Second edition

21.qxd 3/10/08 9:58 AM Page 658
658 Substance use disorders
Intoxication after snorting cocaine lasts from 30 to 60 minutes,
whereas after intravenous administration or smoking
it lasts only 5–20 minutes.
Cocaine is rapidly metabolized by plasma and hepatic
esterases to such inactive metabolites as benzoylecgonine,
and this metabolite may be found in the urine for up to a
week; of note, in some cases the level of this metabolite
may fluctuate, such that a ‘negative’ urine test may occasionally
be followed by a ‘positive’ one (Burke et al. 1990).
Shortly after resolution of the intoxication, most patients
will experience a ‘crash’, lasting from hours to a day, characterized
by fatigue, depressed mood, irritability, and anxiety.
Given that this ‘crash’ may occur with first-time use of
cocaine as well as after widely spaced repeat intoxications, it
may not be appropriate to consider it a withdrawal syndrome.
Clear-cut withdrawal, however, does occur with
chronic use and indeed may appear after only a few days of
heavy use. The withdrawal symptoms (Weddington et al.
1990) include not only those seen in the ‘crash’ but also
anhedonia, hyperphagia, insomnia, and, often, suicidal
ideation; furthermore, during withdrawal there is typically a
tense craving for more cocaine. This withdrawal reaches a
maximum of severity within a few days and then gradually
remits over days or weeks. Rarely, dystonia may appear during
withdrawal (Choy-Kwong and Lipton 1989).
Tolerance may develop rapidly with repeated use;
indeed, with a ‘run’ of intravenous use, tolerance may
appear within a day. Unfortunately, this tolerance applies
only to the euphoriant effects of cocaine and not to its
potentially lethal cardiovascular effects.
After approximately two or more years of frequent cocaine
use, intoxications may become characterized by delusions
of persecution and of reference, and by auditory hallucinations
(Brady et al. 1991; Rosse et al. 1994; Satel et al. 1991;
Sherer et al. 1988). Although initially these symptoms tend
to resolve shortly after the intoxication resolves (Brady
et al. 1991), over time, and with repeated episodes, they
appear with lower doses and also tend to last much longer
(Bartlett et al. 1997), in some cases creating a psychosis that
may persist for weeks (Manschreck et al. 1987), despite
abstinence.
Course
Recreational use of cocaine, that is occasional intoxications
without consequences, is generally seen only with ‘snorting’.
Abusive use, with legal, social, and medical consequences,
may also occur with snorting but is more common
when cocaine is taken intravenously or smoked. Cocaine is
one of the most, perhaps the most, addictive substances in
the world, and craving may develop rapidly, leading to
chronic, frequent use and the development of tolerance and
withdrawal. When addiction does set in, the pattern of
cocaine use may be either continuous or episodic.
Continuous use is characterized by daily intoxication,
either via snorting, injection, or smoking. Episodic use is
characterized by ‘binges’, lasting anywhere from hours to a
week, during which cocaine may be injected or smoked very
frequently, sometimes every 10 or 15 minutes; with such
frequent use, however, the euphoria of the intoxication
becomes progressively briefer and the crashes progressively
more severe, until finally either exhaustion or a lack of
funds ends the binge. The intervals between binges vary
widely, from only a few days to up to weeks or months.
Etiology
Within the central nervous system cocaine both inhibits
the reuptake and facilitates the release of monoamines by
pre-synaptic neurons. Although both serotonin and norepinephrine
are involved, it appears that the euphoriant
effects of cocaine are related to the increased concentration
of dopamine at the terminals of the mesolimbic and mesocortical
dopaminergic pathways.
Differential diagnosis
A clinical differentiation of cocaine intoxication from
stimulant intoxication may not be possible, and the differential
often rests on history or a drug screen.
Withdrawal may suggest depression and, when the history
of cocaine use is unavailable, the differential may rest
on observation in a controlled environment, which will
reveal the fairly rapid resolution of symptoms.
The diagnosis of a persistent cocaine psychosis is generally
straightforward as it is difficult to hide the history of
chronic cocaine addiction. If, however, this history is not
available, then the differential for psychosis, as discussed in
Section 7.1, must be pursued.
Treatment
For most cases of intoxication and post-intoxication
‘crashes’, simple observation is sufficient. Even in cases of
severe intoxication with delirium, observation, given the
brevity of the intoxication, is again generally all that is
required; if, however, agitation is severe, one may give a
dose of parenteral haloperidol in a dose of 5–10 mg.
Patients with severe withdrawal and suicidal ideation may
require hospitalization to protect themselves; hospitalization
may also be required in cases of cocaine abuse or
addiction to effect a period of abstinence, during which
other measures may be initiated.
The overall goal of treatment of cocaine abuse or addiction
is abstinence from cocaine and other substances, such
as alcohol, benzodiazepines, and opioids. Patients may be
referred to organizations such as Cocaine Anonymous or
Narcotics Anonymous, and some may undergo cognitive
behavioral therapy. The efficacy of pharmacologic treatment
for cocaine addiction is uncertain. Earlier claims for the
effectiveness of dopaminergic agents, such as amantadine,