Cocaine addiction as a neurological disorder: implications for treatment.

Clinical and preclinical studies provide convincing evidence for persistent neurological/psychiatric impairments and possible neuronal degeneration associated with chronic cocaine/stimulant abuse. These impairments include multifocal and global cerebral ischemia, cerebral hemorrhages, infarctions, optic neuropathy, cerebral atrophy, cognitive impairments, and mood and movement disorders. These findings may encourage the placement of stimulant addiction into the category of organic brain disorders. Functional and microanatomical anomalies in the frontal and temporal cortex as well as other brain regions may be responsible for certain aspects of phenomenology and neuropsychopathology that are characteristic of stimulant polydrug addictions. These may include broad spectrum of deficits in cognition, motivation, and insight; behavioral disinhibition; attention deficits; emotional instability; impulsiveness; aggressiveness; depression; anhedonia; and persistent movement disorders. Although it is still debated whether the hypofrontality and other brain anomalies observed in stimulant abusers are a consequence or an antecedent of drug abuse, this debate seems purely academic and irrelevant with respect to the importance of compensating for these deficits in the development of treatment strategies. The neuropsychiatric impairments accompanying stimulant abuse may contribute to the very high rate of relapse in addicts that can take place after long periods (years) of abstinence. It is possible that the neurological deficits present in stimulant addicts, whether they are primary or secondary to stimulant abuse, are responsible for perpetual drug abuse which may be a form of self-medication (Weiss et al. 1991, 1992). In this context, addiction to stimulants, once fully developed, may represent a true biological dependency on drugs that temporarily compensate for existing neurological deficits. The concept of self-medication by drug addicts is supported by major theories of biological psychiatry. While a majority of drug addicts are polydrug users, there seems to be a preference for a particular type of drug among different populations of addicts. Addicts who experience distress, anxious dysphoria, and turbulent anger prefer the calming actions of opiates, whereas addicts with preceding attention deficit disorder, depression, or bipolar disorder often prefer stimulants (Khantzian 1985). Figure 1 presents conceptual relationships between brain damage and cocaine/stimulant abuse. More clinical studies are needed to establish unequivocally the epidemiological relationships between preexisting neurological deficits-resulting either from genetic, developmental, traumatic, or neurotoxic factors- and vulnerability to drug addictions. Nonetheless, deducing from the results of preclinical studies, it is conceivable that individuals with neurological deficits associated with attention deficit disorder, developmental neuroanatomical abnormalities, lead poisoning, alcoholism, posttraumatic brain lesions, and PTSD may be more vulnerable to stimulant addiction. This notion has significant empirical support as preclinical studies have shown that animals with lesioned prefrontal cortex became supersensitive to cocaine (Schenk et al. 1991) and animals with lesions at the amygdala, VTA, or raphe nuclei manifest more rapid acquisition of amphetamine self-administration than control rats (Deminiere et al. 1989). The above arguments, postulating neuropathology as an intrinsic component of stimulant addiction, should be taken into consideration with the caveat that the clinical manifestations of the disease are heterogenous and addicts may express varying stages and degrees of the disease as determined by environmental and genetic factors. Therefore, it is likely that stimulant addicts who have less advanced neuropathology may recover spontaneously after detoxification with proper nutritional and psychotherapeutic support if they can sustain abstinence. (ABSTR