Morphine Withdrawal syndrome

Chesher GB and Jackson DM (1985). The quasi-morphine withdrawal syndrome Effect of cannabinol, cannabidiol and THC. Pharmacology, Biochemistry and Behaviour, 23, 13-15. 

Bongianni, F., Carla, V., Moroni, F., Pellegrini, D. Ca2+-channeI inhibitors prevent morphine withdrawal syndrome in rats, Br. J. Pharmacol. 1985, 86, 529 P. 

Valverde O, Noble F, Beslot F, Dauge V, Fournie-Zaluski MC, Roques BP. A9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins reduction in morphine withdrawal syndrome without change in rewarding effect. Eur J Neurosci 2001 13(9) 1816-24. 

Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester Adams, Michael L. Kalicki, Joelle M. Meyer, Edward R. Cicero,... 

Attenuation of morphine withdrawal syndrome by macromolecular synthesis inhibitors in rats... 

Blasig, J. Hen, A. Reinhold, K. and Zieglgansberger, S. Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33 19-38, 1973. 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Aiicioglu-Kartal F, Kayir H, Tayfun U1 (2003) Effects of harman and harmine on naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Life Sci 73 2363-2371 Balerio GN, Aso E, Berrendero E, Murtra P, Maldonado R (2004) Delta9- tetrahydrocanabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice, Eur J Neurosci 20 2737-2748... 

It is inactive orally because of high first pass metabolism in liver. Metabolised by glucuronidation in liver. The main use of naloxone is in the treatment of acute opioid overdose (acute morphine poisoning). It also precipitates withdrawal syndrome when administered to morphine addicts. The constricted pupils of addicts dilate after administration of naloxone. This has been used as a diagnostic tool for opioid addiction. 

The time of onset, intensity, and duration of abstinence syndrome depend on the drug previously used and may be related to its biologic half-life. With morphine or heroin, withdrawal signs usually start within 6-10 hours after the last dose. Peak effects are seen at 36-48 hours, after which most of the signs and symptoms gradually subside. By 5 days, most of the effects have disappeared, but some may persist for months. In the case of meperidine, the withdrawal syndrome largely subsides within 24 hours, whereas with methadone several days are required to reach the peak of the abstinence syndrome, and it may last as long as 2 weeks. The slower subsidence of methadone effects is associated with a less intense immediate syndrome, and this is the basis for its use in the detoxification of heroin addicts. However, despite the... 

Basilico, L., Parolaro, D., Rubino, T., Gori, E., Giagnoni, G. Influence of co-conotoxin on morphine analgesia and withdrawal syndrome in rats, Eur. J. Pharmacol. 1992, 218, 75-81. 

Although psychic factors are undoubtedly important in determining certain features of the withdrawal syndrome, most signs and symptoms have a physiological basis and represent a fundamental imbalance in the homeostatic adaptive mechanisms of the body, which developed in response to the continued use of morphine. At the height of the syndrome, tolerance is still present, and injection of the dose to which the patient was accustomed will quickly relieve all subjective distress and physical signs and completely restore the person s equanimity. By the time withdrawal symptoms have ceased, tolerance has disappeared. 

Therapeutic uses Methadone is used in the controlled withdrawal of addicts from heroin and morphine. Orally administered, methadone is substituted for the injected opioid. The patient is then slowly weaned from methadone. Methadone causes a milder withdrawal syndrome, which also develops more slowly than that seen during withdrawal from morphine. 

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