CASE REPORTS Preliminary Observation With Dronabinol in Patients With Intractable Pruritus Secondary to Cholestatic Liver Disease Guy W. Neff, M.D., Christopher B. O’Brien, M.D., K. Rajender Reddy, M.D., Nora V. Bergasa, M.D., Arie Regev, M.D., Enrique Molina, M.D., Rafael Amaro, M.D., Miguel J. Rodriguez, M.D., VeEtta Chase, M.D., Lennox Jeffers, M.D., and Eugene Schiff, M.D., F.A.C.P., M.A.C.G. Department of Medicine, University of Miami, Miami, Florida; and Division of Digestive and Liver Diseases, College of Physicians and Surgeons, Columbia University, New York, New York ABSTRACT Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of -9-tetrahydrocannabinol (-9-THC) for intrac- table cholestatic related pruritus (ICRP) that has failed con- ventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients had previously been extensively treated with stan- dard therapies for ICRP including: diphenhydramine, chlor- pheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations. All patients were started on 5 mg of -9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approxi- mately 4 – 6 hrs in all three patients suggesting the need for more frequent dosing. -9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus. (Am J Gastroenterol 2002;97:2117–2119. © 2002 by Am. Coll. of Gastroenterology) INTRODUCTION Patients with cholestatic liver disease can suffer from pru- ritus. Although often a trivial symptom, occasionally it can be severe. The clinical course of cholestasis-related pruritus is variable. Some patients can be treated with simple mea- sures, such as cholestyramine or antihistamines. Pruritus that is intractable and distressful may require more aggres- sive pharmacological therapy, invasive treatments including plasmapheresis, charcoal hemoperfusion, or orthotopic liver transplantation. The active substance in dronabinol (Marinol, Unimed Pharmaceuticals, Deerfield, IL) is -9-tetrahydrocannabinol, a cannabinoid designated chemically as (6aR-trans)-6a,7,8,10a- tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1- ol. Dronabinol, the p.o. form of -9-tetrahydrocannabinol, has been synthesized and comes in a capsular form that contains the following inactive ingredients: sesame oil, gel- atin, glycerin, methylparaben, propylparaben, and titanium dioxide (1). Dronabinol is approved in the United States for only two indications: treatment of anorexia associated with weight loss in patients with AIDS, and in the therapy of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to con- ventional antiemetic treatments. A patient not included in our cohort reported relief of her pruritus after the inhalation of marijuana. With this obser- vation in mind, we evaluated and treated three patients with dronabinol. All of these patients had failed multiple phar- macological interventions and plasmapheresis for severe and disabling pruritus due to cholestatic liver disease. Using dronabinol, all three patients experienced dramatic relief of pruritus. CASE 1 A 22-yr-old white female presented with 8 months of in- tractable pruritus, which interrupted her daily lifestyle, forc- ing her to work part-time, and led to serious sleep depriva- tion. Her medical history was significant for systemic lupus erythematosis and glomerulonephritis. She had a positive anticardiolipin antibody and developed deep vein thrombo- sis when placed on birth control pills. The birth control pills were stopped and she was started on medroxyprogesterone acetate i.m., as an alternative form of birth control. Three months after starting medroxyprogesterone acetate therapy, she developed jaundice, followed by pruritus, and fatigue. Medroxyprogesterone acetate was discontinued. Further in- vestigations included a normal ultrasonography and CT of THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 97, No. 8, 2002 © 2002 by Am. Coll. of Gastroenterology ISSN 0002-9270/02/$22.00 Published by Elsevier Science Inc. PII S0002-9270(02)04208-9