Investigation of Cannabinoid Receptor Agonist Dronabinol in Patients With Functional Chest Pain

About 200,000 new cases of Functional Chest Pain (FCP) are diagnosed annually in USA. FCP is
associated with poor quality of life and high health care expenditure. Gastroesophageal
reflux disease (GERD), esophageal motility disorders, and psychological disorders may cause
FCP. However, the mechanism(s) for FCP continue to be explored and include central and
peripheral hypersensitivity as well as biomechanical dysfunction of the esophageal wall. CB1
receptor activation in synaptic clefts fine tunes neuronal firing and may in fact quell the
over excitation associated with hypersensitivity.

Dronabinol, a cannabinoid receptor agonist with a preference for CB1 over CB2, is believed to
reduce the esophageal hypersensitivity. CB1 receptors are located primarily on central and
peripheral neurons (including the enteric nervous system) and myenteric plexus where they
modulate neurotransmitter release. Activation of pre-junctional CB1 receptors may reduce
excitatory enteric transmission and conceivably improve esophageal hyperreactivity and
hypersensitivity, the hallmarks of FCP.

Previously, it was shown that Chest Pain Symptoms were greatly reduced when patients took 5
mg Dronabinol twice daily. Patients had very few side effects from this regiment although
sedation was reported. The goal of this study focuses on reducing the dose of Dronabinol to 5
mg every other day, or essentially, one quarter of the dose. The effect of Dronabinol varies
with CB1 receptor density in various tissues. It is hypothesized that at this reduced dose
relief of chest pain will still be achieved without the sedating effects.

More so, Dronabinol at 5 mg twice daily failed to produce any adverse metabolic outcomes
including measures of glucose, LDL, triglycerides, leptin, or transaminases. Dronabinol
treatment tended to improve some of these measures although the study only lasted 28 days.
Currently the hypothesis is that lower doses at a protracted time course will again fail to
perturb homeostasis.

Inclusion Criteria:

At least one episode of chest pain a week in the past month. Previous negative cardiac
evaluation (EKG ± non invasive stress test ± coronary angiogram). Negative esophageal
evaluation for a motility disorder (eg: achalasia) and GERD (normal endoscopy, normal 24 hr
pH study, or unresponsive to 6 weeks of BID PPI therapy)

Exclusion Criteria:

1. Subjects requiring narcotics or other pain medications,

2. Subjects with known GERD (unless responsive to PPI therapy and on a stable dose),
esophagitis, Barrett's esophagus or peptic stricture on endoscopy

3. Subjects with previous upper gastrointestinal surgery

4. Pregnancy

5. Subjects with diabetes, neuromuscular disorders, cardiac disorders, or other severe
co-morbidities (Cardiovascular, respiratory, renal, hepatic, hematologic, endocrine,
neurologic).

6. Subjects with upper airway symptoms (such as hoarseness, wheezing or laryngospasm)

7. Medications such as baclofen, sucralfate and prokinetic agents or any agent considered
a sedative, hypnotic, or psychoactive drug.

8. Known history of substance abuse.

9. Subject unable to consent.

10. Patient has history of comorbid psychiatric conditions including mania and
schizophrenia. Patients will also be excluded who currently have a diagnosis of
depression or undergoing treatment for depression.