benzoylecgonine and Alcoholism

Modafinil is a medication approved for narcolepsy and shift work sleep disorder. It has both dopaminergic and glutamatergic activity that could be useful for the treatment of cocaine dependence. Modafinil has reduced cocaine subjective effects and cocaine self-administration in human laboratory trials and has reduced cocaine use in cocaine dependent patients in some clinical trials.. This was an 8-week, double blind, placebo controlled clinical trial involving 94 cocaine dependent subjects. Subjects received 300mg of modafinil or identical placebo daily along with weekly individual therapy. The primary outcome measure was cocaine use measured by self-report, and confirmed by twice weekly urine benzoylecgonine tests (UBT). Additional outcome measures included cocaine craving measured by the Brief Substance Craving Scale and global improvement measured by the Clinical Global Impression Scale (CGI).. The odds ratio (OR) in favor of abstinence for modafinil vs. placebo was 2.54 (p=. 03) and modafinil-treated subjects were significantly more likely than placebo-treated subjects to be abstinent from cocaine during the last 3 weeks of the trial, 23% vs. 9%, χ(2)=3.9, p<.05. Modafinil treated subjects were more likely to report very low levels of cocaine craving intensity and duration on the Brief Substance Craving Scale (OR=2.04, p=.03 and OR 1.06, p=.03 respectively). Modafinil-treated subjects were also more likely than placebo-treated subjects to rate themselves as "very much improved" on the CGI (OR=2.69, p=.03).. Modafinil may be an efficacious treatment for cocaine dependence.

Topics: Adolescent; Adult; Alcoholism; Benzhydryl Compounds; Cocaine; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Craving; Double-Blind Method; Female; Humans; Male; Medication Adherence; Middle Aged; Modafinil; Patient Compliance; Psychiatric Status Rating Scales; Treatment Outcome; Young Adult

Substance abuse worsens the course of schizophrenia and significantly impairs the relationship between the patient and the health care team. Recent advances in laboratory studies of substance abuse and the pharmacology of schizophrenia open up new possibilities for pharmacotherapy of substance abuse in schizophrenia patients. D1 dopaminergic receptor agonists may directly block the drive for stimulant use. D2 dopaminergic receptor antagonists may indirectly block the drive for stimulant and nicotine use, while opioid antagonists appear to reduce the drive to use alcohol. New generations of neuroleptics with serotonin (5-HT2) receptor antagonism and/or 5-HT1A agonist activity may reduce substance abuse in schizophrenia patients who self-medicate negative symptoms or neuroleptic side effects. Pharmacotherapy efficacy may be enhanced by adding contingency management, social skills training, and other manualized programs. Tables are provided of potentially useful medications. Preliminary results are presented of cocaine-abusing schizophrenia patient treated with desipramine and traditional neuroleptics.

Topics: Alcoholism; Antipsychotic Agents; Cocaine; Flupenthixol; Humans; Imipramine; Marijuana Abuse; Opioid-Related Disorders; Schizophrenia; Self Medication; Substance-Related Disorders; Tobacco Use Disorder

The interaction between cocaine (COC) and ethyl alcohol (ALC) was investigated in ALC-naive and ALC-pretreated rats. In each group, COC (30 mg/kg ip) was administered 15 min after administration of ALC (3 g/kg, by gavage) or normal saline (NS), in a balanced cross-over experimental design. Cocaethylene (CE) was detected only in the rat plasma when ALC was administered with COC. In the ALC-naive rats, COC area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cpmax) were significantly higher after administration of COC+ALC compared with after administration of COC+NS. However, COC half-life (t1/2) was not different after the two treatments, indicating that the higher COC Cpmax and AUC after COC+ALC primarily resulted from enhanced COC absorption. In the ALC-pretreated rats, COC AUC, Cpmax, and t1/2 were not different after administration of COC+ALC or COC+NS. However, COC t1/2 in the ALC-pretreated rats after COC+ALC and COC+NS were significantly longer than the corresponding COC t1/2 in the ALC-naive rats. This indicates that repeated ALC exposure significantly slows the rate of COC elimination. In the ALC-pretreated rats, CE AUC was significantly larger, and t1/2 was significantly longer than CE AUC and t1/2 in the ALC-naive rats. This indicates that previous ALC exposure inhibits CE elimination and may increase the fraction of COC dose metabolized to CE. Benzoylecgonine formation was significantly reduced, and its t1/2 was significantly prolonged after administration of COC+ALC in the ALC-naive and the ALC-pretreated rats. These results suggest that the combined abuse of COC and ALC leads to higher plasma COC concentrations that can lead to augmentation of cocaine effects in addition to the COC-like effects of CE. Also, repeated use of ALC slows the rate of COC elimination after administration of COC either alone or in combination with ALC, resulting in higher and prolonged COC plasma concentrations that can potentiate COC effects and toxicities. This higher COC concentrations in addition to the formation of CE are, at least partially, responsible for the serious consequences associated with the combined abuse of COC and ALC.

Topics: Alcoholism; Animals; Cocaine; Cross-Over Studies; Drug Interactions; Ethanol; Male; Rats; Rats, Wistar; Substance-Related Disorders