Alexandros Makriyannis

Dr. Alexandros Makriyannis (born September 9, 1939) is a professor of Chemistry and Chemical Biology in the Department of Medicinal Chemistry at Northeastern University in Boston, Massachusetts, where he directs the Center for Drug Discovery and holds the George Behrakis Chair of Pharmaceutical Biotechnology.[1] His research has focused on the biochemical basis of the endocannabinoid system and on the development of synthetic cannabinoids.

Scientific career[edit]

Makriyannis studied chemistry at the University of Cairo.[2] He then earned his Ph.D. in medicinal chemistry at the University of Kansas and went on to research synthetic organic chemistry at the University of California, Berkeley. He worked at Smith, Kline & French Laboratories and Tufts Medical School and then at the University of Connecticut, where he was later appointed Distinguished Professor of Medicinal Chemistry and Professor of Molecular and Cell Biology and Pharmacology.[3][4] He moved to Northeastern University in 2005.[4]

Makriyannis is director of the Center for Drug Discovery at Northeastern University, which he founded in 2005.[3] His work has identified the structure of cannabinoid receptors in the brain, helping to elucidate the psychoactive properties of some of these substances[5][6] and to point towards modifications in the receptors so as to retain the positive effects of cannabinoids while eliminating the negative ones.[7] These studies have informed the development by Makriyannis and his collaborators of synthetic compounds with a view to their use as cannabinergic probes or as medications in drug addiction[8] and in obesity and metabolic disorders. [4] A more recent research interest has been the study of drug interactions with protein targets in membranes.[4] His research has been reported in over 470 publications and his group has filed more than 40 patents.[3]

Subsequent novel inventions include:

2008       “Heteroaryl Urea Compunds as Endocannablnold enzyme Deactivators and a Method of Their Evaluation” – A. Makriyannis, L. Pandarinathan, N. Zvonok, T. Pakkari, L. Chapman

2011        “Method of Developing Cannablnoids with Controlled Duration of Action and Uses Thereof” – A. Makriyannis, G.A Thakur, R. Sharma

2011        “Cannabinergic Resorcinol Analogs” – A. Makriyannis, S. Bajaj, M.R D’Souza, S. Nikas, G. Thakur

2012        “Novel Cannabinerglc Nitrate Esters and Related Analogs” – A. Makriyannis, V.K. Vemuri

2014         Novel urea and carbamates FAAH MAGL or dual FAAH/MAGL inhibitors and their uses thereof” – A. Makriyannis, V.G. Shukla, S.O. Alapafuja

2014        “N·Acylethanolamlne Hydrolyzing Acid Amldase (NAAA) Inhibitors and Their Use Thereof” – A. Makriyannis, M. Malamas, K.V Subramanian, K. Whitten, N. Zvonok, J.M West, S. Pavlopoulos

2017        “Carbarnates ABHD6 and dueal ABHD6/MGL Inhibitors and their use thereof”- A. Makriyannis, M. Malamas, M. Lamani, S.I Farah

Biotechnology Startups[edit]

Makriyannis has founded two biotechnology startups in Burlington, MA dedicated to bringing new and innovative drugs to the market place for human diseases that can be modulated by the endocannabinoid system:

  • MAKScientific (2004)
  • PafosPharma (2014)


  • McNeil Endowment Fellowship (1964-67)
  • Research Scientist Award, NIDA (1990-95, 1995-2000)
  • Fellow, American Association for the Advancement of Science (1993)
  • President, International Cannabinoid Research Society (ICRS) (1993)      
  • Distinguished Scientist Award, University of Connecticut Alumni (1996)
  • Fellow, American Association of Pharmaceutical Sciences (1997)
  • National Institute of Health MERIT Awards (1997-2007, 2007-2017)
  • Senior Scientist NIDA Award (2000-2011)
  • Distinguished Professor, University of Connecticut, Board of Trustees (2002)
  • Research Achievement Award in Drug Design and Discovery, American Association of
  • Pharmaceutical Scientists (AAPS) (2002)
  • Behrakis Trustee Chair in Pharmaceutical Biotechnology, Northeastern University (2004)
  • Honorary Doctorate of Philosophy, University of Athens, Greece (2005)
  • Recognition of Scholarly or Creative Work by Northeastern Faculty and Staff, Northeastern University (2005)
  • Mechoulam Life Achievement Award in Cannabinoid Research (ICRS) (2006)
  • Distinguished Patent Award, University of Connecticut (2007)
  • Kenneth E. Avis Award in Medicinal Chemistry (2007)
  • Marquis Who’s Who in Science and Engineering (2007)
  • ACS Research Lifetime Achievement Award in Medicinal Chemistry (2012)
  • Annual NU Award for Excellence in Research and Creativity (2012)
  • ACS Medicinal Chemistry Hall of Fame (2013)
  • Highly Cited Researcher, Thomson Reuters (2014)
  • Distinguished Professor, Northeastern University (2015)
  • AAPS Distinguished Pharmaceutical Scientist Award (2015)
  • Honorary Doctorate of Philosophy, University of Crete Medical School, Greece (2018)
  • CPDD Nathan B. Eddy Memorial Award (2018)

Publications (since 2018)[edit]

  • Yu T., Ganapathy S., Shen L., Peng B., Kim S.H., A. Makriyannis, Chen C., (2018), A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells. Oncotarget, 9(5):6308-6319.  PMID: 29464074. PMCID: PMC5814214
  • M.A. Sticht, D.J. Lau, C.M. Keenan, J.B. Cavin, M. Morena, V.K. Vemuri, A. Makriyannis, B.F. Cravatt, K.A. Sharkey, M.N. Hill, (2018), Endocannabinoid Regulation of Homeostatic Feeding and Stress-Induced Alterations in Food Intake in Male Rats. British Journal of Pharmacology, PMID: 30051485
  • AV.Gaitán, JT. Wood, F. Zhang, A. Makriyannis, CJ. Lammi-Keefe, (2018), Endocannabinoid Metabolome Characterization of Transitional and Mature Human Milk. Nutrients, 10(9). pii: E1294. PMID: 30213124
  • Y. Liu, L. Ji, M. Eno, S. Kudalkar, A. Li, M. Schimpgen, O. Benchama, P. Morales, S. Xu, DP. Hurst, S. Wu, KA. Mohammad, JT. Wood, N. Zvonok, D. Papahatjis, H. Zhou, C. Honrao, K. Mackie, PH. Reggio, A. Hohmann ,LJ. Marnett, A. Makriyannis, SP. Nikas, (2018), (R)-N-(1-Methyl-2-hydroxyethyl)-13-(S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes. J Med Chem., PMID: 30196704
  • MS. Malamas, JG. Raghav, X. Ma, C. Honrao, JT. Wood,O.  Benchama, H. Zhou, S. Mallipeddi, A. Makriyannis, (2018), Oximes short-acting CB1 receptor agonists. Bioorg Med Chem., pii: S0968-0896(18)31107-6. PMID: 30122284
  • M. Salaga, A. Binienda, RB. Tichkule, GA.Thakur, A. Makriyannis, M. Storr, J. Fichna, (2018), The novel peripherally active cannabinoid type 1 and serotonin type 3 receptor agonist AM9405 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome. Eur J Pharmacol., 836:34-43. PMID: 30121173
  • MA. Sticht, DJ. Lau, CM. Keenan, JB. Cavin, M. Morena, VK. Vemuri, A. Makriyannis, BF. Cravatt, KA. Sharkey, MN. Hill, (2018), Endocannabinoid regulation of homeostatic feeding and stress-induced alterations in food intake in male rats. Br J Pharmacol., PMID: 30051485
  • XH. He, CJ. Jordan, K. Vemuri, GH. Bi, J. Zhan, EL. Gardner, A. Makriyannis, YL. Wang, ZX. Xi, (2018), Cannabinoid CB1 receptor neutral antagonist AM4113 inhibits heroin self-administration without depressive side effects in rats. Acta Pharmacol Sin., PMID: 29967454
  • S. Miller, S. Kulkarni, A. Ciesielski, SP. Nikas, K. Mackie, A. Makriyannis, A. Straiker, (2018), Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure. Pharmaceuticals (Basel)., 11(2). pii: E50. PMID: 29786643
  • BA. Kochert, RE. Iacob, TE. Wales, A. Makriyannis, JR. Engen, (2018), Hydrogen-Deuterium Exchange Mass Spectrometry to Study Protein Complexes. Methods Mol Biol., 1764:153-171. PMID: 29605914
  • T. Yu, S. Ganapathy, L. Shen, B. Peng, SH. Kim, A. Makriyannis, C. Chen, (2018), A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells. Oncotarget., 9(5):6308-6319. PMID: 29464074
  • S. Mallipeddi, N. Zvonok, A. Makriyannis, (2018), Expression, Purification and Characterization of the Human Cannabinoid 1 Receptor. Sci Rep., 8(1):2935. PMID: 29440756
  • S. Tyukhtenko, G. Rajarshi, I. Karageorgos, N. Zvonok, ES. Gallagher, H. Huang, K. Vemuri, JW. Hudgens, X. Ma, ML. Nasr, S. Pavlopoulos, A. Makriyannis, (2018), Effects of Distal Mutations on the Structure, Dynamics and Catalysis of Human Monoacylglycerol Lipase. Sci Rep., 8(1):1719. PMID: 29379013
  • CA. Paronis, GR. Chopda, K. Vemuri, AS. Zakarian, A. Makriyannis, J. Bergman, (2018), Long-Lasting In Vivo Effects of the Cannabinoid CB1 Antagonist AM6538. J Pharmacol Exp Ther., 364(3):485-493. PMID: 29311110
  • S. Pavlopoulos, DN. Pelekoudas, O. Benchama, CM. Rawlins, JN. Agar, JM. West, M. Malamas, N. Zvonok, A. Makriyannis, (2018), Secretion, isotopic labeling and deglycosylation of N-acylethanolamine acid amidase for biophysical studies. Protein Expr Purif., 145:108-117. PMID: 29253688
  • A. Balla, B. Dong, BM. Shilpa, K. Vemuri, A. Makriyannis, SC. Pandey, H. Sershen, RF.  Suckow, KY. Vinod, (2018), Cannabinoid-1 receptor neutral antagonist reduces binge-like alcohol consumption and alcohol-induced accumbal dopaminergic signaling. Neuropharmacology., 131:200-208. PMID: 29109060
  • D. Szymanski, M. Papanastasiou, L. Pandarinathan, N. Zvonok, D.R. Janero, S. Pavlopoulos, P. Vouros, A. Makriyannis, (2018), Aliphatic Azides as Selective Cysteine Labeling Reagents for Integral Membrane Proteins. J Med Chem. PMID: 30444608
  • C. Sagheddu, M. Scherma, M. Congiu, P. Fadda, G. Carta, S. Banni, J.T. Wood, A. Makriyannis, M.S. Malamas, M. Pistis, (2018), Inhibition of N-acylethanolamine acid amidase reduces nicotine-induced dopamine activation and reward. Neuropharmacology. PMID: 30439418
  • S.O. Alapafuja, M.S. Malamas, V. Shukla, A Zvonok, S. Miller, L. Daily, G. Rajarshi, C.Y. Miyabe, H. Chandrashekhar, J. Wood, S. Tyukhtenko, A. Straiker, A, Makriyannis, (2018), Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment. Bioorg Med Chem. PMID: 30446439
  • R.A. Slivicki, S.A. Saberi, V. Iyer, K. Vemuri, A. Makriyannis, A.G. Hohmann, (2018), Brain permeant and impermeant inhibitors of fatty-acid amide hydrolase synergize with the opioid analgesic morphine to suppress chemotherapy-induced neuropathic nociception without enhancing effects of morphine on gastrointestinal transit. J Pharmacol
  • Sticht M.A., D.J. Lau, C.M. Keenan, J.B. Cavin, M. Morena, V.K. Vemuri, A. Makriyannis, B.F. Cravatt, K.A. Sharkey, M.N. Hill, (2018), Endocannabinoid Regulation of Homeostatic Feeding and Stress-Induced Alterations in Food Intake in Male Rats.  British Journal of Pharmacology, PMID: 30051485
  • Szymanski D., M. Papanastasiou, L. Pandarinathan, N. Zvonok, D.R. Janero, S. Pavlopoulos, P. Vouros, A. Makriyannis, (2018), Aliphatic azides as selective cysteine labeling reagents for integral membrane proteins.  J. Med. Chem. PMID: 30444608
  • Tyukhtenko S, G. Rajarshi, I. Karageorgos, N. Zvonok, E.S. Gallagher, H. Huang, K. Vemuri, J.W. Hudgens, X. Ma, M.L. Nasr, S. Pavlopoulos, A. Makriyannis, (2018), Effects of Distal Mutations on the Structure, Dynamics and Catalysis of Human Monoacylglycerol Lipase.  Sci Rep., 8(1):1719.  PMID: 29379013  PMCID: PMC5789057
  • Yu T., S. Ganapathy, L. Shen, B. Peng, S.H. Kim, A. Makriyannis, C. Chen, (2018), A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells. Oncotarget, 9(5):6308-6319. PMID: 29464074  PMCID: PMC5814214
  • D’Souza D.C., J. Cortes-Briones, G. Creature, G. Bluez, H. Thurnauer, E. Deaso, K. Bielen, T. Surti, R. Radhakrishnan, A. Gupta, S. Gupta, J. Cahill, M.A. Sherif, A. Makriyannis, P.T. Morgan, M. Ranganathan, P.D. Skosnik, (2019). Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomized controlled trial.  Lancet Psychiatry, 6(1), 35-45.  PMID: 30528676
  • Li A.L, X. Lin, A.S. Dhopeshwarkar, A.C. Thomaz, L.M. Carey, Y. Liu, S.P. Nikas, A. Makriyannis, K. Mackie, A.G. Hohmann, (2019). Cannabinoid CB2 agonist AM1710 differentially suppresses distant pathological pain states and attenuates morphine tolerance and withdrawal.  Mol. Pharmacol., 95(2). 155-168.  PMID: 30504240  PMCID: PMC6324648
  • Li X., T. Hua, K. Vemuri, J.H. Ho, Y. Wu, L. Wu, P. Popov, O. Benchama, N. Zvonok, K. Locke, L. Qu, G.W. Han, M.R. Iyer, R. Cinar, N.J. Coffey, J. Wang, M. Wu, V. Katritch, S. Zhao, G. Kunos, L.M. Bohn, A. Makriyannis, R.C. Stevens, Z.J. Liu, (2019), Crystal structure of the human cannabinoid receptor CB2.  Cell, 176(3), 459-467.  PMID: 30639103
  • Shields C.M., V. Zvonok, A. Zvonok, A. Makriyannis, (2019), Biochemical and proteomic characterization of recombinant human α/β hydrolase domain 6.  Sci Rep, 9(1), 890.  PMID: 30696836  PMCID: PMC6351631
  • For a complete list of publications, visit PubMed

See also[edit]


  1. ^ "Alexandros Makriyannis". Northeastern University College of Science. Retrieved 2 December 2018.
  2. ^ "Pioneer in Chemical Biology". Ellines. Retrieved 3 January 2019.
  3. ^ a b c "Alexandros Makriyannis". Advancing Drug Development Forum. 2018-08-06. Retrieved 2 December 2018.
  4. ^ a b c d "Alexandros Makriyannis, Ph.D." American Chemical Society, Division of Medicinal Chemistry. Retrieved 2 December 2018.
  5. ^ "Cannabinoid receptor structure revealed". National Institutes of Health (NIH). November 1, 2016.
  6. ^ Singer, Thea (October 20, 2016). "Structure of the brain's 'marijuana receptor' revealed". News@Northeastern. Northeastern University.
  7. ^ Perrier, Jean (October 19, 2017). "Peut-on fumer de l'herbe sans être stone ?" [Could we smoke weed without getting stoned?]. GQ France (in French).
  8. ^ Davi, Christine Regan (August 3, 2018). "Can the opioid crisis be fixed?". News@Northeastern. Northeastern University.

Further reading[edit]