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National Institute on Drug Abuse

Director's Report to the National Advisory Council on Drug Abuse
February, 1998


Research Findings



Behavioral Research


CB1 Receptors May Mediate Marijuana's Effects on Learning

Researchers at Louisiana State University Medical Center recently reported that many of the behavioral and learning deficits induced by the active compound in marijuana, delta-9 THC and other cannabinoid ligands are mediated through the brain receptor CB1. Rats pre-administered delta-9 THC or the cannabinoid agonist R-methandamide increased errors on a learning and memory task. The selective CB1 cannabinoid antagonist (SR141716A) administered concurrent with the cannabinoids resulted in fewer errors. These data suggest that cannabinoids disrupt learning processes as a result of direct stimulation of the CB1 receptor. Brodkin, J. & Moerschbaecher, J.M. The Journal of Pharmacology and Experimental Therapeutics, 282, pp. 1526-1532, 1997.


Does Smoking Increase Your Desire to Smoke?

Researchers at University of Pittsburgh recently explored whether limited prior smoke exposure primes smokers to continue smoking. Following overnight smoking abstinence, smokers were given the opportunity to take between 0-12 puffs, or to smoke an entire cigarette. Following this, they reported their desire to continue smoking, and then chose between earning money vs taking more cigarette puffs. Smokers reported less desire for smoking as prior smoke exposure (number of puffs) increased. However, responding for puffs on the computer task was only modestly reduced by prior smoke exposure and was only significantly reduced following the smoking of an entire cigarette. These results suggest that smoking following a relatively brief abstinence period reduces the stated desire to smoke, but does not result in a priming effect (i.e., an increase in responding for cigarette puffs). Perkins, K. A., Grobe, P., & Fonte, C. Experimental and Clinical Psychopharmacology, 5, pp. 277-285, 1997.


Kappa Agonists and Cocaine Self-Administration

Two kappa opioid agonists, the benzomorphan ethylketocyclazocine (EKC) and the arylacetamide U50,488 were examined for their effects on cocaine self-administration in rhesus monkeys. Monkeys responded for 0.032 mg/kg/injection cocaine (i.v.) and food pellets during alternating daily sessions of cocaine and food availability. Chronic treatment for 10 consecutive days with EKC (0.0032-0.032 mg/kg/hr) or U50,488 (0.032-0.1 mg/kg/hr) dose-dependently decreased self-administration of cocaine, often sustained throughout the 10 days of treatment. Note however that food-maintained responding was reduced as well. In addition, EKC and U50,488 often produced emesis and sedation during the first few days of treatment, although tolerance appeared to develop rapidly to these effects. The kappa antagonist norbinaltorphimine (3.2 mg/kg) did not affect responding maintained by cocaine or food. However, both norbinaltorphimine (3.2 mg/kg) and the opioid antagonist naloxone (1.0 mg/kg/hr) blocked the effects of EKC and U50,488. While chronic administration of EKC and U50,588 produced dose-dependent, kappa receptor-mediated and often sustained decreases in cocaine self-administration, they also produced undesirable behavioral effects that may complicate their use as treatments for cocaine dependence. Negus, S.S., Mello, N.K., Portoghese, P.S., Lin, C.E., Effects of Kappa Opioids on Cocaine Self-Administration by Rhesus Monkeys. J Pharmacol Exp Ther, 282, pp. 44-55, 1997.


Abuse Liability of New Nicotine Delivery Systems

Overnight-deprived adult smokers received between 0-16 active puffs from nicotine-containing cigarettes (0.1 mg per puff); between 0-4 nasal sprays (0.5 mg nicotine per spray), and between 0-120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-S single blinded design. While smokers clearly liked cigarette puffs, they liked nasal spray or vapor inhaler less well, with only modest elevations on a "good drug effects" scale. The spray and inhaler products produced unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increases were dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with inhalers. Nicotine nasal spray and vapor inhaler appear to have substantially lower abuse liability than cigarettes in experienced cigarette smokers initially exposed to these products. Schuh, K.I., Schuh, L.M., Henningfield, J.E., and Stitzer, M.L. Nicotine Nasal Spray and Vapor Inhaler: Abuse Liability Assessment. Psychopharmacology. 130, pp. 352-361, 1997.


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