The Endocannabinoid System : A New Treatment Target for Obsessive Compulsive Disorder ?
Reilly R. Kayser, Ivar Snorrason, Margaret Haney, Francis S. Lee, and H. Blair Simpson1
Cannabis and Cannabinoid Research, 2019, Volume 4, Number 2,
Mary Ann Liebert, Inc.
Introduction : Obsessive-compulsive disorder (OCD) is a disabling illness that is associated with significant functional impairment. Although evidence-based pharmacotherapies exist, currently available medications are ineffective in some patients and may cause intolerable side effects in others. There is an urgent need for new treatments.
Discussion : A growing body of basic and clinical research has showed that the endocannabinoid system(ECS) plays a role in anxiety, fear, and repetitive behaviors. At the same time, some patients with OCD who smoke cannabis anecdotally report that it relieves their symptoms and mitigates anxiety, and several case reports describe patients whose OCD symptoms improved after they were treated with cannabinoids. Taken together, these findings suggest that the ECS could be a potential target for novel medications for OCD. In this study, we review evidence from both animal and human studies that suggests that the ECSmay play a role in OCD and related disorders. We also describe findings from studies in which cannabinoid drugs were shown to impact symptoms of these conditions.
Conclusions : An emerging body of evidence suggests that the ECS plays a role in OCD symptoms and may be a target for the development of novel medications. Further exploration of this topic through well designed human trials is warranted.
Keywords : anxiety, cannabinoid, endocannabinoid system, OCD, repetitive behavior
Obsessive-compulsive disorder (OCD) is a disabling illness with an approximate lifetime prevalence of 2– 3% worldwide.1 The disorder is marked by intrusive repetitive thoughts and behaviors, which must be significantly time consuming, distressing, or functionally impairing to meet DSM 5 criteria.2 There is a bimodal distribution of age at onset, with peaks in childhood and early adulthood, and roughly equal distribution in adults between males and females. The illness typically follows a chronic course, with symptoms waxing and waning over time. OCD is associated with significant functional disability and impairment,3 and many patients do not achieve remission despite evidencebased treatments. Evidence suggests that abnormalities in cortico-striatal-thalamic-cortical circuitry and specific gene variants contribute to the pathogenesis of the disorder.4
The only medications approved by, for example, the Food and Drug Administration (FDA) for the treatment of OCD are serotonin reuptake inhibitors (SRIs, e.g., clomipramine and the selective SRIs).5 However, these drugs often provide only limited relief of symptoms, and are ineffective in some patients. Furthermore, SRIs typically require at least 6 weeks of sustained treatment before clinically meaningful improvement can be seen.5,6 Antipsychotics may be effective when added to SRIs for a subset of patients, but are ineffective in others. Although novel (e.g., second-generation) antipsychotic drugs there is not strong evidence suggesting that these are more effective in OCD. Moreover, antipsychotics as a class are associated with an increased risk for side effects, including weight gain, metabolic syndrome, Parkinsonism, tardive dyskinesia, and even neuroleptic malignant syndrome.7–9 Thus, there is an urgent need for new targets for treatment development.
One potential target is the endocannabinoid system (ECS). Recent studies in both humans and animals have shown a critical role for the ECS in anxiety, stress, fear, and repetitive/habitual behaviors.10 Moreover, many patients with OCD who use cannabis anecdotally report that it improves their symptoms and reduces anxiety. However, to date, few studies have systematically investigated this connection.