Background: Noncardiac chest pain (NCCP) affects 200,000 new cases annually in USA. It is associated with poor quality of life and high health care expenditure of 8 Billion Dollars a year.

Gastroesophageal Reflux Disease(GERD), esophageal motility disorders, and psychological issues may cause NCCP.

The mechanism(s) for pain continue to be explored and include central and peripheral hypersensitivity, and mechanophysical abnormalities. Treatment of NCCP has focused on relieving visceral hypersensitivity through pain modulators, such as tricyclics, trazodone, or adenosine receptor antagonist, theophylline. Typically, only 40-50 % respond and clearly there is a large unmet therapeutic need.

Cannabis is felt to be beneficial for vomiting, diarrhea and intestinal pain. The main component of Cannabis acts through specific receptors, that are located primarily on central and peripheral neurons (including the enteric nervous system) and myenteric plexus where they modulate neurotransmitter release. Activation of these receptors reduces excitatory enteric transmission and may improve esophageal hyperreactivity and hypersensitivity, the hallmarks of NCCP.

STUDY PROTOCOL: The investigators will randomize 40 subjects with non-cardiac, non-reflux chest pain to receive dronabinol (5 mg Bid), or placebo for 4 weeks. Chest pain symptoms and esophageal sensorimotor properties will be assessed at baseline and at 4 weeks using symptom diary and impedance planimetry. The primary outcome measure will be the frequency of chest pain episodes. Secondary outcome measures include improvement in esophageal sensory thresholds, reduced reactive contractions, frequency, amplitude, area under the curve, and global improvement of symptoms.

HYPOTHESIS: Cannabinoids decrease esophageal hypersensitivity and ameliorate chest pain in NCCP patients, when compared to placebo.

AIM: To perform a randomized double blind study to investigate the effects of Dronabinol, a CB1 and CB2 agonist, in the treatment of patients with NCCP and examine its mechanism of action.

Inclusion Criteria:

• Male or Female
• Ages 18-75 years
• Non-GERD related Non cardiac chest pain (Evaluated previously with an EGD, Esophageal manometry, and 24 Hour ambulatory pH study)
• At least one episode of chest pain a week in the past month
• Previous negative cardiac evaluation (EKG ± Non invasive stress test ± Coronary angiogram)

Exclusion Criteria:

• Subjects requiring narcotics or other pain medications
• Subjects with known esophagitis, Barrett's esophagus or peptic stricture on endoscopy
• Subjects with previous upper gastrointestinal surgery
• Pregnancy
• Subjects with Diabetes, neuromuscular disorders, or other severe co-morbidities (Cardiovascular, respiratory, renal, hepatic, hematologic, endocrine, neurologic, and psychiatric)
• Subjects with upper airway symptoms (such as hoarseness, wheezing or laryngospasm)
• Medications such as baclofen, H2 blockers, PPI, sucralfate and prokinetics.
• Known history of substance abuse
• Nursing mothers