements in social anxiety over a placebo in a randomized control trial with 149 patients [145]. However, FAAH inhibitors, CBD and compounds like nabiximols ( purified plant extract of 1 : 1 ratio of CBD and D 9 -THC) have controversial results with mixed evidence of efficacy in social anxiety and ASD [139,142,143] and may have different mechanisms of action in brains of patients with ASD [146]. In a related line of work, plasma anandamide concentrations were found to be lower in children with ASD [147].…”

Medicinal cannabis in children and adolescents with autism spectrum disorder: A scoping review

“…Previous reviews have examined the evidence for medicinal cannabis in treating medical conditions in paediatric populations (Pawliuk et al, 2020; Wong & Wilens, 2017). A 2020 systematic review of cannabinoids in ASD highlighted significant knowledge gaps but did not focus on a paediatric population (Fusar‐Poli et al, 2020). There remains significant concerns about the safety of medicinal cannabis, especially in children who have a developing brain that may be vulnerable to the effects of cannabis (Rieder, 2016).…”