To the Editor: It has been reported that 40%–60% of patients with obsessive-compulsive disorder (OCD) do not respond to first-line treatment. Treatment options for these patients include switching to another agent or augmentation (1). We report on two patients with treatment-resistant OCD and comorbid axis I disorders who responded to an augmentation with the cannabinoid dronabinol.
“Mrs. L” was a 38-year-old woman who was admitted with recurrent major depression and OCD (Yale-Brown Obsessive Compulsive Scale score: 20) after outpatient treatment with paroxetine (60 mg) for 8 months and cognitive behavioral therapy (CBT) were not efficacious. Switching to clomipramine (300 mg) resulted in partial response after 12 weeks of treatment. Based on the patient’s report that smoking marijuana usually relieved her symptoms, an augmentation with dronabinol (2.5%; 10 mg t.i.d.) was started. The prior medication was continued. While undergoing treatment with dronabinol (2.5%), the patient’s OCD symptoms decreased significantly within 10 days (Yale-Brown Obsessive Compulsive Scale score: 10).
“Mr. K” was a 36-year-old man with schizophrenia and OCD who was admitted for deterioration of psychotic and obsessive symptoms (Yale-Brown Obsessive Compulsive Scale score: 23). During his course of illness, Mr. K had been treated with antipsychotics (including haloperidol, olanzapine, risperidone, quetiapine, and aripiprazole), both in monotherapy and in combination with selective serotonin reuptake inhibitors. His OCD symptoms in particular remained predominately treatment resistant. Treatment with clozapine (400 mg), which he had already received for more than 1 year (in combination with paroxetine [60 mg] for 13 weeks) resulted only in partial response of his psychotic and OCD symptoms. Switching paroxetine to clomipramine (for another 10 weeks), followed by an additional course of 18 electroconvulsive therapy treatments (right unilateral high dose), did not improve the patient’s psychotic or OCD symptoms significantly. After the addition of dronabinol to ongoing treatment with clomipramine (150 mg) and clozapine (400 mg), a significant reduction of OCD symptoms was observed within 2 weeks (Yale-Brown Obsessive Compulsive Scale score: 15). In order to prevent psychotic deterioration, dronabinol (2.5%) was carefully increased to 10 mg b.i.d.
Apart from anticholinergic symptoms that preceded the addition of dronabinol (patient 1: dry mouth, constipation; patient 2: constipation, hypotension), both patients reported no side effects. In particular, there was no deterioration of psychotic or mood disorder symptoms.
Based on data from case reports and small clinical trials suggesting that cannabinoids can reduce symptoms of tic disorder (2) and on findings from genetic studies linking tic disorder with OCD (3), we hypothesized that cannabinoids might also reduce OCD symptoms. Moreover, there is evidence suggesting that besides serotonergic and dopaminergic systems, glutamatergic hyperactivity is involved in the pathophysiology of OCD (4, 5). This view is supported by data suggesting the efficacy of glutamate modulating drugs, such as topiramate, memantine, riluzole, or N-acetylcysteine, in the treatment of OCD (6). It has been reported that cannabinoids inhibit glutamate release in the CNS (7, 8). Additionally, cannabinoid type 1 (CB1) receptors are distributed abundantly in the striatum (8), a brain region frequently associated with OCD. Hence, it can be speculated that the anti-obsessive effect observed in our patients may have been a consequence of the glutamate modulation of the cannabinoid dronabinol. Since it is well known that cannabinoids may trigger psychotic symptoms in patients with schizophrenia (8), caution is warranted when prescribing for patients with a history of the disorder.
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8.Pacher P, Bátkai S, Kunos G: The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006; 58:389–462
The authors report no competing interests.
This letter (doi: 10.1176/appi.ajp.2007.07061016) was accepted for publication in September 2007.