The potential of cannabinoids in the treatment of autism
Article written on the platform PebMed by Filipe Fernandes, psychiatrist and Psychiatry resident in Childhood and Adolescence at the Center for Adolescent and Childhood Psychics (CEPAI/Fhemig). Works with children, adolescents, and adults in the city of Belo Horizonte (MG).
Autism Spectrum Disorder (ASD) is the term used to describe an atypical neurodevelopmental form, characterized by early manifestations of communication difficulties and social interaction, and the presence of repetitive or restricted behaviors and/or interests. These are the core symptoms of the disorder, but the form and severity of its presentation vary. It is a pervasive and permanent disorder, with no cure, although early multidisciplinary intervention focused on hyperstimulation (behavioral and educational) can alter the prognosis, improving the functionality and quality of life of the patient.
Pharmacological treatment is formally indicated only for cases of significant irritability or aggression, where the patient puts themselves or others at risk. It may also be indicated for the treatment of comorbid conditions, with sleep disorders and attention deficit/hyperactivity disorder (ADHD) being the most common.
Cannabinoids for the treatment of Autism Spectrum Disorder
The use of cannabinoids - especially cannabidiol (CBD) - has become increasingly common in the treatment of children with refractory epilepsy to conventional treatments and other pathologies, including in Brazil. After several reports on the use of medicinal 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 relieve such symptoms in their children.
Since then, many reports from around the world have been accumulating, showing substantial improvement in behavior, functionality, and quality of life in patients with ASD after starting treatment with medicinal cannabis. There is also curiosity about the possibility of this use also influencing the improvement of the disease's central symptoms. Although many autism patients are already being treated with CBD-based preparations, there is still a great deal of unknowns about the scientific evidence and analysis of safety, tolerability, and efficacy profiles 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 has no psychotropic effect (does not cause a "high", does not induce 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 CBD use in treating the most common behaviors and comorbidities of ASD patients. The study concluded that deficits in social interaction are part of the main phenotypes of ASD, and that CBD has shown some pro-social properties in preclinical studies.
See more content on the subject:
- The discussion and context of medicinal cannabis in Brazil
- Endocannabinoid system and medicinal use of cannabis
- The use of Cannabidiol in the pediatric population
Furthermore, it demonstrated that cannabidiol may be effective as monotherapy or adjunctive treatment in some of the most common comorbidities of autism patients, such as sleep disorders, ADHD, anxiety, and seizures. The level of evidence is still very low regarding the effects on other comorbidities, such as psychosis, addictive behavior, cognitive or mood disorders, and aggression.
The study also concluded that there is certainly a significant gap on the subject, and many more studies are needed before any conclusions can be made about the therapeutic potential of cannabinoid use in ASD patients. It was highlighted that all current evidence is indirect and based on the efficacy of CBD in pathological conditions that could also be present in autism. Therefore, the potential efficacy of CBD in the context of ASD is still a hypothesis.
Nature Journal Study
More recently, the prestigious scientific journal Nature (with a highly relevant impact factor) published the article "Real-life experience in the treatment of autism with medicinal cannabis: analysis of safety and efficacy". In this study, data from 188 ASD patients treated with medicinal cannabis between 2015 and 2017 were collected and analyzed - the group had an average age of 12.9 years, and some patients had associated comorbidities, with epilepsy (14.4%) and ADHD (3.7%) being the most prevalent.
In most patients, the treatment was based on the use of cannabis oil containing 30% CBD and 1.5% THC (a ratio of 20 CBD to 1 THC). Data were collected through structured questionnaires applied to caregivers, containing symptom inventories, global assessments, and side effects. The collection was done 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 moderate response; 6.4% reported slight improvement; and 8.6% reported no improvement. Moreover, improvement or disappearance of symptoms such as restlessness, rage attacks, agitation, sleep problems, anxiety, constipation, and digestion problems were reported in 75% of patients or more. The same efficacy was not observed in improving or eliminating speech disorders, cognitive deficits, incontinence, limited mobility, increased appetite, and lack of appetite.
Side effects were observed in 25.2% of patients, with restlessness (6.6%) being the most common. It is important to note that this was a study conducted without a control group, and therefore no causality between cannabinoid therapy and improved well-being can be established. The study was based on observation reports provided by parents/caregivers, and the evaluation consisted of subjective variables such as quality of life, mood, and general effects - factors that may be influenced by the opinions of parents/caregivers.
Safety of medicinal cannabis use
Report from the World Health Organization (WHO) highlighted that CBD has a good safety profile. And the studies mentioned here suggested that treatment with medicinal cannabis is safe and can improve the behavioral symptoms, functionality, and quality of life of ASD patients. However, it is important to emphasize that controlled clinical trials and double-blind studies are crucial for a better understanding of the efficacy, tolerability, and safety for the medicinal use of cannabinoids in treating autism patients. However, as interest in the subject increases and new evidence emerges worldwide, there is a trend towards increased prescriptions - which is already being practiced by some professionals off-label.
Situation in Brazil
In Brazil, the import of products based on CBD and THC - substances present in the cannabis plant and 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 public consultations open, proposed by Anvisa itself: Public Consultation 654/2019 addresses the procedures for the registration and monitoring of drugs produced based on Cannabis spp., its derivatives, and synthetic analogs. While Public Consultation 655/2019 deals with the technical and administrative requirements for the cultivation of the plant by pharmaceutical companies, solely for medicinal and scientific purposes.