Indiana University
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The Gill Center for Biomolecular Science

Ken Mackie | Faculty

Mackie2015Professor, Department of Psychological and Brain Sciences and Program in Neuroscience

Office: MSBII 120
TEL: 812-855-2042

Lab Website


  • Brown University, ScB, Engineering, 1980
  • Yale University, MD, 1984

Research Interests

  • Regulation of CB1 cannabinoid receptor signaling
  • Regulation of endocannabinoid production
  • Role of endocannabinoids in synaptic plasticity
  • Novel cannabinoid receptors

His research program focuses on cannabinoid receptors, the cell surface receptors responsible for most of the psychoactive and therapeutic actions of cannabis. His group uses a variety of techniques, including electrophysiological, molecular, immunological, and imaging, to better understand how cannabinoid receptors signal and how their signaling interacts with other cellular processes. Much of the current work in his lab centers on endogenous cannabinoids (endocannabinoids), compounds produced by the body that interact with cannabinoid receptors. These molecules have been implicated in processes as diverse as memory, analgesia, anxiety, schizophrenia, and obesity. One of the recent results from his group suggests that cannabis produces some of its effects by blocking the normal actions of endocannabinoids. This contrasts with the mode of action of opiates, which appear to produce their psychoactivity by mimicking the effects of endogenous opiates (endorphins).

Representative Publications

  • For a quick search that will return most recent publications:
  • Bara, A., Manduca, A., Bernabeu, A., Borsoi, M., Servado, M., Lassalle, O., . . . Manzoni, O. J. (n.d.). Sex specific endophenotypes of in-utero cannabinoid exposure. BioRxiv. 10.1101/251348
  • Lin, X., A.S. Dhopeshwarkar, M. Huibregtse, K. Mackie, and A.G. Hohmann, The slowly signaling G protein-biased CB2 cannabinoid receptor agonist LY2828360 suppresses neuropathic pain with sustained efficacy and attenuates morphine tolerance and dependence. Mol Pharmacol, 2017. 93(2):49-62.
  • Westphal, M., M.A. Schafroth, R. Sarott, M. Imhof, C. Bold, P. Leippe, A. Dhopeshwarkar, J. Grandner, V. Katritch, K. Mackie, D. Trauner, E.M. Carreira, and J.A. Frank, Synthesis of Photoswitchable Delta(9)-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling. J Am Chem Soc, 2017.
  • Ruehle, S., J. Wager-Miller, A. Straiker, J. Farnsworth, M.N. Murphy, S. Loch, K. Monory, K. Mackie, and B. Lutz, Discovery and characterization of two novel CB1 receptor splice variants with modified N-termini in mouse. J Neurochem, 2017. 142(4): p. 521-533.
  • Li, A.L., L.M. Carey, K. Mackie, and A.G. Hohmann, Cannabinoid CB2 Agonist GW405833 Suppresses Inflammatory and Neuropathic Pain through a CB1 Mechanism that is Independent of CB2 Receptors in Mice. J Pharmacol Exp Ther, 2017. 362(2): p. 296-305.
  • Lu, H.C. and K. Mackie. An introduction to the endogenous cannabinoid system. Biol Psychiatry, 2016: 79(7): 516-25.
  • Dhopeshwarkar, A., N. Murataeva, A. Makriyannis, A. Straiker, and K. Mackie, Two Janus cannabinoids that are both CB2 agonists and CB1 antagonists. J Pharmacol Exp Ther, 2016. 360(2): p. 300-311.
  • Murataeva, N., A. Dhopeshwarkar, D. Yin, J. Mitjavila, H.B. Bradshaw, A. Straiker, and K. Mackie. Where’s my entourage? The curious case of 2-oleoylglycerol, 2-linolenoylglycerol and 2-palmitoylglycerol, Pharmacol Res, 2016. 110: p. 173-80.
  • Dhopeshwarkar, A. and K. Mackie, Functional Selectivity of CB2 Cannabinoid Receptor Ligands at a Canonical and Noncanonical Pathway. J Pharmacol Exp Ther, 2016. 358(2): p. 342-51.
  • Straiker, A., J. Mitjavila, D. Yin, A. Gibson and K. Mackie. Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal model. Pharmacol Res, 2015. 99: 370-6.
  • Morgan, D.J., B.J. Davis, C.S. Kearn, D. Marcus, A.J. Cook, J. Wager-Miller, A. Straiker, M.H. Myoga, J. Karduck, E. Leishman, L.J. Sim-Selley, T.A. Czyzyk, H.B. Bradshaw, D.E. Selley, and K. Mackie, Mutation of Putative GRK Phosphorylation Sites in the Cannabinoid Receptor 1 (CB1R) Confers Resistance to Cannabinoid Tolerance and Hypersensitivity to Cannabinoids in Mice. J Neurosci, 2014. 34(15): p. 5152-63.
  • Ramikie, T.S., R. Nyilas, R.J. Bluett, J.C. Gamble-George, N.D. Hartley, K. Mackie, M. Watanabe, I. Katona, and S. Patel, Multiple mechanistically distinct modes of endocannabinoid mobilization at central amygdala glutamatergic synapses. Neuron, 2014. 81(5): p. 1111-25.
  • O'Donnell, B.F. and K. Mackie, The mismatch negativity: a translational probe of auditory processing in cannabis users. Biol Psychiatry, 2014. 75(6): p. 428-9.
  • Petrov, R.R., L. Knight, S.R. Chen, J. Wager-Miller, S.W. McDaniel, F. Diaz, F. Barth, H.L. Pan, K. Mackie, C.N. Cavasotto, and P. Diaz, Mastering tricyclic ring systems for desirable functional cannabinoid activity. Eur J Med Chem, 2013. 69: p. 881-907.
  • Chen, D.H., A. Naydenov, J.L. Blankman, H.C. Mefford, M. Davis, Y. Sul, A.S. Barloon, E. Bonkowski, J. Wolff, M. Matsushita, C. Smith, B.F. Cravatt, K. Mackie, W.H. Raskind, N. Stella, and T.D. Bird, Two novel mutations in ABHD12: expansion of the mutation spectrum in PHARC and assessment of their functional effects. Hum Mutat, 2013. 34(12): p. 1672-8.
  • Jain, T., J. Wager-Miller, K. Mackie, and A. Straiker, Diacylglycerol lipasealpha (DAGLalpha) and DAGLbeta cooperatively regulate the production of 2-arachidonoyl glycerol in autaptic hippocampal neurons. Mol Pharmacol, 2013. 84(2): p. 296-302.
  • Cristino, L., G. Busetto, R. Imperatore, I. Ferrandino, L. Palomba, C. Silvestri, S. Petrosino, P. Orlando, M. Bentivoglio, K. Mackie, and V. Di Marzo, Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. Proc Natl Acad Sci U S A, 2013. 110(24): p. E2229-38.
  • Straiker, A., K.T. Min, and K. Mackie, Fmr1 deletion enhances and ultimately desensitizes CB(1) signaling in autaptic hippocampal neurons. Neurobiol Dis, 2013. 56: p. 1-5.
  • Shonesy, B.C., X. Wang, K.L. Rose, T.S. Ramikie, V.S. Cavener, T. Rentz, A.J. Baucum, 2nd, N. Jalan-Sakrikar, K. Mackie, D.G. Winder, S. Patel, and R.J. Colbran, CaMKII regulates diacylglycerol lipase-alpha and striatal endocannabinoid signaling. Nat Neurosci, 2013. 16(4): p. 456-63.
  • Keimpema, E., G. Tortoriello, A. Alpar, S. Capsoni, I. Arisi, D. Calvigioni, S.S. Hu, A. Cattaneo, P. Doherty, K. Mackie, and T. Harkany, Nerve growth factor scales endocannabinoid signaling by regulating monoacylglycerol lipase turnover in developing cholinergic neurons. Proc Natl Acad Sci U S A, 2013. 110(5): p. 1935-40.
  • Atwood, B.K., A. Straiker, and K. Mackie, CB(2) cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons. Neuropharmacology, 2012. 63(4): p. 514-23.
  • Atwood, B.K., A. Straiker, and K. Mackie, CB(2): therapeutic target-in-waiting. Prog Neuropsychopharmacol Biol Psychiatry, 2012. 38(1): p. 16-20.
  • Atwood, B.K., J. Wager-Miller, C. Haskins, A. Straiker, and K. Mackie, Functional selectivity in CB(2) cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB(2) ligands. Mol Pharmacol, 2012. 81(2): p. 250-63.
  • Straiker, A., J. Wager-Miller, J. Hutchens, and K. Mackie, Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones. Br J Pharmacol, 2012. 165(8): p. 2660-71.
  • Straiker, A., J. Wager-Miller, and K. Mackie, The CB1 cannabinoid receptor C-terminus regulates receptor desensitization in autaptic hippocampal neurones. Br J Pharmacol, 2012. 165(8): p. 2652-9.
  • Ho, Y.C., H.J. Lee, L.W. Tung, Y.Y. Liao, S.Y. Fu, S.F. Teng, H.T. Liao, K. Mackie, and L.C. Chiou, Activation of orexin 1 receptors in the periaqueductal gray of male rats leads to antinociception via retrograde endocannabinoid (2-arachidonoylglycerol)-induced disinhibition. J Neurosci, 2011. 31(41): p. 14600-10.
  • Straiker, A., J. Wager-Miller, S.S. Hu, J.L. Blankman, B.F. Cravatt, and K. Mackie, COX-2 and fatty acid amide hydrolase can regulate the time course of depolarization-induced suppression of excitation. Br J Pharmacol, 2011. 164(6): p. 1672-83.
  • Atwood, B.K., D. Lee, A. Straiker, T.S. Widlanski, and K. Mackie, CP47,497-C8 and JWH073, commonly found in 'Spice' herbal blends, are potent and efficacious CB(1) cannabinoid receptor agonists. Eur J Pharmacol, 2011. 659(2-3): p. 139-45.
  • Wu, C.S., J. Zhu, J. Wager-Miller, S. Wang, D. O'Leary, K. Monory, B. Lutz, K. Mackie, and H.C. Lu, Requirement of cannabinoid CB(1) receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections. Eur J Neurosci, 2010. 32(5): p. 693-706.