Autism and medical cannabis

Autism Spectrum Disorder (ASD): when we talk about Autism, we talk about it on a spectrum, meaning each individual will have a unique presentation of strengths, challenges, traits and symptoms. As such, every individual’s experiences and needs will be individual.

“Neurodivergent” is an umbrella term for people who have a variation to their neurological function or brain structure; “neurotypical” means the opposite. Many autistic advocates want to share that many “symptoms” of ASD can be considered positive traits, and they are proudly neurodivergent.

Signs and symptoms of autism can be detected as early as 18 months, and many people receive an ASD diagnosis in early childhood. Unfortunately, children with ASD have long been stigmatized and marginalized, leaving children, parents and caregivers with little help and resources available. Over the past decades, many parent groups and not for profit organizations have been created to support and share resources on ASD (Fédération québécoise de l’autisme, Autisme Québec, Autism Canada). Some of these groups now educate, advocate and promote medical cannabis use in ASD (Whole Plant Access for Autism; Pathfinders for Autism) These groups are critical to policy changes on medical cannabis legislation.

We want to acknowledge that while the following discusses some of the potentially therapeutic benefits of medical cannabis, this is not a statement that we believe all persons with ASD require treatment, but rather it may be appropriate for some.

Exploring the rationale and evidence for the use of medical cannabis in Autism Spectrum Disorder

Medical cannabis is a special treatment in its own way; it does not have the status of a medication (no drug identification number), but it is available as a treatment in a separate access program (Health Canada). Indeed, while there is ample historical evidence that cannabis was used for a wide array of medical conditions, it makes sense that cannabis’ safety and efficacy must be proven by our modern standards before 21st-century medicine assimilates it completely.

Cannabis became extremely trendy in Canada after its legalization for adult recreational use in 2018. One positive outcome is the decreased stigma and people now talk more freely about cannabis – also sharing anecdotes about potential therapeutic effects in a variety of medical conditions.

Autism spectrum disorder is one such condition, and this post aims to explain why medical cannabis may help and why it is not widely prescribed at this time.

What is Autism Spectrum Disorder (ASD)?

Autism Spectrum Disorder is a neurodevelopmental condition affecting social, communication and behavioral spheres, in varying intensity. It’s worth noting that in recent years, the term Autism Spectrum Condition (ASC) has been used to decrease the stigmatization associated with the word “disorder” and embrace both the strengths and adversities of people living with the condition. For the purpose of this blog we will use the medical term found in the majority of the literature we reviewed, ASD.

The prevalence of ASD has increased in the past decade to 1 in 54 children (Center for Disease Control and Prevention). It appears to affect more boys than girls(Center for Disease Control and Prevention). Even though sex differences may exist in autism, this ratio may also be biased by the fact that girls are often misdiagnosed or diagnosed later in life (Rynkiewicz et al., 2019). The issue of male-centric research methodology is not new and we discuss it further in a previous post on gaps in women’s health research.

ASD, a multifaceted condition

The core symptoms of ASD typically cohabit with a myriad of non-core symptoms making the presentation of ASD in patients unique to the individual. The core symptoms include significant impairment in social interaction and communication as well as restricted, repetitive patterns of behavior (DSM-V). The non-core symptoms include motor impairment, anxiety, abnormal behavior, and sleep problems. Other comorbidities are epilepsy, pain, headaches, obsessive-compulsive disorder (OCD), Tourette syndrome, respiratory and skin allergies, and gastrointestinal symptoms (constipation, diarrhea, irritable bowel syndrome). Intellectual disability is present in about a third of patients with ASD and may aggravate some of those symptoms (Center for Disease Control and Prevention).

Both core and non-core symptoms can substantially affect the quality of life of the child as well as of the whole family. Furthermore, the communication issues present in ASD make it difficult to identify comorbidities. For example, a child with ASD may not perceive and communicate pain as a neurotypical child would.

“As with any family, there is a whole dynamic with the child with ASD or ASD-like symptoms, parents, and siblings. The violent anger crises and subsequent suicidal behavior are extremely difficult to deal with and traumatic for everyone. Finding the right treatment helps the affected child as well as the whole family dynamic.” Ramzy Wahhab, parent of a child with ASD-like symptoms.

Diagnosing ASD is a complex task and it can take several months to confirm. Currently, the diagnosis relies on physician evaluation of behaviors and their developmental trajectories.

Etiology: Causes and risk factors

Several factors come into play, such as genetic, perinatal, and environmental factors.

With regards to the genetic factors, some studies point to a higher risk of developing ASD if a sibling has it; others show that certain genetic conditions (fragile X syndrome or chromosomal abnormalities for example) have a higher risk of developing ASD (Huguet et al., 2013).

Current literature indicates that exposure to multiple perinatal factors could increase risk of developing ASD such as congenital malformation, delivery complications, poor condition at birth, and maternal use of medication (i.e. antidepressants, valproate) (Gardener et al 2011).

Some environmental factors may also play a role in developing ASD, for example having older parents may increase the risk for ASD (Karimi et al 2017).

However, no links between vaccines and ASD have been found – for more debunking information, read this post by a Quebec pharmacist.

ASD is a highly complex condition with various etiologies and presentation of symptoms. This increases the challenge of developing targeted pharmacological treatments, especially for the core symptoms of ASD. Most studies have investigated non-core symptoms and comorbidities of ASD, but there is a great lack of research on the core symptoms – for which no treatment is currently approved.

Available treatments for non-core symptoms

At the time of this writing, two antipsychotic medications (namely risperidone and aripiprazole), have been approved by the American regulatory body (FDA) for ASD-associated behavioral disturbances in children (aggressivity and irritability).

These medications are generally used in psychiatric disorders such as schizophrenia. Other treatments frequently used include sedatives, antidepressants and anticonvulsants. Usually, a combination of non-pharmacological interventions (such as behavioral therapy) and pharmacological treatment will help reduce symptoms and improve quality of life.

However, these pharmacological treatments mainly target non-core symptoms of ASD and present strong side-effects, such as weight gain. Parents, caregivers and providers are thus looking into alternative treatments with a more desirable risk to benefit ratio.

How can medical cannabis help in ASD?

Endocannabinoid System 101

The endocannabinoid system is found throughout the central and peripheral nervous system as specific neurotransmitters and receptors. Our body produces many naturally occurring endocannabinoids; when they bind to the receptors it generates effects on our nervous system ( Bricaire et Brue, 2007; Zou et al., 2019). We can supplement or adapt this system by ingesting synthetic or plant-based cannabinoids that bind to specific cannabinoid receptors.

These receptors are expressed at very low levels in the brain region responsible for breathing, so it is not possible to die of an overdose with cannabis (World Health Organization) as compared to other drugs.

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Interestingly, the endocannabinoid system seems affected in autism: levels of the endocannabinoid anandamide are lower in children with ASD compared to the control group. (Karhson et al. 2018; Aran et al. 2019) This measurable decrease in anandamide may be a sign of unbalance in the endocannabinoid system, possibly impacting body functions.

If indeed the endocannabinoid system is unbalanced, a therapeutic avenue could consist in an attempt to restore balance with synthetic or plant-based cannabinoids. Currently more research is required to better understand how the endocannabinoid system works and how it may be affected in ASD.

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Clinical research on medical cannabis and ASD

At the time of this writing, there is a very small number of published clinical trials on cannabinoids and ASD, and only one randomized controlled trial (RCT) – the gold standard of clinical trials. For this reason, there is currently not enough evidence on the potential benefits and risks of cannabinoids/medical cannabis in autism spectrum disorder (Agarwal et al. 2019). The level of evidence is only preliminary (Fusar-poli et al. 2020), as indeed research is just getting started.

Let’s take a look at the preliminary evidence obtained from these few clinical trials. (Kurz and Blaas, 2010; Kuester et al. 2017; Aran et al. 2019; Barchel et al. 2019; Bar-Lev Schleider et al. 2019; Fleury-Teixeira et al. 2019; Ponton et al. 2020; McVige et al. 2020; Mostafavi et al. 2020; Aran et al. 2021).

Most studies investigated a formulation of cannabidiol (CBD) and delta-9-Tetrahydrocannabinol (THC), several using a 20:1 ratio of CBD:THC
One study evaluated the effects of dronabinol (synthetic THC) on one patient with ASD
All studies report improvement in some symptoms (behavior, epilepsy, sleep disturbances, hyperactivity)
Some report improvements in core symptoms (communication, social interaction) (Bar-Lev Schleider et al. 2019; Fleury-Teixeira et al. 2019; Ponton et al. 2020; Aran et al. 2021)

A recent study compared a whole-plant cannabis extract (20:1 CBD/THC ratio) to a purified THC and CBD formulation (also 20:1 CBD/THC ratio) and to placebo (Aran et al. 2021). This design choice is especially interesting as it helps understand if minor cannabinoids and terpenes in whole plant cannabis may contribute to the potential therapeutic effects.

49% of patients had a positive response with the whole-plant extract, which is significant compared to the 21% positive response with placebo;
38% of patients had a positive response with the purified cannabinoid extract, but the difference is not significant compared to the whole-plant extract.

Overall, these studies point to a potential effect of CBD-rich treatment on some symptoms of ASD, mainly anxiety, epilepsy and sleep disturbances. Compared to THC, CBD does not have a psychoactive effect and has been shown to produce anxiolytic effects (reduction in anxiety) (Skelley et al., 2020). This could explain why CBD-rich treatments are a preferred avenue for symptom management in pediatric conditions such as ASD. Medical cannabis, especially CBD-rich treatments, may help with non-core symptoms which in turn could improve overall quality of life. Proper conclusions are difficult to draw right now but it is encouraging to notice research is ongoing with a few clinical trials further investigating the impact of cannabidiol (CBD) underway (clinical trials.gov).

However, on top of obstacles related to cannabis regulations (obtaining cannabis products and a cannabis research license), we must also acknowledge the particular challenge of leading clinical trials in the pediatric population, as it requires parental consent, specific ethics reviews and other measures to ensure this vulnerable population is adequately protected.

So why use medical cannabis for ASD symptom management?

The current level of scientific knowledge is insufficient to positively confirm the potential therapeutic role of cannabinoid-based medicines in ASD.

As with many medical cannabis potential indications, the scientific evidence from high quality, meaningful and long term studies is lower than what we’d like when moving into clinical practice; however, the reality of many of our patients and their caregivers is that conventional treatments didn’t work and medical cannabis often represents the last line of treatment.

Similarly to off-label use of pharmaceutical drugs, medical cannabis is sometimes trialled for conditions in which supporting evidence is low, but the risks are low as well. Common side effects associated with medical cannabis (including both CBD and THC) include dizziness, somnolence, sedation, headaches, nausea and dry mouth, most of which are mild and transitory (Wang et al., 2008; Chesney et al., 2020 for CBD only), serious side effects are rare. In fact, a purified CBD-rich extract was recently approved by the FDA for seizures management in child refractory epilepsy (FDA press release), but is not yet approved in Canada. With moderate indications of symptom improvement combined with an acceptable safety profile, medical cannabis may represent a more desirable risk to benefit ratio to treat some ASD symptoms.

Before prescribing a patient, in particular a pediatric patient, a “non-conventional” treatment such as medical cannabis, a careful calculation by the medical team and family is warranted: understanding the overall risks, having trialled other medications without success, and being ready to try a new medication that may or may not work perfectly, but is less likely to cause any severe adverse effects. In such risk-benefit calculations, Real-World evidence based on observational studies can be a substitute for an RCT.

ASD at Santé Cannabis

At our clinic, we treat pediatric patients with extreme caution; we only accept pediatric patients with a formal reference from their child specialist or primary care physician stating several conventional treatments have been tried unsuccessfully and that they would like to approach medical cannabis as a last-line of treatment. Ongoing communication between our clinic physician and the child referring physician is also essential to insure proper care and monitoring of medical cannabis treatment.

At Santé Cannabis, we do not currently do observational research on patients under 18. However, we record how many patients (adult and pediatric) were seen: from July 14th 2020 through March 31st 2021, we saw about 1,460 patients, and 17 (1.16%) have a diagnosis of ASD (shortened to Autism in our records).

What’s next?

On top of further investigation of safety and efficacy of medical cannabis in ASD, more research is needed on the long-term use of medical cannabis to assess its side-effects as well as potential impacts on children’s brain development. Differentiating the benefits and side effects of CBD and THC will help develop medication especially targeted for the pediatric population.

We need more information on the other cannabinoids and terpenes present in medical cannabis products, from precise concentration information to the potential therapeutic effects of these lesser-known compounds, allowing us to better understand the distinct nature of synthetic versus whole-plant derived cannabinoid-based medicines.

On the bright side, some resources are available to supplement our gaps in knowledge. In particular, Real-World Evidence (RWE) from observational studies can provide evidence that can help direct randomized controlled research. Every piece of information we can extract is essential to evaluate the risk-benefit ratio for medical cannabis in ASD. While randomized clinical trials remain the gold standard and the mandatory path for prescription drug development, RWE can complement RCT findings and provide information closer to clinical practice reality. At Santé Cannabis, we strive to advance medical cannabis research, from our observational studies, and research offering to the essential dissemination work through events and publications

Furthering research could also incite provincial health insurances (i.e. RAMQ) to cover medical cannabis if it is demonstrated to possess therapeutic effects. For many interested in exploring medical cannabis to treat behavioural symptoms, the cost of purchasing this medicine is prohibitively expensive; currently, treatment plans relying on CBD products – preferred for children over THC, but more expensive – can cost up to $1,000 a month, $12,000 per year.

As part of our patient advocacy we see high-quality research as the way to bring these complementary treatments into the mainstream, allow doctors to prescribe with clarity, allow for insurance coverage, and reduce trial and error in finding the right dosage. As such, we will continue to treat and study ASD through our clinic, contributing to the knowledge base; and as with any diagnosis or symptom, we’re interested in exploring further with the right partners.

To find out more about ongoing research and potential new projects, explore our page

Authors: Charlotte Bastin, Dr. Lucile Rapin

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