As to the biologic basis of addiction and physical dependence, our understanding is still very limited. Experiments in animals have provided insights into the neurotransmitter and neuronal systems involved. As a result of microdialyzing opiates and their antagonists into the central brain structures of animals, it has been tentatively concluded that mesolimbic structures, particularly the nucleus accumbens, ventral tegmentum of the midbrain, and locus ceruleus are activated or depressed under conditions of repeated opiate exposure. Thus, chronic opiate usage increases the levels of intracellular messengers (G-proteins) as noted earlier that drive cAMP activity in the locus ceruleus and in the nucleus accumbens; blocking the expression of these proteins markedly increases the self-administration of opiates by addicted rats. As in alcoholism, certain subtypes of the serotonin and dopamine receptors in limbic structures have been implicated in the psychic aspects of addiction and habituation. These same structures are conceived as a common pathway for the impulse to human drives such as sex, hunger, and psychic fulfillment. Camí and Farré reviewed the neurochemical mechanism of addiction.
The diagnosis of addiction is usually made when the patient admits to using and needing drugs. Should the patient conceal this fact, one relies on collateral evidence such as miosis, needle marks, emaciation, abscess scars, or chemical analyses. Meperidine addicts are likely to have dilated pupils and twitching of muscles. The finding of morphine or opiate derivatives (heroin is excreted as morphine) in the urine is confirmatory evidence that the patient has taken or has been given a dose of such drugs within 24 h of the test. The diagnosis of opiate addiction is also at once apparent when the treatment of acute opiate intoxication precipitates a characteristic abstinence syndrome.
Treatment of the Opioid Abstinence Syndrome
Views on the nature of drug addiction and appropriate methods of treatment are as much national and sociologic as they are biologic. One approach that has achieved some degree of success over the past 40 years has been the substitution of methadone for opioid, in the ratio of 1 mg methadone for 3 mg morphine, 1 mg heroin, or 20 mg meperidine. Because methadone is long acting and effective orally, it needs to be given only twice daily by mouth—10 to 20 mg per dose being sufficient to suppress abstinence symptoms. After a stabilization period of 3 to 5 days, this dosage of methadone is reduced and the drug is withdrawn over a similar period. An alternative but probably less effective method has been the use of clonidine (0.2 to 0.6 mg bid for a week), a drug that counteracts most of the noradrenergic withdrawal symptoms; however, the hypotension that is induced by this drug may be a problem (Jasinski et al).
In Europe, addicts who could not be detoxified and kept free of drugs by any other means have been given diacetylmorphine, the active ingredient in heroin, with some success when compared in clinical trials to methadone (see Oviedo-Joekes et al). Special settings that are capable of medical reversal of overdose are required but the notion of overall reduction in personal and societal harm seems to be attained by even this seemingly extreme measure.