Autism

Understanding Social Problems in Autism: A Potential Role for the Endocannabinoid System

social problems in autism

For parents, it can be heartbreaking to watch a child with autism spectrum disorder (ASD) struggle with one of the most debilitating symptoms of the condition: social anxiety. From early childhood, patients with autism often have social problems due to the high anxiety they experience when trying to cope in social situations. In fact, many of the symptoms in patients with autism directly mirror those experienced by patients with social anxiety disorder. As a result, they often struggle to find friends at school, and the severity of their social anxiety may not wear off as they get older; these patients may find themselves increasingly isolated in adolescence and early adulthood, which can significantly limit their opportunities in later life.

Because social anxiety can have such extensive effects on the life outcomes of patients with autism, its pathophysiological underpinnings have long been a subject of study for researchers. The etiology of social anxiety still remains poorly understood, but research over the last few decades suggests that the endocannabinoid system may play a role in mediating symptoms that lead to social problems. As a result, some researchers are now considering the endocannabinoid system as a possible target for future therapeutics that treat social anxiety in patients with autism.

Links Between the Endocannabinoid System and Social Anxiety in Patients with Autism

The endocannabinoid system is considered a major neuromodulatory system, affecting a wide range of cellular processes, including neuroinflammation, energy metabolism, and immune system control. It consists of a complex system of lipid signaling pathways, in which the major players are two arachidonic acid-derived compounds (anandamide and 2-arachidonoyl glycerol) and their cannabinoid receptor targets (CB1 and CB2), along with a variety of associated enzymes and transporters. So far, studies have linked the endocannabinoid system to the regulation of emotional and behavioral responses in social contexts, as well as social interactions, all of which play a role in social anxiety in patients with autism. While the connections between the endocannabinoid system and the symptoms of autism are indirect, the preliminary findings have contributed to an increasingly well-regarded hypothesis that dysregulation of the endocannabinoid system may be one of the etiological foundations of autism.

One of the strongest early studies providing support for this hypothesis was published in the journal Current Neuropharmacology. In this study, a group of researchers from around the world collaborated on a joint project in which they evaluated the effects of endocannabinoid system disruption in mouse models of autism. Using a combination of behavioral and neurochemical tests, they were able to show that the disruption could enhance stereotypic autism-related behaviors in the mouse models, including those associated with social anxiety.

A more comprehensive systematic review of the evidence, conducted by a group of Stanford University researchers in 2016, provides even more convincing evidence about the broader role of endocannabinoid signaling in social functioning. Recognizing the growing body of evidence that cannabinoid signaling may be involved in social functioning, the researchers used a well-established systematic research construct to integrate and analyze the role of endocannabinoid signaling social functioning across multiple diagnostic categories, including autism. They found that the majority of the evidence supports the hypothesis that primary receptors and effectors in the cannabinoid system—including delta-9-tetrahydrocannabinol, cannabidiol, anandamide, and 2-arachidonoylglycerol—all have relevant effects on measures of social functioning, such as anxiety, chronic stress, attachment, affiliation, and communication. It is important to note that the authors drew data from studies on autism, as well as other psychological and psychiatric disorders (like major depressive disorder, PTSD, and bipolar disorder), but their conclusion regarding the role of endocannabinoids on social functioning in general has promising implications for patients with autism who are specifically interested in therapeutics that target symptoms of social anxiety.

The Endocannabinoid System as a Treatment Target for Social Problems in Autism

As yet, there are no major studies in which researchers have specifically tested therapeutics that target the endocannabinoid system in the treatment of autism. Nevertheless, related research has produced promising results. For instance, in some animal models of autism, treatment with cannabidiol has been shown to impact social deficits, but more research is needed to solidify the results and establish statistical significance. A case report on a young patient with PTSD-related anxiety may also be relevant: when treated with cannabidiol oil, the patient showed significant improvements in anxiety levels, and there were no major safety concerns associated with targeting the endocannabinoid system. Given the parallels between this patient’s symptoms and those commonly experienced by patients with autism, it is possible that similar treatments targeting the endocannabinoid system may have comparable effects on social anxiety in such patients.

Additionally, the endocannabinoid system’s role in neuroinflammation suggests that it may be possible to address endocannabinoid disruption in patients with autism with anti-inflammatory dietary supplements, such as curcumin. Studies show that levels of neuroinflammatory cytokines are elevated in patients with autism, and some scientists believe that this may be the result of endocannabinoid disruption. According to a 2015 study published in Life Sciences, it may be possible to reduce the levels of these same cytokines through curcumin supplementation. In this study, the researchers treated rat models of autism with oral doses of curcumin (either 50 mg/kg, 100 mg/kg, or 200 mg/kg), and they found significant improvements in multiple behavioral paradigms associated with social anxiety, including social interaction, general anxiety, and repetitive coping behavior. Therefore, addressing the neuroinflammatory effects of endocannabinoid disruption may be another way in which this system can be targeted to alleviate symptoms of social anxiety in patients with autism.

Overall, the research on the connection between disruption of the endocannabinoid system and social problems in autism is limited, but it remains one of the most promising areas in the field. As the theoretical and in vitro evidence accumulates, more scientists are suggesting that the time has come to develop and test targeted therapeutics. However, even now, physicians can consider how the endocannabinoid system may be affected in individual patients and whether supplements like cannabidiol oil and curcumin may be appropriate treatment options for those who struggle with autism-related social anxiety.

Foundational Medicine Review highlights key findings and new opportunities in autism research and treatment, as well as a wide variety of other neurological and gastrointestinal conditions. To stay up-to-date on the most innovative work in these fields, sign up for our mailing list.

Works Cited

Bhandari R, Khuad A. 2015. Neuropsychopharmacotherapeutic efficacy of curcumin in experimental paradigm of autism spectrum disorders. Life Sciences. 141:156-69. https://www.sciencedirect.com/science/article/pii/S0024320515300151?via%3Dihub

Brigida AL, Schultz S, Cascone M, Antonucci N, Siniscalco D. 2017. Endocannabinoid signal dysregulation in autism spectrum disorders: A correlation link between inflammatory state and neuro-immune alterations. International Journal of Molecular Sciences. 18(7):1425. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535916/

Chakrabarti B, Persico A, Battista N, Maccarrone M. 2015. Endocannabinoid signaling in autism. Neurotherapeutics. 12(4):837-47. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604173/

Habib SS, Al-Regaeiey K, Bashir S, Iqbal M. 2017. Role of endocannabinoids on neuroinflammation in autism spectrum disorder prevention. Journal of Clinical & Diagnostic Research. 11(6):CE01-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535348/

Hollander E, Uzunova G. 2017. Are there new advances in the pharmacotherapy of autism spectrum disorders? World Psychiatry. 16(1):101-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269487/

Kharson DS, Hardan AY, Parker KJ. 2016. Endocannabinoid signaling in social functioning: An RDoC perspective. Translational Psychiatry. 6(9):e905. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048207/

Shannon S, Opila-Lehman J. 2016. Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: A case report. The Permanente Journal. 20(4):108-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101100/

Onaivi ES, Benno R, Halpern T, Mehanovid M, Schanz N et al.  2011. Consequences of cannabinoid and monoaminergic system disruption in a mouse model of autism spectrum disorders. Current Neuropharmacology. 9(1):209-14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137184/

Xu N, Li X, Zhong Y. 2015. Inflammatory cytokines: Potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediators of Inflammation. 2015:531518. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333561/

Zamberletti E, Gabaglio M, Parolaro D. 2017. The endocannabinoid system and autism spectrum disorders: Insights from animal models. International Journal of Molecular Sciences. 18(9):1916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618565/

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