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Evidence for the Use of Cannabinoid-based Treatment for Autism

Published: 18/02/2021

While cannabis has been used medicinally for thousands of years, modern prohibition has meant that there remains a paucity of clinical and scientific research in many domains. However, there is a growing appetite for research into medical cannabis as countries around the world legalise its use for medicinal properties.

Over the past decade, an increasing number of autistic people and their families have reported experimenting with medical cannabis and cannabinoids. There has been some reported evidence that cannabinoids may have the potential to alleviate some autism-related symptoms and problems, however, much of this evidence remains anecdotal.

Autism Spectrum Disorder (ASD) and Medical Cannabis

Generally, the efficacy and tolerability of treatments used for addressing challenging behaviours associated with autism spectrum disorder are relatively low. Furthermore, there remains no pharmacological treatment for the common symptoms of autism spectrum disorder (ASD) such as challenges in social communication, and repetitive and restrictive patterns of behaviour.

Anecdotal reports from patients and their families that cannabis consumption may help to improve some symptoms of ASD. Some reports have shown that cannabis use may particularly enhance interpersonal communication and decrease hostile feelings. Observational data is now beginning to be supplemented with that from randomised controlled clinical trials.

Current Medical Cannabis Trials

It is thought that Epidyolex – a licensed preparation of cannabidiol for the treatment of drug-resistant epilepsy – could also be beneficial in the treatment of ASD, as 10-30% of ASD patients also have epilepsy and associated improvements in ASD outcomes have been seen in those prescribed cannabidiol for their epilepsy. In addition, several pathophysiological pathways are implicated in both disorders.

The manufacturer of Epidyolex, GW Pharmaceuticals, is now also conducting trials of the drug for Rett syndrome – a neurodevelopmental condition related to autism with a focus on improving cognitive and behavioural problems associated with the condition.

The company is also currently recruiting children and teenagers to take part in a phase 2 trial of cannabidivarin (a minor cannabinoid) to determine its effects on a number of factors associated with autism.

Furthermore, a recent double-blind, randomised controlled trial was carried out to assess the efficacy of two oral cannabinoid solutions for participants with autism spectrum disorder (ASD). The study aimed to build on existing evidence of endocannabinoid dysfunction in animal models of ASD and anecdotal evidence for efficacy of medical cannabis in humans.

Aims and Methods of the Study

While cannabidiol (CBD) and tetrahydrocannabinol (THC) are the most common compounds produced by the cannabis plants, other cannabinoids, as well as terpenes and flavonoids, have also been attributed to the medical potential of the full cannabis flower and its extract. Therefore, this study aimed to assess the effects of both a full-spectrum plant extract and a purified cannabinoid preparation in order to determine whether these compounds may also contribute to the therapeutic potential of cannabis in the treatment of ASD.

A total of 150 participants (aged 5-21 years) with ASD diagnosis took part in this placebo-controlled, double-blind trial. Researchers aimed to determine the effects of two medical cannabis preparations – a whole-plant extract containing a CBD:THC ratio of 20:1, and a purified CBD and THC preparation with the same ratio.

Patients were randomly assigned to one of these two active treatments or to a placebo treatment for 12 weeks. After this first period and following a 4-week washout period, all participants were then crossed-over to a second 12-week treatment. This cross-over design meant that all participants would receive treatment with a cannabis-based medicinal product at least once.

Study Outcomes

The two primary outcome measures were to assess ASD associated disruptive behaviours throughout the study period using parent-rated scales, the HSQ-ASD and CGI-Improvement.

The researchers also aimed to identify some secondary outcomes, including adverse events.

Results of the Study

Impact of cannabinoid treatment on behaviour

No significant difference was seen in total HSQ-ASD total scores between participants who received cannabis-based medicinal products and participants who received placebo.

However, on analysis of CGI-I reports, 49% of 45 participants who received the whole-plant cannabinoid preparation positively responded (either much or very much improved) in comparison to 21% of 47 treated with placebo. Of the 45 participants who were treated with isolated cannabinoid preparation, 38% responded positively, however, this was not deemed to be significantly higher than with placebo.

Researcher Conclusions

This study demonstrates, for the first time in a placebo-controlled trial, that cannabinoid treatment has the potential to decrease disruptive behaviours often associated with ASD as assessed by a subjective scoring assessment. Furthermore, both the pure cannabinoid preparation and whole-plant extract were found to have acceptable tolerability among the patient sample.

In addition to potentially improving behaviour and ASD symptoms, cannabinoid treatment was also associated with a surprising finding of net weight loss, in comparison to the significant weight gain often produced by antipsychotics.

While this preliminary study offers some promising insight into the potential of cannabinoids for the treatment of ASD, the researchers also note that there are some limitations to this research. It is noted that the cross-over design revealed a treatment order effect which prevented the use of data from the second period. Further, the sample size was relatively small, which may add further limitations to these findings.

In conclusion, this study demonstrated that whole-plant extract with a 20:1 CBD and THC ratio may improve disruptive behaviours and ASD core symptoms with acceptable adverse events. These findings warrant further investigation of cannabinoids for the treatment of autism spectrum disorder.

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