Cannabinoids withdrawal

Lichtman et al. 2001 Tzavaraet al. 2000). A dog model of precipitated cannabinoid withdrawal, which includes increased salivation, vomiting, diarrhea, restless behavior, and trembling, has also been described (Lichtman et al. 1998). 

Cornelius JR, Salloum IM, EhlerJG, et al Fluoxetine in depressed alcoholics a doubleblind, placebo-controlled trial. Arch Gen Psychiatry 54 700—705, 1997 Cornelius JR, Salloum IM, Haskett RF, et al Fluoxetine versus placebo for the marijuana use of depressed alcoholics. Addict Behav 24 111—114, 1999 Cui S-S, Bowen RC, Gu G-B, et al Prevention of cannabinoid withdrawal syndrome by lithium involvement of oxytocinergic neuronal activation. J Neurosci 21 9867— 9876, 2001... 

Tzavara ET, Valjent E, Firmo C, et al Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum. Eur J Neuroscience 12 1038-1046, 2000... 

Diana M, Melis M, Muntoni AL, Gessa GL. (1998b). Mesolimbic dopaminergic decline after cannabinoid withdrawal. Proc Natl Acad Sci USA. Aug. 18 95(17) 10269-73. 

Rodriguez de Fonseca F, Carrera MRA, Navarro M, Koob GF, Weiss F. (1997). Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science. 

Gadzicki, D., K. R. Muller-Vahl, D. Heller, et al. Tourette syndrome is not caused by mutations in the central cannabinoid receptor (CNRl) gene. Am J Med Genet 2004 127B(1) 97-103. Oliva, ]. M., S. Ortiz, T. Palomo, and ]. Manzanares. Spontaneous cannabinoid withdrawal produces a differential time-related responsiveness in cannabinoid GBl receptor gene expression in the mouse brain. J Psychopharmacol 2004 18(1) 59-65. 

Rubino T, Patrini G, Massi P, Fuzio D, Vigano D, Giagnoni G, Parolaro D. Cannabinoid-precipitated withdrawal a time-course study of the behavioral aspect and its correlation with cannabinoid receptors and G protein expression. J Pharmacol Exp Ther 1998 285(2) 813-9. Rodriguez de Fonseca F, Carrera MR, Navarro M, Koob GF, Weiss F. Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 1997 276(5321) 2050 1. 

Valverde O, Maldonado R, Valjent E, Zimmer AM, Zimmer A. Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-out mice. J Neurosci 2000 20(24) 9284-9. 

Lichtman AH, Fisher J, Martin BR. Precipitated cannabinoid withdrawal is reversed by A(9)-tetrahydrocannabinol or clonidine. Pharmacol Biochem Behav 2001 69(1-2) 181-8. 

Behavioural and neurochemical studies have now clarified the controversy about the abuse liability of cannabinoids by demonstrating that such drugs fulfil most of the common features attributed to compounds with reinforcing properties. Cannabinoid rewarding properties have been identified using intracranial selfstimulation, conditioned place preference and intravenous self-administration paradigms. Furthermore, a cannabinoid withdrawal syndrome has also been characterized in different animal species (Lichtman and Martin 2002 Maldonado and Rodriguez de Fonseca 2002). 

Castane A, Robledo P, Matifas A, Kieffer BL, Maldonado R (2003) Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice. Eur J Neurosci 17 155-159... 

Investigation of Cannabinoid Withdrawal in Laboratory Animal Models. . . 700... 

Although it has been contended that further controlled research is needed to diagnose a withdrawal syndrome in human marijuana users (Smith 2002), criteria for cannabinoid withdrawal have been proposed (Budney et al. 2003). Moreover, converging lines of evidence from retrospective, outpatient, and inpatient stud-... 

Functional evidence also suggests that the adenylyl cyclase second messenger cascade in the cerebellum may be involved in cannabinoid withdrawal. An intrac-erebellar infusion of the cAMP blocker Rp-8Br-cAMPs reduced several behavioral... 

Currently, oral THC appears to be the best candidate agent to treat marijuana dependence. Of significance, THC was also shown to ameliorate withdrawal symptoms in both monkeys and mice (Beardsley et al. 1986 Lichtman et al. 2001a). However, none of the other agents listed in Table 1 has been evaluated in preclinical models of cannabinoid withdrawal. Thus, it will be important to establish whether the various animal models of cannabinoid dependence are relevant to marijuana-dependent humans. Clearly, the availability of a viable animal model could facilitate the development of effective pharmacotherapies to treat cannabis dependence. 

Oliva JM, Ortiz S, Palomo T, Manzanares J (2004) Spontaneous cannabinoid withdrawal produces a differential time-related responsiveness in cannabinoid CBl receptor gene expression in the mouse brain. J Psychopharmacol 18 59-65... 

Oliva, J.M., Ortiz, S., Palomo, T., Manzanares, J. (2003) Behavioral and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice. J. Neurochem. 85, 94-104. 

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