Cannabis – therapy for the future?

Czech version

Authors: Jan Hajer
Authors‘ workplace: II. interní klinika 3. LF UK a FN Královské Vinohrady Praha, přednosta prof. MUDr. Michal Anděl, CSc.
Published in: Vnitř Lék 2015; 61(7-8): 680-685
Category: Vanýsek´s day 2015

Přes veškeré pokroky v léčbě chronických gastrointestinálních onemocnění u části pacientů nedosahuje léčba dlouhodobé optimální efektivity. Proto se řada pacientů uchyluje ke komplementární a alternativní medicíně (complementary and alternative medicine – CAM). Z různých typů CAM je pacienty s GIT onemocněními preferována především homeopatie, akupunktura a v neposlední řadě i fytoterapie, pod kterou lze řadit i léčebné užití Cannabis sativa. Patofyziologická báze terapeutického efektu léčebného konopí není doposud zcela objasněná.

Overview

Despite all the progress achieved in the treatment of chronic gastrointestinal diseases, in some patients the treatment does not reach long-term optimum effectiveness. Therefore a number of patients have turned to complementary and alternative medicine (CAM). Of the different types of CAM patients with GIT diseases tend to prefer in particular homeopathy, acupuncture and not least phytotherapy, where therapeutic use of cannabis may also be included. The pathophysiological basis of therapeutic effect of curative cannabis has not been fully clarified so far. Many scientists in many fields of medicine and pharmacology have been engaged in the study of effects of cannabinoids on the body since the beginning of the 20th century with the interest significantly increasing in the 1980s. The discovery of CB receptors (1988) and endogenous molecules which activate these receptors (1992) led to the discovery of the endocannabinoid system. Pharmacological modulation of the endogenous cannabinoid system offers new therapeutic possibilities of treatment of many illnesses and symptoms including the GIT disorders, including of nausea, vomiting, cachexia, IBS, Crohn’s disease and some other disorders. Cannabinoids are attractive due to their therapeutic potential – they affect a lot of symptoms with minimum side effects. Experience of patients with GIT disorders show that the use of cannabis is effective and helps in cases where the standard therapy fails.

Key words:
cannabis – endocannabinoid system – phytotherapy – complementary alternative medicine (CAM)

Sources

1. Vochyánová Z, Sikorová K, Šmejkal K et al. Rostliny v terapiii diopatických střevních zánětů. Gastroent Hepatol 2014; 68(3): 248–254.

2. Mohamed BA. Cannabinoids in medicine: a review of their therapeutic potential. J Ethnopharmacol 2006; 105(1–2): 1–25.

3. Hawks RL. The constituents of cannabis and the disposition and metabolism of cannabinoids. NIDA Res Monogr 1982; 42: 125–137.

4. Devane WA, Hanus L, Breuer A et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258 (5090): 1946–1949.

5. Wilson RI, Nicoll RA. Endocannabinoid signalling in the brain. Science 2002; 296 (5568): 678–682.

6. Baker D, Pryce G, Giovannoni G et al. The therapeutic potential of cannabis. Lancet Neurol 2003; 2(5): 291–298.

7. Basu S, Ray A, Dittel BN. Cannabinoid Receptor 2 (CB2) is Critical for the Homing and Retention of Marginal Zone B Lineage Cells and for Efficient T-independent Immune Responses. J Immunol 2011; 187(11): 5720–5732.

8. Wright KL, Duncan M, Sharkey KA. Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. Br J Pharmacol 2008; 153(2): 263–270.

9. Pertwee RG. Inverse agonism and neutral antagonism at cannabinoid CB1 receptors. Life Sci 2005; 76(12): 1307–1324.

10. Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr 2008; 30(3): 271–280.

11. Leweke FM, Piomelli D, Pahlisch F et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2012; 2: e94. Dostupné z DOI: <http://dx.doi.org/10.1038/tp.2012.15>.

12. Morgan NH, Stanford IM, Woodhall GL Functional CB2 type cannabinoid receptors at CNS synapses. Neuropharmacology 2009; 57(4): 356–368.

13. Schubart CD, Sommer IEC, van Gastel WA et al. Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr Res 2011; 130(1–3): 216–221.

14. 14 .Mechoulam R. The pharmacohistory of Cannabis sativa. In: Mechoulam R (ed). Cannabinoids as therapeutic agents. CRC Press: Boca Raton 1986, 1–19. ISBN 978–0849357725.

15. Novotna A, Mares J, Ratcliffe S et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex (R), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 2011; 18(2): 1122–1131.

16. Rintala DH, Fiess RN, Tan G et al. Effect of dronabinol on central neuropathic pain after spinal cord injury: a pilot study. Am J Phys Med Rehabil 2010; 89(10): 840–848.

17. Selvarajah D, Gandhi R, Emery CJ et al. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy. Diabetes Care 2010; 33(1): 128–130.

18. Muller-Vahl KR, Schneider U, Koblenz A et al. Treatment of Tourette’s syndrome with Delta 9- tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry 2002; 35(2): 57–61.

19. Collins TR. Special Report: What Neurologists Are Doing About Medical Marijuana. Neurology Today 2014; 14(8): 1, 28–33. Dostupné z WWW: <http://journals.lww.com/neurotodayonline/Citation/2014/04170/Special_Report__What_Neurologists_Are_Doing_About.2.aspx>.

20. Ringen PA, Vaskinn A, Sundet K et al. Opposite relationship between cannabis use and neurocognitive function in bipolar disorder and schizophrenia. Psychol Med 2010; 40(8):1337–1347. Dostupné z DOI: <http://dx.doi.org/10.1017/S0033291709991620>.

21. Bergamaschi MM1, Queiroz RH, Chagas MH et al. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients. Neuropsychopharmacology 2011; 36(6): 1219–1226.

22. Fagherazzi EV1, Garcia VA, Maurmann N et al. Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders. Psychopharmacology (Berl) 2012; 219(4): 1133–1140.

23. Grant JA, Courtemanche J, Rainville P et al. A non-elaborative mental stance and decoupling of executive and pain-related cortices predicts low pain sensitivity in Zen meditators. Pain 2011; 152(1): 150–156.

24. Rubino T, Zamberletti E, Parolaro D et al. Adolescent exposure to cannabis as a risk factor for psychiatric disorders. J Psychopharmacol 2012; 26(1): 177–188.

25. Campos AC, Moreira FA, Gomes FV et al. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R SocLond B BiolSci 2012; 367(1607): 3364–3378.

26. Campbell FA, Tramer MR, Carroll D et al. Are cannabinoids an effective and safe treatment option in the management of pain? BMJ 2001; 323(7303: 13–16.

27. 27.Notcutt W, Price M, Blossfeldt P et al. Clinical experience of the synthetic cannabinoid nabilone for chronic pain. In: Nahas GG, Sutin KM, Harvey D et al(eds.) Marihuana and medicine. Humana Press: Totowa 1999: 567–572. ISBN 978–0896035935.

28. 28.Gieringer D. Review of Human Studies on the Medical Use of Marijuana. Dostupné z WWW: <http://www.safeaccessnow.org/gastrointestinal_disorders>.

29. Izzo AA, Fezza F, Capasso R et al. Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation. Br J Pharmacol 2001; 134(3): 563–570.

30. De Mei C, Ramos M, Iitaka C et al. Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. Curr Opin Pharmacol 2009; 9(1): 53–58.

31. Pertwee RG. Cannabinoids and the gastrointestinal tract. Gut 2001; 48(6): 859–867.

32. Kulkarni-Narla A, Brown DR. Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system. Cell Tissue Res 2000; 302(1):73–80.

33. Greenberg I, Kuehnle J, Mendelson JH et al. Effects of marihuana use on body weight and caloric intake in humans. Psychopharmacology (Berl) 1976; 49(1): 79–84.

34. Foltin R et al. Behavioral analysis of marijuana effects on food intake in humans. Pharmacol Biochem Behav 1986; 25(3): 577–582.

35. Foltin R et al. Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory Appetite 1988; 11(1): 1–14.

36. Beal JE, Olson R, Laubenstein L et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995; 10(2): 89–97.

37. Gonzalez-Rosales F, Walsh D Intractable nausea and vomiting due to gastrointestinal mucosal metastases relieved by tetrahydrocannabinol (dronabinol). J Pain Symptom Manage 1997; 14:311–314.

38. Musty R, Rossi R. Effects of smoked cannabis and oral delta-9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: a review of state clinical trials. Journal of Cannabis Therapeutics 2001; 1(1): 29–56.

39. Partosoedarso ER, Abrahams TP, Scullion RT et al. Cannabinoid 1 receptor in the dorsal vagal complex modulates lower oesophageal sphincter relaxation in ferrets. J Physiol 2003; 550(Pt 1): 149–158.

40. Lehmann A, Blackshaw LA, Brändén L et al. Cannabinoid receptor agonism inhibits transient lower esophageal sphincter relaxations and reflux in dogs. Gastroenterology 2002; 123(4): 1129–1134.

41. Izzo AA, Mascolo N, Pinto L et al. The role of cannabinoid receptors in intestinal motility, defecation and diarrhoea in rats. Eur J Pharmacol 1999; 384(1): 37–42.

42. Mancinelli R, Fabrizi A, Del Monaco S et al. Inhibition of peristaltic activity by cannabinoids in the isolated distal colon of mouse. Life Sci 2001; 69(1):101–111.

43. Singh U, Singh NP, Singh B et al. Role of resveratrol-induced CD11b+ Gr-1+ myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3+ T cells and amelioration of chronic colitis in IL-10−/− mice. Brain Behav Immun 2012; 26(1): 72–82.

44. Schicho R, Storr M Patients with IBD find symptom relief in the Cannabis field. Nat Rev Gastroenterol Hepatol.2014; 11(3): 142–143.

45. Marquéz L, Suárez J, Iglesias M et al. Ulcerative colitis induces changes on the expression of the endocannabinoid system in the human colonic tissue. PLoS One 2009; 4(9): e6893. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0006893>.

46. Di Sabatino A, Battista N, Biancheri P et al. The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease. Mucosal immunol 2011; 4(5): 574–583.

47. Alhouayek M, Muccioli GG. The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends Mol Med 2012; 18(10): 615–625.

48. Capasso R, Borrelli F, Aviello G et al. Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. Br J Pharmacol 2008; 154(5):1001–1008.

49. Naftali T, Lev LB, Yablecovitch D, Half E et al. Treatment of Crohn’s disease with cannabis: an observational study. Isr Med Assoc J 2011; 13(8): 455–458.

50. Naftali T, Bar-Lev Schleider L, Dotan I et al. Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol 2013; 11(10): 1276–1280.

51. Hazekamp A, Ruhaak R, Zuurman L et al. Evaluation of a vaporizing device (Volcano(R)) for the pulmonary administration of tetrahydrocannabinol. J Pharm Sci 2006; 95(6): 1308–1317.