Cannabis as a treatment for autism spectrum disorders patients appears to be well-tolerated, safe and seemingly effective option to relieve symptoms, mainly: seizures, tics, depression, restlessness and rage attacks. The compliance with the treatment regimen appears to be high with less than 15% stopping the treatment at six months follow-up. Overall, more than 80% of the parents reported at significant or moderate improvement in the child global assessment.

The exact mechanism of the cannabis effects in patients with ASD is not fully elucidated. Findings from ASD animal models indicate a possible dysregulation of the endocannabinoid (EC) system^11–16 signalling behaviours, a dysregulation that was suggested to be also present in ASD patients¹⁷. Mechanism of action for the effect of cannabis on ASD may possibly involve GABA and glutamate transmission regulation. ASD is characterized by an excitation and inhibition imbalance of GABAergic and glutamatergic signalling in different brain structures¹⁸. The EC system is involved in modulating imbalanced GABAergic¹⁹ and glutamatergic transmission²⁰.

Other mechanism of action can be through oxytocin and vasopressin, neurotransmitters that act as important modulators of social behaviours²¹. Administration of oxytocin to patients with ASD has been shown to facilitate processing of social information, improve emotional recognition, strengthen social interactions, reduce repetitive behaviours²² and increase eye gaze²³. Cannabidiol was found to enhance oxytocin and vasopressin release during activities involving social interaction¹⁶.

Two main active ingredients (THC and CBD) can have different psychoactive action mechanisms. THC was previously shown to improve symptoms characteristic to ASD patients in other treated populations. For example, patients reported lower frequency of anxiety, distress and depression²⁴, following THC administration, as well as improved mood and better quality of life in general²⁵. In patients suffering from anxiety, THC led to improved anxiety levels compared to placebo²⁶ and in dementia patients, it led to reduction in nocturnal motor activity,violence^27,28 behavioural and severity of behavioural disorders²⁹. Moreover, cannabis was shown to enhances interpersonal communication³⁰ and decrease hostile feelings within small social groups³¹.

In our study we have shown that a CBD enriched treatment of ASD patients can potentially lead to an improvement of behavioural symptoms. These findings are consistent with the findings of two double-blind, placebo-controlled crossover studies demonstrating the anxiolytics properties of CBD in patients with anxiety disorder^32,33. In one, CBD had a significant effect on increased brain activity in the right posterior cingulate cortex, which is thought to be involved in the processing of emotional information³², and in the other, simulated public speaking test was evaluated in 24 patients with social anxiety disorder. The CBD treated group had significantly lower anxiety scores than the placebo group during simulated speech, indicating reduction in anxiety, cognitive impairment, and discomfort factors³³.

The cannabis treatment appears to be safe and side effects reported by the patients and parents were moderate and relatively easy to cope with. The most prevalent side effects reported at six months was restlessness, appearing in less than 6.6% of patients. Moreover, the compliance with the treatment was high and only less than 5% have stopped the treatment due to the side effects. We believe that the careful titration schedule especially in the ASD paediatric population is important for maintaining a low side effects rate and increase of the success rate. Furthermore, we believe that a professional instruction and detailed parents’ training sessions are highly important for the increasing of effect to adverse events ratio.

The present findings should be interpreted with caution for several reasons. Firstly, this is an observational study with no control group and therefore no causality between cannabis therapy and improvement in patients’ wellbeing can be established. Children of parents seeking cannabis therapy might not constitute a representative sample of the patient with the specific disease (self-selection bias). We have not formally confirmed the ASD diagnosis, however all the children included in the study were previously diagnosed with ASD by certified neurologist or psychiatrist, as required by Ministry of Health prior to the initiation of the cannabis-based treatment.

This study was based on a subjective self-report of the patient’s parent’s observation and not by the patients themselves. These reports, with subjective variables such as quality of life, mood, and general effects, may be biased by the parent’s opinion of the treatment. Moreover, even though the effect was assessed at six months, the possibility of the inflated expectations of the novel treatment “miracle” effect cannot be excluded. The questionnaire response rate at 6 months was 60%, thus the estimates of the efficacy and safety of the treatment can be biased. However, high compliance (above 80%) with the treatment provides a good evidence of the patients and parents satisfaction with the treatment.

While this study suggest that cannabis treatment is safe and can improve ASD symptoms and improve ASD patient’s quality of life, we believe that double blind placebo-controlled trials are crucial for a better understanding of the cannabis effect on ASD patients.