Cocaine dependence potential

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

II Accepted for medical use, strict limitations due to recognized high abuse and dependency potential. Prescriptions must be signed by practitioners and cannot be refilled. Cocaine, oxycodone with acetaminophen... 

Simultaneous abuse of cocaine and alcohol is common and alcohol reduces negative stimulant effects and potentiates highs. Disulfiram has therefore also been used to treat cocaine dependence, with the rationale that an inability to modulate the effects of cocaine with alcohol may reduce cocaine use. 

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]. 

In an interview study (Robson and Bruce 1997), the dependence potential of various street drugs was assessed in 201 problem and 380 social users of heroin, cocaine or amphetamine using the well-validated Severity of Dependence Scale (SDS). Scores (maximum = 15) in the problem group were 12.9 for heroin, 9.6 for other opioids, 6.1 for amphetamine and 5.5 for crack cocaine. All of these scores were consistent with findings in other studies. Cannabis SDS score was 2.6 and comparable with those of LSD (3.1) and ecstasy (1.3), two drugs that are generally not associated with physical or psychological dependence. In the parallel sample of social users, the cannabis SDS was similar at 3.4. 

Reith, 1988), and the extensive literature which suggests that cocaine s reinforcing effects are mediated by increases in extracellular dopamine levels in the mesolim-bic dopamine system (Ritz et al., 1987 Koob and Bloom, 1988 Johanson and Fischman, 1989 Kuhar et al., 1991 Woolverton and Johnson, 1992). Dopamine receptor antagonists have been evaluated for their potential utility in treating cocaine abuse (Mello and Negus, 1996) but such agents produce extrapyramidal motor effects and other unwanted effects that complicate their use in the treatment of cocaine dependence. 

Neumeyer, J.L., Bidlack, J.M., Zong, R., Bakthavachalam, V., Gao, P., Cohen, D.J., Negus, S.S., Mello, N.K., 1999. Synthesis and opioid receptor affinity of morphinan and benzomorphan derivatives. Mixed kappa agonists and mu agonists/antagonists as potential pharma-cotherapeutics for cocaine dependence. J. Med. Chem. (in press). 

Schedule 11 drugs have an accepted medical use in the United States and a high rate of abuse, with either severe psychological or physical dependence potential. These drugs include morphine, codeine, cocaine, amphetamine, and most barbiturate preparations containing amobarbital, secobarbital, and pentobarbital. 

Schedule II—The drug or other substance has (1) a high potential for abuse, (2) a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions, and (3) abuse of the drug or other substances may lead to severe psychological or physical dependence. Examples cocaine, PCP, morphine, fentanyl and meperidine, codeine, amphetamine and methamphetamine, Ritalin . 

Once in the blood stream, cocaine levels quickly rise in the brain, faster than plasma levels, which then redistribute to other tissues. Cocaine is rapidly metabolized in the blood and liver, with a half-life of 30 to 90 minutes. The major metabolites have a half-life of approximately 8 hours. Although cocaine itself is detected in urine for only 12 hours, the metabolite benzoylecgonine can be detected in urine for at least 48 hours and sometimes up to 2 weeks. Concurrent use of cocaine and ethanol produces an ethyl ester of benzoylecgonine called cocaethylene. Cocaethylene is an active metabolite, blocking dopamine reuptake, and potentiating the effect of cocaine. Thus, concurrent use of cocaine and ethanol can further increase the additional effects of the drugs and the risk of dependency. 

Ibogaine itself stimulates locomotor activity in rats. However, it reduces the locomotor activity induced by morphine, with greater effects in female animals than males (Pearl et al. 1997). It also reduces locomotor activity induced by cocaine and amphetamine (Sershen et al. 1992a, 1992b Blackburn and Szumlinski 1997). However, the interaction between ibogaine and cocaine is time-dependent, with motor activity inhibited at short delays, but potentiated at long delays (Maisonneuve et al. 1997). 

Cannabis carries some potential for dependence and addiction. Compared to cocaine, heroin, alcohol, and nicotine, cannabis has lesser addictive potential and withdrawal effects, but some users do develop compulsive and maladaptive use patterns that require treatment (Taylor 1998). Individuals with underlying psychopathology or tendencies for substance abuse should be particularly leery of using cannabis in the interests of avoiding compulsive use patterns. 

Cronan T, Conrad J, et al (1985) Effects of chronically administered nicotine and sahne on motor activity in rats. Pharmacol Biochem Behav 22(5) 897-899 Curtis L, Buisson B, et al (2002) Potentiation of human alpha4beta2 neuronal nicotinic acetylcholine receptor by estradiol. Mol Pharmacol 61(1) 127-135 Dalton JC, Vickers GJ, et al (1986) Increased self-administration of cocaine following haloperidol sex-dependent effects of the antiestrogen tamoxifen. Pharmacol Biochem Behav 25(3) 497-501 Damsma G, Day J, et al (1989) Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens. Eur J Pharmacol 168(3) 363-368 Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85(14) 5274-5278... 

Weiss JM, Bonsall RW, Demetrikopoulos MK, Emery MS, West CH Galanin (1998) A significant role in depression Ann N Y Acad Sci 863 364-382 Wniick ML, Kokkinidis L (1995) Cocaine enhances the expression of fear-potentiated startle evaluation of state-dependent extinction and the shock-sensitization of acoustic startle. Behav Neurosci 109 929-938... 

Schedule II Substances with a medicinal use but also a high potential for psychological or physical dependence. A written prescription is required for use for example, morphine, cocaine, and oxycodone. 

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