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Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug. [ABSTRACT FROM AUTHOR]

We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lamotrigine 125 mg, or lamotrigine 250 mg was administered orally in the morning, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. Measurements of heart rate and blood pressure were acquired, and subjects responded to mood state questionnaires at predetermined time intervals. Cocaine alone produced increases in heart rate, blood pressure, and several measures of pleasurable mood and drug effects. Lamotrigine alone produced a mild relaxing effect. Lamotrigine pretreatment altered neither the physiological responses nor the subjective ratings of cocaine's pleasurable or aversive mood effects. [ABSTRACT FROM AUTHOR]

This double blind, placebo controlled study of acute calcium channel antagonist use during cocaine administration in five patients found that 60 mg of nimodipine treatment attenuated the systolic, but not diastolic, blood pressure effects of cocaine. In three subjects, a 90 mg dose of nimodipine showed a greater attenuation than that of 60 mg. Subjective effects of cocaine were not altered by either dose of nimodipine. [ABSTRACT FROM AUTHOR]

The cost to society of alcohol, tobacco, and illicit drug dependence is enormous. Although the importance of treatment for substance abuse to public health is increasingly acknowledged, pharmacotherapy is generally underutilized. However, the selection of medications for clinical testing is increasingly guided by the rapidly evolving science of addictive drugs and behavior. The benefit of medication for smoking cessation is firmly established, particularly for nicotine replacement and antidepressant therapy. Naltrexone is an important addition to the pharmacopoeia, and acamprosate may soon be approved as well. Although no new medications are approved for cocaine and amphetamine abuse, a variety of candidate treatments have shown promise in ongoing studies. Opiate substitution therapy is highly effective for rehabilitation of heroin addiction, and several alternative forms will soon be available; alternative forms of opiate detoxification have also received attention. Overall, there is increasing recognition that physicians have an obligation to identify and treat all forms of substance dependence, although knowledge of the efficacy of the available treatments is steadily increasing. [ABSTRACT FROM AUTHOR]

Objective: To review the scientific literature on the effectiveness of rapid opioid detoxification (RD) (opioid withdrawal precipitated by naloxone hydrochloride or naltrexone) and ultrarapid opioid detoxification (URD) (opioid withdrawal precipitated by naloxone or naltrexone under anesthesia or heavy sedation) techniques.Data Sources: The MEDLINE database was searched from 1966 through 1997 using the indexing terms naloxone, naltrexone, substance dependence, and substance withdrawal syndrome. Additional data sources included bibliographies of papers identified on MEDLINE and bibliographies in textbooks on substance abuse.Study Selection: Inclusion criteria were studies of RD or URD, pharmacologic protocols specified, and clinical outcomes specified and reported. Exclusion criteria were unpublished data, data not in peer-reviewed journals, abstract-only publications, and review articles.Data Extraction: The methodologic characteristics of studies were extracted by the authors and summarized according to key components of research design concerning subject characteristics, therapy allocation, and outcomes assessed.Data Synthesis: A qualitative analysis was performed on the 12 studies of RD and the 9 studies of URD identified in our search. The RD studies enrolled 641 subjects (range for individual studies, 1-162): 7 were inpatient studies, and the protocols varied considerably, as did the outcomes assessed. Three RD studies included a control group, 2 used a randomized design, and 3 reported outcomes beyond 12 days. The URD studies enrolled 424 subjects (range for individual studies, 6-300): all were inpatient studies, the detoxification and anesthesia protocols varied, 3 included a control group, 2 used a randomized design, and 2 reported outcomes for URD beyond 7 days.Conclusions: The existing literature on RD and URD is limited in terms of the number of subjects evaluated, the variation in protocols studied, lack of randomized design and use of control groups, and the short-term nature of the outcomes reported. Further research is needed using more rigorous research methods, longer-term outcomes, and comparisons with other methods of treatment for opioid dependence. [ABSTRACT FROM AUTHOR]

Background: Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients.Objective: To compare three pharmacologic protocols for opioid detoxification in a primary care setting.Design: Randomized, double-blind clinical trial with random assignment to treatment protocols.Setting: A free-standing primary care clinic affiliated with drug treatment programs.Patients: 162 heroin-dependent patients.Interventions: Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine.Measurements: Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms.Results: Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone.Conclusions: Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups. [ABSTRACT FROM AUTHOR]

Using the newly revised DSM-III-R criteria for substance-abuse diagnoses, we examined dependence syndrome elements among 83 psychiatric patients. The sample included 14 with no history of substance abuse. The remainder abused alcohol (52), sedatives (31), hallucinogens (12), stimulants (33), cannabis (44), cocaine (52), or opiates (47). Many patients (52) had abused more than one type of drug. Ten items assessing the proposed dependence symptoms for each type of drug were factor-analysed. The dependence syndrome items formed a single factor for opiates, cocaine, and alcohol, but not for other drugs. When the items were combined into cumulative scales, they had excellent internal consistency. Furthermore, they formed good approximations of unidimensional Guttman scales on which higher scores indicated greater syndrome severity. The items associated with higher scores differed across drugs, with opiates having the most striking differences from the other substances. Medical-psychosocial consequences were relatively independent of the dependence syndrome, although alcohol and cocaine dependence had some association with other problem areas. These findings support the utility of a common dependence syndrome concept for drugs of abuse as well as alcohol, and provide empirical support for the current revision of the DSM-III diagnostic criteria. [ABSTRACT FROM AUTHOR]