Paranoia, with cocaine

Cubells, J.F., Kranzler, H.R., McCance-Katz, E., Anderson, G.M., Malison, R.T., Price, L.H., and Gelernter, J. (2000) A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 5 56-63. 

At higher doses, cocaine can produce undesirable effects, including tremor, emotional lability, restlessness, irritability, paranoia, panic, and repetitive stereotyped behavior. At even higher doses, it can induce intense anxiety, paranoia, and hallucinations, along with hypertension, tachycardia, ventricular irritability, hyperthermia, and respiratory depression. In overdose, cocaine can cause acute heart failure, stroke, and seizures. Acute intoxication with cocaine produces these various clinical effects, depending on the dose these effects are mediated by inhibition of the dopamine transporter and in turn by the effects of excessive dopamine activity in dopamine synapses, as well as by norepinephrine and serotonin in their respective synapses. 

The possible genetic basis of cocaine-induced paranoia has been studied in 45 European Americans with cocaine dependency (181). Low activity of the enzyme dopamine P-hydroxylase (the enzyme that catalyses the conversion of dopamine to noradrenaline) in the serum or cerebrospinal fluid was positively associated with the occurrence of positive psychotic symptoms in several psychiatric disorders. The activity of dopamine P-hydroxylase is a stable, genetically determined trait that is regulated by genes located at the DBH locus. The haplotype associated with low dopamine P-hydroxylase activity, Del-a, occurred more often in 29 subjects with cocaine-induced paranoia than in 16 without. These findings may have implications for the pharmacological treatment of cocaine dependence. 

Cocaine abusers have reported that alcohol prolongs the euphoriant properties of cocaine, while ameliorating the acutely unpleasant physical and psychological sequelae, primarily paranoia and agitation. It may also lessen the dysphoria associated with acute cocaine abstinence. It has also been proposed that concurrent alcohol abuse may be an integral part of cocaine abuse. The combination of cocaine with alcohol can cause enhanced hepatotoxicity... 

Vaccines have been tested as a potential pharmacotherapy for cocaine addiction. A cocaine vaccine (Table 1) of succinyl norco-caine conjugated to the cholera toxin (TA-CD) was administered to cocaine-dependent individuals [86], Individuals who produced adequate antibody levels showed reduced cocaine use. Genetic analysis showed that T allele carriers of variant rsl611115 (which has been shown to be associated with low DpH expression) reduced cocaine use with vaccine, while subjects with the CC genotype did not [87]. This may be related to the increase incidence of paranoia while using cocaine in subjects with the low expressing DBH genotype [80]. 

There are anecdotal reports that cannabis is useful in countering both the withdrawal symptoms (Labigalini et al. 1999) and paranoia and weightless (Dreher 2002) associated with smoking crack cocaine. 

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