Uso terapéutico de los cannabinoides

Autores/as

  • Marta Durán Delmàs Médico adjunto de la Fundación Institut Català de Farmacología. Hospitals Vall d’Hebron. Enviar correspondencia a: Marta Duran Delmàs. Fundació Institut Català de Farmacologia. Escola d’infermeria 3er Piso. Servicio de Farmacología Clínica. Hospitals Vall d’Hebron. Pg Vall d’Hebron 119-129. Barcelona 08035. Tel: 93.4283029. Fax: 93. 4894109.
  • Dolors Capellà Hereu Profesora titular de Farmacología Toxicología y Terapéutica. Universidad Autónoma de Barcelona.

DOI:

https://doi.org/10.20882/adicciones.412

Palabras clave:

sistema cannabinoide, cannabis, cannabinoides, dolor, espasticidad, nauseas, vómitos, eficacia, efectos indeseados, revisión

Resumen

Actualmente hay dos cannabinoides comercializados en algunos países para uso terapéutico. El dronabinol o D9tetrahidrocannabinol (THC) y su análogo babilona para el tratamiento de las náuseas y vómitos secundarios a la quimioterapia antineoplásica que no responde a los tratamientos habituales; pero su lugar en terapéutica como antieméticos ha sido cuestionado porque no se dispone de ensayos clínicos comparativos con los tratamientos de referencia (inhibidores de la serotonina). El dronabinol también está aprobado en algunos países para el síndrome de anorexiacaquexia de pacientes con sida. Aunque la investigación preclínica actual tiende a desarrollar nuevos fármacos que interactúen con el sistema cannabinoide, la investigación clínica se está realizando sobretodo con THC y extractos estandarizados de cannabis (que contienen mayoritariamente THC y cannabidiol). Empiezan a acumularse pruebas clínicas que sugieren que los cannabinoides podrían ser eficaces en el tratamiento sintomático del dolor neuropático, la esclerosis múltiple (EM) y en la mejoría de los tics del síndrome de Gilles de la Tourette y determinadas discinesias, sin embargo, habrá que esperar los resultados de los estudios en curso para llegar a conclusiones mejor fundamentadas. En relación al tratamiento sintomático de la EM, los cannabinoides no han mostrado eficacia antiespástica según > variables objetivas, sin embargo algunos datos informan de que puede mejorar la sensación subjetiva de rigidez, el dolor y la calidad del sueño de estos pacientes a la espera de que nuevos ensayos clínicos lo confirmen.

Citas

Duran M, Laporte JR, Capellà D. Novedades sobre las potencialidades terapéuticas del Cannabis y el sistema cannabinoide. Med Clin (Barc) 2004; 122; 390-8.

Anónimo. GW Pharma looks for cannabis partner. Scrip 2003;2818:8.

Institute For Clinical Research [formato electrónico] 2003; 1 (1): Disponible en:http://www.ikf-berlin.de [consultado 20-5-04]

Fundació Institut Català de Farmacología. Duran M, Laporte JR, Capellà D. Ús terapèutic del cannabis i els seus derivats 2003. Barcelona: Departament de Sanitat i Seguretat Social de la Generalitat de Catalunya, 2003.

Duran M, Capellà D. Novetats sobre l’ús terapèutic dels cannabinoides. BIT 2003; 15: 39-42.

Ozyurt E, Graham DI, Woodruff GN, McCulloch J. Protective effect of the glutamate antagonist, MK-801 in focal cerebral ischemia in the cat. J Cereb Blood Flow Metab 1988;8:138-43.

Costa B, Conti S, Giagnomi G, Colleoni M. The nonpsychoactive

cannabis constituent cannabidiol as anti-inflammatory drug in animal model in acute inflammation. Program and abstracts of the 12th Annual Symposium on the Cannabinoids [formato electrónico] 2002; 165 (44) Disponible en: http://www.cannabinoidsociety.org/ [consultado 06-05-04]:

Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andrakos E, Mechoulam, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA 2000;97:9561-6.

Massi P, Vaccani A, Sacerdote P, Parolano D. Effects of cannabidiol, a non psychoactive constituent of marijuana, on immune system. Program and abstracts of the 12th Annual Symposium on the Cannabinoids [formato electrónico] 2002; 165 (43). Disponible en: http://www.cannabinoidsociety.org/ [consultado 06-05-03].

Parker AL, Mechoulam R, Schlievert C. Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport 2002;13:567-70.

Onaivi ES, Green MR, Martin BR. Pharmacological characterization of cannabinoids in the elevated plus maze. J Pharmacol Exp Ther 1990;253: 1002-9.

Pertwee RG. Pharmacology of CB1 and CB2 receptors. Pharmacol Ther 1997;74:129-80.

Mechoulam R, Ben Shabat S, Hanus L, Fride E, Vogel Z, Bayewitch M, et al. Endogenous cannabinoid ligands—chemical and biological studies. J Lipid Mediat Cell Signal 1996;14:45-9.

Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, et al. 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 2001;98:3662-35.

Porter AC, Felder CC. The endocannabinoid nervous system. Unique opportunities for therapeutic intervention. Pharmacol Ther 2001;90:45-60.

Berdyshev EV. Cannabinoid receptors and the regulation of immune response. Chem Phys Lipids 2000;108:169-90.

Kunos G, Jarai Z, Batkai S, Goparaju SK, Ishac EJ, Liu J, et al. Endocannabinoids as cardiovascular modulators. Chem Phys Lipids 2000;108;159-68.

Paria BC, Dey SK. Ligand-receptor signalling with endocannabinoids in preimplant ation embr yo development and implantation. Chem Phys Lipids 2000;108;211-20.

Piomelli D, Giuffrida A, Calignano A, Rodríguez de Fonseca F. The endocannabinoid system as target for therapeutic drugs. Trends Pharmacol Sci 2000;21:218-24.

Ashton CH. Adverse effects of cannabis and cannabinoids. Br J Anaesth 1999;83:637-49.

Bovasso GB. Cannabis abuse as risk factor for depressive symptoms. Am J Psychiatry 2001;158:2033-37.

Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W. Cannabis use and mental health in young people: cohort study. BMJ 2002; 325:1195-8.

Pope HGJ, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D. Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 2001;58:909-15.

Solowij N, Stephens RS, Roffman RA, Babor T, Kadden R, Miller M, et al. Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA 2002;287:1123-31.

Grant I, Gonzalez R, Carey C, Natarajan L. Longterm neurocognitive consequences of marijuana: a meta-analytic study. A: National Institute on Drug Abuse Workshop on Clinical Consequences of Marijuana [formato electrónico] 2001(1)11. Disponible en http://www.nida.gov/MeetSu/marijuanaabstracts.html. Accessibility [consultado 08-03-03].

Pope HG. Cannabis, cognition and residual confounding. JAMA 2002;287;1172-74.

Van Os J, Bak M, Hanssen M, Bijl RV, de Graaf R, Verdoux H. Cannabis use and psicosis: a longitudinal populationbased study. Am J Epidemiol 2002;156:319-27.

8 . G r o t e n h e r m e n F. P h a r m a c o k i n e t i c s a n d p h a r m a c o d y n a m i c s o f c a n n a b i n o i d s . C l i n Pharmacokinet 2003;42:327-60.

The United Kingdom Parliament House of Lords. Science and Technology. Ninth report on therapeutic uses of cannabis [formato electrónico] 1998. Disponible en: http://www.parliament.the-stationery office.co.uk/pa/Id199798/Idselect/Idsctec /151/15101.htm [consultado 03-05-04].

Institute of Medicine. Marijuana and medicine [formato electrónico] 1999; 196 (196) Disponible en: http://www.bob.nap.edu/books/0309071550/html. [consultado 03-

-03].

Knoller N, Levi L, Shoshan I, Reichenthal E, Razon N, Rappaport ZH, et al. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomised, placebo-controlled, phase II clinical trial. Crit Care Med 2002;30:548-54.

Guzmán M. Cannabinoids: Potential anticancer agents. Nat Rev Cancer 2003;3:745-55.

Musty RE, Rossi R. Effects of smoked cannabis and oral D9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: A review of state clinical trials. J CANT formato electrónico] 2001;1:29-56. Disponible en: http//www.cannabis-med.org/science-international/JCANT.btm. [consultado 30.12.03].

Vicinguerra V, Moore T, Brennan E. Inhalation marijuana as an antiemetic for cancer chemotherapy. NY State Med 1988;88:525-7.

Levitt M, Faiman C, Hawks R, Wilson A. Randomized double blind comparison of delta-9-tetrahydrocannabinol (THC) and marihuana as chemotherapy antiemetics. ASCO Abstracts 1984;3:91.

Chang AE, Shiling DJ, Stillman C, Goldberg NH, Seipp CA, Barofsky I, et al. Delta-9-tetrahydrocannabinol as antiemetic in cancer patients receiving high dose methotrexate. Ann Intern Med 1979;91:819-24.

Tramèr MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting, quantitative systematic review. BMJ 2001;323:16-21.

Morrow GR, Hickok JT, Rosenthal SN. Progress in reducing nausea and emesis. Cancer 1995;76:343-57.

Roscoe JA, Morrow GR, Hickok JT, Stern RM. Nausea and vomiting remain a significant clinical problem: Trends over time in controlling chemotherapy-induced nausea and vomiting in 1413 patients treated in community clinical practices. J Pain Symptom Manage 2000;20:113-21.

Hickok JT, Roscoe JA, Morrow GR, Stern RM, Yang B, Flynn PJ, et al. Use of 5-HT3 receptor antagonists to prevent nausea and emesis caused by chemotherapy for patients with breast carcinoma in community practice settings. Cancer 1999;86:64-71.

Beal JE, Olson R, Laubenstein L, Morales JP, Bellman P, Yangco B, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manag 1995;10:89-97.

Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Sherpard KV, et al. Effect of dronabinol on nutritional status in HIV infection. Ann Pharmacother 1993; 27:827-31.

Timpone JG, Wright DJ, Li N, Egorin MJ, Enama ME, Mayers J, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. AIDS Res Hum Retroviruses 1997;13: 305-15.

Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group Study. J Clin Oncol 2002;15:567-73.

Pacifici R, Zuccaro P, Pichini S, Roset PN, Poudevida S, Farre M i col·ls. Modulation of the immune system in cannabis users. JAMA 2003; 289: 1929-31.

Parolaro D. Presence and functional regulation of cannabinoid receptors in immune cells. Life Sci 1999;65:637-44.

Di Franco MJ, Shepard HW, Hunter DJ. The lack of association of marihuana and other recreational drugs with progression to AIDS in San Francisco Men’s Health Study. Ann Epidemiol 1996;6:283-89.

Whitfield RM, Bechtel LM, Starich GH. The impact of ethanol and Marinol/marijuana usage on HIV+AIDS patients undergoing azidothymidine, azidothymidine/dideoxycytine, or dideoxyinosine therapy. Alcohol Clin Exp Res 1997; 21: 122-27.

Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT et al. Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebocontrolled clinical trial. Ann Intern Med 2003;139:258-66.

Strasser F, Lueftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W et al. Oral cannabis extract versus delta 9-tetrahydrocannabinol for patients with cancer related anorexia: a randomized, double blind placebo controlled multicenter study. Program and abstracts of the IACM 2nd Conference on Cannabinoids in Medicine [formato electrónico] 2003;35(20). Disponible en: http://www.acmed.org/spanish/nav/home-conference.htm [consultado26-5-04].

Campbell FA, Tràmer MR, Carroll D, Reynolds DJM, Moore RA, McQuay HJ. Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review. BMJ 2001;323:13-6.

Baker D, Pryce G, Giovannoni G, Thompson AJ. The therapeutic potential of cannabis. Lancet Neurol 2003;2:291-8.

GW Pharmaceuticals. Research and devolopement [en formato electrónico]. Disponible en: www.gwpharm.com/corp_glan-phas-3.html [consultado 27-5-04].

Abrams DI, Jay C, Petersen K, Shade S, Vizoso H, Reda H et al. The effects of smoked cannabis in painful peripheral neuropathy and cancer pain refractory to opioids. Program and abstracts of the 2nd conference on Cannabinoids in Medicine [en formato electrónico] 2003. Disponible en http// www.cannabismed.org/

Meeting/cologne2003/reader.pdf [consultado 26-5-04].

Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain. JAMA 2003; 290:1757-62.

Notcutt W, Prince M, Chapman G. Clinical experience with nabilone for chronic pain. Pharmaceut Sci 1997;3:551-5.

Berman J, Lee J, Cooper M, Cannon A,Sach J. Efficacy of two cannabis-based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Anaesthesia 2003;58:936-40.

Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmons S, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘n of 1’ studies. Anaesthesia 2004;59:440-52.

Buggy DJ, Toogood L, Maric S, Sharpe P, Lambert DG, Rowbotham DJ. Lack of analgesic efficacy of oral delta 9-tetrahydrocannabinol in postoperative pain. Pain 2003;106:169-72.

Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol 2001;63:569-611.

Rice ASC. Cannabinoids and pain. Curr Opin Investig Drugs 2001;2:399-414.

Petro DJ, Ellenberger Jr C. Treatment of human spasticity with delta 9-tetrahydrocannabinol. J Clin Pharmacol 1981;21(8-9 Suppl):413S-416S.

Ungerleider JT, Andyrsiak T, Fairbanks L, Ellison GW, Myers LW. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse 1987;7:39-50.

Martyn CN, Illis LS, Thom J. Nabilone in the treatment of multiple sclerosis. Lancet 1995;345:579.

Killestein J, Hoogervorst EL, Reif M, Kalkers NF, Van Loenen AC, Staats PG, et al. Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology 2002;58:1404-7.

Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A et al. Cannabinoids for treatment of spasticity and other symptoms related to múltiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lacet 2003;362:1517-26.

Vaney C, Heinzel-Gutenbrunner M. Efficacy, safety and tolerability of an orally administered cannabis extract in treatment of spasticity in patients with multiple sclerosis: a randomized, double blind, placebocontrolled, crossover study. Multiple Sclerosis

ECTRIMS 2003;9:S14.

Rog D, Young CA. Randomized controlled trial of cannabis-based medicinal extracts in the treatment of neuropatic pain due to multiple sclerosis. Multiple Sclerosis ECTRIMS 2003;9:S25.

Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil 2003;17:21-9.

Greenberg HS, Werness SAS, Pugh JE, Andrus RO, Anderson DJ, Domino EF. Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clin Pharmacol Ther 1994;55:324-8.

Brady CM, Dasgupta P, Wieman OJ, Berkley K, Fowler CJ. Acute and chronic effects of cannabis based medicinal extract on refractory lower urinary tract dysfunction in patients with advanced multiple sclerosis. J Neurol Neurosurg Psych 2002;72:139.

Clifford DB. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann Neurol 1983;13:669-71.

GW Pharmaceuticals. GW announces positive results from each of four phase three clinical trials [en formato electrónico]. Disponible en: http://www.gwpharma.com/news_pres_05_nov_02.html [consultado 26-05-04]:

Shakespeare DT, Young CA, Boggild M. Anti-spasticity agents for multiple sclerosis (Cochrane Review). The Cochrane Library, Issue 4, 2000.

Karler R, Turkanis SA. The cannabinoids as potential antiepileptics. J Clin Pharmacol 1981; 21: 437S-48S.

Consroe P, Laguna J, Allender J, Snider S, Stern L, Sandyk R, et al. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 1991;40:701-08.

Muller-Vahl KR, Schneider U, Prevedel H, Theloe K, Kolbe H, Daldrup T et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry 2003;64:459-65.

Frankel JP, Huges A, Lees AJ. Marijuana for parkinsonian tremor. J Neurol Neurosurg Psychiatry 1990;53:436.

Sieradzan KA, Fox SH, Mill M, Dick JPR, Crossman AR, Brotchie JM. Cannabinoids reduced levodopa induced dyskinesias Parkinson’s disease. A pilot study. Neurology 2001;57:2108-11.

Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 1997;12:913-9.

Ross JS, Shua-Haim JR. Open label study of dronabinol in treatment of refractory agitacion in Alzheimer’s disease: a pilot study. Program and abstracts of 34th Congress of ASCP [en línea] 2003 Novembre 14. EurekAlert [accedido el día 7 de junio de 2004]; 1 (1). URL disponible en http://www.cannabis-med.org/studies/study.php

Hepler RS, Frank IR. Marihuana smoking and intraocular pressure JAMA 1971;217:1392.

Porcella A, Maxia C, Gessa GL, Pani L. The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. Eur J Neurosci 2001;13:409-12.

Tashkin DP, Reiss S, Shapiro BJ, Calvarese B, Olsen JL, Lodge JW. Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy asthmatic subjects. Am Rev Respir Dis 1977;115:57-65.

Fabre LFR, McLendon D. The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. J Clin Pharmacol 1981;21 (Suppl 8-9):377S-82S.

Glass RM, Uhlenhuth EH, Hartel FW. The effects of nabilone, a synthetic cannabinoid on anxious human volunteers. Psychopharmacol Bull 1979;15:88.

Glass RM, Uhlenhuth EH, Hartel FW. Single dose study of nabilone in anxious volunteers. J Clin Pharmacol 1981;21S:383.

Voth EA, Schwartz RH. Medicinal applications of delta 9-tetrahydrocannabinol and marijuana. Ann Intern Med 1997;126:791-8.

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2004-06-15

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