Paranoia cocaine-induced

Gelernter J, Kranzler HR, Satel SL, et al Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia. Neuropsychopharmacology 11 195-200, 1994... 

Gawin F. Neuroleptic reduction of cocaine-induced paranoia, but not euphoria Psychopharmacology. 90 142, 1986. 

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. 

Gelemter, J., H. R. Kranzler, S. L. Satel, and P. A. Rao. 1994. "Genetic Association Between Dopamine Transporter Protein Alleles and Cocaine-Induced Paranoia." Neuropsychopftamtacology 11 195-200. 

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. 

The hypothetical link between dopamine and schizophrenia was forged by two reciprocally related findings. The first was that potent dopamine agonist stimulants like d-amphetamine and cocaine could cause a psychosis that was schizophrenia-like, in that it had auditory hallucinations and paranoia. The second was that the neuroleptic drugs that were effective in reversing both schizophrenia and stimulant-induced psychosis were dopamine blockers. Moreover, the antipsychotic potency of the neuroleptics was proportional to their binding affinity to the D2 receptor. 

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. 

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