Cannabinoides y conducta adictiva

Autores/as

  • M. Navarro Departamento de Psicobiología. Instituto Universitario de Drogodependencias
  • F. Rodríguez de Fonseca Departamento de Psicobiología. Instituto Universitario de Drogodependencias

DOI:

https://doi.org/10.20882/adicciones.674

Palabras clave:

cannabis, sistema cannabinoide, adicción, dopamina, sistema de recompensa, modelos animales, opiáceos, cerebro, dependencia

Resumen

Los cannabinoides son compuestos psicoactivos presentes en el cannabis y que actúan en el sistema nervioso a través de receptores específicos de membrana, los receptores CB-1. Estos receptores están situados en neuronas de muchos circuitos encefálicos, incluyendo el sistema de recompensa cerebral. Este sistema es clave para entender la conducta adictiva, y de él forman parte las neuronas dopaminérgicas mesotelencefálicas, así como algunas neuronas peptidérgicas de entre las que destacan las neuronas encefalinérgicas. Los cannabinoides, al igual que el resto de las drogas de abuso, activan las neuronas mesotelencefálicas y disminuyen el umbral de recompensa cerebral. Del mismo modo que la cocaína, los opiáceos o el etanol, estos compuestos inducen conductas de autoadministración en animales de experimentación y provocan condicionamiento de lugar preferencial. La administración crónica de cannabinoides provoca tolerancia y dependencia, e induce neuroadaptaciones en el circuito de la recompensa que son idénticas a las inducidas por la principales drogas de abuso y que se pueden poner de manifiesto mediante el cese de la administración de estos compuestos (síndrome de abstinencia comportamental y bioquímico específico). Los cannabinoides actúan sinérgicamente con el sistema opioide endógeno, en especial con el sistema encefalinas-receptor-F -opioide, lo que les permite actuar como factores de vulnerabilidad en el desarrollo de la conducta adictiva. La existencia de una interacción opioide-cannabinoide permitirá abrir nuevas puertas terapéuticas para la adicción a heroína y a etanol. 

Citas

Abood, M.E. y Martin, B.R. (1992) Neurobiology of Marijuana Abuse. T.I.P.S., 13: 201.

Aceto, M.D., Scates, S.M., Lowe, J.A. & Martin, B.R. (1995) Cannabinoid precipitated withdrawal by the selective cannabinoid receptor antagonist, SR 141716A. Eur. J. Pharmacol., 282: R1-R2.

Ambrosio, E., Martin, S., García-Lecumberri, C & Crespo, J.A. (1999) The neurobiology of cannabinoid dependence: Sex differences and potential interactions between cannabinoid and opioid systems. Life Sci., 65(6-6): 687-94.

American Academy of Pediatrics Committee on Substance Abuse (1999) Marijuana: A continuing Continuing Concern for Pediatricians. Pediatrics, 104(4): 982-985.

Andreàsson, S., Allebeck, P., Engström, A. Y Rydberg, V. (1987) Cannabis and Schizophrenia: A longitudinaal study of Swedish conscripts., Lancet, ii: 1483-1486.

Anthony J.C., Warner, L.A., Kessler, R.C. (1994) Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalant: basic findings from the national comorbidity survey. Exp. Clin. Psychopharmacol., 2: 244-268.

Beardsley, P.M., Balster, R.L. & Harris, L.S. (1986) Dependence on thtrahydrocannabinol in Rhesus monkeys. J. Pharmacol. Exp. Ther., 239: 311-319.

Castle, D.J. & Ames, F.R. (1996) Cannabis and the brain. Austr. New Zeal.. J. Psych., 30: 179-183.

Chen, J., Paredes, W., Lowinson, J.H. y Gardner, E.L. (1990) Δ9-Tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex. Eur. J. Pharmacol., 190: 259-262.

Corbett, D. y Wise, R.A. (1980): Intracraneal self-stimulation in relation to the ascending dopaminergic systems of the midbrain: a moveable electrode mapping study. Brain Res, 185:1.

Crowley, T.J., Macdonald, M.J., Whitmore, E.A. & Mikulich, S.K. (1998) Cannabis dependence, withdrawal, and reinforcing effects among adolescents with conduct symptoms and substance use disorders. Drug Alcohol Depend., 50(1): 27-37.

Dewey, W.L. (1986) Cannabinoid Pharmacology. Pharmacol. Rev., 38(2): 151-178.

Diana, M., Melis, M., Muntoni, A.L. & Gessa, G.L. (1998) Mesolimbic dopaminergic decline after cannabinoid withdrawal. Proc. Natl- Acad. Sci., 95: 10269-10273.

Diana, M., Muntoni, A.L., Pistis, M., Melis, Miriam & Gessa, G.L. (1999) Lasting reduction in mesolimbic dopamine neuronal activity after morphine withdrawal. Proc. Natl- Acad. Sci.,11: 1037-1041.

Diana, M., Pistis, M., Carboni, S., Gessa, G.L. & Rossetti, Z.L. (1993) Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: Electrophysiological and biochemical evidence. Proc. Natl. Acad. Sci., U.S.A., 90: 7966-7969.

Emrich, H.M., Leweke, F.M. y Schneider, U. (1997) Towards a Cannabinoid Hypothesis of Schizophrenia: Cognitive Impairments Due to Dysregulation of the Endogenous Cannabinoid System. Pharmacol. Biochem. & Behav., 56(4): 803-807.

Fray, P.J.; Dunnett, S.B.; Iversen, S.D.; Björklund, A. y Stenevi, U. (1983): Nigral transplants reinnervating the dopamine-depleted neostriatum can sustain intracranial self-stimulation. Science, 219: 416.

Fredericks, A.B. y Benowitz, N.L. (1980) An abstinence syndrome following.chronic administration of delta-9-tetrahydrocannabinol in Rhesus monkeys. Psychopharmacology, 71: 201-202

French, E.D. (1997) Δ9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. Neurosci. Lett, 226: 159-162.

Gaoni, Y. y Mechoulam, R. (1964) Isolation, structure elucidation and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc., 86: 1646-1647.

Gardner, E.L. (1997) Brain reward mechanisms. En: Substance Abuse: A Comprehensive Texbook (Eds.: J.H. Lowinson, P. Ruiz, R.B, Millman & J.G. Langrod), 3ª ed. Williams & Wilkins, Baltimore, pág: 51-85.

Gardner, E.L. y Lowinson, J.H. (1991) Marijuana’s Interaction With Brain Reward Systems: Update 1991. Pharmacol. Biochem. & Behav., 40: 571-580.

Gardner E.L. & Vorel, S.R.(1998) Cannabinoid transmission and reward-related events. Neurobiol. Disease, 5: 502-533.

Gueudet, C., Santucci, V., Rinaldi-Carmona, M., Soubrié, P. y Le Fur, G. (1995) The CB1 cannabinoid receptor antagonist SR 141716A affects A9 dopamine neuronal activity in the rat. NeuroReport, 6: 1293-1297.

Jones, R.T., Benowitz, N. & Bachman, J. (1976) Clinical studies of cannabis tolerance and dependence. Ann. N.Y. Acad. Sci., 282: 221-239.

Johnston, L.D., O’Malley, P.M. & Bachman, J.G. (1997) Monitoring the future study: 1975-1995: US Dept Health and Human Services. Washington. D.C.

Hall, W., Solowij, N. & Lemon, J (1994) The health and psychological consequences of cannabis use. Monografía de la serie nº 25. Australian Goverment Publishing Service. Camberra.

Haney, M., Ward, A.S., Comer, S.D., Foltin, R.W & Fischman, M.W. (1999) Abstinence symptons following oral THC administration to humans. Psychopharmacology, 141: 385-394.

Herkenham, M. (1992) Cannabinoid Receptor Localization in Brain: Relati: 491-496on-ship to Motor and Reward Systems. Annu.. New York Acad. Sci., 654: 19-32.

Hine, B., Friedman, E., Torrelio, M. & Gershon, S. (1975) Morphine-dependent rats: Blockade of precipitated abstinence by tetrahydrocannabinol. Science, 187: 443-445.

Hutcheson, D.M., Tzavara, E.T, Smadja, C., Valjent, E., Roques, B.P., Hanoune, J. & Maldonado, R. (1998) Behavioural and biochemical evidence for signs of abstinence in mice chronically treated with Δ-9-tetrahydrocannabinol. Br. J. Pharmacol., 124.

Koob, G.F.; Sanna, P.P. & Bloom, F.E. (1998) Neuroscience of Addiction. Neuron, 21: 467-476.

Kouri, E.M., Pope, H.G(Jr.) & Lukas, S.E. (1999) Changes in aggressive behavior during withdrawal from long-term marijuana use. Psychopharmacology, 143: 302-308.

Laszlo, J., Lucas, V.S., Hanson, D.C., Cronin, C.M. y Sallan, S.E. (1981) Levonantradol for chemotherapy-induced emesis: Phases I-II oral administration. J. Clin. Pharmacol., 21: 51-56.

Ledent, C., Valverde, O., Cossu, G., Petite, F., Aubert, J-F., Beslot, F., Böhme, G.A., Imperato, A., Pedrazzini, T., Roques, B.P., Vassart, G., Fratta, W. y Parmentier, M. (1999) Unresponsiveness to Cannabinoids and Reduced Addictive Effects of Opiates in CB1 Receptor Knockout Mice. Science, 283: 401-404.

Lynn, A.B., Little, M.D., Johnson, M.R., Melvin, L.S., De Costa, B.R. & Rice, K.C. (1990). Cannabinoid receptor localization in brain. Proc. Natl- Acad. Sci., 87: 1932-1936.

Manzanares, J., Corchero, J., Romero, J., Fernández-Ruiz, Ramos, J.A. & Fuentes, J.A. (1999) Pharmacological and biochemical interactions between opioids and cannabinoids. TiPS, 20: 287-294.

Martellotta, M.C., Cossu, G., Fattore, G.L., Gessa, G.L. y Fratta, W. (1998) Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug naive mice. Neuroscience, 85(2): 327-330.

Martín-Calderón, J.L., Muñoz, R.M., Villanúa, M.A, del Arco, I., Moren, J.L., Rodríguez de Fonseca, F. y Navarro, M. (1998) Characterization of the acute endocrine actions of HU-210, a potent synthetic cannabinoid in rats. Eur. J. Pharmacol., 344: 77-86.

Navarro, M., Fernández-Ruiz, J., de Miguel, R., Hernández, M.L., Cebeira, M. y Ramos, J.A. (1993) An acute dose of Δ9-tetrahydrocannabinol affects behavioral and neurochemical indices of mesolimbic dopaminergic activity. Behav. Brain. Res.57: 37-46.

Navarro, M., Hernández, E., Muñoz, R.M., del Arco, I., Villanúa, M.A., Carrera, M.R. y Rodríguez de Fonseca, F. (1997) Acute administration of the CB1 cannabinoid receptor antagonist SR 141716ª induces anxiety-like responses in the rat. NeuroReport, 8.

Noyes, J.R., Brunk, S.F., Avery, D.H. y Canter, A. (1975) The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clin. Pharmacol., Ther., 18: 84-89.

Olds, J. & Milner, P. (1954): Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J. Comp. Physiol. Psychol., 47: 419-27.

Piazza, P.V.; Barrot, M.; Rougè-Pont, F. & al. (1996) Suppression of glucocorticoid secretion and antipsychotic drugs have similar effects on the mesolimbic dopaminergic transmission. Proc. Natl. Acad. Sci. USA, 93: 15445-50.

Piazza, P.V. & Le Moal, M. (1996) Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucorticoids and dopaminergic neurons. Annu. Rev. Pharmacol. Toxicol., 36: 359-78.

Poddar, M.K. y Dewey, W.L. (1980) Effects of Δ9-tetrahydrocannabinol on catecholamines uptake and release in hypothalamic and striatal synaptosomes. J. Pharmacol. Exp. Ther. 221: 97-103.

Pope, H.G. (Jr.), Gruber, A.J. & Yurgelun-Todd, D. (1995) The residual neuropsychological effects of cannabis: the current status of research. Drug Alcohol & Depend., 38: 25-34.

Raft, D., Gregg, J., Ghia, J. Y Harris, L. (1977) Effects of intravenous tegrahydrocannabinol on experimental and surgical pain. Psychological correlate of the analgesic response. Clin. Pharmacol. Ther., 21: 26-33.

Rodríguez de Fonseca, F., Rubio, P., Menzaghi, F., Merlo-Pich, E., Rivier, J., Koob, G.F y Navarro, M. (1996) Corticotropin-Releasing Factor (CRF) Antagonist [D-Phe12, Nle21,38, CαMeLeu37]CRF Attenuates the Acute Actions of the Highly Potent Cannabinoid Receptor Agonist HU-210 on Defensive-Withdrawal Behavior in Rats. J. Pharmacol.Exp. Ther, 276(1): 56-64.

Rubio, P., Rodríguez de Fonseca, F., Muñoz, R.M., Ariznavarreta, C., Martín-Calderón, J.L. & Navarro, M. (1995) Long-term behavioral effects of perinatal exposure to Δ9-tetrahydrocannabinol in rats: Possible role of pituitary-adrenal axis. Life Sci., 56(23/24): 2169-2176.

Salamone, J.D, Aberman, J.E, Sokolowsk, J.D. & Cousins, M.S. Nucleus accumbens dopamine and rate of responding: Neurochemical and behavioral studies. Psychobiology, 27(2): 236-247 (1999).

Seth, R. & Sinha, S. (1991) Chemistry and pharmacology of cannabis. Prog. Drug Res., 36: 71-115.

Schultz, W.; Dayan, P. y Montague, P.R. (1997): A neural substrate for prediction and reward. Science, 275: 1593-9.

Tanda, G, Pontieri, F.E. y Di Chiara, G. (1997) Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common M1 Opioid Receptor Mechanism. Science, 276: 248-250.

Vela, G., Ruiz-Gayo, M & Fuentes, J.A. (1995) Anandamide decreases naloxone-precipitated withdrawal signs in mice chronically treated with morphine. Neuropharmacology, 34: 665-668.

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Publicado

2000-06-15

Número

Vol. 12 (2000): Especial

Sección

Originales