Cannabinoids for prophylactic treatment of involuntary weight loss

Abstract

The present invention provides a new use for cannabinoids in the prevention of pre-cachexia or cachexia in a patient suffering from cancer, wherein said cannabinoid is administered-at low dosage and wherein administration is started prior to chemotherapy and is maintained for at least the duration of the chemotherapy.

1 . A method of prophylactically treating pre-cachexia or cachexia in a patient suffering from cancer, comprising the step of administering a cannabinoid in an amount of 0.1 mg to 5 mg/day, wherein administration of the cannabinoid is started prior to chemotherapy and is maintained for at least the duration of the chemotherapy. 
     
     
         2 . The method of  claim 1 , wherein said cannabinoid is administered in an amount of 0.25 mg to 0.5 mg/day. 
     
     
         3 . The method of  claim 1 , wherein said cannabinoid is a natural or synthetic cannabinoid. 
     
     
         4 . The method of  claim 1 , wherein said cannabinoid is formulated for oral, inhalative or parenteral delivery. 
     
     
         5 . The method of  claim 4 , wherein the oral formulation is in the form of a tablet, a capsule, a sachet, sprinkles, or a suspension. 
     
     
         6 . The method of  claim 1 , wherein the cancer is selected from the group consisting of prostate cancer, breast cancer, small cell lung carcinoma, non-small cell lung carcinoma, colon cancer, rectum cancer, bladder cancer, kidney cancer, leukemia, mouth cancer, esophagus cancer, larynx cancer, stomach cancer, melanoma, pancreatic cancer, endometrial cancer, uterine sarcoma, ovarian cancer, testicular cancer, multiple myeloma, brain tumor, thyroid cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, liver cancer, gastric cancer, sarcoma, osteosarcoma, acute non-lymphocytic leukemia and glioma. 
     
     
         7 . The method of  claim 1 , wherein the pre-cachexia is characterized by a weight loss of >1 kg and <5% of the patient's weight compared to the weight before the start of a chemotherapy treatment cycle. 
     
     
         8 . The method of  claim 1 , wherein the cachexia is characterized by a weight loss of >5% of the patient's weight compared to the weight before the start of a chemotherapy treatment cycle. 
     
     
         9 . The method of  claim 1 , wherein the patient further suffers from one or more of the following conditions:
 a) progressive loss of both fat and skeletal muscle,   b) refractoriness of weight loss to increased nutritional input,   c) elevated resting energy expenditure (REE),   d) decreased protein synthesis,   e) altered carbohydrate metabolism,   f) hyper-catabolism of muscle via the ATP-ubiquitin-proteasome pathway of proteolysis,   g) increased degradation of adipose tissue via lipolysis,   h) asthenia,   i) anemia,   j) chronic fatigue,   k) nausea,   l) loss of bone mass, and   m) a Glasgow prognostic score lower than 2.   
     
     
         10 . The method of  claim 1 , wherein administration is started immediately after a first diagnosis of cancer or immediately after a diagnosis of relapse of cancer disease. 
     
     
         11 . The method of  claim 1 , wherein administration starts at least 1 week before chemotherapy. 
     
     
         12 . The method of  claim 1 , wherein the cannabinoid is continuously administered from the beginning until the end of a complete chemotherapy treatment. 
     
     
         13 . The method of  claim 1 , wherein weight loss of the patient after one chemotherapy treatment cycle is less than 15%, less than 10%, less than 5%, less than 2.5%, less than 2%, or less than 1% compared to the weight of the patient before the start of a chemotherapy treatment cycle. 
     
     
         14 . The method of  claim 1 , wherein C-reactive protein levels of the patient are less than 10 mg/l and albumin levels are higher than 35 g/l. 
     
     
         15 . The method of  claim 3 , wherein the cannabinoid is selected from the group consisting of cannabidiol (CBD), 9-tetrahydrocannabinol, 8-tetrahydrocannabinol, (+)-1,1-dimethylheptyl analog of 7-hydroxy-delta-6-tetrahydrocannabinol, 3-(5′-cyano-1,1′-dimethylpentyl)-1-(4-N-morpholinobutyryloxy) delta8-tetrahydrocannabinol hydrochloride, dexanabinol, nabilone, levonantradol, N-(2-hydroxyethyl) hexadecanamide, and delta-8-tetrahydrocannabinol. 
     
     
         16 . The method of  claim 15 , wherein the cannabinoid is a 9-tetrahydrocannabinoid selected from the group consisting of 9-tetrahydrocannabinol, nabilone, and dronabinol. 
     
     
         17 . The method of  claim 5 , wherein the oral formulation is a slow release formulation. 
     
     
         18 . The method of  claim 11 , wherein administration starts at least 2 weeks before chemotherapy. 
     
     
         19 . The method of  claim 1 , wherein the cannabinoid is continuously administered for up to 12 months after termination of chemotherapy. 
     
     
         20 . The method of  claim 1 , wherein said cannabinoid is administered in an amount of 0.25 mg to 5 mg/day.