Updated on March 27, 2023
For parents, it can be heartbreaking to watch an autistic child struggle with one of the most debilitating symptoms of the condition: social anxiety. From early childhood, autistic children often have social problems due to the anxiousness they experience when trying to cope with social situations. As a result, autistic children often struggle to find friends at school, and the severity of this circumstance might not wear off as they get older. The sad reality is that these children often find themselves increasingly isolated in adolescence, as well as later in early adulthood, which can significantly limit their opportunities.
Because social anxiety can have such extensive adverse effects on the life outcomes of autistic children, 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 past several decades suggests the endocannabinoid system plays 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 address social anxiety in autistic patients while also investigating a number of existing therapies that could address endocannabinoid disruption, including CBD and curcumin.
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 autistic patients. Although 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 might 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 is involved in social functioning, the researchers used a well-established systematic research construct to integrate and analyze the role of endocannabinoid signaling in 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 although the authors drew data not only from studies on autism, but also from other psychological and psychiatric disorders (like major depressive disorder, PTSD, and bipolar disorder), their conclusion regarding the role of endocannabinoids on social functioning, in general, has promising implications for autistic patients who are specifically interested in therapeutics that target symptoms of social anxiety.
As yet, there are no major human studies in which researchers have specifically tested therapeutics that target the endocannabinoid system. Nevertheless, related research has produced promising results. For instance, in some animal models of autism, cannabidiol has been shown to impact social deficits, although more research is needed to solidify the results and establish statistical significance. A case report on a young patient with PTSD-related anxiety could also be relevant: when administered cannabidiol (CBD) 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 autistic patients, it is possible that similar therapies targeting the endocannabinoid system might have comparable beneficial effects on social anxiety in such patients.
Additionally, the endocannabinoid system’s role in maintaining healthy neurological status suggests that it might be possible to address endocannabinoid disruption in autistic patients with nutritional supplements, such as curcumin. Studies show that levels of neuroinflammatory cytokines are elevated in autistic patients, and some scientists believe this circumstance could be the result of endocannabinoid disruption. According to a 2015 study published in Life Sciences, it is possible to lower the levels of these same cytokines through curcumin supplementation. In this study, the researchers gave rat models of autism 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 and repetitive coping behavior. Therefore, addressing the neurological issues associated with endocannabinoid disruption could be another way in which this system can be targeted to address the symptoms of social anxiety in autistic patients.
Although research on the connection between disruption of the endocannabinoid system and social problems in autism is limited, it remains one of the most promising areas of investigation in the field. As the theoretical and in vitro evidence accumulates, more scientists are suggesting the time has come to develop and test targeted therapeutics. However, even now, physicians can consider how the endocannabinoid system might be affected in individual patients and whether supplements like cannabidiol oil and curcumin are appropriate therapy options for individuals who struggle with autism-related social functioning.
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