Dr John C. Ashton

Dr JC Ashton Interests: cannabinoid drugs, neurodegeneration, neuroinflammation, hyperalgesia and pain, interactions of cannabinoids with selective serotonin reuptake inhibitors, cannabinoid CB2 receptors as drug targets, endocannabinoid signalling

Pharmacology is a single discipline that allows me to pursue a number of my professional interests: basic exploratory science, applied biomedical science, and commercial development. Rather than make the choice of being a “pure” scientist versus an applied scientist, or being entirely based in academia or in the business world, pharmacology allows me to do all of these things and more. Pharmacology requires study of physiology, chemistry and biochemistry, molecular biology, anatomy, cell biology, and a range of technologies. More than that, it allows me to follow my passion for basic exploratory research into how living organisms work, and at the same time work towards the development of new drugs that could help solve real human problems and have a clinical and social impact. Even more, the drug development process requires engagement with bioethics, clinical trial design, statistical analysis, intellectual property law, as well as interacting with the business world (the so-called “real world”).

The particular focus of my lab is the endocannabinoid system. Discovered less than two decades ago, this is a system of receptors, messengers, and enzymes that regulates a number of physiological processes. Cannabinoid drugs act on this system with a variety of effects, some of therapeutic benefit, and some potentially harmful. Our lab seeks to better understand the endocannabinoid system to tease out the beneficial effects of new cannabinoid drugs from their side effects. In particular, we are focusing on the “CB2” receptor, which we and other research groups have recently found to be involved in a number of pathological processes in the central nervous system. We are focusing upon two major medical problems that cause enormous social costs and carry a huge burden of individual suffering: ischemic brain damage (stroke) and chronic, neuropathic pain. Along with our collaborating labs in Auckland and the USA, we have found exciting preliminary data that shows that drugs that can activate the CB2 receptor can reduce brain damage due to brain ischemia and relieve chronic pain from nerve injuries. In 2008, the Marsden Fund of New Zealand recognised the potential of this research, and awarded us a 3 year grant to fully investigate these promising new drugs.

Selected Publications

Rivers, J.R., Ashton, J.C. The development of cannabinoid CBII receptor agonists for the treatment of central neuropathies. Central Nervous System Agents in Medicinal Chemistry (In Press)

Graham, E.S., Ashton, J.C., Glass, M. Cannabinoid Receptors: A brief history and “what’s hot”. In, G Protein-Coupled receptors: Frontiers in Bioscience. Editor: Pfleger. K. (In Press).

Ashton, J.C. (2008). Pro-drugs for indirect cannabinoids as therapeutic agents. Current Drug Delivery 5(4): 243-247

Ashton, J.C., Wright, J.L., McPartland, J.M., Tyndall, J. (2008). Cannabinoid CB1 and CB2 receptor ligand specificity and the development of CB2-selective agonists. Current Medicinal Chemistry 15(14):1428-43

Ashton, J.C., Glass, M. (2008).Multiple roles in neuroprotection during oxidative stress injury. In, Brain Hypoxia-Ischemia Research Progress, pp. 229-44. Editor: Roux, M.O., Nova Science Publications, Inc

Ashton, J.C., Milligan, E.D. (2008). Cannabinoids for the treatment of neuropathic pain; Clinical evidence. Curr Opin Investig Drugs 9(1):65-75

Ashton, J.C., Smith, P.F., Darlington, C.D. (2008). The effect of delta-9-THC on extinction of an adverse memory. Pharmacology 81:18-20

Ashton, J.C., Smith, P.F. (2007). Cannabinoids and cardiovascular disease: the outlook for clinical treatments. Current Vascular Pharmacology 5(3):175-84

Ashton, J.C. (2007). Cannabinoids for the treatment of inflammation. Current Opinion in Investigational Drugs 8(5):373-84

Ashton, J.C., Glass, M. (2007). The cannabinoid CB2 receptor as a target for inflammatory neurodegenerative disease. Current Neuropharmacology. 5:73-80

Ashton, J.C., Smith, P.F. (2007). Bcl-2 and Mitochondrial control of apoptosis as a mechanism for regulating neural plasticity. In, Cell Apoptosis: Regulation and Environmental Factors, pp 1-25. Editor: Shultz, L.B., Nova Science Publishers, Inc

Ashton, J.C. Oxidative stress induces the upregulation of the CB2 receptor in a population of cells in the dentate gyrus subgranular layer. (2007). Recent Research Developments in Neurosciences. Editor: S.G. Pandalai, Research Signpost Publications

Ashton, J.C., Rahman, R., Nair, S., Sutherland, B., Glass, M., Appleton, I. (2007) Cerebral hypoxia-ischemia and middle cerebral artery occlusion induce expression of the cannabinoid CB2 receptor in the brain. Neuroscience Letters 412(2):114-7

Ashton J.C., Darlington C.L., Smith P.F. (2006) Co-distribution of the cannabinoid CB1 receptor and the 5-HT transporter in the rat amygdale. European Journal of Pharmacology 537(1-3):70-1

Smith P.F., Ashton J.C., Darlington C.L. (2006) The endocannabinoid system: a new player in the neurochemical control of vestibular function? Audiology & Neurotology 11(4):207-12

Ashton, J.C., Friberg, D, Darlington, C.D., Smith, P.F. (2006). Expression of the Cannabinoid CB2 Receptor in the Rat Cerebellum: an Immunohistochemical Study. Neuroscience Letters 396(2):113-6

Ashton J.C., Little E., Muir M., Smith P.F., Darlington C.D. (2005) Mitochondrial Ultrastructure and Apoptotic Protein Expression in the Vestibular Nucleus Complex following Unilateral Labyrinthectomy. Brain Research 1055(1-2):165-70

Zhang R., Ashton J.C., Horii A., Darlington CL., Smith P.F. (2005). Immunocytochemical and stereological analysis of GABAB receptor subunit expression in the rat vestibular nucleus following unilateral vestibular deafferentation. Brain Research 1037(1-2): 107-13

Ashton J.C., Khalessi A., Kapoor M., Clarkson A., Sammut, I.A., Darlington C.L., Smith P.F. (2004). Characterisation of Mitochondrial Respiratory Chain Energetics in the Vestibular Nucleus Complex. Acta Otolaryngologica 125: 1-4

Ashton J.C., Appleton I.A., Darlington C.L., Smith P.F. (2004) Immunohistochemical Localisation of Cerebrovascular CB1 Receptor Protein. Journal of Cardiovascular Pharmacology 44(5):517-9

Ashton J.C., Zheng Y., Liu P., Darlington C.L., Smith P.F. (2004) Immunohistochemical Characterisation and Localisation of Cannabinoid CB1 Receptor Protein in the Vestibular Nucleus Complex and the Effect of Unilateral Vestibular Deafferentation. Brain Research 1021(2):264-71

Ashton, J.C., Appleton, I, Darlington, C.L., Smith, P.F. (2004). Immunohistochemical localization of CB1 receptor protein in cerebellum inhibitory interneurons. The Cerebellum 3: 1-5

Ashton, J.C., I. Appleton, Darlington, C.L., Smith, P.F. (2004) Cannabinoid CB1 receptor protein expression in the rat choroid plexus: a possible involvement of cannabinoids in the regulation of cerebrospinal fluid. Neuroscience Letters 364, 40-42

Ashton, J.C., Gliddon, C.G., Darlington, C.L., P.F. Smith. (2003). Effect of Low Body Temperature During Unilateral Labyrinthectomy on Vestibular Compensation in the Guinea Pig. Acta Otolaryngologica 123, 448–452

Recent Conference Abstracts

Wilkerson, J.L., Dengler, E.C., Wallace, J.A., Zvonok, A.M., Thakur, G.A., Makriyannis, A., Ashton, J.C., Milligan, E.D. Administration of AM 1241, a Cannabinoid 2 (CB2) Receptor Selective Agonist, to the Spinal Cord Reverses Chronic Constriction Injury (CCI) Induced Allodynia. American Pain Society, San Diego, 2009 (abstract submitted)

Ashton, J.C., Wright, J.L., McPartland, J.M., J Gertsch, J., Tyndall, JDA. Development of drugs targeting the cannabinoid CB2 receptor for therapeutic use. ASCEPTNZ, Queenstown, 2008

Rivers, J.R., Sutherland B.A., Brownjohn, P.W., Glass, M., Ashton, J.C. Preliminary investigations into the specificity of antibody probes raised agains the cannabinoid CBII receptor. ASCEPTNZ, Queenstown, 2008

Brownjohn, P.W., Rivers, J.R., Wilkinson, J., Milligan, E.D., Ashton, J.C. Mechanisms of GW405833 induced amelioration of hyperalgesia in 2 models of neuropathic pain. ASCEPTNZ, Queenstown, 2008

Goddard, M., Smith, P.F., Ashton, J.C. Interaction between 5-HT pathways and the endocannabinoid system in the regulation of anxiety. Proceedings of the 26th International Australasian Winter Conference on Brain Research, 2008

Ashton, J.C., Erin, Milligan et al. Effect of a selective cannabinoid CB2 receptor agonist on hyperalgesia following chronic constriction injury and sciatic nerve injury in the rat. ASCEPTNZ, Auckland, 2007

Ashton, J.C., Milligan, E.D et al. A cannabinoid CB2 receptor agonist reverses hyperalgesia following chronic constriction injury in rats when delivered intrathecally. Society for Neuroscience, San Diego, 2007

Baek J., Hooton, K., Goddard, M., Lee, H., Ashton, J.C., Green, H., Zheng, Y., Smith, P.F., Darlington, C.L. A modified behavioural model of tinnitus for drug testing. International Brain Research Organisation conference, Melbourne, 2007

Ashton, J.C., Glass M., Rahman, R., Nair, S.M., Sutherland, B., Appleton, I. Cerebral hypoxia/ischaemia and medial carotid artery occlusion induce expression of the cannabinoid CB2 receptor in the brain. ASCEPT Annual NZ Scientific Meeting, Auckland. August 30-Sept. 2, 2006

Rahman, R.M.A., Nair, S.M., McKelvey, K., Ashton, J.C., Appleton I. Immune cells in a model of cerebral ischaemia. APSN Singapore 2006. J. Neurochem. 98, supplement 1, PS2C-10

Ashton J.C., Glass M., Sutherland B., Rahman R., Appleton I. Induction of cannabinoid CB2 receptor positive cells in the brain by stroke. APSN Singaapore 2006. J. Neurochem. 98, supplement 1, PS2C-09

Zheng, Y., Lee, H., Ashton, J.C., Smith, P.F., Darlington, C.L. A Modified Animal Model for detecting Tinnitus in rats 24th Meeting of the Báràny Society, Uppsala, June 11-14th, 2006