The potential of cannabinoids in the treatment of autism
 

Autism Spectrum Disorder (ASD) is the name given to a form of atypical neurodevelopment, characterized by the early manifestation of difficulties in communication and social interaction and by the presence of repetitive or restricted behaviors and/or interests. These are the core symptoms of the disorder, but the form and severity of their presentation are variable. It is a pervasive and permanent disorder, with no cure, although early multidisciplinary intervention focused on hyperstimulation (behavioral and educational) can change the prognosis, improving the functionality and quality of life of the patient.

Pharmacological treatment has formal indication only for cases of significant irritability or aggressiveness, where the patient puts himself or others at risk. It may also be indicated in the treatment of comorbid conditions, with sleep disorders and attention-deficit/hyperactivity disorder (ADHD) being the most common.

Cannabinoids for treating Autism Spectrum Disorder
The use of cannabinoids – especially cannabidiol (CBD) – has been increasingly frequent in the treatment of children with epilepsy refractory to conventional treatments and other pathologies, including in Brazil. After several reports on the use of medical cannabis in reducing, for example, anxiety, irritability, insomnia and aggression, parents of children with autism began to see the use of cannabinoids as an alternative to alleviate such symptoms in their children.

Since then, many case reports have been accumulating around the world showing substantial improvement in behavior, functionality and quality of life in patients with ASD after starting treatment with medical cannabis. In addition to curiosity about the possibility of this use also influencing the improvement of the central symptoms of the disease. Although many people with autism are already being treated with CBD-based preparations, there is still a great lack of knowledge about the scientific evidence and analyzes of the safety, tolerability and efficacy profile for use in patients with ASD.

Elsevier study
A recent study by Poleg et al (2018), entitled “Cannabidiol as a suggested candidate for the treatment of Autism Spectrum Disorder”, was published by Elsevier. CBD does not have a psychotropic effect (does not “high”, does not cause changes in perception or mood), is not addictive and has low toxicity.

The article evaluated preclinical and clinical studies in search of findings on the involvement of the endocannabinoid system in neurodevelopment and physical and mental disorders, as well as on the safety and efficacy of the use of CBD in the treatment of the most common behaviors and comorbidities of ASD patients. The work concluded that social interaction deficits are part of the main phenotypes of ASD, and that CBD has demonstrated some prosocial properties in preclinical studies.

In addition, it demonstrated that it is possible that cannabidiol could be effective as a monotherapy or adjunctive treatment in some of the most common comorbidities of the person with autism, such as sleep disorders, ADHD, anxiety and seizures. The level of evidence is still very low regarding effects on other comorbidities, such as psychosis, addictive behavior, cognitive or mood disorders, and aggressiveness.

The study also concludes that there is certainly a large gap on the subject and many more studies are needed before making any conclusions about the therapeutic potential of the use of cannabinoids in patients with ASD. It was highlighted that all current evidence is indirect and based on the effectiveness of CBD in pathological conditions that could also be present in autism. Therefore, the potential effectiveness of CBD in the context of ASD is still a hypothesis.

Nature Magazine Study
More recently, the renowned scientific journal Nature (whose impact factor is highly relevant) released the article “Real-life experience in the treatment of autism with medical cannabis: analysis of safety and efficacy”. In this study, data were collected and analyzed from 188 patients with ASD treated with medical cannabis between 2015 and 2017 – the group had a mean age of 12.9 years and some patients had associated comorbidities, including epilepsy (14.4%) and ADHD (3.7%) the most prevalent.

In most patients, treatment was based on the use of cannabis oil containing 30% CBD and 1.5% THC (ratio of 20 CBD to 1 THC). Data were collected through structured questionnaires applied to caregivers, containing an inventory of symptoms, global assessment and side effects. Collection was performed at three different times (before the start of treatment, one month after the start and six months after the start).

It was concluded that, after six months of treatment, 30.1% of patients reported significant improvement in symptoms; 53.7% reported a moderate response; 6.4% reported slight improvement; and 8.6% reported no improvement. In addition, improvement or disappearance of symptoms such as restlessness, temper tantrums, agitation, sleep problems, anxiety, constipation and digestive problems were reported in 75% of patients or more. The same effectiveness was not observed in the improvement or disappearance of speech disorders, cognitive deficits, incontinence, limited mobility, increased appetite and lack of appetite.

Side effects were observed by 25.2% of patients, with restlessness (6.6%) being the most common. It is important to point out that this was a study carried out without a control group and, therefore, no causality between cannabinoid therapy and improvement in well-being could be established. The study was based on observation reports provided by parents/caregivers, in addition to the evaluation being composed of ​​subjective variables, such as quality of life, mood and general effects – factors that can be influenced by the opinion of parents/caregivers.

Safety of medical cannabis use
A report by the World Health Organization (WHO) highlighted that CBD has a good safety profile. And the studies mentioned here suggested that treatment with medical cannabis is safe and can improve the behavioral symptoms, functionality and quality of life of the patient with ASD. Despite this, it is important to highlight that controlled clinical trials and double-blind studies are crucial for a better understanding of the efficacy, tolerability and safety of the medicinal use of cannabinoids in the treatment of patients with autism. However, as interest in the topic increases and new evidence emerges around the world, there is a tendency towards an increase in prescriptions – which is already practiced by some professionals off-label.

situation in Brazil
In Brazil, the importation of products based on CBD and THC – substances present in the cannabis plant and which are currently the most studied in health research – was regulated by the National Health Surveillance Agency (Anvisa) through RDC 17/2015 . To import the product, prior authorization from the agency is required, upon presentation of a prescription, medical report and consent form.

Currently, there are two open public consultations, proposed by Anvisa itself: Public Consultation 654/2019 addresses procedures for the registration and monitoring of medicines produced from Cannabis spp., its derivatives and synthetic analogues. While Public Consultation 655/2019 deals with the technical and administrative requirements for the cultivation of the plant by pharmaceutical companies, solely and exclusively for medicinal and scientific purposes.

 

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