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Pharmacology of Medical Cannabis

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Book cover Recent Advances in Cannabinoid Physiology and Pathology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1162))

Abstract

The Cannabis plant has been used for many of years as a medicinal agent in the relief of pain and seizures. It contains approximately 540 natural compounds including more than 100 that have been identified as phytocannabinoids due to their shared chemical structure. The predominant psychotropic component is Δ9-tetrahydrocannabinol (Δ9-THC), while the major non-psychoactive ingredient is cannabidiol (CBD). These compounds have been shown to be partial agonists or antagonists at the prototypical cannabinoid receptors, CB1 and CB2. The therapeutic actions of Δ9-THC and CBD include an ability to act as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds and as protective agents in neurodegeneration. However, there is a lack of well-controlled, double blind, randomized clinical trials to provide clarity on the efficacy of either Δ9-THC or CBD as therapeutics. Moreover, the safety concerns regarding the unwanted side effects of Δ9-THC as a psychoactive agent preclude its widespread use in the clinic. The legalization of cannabis for medicinal purposes and for recreational use in some regions will allow for much needed research on the pharmacokinetics and pharmocology of medical cannabis. This brief review focuses on the use of cannabis as a medicinal agent in the treatment of pain, epilepsy and neurodegenerative diseases. Despite the paucity of information, attention is paid to the mechanisms by which medical cannabis may act to relieve pain and seizures.

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Abbreviations

Δ9-THC:

tetrahydrocannabinol

2-AG:

2-arachiodonoylglycerol

AEA:

anandamide

AD:

Alzheimer’s disease

cAMP:

cyclic adenosine monophosphate

CB1:

cannabinoid receptor 1

CB2:

cannabinoid receptor 2

CB3:

cannabinoid receptor 3

CBD:

cannabidiol

CBN:

cannabinol

CNS:

central nervous system

CHO:

Chinese hamster ovary

DRG:

dorsal root ganglion

EAE:

experimental autoimmune encephalomyelitis

GABA:

gamma-aminobutyric acid, or γ-aminobutyric acid

GPCR55:

G protein-coupled receptor 55

IP3:

Inositol trisphosphate

KA:

kainic acid

LPI:

L-α-lysophosphatidylinositol

MS:

multiple sclerosis

SCBs:

synthetic cannabinoids

TRPA1:

transient receptor potential cation channel, subfamily A, member 1

TRPV1:

transient receptor potential cation channel, subfamily V, member 1

TRPV2:

transient receptor potential cation channel, subfamily V, member 2

References

  1. Friedman D, Sirven JI (2017) Historical perspective on the medical use of cannabis for epilepsy: ancient times to the 1980s. Epilepsy Behav 70(Pt B):298–301

    Article  PubMed  Google Scholar 

  2. Russo EB (2017) Cannabis and epilepsy: an ancient treatment returns to the fore. Epilepsy Behav 70(Pt B):292–297

    Article  PubMed  Google Scholar 

  3. Aggarwal SK, Carter GT, Sullivan MD, ZumBrunnen C, Morrill R, Mayer JD (2009) Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions. J Opioid Manag 5(3):153–168

    Article  PubMed  Google Scholar 

  4. Epstein HA (2010) A natural approach to soothing atopic skin. Skinmed 8(2):95–97

    PubMed  Google Scholar 

  5. Stevens CJ, Murphy C, Roberts R, Lucas L, Silva F, Fuller DQ (2016) Between China and South Asia: a middle Asian corridor of crop dispersal and agricultural innovation in the Bronze Age. The Holocene 26(10):1541–1555

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jiang HE, Li X, Zhao YX, Ferguson DK, Hueber F, Bera S et al (2006) A new insight into Cannabis sativa (Cannabaceae) utilization from 2500-year-old Yanghai Tombs, Xinjiang, China. J Ethnopharmacol 108(3):414–422

    Article  PubMed  Google Scholar 

  7. Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M et al (2018) Cannabis sativa: a comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol 227:300–315

    Article  CAS  PubMed  Google Scholar 

  8. Hanus LO, Meyer SM, Munoz E, Taglialatela-Scafati O, Appendino G (2016) Phytocannabinoids: a unified critical inventory. Nat Prod Rep 33(12):1357–1392

    Article  CAS  PubMed  Google Scholar 

  9. Hill AJ, Williams CM, Whalley BJ, Stephens GJ (2012) Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 133(1):79–97

    Article  CAS  PubMed  Google Scholar 

  10. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346(6284):561–564

    Article  CAS  PubMed  Google Scholar 

  11. Gerard C, Mollereau C, Vassart G, Parmentier M (1990) Nucleotide sequence of a human cannabinoid receptor cDNA. Nucleic Acids Res 18(23):7142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365(6441):61–65

    Article  CAS  PubMed  Google Scholar 

  13. Gerard CM, Mollereau C, Vassart G, Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279. (Pt 1:129–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA et al (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54(2):161–202

    Article  CAS  PubMed  Google Scholar 

  15. Jordan CJ, Xi ZX (2019) Progress in brain cannabinoid CB2 receptor research: from genes to behavior. Neurosci Biobehav Rev 98:208–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR et al (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A 87(5):1932–1936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 153(2):199–215

    Article  CAS  PubMed  Google Scholar 

  18. Howlett AC, Mukhopadhyay S (2000) Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chem Phys Lipids 108(1–2):53–70

    Article  CAS  PubMed  Google Scholar 

  19. Childers SR, Sexton T, Roy MB (1994) Effects of anandamide on cannabinoid receptors in rat brain membranes. Biochem Pharmacol 47(4):711–715

    Article  CAS  PubMed  Google Scholar 

  20. Gonsiorek W, Lunn C, Fan X, Narula S, Lundell D, Hipkin RW (2000) Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol Pharmacol 57(5):1045–1050

    CAS  PubMed  Google Scholar 

  21. Rhee MH, Vogel Z, Barg J, Bayewitch M, Levy R, Hanus L et al (1997) Cannabinol derivatives: binding to cannabinoid receptors and inhibition of adenylylcyclase. J Med Chem 40(20):3228–3233

    Article  CAS  PubMed  Google Scholar 

  22. Rhee MH, Bayewitch M, Avidor-Reiss T, Levy R, Vogel Z (1998) Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J Neurochem 71(4):1525–1534

    Article  CAS  PubMed  Google Scholar 

  23. Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y et al (2016) Crystal structure of the human cannabinoid receptor CB1. Cell 167(3):750–62 e14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J et al (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152(7):1092–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A 105(7):2699–2704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sylantyev S, Jensen TP, Ross RA, Rusakov DA (2013) Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci U S A 110(13):5193–5198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V et al (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400(6743):452–457

    Article  CAS  PubMed  Google Scholar 

  28. Zheng J (2013) Molecular mechanism of TRP channels. Compr Physiol 3(1):221–242

    PubMed  PubMed Central  Google Scholar 

  29. Akopian AN, Ruparel NB, Patwardhan A, Hargreaves KM (2008) Cannabinoids desensitize capsaicin and mustard oil responses in sensory neurons via TRPA1 activation. J Neurosci 28(5):1064–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim D, Cavanaugh EJ, Simkin D (2008) Inhibition of transient receptor potential A1 channel by phosphatidylinositol-4,5-bisphosphate. Am J Physiol Cell Physiol 295(1):C92–C99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM (2008) TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 28(24):6231–6238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cristino L, de Petrocellis L, Pryce G, Baker D, Guglielmotti V, Di Marzo V (2006) Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain. Neuroscience 139(4):1405–1415

    Article  CAS  PubMed  Google Scholar 

  33. Ahluwalia J, Urban L, Capogna M, Bevan S, Nagy I (2000) Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons. Neuroscience 100(4):685–688

    Article  CAS  PubMed  Google Scholar 

  34. Caterina MJ, Julius D (1999) Sense and specificity: a molecular identity for nociceptors. Curr Opin Neurobiol 9(5):525–530

    Article  CAS  PubMed  Google Scholar 

  35. Kowase T, Nakazato Y, Yoko OH, Morikawa A, Kojima I (2002) Immunohistochemical localization of growth factor-regulated channel (GRC) in human tissues. Endocr J 49(3):349–355

    Article  CAS  PubMed  Google Scholar 

  36. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR et al (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112(6):819–829

    Article  CAS  PubMed  Google Scholar 

  37. Diogenes A, Akopian AN, Hargreaves KM (2007) NGF up-regulates TRPA1: implications for orofacial pain. J Dent Res 86(6):550–555

    Article  CAS  PubMed  Google Scholar 

  38. Diogenes MJ, Assaife-Lopes N, Pinto-Duarte A, Ribeiro JA, Sebastiao AM (2007) Influence of age on BDNF modulation of hippocampal synaptic transmission: interplay with adenosine A2A receptors. Hippocampus 17(7):577–585

    Article  CAS  PubMed  Google Scholar 

  39. Nahas GG, Frick HC, Lattimer JK, Latour C, Harvey D (2002) Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa. Hum Psychopharmacol 17(2):103–113

    Article  CAS  PubMed  Google Scholar 

  40. Perez-Reyes M (1990) Marijuana smoking: factors that influence the bioavailability of tetrahydrocannabinol. NIDA Res Monogr 99:42–62

    CAS  PubMed  Google Scholar 

  41. Huestis MA (2007) Human cannabinoid pharmacokinetics. Chem Biodivers 4(8):1770–1804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. McGilveray IJ (2005) Pharmacokinetics of cannabinoids. Pain Res Manag 10(Suppl A):15A–22A

    Article  PubMed  Google Scholar 

  43. Huestis MA, Mitchell JM, Cone EJ (1996) Urinary excretion profiles of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol in humans after single smoked doses of marijuana. J Anal Toxicol 20(6):441–452

    Article  CAS  PubMed  Google Scholar 

  44. Huestis MA, Henningfield JE, Cone EJ (1992) Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol 16(5):276–282

    Article  CAS  PubMed  Google Scholar 

  45. Huestis MA, Sampson AH, Holicky BJ, Henningfield JE, Cone EJ (1992) Characterization of the absorption phase of marijuana smoking. Clin Pharmacol Ther 52(1):31–41

    Article  CAS  PubMed  Google Scholar 

  46. Perez-Reyes M, Timmons MC, Lipton MA, Davis KH, Wall ME (1972) Intravenous injection in man of 9 -tetrahydrocannabinol and 11-OH- 9 -tetrahydrocannabinol. Science 177(4049):633–635

    Article  CAS  PubMed  Google Scholar 

  47. Alles SRA, Smith PA (2018) Etiology and pharmacology of neuropathic pain. Pharmacol Rev 70(2):315–347

    Article  CAS  PubMed  Google Scholar 

  48. Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S et al (2007) Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 68(7):515–521

    Article  CAS  PubMed  Google Scholar 

  49. Ellis RJ, Toperoff W, Vaida F, van den Brande G, Gonzales J, Gouaux B et al (2009) Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 34(3):672–680

    Article  CAS  PubMed  Google Scholar 

  50. Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B et al (2008) A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain 9(6):506–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Borgelt LM, Franson KL, Nussbaum AM, Wang GS (2013) The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 33(2):195–209

    Article  CAS  PubMed  Google Scholar 

  52. Rog DJ, Nurmikko TJ, Young CA (2007) Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther 29(9):2068–2079

    Article  CAS  PubMed  Google Scholar 

  53. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D (2007) Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain 133(1–3):210–220

    Article  CAS  PubMed  Google Scholar 

  54. Hauser W, Fitzcharles MA, Radbruch L, Petzke F (2017) Cannabinoids in pain management and palliative medicine. Deutsches Arzteblatt Int 114(38):627–634

    Google Scholar 

  55. Fitzcharles MA, Baerwald C, Ablin J, Hauser W (2016) Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): a systematic review of randomized controlled trials. Schmerz 30(1):47–61

    Article  PubMed  Google Scholar 

  56. Fitzcharles MA, Ste-Marie PA, Hauser W, Clauw DJ, Jamal S, Karsh J et al (2016) Efficacy, tolerability, and safety of cannabinoid treatments in the rheumatic diseases: a systematic review of randomized controlled trials. Arthritis Care Res (Hoboken) 68(5):681–688

    Article  CAS  Google Scholar 

  57. Volz MS, Siegmund B, Hauser W (2016) Efficacy, tolerability, and safety of cannabinoids in gastroenterology: a systematic review. Schmerz 30(1):37–46

    Article  CAS  PubMed  Google Scholar 

  58. de Vries M, van Rijckevorsel DCM, Vissers KCP, Wilder-Smith OHG, van Goor H (2017) Tetrahydrocannabinol does not reduce pain in patients with chronic abdominal pain in a phase 2 placebo-controlled study. Clin Gastroenterol Hepatol 15(7):1079–1086. e4

    Article  PubMed  CAS  Google Scholar 

  59. Brents LK, Zimmerman SM, Saffell AR, Prather PL, Fantegrossi WE (2013) Differential drug-drug interactions of the synthetic cannabinoids JWH-018 and JWH-073: implications for drug abuse liability and pain therapy. J Pharmacol Exp Ther 346(3):350–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R (2009) Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 30(10):515–527

    Article  CAS  PubMed  Google Scholar 

  61. Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ et al (2007) Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat Neurosci 10(7):870–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Patwardhan AM, Jeske NA, Price TJ, Gamper N, Akopian AN, Hargreaves KM (2006) The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci U S A 103(30):11393–11398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Philpott HT, O’Brien M, McDougall JJ (2017) Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain 158(12):2442–2451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Barrese V, Miceli F, Soldovieri MV, Ambrosino P, Iannotti FA, Cilio MR et al (2010) Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine. Clin Pharmacol 2:225–236

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Korczyn AD, Schachter SC, Amlerova J, Bialer M, van Emde Boas W, Brazdil M et al (2015) Third international congress on epilepsy, brain and mind: Part 1. Epilepsy Behav 50:116–137

    Article  PubMed  PubMed Central  Google Scholar 

  66. Rektor I, Schachter SC, Arya R, Arzy S, Braakman H, Brodie MJ et al (2015) Third international congress on epilepsy, brain, and mind: part 2. Epilepsy Behav 50:138–159

    Article  PubMed  Google Scholar 

  67. Hesdorffer DC, Beck V, Begley CE, Bishop ML, Cushner-Weinstein S, Holmes GL et al (2013) Research implications of the institute of medicine report, epilepsy across the Spectrum: promoting health and understanding. Epilepsia 54(2):207–216

    Article  PubMed  PubMed Central  Google Scholar 

  68. Tang F, Hartz AMS, Bauer B (2017) Drug-resistant epilepsy: multiple hypotheses, few answers. Front Neurol 8:301

    Article  PubMed  PubMed Central  Google Scholar 

  69. Hill AJ, Mercier MS, Hill TD, Glyn SE, Jones NA, Yamasaki Y et al (2012) Cannabidivarin is anticonvulsant in mouse and rat. Br J Pharmacol 167(8):1629–1642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hill TD, Cascio MG, Romano B, Duncan M, Pertwee RG, Williams CM et al (2013) Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Br J Pharmacol 170(3):679–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jones NA, Glyn SE, Akiyama S, Hill TD, Hill AJ, Weston SE et al (2012) Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure 21(5):344–352

    Article  PubMed  Google Scholar 

  72. Wallace MJ, Wiley JL, Martin BR, DeLorenzo RJ (2001) Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. Eur J Pharmacol 428(1):51–57

    Article  CAS  PubMed  Google Scholar 

  73. Wallace MJ, Martin BR, DeLorenzo RJ (2002) Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol 452(3):295–301

    Article  CAS  PubMed  Google Scholar 

  74. Luszczki JJ, Andres-Mach M, Barcicka-Klosowska B, Florek-Luszczki M, Haratym-Maj A, Czuczwar SJ (2011) Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice. Prog Neuro-Psychopharmacol Biol Psychiatry 35(8):1870–1876

    Article  CAS  Google Scholar 

  75. Luszczki JJ, Misiuta-Krzesinska M, Florek M, Tutka P, Czuczwar SJ (2011) Synthetic cannabinoid WIN 55,212-2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock-induced seizures in mice. Pharmacol Biochem Behav 98(2):261–267

    Article  CAS  PubMed  Google Scholar 

  76. Mechoulam R (1970) Marihuana chemistry. Science 168(3936):1159–1166

    Article  CAS  PubMed  Google Scholar 

  77. Cunha JM, Carlini EA, Pereira AE, Ramos OL, Pimentel C, Gagliardi R et al (1980) Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21(3):175–185

    Article  CAS  PubMed  Google Scholar 

  78. Hausman-Kedem M, Menascu S, Kramer U (2018) Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents – an observational, longitudinal study. Brain Dev 40(7):544–551

    Article  PubMed  Google Scholar 

  79. Alger BE (2002) Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog Neurobiol 68(4):247–286

    Article  CAS  PubMed  Google Scholar 

  80. Chevaleyre V, Takahashi KA, Castillo PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29:37–76

    Article  CAS  PubMed  Google Scholar 

  81. Marsicano G, Lutz B (2006) Neuromodulatory functions of the endocannabinoid system. J Endocrinol Investig 29(3 Suppl):27–46

    CAS  Google Scholar 

  82. Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A et al (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302(5642):84–88

    Article  CAS  PubMed  Google Scholar 

  83. Gerdeman GL, Lovinger DM (2003) Emerging roles for endocannabinoids in long-term synaptic plasticity. Br J Pharmacol 140(5):781–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ (2003) The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 307(1):129–137

    Article  CAS  PubMed  Google Scholar 

  85. Monory K, Massa F, Egertova M, Eder M, Blaudzun H, Westenbroek R et al (2006) The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 51(4):455–466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Guggenhuber S, Monory K, Lutz B, Klugmann M (2010) AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity. PLoS One 5(12):e15707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mackie K, Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci U S A 89(9):3825–3829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hampson RE, Evans GJ, Mu J, Zhuang SY, King VC, Childers SR et al (1995) Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium “A-current” in cultured rat hippocampal neurons. Life Sci 56(23–24):2081–2088

    Article  CAS  PubMed  Google Scholar 

  89. Mackie K, Lai Y, Westenbroek R, Mitchell R (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci 15(10):6552–6561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Lakhan SE, Rowland M (2009) Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol 9:59

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR (2007) Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin 23(1):17–24

    Article  CAS  PubMed  Google Scholar 

  92. Centonze D, Bari M, Rossi S, Prosperetti C, Furlan R, Fezza F et al (2007) The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis. Brain 130(Pt 10):2543–2553

    Article  PubMed  Google Scholar 

  93. Centonze D, Rossi S, Finazzi-Agro A, Bernardi G, Maccarrone M (2007) The (endo)cannabinoid system in multiple sclerosis and amyotrophic lateral sclerosis. Int Rev Neurobiol 82:171–186

    Article  CAS  PubMed  Google Scholar 

  94. Jean-Gilles L, Feng S, Tench CR, Chapman V, Kendall DA, Barrett DA et al (2009) Plasma endocannabinoid levels in multiple sclerosis. J Neurol Sci 287(1–2):212–215

    Article  CAS  PubMed  Google Scholar 

  95. Pryce G, Ahmed Z, Hankey DJ, Jackson SJ, Croxford JL, Pocock JM et al (2003) Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126(Pt 10):2191–2202

    Article  PubMed  Google Scholar 

  96. Wade DT, Makela P, Robson P, House H, Bateman C (2004) Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler 10(4):434–441

    Article  CAS  PubMed  Google Scholar 

  97. Wade DT, Collin C, Stott C, Duncombe P (2010) Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler 16(6):707–714

    Article  CAS  PubMed  Google Scholar 

  98. Westlake TM, Howlett AC, Bonner TI, Matsuda LA, Herkenham M (1994) Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer’s brains. Neuroscience 63(3):637–652

    Article  CAS  PubMed  Google Scholar 

  99. Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML (2005) Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 25(8):1904–1913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Benito C, Nunez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ et al (2003) Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23(35):11136–11141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Pazos MR, Nunez E, Benito C, Tolon RM, Romero J (2004) Role of the endocannabinoid system in Alzheimer’s disease: new perspectives. Life Sci 75(16):1907–1915

    Article  CAS  PubMed  Google Scholar 

  102. Eubanks LM, Rogers CJ, AEt B, Koob GF, Olson AJ, Dickerson TJ et al (2006) A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol Pharm 3(6):773–777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Milton NG (2002) Anandamide and noladin ether prevent neurotoxicity of the human amyloid-beta peptide. Neurosci Lett 332(2):127–130

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was supported by the Natural Sciences and Engineering Research Council of Canada Discovery Grant to DWA.

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Authors and Affiliations

  1. Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada

    Md Ruhul Amin & Declan W. Ali

  2. Department of Physiology, The Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada

    Declan W. Ali

  3. The Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada

    Declan W. Ali

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  1. Md Ruhul Amin
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  2. Declan W. Ali
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Correspondence to Declan W. Ali .

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Editors and Affiliations

  1. Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA

    Anna N. Bukiya

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Amin, M.R., Ali, D.W. (2019). Pharmacology of Medical Cannabis. In: Bukiya, A. (eds) Recent Advances in Cannabinoid Physiology and Pathology. Advances in Experimental Medicine and Biology, vol 1162. Springer, Cham. https://doi.org/10.1007/978-3-030-21737-2_8

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