Cannabis and Autism

By Kaylee Martig

Autism Spectrum Disorder (ASD) is characterized by persistent social, communicative, and locomotor deficits across multiple contexts. Symptoms may include deficits in social-emotional reciprocity, nonverbal communicative behaviors, and relationships; and restricted, repetitive patterns of behavior, interests, or activities, such as stereotyped or repetitive movements, insistence on sameness, fixated interests, or sensory processing differences (1). Comorbidities of ASD may include sleep disorders (54.7% prevalence), Attention Deficit Hyperactivity Disorder (ADHD; 88.7% prevalence), self-injury (88.7% prevalence), anxiety (49.1% prevalence) and epilepsy (2, 3). As many as 1.6% of 8-year-old children are diagnosed with ASD. Currently, there are no treatments for its core symptoms, including social and communication deficits, only for its comorbid symptoms, such as self-injury and anxiety, which are often treated with drugs including antipsychotics and antidepressants (4). Because conventional treatments are not always effective, and often have adverse side-effects, more parents are turning to less conventional treatments, including using medical cannabis, to treat severe symptoms.

There are many neurological underpinnings of ASD, including excess cortical excitation and impaired anandamide signaling, which are based in the body’s endocannabinoid system. As previously described, the endocannabinoid system is comprised of CB1 and CB2 receptors which are activated by endogenous cannabinoid neurotransmitters 2-AG and anandamide. Through various mechanisms, the endocannabinoid system controls emotional responses, contextual behavioral reactivity, social interaction, and circadian rhythms (4). This suggests that many of the symptoms and comorbidities of ASD, including deficits in social-emotional reciprocity, anxiety, and sleep disturbances, may be mediated by the endocannabinoid system.

One function of the endocannabinoid system is to regulate levels of cortical inhibition/excitation. Excess cortical excitation can cause hyper-sensitivity and hyper-reactivity, which are related to many of the symptoms and comorbidities of ASD. The inhibition/excitation balance could be restored by decreasing excitation or increasing inhibition. A recent study found CBD to contribute to this regulation in people with ASD (5). Additionally, decreased levels of the cannabinoid anandamide in the endocannabinoid system may contribute to symptoms of ASD. The first study of anandamide in children with ASD found significantly lower plasma levels of anandamide in children with ASD, supporting impaired anandamide signaling as a key factor in ASD (6). These connections are promising in considering treatment with cannabis, which can regulate inhibition/excitation and increase levels of anandamide.

A report from one early-stage clinical trial found improvement in “at least one of the core symptoms of ASD” in most cases of children being treated with cannabis with various THC:CBD ratios (7). This study also noted improvement in comorbid symptoms, including sensory difficulties, feeding and sleep disorders, and seizures. Additional studies have focused on using CBD-rich cannabis (1:20 ratio of THC:CBD) to treat comorbid symptoms, including behavioral outbreaks/self-injury, hyperactivity, anxiety, and feeding and sleep disorders in children with ASD (2, 8). Improvement was noted in the majority of children, with minimal adverse effects, which included sleep disturbances, drowsiness, irritability, and changes in appetite. These findings suggest non-inferiority of treatment with CBD (see table 1.1), although more research is needed to establish efficacy in treating core symptoms.

 

Table 1.1 Comparison of Cannabis to Conventional Treatments

Symptom	Improvement with cannabis (1:20 THC:CBD)	Improvement with conventional treatment
hyperactivity	68.4%	80% (methylphenidate)
self-injury	67.6%	82% (aripiprazole)
sleep problems	71.4%	60% (melatonin)
anxiety	47.1%	55-73% (SSRIs)

In all comorbid symptoms of ASD, non-inferiority of CBD was observed (2).

 

The benefits of cannabis for epilepsy, another common comorbidity of ASD due to similar neural mechanisms that reflect decreased inhibition, are also being increasingly researched, and have appeared effective in preventing seizures preclinical models as well as numerous case studies (9, 10). Extensive research supports the use of CBD-rich cannabis to reduce seizure frequency in cases of treatment-resistant epilepsy, particularly in children with Dravet Syndrome and Lennox-Gastaut Syndrome (11, 12). One recent study found that in a group of children with drug-resistant Dravet Syndrome, 62% of children experienced improvement in their overall condition while using CBD-rich cannabis (13). While it is difficult to ascertain the prevalence of cannabis use for ASD or its comorbidities, it appears more parents are administering cannabis to their children, especially in cases where conventional drugs have failed. One mother credits cannabis for reducing self-injurious and violent behavior in her 12-year-old son with low-functioning ASD who, even while taking antipsychotics, could have as many as 300 violent episodes in a day (14).

In summary, more research is required to establish whether cannabis is an effective and safe treatment for ASD in children. Abnormalities in the endocannabinoid system likely contribute to ASD symptoms and comorbidities, making CBD a plausible treatment by increasing anandamide to normal levels. In preclinical and early clinical studies, adverse effects appear to be limited. However, more research should be conducted to demonstrate long-term safety of cannabis use, particularly in children. It is important to note that any drug should be used only when benefits outweigh the potential risks, and as such conversation surrounding the use of cannabis to treat ASD should be for the treatment of severe symptoms, such as severe feeding disorders and self-harm, rather than neurodivergence. The goal is not to eradicate diversity but to improve functioning and quality of life.

References

1. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5^th ed.). doi:10.1176/appi.books.9780890425596
2. Barchel, D., Stolar, O., De-Haan, T., Ziv-Baran, T., Saban, N., Fuchs, D. O., . . . Berkovitch, M. (2019). Oral cannabidiol use in children with autism spectrum disorder to treat related symptoms and co-morbidities. Frontiers in Pharmacology. doi:10.3389/fphar.2018.01521
3. Poleg, S., Golubchik, P., Offen, D., & Weizman, A. (2018). Cannabidiol as a suggested candidate for treatment of autism spectrum disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 89, 90-96. doi:10.1016/j.pnpbp.2018.08.030
4. Chakrabarti, B., Persico, A., Battista, N, & Maccarrone, M. (2015). Endocannabinoid signaling in autism. Neurotherapeutics, 12, 837-847. doi:10.1007/s13311-015-0371-9
5. Pretzsch, C. M., Freyberg, J., Voinescu, B., Lythgoe, D., Horder, J., Mendez, M. A., . . . McAlonan, G. M. (2019). Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Neuropsychopharmacology. doi:10.1038/s41386-019-0333-8
6. Karhson, D. S., Krasinska, K. M., Dallaire, J. A., Libove, R. A., Phillips, J. M., Chien, A. S., . . . Parker, K. J. (2018). Plasma anandamide concentrations are lower in children with autism spectrum disorder. Molecular autism, 9. doi:10.1186/s13229-018-0203-y
7. Kuester, G., Vergara, K., Ahumada, A., & Gazmuri, A. M. (2017). Oral cannabis extracts as a promising treatment for the core symptoms of autism spectrum disorder: Preliminary experience in Chilean patients. Journal of the Neurological Sciences, 381, 932-933. doi:10.1016/j.jns.2017.08.2623
8. Aran, A., Cassuto, H., & Lubotzky, A. (2018). Cannabidiol based medical cannabis in children with Autism – a retrospective feasibility study. Neurology, 90. Retrieved from http://n.neurology.org/content/90/15_Supplement/P3.318
9. Devinsky, O., Cilio, M. R., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., . . . Friedman, D. (2014). Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55. doi:10.1111/epi.12631
10. Porter, B. E., & Jacobson, C. (2013). Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior, 29, 574-577. doi:10.1016/j.yebeh.2013.08.037
11. Elliot, J., DeJean, D., Clifford, T., Coyle, D., Potter, B. K., Skidmore, B., . . . Wells, G. A. (2018). Cannabis-based products for pediatric epilepsy: A systematic review. Epilepsia, 60. doi:10.1111/epi.14608
12. O’Connell, B. K., Gloss, D., & Devinsky, O. (2017). Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy & Behavior, 70, 341-348. doi:10.1016/j.yebeh.2016.11.012
13. Devinsky, O., Cross, H., Laux, L., Marsh, E., Miller, I., Nabbout, R., . . . Thiele, E. A. (2017). Trial of cannabidiol for drug-resistant seizures in the Dravet Syndrome. New England Journal of Medicine. doi:10.1056/NEJMoa1611618
14. Myung-Ok Lee, M. (2017). I made my son cannabis cookies. They changed his life. The Washington Post. Retrieved from https://www.washingtonpost.com/opinions/i-made-my-son-cannabis-cookies-they-changed-his-life/2017/01/06/699b1d20-d1ef-11e6-a783-cd3fa950f2fd_story.html?noredirect=on&utm_term=.a8c07e3c9bc6