Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

9. Cocaine and Stimulants 191postsynaptic receptor sensitivity for dopamine and noradrenaline, increasedtyrosine hydroxylase activity (a major enzyme in norepinephrine and dopaminesynthesis), and hyperprolactinemia. These are expected results for a negativefeedback system. Chronic use is also associated with volume losses in theprefrontal cortex and nucleus accumbens. In addition, striatal dopamine responseis significantly lower in cocaine abusers during withdrawal than incocaine nonabusers. Furthermore, lower levels of dopamine receptors in thestriatum are associated with lower metabolism in the orbitofrontal cortex andanterior cingulate gyrus in cocaine-addicted subjects (Goldstein & Volkow,2002).Clinical features of chronic cocaine use include depression, fatigue, poorconcentration, loss of self-esteem, decreased libido, mild parkinsonian features(myoclonus, tremor, bradykinesis), paranoia, and insomnia. Tolerance to thestimulant effects of cocaine, particularly the anorexic effects, develops rapidly.However, repeated phasic use of low-dose cocaine can lead to enhanced sensitivityand potentiation of motor activity, including exaggerated “startle” reactions,dyskinesias, and postural abnormalities. Increased stereotypical behaviorand a toxic psychosis can occur after repeated cocaine use. The eliminationhalf-life of cocaine is under 1 hour by the intravenous route, and just over 1hour by the intranasal route. The physiological and subjective effects dueto cocaine correlate well with plasma levels (Javaid, Fischman, Schuster,Dekirmenjian, & Davis, 1978), although, with repeated use, pharmacodynamictachyphylaxis does occur. Cocaine euphoria is of short duration, with a 10- to20-second “rush,” followed by 15–20 minutes of a lower level of euphoria andthe subsequent onset of irritability and craving. Cocaine users who try to maintainthe euphoric state readminister the drug frequently, until their supply disappears.Cocaine binges average 12 hours but can last as long as 7 consecutivedays.WithdrawalA withdrawal syndrome, often referred to as the “crash,” consists of strong craving,electroencephalograph abnormalities, depression, alterations in sleep patterns,hypersomnolence, and hyperphagia (Jones, 1984). However, becauseabrupt discontinuation of cocaine does not cause any major physiologicalsequelae, cocaine is stopped and not tapered or substituted by a cross-tolerantdrug during medically supervised withdrawal. Following the resolution of intoxicationand acute withdrawal symptoms, there is a 1- to 10-week period ofchronic dysphoria, anergia, and anhedonia. Relapses frequently occur, becausethe memory of cocaine euphoria is quite compelling in contrast to a bleak backgroundof intense boredom. If patients can remain abstinent from illicit moodalteringdrugs during this period, the dysphoria gradually improves. Thereafter,intense cocaine craving is replaced by episodic craving that is frequently trig-