Vaccines against nicotine: how effective are they likely to be in preventing smoking?

Cigarette smoking is the most preventable cause of death in industrialised countries. 30% of all deaths in smokers in the 35 to 69 years age range are attributed to chronic cigarette smoking; smokers dying in this age cohort lose an average of 23 years of life. Public health campaigns have attempted to reduce initiation of smoking in adolescents and to foster quitting in dependent smokers. The prevalence of smoking has declined in the US to 25% of the population, but this figure has held constant for the last decade. Vaccines against nicotine are a novel concept in the field of smoking cessation research and have not yet reached the stage of clinical testing. Vaccines could reduce smoking behaviour in 3 groups of smokers: (i) current smokers attempting to quit; (ii) former smokers wanting to avoid the possibility of relapse; and (iii) adolescent smokers before they become confirmed smokers. The rationale behind the approach is that nicotine is the pharmacological agent controlling the rate of cigarette smoking, and reducing its rate and extent of uptake into the brain may have therapeutic benefits.

Competence and behavioral/emotional problems among Taiwanese adolescents as reported by parents and teachers.

OBJECTIVE: To investigate competence and behavioral/emotional problems among nonreferred adolescents in Taiwan, using a Chinese version of the Child Behavior Checklist (CBCL-C) and the Teacher's Report Form (TRF-C). The psychometric properties of these instruments and cross-cultural differences were also examined. METHOD: Parents of 854 junior high school students aged 12 to 16 years in Taipei, Taiwan, were asked to complete the CBCL-C. Among these students, 162 had their teachers' ratings of the TRF-C. RESULTS: The internal consistency and 1-month test-retest reliability were satisfactory for both the CBCL-C and TRF-C, which were moderately correlated. Both exploratory and confirmatory factor analysis provided some support for the validity of Achenbach's cross-informant model. Parents' reports showed that compared with their American counterparts, Taiwanese adolescents tended to have lower scores on most competence scales, higher scores on scales that reflect covert behavior problems, and lower scores on scales that reflect more overt behavior problems. However, teachers' reports showed no significant differences on most competence and behavior problem scales. CONCLUSION: The CBCL-C and TRF-C are useful tools for assessing the mental health status of Taiwanese adolescents. The cross-cultural differences in adolescent behavior problems are discussed.

Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts.

The present study, conducted as part of the development of a buprenorphine/naloxone combination product, was designed to evaluate the individual and combined effects of intravenously administered buprenorphine and naloxone. This in-patient trial used a randomized, double-blind, crossover design. Ten opioid-dependent male subjects were stabilized and maintained on morphine, 15 mg given intramuscularly four times daily. Then, at 48- to 72-h intervals, subjects received one of the following by intravenous injection: (1) placebo, (2) morphine 15 mg, (3) buprenorphine 2 mg, (4) buprenorphine 2 mg/naloxone 0.5 mg, and (5) naloxone 0.5 mg. Both naloxone and buprenorphine/naloxone produced significant (P < 0.005) opioid withdrawal effects compared to placebo as assessed with the CINA scale, an instrument which utilizes subject- and observer-reported, as well as physiological parameters. The combination of buprenorphine with naloxone in a 4:1 ratio produced opioid antagonist-like effects which should limit its potential for intravenous abuse by opioid addicts.

Overview: medications development for the treatment of drug abuse.

Drug abuse is of great public concern, and effective treatment strategies for opiate and cocaine dependence are urgently needed for the general addict population as well as for pregnant women and their infants. NIDA's effort to develop new pharmacotherapies as an adjunct to the treatment of opiate addiction has already led to the approval of LAAM and an NDA development program for buprenorphine. The momentum achieved by the new Medications Development Program's success with opiate addiction treatment must now be applied to the development of new treatments for cocaine addiction. With recent advances in neuroscience, imaging techniques, and pharmaceutical technology, the development of medications for significantly improving drug abuse treatment in a variety of directions holds real promise.

Quantitative versus qualitative urinalysis for benzoylecgonine in clinical trials for the assessment of cocaine use.

Urinalysis of benzoylecgonine (BE) concentrations is a primary outcome measure for evaluating medications for treating cocaine addiction. Using simulated BE data from a set of simple clinical models, the advantages of quantitative versus qualitative urinalysis were evaluated, as well as the advantages of once-weekly versus thrice-weekly sampling schedules. A 60 percent reduction in cocaine use, either in daily amount or in weekly frequency, was considered clinically significant. Quantitative urinalysis can detect reductions in both amount and frequency, whereas qualitative urinalysis can detect only a decrease in frequency. For quantitative urinalysis, changes are more easily detected when urine is collected three times a week than when it is collected once a week. For qualitative urinalysis, the majority rule analysis for a thrice-weekly sampling schedule yields an artificially high estimate of the percentage of positive samples, whereas a once-weekly schedule gives a highly variable estimate.

Implications of drug levels in body fluids: basic concepts.

Drug concentrations in biological fluids are affected by the dose, route of administration, pattern of drug use, and the dispositional kinetics (distribution, metabolism, and excretion) of the drug. As most drugs are distributed to the site of action by blood, drug concentration measurement in this body fluid provides the best information as to the potential effect on behavior such as driving impairment or on psychological high. Due to wide individual variations in the pharmacokinetics and pharmacodynamics of drugs, however, the use of plasma drug concentrations for the estimation of impairment has not been established for most drugs. As for urinalysis, drug concentrations in the urine are further complicated by other factors such as urine flow and pH. Even if a specific method is used for the quantitation of a specific drug (the active species, not the inactive metabolite), interpretation in forensic samples to predict time of drug use or impairment is not possible, except within broad time periods, because of the variations in urine drug concentration as well as the limited knowledge available about the dose or the route of administration.

Clinical evaluation of a naltrexone sustained-release preparation.

A clinical evaluation of the naltrexone bead, a biodegradable sustained-release dosage form of 3.0 mg in weight containing 70% naltrexone in a copolymer of lactic and glycolic acids, was carried out in 4 healthy normal males. Subjects were given an intravenous dose of 10 mg naltrexone and approx. 1 week later a 63-mg dose of naltrexone by subcutaneous administration of the beads. Challenge doses of 15 mg morphine were given to each subject during the study for the assessment of narcotic blockade effects of naltrexone. For a 2-4-week period after bead administration, relatively constant plasma levels were maintained at 0.30-0.46 ng/ml for naltrexone and were 0.64-1.07 ng/ml for naltrexol. Urine levels for unchanged and conjugated naltrexone were 79-215 ng/ml and for naltrexol were 315-500 ng/ml. From kinetic analysis, an average of 2.4-2.7% of implanted dose was absorbed each day from the administration of the beads. Opiate effects of morphine challenges were mitigated during the 2-4-week period after administration of naltrexone beads.

Kinetics of a naltrexone sustained-release preparation.

A biodegradable sustained-release naltrexone bead preparation containing 70% naltrexone in a physical mixture with a copolymer of 90% lactic acid and 10% glycolic acid was evaluated in three male subjects. Each subject received a 10-mg iv dose of naltrexone HCl and a 63-mg dose by subcutaneous implantation of naltrexone beads. Kinetics of naltrexone estimated from the intravenous dose indicated a plasma clearance range of 3.1 to 3.4 l/min and a t 1/2 range of 1.7 to 3.7 hr. After bead implantation, average plasma naltrexone levels were maintained at 0.3 to 0.4 ng/ml and naltrexol levels were at 0.4 to 1.0 ng/ml for a period of approximately 1 mo, during which urine naltrexone and naltrexol levels were about 20 to 30 and 70 to 200 ng/ml. It was estimated that approximately 70% to 77% of the dose was absorbed after bead implantation. There were no serious adverse effects other than tissue irritation in two of the three subjects.