Effects of opioids

A dramatically different pattern is found in surveys of drug abuse treatment facilities. Substance abuse treatment centers have reported that more than 20% of patients use benzodiazepines weekly or more frequently, with 30%— 90% of opioid abusers reporting illicit use (Iguchi et al. 1993 Stitzer et al 1981). Methadone clinics reported that high proportions ofurine samples are positive for benzodiazepines (Darke et al. 2003 Dinwiddle et al. 1996 Ross and Darke 2000 Seivewright 2001 Strain et al. 1991 Williams et al. 1996). The reasons for the high rates of benzodiazepine use in opioid addicts include self-medication of insomnia, anxiety, and withdrawal symptoms, as well as attempts to boost the euphoric effects of opioids. 

Since initial studies identified opioid receptors on T-lymphocytes (Wybran et al. 1979), the effects of opioids on immune function have been extensively studied. Details of these studies have been exhaustively reviewed (Madden et al. 1991 Adler et al. 1993 Peterson et al. 1998 Donahoe and Vlahov 1998 Roy et al. 2006), and will only be briefly mentioned here. In general, opioids suppress immune function. Peripheral leukocytes, including lymphocytes and peripheral blood mononuclear cells (PBMCs) can express the four major opioid receptor types, MOP, DOP, KOP,... 

Finally, there is little or no clinical evidence that morphine causes psychological dependence or drug-seeking behaviour, tolerance or problematic respiratory depression in patients. These events simply do not occur when opioids are used to control pain. The reason is likely to be that the actions of morphine and the context of its use in a person in pain are neurobiologically quite different from the effects of opioids in street use. These actions of opioids are described in more detail in Chapter 23. 

The mechanisms of pain and the ability to control pain may vary in different pain states. This is of particular importance in consideration of a rational basis for the treatment of both inflammatory and neuropathic pain where the damage to tissue and nerve leads to alterations in both the peripheral and central mechanisms of pain signalling. In respect of existing drug therapies, this plasticity, the ability of the system to change in the face of a particular pain syndrome, explains the effectiveness of NSAIDs in inflammatory conditions and yet is also responsible for some of the limitations in the effectiveness of opioids in neuropathic pain. 

Holtzman, S.G. Phencyclidine-1ike discriminative effects of opioids in the rat. J Pharmacol Fxp Ther 214 614-619, 1980. 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Treating adverse effects of opioids is part of pain management... 

B3. Barbarion, A., de Marinis, L Tofani, A., Casa, S. D D Amico, C., Mancini, A., Corsello, S. M Sciuto, R, and Barini, A., Corticotropin-releasing hormone inhibition of gonadotropin release and the effect of opioid blockade. J. Clin. Endocrinol, Metab. 68,523-528 (1989). 

Marien, M., Brien, J., and Jhamandas, K., Regional release of [3H]dopamine from rat brain in vitro effects of opioids on release induced by potassium nicotine, and L-glutamic acid, Can. J. Physiol. Pharmacol., 61, 43, 1983. 

Spanagel R., Herz A., Shippenberg T. The effects of opioid peptides on dopamine release in the nucleus accumbens an in vivo microdialysis study. J. Neurochem. 55 1734, 1990. 

Smart D, Lambert DG. The stimulatory effects of opioids and their possible role in the development of tolerance. Trends Pharmacol Sci 1996 17 264—269. 

Several investigators have shown that many of the physiological and behavioral effects of opioids can be conditioned. For example, environmental stimuli that have been paired with morphine administration can elicit morphine-like effects, such as hyperthermia, when presented in the absence of morphine [76-79], In line with these studies, our laboratory provided the first demonstration that alterations of immune status can be conditioned to environmental stimuli that have been paired with morphine administration [80-82], In that investigation, rats received subcutaneous injections of morphine in a distinctive environment. When rats subsequently were re-exposed to the distinctive... 

Shippenberg, T. S., Bals-Kubik, R., and Herz, A., Examination of the neurochemical substrates mediating the motivational effects of opioids Role of the mesolimbic dopamine system and D-l vs. D-2 dopamine receptors, J. Pharmacol. Exp. Ther., 265, 53, 1993. 

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