McLean Hospital Title:
- Director, Laboratory of Preclinical Pharmacology
Harvard Medical School Title:
- Assistant Professor of Psychiatry
Carol A. Paronis, PhD, is director of the Laboratory of Preclinical Pharmacology at McLean Hospital and an assistant professor of psychiatry at Harvard Medical School. Dr. Paronis received her PhD in pharmacology from Emory University and completed post-doctoral fellowships in pharmacology at the University of Michigan and in biopsychology at Harvard University. She is interested in understanding the behavioral consequences of repeated exposure to drugs and how drug properties influence the expression of drug dependence, addiction, or tolerance.
Dr. Paronis currently serves on the editorial board for Behavioural Pharmacology, is the president of the Behavioral Pharmacology Society, and serves on several committees for the American Society for Pharmacology and Experimental Therapeutics.
Dr. Paronis dedicates a large part of her research to understanding the behavioral consequences of chronic drug exposure leading to drug tolerance and/or physical dependence. Dr. Paronis and her colleagues hope that their work improves our understanding of pharmacological influences on the behavioral effects of drugs. They seek to advance the development of new therapeutics with decreased potential for misuse.
Early research by Dr. Paronis demonstrated that the tolerance that develops to opioid or benzodiazepine drugs is dynamic. Several factors influence the expression of drug tolerance. These include the behavioral endpoint used to measure drug effects, the context under which the drug is administered, or the intrinsic activity of the drug administered chronically.
Ongoing work in her laboratory includes studies of cannabinoid drugs, such as the psychoactive component of marijuana. For example, cannabinoid dependence is a clinical problem in heavy marijuana smokers. But it has been difficult to establish markers of cannabinoid dependence in animals. To address this problem, Dr. Paronis and her team identified reproducible and robust measures of cannabinoid dependence in mice. The researchers have extended this work to test concurrent sleep disturbances in cannabinoid-dependent subjects as they continue to check the role of drug efficacy in the development of cannabinoid dependence.
In another aspect of her research program, Dr. Paronis and her colleagues have built on in vitro findings to ask whether between-drug differences in cell-signaling mechanisms (often referred to as signaling bias) predict differences in their acute or chronic behavioral effects. Ongoing work in her laboratory aims to identify behavioral and physiological biomarkers that vary with the pharmacological effectiveness of opioid drugs.
Her lab engages in work with novel opioid analgesics, currently under development at other institutions. This research centers on the association of biased signaling (i.e., preferential activation of G-protein vs. beta-arresting signaling cascades) with reduced opioid side effects. This work is of interest because of the great need for safer analgesics.
Also, Dr. Paronis works toward identifying candidate medications for different types of drug abuse. Part of this effort includes the refinement of behavioral methods in nonhuman primates to improve our ability to recognize promising lead compounds. Previously, her lab’s emphasis was on cocaine and other psychomotor stimulants. Because of the current opioid addiction crisis, the work now includes heroin and other morphine-like opioids.
- Jack Bergman, PhD, McLean Hospital
- Bill Carlezon, PhD, McLean Hospital
- Rajeev I. Desai, PhD, McLean Hospital
- Arthur Jacobson, PhD, National Institute on Drug Abuse
- Brian D. Kangas, PhD, McLean Hospital
- Stephen J. Kohut, PhD, McLean Hospital
- Alexandros Makriyannis, PhD, Northeastern University
- Spyros P. Nikas, PhD, Northeastern University
- Kenner C. Rice, PhD, National Institute on Drug Abuse
- Kiran Vemuri, PhD, Northeastern University
- Sarah L. Withey, PhD, McLean Hospital
Paronis CA, Nikas SP, Shukla VG, Makriyannis A. Δ9-Tetrahydrocannabinol acts as a partial agonist/antagonist in mice. Behavioural Pharmacology. 2012;23: 802-805.
Gasior M, Bergman J, Kallman MJ, Paronis CA. Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and I.V. drug delivery in rhesus monkeys. Neuropsychopharmacology. 2015;30:758-764.
Withey SL, Spealman RD, Bergman J, Paronis CA. Behavioral effects of opioid full and partial agonists during chronic buprenorphine treatment. Journal of Pharmacology and Experimental Therapeutics. 2019;371:544-554.
Education & Training:
- 1985 BS, Tufts University
- 1993 PhD, Emory University
- 1993-1995 Post-Doctoral Fellow, University of Michigan
- 1996-1997 Post-Doctoral Fellow, NERPRC, Harvard University
Belmont campus - Oaks Building