Skip to main content

The Pharmacology and Therapeutic Potential of Plant Cannabinoids

  • Chapter
  • First Online:
Cannabis sativa L. - Botany and Biotechnology

Abstract

The plant Cannabis sativa has been widely used by humans over many centuries as a source of fibre, for medicinal purposes, for religious ceremonies and as a recreational drug. Since the discovery of its main psychoactive ingredient, Δ9-tetrahydrocannabinol (THC), significant progress has been made towards the understanding (1) of the in vitro and in vivo pharmacology both of THC and of certain other cannabis-derived compounds, and (2) of the potential and actual uses of these “phytocannabinoids” as medicines. There is now extensive evidence that the pharmacological effects of some widely-studied phytocannabinoids, are due to their ability to interact with cannabinoid receptors and/or with other kinds of pharmacological targets, including non-cannabinoid receptors, and this makes the pharmacology of the phytocannabinoids rather complex and interesting. In this chapter, we provide an overview of the in vitro pharmacology of five selected phytocannabinoids and report findings that have identified potential new therapeutic uses for these compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

THC:

Tetrahydrocannabinol

CBD:

Cannabidiol

CBG:

Cannabigerol

THCV:

Tetrahydrocannabivarin

CBC:

Cannabichromene

CBDV:

Cannabidivarin

CBDA:

Cannabidiolic acid

CBGV:

Cannabigerovarin

CBGA:

Cannabigerolic acid

THCA:

Tetrahydrocannabinolic acid

THCVA:

Tetrahydrocannabivarinic acid

TRP:

Transient receptor potential

PPAR:

Peroxisome-proliferator activated receptor

GPCR:

G-protein coupled receptor

CB:

Cannabinoid

HT:

Hydroxytryptamine

8-OH-DPAT:

8-hydroxy-2-(di-n-propylamino)-tetralin

HU-201:

6aR,10aR)- 9-(Hydroxymethyl)- 6,6-dimethyl- 3-(2-methyloctan-2-yl)- 6a,7,10,10a-tetrahydrobenzo [c]chromen- 1-ol

WIN55212:

[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate

CP55940:

(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol

GTPγS:

Guanosine 5′-O-[gamma-thio]triphosphate)

AMP:

Adenosine monophosphate

ERK:

Extracellular signal-regulated kinases

CHO:

Chinese hamster ovary

NAM:

Negative allosteric modulator

SR141716A:

N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride

WAY100135:

(S)-N-tert-Butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide dihydrochloride

WAY100635:

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate

AM251:

N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide

References

  • Alexander SP (2016) Therapeutic potential of cannabis-related drugs. Prog Neuropsychopharmacol Biol Psychiatry 64:157–166. Review

    Google Scholar 

  • Anavi-Goffer S, Baillie G, Irving AJ, Gertsch J, Greig IR, Pertwee RG, Ross RA (2012) Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. J Biol Chem 287:91–104

    Article  CAS  PubMed  Google Scholar 

  • Baek SH, Kim YO, Kwag JS, Choi KE, Jung WY, Han DS (1998) Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of Cannabigerol against human oral epitheloid carcinoma cells. Arch Pharm Res 21:353–356

    Article  CAS  PubMed  Google Scholar 

  • Bayewitch M, Rhee M-H, Avidor-Reiss T, Breuer A, Mechoulam R, Vogel Z (1996) (-)-Δ9-tetrahydrocannabinol antagonizes the peripheral cannabinoid receptor-mediated inhibition of adenylyl cyclase. J Biol Chem 271:9902–9905

    Article  CAS  PubMed  Google Scholar 

  • Bolognini D, Costa B, Maione S, Comelli F, Marini P, Di Marzo V, Parolaro D, Ross RA, Gauson LA, Cascio MG, Pertwee RG (2010) The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Br J Pharmacol 160:677–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolognini D, Cascio MG, Parolaro D, Pertwee RG (2012) AM630 behaves as a protean ligand at the human cannabinoid CB2 receptor. Br J Pharmacol 165:2561–2574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolognini D, Rock EM, Cluny NL, Cascio MG, Limebeer CL, Duncan M, Stott CG, Javid FA, Parker LA, Pertwee RG (2013) Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Br J Pharmacol 168:1456–1470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown NK, Harvey DJ (1990) In vitro metabolism of cannabichromene in 7 common laboratory animals. Drug Metab Dispos 18:1065–1070

    CAS  PubMed  Google Scholar 

  • Carrier EJ, Auchampach JA, Hillard CJ (2006) Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A 103:7895–7900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cascio MG, Marini P (2015) Biosynthesis and fate of endocannabinoids. In: Pertwee RG (ed) Endocannabinoids. Springer, Heidelberg, pp 39–58

    Chapter  Google Scholar 

  • Cascio MG, Pertwee RG (2014) Known pharmacological actions of nine non-psychotropic phytocannabinoids. In: Pertwee RG (ed) Handbook of Cannabis. Oxford University Press, Oxford, pp 137–156

    Chapter  Google Scholar 

  • Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG (2010) Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br J Pharmacol 159:129–141

    Google Scholar 

  • Cascio MG, Zamberletti E, Marini P, Parolaro D, Pertwee RG (2015) The phytocannabinoid, Δ9-tetrahydrocannabivarin, can act through 5-HT1A receptors to produce antipsychotic effects. Br J Pharmacol 172:1305–1318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cluny NL, Naylor RJ, Whittle BA, Javid FA (2008) The effects of cannabidiol and tetrahydrocannabinol on motion-induced emesis in Suncus murinus. Basic Clin Pharmacol Toxicol 103:150–156

    Article  CAS  PubMed  Google Scholar 

  • Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M (2007) The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol 556:75–83

    Article  CAS  PubMed  Google Scholar 

  • De Petrocellis L, Ligresti A, Moriello AS, Allarà M, Bisogno T, Petrosino S, Stott CG, Di Marzo V (2011) Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol 163:1479–1494

    Article  PubMed  PubMed Central  Google Scholar 

  • De Petrocellis L, Orlando P, Moriello AS, Aviello G, Stott C, Izzo AA, Di Marzo V (2012) Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol 204:255–266

    Article  Google Scholar 

  • De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V (2008) Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther 325:1007–1015

    Article  PubMed  Google Scholar 

  • Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613

    CAS  PubMed  Google Scholar 

  • Duran M, Pérez E, Abanades S, Vidal X, Saura C, Majem M, Arriola E, Rabanal M, Pastor A, Farre M, Rams N, Laporte JR, Capella D (2010) Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 70:656–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallily R, Even-Chen T, Katzavian G, Lehmann D, Dagan A, Mechoulam R (2003) γ-Irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells. Leuk Lymphoma 44:1767–1773

    Article  CAS  PubMed  Google Scholar 

  • Galve-Roperh I, Sánchez C, Cortés ML, Gómez del Pulgar T, Izquierdo M, Guzmán M (2000) Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med 6:313–319

    Article  CAS  PubMed  Google Scholar 

  • Gill EW, Paton WDM, Pertwee RG (1970) Preliminary experiments on the chemistry and pharmacology of cannabis. Nature 228:134–136

    Article  CAS  PubMed  Google Scholar 

  • Govaerts SJ, Hermans E, Lambert DM (2004) Comparison of cannabinoid ligands affinities and efficacies in murine tissues and in transfected cells expressing human recombinant cannabinoid receptors. Eur J Pharm Sci 23:233–243

    Article  CAS  PubMed  Google Scholar 

  • Guindon J, Hohmann AG (2008) Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. Br J Pharmacol 153:319–334

    Article  CAS  PubMed  Google Scholar 

  • Guzmán M, Duarte MJ, Blázquez C, Ravina J, Rosa MC, Galve-Roperh I, Sánchez C, Velasco G, González-Feria L (2006) A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer 95:197–203

    Google Scholar 

  • Hart S, Fischer OM, Ullrich A (2004) Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res 64:1943–1950

    Article  CAS  PubMed  Google Scholar 

  • Howlett AC (2002) The cannabinoid receptors. Prostaglandins Other Lipid Mediat 68–9:619–631

    Article  Google Scholar 

  • Howlett AC (2005) Cannabinoid receptor signaling. In: Pertwee RG (ed) Cannabinoids. Springer, Heidelberg, pp 53–79

    Chapter  Google Scholar 

  • Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202. Review

    Google Scholar 

  • 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 30:515–527, 609

    Google Scholar 

  • Kelley BG, Thayer SA (2004) Δ9-Tetrahydrocannabinol antagonizes endocannabinoid modulation of synaptic transmission between hippocampal neurons in culture. Neuropharmacology 46:709–715

    Article  CAS  PubMed  Google Scholar 

  • Kimura M, Okamoto K (1970) Distribution of tetrahydrocannabinolic acid in fresh wild cannabis. Experientia 26:819–820

    Article  CAS  PubMed  Google Scholar 

  • Kramer JL (2015) Medical marijuana for cancer. CA-Cancer J Clin 65:109–122

    Article  PubMed  Google Scholar 

  • Kwiatkowska M, Parker LA, Burton P, Mechoulam R (2004) A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology 174:254–259

    Article  CAS  PubMed  Google Scholar 

  • Laprairie RB, Bagher AM, Kelly MEM, Denovan-Wright EM (2015) Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol 172:4790–4805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ligresti A, Schiano Moriello A, Starowicz K, Matias I, Pisanti S, De Petrocellis L, Laezza C, Portella G, Bifulco M, Di Marzo V (2006) Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther 318:1375–1387

    Article  CAS  PubMed  Google Scholar 

  • Massi P, Valenti M, Vaccani A, Gasperi V, Perletti G, Marras E, Fezza F, Maccarrone M, Parolaro D (2008) 5-lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. J Neurochem 104:1091–1100

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • McKallip RJ, Jia WT, Schlomer J, Warren JW, Nagarkatti PS, Nagarkatti M (2006) Cannabidiol-induced apoptosis in human leukemia cells: a novel role of cannabidiol in the regulation of p22(phox) and Nox4 expression. Mol Pharmacol 70:897–908

    Article  CAS  PubMed  Google Scholar 

  • Mechoulam R, Lander N, Varkony TH, Kimmel I, Becker O, Ben Zvi, Edery H, Porath G (1980) Stereochemical requirements for cannabinoid activity. J Med Chem 23:1068–1072

    Article  CAS  PubMed  Google Scholar 

  • Mechoulam R, Feigenbaum JJ, Lander N, Segal M, Järbe TUC, Hiltunen AJ, Consroe P (1988) Enantiomeric cannabinoids—stereospecificity of psychotropic activity. Experientia 44:762–764

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA (1975) Anti-neoplastic activity of cannabinoids. J Nat Cancer Instit 55:587–602

    Article  Google Scholar 

  • Onaivi ES, Ishiguro H, Gong JP, Patel S, Perchuk A, Meozzi PA, Myers L, Mora Z, Tagliaferro P, Gardner E, Brusco A, Akinshola BE, Liu QR, Hope B, Iwasaki S, Arinami T, Teasenfitz L, Uhl GR (2006) Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann N Y Acad Sci 1074:514–536

    Article  CAS  PubMed  Google Scholar 

  • O’Sullivan SE (2007) Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br J Pharmacol 152:576–582

    Article  PubMed  PubMed Central  Google Scholar 

  • Oz M (2006) Receptor-independent effects of endocannabinoids on ion channels. Curr Pharm Design 12:227–239

    Article  CAS  Google Scholar 

  • Parker LA, Kwiatkowska M, Burton P, Mechoulam R (2004) Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew). Psychopharmacology 171:156–161

    Article  CAS  PubMed  Google Scholar 

  • Parker LA, Rana SA, Limebeer CL (2008) Conditioned nausea in rats: assessment by conditioned disgust reactions, rather than conditioned taste avoidance. Can J Exp Psychol 62:198–209

    Article  PubMed  Google Scholar 

  • Perez J, Ribera MV (2008) Managing neuropathic pain with Sativex®: a review of its pros and cons. Expert Opin Pharmacother 9:1189–1195

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG (1988) The central neuropharmacology of psychotropic cannabinoids. Pharmacol Ther 36:189–261

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG (1997) Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 74:129–180

    CAS  PubMed  Google Scholar 

  • Pertwee RG (2001) Cannabinoid receptors and pain. Prog Neurobiol 63:569–611

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG (2004a) The pharmacology and therapeutic potential of cannabidiol. In: Di Marzo V (ed) Cannabinoids. Kluwer Academic/Plenum Publishers, New York, pp 32–83

    Google Scholar 

  • Pertwee RG (2004b) Pharmacological and therapeutic targets for Δ9-tetrahydrocannabinol and cannabidiol. Euphytica 140:73–82

    Article  CAS  Google Scholar 

  • Pertwee RG (2005) Pharmacological actions of cannabinoids. In: Pertwee RG (ed) cannabinoids. Springer-Verlag, Heidelberg, pp 1–51

    Chapter  Google Scholar 

  • Pertwee RG (2007) Cannabinoids and multiple sclerosis. Mol Neurobiol 36:45–59

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG (2009) Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 156:397–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pertwee RG (2010) Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr Med Chem 17:1360–1381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pertwee RG (2015) Endocannabinoids and their pharmacological actions. In: Pertwee RG (ed) Endocannabinoids. Springer-Verlag, Heidelberg, pp 1–37

    Chapter  Google Scholar 

  • Pertwee RG, Ross RA (2002) Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fatty Acids 66:101–121. Review

    Google Scholar 

  • Pertwee RG, Cascio MG (2014) Known pharmacological actions of delta-9-tetrahydrocannabinol and of four other chemical constituents of cannabis that activate cannabinoid receptors. In: Pertwee RG (ed) Handbook of Cannabis. Oxford University Press, Oxford, pp 115–136

    Chapter  Google Scholar 

  • Pertwee RG, Ross RA, Craib SJ, Thomas A (2002) (-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens. Eur J Pharmacol 456:99–106

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG, Howlett AC, Abood ME, Alexander SPH, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA (2010) International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 62:588–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pertwee RG, Thomas A, Stevenson LA, Ross RA, Varvel SA, Lichtman AH, Martin BR, Razdan RK (2007) The psychoactive plant cannabinoid, Δ9-tetrahydrocannabinol, is antagonized by Δ8- and Δ9-tetrahydrocannabivarin in mice in vivo. Br J Pharmacol 150:586–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petitet F, Jeantaud B, Reibaud M, Imperato A, Dubroeucq M-C (1998) Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of Δ9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Life Sci 63:PL1–6

    Google Scholar 

  • Pinsger M, Schimetta W, Volc D, Hiermann E, Riederer F, Pölz W (2006) Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain—a randomized controlled trial. Wien Klin Wochenschr 118:327–335

    Google Scholar 

  • Rahn EJ, Hohmann AG (2009) Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics 6:713–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramer R, Hinz B (2008) Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1. J Natl Cancer Inst 100:59–69

    Article  CAS  PubMed  Google Scholar 

  • Rock EM, Bezaquen J, Limebeer CL, Parker LA (2008) Potential of the rat model of conditioned gaping to detect nausea produced by rolipram, a phosphodiesterase-4 (PDE4) inhibitor. Pharmacol Biochem Behav 91:537–541

    Article  PubMed  Google Scholar 

  • Rock EM, Goodwin JM, Limebeer CL, Breuer A, Pertwee RG, Mechoulam R, Parker LA (2011) Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews. Psychopharmacology 215:505–512

    Article  CAS  PubMed  Google Scholar 

  • Rock EM, Bolognini D, Limebeer CL, Cascio MG, Anavi-Goffer S, Fletcher PJ, Mechoulam R, Pertwee RG, Parker LA (2012) Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT1A somatodendritic autoreceptors in the dorsal raphe nucleus. Br J Pharmacol 165:2620–2634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross RA (2009) The enigmatic pharmacology of GPR55. Trends Pharmacol Sci 30:156–163

    Article  CAS  PubMed  Google Scholar 

  • Ruiz L, Miguel A, Diaz Laviada I (1999) Δ9-Tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism. FEBS Lett 458:400–404

    Article  CAS  PubMed  Google Scholar 

  • Russo EB, Burnett A, Hall B, Parker KK (2005) Agonistic properties of cannabidiol at 5-HT1A receptors. Neurochem Res 30:1037–1043

    Article  CAS  PubMed  Google Scholar 

  • Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson N-O, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sacerdote P, Martucci C, Vaccani A, Bariselli F, Panerai AE, Colombo A, Parolaro D, Massi P (2005) The nonpsychoactive component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both in vivo and in vitro. J Neuroimmunol 159:97–105

    Article  CAS  PubMed  Google Scholar 

  • Sánchez C, Galve-Roperh I, Canova C, Brachet P, Guzmán M (1998) Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Lett 436:6–10

    Google Scholar 

  • Shen M1, Thayer SA (1999) Delta9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture. Mol Pharmacol 55:8–13

    Google Scholar 

  • Showalter VM, Compton DR, Martin BR, Abood ME (1996) Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands. J Pharmacol Exp Ther 278:989–999

    CAS  PubMed  Google Scholar 

  • Sim LJ, Hampson RE, Deadwyler SA, Childers SR (1996) Effects of chronic treatment with delta9-tetrahydrocannabinol on cannabinoid-stimulated [35S]GTPgammaS autoradiography in rat brain. J Neurosci 16:8057–8066

    Google Scholar 

  • Skrabek RQ, Galimova L, Ethans K, Perry D (2008) Nabilone for the treatment of pain in fibromyalgia. J Pain 9:164–173

    Google Scholar 

  • Straiker A, Mackie K (2005) Depolarization-induced suppression of excitation in murine autaptic hippocampal neurones. J Physiol 569:501–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas A, Ross RA, Saha B, Mahadevan A, Razdan RK, Pertwee RG (2004) 6″-Azidohex-2″-yne-cannabidiol: a potential neutral, competitive cannabinoid CB1 receptor antagonist. Eur J Pharmacol 487:213–221

    Article  CAS  PubMed  Google Scholar 

  • Thomas A, Stevenson LA, Wease KN, Price MR, Baillie G, Ross RA, Pertwee RG (2005) Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. Br J Pharmacol 146:917–926

    Google Scholar 

  • Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG (2007) Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol 150:613–623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaccani A, Massi P, Colombo A, Rubino T, Parolaro D (2005) Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism. Br J Pharmacol 144:1032–1036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332

    Article  PubMed  Google Scholar 

  • Walter L, Franklin A, Witting A, Wade C, Xie YH, Kunos G, Mackie K, Stella N (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23:1398–1405

    CAS  PubMed  Google Scholar 

  • Yamaori S, Kushihara M, Yamamoto I, Watanabe K (2010) Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem Pharmacol 79:1691–1698

    Article  CAS  PubMed  Google Scholar 

  • Yang KH, Galadari S, Isaev D, Petroianu G, Shippenberg TS, Oz M (2010) The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptor-mediated currents in Xenopus laevis oocytes. J Pharmacol Exp Ther 333:547–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin H, Chu A, Li W, Wang B, Shelton F, Otero F, Nguyen DG, Caldwell JS, Chen YA (2009) Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter (TM) assay. J Biol Chem 284:12328–12338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sørgård M, Di Marzo V, Julius D, Högestätt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Grazia Cascio .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Cascio, M.G., Pertwee, R.G., Marini, P. (2017). The Pharmacology and Therapeutic Potential of Plant Cannabinoids. In: Chandra, S., Lata, H., ElSohly, M. (eds) Cannabis sativa L. - Botany and Biotechnology. Springer, Cham. https://doi.org/10.1007/978-3-319-54564-6_9

Download citation

Publish with us

Policies and ethics