Opiates endogenous opioids

Similar to endogenous opioids, opiates like morphine and other synthetic opioids activate G-protein-coupled receptors which couple to G-proteins of the Gi/0 family. 

When Montgomery and I published our article, we thought we had disproven another theory of placebo effects - the theory that placebo effects are produced by the release of endorphins in the brain. In 1978 researchers at the University of California in San Francisco discovered that when placebos reduce pain, they may stimulate the release of endorphins.18 Endorphins, the existence of which had only been discovered a few years earlier, are opioids that are produced naturally by the brain. Just like the opiates that are derived from opium - morphine and codeine, for example - endorphins reduce the sensation of pain. The University of California researchers reasoned that if placebos can mimic the effects of opiate drugs, maybe they do so by stimulating the release of the brain s endogenous opioids. 

Upregulation of the cyclic AMP pathway is one mechanism underlying opiate addiction. The mechanisms by which opiates induce tolerance, dependence and withdrawal in specific target neurons has been a major focus of research for many years. The inability to account for prominent aspects of opiate addiction solely on the basis of alterations in endogenous opioid peptides or in opiate receptors has shifted attention to postreceptor mechanisms [66]. 

The body modulates pain through several processes. The endogenous opiate system consists of neurotransmitters (e.g., enkephalins, dynorphins, and /1-endorphins) and receptors (e.g., fl, S, k) that are found throughout the CNS. Endogenous opioids bind to opioid receptors and modulate the transmission of pain impulses. 

Nicotine injection immediately reverses somatically expressed nicotine withdrawal syndrome (Malin et al. 1992), but it fails to do so after pretreatment with naloxone to block opiate receptors (Malin et al. 1996a). This suggests that nicotine relieves this aspect of nicotine withdrawal syndrome through inducing renewed release of endogenous opioid peptides. 

Birdsall, N.J.M., Hulme, E.C., Bradbury, A.F., Smyth, O.G. and Snell, C.R., Opiates and Endogenous Opioid Peptides, 1976, Elsevier/North-Holland Biomedical Press, Amsterdam, p. 19. 

Gillberg, C. (1995) Endogenous opioids and opiate antagonists in autism brief review of empirical findings and implications for clinicians. Dev Med Child Neurol 37 239-245. 

The part played by endogenous opioid systems in the regulation of these various physiological and behavioral functions has led to the experimental application of opiate antagonists in psychiatric disorders. This chapter focuses on autism and self-injury, which are two potential indications for opiate antagonists in pediatric populations. In adults, treatment with opiate antagonists has shown to be useful in the relapse prevention of alcoholism as part of a comprehensive treatment approach (Anton et ah, 1999, 2001). 

There are two main hypotheses about the involvement of endogenous opioid systems in the maintenance of self-injurious behaviors (Sandman, 1988 Buitelaar, 1993). The pain hypothesis suggests that in some subjects self-injury does not induce pain because excessive basal activity of opioid systems in the CNS has led to an opioid analgesic state. The addiction hypothesis posits that particularly repetitive and stereotyped forms of self-injury stimulate the production and release of en-dogeneous opioids. Therefore, chronic maintenance of self-injury may be due to addiction to endogenous opioids or to positive reinforcement by a central release of opioids triggered by the self-injurious behavior. Irrespective of which hypothesis one favors, treatment with opiate antagonists seems to be a rational approach. 

BLTG. Endogenous Opioids. Available online at http //www.opioids.com/ opiates.html. Accessed June 2, 2006. 

Endogenous opioid peptides. Extensive processing is also involved in formation of analgesic opioid peptides, which are present naturally in the brain (see also Section B). Tire formation of (1-endorphin in the hypothalamus from prepro-opiomelanocortin (Fig. 30-2) has already been mentioned. Prior to the discovery of P-endorphin, the pentapeptides Met-enkephalin and Leu-enkephalin (Table 30-4) were discovered and were found to compete with opiate drugs for receptors in the brain. Tire larger P-endorphin, which contains the Met-enkephalin sequence at its N terminus, is a far more potent opiate antagonist than are the enkephalins. Since the Met-enkephalin sequence within P-endorphin is not flanked by basic residues, it apparently is normally not released. Two other recently discovered brain peptides are endomorphin-1 (YPWF-NH2) and endomorphin-2 (YPFF-NH2). They are also potent agonists for the opioid receptors, especially the p receptor (see Section B,10).,61a,61b... 

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

Opioids are known to alter mood states. For example, opiates such as morphine produce euphoria and pain relief. Prolonged use of and withdrawal from opiates produce depressive-like symptoms as well. Based on the mood-altering effects of opiates, the role of endogenous opiates in psychiatric symptoms of various diseases has been studied. In addition, endogenous opioids are believed to play a role in neuronal circuitry responsible for reward and pleasure. Therefore, it is thought that perhaps the anhedonia observed in depressed patients is due to dysregulation of endogenous opioids in neuronal reward circuitry. 

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