Dronabinol in Trichotillomania and Other Body Focused Repetitive Behaviors

Pathological hair-pulling, trichotillomania, has been defined as repetitive, intentionally
performed pulling that causes noticeable hair loss and results in clinically significant
distress or functional impairment. Although discussed in the medical literature for over one
hundred years, and affecting all strata of society, there have been no epidemiological
studies detailing how common trichotillomania is and there are no clear treatment approaches
for everyone with trichotillomania. Behavioral therapy is generally regarded as the
first-line treatment but trained therapists are difficult to find. In addition, there is no
medication currently approved by the Food and Drug Administration for trichotillomania.
Trichotillomania is related clinically to other BFRBs, specifically skin picking disorder. In
fact, it appears that trichotillomania and skin picking disorder may in fact share a common
neurobiology. Other BFRBs such as skin ppicking disorder also lack any agreed upon medication
intervention, but evidence suggests that both skin picking disorder and trichotillomania may
respond to the same interventions.

The Trichotillomania Impact Project survey showed that only 15% of adults in the community
with trichotillomania reported experiencing significant improvement with treatment of their
symptoms. This may be because of the ongoing difficulty of finding a therapist experienced in
trichotillomania treatments. More than 55% of persons in this survey believed that their
clinician did not have sufficient knowledge of the disorder, and less than one-third were
receiving evidence-based treatments for trichotillomania.

A recent meta-analytic study of randomized treatment trials in adults demonstrated that
behavioral treatments, mainly habit reversal therapy, have the greatest efficacy in treatment
of trichotillomania. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used
treatment for adults with trichotillomania, despite evidence that their efficacy is no
greater than placebo.

Instead of using SSRIs, the investigators conducted an open-label study of dronabinol a
synthetic form of tetrahydrocannabinol (THC) approved by the FDA as an appetite stimulant for
people with AIDS and antiemetic for people receiving chemotherapy, in 14 women with
trichotillomania and found that 9 (64.3%) responded to treatment and that the mean effective
dose was 11.6 ± 4.1 mg/day.

A recent study using diffusion tensor imaging demonstrated that both trichotillomania and
skin-picking subjects exhibited significantly reduced fractional anisotropy in anterior
cingulate, presupplementary motor area, and temporal cortices. These data suggest that the
disorganization of white matter tracts in motor habit generation and suppression may underlie
the pathophysiology of these disorders. Neurochemically, motor habits may rely partially on
the endocannabinoid system. CB1 receptors are highly expressed in the basal ganglia nuclei,
the hippocampus, cerebellum, and neocortex and are implicated in attenuating glutamatergic
exocitotoxic damage by suppressing the neuronal release of glutamate via inhibition of
calcium channels. The activation of CB1 receptors reduces glutamate release in the dorsal and
ventral striatum [possibly through an interaction with brain-derived neurotrophic factor],
thereby modulating neurotransmission in the basal ganglia and mesolimbic reward system .
Stress-induced anxious behavior has been associated with the loss of CB1 receptor function in
the striatum.

Glutamatergic dysfunction has been implicated in the pathophysiology of trichotillomania.
Pharmacotherapies, such as dronabinol, that target excessive glutamatergic drive through its
effects on CB! Receptors may, therefore, be expected to correct the underlying
pathophysiology and symptoms of trichotillomania.

In the USA, dronabinol is FDA-approved for the treatment of anorexia associated with weight
loss in patients with AIDS and nausea and vomiting associated with cancer chemotherapy. In
our previous study examining dronabinol for trichotillomania, doses between 5 and 15mg/day
were well tolerated and beneficial. This lack of significant side effects is consistent with
other studies of dronabinol where it has been associated primarily with central nervous
system-related adverse events (for example, confusion, dizziness, euphoria, and somnolence),
but these adverse events are generally mild to moderate in severity and generally reversible
upon dose modification.

Given the serious personal consequences associated with trichotillomania, and the likelihood
of success of dronabinol in treating the disorder, the aim of the present study was to
examine the efficacy and safety of dronabinol vs placebo in adults with trichotillomania
using a double-blind, placebo-controlled design.

The investigators hypothesize that dronabinol will be more effective than placebo in reducing
the frequency of hair pulling and in improving overall psychosocial functioning after 10
weeks of treatment when compared to baseline.

Inclusion Criteria:

- current DSM-5 trichotillomania

- ability to understand and sign the consent form

Exclusion Criteria:

- Unstable Medical illness based on history of clinically significant abnormalities on
baseline physical examination

- Current pregnancy or lactation, or inadequate contraception in women of childbearing
potential

- Subjects considered an immediate suicide risk based on the Columbia Suicide Severity
Rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)

- Past 12-month DSM-5 psychiatric disorder other than trichotillomania

- Illegal substance use based on urine toxicology screening

- Use of any other psychotropic medication (except a PRN hypnotic)

- Previous treatment with dronabinol

- Cognitive impairment that interferes with the capacity to understand and self
administer medication or provide written informed consent