Lance McMahon, Ph.D.
Dr. Lance McMahon
Department of Pharmacodynamics
University of Florida College of Pharmacy 1345 Center Drive; Building JHMHSC, Room P1-20
P.O. Box 100487
Gainesville, FL 32610
Phone: (352) 273-7700
FAX: (352) 273-7705
Professor and Chair, Department of Pharmacodynamics College of Pharmacy
Research in my laboratory integrates principles of behavior and receptor theory to identify central nervous system mechanisms responsible for drug dependence.
MS, PhD Psychology Texas A&M University; postdoctoral training with Kathryn Cunningham, PhD, Department of Pharmacology and Toxicology, University of Texas Medical Branch
Current Research Focus
Drug misuse and dependence can devastate individuals, family, friends, public health, and society. Effective therapies for drug dependence must consider environmental, behavioral, and pharmacologic determinants responsible for drug misuse. Research in my laboratory integrates principles of behavior and receptor theory to identify central nervous system mechanisms responsible for drug dependence. We also investigate novel pharmacological strategies that maximize therapeutic potential and minimize dependence and abuse liability. Our research incorporates a combination of behavioral and physiological approaches, receptor-selective ligands, and quantitative analyses of drug interactions.
Two ongoing research areas in the McMahon laboratory include:
a) Cannabinoids (i.e., any drug that binds to cannabinoid receptors) include cannabis-derived tetrahydrocannabinols, numerous synthetic cannabinoids, and endogenous cannabinoid neurotransmitters. Synthetic cannabinoids have been misused more recently under the guise of such brand names as Spice or K2. Endogenous cannabinoids are degraded by the enzymes fatty acid amide hydrolase and monoacylglycerol lipase, and novel drug inhibitors of these enzymes have been identified. We systematically compare the effects of these diverse cannabinoid drugs and evaluate underlying receptor mechanisms to better understand dependence and therapeutic potential.
b) FDA-approved smoking cessation aids such as nicotine, varenicline, and bupropion can double abstinence rates; however, relapse within one year can be 75%. We compare the in vivo pharmacology of novel, investigational nicotinic acetylcholine receptor drugs to FDA-approved compounds to better understand relationships between receptor subtypes, intrinsic activity, and behavioral effects. In addition to these so-called orthosteric ligands, we study the effects of acetylcholinesterase inhibitors and nicotine acetylcholine receptor modulators. Overall, our efforts have the potential to inform upon the development of novel drug treatments for tobacco dependence and other cholinergic-related disorders such as dementia.
Hruba L, McMahon LR. Apparent affinity estimates and reversal of the effects of synthetic cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by rimonabant in rhesus monkeys. J Pharmacol Exp Ther 2017 Aug;362(2):278-286.
De Moura FB, McMahon LR. The contribution of α4β2 and non-α4β2 nicotinic acetylcholine receptors to the discriminative stimulus effects of nicotine and varenicline in mice. Psychopharmacology (Berl) 2017 Mar;234(5):781-792.
Moerke MJ, Zhu AZ, Tyndale RF, Javors MA, McMahon LR. The discriminative stimulus effects of i.v. nicotine in rhesus monkeys: Pharmacokinetics and apparent pA2 analysis with dihydro-β-erythroidine. Neuropharmacology 2016 Dec;116:9-17.
Cunningham CS, Moerke MJ, Javors MA, Carroll FI, McMahon LR. Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily. Br J Pharmacol 2016 Dec;173:3454-3466.
McMahon LR. Enhanced discriminative stimulus effects of Δ9-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys. Drug Alcohol Depend 2016 Aug;165:87-93.
Moerke MJ, de Moura FB, Koek W, McMahon LR. Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice. Eur J Pharmacol 2016 May;786:169-178.