Cannabis for Autism: A Meta-Analysis of the Research

Autism is classified as a condition that exists across a spectrum, meaning that it manifests in various degrees. For this reason, it is often referred to as Autism Spectrum Disorder (ASD) or Autism Spectrum Condition (ASC).

“Asperger’s syndrome” is a term that is often used in reference to a type of ASD with moderate signs and symptoms, and often certain “enhanced” functional characteristics (for example, regarding cognitive function or I.Q.).

Across the spectrum of ASD or autism, there are several signs and symptoms that are characteristically present, including:

• Difficulty communicating and interacting with others, or understanding their thoughts and feelings
• Repetitive, ritualistic behavior patterns or movements (“stimming”)
• Anxiety or disturbing emotions when in unfamiliar social situations or environments
• Gastrointestinal problems (e.g. constipation)
• Sensory overload – bright lights and loud noises can be stressful, uncomfortable or overwhelming

The usual presentation of autism tends to be of the “low functioning” type, involving

difficulties with learning spoken language (“delayed speech”), tantrums, bouts of aggression (towards self- and/or others), and delayed cognitive development.

Existing Therapies for Autism

Autism therapies include a wide variety of approaches intended to improve quality-of-life and lessen any disabling deficits or problematic behaviors. Among these are several behavioral therapies, including: cognitive behavior therapy (CBT), behavioral management therapy, speech-language therapy, occupational therapy (OT), social skills training, educational and school-based therapies.

The principal medications applied in the treatment of ASD are given to support the ability of a patient to participate more fully in life and activities at home or in school. The most commonly prescribed medications are anticonvulsant or various types of psychoactive drugs, including stimulants, and antipsychotics.

Antipsychotic drugs may also be used to help with the depression, tic disorders and irritability that are often part of life with autism. Some classes of antidepressant drugs may also be prescribed to reduce repetitive and ritualistic behaviors, or for management of ADHD or symptoms of anxiety. Unfortunately, many of these drugs carry severe side-effects, particularly when taken since childhood, or over a long period of time.

How Might Medical Marijuana Help With Autism?

Given that the majority of drugs approved by the FDA for the treatment of autism carry harsh side-effects, many seek effective, alternative medications. Because cannabis and its many compounds (like CBD) have been found to be so helpful in other behavioral and mood disorders, medical marijuana is seen as a prime candidate for developing breakthrough autism therapies.

At the top of the list of helpful compounds present in cannabis is the popular cannabinoid, cannabidiol, also known as CBD. CBD possesses some antipsychotic and anxiolytic (anti-anxiety) properties that may be helpful in reducing the behavioral and emotional difficulties experienced with autism.

There is some evidence to suggest that medical cannabis may be useful for autism directly. An unhealthy endocannabinoid system (ECS) and inflammation early in life may trigger long-term immune system dysregulation. Cannabis may help restore balance to the immune and central nervous systems– in particular by supporting anandamide signaling– which could in turn help retune the e.

Autism, the ECS and the Gut-Brain Connection

Utilizing medical cannabis could also help manage other symptoms and conditions associated with autism, such as IBD, epilepsy and ADHD. The anti-inflammatory properties of CBD and tetrahydrocannabinolic acid (THCA) could help regulate gut function, reduce seizures and improve concentration levels.

Recent studies have also shown a direct connection between the severity of autism spectrum symptoms and digestive health. The endocannabinoid system (ECS) plays an important role in the health of our microbiome, or the beneficial bacteria that live and work in our digestive tracts. Many of us are familiar with taking probiotic capsules or special yogurt drinks to support digestive health and help relieve the symptoms of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).

The gut microbiome directly influences our neuropsychiatric health via what is called the “gut-brain axis.” Recent studies have shown that microbiome-targeted therapies can modulate brain activity, and in this way promote behavioral and functional improvement in children with ASD.

The endocannabinoid system (ECS) plays a key role in regulating the microbiome and overall gastrointestinal function. In autism, the ability of the ECS to influence gastrointestinal inflammation, the microbiome and gut permeability, provides supporting evidence for why many patients with autism experience significant therapeutic improvements from the cannabinoids present in effective medicinal cannabis products.

More Benefits from the Cannabinoids in Medicinal Cannabis

Those with autism may have an awry default mode network (DMN). The default mode network (DMN) is a network of interacting brain regions that is active when a person is not focused on the outside world, measurable with the fMRI technique. Cannabinoids like CBD could help reset the DMN to some extent, which could help reduce anxiety and improve social awareness.

With all of these potential benefits, it would be fair to say that medical cannabis has a lot of promise when it comes to managing symptoms associated with autism. However, more research is needed on which cannabinoids, ratios and terpenes might be most helpful.

There is every possibility that using too much THC may increase anxiety, and too little CBD may be overstimulating for some. It is possible that improper dosing of medical cannabis may produce negative outcomes for some autistic patients, but more research is needed.

What Do the Studies Say?

Total No. of Studies: 34

Positive: 27

Inconclusive: 6

Negative: 1

Meta-analysis = 19 (14 positive, 5 inconclusive)

Animal study = 7 (all positive)

Double-blind human trial = 4 (3 positive, 1 inconclusive)

Human trial = 3 (all positive)

Laboratory study = 1 (negative)

16 studies included CBD (13 positive, 3 inconclusive)

11 studies included THC (10 positive, 1 inconclusive)

1 study included a 1:1 THC:CBD extract (positive)

6 studies included anandamide (5 positive, 1 inconclusive)

Quotes

“There has been a dramatic increase in the number of children diagnosed with autism spectrum disorders (ASD) worldwide. Recently anecdotal evidence of possible therapeutic effects of cannabis products has emerged. The aim of this study is to characterize the epidemiology of ASD patients receiving medical cannabis treatment and to describe its safety and efficacy. We analysed the data prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017.

The treatment in [the] majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires.

After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition. Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%). Cannabis in ASD patients appears to be [a] well tolerated, safe and effective option to relieve symptoms associated with ASD.”

Source: Bar-Lev Schleider, Lihi et al. ‘Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy‘ Scientific reports vol. 9,1 200. 17 Jan. 2019, doi:10.1038/s41598-018-37570-y

“53 children at a median age of 11 (4-22) year received cannabidiol for a median duration of 66 days (30-588). Self-injury and rage attacks (n = 34) improved in 67.6% and worsened in 8.8%. Hyperactivity symptoms (n = 38) improved in 68.4%, did not change in 28.9% and worsened in 2.6%. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5%. Adverse effects, mostly somnolence and change in appetite were mild.”

Source: Barchel, Dana et al. ‘Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities‘, Front Pharmacol. 2019 Jan 9;9:1521. doi: 10.3389/fphar.2018.01521. eCollection 2018.

“Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n = 45) versus 21% on placebo (n = 47; p = 0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n = 34) versus 3.6 points after placebo (n = 36); p = 0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n = 95); 23% and 21% on pure-cannabinoids (n = 93), and 8% and 15% on placebo (n = 94).”

Source: Aran, A., Harel, M., Cassuto, H. et al. ‘Cannabinoid treatment for autism: a proof-of-concept randomized trial’ Molecular Autism 12, 6 (2021). https://doi.org/10.1186/s13229-021-00420-2

“[F]or the first time at our knowledge, we have observed in children without GI symptoms treated with probiotics significant modification of core ASD symptoms measured by the ADOS-CSS scores (specifically Social-Affect domain) that are unrelated to the specific intermediation of the probiotic effect on GI symptoms. As far as children with GI symptoms, the six-month supplementation with DSF showed significant effects, when compared to placebo, in improving not only GI symptoms but also multisensory processing and adaptive functioning.”

Source: Santocchi, Elisa et al. ‘Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial’ Frontiers in Psychiatry, 11, 550593 (2020). https://doi.org/10.3389/fpsyt.2020.550593

Potential Pros of Medical Cannabis for Autism

• Reduced rates of self-injury and bouts of rage
• Reduced anxiety and depression
• May help reduce or replace the need for some pharmaceutical medications
• Can help manage associated symptoms, such as digestive or gastrointestinal problems, insomnia, hyperactivity, seizures etc.

Potential Cons of Medical Cannabis for Autism

• May induce anxiety and restlessness in some
• Somnolence (drowsiness)
• Decreased appetite
• Some studies show that autism spectrum symptoms worsened in a minority of patients, suggesting that medical cannabis may not be useful for all ASD patients. It is possible that certain patients may require very specific cannabinoid-terpene profiles, ratios and dosages to show the anticipated benefits.

Summary

There are few medications available for autism spectrum disorder (ASD), and those tend to cause a number of adverse side-effects. New medications are needed, and there is research to suggest that medical cannabis may help manage anxiety, depression, bowel disorders, neuroinflammation and immune system dysregulation in those with ASD.

Several studies, including some clinical trials, indicate that certain medical cannabis products may be useful adjunct or alternative treatments. The most promising reports are for cannabis-derived agents taken to manage several symptoms associated with autism, such as: anxiety, gastrointestinal or digestive problems, and symptoms arising from other associated health conditions.

Both THC and CBD may help regulate the immune system and anandamide signaling in those with autism. Their acidic counterparts — THCA and CBDA — also have anti-inflammatory properties that could be of use in managing autism.

More research is needed on dosing and determining the cannabinoid ratios that are most helpful for managing autism, as well as the age groups in which medical cannabis therapy is most appropriate.