Biobehavioral Studies of Drug and Alcohol Abuse
Behavioral Psychopharmacology Research Laboratory, McLean Hospital
Scott E. Lukas, Ph.D., Ron Cowan, M.D., Ph.D., Cynthia M. Dorsey, Ph.D., Igor Elman, M.D., Gene M. Heyman, Ph.D., James Hopper, Ph.D., Gopinath Mallya, M.D., Christopher Palmer, M.D., David Penetar, Ph.D., John Rodolico, Ph.D.
This multidisciplinary clinical research program explores the contributions of family history of alcoholism, bioavailability, pharmacokinetics and drug history on sex- and ethnic-related differences in the response to acute ethanol, cocaine and marihuana administration in healthy occasional drug users. Data from these studies are then applied to evaluate potential behavioral and pharmacological interventions that may be effective in modifying drug-induced effects and drug self-administration. Drug effects are quantified using EEG activity, event-related potentials, heart rate, blood pressure, skin temperature, subjective mood states and cognitive function. Changes in brain electrical activity during intoxication are quantified using topographic mapping techniques to determine the source of drug effect. EEG brain maps are then matched with magnetic resonance images to more precisely locate the origins of the activity. The nature of cue-induced craving is also explored using brain imaging techniques. An affiliation with the Sleep Disorders Research Program allows the opportunity to study the effects of various drugs of abuse on sleep architecture and sleep-related breathing disorders. Active collaborations with the Brain Imaging Center include a wide range of studies using fMRI and MRS to study the kinetics of brain alcohol and cue-induced craving. Many studies also involve pharmacokinetic analyses as we explore polydrug related issues such as the impact tha the nicotine patch has on alcohol and marihuana effects. A second major aim of the program is to develop novel medications for treating drug and alcohol abuse. The strategies for pursuing new medications differs from the traditional neurotransmitter models and focuses on a variety of different medications including: hormones, naturally occurring nucleotides such as CDP-choline, current medications such as the nicotine patch and a Chinese herb.
Data obtained from these studies will enhance our basic understanding of the nature of the interactions among multiple drugs of abuse and how this relationship alters drug reinforcement and ultimately, drug-taking behavior. In addition, the issue of vulnerability to drug abuse is being explored by correlating pre-drug control measures of EEG and event-related potentials with the subsequent post-drug responses. Finally, the role of other factors in predicting the efficacy of new pharmacotherapies for drug and alcohol abuse is being studied.
Key words: cocaine, marihuana, ethanol, nicotine, EEG, kudzu, polydrug abuse, sex differences, pharmacokinetics, brain imaging, clinical trials, cue-induced craving, pharmacotherapies, family history of alcoholism.
Grant Support: NIDA: RO1 DA03994, Polydrug Abuse: Imaging and Behavior (SEL); RO1 DA11098, Medication Development for Cocaine Abuse: CDP-choline, (SEL); KO5 DA00343, Behavioral and Pharmacologic Analysis of Drug Abuse (SEL-Research Scientist Award); RO1 DA12014, Nicotine's Effects on Other Drugs of Abuse (EK); T32 DA15036, Training in Drug Abuse and Brain Imaging (SEL); NIA: R29 AG13961, Insomnia in Elderly: Passive Body Heating (CMD). NIAAA: RO1 AA10536, Isoflavone Treatment for Alcohol Abuse (SEL).
Program Site: Behavioral Psychopharmacology Laboratory/NeuroImaging Center, McLean Hospital.
Program Director: Scott E. Lukas, Ph.D., Behavioral Psychopharmacology Research Laboratory, McLean Hospital, 115 Mill St., Belmont, MA 02478. e-mail address: Lukas@.mcLean.harvard.edu
Contact Person: Carol Buchanan, Administrative Assistant, (617) 855-2767; FAX (617) 855-3711.
Training Opportunities: Both pre- and post-doctoral training positions are available.
Representative Publications:
Lukas SE, Sholar M, Kouri E, Fukuzako H, Mendelson JH. Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers. Pharmacol Biochem Behav 1994;48:715-21
Lukas SE, Mendelson JH, Benedikt R. Electroencephalographic correlates of marihuana-induced euphoria. Drug Alcohol Depend 1995;37:131-40
Lukas SE, Sholar M, Lundahl L, Lamas X, Kouri E, Wines J, Kragie L, Mendelson J. Sex differences in plasma cocaine levels and subjective effects after acute cocaine administration in human volunteers.Psychopharmacology 1996;124:346-54
Maas LC, Lukas SE, Kaufman MJ, Weiss RD, Daniels SL, Rogers VW, Kukes TJ, Renshaw PF. Functional magnetic resonance imaging of cue-induced cocaine craving in the human brain. Am J Psychiatry 1998;155: 124-26
Dorsey CM, Teicher M, Cohen-Zion M, Stefanovic L, Harper D, Satlin A, Tartarini W, Harper D, Lukas SE. Core body temperature and sleep of older female insomniacs before and after passive body heating. Sleep 1999;22:891-8
Renshaw PF, Daniels S, Lundahl LH, Rogers V, Lukas SE. Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: A preliminary report. Psychopharmacology 1999;142:132-8
Cowan RL, de Frederick B, Rainey M, Levin JM, Maas LC, Bang J, Hennen J, Lukas SE, Renshaw PF. Sex differences in response to red and blue light in human primary visual cortex:a bold fMRI study.Psychiatry Res Neuroimag 2000;100: 129-38
Kouri, EM, Stull, M, Lukas, SE. Nicotine alters some of cocaine's subjective effects in the absence of physiological or pharmacokinetic changes. Pharmacol Biochem Behav 2001;69: 209-17
Lukas SE, Orozco S. Ethanol increases plasma ∆9-tetrahydrocannabinol (THC) levels and subjective effects after marihuana smoking in human volunteers. Drug Alcohol Depend 2001; 64: 143-149