Research into the endocannabinoid system provides promising evidence for the use of cannabis to treat autism.
As cannabis liberalisation policies come into effect in countries all over the world, study of the therapeutic potential of this medicinal plant is experiencing an unparalleled resurgence. Within the renaissance of scientific exploration in cannabis, Dr. Michelle Roche, principal investigator and senior lecturer in physiology at the National University of Ireland Galway, outlines the latest research into cannabis as a viable treatment for autism, at the latest GCI Summit.
What is Autism?
Autism Spectrum Disorder (ASD) is an “umbrella term grouping neurodevelopmental disorders,” explains Dr. Roche. These are characterised by “two core behavioural changes: deficits in social interaction and communication, and repetitive and restrictive behaviours and interests.” In addition to these core symptoms, individuals with ASD commonly report anxiety, irritability, epilepsy, sensory and sleep dysfunction and gastrointestinal (GI) disturbances.
The prevalence of this disorder has increased significantly over recent decades, affecting roughly 1 in every 54 children. Males are four times more likely to be diagnosed with autism than females. The current economic cost of autism in the US alone is $260 billion per annum, which is on par with diabetes and five times greater than that of stroke or hypertension. This figure is expected to rise to $460 billion by 2025.
“The lack of specific pharmacological-based treatments for ASD is widely recognised,” admits Dr. Roche. Yet, the last decade has seen an increased popularity in the use of cannabis to manage the symptoms of ASD. Cannabis can currently be prescribed to manage symptoms associated with autism in 14 U.S. states. However, Dr. Roche warns, “despite the reported beneficial effects of the treatment, the research on cannabis and ASD is really still in its infancy.”
“The endocannabinoid system is a viable target for the management of ASD symptomatology.”
— Dr. Michelle Roche, principal investigator and senior investigator in physiology.
Why is cannabis a good fit for autism?
Cannabis interacts with the body via a widespread neuromodulatory structure known as the endocannabinoid system (EDS). This network plays a crucial role in modulating neuroimmune and behavioural responses. It is “well-documented” that the EDS is altered in individuals with ASD. Particularly, individuals with ASD show an “increased expression” of the cannabinoid CB2 receptor and the enzymes responsible for breaking down the primary endocannabinoids produced by the body.
Recent clinical trials evaluating the safety and efficacy of using cannabis to treat ASD is encouraging and supports the mounting evidence that “the endocannabinoid system is a viable target for the management of ASD symptomatology.” This may be because the endocannabinoid system plays a key role in social responsiveness (Trezza and Vanderschuren, 2008). It has been proposed that alterations in the EDS may be a cause of the social impairments seen in ASD individuals.
Treatment development using the VPA model
While the causes of ASD are unclear, it is understood that a variety of genetic, epigenetic and environmental factors come into play. One environmental factor known to give rise to an increased incidence of autism is the prenatal exposure to valproic acid (VPA), an antiepilepsy, mood-stabilising medication also known as Epilim. VPA induces foetal reprogramming that alters neuronal circuits and governs behaviour changes characteristic of autism. This known environmental trigger can be utilised in pre-clinical animal models by studying the endocannabinoid system of VPA-exposed rats.
A recent study shows that activating CB1 receptors by raising levels of anandamide (AEA) — a cannabinoid-like substance produced by the body — in VPA-exposed rats increases social response (Kerr et al. 2016). This appears to reverse core social and repetitive behaviours related to ASD in male rats, which are most likely caused by impaired CB1 receptor signalling. However, effects on female rats are more variable.
Zamberletti’s 2019 research demonstrates the beneficial effects that the repeated administration of cannabinoids has on social and repetitive behaviours. Cannabidivarin, the cannabis-derived treatment used in this study, is currently being investigated as part of several clinical trials for the treatment of ASD. It works by normalising the individual’s endocannabinoid system, as well as their enhanced glial activity and neuroimmune profile.
Is cannabis “the missing piece”?
Pre-clinical evidence supports the potential for treating ASD by mediating and modulating the endocannabinoid system to elicit neuroimmune and behavioural responding. So, is cannabis “the missing piece in the ASD puzzle?” Dr. Roche admits that it’s “too early to tell,” and that further research into the effects of sex, age and long-term effects of treatment is warranted. Nevertheless, Dr. Roche is hopeful, concluding that “we know that the initial clinical trial data on cannabis and cannabinoids for treating ASD symptomatology is extremely promising.”
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