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.
BACKGROUND
Taranabant is a cannabinoid 1 receptor inverse agonist that was in development for treatment of obesity. Because of central nervous system effects, the study was performed to assess the abuse potential and cognitive effects of taranabant in recreational polydrug users compared with phentermine, dronabinol, and placebo.


METHODS
Stimulant- and cannabis-experienced polydrug users (N = 30) were randomized in a double-blind crossover study to receive taranabant 2, 4, 10, and 20 mg; phentermine 45 and 90 mg; dronabinol 20 mg; and placebo. Subjective and neurocognitive measures were administered for 24 hours, and peak/peak change from baseline effects were analyzed using a linear mixed-effects model.


RESULTS
Phentermine 45 and 90 mg showed abuse-related subjective effects versus placebo, including drug liking, overall drug liking, and other positive/stimulant effects, whereas dronabinol 20 mg showed abuse-related positive, cannabis-like, and sedative effects. Taranabant was not significantly different from placebo on most of the subjective measures other than negative/dysphoric effects at the highest dose, and its effects were significantly less pronounced relative to phentermine and dronabinol on most measures. Phentermine improved cognitive/motor performance and dronabinol impaired motor/cognitive performance on some measures, whereas taranabant 4 and 20 mg had minor impairment effects on manual tracking.


CONCLUSIONS
The phentermine and dronabinol results demonstrate the validity and sensitivity of the study. Taranabant did not consistently show stimulant/cannabis-like effects or abuse potential in recreational polydrug users, indicating that cannabinoid 1 receptor inverse agonists/antagonists are unlikely to be recreationally abused.
INC Research, Toronto, Ontario, Canada. Kerri.Schoedel@incresearch.com
Kerri A
KA
Schoedel
Carol
C
Addy
Bijan
B
Chakraborty
Kim
K
Rosko
Stephanie
S
Dunbar
Andrea
A
Maes
Nancy
N
Chen
Selwyn Aubrey
SA
Stoch
John
J
Wagner
Jeff
J
Chodakewitz
Edward M
EM
Sellers
D000328:Adult; D000577:Amides / Q000009:adverse effects*; D016739:Behavior, Addictive / Q000139:chemically induced / Q000523:psychology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects; D054314:Drug Inverse Agonism; D055030:Drug Users / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000523:psychology*; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010645:Phentermine / Q000009:adverse effects; D011597:Psychomotor Performance / Q000187:drug effects; D011674:Pulse / Q000706:statistics & numerical data; D011725:Pyridines / Q000009:adverse effects*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*
D000577:Amides; C571130:CNR1 protein, human; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D010645:Phentermine; C521311:N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide