PRINCIPAL INVESTIGATORS

Marilyn A. Huestis, Ph.D., Senior Investigator

Chief, Chemistry and Drug Metabolism Section

Ph.D. - Toxicology, University of Maryland Baltimore School of Medicine Advisor: Dr. Edward Cone

M.S. - Clinical Chemistry, University of New Mexico

A.B. - Physiology and Biochemistry, Mount Holyoke College

RESEARCH INTERESTS

Our current research efforts are focused on mechanisms of action of cannabinoid agonists and antagonists, effects of in utero drug exposure, and the neurobiology and pharmacokinetics of MDMA or Ecstasy. We conduct controlled drug administration studies in human drug users to investigate the pharmacodynamic effects of abused drugs and licit pharmacotherapies. The onset, peak, and duration of drug effects are correlated to the drug’s pharmacokinetics. We study the disposition of drugs and metabolites in a wide variety of biological fluids and tissues to provide a scientific database for interpreting drug concentrations in many alternative matrices. We utilize pharmacological tools such as the CB1-cannabinoid receptor antagonist rimonabant, the exogenous agonist Δ9-tetrahydrocannabinol, and other cannabinoids such as cannabidiol to probe the endogenous cannabinoid system. We currently are evaluating cannabis dependence, the development of tolerance after chronic cannabis exposure, and cannabis withdrawal. We have a strong research interest in the neurobehavioral, neurophysiological, and physical effects of in utero drug exposure to methamphetamine, heroin, cocaine, tobacco, and cannabis. We are determining whether there are fetal drug syndromes, analogous to the fetal alcohol syndrome, in neonates exposed in utero to drugs. We have recently found non-linear pharmacokinetics of MDMA within the recreational dose range and significant differences in MDMA half-lives between males and females. Our research group utilizes sensitive and specific liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry methods to address the problems of drug addiction and prevention and treatment of drug abuse.

Selected Publications:

1. Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA. Plasma cannabinoid pharmacokinetics following controlled oral Δ9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clinical Chemistry. In press.

2. de Castro A, Jones, HE, Johnson RE, Gray TR, Shakleya DM, Huestis MA. Maternal methadone dose, placental methadone concentrations and neonatal outcomes. Clinical Chemistry. In press.

3. Karschner EL, Darwin WD, McMahon RP, Liu F, Wright S, Goodwin RS, Huestis MA. Subjective and physiological effects after controlled Sativex and oral THC administration. Clinical Pharmacology and Therapeutics. In press.

4. Gray TR, Choo RE, Concheiro M, Williams E, Elko A, Jansson LM, Jones HE, Huestis MA. Prenatal methadone exposure, meconium biomarker concentrations and neonatal abstinence syndrome. Addiction, 2010 Dec:105(12); 2151-2159. Epub 2010 Sep 20.

5. Schwilke EW, Gullberg RG, Darwin WD, Chiang N, Cadet JL, Gorelick DA, Pope HG, Huestis MA. Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users. Addiction, In press.

6. Milman G, Barnes AJ, Schwope DM, Schwilke EW, Darwin WD, Goodwin RS, Kelly DL, Gorelick DA, Huestis MA. Disposition of cannabinoids in oral fluid following controlled around-the-clock oral THC administration. Clinical Chemistry, 2010 Aug;56(8):1261-9. Epub 2010 Jun 8.

7. Gray TR, Eiden RD, Leonard KE, Connors G, Shisler S, Huestis MA. Nicotine and metabolites in meconium as evidence of maternal cigarette smoking during pregnancy and predictors of neonatal outcome. Nicotine & Tobacco Research, 2010 Jun;12(6):658-64. Epub 2010 Apr 28.

8. Gray TR, Kelly T, LaGasse LL, Smith LM, Derauf C, Grant P, Shah R, Arria A, Haning W, Della Grotta S, Strauss A, Lester BM, and Huestis MA. New meconium biomarkers of prenatal methamphetamine exposure increase identification of affected neonates? Clinical Chemistry, 2010 May;56(5):856-60. Epub 2010 Feb 25.

9. Milman G, Barnes AW, Lowe RW, Huestis MA. Simultaneous quantification of cannabinoids and metabolites in oral fluid by two-dimensional gas chromatography mass spectrometry. Journal of Chromatography A, 2010 Feb 26; 1217(9): 1513-1521. Epub 2010 Jan 4.

10. Concheiro M, Jones HE, Johnson RE, Choo R, Shakleya DM, Huestis MA. Maternal Buprenorphine Dose, Placenta Buprenorphine and Metabolite Concentrations and Neonatal Outcomes. Therapeutic Drug Monitoring, 2010 Apr;32(2):206-15.