Department of Psychology; Centers for Neuroscience
Ph.D., Psychology: Behavioral Neuroscience, The Ohio State University
Institute for Behavioral Medicine Research, The Ohio State University;
Department of Pharmacology & Toxicology, Virginia Commonwealth University
Personal Site: http://community.wvu.edu/~sgkinsey/
- Endocannabinoid System
- Phytocannabinoids are plant-based cannabinoids. Some examples are delta-9 tetrahydrocannabinol (THC), which is the primary psychoactive component of marijuana, cannabidiol, and cannabichromene.
- Synthetic cannabinoids are laboratory produced compounds that are known to bind to cannabinoid receptors. These synthetic cannabinoids have been in the news lately because they are being sold as "incense" to be smoked by people. Synthetic cannabinoids are not intended for human consumption and are dangerous to use because their effects are largely unknown. Many hospitalizations have been reported by people who smoke synthetic cannabinoids.
- Endocannabinoids are cannabinoids that are naturally produced in the body (that is, endogenously produced).
- Two cloned cannabinoid receptors (CB1 and CB2)
- The endocannabinoids anandamide and 2-arachidonylglycerol (2-AG). In addition, there are some other compounds that have been shown to bind to CB1 and CB2 but may have limited effects in live animals.
- The enzymes that regulate the biosynthesis and catabolism of the endocannabinoids. For example, fatty acid amide hydrolase (FAAH) metabolizes anandamide into ethanolamine and arachydonic acid (AA), whereas monoacylglycerol lipase (MAGL) is the primary enzyme responsible for metabolizing 2-AG into glycerol and arachydonic acid.
- Stress, Drug Dependence, and Emotion
One line of federally funded research investigates how endocannabinoids affect emotionality, that is, stress, anxiety, and depression. Cannabis has been used for millennia to decrease stress, reduce anxiety and depression, and bring about feelings of euphoria. Endocannabinoids are released on demand in response to stress, and appear to have anxiety-reducing effects in animals. Thus, the overall goal of this line of research is to develop novel endocannabinoid-based treatments for disorders involving anxiety and depression.
In addition, we are investigating how drug dependence represents a stressor, and how the endocannabinoid system affects the development of anxiety-like and depressive-like behaviors over the lifespan of the animal.
We use an array of automated behavioral systems to investigate the effects of cannabinoids on anxiety-like and depressive-like behaviors in a range of rodent models.
- Inflammation and Analgesia
My first line of funded research focuses on the anti-inflammatory role of endocannabinoids. Chronic pain is a problem for a large segment of our population, and pain resulting from nerve injury is particularly resistant to existing drug treatments, including opiates and non-steroidal anti-inflammatory drugs (NSAIDs), like aspirin and ibuprofen.
The endocannabinoid system offers many promising targets for the development of alternative analgesics (i.e., pain reducing drugs). Published reports from our lab and others indicate that manipulation of the endocannabinoid system reduces systemic inflammation. We use models of inflammatory arthritis, as well as both inflammatory and neuropathic pain in animal models, with the goal of finding new treatments for these chronic conditions.
In addition, we also study the role of endocannabinoids in gastric inflammation, using models of chemical- and stress-induced gastritis. The primary side effect of existing NSAIDs is that they cause gastric inflammation. As people build tolerance to these drugs and take higher doses, the occurrence and severity of these side effects increases, leading to ulceration and hemorrhaging. The overall goal of these projects of to use the analgesic anti-inflammatory properties of endocannabinoids to prevent and treat gastric pain and inflammation.
What is a cannabinoid?
Cannabinoids are compounds that are similar to those compounds found in Cannabis sativa (marijuana). Cannabinoids are categorized based on their origin:
The endocannabinoid system
The endogenous cannabinoid (i.e., endocannabinoid) system consists of:
Effects of endocannabinoids
Systemic administration of anandamide or 2-AG has limited efficacy in vivo, because these endocannabinoids are so rapidly degraded by FAAH or MAGL (along with ABHD6 and ABHD12), respectively. However, pharmacological inhibiton of FAAH, for eample with the Pfizer compound PF-3845, increases tissuelevels of anandamide as well as some other fatty acid amides that FAAH hydrolizes. Similarly, the inhibition of MAGL, for example with the compound JZL184, increases tissue levels of 2-AG. Alterations in endocannabinoid levels affect a broad range of physiological and behavioral systems. Our lab as well as others have demonstrated that PF-3845 and JZL184 produce a range of effects including analgesia and decreases in anxiety-like behaviors.
For further reading, please see our recent minireview in Brain, Behavior and Immunity.
Molly S. Crowe, MS
Behavioral Neuroscience Graduate Student
Molly is a fifth year PhD student in the Behavioral Neuroscience program. She is interested in many aspects of cannabinoid function, with special regard to the effects of stress on inflammatory processes, including wound healing, gastric hemorrhages, and algesia.
When not in the lab, Molly is also an avid cyclist and hiker.
Sara R. Nass, MS
Behavioral Neuroscience Graduate Student
Sara is a fourth year PhD student in the Behavioral Neuroscience program. She is interested in various aspects of cannabinoid function, with special regard to the effects of cannabinoids on inflammation and nociception.
When not in the lab, Sara enjoys reading science fiction and fantasy literature, and exploring new recipes.
Kristen R. Trexler, MS
Kristen is a second year PhD student in the Behavioral Neuroscience program. Kristen's work investigates the psychoactive properties of cannabinoid administration, with specific emphasis on the behavioral effects of cannabinoid withdrawal.
When not in the lab, Kristen enjoys swimming and hiking.
- Ghosh, S., Kinsey, S.G., Liu, Q., Hruba, L, McMahon, L.R., Wise, L.E., Abdullah, R.A., Selley, D.E., Sim-Selley, L.J., Cravatt, B.F., Lichtman, A.H. (2015). Full FAAH inhibition combined with partial monoacylglycerol lipase inhibition: Augmented and sustained antinociceptive effects with negligible cannabimimetic side effects in mice. Journal of Pharmacology and Experimental Therapeutics. In press.
- Nass*, S.R., Long, J.Z., Schlosburg, J.E., Cravatt, B.F., Lichtman, A.H., Kinsey, S.G. (2015). Endocannabinoid catabolic enzymes function to maintain thermal homeostasis in response to environmental or immunological challenge. Journal of Neuroimmune Pharmacology. In press.
- Crowe*, M.S., Leishman, E., Gujjar, R., Mahadevan, A., Banks, M.L., Bradshaw, H.B., Kinsey, S.G. (2015). Dual Cyclooxygenase and Monoacylglycerol Lipase Inhibition Synergistically Attenuates Neuropathic Pain. British Journal of Pharmacology. In press.
- Grim, T.W., Ghosh, S., Hsu, K, Cravatt, B.F., Kinsey, S.G., Lichtman, A.H. (2014). Co-administration of a FAAH inhibitor and an NSAID produces enhanced anti-allodynic effects in murine neuropathic and inflammatory pain models. Pharmacology, Biochemistry, and Behavior. 124:405-411.
- Crowe*, M.S., Nass*, S.R., Gabella*, K.M., Kinsey, S.G. (2014). The endocannabinoid system modulates stress, emotionality, and inflammation. Brain, Behavior, and Immunity. 42:1-5.
- Schlosburg, JE, Kinsey, SG, Ignatowska-Jankowska, B, Ramesh, D, Abdullah, RA, Tao, Q, Booker, L, Long, JZ, Selley, DE, Cravatt, BF, and Lichtman, AH (2014). Prolonged monoacylglycerol lipase blockade causes equivalent CB1-receptor mediated adaptations in FAAH wild type and knockout mice. Journal of Pharmacology and Experimental Therapeutics. 350(2):196-204.
- Ignatowska-Jankowska, BM, Ghosh, S, Crowe*, MS, Kinsey, SG, Niphakis, MJ, Abdullah, RA, O'Neal, ST, Walentiny, DM, Wiley, JL, Cravatt, BF, and Lichtman, AH (2013). In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML29: Antinociceptive activity without cannabimimetic side effects. British Journal of Pharmacology. 171(6):1392-1407.
- Kinsey, S.G. and Cole**, E.C. (2013). Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice. European Journal of Pharmacology. 715(1-3):111-116.
- Kinsey, S.G., Wise, L.E., Ramesh, D., Long, J.Z., Selley, D.E., Cravatt, B.F., Lichtman, A.H. (2013). Repeated Low Dose Administration of the Monoacylglycerol Lipase Inhibitor JZL184 Retains CB1 Receptor Mediated Antinociceptive and Gastroprotective Effects. The Journal of Pharmacology and Experimental Therapeutics. 345(3), 492-501.
- Booker, L., Kinsey, S.G., Abdullah, R.A., Long, J.Z., Boger, D., Cravatt, B.F., Lichtman, A.H. (2012). The FAAH Inhibitor PF-3845 Acts in the Nervous System to Reverse Lipopolysaccharide-induced Tactile Allodynia in Mice. British Journal of Pharmacology. 165(8), 2485-2496.