Aron H. Lichtman, Ph.D.
- Dartmouth College, 1989
- Drugs of abuse
- Learning and memory
- Pain and inflammation
My research program focuses on four general areas: 1) understanding the physiological function of the endocannabinoid system; 2) elucidating the mechanisms of action underlying the pharmacological effects of THC and other cannabinoids; 3) investigating medicinal uses of cannabinoids and 4) determining the impact of the drugs of abuse via the inhalation route of administration. Much of this research employs a multidisciplinary approach using a combination of behavioral/physiological measures, pharmacological agents, genetically altered mice and quantification of drug, as well as endogenous compounds in body and brain. The endocannabinoid system in the central nervous system comprises the endogenous cannabinoids arachidonoylethanolamide (anandamide) and the monoacylglycerol 2-arachidonoylglycerol (2-AG) that bind to CB1 cannabinoid receptors in the brain and spinal cord. Most recently we have found that the enzyme fatty acid amide hydrolase (FAAH) is a key in vivo regulator of anandamide and other fatty acid amides, which sets an endogenous tone that modulates several physiological functions including the modulation of pain, inflammation, cognition and drug dependence. In addition, we have found that disruption of endocannabinoid signaling facilitates the extinction of non-reinforced behavior from memory. These extinction deficits appear in some models as improved memory, while in tasks that require the suppression of previously learned responses, they appear as a disruption in learning. Finally, other research in my laboratory demonstrates that FAAH modulates both pain and inflammatory responses. This work taken together may ultimately contribute to the development of endocannabinoid/FAAH-based therapeutic agents for the treatment of pain, cognitive disorders and drug addiction.
Schlosburg JE, O’Neal ST, Conrad DH and Lichtman AH. (2011) CB(1) receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology (Berl).
Soderstrom K, Poklis JL and Lichtman AH. (2011) Cannabinoid exposure during zebra finch sensorimotor vocal learning persistently alters expression of endocannabinoid signaling elements and acute agonist responsiveness. BMC Neuroscience. 12:3.
Kinsey SG, O’Neal ST, Long JZ, Cravatt BF and Lichtman AH. (2011) Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay. Pharmacology, Biochemistry and Behavior. 98(1):21-7.
Kinsey SG, Mahadevan A, Zhao B, Sun H, Naidu PS, Razdan RK, Selley DE, Imad Damaj M and Lichtman AH. (2011) The CB(2) cannabinoid receptor-selective agonist O-3223 reduces pain and inflammation without apparent cannabinoid behavioral effects. Neuropharmacology. 60(2-3):244-51.
Poklis JL, Thompson CC, Long KA, Lichtman AH and Poklis A. (2010) Disposition of cannabichromene, cannabidiol, and δ-tetrahydrocannabinol and its metabolites in mouse brain following marijuana inhalation determined by high-performance liquid chromatography-tandem mass spectrometry. Journal of Analytical Toxicology. 34(8):516-520.
Bu DX and Lichtman AH. (2010) T cells and blood vessels: costimulation turns up the pressure. Circulation. 122(24):2495-8.
Avraham Y, Saidian M, Burston JJ, Mevorach R, Vorobiev L, Magen I, Kunkes E, Borges B, Lichtman AH and Berry EM. (2010) Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals. Journal of Nutritional Biochemistry.
Lichtman AH, Blankman JL and Cravatt BF. (2010) Endocannabinoid overload. Molecular Pharmacology. 78(6):993-5.
Schlosburg JE, Blankman JL, Long JZ, Nomura DK, Pan B, Kinsey SG, Nguyen PT, Ramesh D, Booker L, Burston JJ, Thomas EA, Selley DE, Sim-Selley LJ, Liu QS, Lichtman AH and Cravatt BF. (2010) Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nature Neuroscience. 13(9):1113-9.
DeLong GT, Wolf CE, Poklis A and Lichtman AH. (2010) Pharmacological evaluation of the natural constituent of cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol. Drug and Alcohol Dependence. Nov 1;112(1-2):126-33.
Kinsey SG, Long JZ, Cravatt BF and Lichtman AH. (2010) Fatty acid amide hydrolase and monoacylglycerol lipase inhibitors produce anti-allodynic effects in mice through distinct cannabinoid receptor mechanisms. Journal of Pain. 11(12):1420-8.
Bu DX, Tarrio M, Grabie N, Zhang Y, Yamazaki H, Stavrakis G, Maganto-Garcia E, Pepper-Cunningham Z, Jarolim P, Aikawa M, García-Cardeña G and Lichtman AH. (2010) Statin-induced Krüppel-like factor 2 expression in human and mouse T cells reduces inflammatory and pathogenic responses. Journal of Clinical Investigation. Jun 1;120(6):1961-70.
Naidu PS, Kinsey SG, Guo TL, Cravatt BF and Lichtman AH. (2010) Regulation of inflammatory pain by inhibition of fatty acid amide hydrolase. Journal of Pharmacology and Experimental Therapeutics. 334(1):182-90.
Falenski KW, Thorpe AJ, Schlosburg JE, Cravatt BF, Abdullah RA, Smith TH, Selley DE, Lichtman AH and Sim-Selley LJ. (2010) FAAH-/- mice display differential tolerance, dependence and cannabinoid receptor adaptation after delta 9-tetrahydrocannabinol and anandamide administration. Neuropsychopharmacology. 35(8):1775-87.