SavedAdd your journal

Journals / Ankara Üniversitesi Eczacılık Fakültesi Dergisi / 2021 / Cilt: 45 Sayı: 3

MEDICAL CANNABIS AND HEALTH: A PHARMACOLOGICAL REVIEW

TIBBİ KENEVİR VE SAĞLIK: FARMAKOLOJİK BİR DERLEME

Özge Balpınar(ONDOKUZ MAYIS ÜNİVERSİTESİ)0000-0003-4235-9241
Selim Aytaç(ONDOKUZ MAYIS ÜNİVERSİTESİ)0000-0003-1786-9725
Pages
631–651
Publication Date
2021-09-27
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The aim of this study was to provide evidence that the endocannabinoid system could be a potential therapeutic target in many pathological conditions.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: Cannabis sativa L. is a plant that has been used for therapeutic purposes since ancient times.
📊
Key Findings & Data:However, its use has been limited due to its content.
💡
Conclusion & Impact:The aim of this study was to provide evidence that the endocannabinoid system could be a potential therapeutic target in many pathological conditions.
🔬Design:Derleme
📍Scope:Comprehensive Sample
⚙️Variables:Kannabinoid · kanser · kenevir

Abstract

Objective: Cannabis sativa L. is a plant that has been used for therapeutic purposes since ancient times. However, its use has been limited due to its content. Cannabis causes many changes at the gene level in the endocannabinoid system with the phytocannabinoids it contains. The aim of this study was to provide evidence that the endocannabinoid system could be a potential therapeutic target in many pathological conditions.

Özet

Amaç: Kenevir antik çağlardan bugüne dek tedavi amaçlı kullanılmakta olan bir bitkidir. Her ne kadar kullanımı içerdiği psikoaktif bileşenler dolayısıyla sınırlandırılmış olsa da, kenevirin tıbbi yönüne dair araştırmalar literatürde oldukça yoğundur. Cannabis sativa L., içerdiği fitokannabinoidler ile endokannabinoid sistemde gen düzeyinde pek çok değişikliğe sebep olabilmektedir. Endokannabinoid sistemin pek çok patolojik durumda potansiyel bir terapötik hedef olabileceğine dair kanıtların derlenmesi hedefiyle bu çalışma ortaya koyulmuştur.

🔖

Cite This Article

Balpınar, Ö., Aytaç, S. (2021). MEDICAL CANNABIS AND HEALTH: A PHARMACOLOGICAL REVIEW. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, Cilt: 45 Sayı: 3, 631–651. https://doi.org/10.33483/jfpau.859372

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (137)

  1. Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H., Reda, H., Press, S.,. Petersen, K. L. (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology, 68(7), 515-521. doi:10.1212/01.wnl.0000253187.66183.9c
  2. Alles, S. R. A., & Smith, P. A. (2018). Etiology and Pharmacology of Neuropathic Pain. Pharmacol Rev, 70(2), 315-347. doi:10.1124/pr.117.014399
  3. Amin, M. R., & Ali, D. W. (2019). Pharmacology of Medical Cannabis. Adv Exp Med Biol, 1162, 151-165. doi:10.1007/978-3-030-21737-2_8
  4. Basavarajappa, B. S., Shivakumar, M., Joshi, V., & Subbanna, S. (2017). Endocannabinoid system in neurodegenerative disorders. J Neurochem, 142(5), 624-648. doi:10.1111/jnc.14098
  5. Benito, C., Núñez, E., Tolón, R. M., Carrier, E. J., Rábano, A., Hillard, C. J., & Romero, J. (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. doi:10.1523/jneurosci.23-35-11136.2003
  6. Benito, C., Romero, J. P., Tolón, R. M., Clemente, D., Docagne, F., Hillard, C. J.,. Romero, J. (2007). Cannabinoid CB 1 and CB 2 Receptors and Fatty Acid Amide Hydrolase Are Specific Markers of Plaque Cell Subtypes in Human Multiple Sclerosis. The Journal of Neuroscience, 27(9), 2396. doi:10.1523/JNEUROSCI.4814-06.2007
  7. Bisogno, T., Katayama, K., Melck, D., Ueda, N., De Petrocellis, L., Yamamoto, S., & Di Marzo, V. (1998). Biosynthesis and degradation of bioactive fatty acid amides in human breast cancer and rat pheochromocytoma cells--implications for cell proliferation and differentiation. Eur J Biochem, 254(3), 634-642. doi:10.1046/j.1432-1327.1998.2540634.x
  8. Borgelt, L. M., Franson, K. L., Nussbaum, A. M., & Wang, G. S. (2013). The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy, 33(2), 195-209. doi:10.1002/phar.1187
  9. Bridgeman, M. B., & Abazia, D. T. (2017). Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P & T: a peer-reviewed journal for formulary management, 42(3), 180-188. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28250701
  10. Caffarel, M. M., Andradas, C., Mira, E., Pérez-Gómez, E., Cerutti, C., Moreno-Bueno, G.,. Sánchez, C. (2010). Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol Cancer, 9, 196. doi:10.1186/1476-4598-9-196
  11. Cannabinoids in Parkinson's Disease. (2017). Cannabis and Cannabinoid Research, 2(1), 21-29. doi:10.1089/can.2017.0002
  12. Chung, S. C., Hammarsten, P., Josefsson, A., Stattin, P., Granfors, T., Egevad, L.,. Fowler, C. J. (2009). A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer. Eur J Cancer, 45(1), 174-182. doi:10.1016/j.ejca.2008.10.010
  13. Cipriano, M., Häggström, J., Hammarsten, P., & Fowler, C. J. (2013). Association between Cannabinoid CB1 Receptor Expression and Akt Signalling in Prostate Cancer. PLoS One, 8(6), e65798. doi:10.1371/journal.pone.0065798
  14. Collin, C., Ehler, E., Waberzinek, G., Alsindi, Z., Davies, P., Powell, K.,. Ambler, Z. (2010). A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurological Research, 32(5), 451-459. doi:10.1179/016164109X12590518685660
  15. Console-Bram, L., Marcu, J., & Abood, M. E. (2012). Cannabinoid receptors: nomenclature and pharmacological principles. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 38(1), 4-15. doi:https://doi.org/10.1016/j.pnpbp.2012.02.009
  16. Consroe, P., Laguna, J., Allender, J., Snider, S., Stern, L., Sandyk, R.,. Schram, K. (1991). Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacol Biochem Behav, 40(3), 701-708. doi:10.1016/0091-3057(91)90386-g
  17. Crippa, J. A., Zuardi, A. W., Martín-Santos, R., Bhattacharyya, S., Atakan, Z., McGuire, P., & Fusar-Poli, P. (2009). Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol, 24(7), 515-523. doi:10.1002/hup.1048
  18. Cunha, P., Romão, A., Mascarenhas-Melo, F., Teixeira, H., & Reis, F. (2011). Endocannabinoid system in cardiovascular disorders - new pharmacotherapeutic opportunities. Journal of Pharmacy And Bioallied Sciences, 3(3), 350-360. doi:10.4103/0975-7406.84435
  19. Curtis, A., Mitchell, I., Patel, S., Ives, N., & Rickards, H. (2009). A pilot study using nabilone for symptomatic treatment in Huntington's disease. Movement Disorders, 24(15), 2254-2259. doi:https://doi.org/10.1002/mds.22809
  20. Darmani, N. A. (2001). Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew. Pharmacol Biochem Behav, 69(1-2), 239-249. doi:10.1016/s0091-3057(01)00531-7
  21. Darmani, N. A. (2001). Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB(1) receptor antagonist/inverse agonist SR 141716A. Neuropsychopharmacology, 24(2), 198-203. doi:10.1016/s0893-133x(00)00197-4
  22. DeMorrow, S., Francis, H., Gaudio, E., Venter, J., Franchitto, A., Kopriva, S.,. Alpini, G. (2008). The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway. American journal of physiology. Gastrointestinal and liver physiology, 295(6), G1150-G1158. doi:10.1152/ajpgi.90455.2008
  23. Denovan-Wright, E. M., & Robertson, H. A. (2000). Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington's disease mice. Neuroscience, 98(4), 705-713. doi:10.1016/s0306-4522(00)00157-3
  24. Di Marzo, V. (2008). Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov, 7(5), 438-455. doi:10.1038/nrd2553
  25. Dowie, M. J., Bradshaw, H. B., Howard, M. L., Nicholson, L. F., Faull, R. L., Hannan, A. J., & Glass, M. (2009). Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington's disease. Neuroscience, 163(1), 456-465. doi:10.1016/j.neuroscience.2009.06.014
  26. El Banoua, F., Caraballo, I., Flores, J. A., Galan-Rodriguez, B., & Fernandez-Espejo, E. (2004). Effects on turning of microinjections into basal ganglia of D1 and D2 dopamine receptors agonists and the cannabinoid CB1 antagonist SR141716A in a rat Parkinson's model. Neurobiology of Disease, 16(2), 377-385. doi:https://doi.org/10.1016/j.nbd.2004.03.002
  27. Ellert-Miklaszewska, A., Grajkowska, W., Gabrusiewicz, K., Kaminska, B., & Konarska, L. (2007). Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors. Brain Res, 1137(1), 161-169. doi:10.1016/j.brainres.2006.12.060
  28. Ellis, R. J., Toperoff, W., Vaida, F., van den Brande, G., Gonzales, J., Gouaux, B.,. Atkinson, J. H. (2009). Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology, 34(3), 672-680. doi:10.1038/npp.2008.120
  29. Ellison, J. M., Gelwan, E., & Ogletree, J. (1990). Complex partial seizure symptoms affected by marijuana abuse. J Clin Psychiatry, 51(10), 439-440.
  30. ElSohly, M. A., Radwan, M. M., Gul, W., Chandra, S., & Galal, A. (2017). Phytochemistry of Cannabis sativa L. Prog Chem Org Nat Prod, 103, 1-36. doi:10.1007/978-3-319-45541-9_1
  31. Esposito, G., Scuderi, C., Savani, C., Steardo Jr, L., De Filippis, D., Cottone, P.,. Steardo, L. (2007). Cannabidiol in vivo blunts β-amyloid induced neuroinflammation by suppressing IL-1β and iNOS expression. British journal of pharmacology, 151(8), 1272-1279. doi:https://doi.org/10.1038/sj.bjp.0707337
  32. Fitzcharles, M. A., Baerwald, C., Ablin, J., & Häuser, 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. doi:10.1007/s00482-015-0084-3
  33. Fitzcharles, M. A., Ste-Marie, P. A., Häuser, W., Clauw, D. J., Jamal, S., Karsh, J.,. Walsh, Z. (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. doi:10.1002/acr.22727
  34. Fowler, C. J., Jonsson, K. O., Andersson, A., Juntunen, J., Järvinen, T., Vandevoorde, S.,. Smart, D. (2003). Inhibition of C6 glioma cell proliferation by anandamide, 1-arachidonoylglycerol, and by a water soluble phosphate ester of anandamide: variability in response and involvement of arachidonic acid. Biochem Pharmacol, 66(5), 757-767. doi:10.1016/s0006-2952(03)00392-7
  35. Fraguas-Sánchez, A. I., Martín-Sabroso, C., & Torres-Suárez, A. I. (2018). Insights into the effects of the endocannabinoid system in cancer: a review. British journal of pharmacology, 175(13), 2566-2580. doi:https://doi.org/10.1111/bph.14331
  36. Frampton, G., Coufal, M., Li, H., Ramirez, J., & DeMorrow, S. (2010). Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling. Experimental cell research, 316(9), 1465-1478. doi:10.1016/j.yexcr.2010.03.017
  37. Glass, M., Faull, R. L., & Dragunow, M. (1993). Loss of cannabinoid receptors in the substantia nigra in Huntington's disease. Neuroscience, 56(3), 523-527. doi:10.1016/0306-4522(93)90352-g
  38. Gofshteyn, J. S., Wilfong, A., Devinsky, O., Bluvstein, J., Charuta, J., Ciliberto, M. A.,. Marsh, E. D. (2017). Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases. Journal of Child Neurology, 32(1), 35-40. doi:10.1177/0883073816669450
  39. Gross, D. W., Hamm, J., Ashworth, N. L., & Quigley, D. (2004). Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center. Neurology, 62(11), 2095-2097. doi:10.1212/01.wnl.0000127623.03766.75
  40. Hamerle, M., Ghaeni, L., Kowski, A., Weissinger, F., & Holtkamp, M. (2014). Cannabis and other illicit drug use in epilepsy patients. European Journal of Neurology, 21(1), 167-170. doi:https://doi.org/10.1111/ene.12081
  41. Hasenoehrl, C., Taschler, U., Storr, M., & Schicho, R. (2016). The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease. Neurogastroenterology & Motility, 28(12), 1765-1780. doi:https://doi.org/10.1111/nmo.12931
  42. Häuser, W., Fitzcharles, M. A., Radbruch, L., & Petzke, F. (2017). Cannabinoids in Pain Management and Palliative Medicine. Dtsch Arztebl Int, 114(38), 627-634. doi:10.3238/arztebl.2017.0627
  43. Henstridge, C. M. (2012). Off-Target Cannabinoid Effects Mediated by GPR55. Pharmacology, 89(3-4), 179-187. doi:10.1159/000336872
  44. Hohmann, T., Grabiec, U., Ghadban, C., Feese, K., & Dehghani, F. (2017). The influence of biomechanical properties and cannabinoids on tumor invasion. Cell adhesion & migration, 11(1), 54-67. doi:10.1080/19336918.2016.1183867
  45. Hurley, M. J., Mash, D. C., & Jenner, P. (2003). Expression of cannabinoid CB1 receptor mRNA in basal ganglia of normal and parkinsonian human brain. Journal of Neural Transmission, 110(11), 1279-1288. doi:10.1007/s00702-003-0033-7
  46. Hurley, M. J., Mash, D. C., & Jenner, P. (2003). Expression of cannabinoid CB1 receptor mRNA in basal ganglia of normal and parkinsonian human brain. J Neural Transm (Vienna), 110(11), 1279-1288. doi:10.1007/s00702-003-0033-7
  47. Hussain, S. A., Zhou, R., Jacobson, C., Weng, J., Cheng, E., Lay, J.,. Sankar, R. (2015). Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox–Gastaut syndrome. Epilepsy & Behavior, 47, 138-141. doi:https://doi.org/10.1016/j.yebeh.2015.04.009
  48. Jacobsson, S. O., Wallin, T., & Fowler, C. J. (2001). Inhibition of rat C6 glioma cell proliferation by endogenous and synthetic cannabinoids. Relative involvement of cannabinoid and vanilloid receptors. J Pharmacol Exp Ther, 299(3), 951-959.
  49. Jean-Gilles, L., Feng, S., Tench, C. R., Chapman, V., Kendall, D. A., Barrett, D. A., & Constantinescu, C. S. (2009). Plasma endocannabinoid levels in multiple sclerosis. Journal of the Neurological Sciences, 287(1), 212-215. doi:https://doi.org/10.1016/j.jns.2009.07.021
  50. Kalant, H. (2001). Medicinal use of cannabis: history and current status. Pain Res Manag, 6(2), 80-91. doi:10.1155/2001/469629
  51. Katchan, V., David, P., & Shoenfeld, Y. (2016). Cannabinoids and autoimmune diseases: A systematic review. Autoimmunity Reviews, 15(6), 513-528. doi:https://doi.org/10.1016/j.autrev.2016.02.008
  52. Kelsey, J. E., Harris, O., & Cassin, J. (2009). The CB1 antagonist rimonabant is adjunctively therapeutic as well as monotherapeutic in an animal model of Parkinson's disease. Behavioural Brain Research, 203(2), 304-307. doi:https://doi.org/10.1016/j.bbr.2009.04.035
  53. Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Frontiers in Cellular Neuroscience, 10(294). doi:10.3389/fncel.2016.00294
  54. Killestein, J., Hoogervorst, E. L., Reif, M., Kalkers, N. F., Van Loenen, A. C., Staats, P. G.,. Polman, C. H. (2002). Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology, 58(9), 1404-1407. doi:10.1212/wnl.58.9.1404
  55. Kleine-Brueggeney, M., Greif, R., Brenneisen, R., Urwyler, N., Stueber, F., & Theiler, L. G. (2015). Intravenous Delta-9-Tetrahydrocannabinol to Prevent Postoperative Nausea and Vomiting: A Randomized Controlled Trial. Anesth Analg, 121(5), 1157-1164. doi:10.1213/ane.0000000000000877
  56. Koppel, J., Vingtdeux, V., Marambaud, P., d’Abramo, C., Jimenez, H., Stauber, M.,. Davies, P. (2014). CB2 Receptor Deficiency Increases Amyloid Pathology and Alters Tau Processing in a Transgenic Mouse Model of Alzheimer’s Disease. Molecular Medicine, 20(1), 29-36. doi:10.2119/molmed.2013.00140.revised
  57. Laprairie, R. B., Bagher, A. M., & Denovan-Wright, E. M. (2017). Cannabinoid receptor ligand bias: implications in the central nervous system. Current Opinion in Pharmacology, 32, 32-43. doi:https://doi.org/10.1016/j.coph.2016.10.005
  58. Ligresti, A., Moriello, A. S., Starowicz, K., Matias, I., Pisanti, S., De Petrocellis, L.,. 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(3), 1375-1387. doi:10.1124/jpet.106.105247
  59. Ligresti, A., Petrocellis, L. D., & Marzo, V. D. (2016). From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology. Physiological Reviews, 96(4), 1593-1659. doi:10.1152/physrev.00002.2016
  60. López-Sendón Moreno, J. L., García Caldentey, J., Trigo Cubillo, P., Ruiz Romero, C., García Ribas, G., Alonso Arias, M. A. A.,. García de Yébenes Prous, J. (2016). A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease. Journal of Neurology, 263(7), 1390-1400. doi:10.1007/s00415-016-8145-9
  61. Ma, C., Wu, T.-T., Jiang, P.-C., Li, Z.-Q., Chen, X.-J., Fu, K.,. Gong, R. (2016). Anti-carcinogenic activity of anandamide on human glioma in vitro and in vivo. Molecular medicine reports, 13(2), 1558-1562. doi:10.3892/mmr.2015.4721
  62. Maule, W. J. (2015). Medical uses of marijuana (Cannabis sativa): fact or fallacy? British Journal of Biomedical Science, 72(2), 85-91. doi:10.1080/09674845.2015.11666802
  63. McCaw, E. A., Hu, H., Gomez, G. T., Hebb, A. L., Kelly, M. E., & Denovan-Wright, E. M. (2004). Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington's disease transgenic mice. Eur J Biochem, 271(23-24), 4909-4920. doi:10.1111/j.1432-1033.2004.04460.x
  64. Mechoulam, R., Peters, M., Murillo-Rodriguez, E., & Hanus, L. O. (2007). Cannabidiol--recent advances. Chem Biodivers, 4(8), 1678-1692. doi:10.1002/cbdv.200790147
  65. Meiri, E., Jhangiani, H., Vredenburgh, J. J., Barbato, L. M., Carter, F. J., Yang, H. M., & Baranowski, V. (2007). Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin, 23(3), 533-543. doi:10.1185/030079907x167525
  66. Melck, D., De Petrocellis, L., Orlando, P., Bisogno, T., Laezza, C., Bifulco, M., & Di Marzo, V. (2000). Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology, 141(1), 118-126. doi:10.1210/endo.141.1.7239
  67. Meschler, J. P., Howlett, A. C., & Madras, B. K. (2001). Cannabinoid receptor agonist and antagonist effects on motor function in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human primates. Psychopharmacology (Berl), 156(1), 79-85. doi:10.1007/s002130100728
  68. Mimeault, M., Pommery, N., Wattez, N., Bailly, C., & Hénichart, J. P. (2003). Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: implication of epidermal growth factor receptor down-regulation and ceramide production. Prostate, 56(1), 1-12. doi:10.1002/pros.10190
  69. Mortati, K., Dworetzky, B., & Devinsky, O. (2007). Marijuana: an effective antiepileptic treatment in partial epilepsy? A case report and review of the literature. Rev Neurol Dis, 4(2), 103-106.
  70. Nithipatikom, K., Isbell, M. A., Endsley, M. P., Woodliff, J. E., & Campbell, W. B. (2011). Anti-proliferative effect of a putative endocannabinoid, 2-arachidonylglyceryl ether in prostate carcinoma cells. Prostaglandins & other lipid mediators, 94(1-2), 34-43. doi:10.1016/j.prostaglandins.2010.12.002
  71. Nurmikko, T. J., Serpell, M. G., Hoggart, B., Toomey, P. J., Morlion, B. J., & 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. doi:10.1016/j.pain.2007.08.028
  72. ONAIVI, E. S., ISHIGURO, H., GONG, J.-P., PATEL, S., PERCHUK, A., MEOZZI, P. A.,. UHL, G. R. (2006). Discovery of the Presence and Functional Expression of Cannabinoid CB2 Receptors in Brain. Annals of the New York Academy of Sciences, 1074(1), 514-536. doi:https://doi.org/10.1196/annals.1369.052
  73. Orellana-Serradell, O., Poblete, C. E., Sanchez, C., Castellón, E. A., Gallegos, I., Huidobro, C.,. Contreras, H. R. (2015). Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncol Rep, 33(4), 1599-1608. doi:10.3892/or.2015.3746
  74. Pacher, P., & Mechoulam, R. (2011). Is lipid signaling through cannabinoid 2 receptors part of a protective system? Progress in Lipid Research, 50(2), 193-211. doi:https://doi.org/10.1016/j.plipres.2011.01.001
  75. Pagotto, U., Marsicano, G., Cota, D., Lutz, B., & Pasquali, R. (2006). The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance. Endocrine Reviews, 27(1), 73-100. doi:10.1210/er.2005-0009
  76. Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British journal of pharmacology, 153(2), 199-215. doi:10.1038/sj.bjp.0707442
  77. Pisanti, S., & Bifulco, M. (2017). Modern History of Medical Cannabis: From Widespread Use to Prohibitionism and Back. Trends in Pharmacological Sciences, 38(3), 195-198. doi:https://doi.org/10.1016/j.tips.2016.12.002
  78. Polito, S., MacDonald, T., Romanick, M., Jupp, J., Wiernikowski, J., Vennettilli, A.,. Dupuis, L. L. (2018). Safety and efficacy of nabilone for acute chemotherapy-induced vomiting prophylaxis in pediatric patients: A multicenter, retrospective review. Pediatr Blood Cancer, 65(12), e27374. doi:10.1002/pbc.27374
  79. Pomeroy, M., Fennelly, J. J., & Towers, M. (1986). Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis. Cancer Chemother Pharmacol, 17(3), 285-288. doi:10.1007/bf00256701
  80. Porter, B. E., & Jacobson, C. (2013). Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior, 29(3), 574-577. doi:https://doi.org/10.1016/j.yebeh.2013.08.037
  81. Qamri, Z., Preet, A., Nasser, M. W., Bass, C. E., Leone, G., Barsky, S. H., & Ganju, R. K. (2009). Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol Cancer Ther, 8(11), 3117-3129. doi:10.1158/1535-7163.Mct-09-0448
  82. Ramer, R., Schwarz, R., & Hinz, B. (2019). Modulation of the Endocannabinoid System as a Potential Anticancer Strategy. Frontiers in pharmacology, 10, 430-430. doi:10.3389/fphar.2019.00430
  83. Ramírez, B. G., Blázquez, C., del Pulgar, T. G., Guzmán, M., & de Ceballos, M. L. (2005). Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation. The Journal of Neuroscience, 25(8), 1904. doi:10.1523/JNEUROSCI.4540-04.2005
  84. Richfield, E. K., & Herkenham, M. (1994). Selective vulnerability in Huntington's disease: Preferential loss of cannabinoid receptors in lateral globus pallidus. Annals of Neurology, 36(4), 577-584. doi:https://doi.org/10.1002/ana.410360406
  85. Rog, D. J., Nurmikko, T. J., & Young, C. A. (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. doi:10.1016/j.clinthera.2007.09.013
  86. Rog, D. J., Nurmikko, T. J., & Young, C. A. (2007). Oromucosal Δ9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: An uncontrolled, open-label, 2-year extension trial. Clinical Therapeutics, 29(9), 2068-2079. doi:https://doi.org/10.1016/j.clinthera.2007.09.013
  87. Sallan, S. E., Zinberg, N. E., & Frei, E., 3rd. (1975). Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med, 293(16), 795-797. doi:10.1056/nejm197510162931603
  88. Sánchez, C., de Ceballos, M. L., Gomez del Pulgar, T., Rueda, D., Corbacho, C., Velasco, G.,. Guzmán, M. (2001). Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res, 61(15), 5784-5789.
  89. Sarfaraz, S., Afaq, F., Adhami, V. M., & Mukhtar, H. (2005). Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res, 65(5), 1635-1641. doi:10.1158/0008-5472.Can-04-3410
  90. Schley, M., Ständer, S., Kerner, J., Vajkoczy, P., Schüpfer, G., Dusch, M.,. Konrad, C. (2009). Predominant CB2 receptor expression in endothelial cells of glioblastoma in humans. Brain Res Bull, 79(5), 333-337. doi:10.1016/j.brainresbull.2009.01.011
  91. Solas, M., Francis, P. T., Franco, R., & Ramirez, M. J. (2013). CB2 receptor and amyloid pathology in frontal cortex of Alzheimer's disease patients. Neurobiology of Aging, 34(3), 805-808. doi:https://doi.org/10.1016/j.neurobiolaging.2012.06.005
  92. Sredni, S. T., Huang, C.-C., Suzuki, M., Pundy, T., Chou, P., & Tomita, T. (2016). Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system. Child's Nervous System, 32(11), 2061-2067. doi:10.1007/s00381-016-3243-7
  93. Suraev, A., Lintzeris, N., Stuart, J., Kevin, R. C., Blackburn, R., Richards, E.,. McGregor, I. S. (2018). Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community. Scientific Reports, 8(1), 10154. doi:10.1038/s41598-018-28127-0
  94. Svíženská, I., Dubový, P., & Šulcová, A. (2008). Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures — A short review. Pharmacology Biochemistry and Behavior, 90(4), 501-511. doi:https://doi.org/10.1016/j.pbb.2008.05.010
  95. Szulakowska, A., & Milnerowicz, H. (2007). Cannabis sativa in the Light of Scientific Research. Advances in Clinical and Experimental Medicine, 16, 807-815.
  96. Tolón, R. M., Núñez, E., Pazos, M. R., Benito, C., Castillo, A. I., Martínez-Orgado, J. A., & Romero, J. (2009). The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages. Brain Research, 1283, 148-154. doi:https://doi.org/10.1016/j.brainres.2009.05.098
  97. Touw, M. (1981). The Religious and Medicinal Uses of Cannabis in China, India and Tibet. Journal of Psychoactive Drugs, 13(1), 23-34. doi:10.1080/02791072.1981.10471447
  98. Ungerleider, J. T., Andyrsiak, T., Fairbanks, L., Ellison, G. W., & Myers, L. W. (1987). Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse, 7(1), 39-50. doi:10.1300/j251v07n01_04
  99. Van Sickle, M. D., Duncan, M., Kingsley, P. J., Mouihate, A., Urbani, P., Mackie, K.,. Sharkey, K. A. (2005). Identification and Functional Characterization of Brainstem Cannabinoid CB 2 Receptors. Science, 310(5746), 329-332. doi:10.1126/science.1115740
  100. Vara, D., Salazar, M., Olea-Herrero, N., Guzmán, M., Velasco, G., & Díaz-Laviada, I. (2011). Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ, 18(7), 1099-1111. doi:10.1038/cdd.2011.32
  101. Wade, D. T., 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. Multiple Sclerosis Journal, 10(4), 434-441. doi:10.1191/1352458504ms1082oa
  102. Wallace, M. J., Blair, R. E., Falenski, K. W., Martin, B. R., & DeLorenzo, R. J. (2003). The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy. Journal of Pharmacology and Experimental Therapeutics, 307(1), 129. doi:10.1124/jpet.103.051920
  103. Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J., Bentley, H., Gouaux, B., & Fishman, S. (2008). A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. The journal of pain: official journal of the American Pain Society, 9(6), 506-521. doi:10.1016/j.jpain.2007.12.010
  104. Wu, J., Bie, B., Yang, H., Xu, J. J., Brown, D. L., & Naguib, M. (2013). Activation of the CB2 receptor system reverses amyloid-induced memory deficiency. Neurobiology of Aging, 34(3), 791-804. doi:https://doi.org/10.1016/j.neurobiolaging.2012.06.011
  105. Wu, X., Han, L., Zhang, X., Li, L., Jiang, C., Qiu, Y.,. Fu, J. (2012). Alteration of endocannabinoid system in human gliomas. Journal of Neurochemistry, 120(5), 842-849. doi:https://doi.org/10.1111/j.1471-4159.2011.07625.x
  106. Xu, D., Wang, J., Zhou, Z., He, Z., & Zhao, Q. (2015). Cannabinoid WIN55, 212-2 induces cell cycle arrest and inhibits the proliferation and migration of human BEL7402 hepatocellular carcinoma cells Corrigendum in /mmr/13/1/1054. Mol Med Rep, 12(6), 7963-7970. doi:10.3892/mmr.2015.4477
  107. Zajicek, J. P., Hobart, J. C., Slade, A., Barnes, D., & Mattison, P. G. (2012). MUltiple Sclerosis and Extract of Cannabis: results of the MUSEC trial. Journal of Neurology, Neurosurgery & Psychiatry, 83(11), 1125. doi:10.1136/jnnp-2012-302468
  108. Zuardi, A. W. (2006). History of cannabis as a medicine: a review. Brazilian Journal of Psychiatry, 28, 153-157. Retrieved from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462006000200015&nrm=iso
  109. Zuardi, A. W., Morais, S. L., Guimarães, F. S., & Mechoulam, R. (1995). Antipsychotic effect of cannabidiol. J Clin Psychiatry, 56(10), 485-486.
  110. Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H., Reda, H., Press, S.,. Petersen, K. L. (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology, 68(7), 515-521. doi:10.1212/01.wnl.0000253187.66183.9c
  111. Benito, C., Romero, J. P., Tolón, R. M., Clemente, D., Docagne, F., Hillard, C. J.,. Romero, J. (2007). Cannabinoid CB 1 and CB 2 Receptors and Fatty Acid Amide Hydrolase Are Specific Markers of Plaque Cell Subtypes in Human Multiple Sclerosis. The Journal of Neuroscience, 27(9), 2396. doi:10.1523/JNEUROSCI.4814-06.2007
  112. Bridgeman, M. B., & Abazia, D. T. (2017). Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P & T: a peer-reviewed journal for formulary management, 42(3), 180-188. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28250701
  113. Caffarel, M. M., Andradas, C., Mira, E., Pérez-Gómez, E., Cerutti, C., Moreno-Bueno, G.,. Sánchez, C. (2010). Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol Cancer, 9, 196. doi:10.1186/1476-4598-9-196
  114. Chung, S. C., Hammarsten, P., Josefsson, A., Stattin, P., Granfors, T., Egevad, L.,. Fowler, C. J. (2009). A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer. Eur J Cancer, 45(1), 174-182. doi:10.1016/j.ejca.2008.10.010
  115. Collin, C., Ehler, E., Waberzinek, G., Alsindi, Z., Davies, P., Powell, K.,. Ambler, Z. (2010). A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurological Research, 32(5), 451-459. doi:10.1179/016164109X12590518685660
  116. Consroe, P., Laguna, J., Allender, J., Snider, S., Stern, L., Sandyk, R.,. Schram, K. (1991). Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacol Biochem Behav, 40(3), 701-708. doi:10.1016/0091-3057(91)90386-g
  117. DeMorrow, S., Francis, H., Gaudio, E., Venter, J., Franchitto, A., Kopriva, S.,. Alpini, G. (2008). The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway. American journal of physiology. Gastrointestinal and liver physiology, 295(6), G1150-G1158. doi:10.1152/ajpgi.90455.2008
  118. Ellis, R. J., Toperoff, W., Vaida, F., van den Brande, G., Gonzales, J., Gouaux, B.,. Atkinson, J. H. (2009). Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology, 34(3), 672-680. doi:10.1038/npp.2008.120
  119. Esposito, G., Scuderi, C., Savani, C., Steardo Jr, L., De Filippis, D., Cottone, P.,. Steardo, L. (2007). Cannabidiol in vivo blunts β-amyloid induced neuroinflammation by suppressing IL-1β and iNOS expression. British journal of pharmacology, 151(8), 1272-1279. doi:https://doi.org/10.1038/sj.bjp.0707337
  120. Fitzcharles, M. A., Ste-Marie, P. A., Häuser, W., Clauw, D. J., Jamal, S., Karsh, J.,. Walsh, Z. (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. doi:10.1002/acr.22727
  121. Fowler, C. J., Jonsson, K. O., Andersson, A., Juntunen, J., Järvinen, T., Vandevoorde, S.,. Smart, D. (2003). Inhibition of C6 glioma cell proliferation by anandamide, 1-arachidonoylglycerol, and by a water soluble phosphate ester of anandamide: variability in response and involvement of arachidonic acid. Biochem Pharmacol, 66(5), 757-767. doi:10.1016/s0006-2952(03)00392-7
  122. Gofshteyn, J. S., Wilfong, A., Devinsky, O., Bluvstein, J., Charuta, J., Ciliberto, M. A.,. Marsh, E. D. (2017). Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases. Journal of Child Neurology, 32(1), 35-40. doi:10.1177/0883073816669450
  123. Hussain, S. A., Zhou, R., Jacobson, C., Weng, J., Cheng, E., Lay, J.,. Sankar, R. (2015). Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox–Gastaut syndrome. Epilepsy & Behavior, 47, 138-141. doi:https://doi.org/10.1016/j.yebeh.2015.04.009
  124. Killestein, J., Hoogervorst, E. L., Reif, M., Kalkers, N. F., Van Loenen, A. C., Staats, P. G.,. Polman, C. H. (2002). Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology, 58(9), 1404-1407. doi:10.1212/wnl.58.9.1404
  125. Koppel, J., Vingtdeux, V., Marambaud, P., d’Abramo, C., Jimenez, H., Stauber, M.,. Davies, P. (2014). CB2 Receptor Deficiency Increases Amyloid Pathology and Alters Tau Processing in a Transgenic Mouse Model of Alzheimer’s Disease. Molecular Medicine, 20(1), 29-36. doi:10.2119/molmed.2013.00140.revised
  126. Ligresti, A., Moriello, A. S., Starowicz, K., Matias, I., Pisanti, S., De Petrocellis, L.,. 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(3), 1375-1387. doi:10.1124/jpet.106.105247
  127. López-Sendón Moreno, J. L., García Caldentey, J., Trigo Cubillo, P., Ruiz Romero, C., García Ribas, G., Alonso Arias, M. A. A.,. García de Yébenes Prous, J. (2016). A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease. Journal of Neurology, 263(7), 1390-1400. doi:10.1007/s00415-016-8145-9
  128. Ma, C., Wu, T.-T., Jiang, P.-C., Li, Z.-Q., Chen, X.-J., Fu, K.,. Gong, R. (2016). Anti-carcinogenic activity of anandamide on human glioma in vitro and in vivo. Molecular medicine reports, 13(2), 1558-1562. doi:10.3892/mmr.2015.4721
  129. ONAIVI, E. S., ISHIGURO, H., GONG, J.-P., PATEL, S., PERCHUK, A., MEOZZI, P. A.,. UHL, G. R. (2006). Discovery of the Presence and Functional Expression of Cannabinoid CB2 Receptors in Brain. Annals of the New York Academy of Sciences, 1074(1), 514-536. doi:https://doi.org/10.1196/annals.1369.052
  130. Orellana-Serradell, O., Poblete, C. E., Sanchez, C., Castellón, E. A., Gallegos, I., Huidobro, C.,. Contreras, H. R. (2015). Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncol Rep, 33(4), 1599-1608. doi:10.3892/or.2015.3746
  131. Polito, S., MacDonald, T., Romanick, M., Jupp, J., Wiernikowski, J., Vennettilli, A.,. Dupuis, L. L. (2018). Safety and efficacy of nabilone for acute chemotherapy-induced vomiting prophylaxis in pediatric patients: A multicenter, retrospective review. Pediatr Blood Cancer, 65(12), e27374. doi:10.1002/pbc.27374
  132. Sánchez, C., de Ceballos, M. L., Gomez del Pulgar, T., Rueda, D., Corbacho, C., Velasco, G.,. Guzmán, M. (2001). Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res, 61(15), 5784-5789.
  133. Schley, M., Ständer, S., Kerner, J., Vajkoczy, P., Schüpfer, G., Dusch, M.,. Konrad, C. (2009). Predominant CB2 receptor expression in endothelial cells of glioblastoma in humans. Brain Res Bull, 79(5), 333-337. doi:10.1016/j.brainresbull.2009.01.011
  134. Suraev, A., Lintzeris, N., Stuart, J., Kevin, R. C., Blackburn, R., Richards, E.,. McGregor, I. S. (2018). Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community. Scientific Reports, 8(1), 10154. doi:10.1038/s41598-018-28127-0
  135. Van Sickle, M. D., Duncan, M., Kingsley, P. J., Mouihate, A., Urbani, P., Mackie, K.,. Sharkey, K. A. (2005). Identification and Functional Characterization of Brainstem Cannabinoid CB 2 Receptors. Science, 310(5746), 329-332. doi:10.1126/science.1115740
  136. Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J., Bentley, H., Gouaux, B., & Fishman, S. (2008). A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. The journal of pain: official journal of the American Pain Society, 9(6), 506-521. doi:10.1016/j.jpain.2007.12.010
  137. Wu, X., Han, L., Zhang, X., Li, L., Jiang, C., Qiu, Y.,. Fu, J. (2012). Alteration of endocannabinoid system in human gliomas. Journal of Neurochemistry, 120(5), 842-849. doi:https://doi.org/10.1111/j.1471-4159.2011.07625.x