A 4-week Pilot Study with the Cannabinoid Receptor Agonist Dronabinol and Its Effect on Metabolic Parameters in a Randomized Trial

Clinical Therapeutics

Volumn 37, Issue 10, 2015, Pages 2267-2274

  Reichenbach, Zachary Wilmer ^a,b   Sloan, Joshua ^a   Rizvi Toner, Amna ^c   Bayman, Levent ^c   Valestin, Jessica ^c   Schey, Ron ^a,c  

^a TEMPLE UNIVERSITY HOSPITAL   (United States)

^b TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF IOWA HOSPITALS AND CLINICS   (United States)

Author keywords

cannabinoid receptors; CB1 agonist; metabolic parameters; noncardiac chest pain

Indexed keywords

ALANINE AMINOTRANSFERASE; ANALGESIC AGENT; ASPARTATE AMINOTRANSFERASE; C REACTIVE PROTEIN; DRONABINOL; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LACTATE DEHYDROGENASE; LEPTIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; TRIACYLGLYCEROL; CANNABINOID RECEPTOR AGONIST;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BALLOON DISTENTION TESTING; BODY MASS; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; COMORBIDITY; CONTROLLED STUDY; DIAGNOSTIC PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG EFFECT; ESOPHAGEAL HYPERSENSITIVITY; ESOPHAGUS DISEASE; FEMALE; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN BLOOD LEVEL; LACTATE DEHYDROGENASE BLOOD LEVEL; LONG TERM CARE; MALE; METABOLIC DISORDER; METABOLIC PARAMETERS; PILOT STUDY; PSYCHIATRIC DIAGNOSIS; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; THORAX PAIN; TREATMENT DURATION; TRIACYLGLYCEROL BLOOD LEVEL; CHEMICALLY INDUCED; CHEST PAIN; METABOLISM; MIDDLE AGED; NAUSEA; TIME FACTOR; VOMITING;

ADULT; AGED; BODY MASS INDEX; C-REACTIVE PROTEIN; CANNABINOID RECEPTOR AGONISTS; CHEST PAIN; DOUBLE-BLIND METHOD; DRONABINOL; FEMALE; HUMANS; MALE; MIDDLE AGED; NAUSEA; PILOT PROJECTS; TIME FACTORS; VOMITING;

EID: 84945443722     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2015.07.023     Document Type: Article

References (41)

1. R.G. Pertwee The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin Br J Pharmacol 153 2 2008 199 215
2. A.C. Howlett, F. Barth, T.I. Bonner, and et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors Pharmacol Rev 54 2 2002 161 202
3. W.A. Devane, F.A. Dysarz 3rd, M.R. Johnson, and et al. Determination and characterization of a cannabinoid receptor in rat brain Mol Pharmacol 34 5 1988 605 613
4. C.M. Williams, and T.C. Kirkham Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors Psychopharmacology (Berl) 143 3 1999 315 317
5. T.C. Kirkham, and C.M. Williams Endogenous cannabinoids and appetite Nutr Res Rev 14 1 2001 65 86
6. A.A. Coutts, A.J. Irving, K. Mackie, and et al. Localisation of cannabinoid CB(1) receptor immunoreactivity in the guinea pig and rat myenteric plexus J Comp Neurol 448 4 2002 410 422
7. Z.A. Malik, and R. Schey Dronabinol increases pain threshold in non-cardiac chest pain: a double blind placebo controlled trial Am J Gastroenterol 3 S1 2014
8. N.J. Shaheen, R.A. Hansen, D.R. Morgan, and et al. The burden of gastrointestinal and liver diseases, 2006 Am J Gastroenterol 101 9 2006 2128 2138
9. L.E. Hollister Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine Clin Pharmacol Ther 12 1 1971 44 49
10. T. Esfandyari, M. Camilleri, I. Busciglio, and et al. Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study Am J Physiol Gastrointest Liver Physiol 293 1 2007 G137 G145
11. T. Esfandyari, M. Camilleri, I. Ferber, and et al. Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebo-controlled study Neurogastroenterol Motil 18 9 2006 831 838
12. A. Hazekamp, and Franjo Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids Special Issue 5 Special Issue 2010 1 21
13. L.L. Senin, O. Al-Massadi, C. Folgueira, and et al. The gastric CB1 receptor modulates ghrelin production through the mTOR pathway to regulate food intake PLoS One 8 11 2013 e80339
14. I. Merroun, C. Sánchez-González, R. Martínez, and et al. Novel effects of the cannabinoid inverse agonist AM 251 on parameters related to metabolic syndrome in obese Zucker rats Metabolism 62 11 2013 1641 1650
15. Q. Feng, K.C. Vickers, M.P. Anderson, and et al. A common functional promoter variant links CNR1 gene expression to HDL cholesterol level Nat Commun 4 2013 1973
16. F.X. Pi-Sunyer, L.J. Aronne, H.M. Heshmati, and et al. Group R-NAS. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial JAMA 295 7 2006 761 775
17. C.L. Schaich, H.A. Shaltout, K.B. Brosnihan, and et al. Acute and chronic systemic CB1 cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2)27 rats Physiol Rep 2 2014
18. Marinol-(dronabinol) capsules-prescribing information. 2013.
19. U.E. Bauer, P.A. Briss, R.A. Goodman, and B.A. Bowman Prevention of chronic disease in the 21st century: elimination of the leading preventable causes of premature death and disability in the USA Lancet 384 9937 2014 45 52
20. T.M. Wallace, J.C. Levy, and D.R. Matthews Use and abuse of HOMA modeling Diabetes Care 27 6 2004 1487 1495
21. D.R. Matthews, J.P. Hosker, A.S. Rudenski, and et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man Diabetologia 28 7 1985 412 419
22. E.A. Penner, H. Buettner, and M.A. Mittleman The impact of marijuana use on glucose, insulin, and insulin resistance among US adults Am J Med 126 7 2013 583 589
23. F.X. Pi-Sunyer, L.J. Aronne, H.M. Heshmati, and et al. Group RI-NAS. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial JAMA 295 7 2006 761 775
24. A.P. Chambers, K.A. Sharkey, and H.S. Koopmans Cannabinoid (CB)1 receptor antagonist, AM 251, causes a sustained reduction of daily food intake in the rat Physiol Behav 82 5 2004 863 869
25. M. Bouaboula, S. Perrachon, L. Milligan, and et al. A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions J Biol Chem 272 35 1997 22330 22339
26. W. Slikker, M.G. Paule, S.F. Ali, and et al. Chronic marijuana smoke exposure in the rhesus monkey, I: plasma cannabinoid and blood carboxyhemoglobin concentrations and clinical chemistry parameters Fundam Appl Toxicol 17 2 1991 321 334
27. E.T. Wargent, M.S. Zaibi, C. Silvestri, and et al. The cannabinoid Δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity Nutr Diabetes 3 2013 e68
28. J.J. Ghosh, G. Mitra, M.K. Poddar, and D.K. Chatterjee Effect of delta9-tetrahydrocannabinol administration on hepatic functions Biochem Pharmacol 26 19 1977 1797 1801
29. M. Bouaboula, N. Desnoyer, P. Carayon, and et al. Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2: implication for intracellular signalization cross-regulation Mol Pharmacol 55 3 1999 473 480
30. V. Di Marzo "De-liver-ance" from CB(1): a way to counteract insulin resistance? Gastroenterology 142 5 2012 1063 1066
31. V. Di Marzo The endocannabinoid system in obesity and type 2 diabetes Diabetologia 51 8 2008 1356 1367
32. P.K. Riggs, F. Vaida, S.S. Rossi, and et al. A pilot study of the effects of cannabis on appetite hormones in HIV-infected adult men Brain Res 1431 2012 46 52
33. D. Osei-Hyiaman, J. Liu, L. Zhou, and et al. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice J Clin Invest 118 9 2008 3160 3169
34. V. Di Marzo Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 7 5 2008 438 455
35. J.M. Friedman, and J.L. Halaas Leptin and the regulation of body weight in mammals Nature 395 6704 1998 763 770
36. Z.D. Cooper, and M. Haney Investigation of sex-dependent effects of cannabis in daily cannabis smokers Drug Alcohol Depend 136 2014 85 91
37. R.M. Craft, A.A. Wakley, K.T. Tsutsui, and J.D. Laggart Sex differences in cannabinoid 1 vs. cannabinoid 2 receptor-selective antagonism of antinociception produced by delta9-tetrahydrocannabinol and CP55,940 in the rat J Pharmacol Exp Ther 340 3 2012 787 800
38. R.M. Craft, R. Kandasamy, and S.M. Davis Sex differences in anti-allodynic, anti-hyperalgesic and anti-edema effects of Δ(9)-tetrahydrocannabinol in the rat Pain 154 9 2013 1709 1717
39. M.P. Viveros, E.M. Marco, M. López-Gallardo, and et al. Framework for sex differences in adolescent neurobiology: a focus on cannabinoids Neurosci Biobehav Rev 35 8 2011 1740 1751
40. J.L. Wiley, and J.J. Burston Sex differences in Δ(9)-tetrahydrocannabinol metabolism and in vivo pharmacology following acute and repeated dosing in adolescent rats Neurosci Lett 576 2014 51 55
41. S. Narimatsu, K. Watanabe, I. Yamamoto, and H. Yoshimura Sex difference in the oxidative metabolism of delta 9-tetrahydrocannabinol in the rat Biochem Pharmacol 41 8 1991 1187 1194