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Overview
Autism spectrum disorder (ASD), is a developmental disability affecting social interaction, communication and behavior. It is a worldwide phenomenon affecting 1 in 160 children. With ASD diagnoses tripling over the last 15 years, the burden on society is growing exponentially. Parents often find themselves with limited treatment options which may not significantly help their loved ones. In recent years, a number of parents have turned to medical cannabis as a relatively side effect-free alternative. Thankfully, science is now catching up, with several studies linking abnormalities in the endocannabinoid system to some key ASD traits, as well as some promising research suggesting cannabis may be a safe, effective treatment for autism.
The Endocannabinoid System
Discovered when scientists were investigating how compounds in the cannabis plant affect the body, the endocannabinoid system (ECS) is a complex network of fatty ligands called endocannabinoids (primarily anandamide and 2-AG, but also related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA)), their receptors (CB1 and CB2), and the enzymes responsible for their formation and degradation (FAAH and MAGL).
The ECS is involved in all biological function. Indeed, in the paper “Neuromodulatory functions of the endocannabinoid system,” the ECS has been termed “one of the key regulatory mechanisms in the brain controlling multiple events such as mood, pain perception, learning and memory.”
Thus we can think of the ECS as the conductor of our biological orchestra, keeping all the sections playing in harmony. But what happens if this master regulator is out of balance? Could a dysregulated endocannabinoid system play some part in the development of autism?
Indeed, a gene expression study on postmortem brains of subjects with autism found they shared reduced CB1 receptor expression. CB1 receptors are abundant throughout the central nervous system. Another study analysing the levels of the main endocannabinoids and their related endogenous compounds in 93 children with ASD found the subjects had lower levels of Anandamide (AEA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), suggesting some kind of endocannabinoid deficiency may contribute to autism.
Other ECS abnormalities noted include alterations in the levels of the enzymes responsible for breaking down 2-AG, as well as a lack of anandamide discovered in the hippocampus area of the brain causing a deficit in social play behaviour; both in rodent models of autism.
Some of these studies do have their limitations; ASD only exists in humans and animal models only go some way towards replicating the condition. Furthermore, unusual endocannabinoid activity can be evidence of the ECS merely doing its job — trying to get our brain function back into balance again. Take for instance the overexpression of CB2 receptors found in three- to nine-year-olds with autism. In this case scientists speculated that the increase in CB2 expression was merely the ECS mitigating the inflammatory state commonly associated with autism.
However, an exciting area of research lies in the possibility that manipulating the ECS may have a therapeutic effect on some autism symptoms.
Low levels of oxytocin, a neuropeptide associated with social behavior, have been associated with ASD, in particular social reward behavior. Furthermore, research shows that administering oxytocin can be an effective therapeutic approach for people with ASD with below normal levels of oxytocin. One study using a mouse model of ASD suggests the ECS may regulate oxytocin signalling and that by increasing anandamide a total reversal of any socially impaired behavior can be achieved. Could this explain why one positive effect noted by parents of autistic children given medical cannabis is their greater ability and ease at interacting socially?
Cannabis & Autism
Cannabis has been used for thousands of years for a broad range of health conditions without doctors understanding exactly how it affects the body. These days, we know that the cannabis plant comprises at least 144 compounds called cannabinoids, the most abundant being Tetrahydrocannabinol (THC) and Cannabidiol (CBD).
While much still remains to be discovered about how THC and CBD affect the body, we do know they interact with the endocannabinoid system. Like anandamide and 2-AG, THC binds with both CB1 and CB2 receptors, while CBD works more subtly, inhibiting the enzyme responsible for breaking anandamide down in the body (FAAH).
It is suggested that cannabinoids act to support the endocannabinoid system, which as we know regulates everything from sleep, appetite, mood, the immune system, and memory. This may explain the striking number of cases in which children with severe ASD have found their symptoms improved while taking medical marijuana.
This anecdotal evidence has inspired two recent retrospective studies, both coming from different teams in Israel, where currently 2,500 children and adults with ASD receive cannabinoid treatment from the national medical cannabis program.
The first study coming out of the lab of Raphael Mechoulam, was based on the experiences of 188 ASD patients between 2015-2017. They were given medical cannabis with a ratio of 30% CBD to 1.5% THC. A cannabidiol rich treatment was the obvious choice as the non-intoxicating cannabinoid has already been found to have anti-anxiety and anti-seizure effects, while being well tolerated and safe in children.
After six months of medical marijuana treatment, 30.1% of subjects noted a significant improvement in their condition, 53.7% moderate, and 6.4% a slight improvement. Additionally, quality of life markers such as the ability to shower and dress independently with no difficulty also doubled and 84% of ASD subjects who also had epilepsy reported a “disappearance of symptoms.”
Thus, the authors concluded cannabis treatment is a “well tolerated safe and effective option to relieve symptoms associated with ASD.”
The second study published soon after in March 2019 assessed 60 children with ASD who were given CBD-rich cannabis as an adjunct treatment over 7-13 months. Considerable improvement in behaviour problems was noted in 61% of subjects, 39% improvement in anxiety and 47% in communication difficulties. Most children were taking other medication alongside the cannabis, with 33% taking a lower dosage and 24% stopping their medication altogether by the end of the study.
Despite the positive results and relatively few side effects, the author Dr Adi Aran suggests a cautious approach to prescribing cannabis for ASD as the study had no control group and used a wide variety of strains and strengths of cannabis. Dr Aran has gone on to conduct a stage 2 clinical trial, the results of which are awaiting publication.
A further stage 2 clinical trial is currently being conducted using the purified CBD drug Epidiolex in children and adolescents with ASD, while another compares the administration of CBD and another cannabinoid, CBDV, in men with autism.
Conclusion
People with autism and their families are in dire need of effective therapies, and perhaps cannabis can play a role in their treatment. More studies are certainly needed, and have been lacking due to the regulatory environment of cannabis up until now.
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