Human abuse potential and cognitive effects of taranabant, a cannabinoid 1 receptor inverse agonist: A randomized, double-blind, placebo-and active-controlled, crossover study in recreational polydrug users

Journal of Clinical Psychopharmacology

Volumn 32, Issue 4, 2012, Pages 492-502

  Schoedel, Kerri A ^a   Addy, Carol ^b   Chakraborty, Bijan ^a   Rosko, Kim ^b   Dunbar, Stephanie ^b   Maes, Andrea ^b,c   Chen, Nancy ^a   Stoch, Selwyn Aubrey ^b   Wagner, John ^b   Chodakewitz, Jeff ^b   Sellers, Edward M ^a,d  

^a SYNEOS HEALTH   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c NOVARTIS PHARMA AG   (Switzerland)

^d UNIVERSITY OF TORONTO   (Canada)

Author keywords

Abuse potential; Cannabinoid; Clinical; Neurocognitive; Subjective; Taranabant

Indexed keywords

DRONABINOL; PHENTERMINE; PLACEBO; RECREATIONAL DRUG; TARANABANT;

ADULT; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIZZINESS; DOUBLE BLIND PROCEDURE; DROWSINESS; DRUG ABUSE; DRUG EFFECT; DRUG USE; DRUG WITHDRAWAL; DYSPHORIA; FEMALE; HUMAN; MALE; MENTAL PERFORMANCE; MOTOR PERFORMANCE; NAUSEA; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; SYNCOPE; TACHYCARDIA; TOOTH PAIN;

ADULT; AMIDES; BEHAVIOR, ADDICTIVE; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG INVERSE AGONISM; DRUG USERS; FEMALE; HUMANS; MALE; MARIJUANA ABUSE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; PHENTERMINE; PSYCHOMOTOR PERFORMANCE; PULSE; PYRIDINES; RECEPTOR, CANNABINOID, CB1; TETRAHYDROCANNABINOL;

EID: 84863721433     PISSN: 02710749     EISSN: 1533712X     Source Type: Journal    
DOI: 10.1097/JCP.0b013e31825d380d     Document Type: Article

References (49)

1. Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance. Nat Neurosci. 2005;8(5):585-589. (Pubitemid 40594198)
2. Kirkham TC. Endocannabinoids in the regulation of appetite and body weight. Behav Pharmacol. 2005;16:297-313. (Pubitemid 41404803)
3. Fong TM, Heymsfield SB. Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions. Int J Obes (Lond). 2009;33:947-955.
4. Fong TM, Addy C, Erondu N, et al. CB1 receptor inverse agonist pharmacotherapy for metabolic disorders. Drug Dev Res. 2009;70:566-576.
5. Addy C, Wright H, Van Laere K, et al. The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab. 2008a;7:68-78.
6. Beardsley PM, Thomas BF, McMahon LR. Cannabinoid CB1 receptor antagonists as potential pharmacotherapies for drug abuse disorders. Int Rev Psychiatry. 2009a;21:134-142.
7. Parolaro D, Rubino T. The role of the endogenous cannabinoid system in drug addiction. Drug News Perspect. 2008;21:149-157. (Pubitemid 351809138)
8. Black MD, Stevens RJ, Rogacki N, et al. AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents. Psychopharmacology (Berl). 2011;215(1):149-163.
9. Dillon GM, Lubbers LS, Ferguson MT, et al. MK-7128, a novel CB1 receptor inverse agonist, improves scopolamine-induced learning and memory deficits in mice. Behav Pharmacol. 2011;22:91-100.
10. Guidali C, Viganò D, Petrosino S, et al. Cannabinoid CB1 receptor antagonism prevents neurochemical and behavioral deficits induced by chronic phencyclidine. Int J Neuropsychopharmacol. 2011;14(1):17-28.
11. Wise LE, Iredale PA, Stokes RJ, et al. Combination of rimonabant and donepezil prolongs spatial memory duration. Neuropsychopharmacology. 2007;32:1805-1812. (Pubitemid 47076380)
12. de Bruin NM, Prickaerts J, Lange JH, et al. SLV330, a cannabinoid CB1 receptor antagonist, ameliorates deficits in the T-maze, object recognition and social recognition tasks in rodents. Neurobiol Learn Mem. 2010;93:522-531.
13. Roser P, Vollenweider FX, Kawohl W. Potential antipsychotic properties of central cannabinoid (CB1R) receptor antagonists. World J Biol Psychiatry. 2010;11:208-219.
14. Huestis MA, Gorelick DA, Heishman SJ, et al. Blockade of effects of smoked marijuana by the CB1R-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001;58:322-328. (Pubitemid 32299527)
15. Beardsley PM, Dance ME, Balster RL, et al. Evaluation of the reinforcing effects of the cannabinoid CB1 receptor antagonist, SR141716, in rhesus monkeys. Eur J Pharmacol. 2002;435:209-216. (Pubitemid 34131702)
16. Beardsley PM. Evaluation of taranabant (MK-0364) for its selfadministration in rhesus monkeys and for its discriminative stimulus effects in rats. Drug Dev Res. 2009b;70:577-584.
17. Kipnes MS, Hollander P, Fujioka K, et al. A one-year study to assess the safety and efficacy of the CB1R inverse agonist taranabant in overweight and obese patients with type 2 diabetes. Diabetes Obes Metab. 2010;12:517-531.
18. Addy C, Li S, Agrawal N, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, for the treatment of obesity: results from a double-blind, placebo-controlled, single oral dose study in healthy volunteers. J Clin Pharmacol. 2008b;48:418-427. (Pubitemid 351389116)
19. Addy C, Rothenberg P, Li S, et al. Multiple-dose pharmacokinetics, pharmacodynamics, and safety of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, in healthy male volunteers. J Clin Pharmacol. 2008c;48:734-744. (Pubitemid 351713158)
20. Scheen AJ, Finer N, Hollander P, et al. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 2006;368:1660-1672. (Pubitemid 46048528)
21. FDA Center for Drug Evaluation and Research. Guidance for Industry: Assessment of Abuse Potential of Drugs. Silver Spring, MD: US Department of Health and Human Services; 2010.
22. Rowley HL, Butler SA, Prow MR, et al. Comparison of the effects of sibutramine and other weight-modifying drugs on extracellular dopamine in the nucleus accumbens of freely moving rats. Synapse. 2000;38:167-176.
23. Jasinski DR, Faries DE, Moore RJ, et al. Abuse liability assessment of atomoxetine in a drug-abusing population. Drug Alcohol Depend. 2008;95:140-146.
24. Cole JO, Levin A, Beake B, et al. Sibutramine: a new weight loss agent without evidence of the abuse potential associated with amphetamines. J Clin Psychopharmacol. 1998;18:231-236. (Pubitemid 28266889)
25. Schuh LM, Schuster CR, Hopper JA, et al. Abuse liability assessment of sibutramine, a novel weight control agent. Psychopharmacology (Berl). 2000;147:339-346. (Pubitemid 30048480)
26. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-613. (Pubitemid 32823891)
27. Schoedel KA, Chen N, Stott C, et al. A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use. Hum Psychopharmacol. 2011;26:224-236.
28. Williams EJ. Experimental designs balanced for the estimation of residual effects of treatments. Aus J Sci Res Ser. 1949A;2:149-168.
29. Curran HV, Brignell C, Fletcher S, et al. Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berl). 2002;164:61-70. (Pubitemid 35203843)
30. Kirk JM, de Wit H. Responses to oral delta9-tetrahydrocannabinol in frequent and infrequent marijuana users. Pharmacol Biochem Behav. 1999;63:137-142. (Pubitemid 29206572)
31. Schoedel KA, Meier D, Chakraborty B, et al. Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users. Clin Pharmacol Ther. 2010;88:69-78.
32. Martin WR, Sloan JW, Sapira JD, et al. Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. 1971;12:245-258.
33. Chait LD, FischmanMW, Schuster CR. "Hangover" effects the morning after marijuana smoking. Drug Alcohol Depend. 1985;15:229-238. (Pubitemid 15031761)
34. Haertzen CA. Addiction Research Center Inventory (ARCI): development of a general drug estimation scale. J Nerv Ment Dis. 1965;141:300-307.
35. Kaplan HL. When do professional psychologists need professional programmers' tools? Behav Res Methods Instrum Comput. 1985;17:546-550.
36. Sternberg S. High-speed scanning in human memory. Science. 1966;153:652-654.
37. Milovan D, Schoedel K, Romach MK, et al. Clinically relevant effects of abused drugs in human abuse potential studies based on subjective response patterns. College on Problems of Drug Dependence 71st Annual Meeting, Reno/Sparks, NV, June 20-25, 2009, AB412, p. 103.
38. Griffiths RR, Bigelow GE, Ator NA. Principles of initial experimental drug abuse liability assessment in humans. Drug Alcohol Depend. 2003;70:S41-S54. (Pubitemid 36577514)
39. Jasinski DR, Johnson RE, Henningfield JE. Abuse liability assessment in human subjects. Trends Pharmacol Sci. 1984;5:196-200.
40. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B. 1995;571:289-300.
41. Chait LD, Zacny JP. Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. Psychopharmacology (Berl). 1992;107:255-262.
42. Hart CL, Haney M, Vosburg SK, et al. Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. Psychopharmacology (Berl). 2005;181:237-243. (Pubitemid 41492193)
43. Kirk JM, Doty P, De Wit H. Effects of expectancies on subjective responses to oral delta9-tetrahydrocannabinol. Pharmacol Biochem Behav. 1998;59:287-293. (Pubitemid 28072719)
44. Hart CL, van GorpW, Haney M, et al. Effects of acute smoked marijuana on complex cognitive performance. Neuropsychopharmacology. 2001;25:757-765. (Pubitemid 32995958)
45. Peters BA, Lewis EG, Dustman RE, et al. Sensory, perceptual, motor and cognitive functioning and subjective reports following oral administration of delta9-tetrahydrocannabinol. Psychopharmacologia. 1976;47:141-148.
46. Ramaekers JG, Moeller MR, van Ruitenbeek P, et al. Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment. Drug Alcohol Depend. 2006;85:114-122. (Pubitemid 44468137)
47. D'Souza DC, Ranganathan M, Braley G, et al. Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology. 2008;33:2505-2516.
48. Ramaekers JG, Kauert G, Theunissen EL, et al. Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. J Psychopharmacol. 2009;23:266-277.
49. Comer SD, Ashworth JB, Foltin RW, et al. The role of human drug self-administration procedures in the development of medications. Drug Alcohol Depend. 2008;96:1-15.