PubMed Health⌕ Search

Biomedical subjects

Kenzie L Preston

Publications and source records attributed to Kenzie L Preston.

At least 19 recordsLinked to original sources
PubMed2006

Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure.

BACKGROUND AND RATIONALE: The reinstatement model is widely used to study relapse to drug addiction. However, the model's validity is open to question. OBJECTIVE: We assess the reinstatement model in terms of criterion and construct validity. RESEARCH HIGHLIGHTS AND CONCLUSIONS: We find that the reinstatement model has adequate criterion validity in the broad sense of the term, as evidenced by the fact that reinstatement in laboratory animals is induced by conditions reported to provoke relapse in humans. The model's criterion validity in the narrower sense, as a medication screen, seems promising for relapse to heroin, nicotine, and alcohol. For relapse to cocaine, criterion validity has not yet been established primarily because clinical studies have examined medication's effects on reductions in cocaine intake rather than relapse during abstinence. The model's construct validity faces more substantial challenges and is yet to be established, but we argue that some of the criticisms of the model in this regard may have been overstated.

Alcoholism↗
PubMed2006

Nonreporting of cannabis use: Predictors and relationship to treatment outcome in methadone maintained patients.

Underreporting of drug use is common and influenced by multiple factors. Cannabis (THC) use nonreporting and its relationship to heroin and cocaine use were investigated in 690 patients enrolled in 25- to 29-week clinical trials of contingency management plus methadone maintenance. Urine specimens and self-reports of drug use were collected 3 times/week. Potential predictors of THC use nonreporting were analyzed by multiple logistic regression; relationships between THC use nonreporting and % cocaine- and opiate-positive urines were analyzed by multiple regression. Compared to non-THC users (n=317), patients with THC-positive urines (n=373) were more likely to be male and have more years of THC use, but were not different on other characteristics. Nonreporting to user ratios were: THC 191/373 (51.2%); opiates 17/686 (2.5%); cocaine 21/681 (3.1%). Predictors of THC use nonreporting were low rate of THC-positive urines during treatment, fewer days of THC use in the last 30 before treatment, African-American race, and absence of antisocial personality disorder. Nonreporting of THC use was associated with significantly greater opiate and cocaine use. Contingency management decreased cocaine use in THC nonreporters to the level of reporters. Nonreporting of THC use is a significant predictor of greater cocaine and heroin use. This association can be eliminated with contingency management therapy.

Administration, Oral↗
PubMed2006

Heroin and cocaine craving and use during treatment: measurement validation and potential relationships.

Although commonly assessed with unidimensional scales, craving has been suggested to be multifaceted and to have a complex relationship with drug use and relapse. This study assessed the consistency and predictive validity of unidimensional and multidimensional craving scales. At the beginning of a 12-week outpatient treatment trial, opiate users (n = 101) and cocaine users (n = 72) completed unidimensional visual analog scales (VASs) assessing "want," "need," and "craving" and multidimensional 14- and 45-item versions of the Cocaine Craving Questionnaire (CCQ) or Heroin Craving Questionnaire (HCQ). Spearman correlations between the VASs and the first-order factors from the 45-item CCQ/HCQ were .20-.40, suggesting that the two types of assessment were not redundant. Treatment dropout and in-treatment drug use were more frequently predicted by scores on the 14- or 45-item CCQ than by VAS ratings. Results suggest that the CCQ/HCQ and the 14-item CCQ provide information that unidimensional VASs do not.

Adult↗
PubMed2006

Abuse liability, behavioral pharmacology, and physical-dependence potential of opioids in humans and laboratory animals: lessons from tramadol.

Assessment of abuse potential of opioid analgesics has a long history in both laboratory animals and humans. This article reviews the methods used in animals and in humans and then presents the data collected in the evaluation of tramadol, an atypical centrally acting opioid analgesic approved for marketing in the United States in 1998. Finally, data on the abuse of tramadol from postmarketing surveillance and case reports are presented. The consistency between animal and human study results and the predictive value of both are discussed. Overall, there was substantial agreement between animal and human data, with each having predictive value. Nonetheless, it is suggested that abuse-potential screening of new medications would benefit from an organized, integrated cross-species program.

Animals↗
PubMed2006

The cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers.

BACKGROUND: Animal studies suggest that cannabinoid CB1 receptors play a role in regulating blood pressure (BP). In human studies, activation of CB1 receptors by cannabis or its active ingredient, Delta9-tetrahydrocannabinol (THC), has modest and inconsistent effects on BP. METHODS: We evaluated this phenomenon in 63 male cannabis smokers (mean [SD] age 27.7 +/- 5.4 years, 70% African American, 10.3 +/- 5.9 years of lifetime cannabis use) by administering escalating oral doses (1, 3, 10, 30, 90 mg) of the selective CB1 receptor antagonist rimonabant (or placebo) in a randomized, parallel-group, double-blind, placebo-controlled design. Subjects smoked an active (2.64% THC) or placebo marijuana cigarette 2 and 6 hours after rimonabant dosing. Blood pressure and symptoms were monitored for 90 minutes after smoking while subjects remained seated. RESULTS: Marijuana smoking alone (ie, after placebo rimonabant) had no consistent effect on BP, but 22% of subjects experienced symptomatic (dizziness, lightheadedness) hypotension, as did 20% to 33% of subjects who received pretreatment with rimonabant, 1, 3, or 10 mg. No subject receiving rimonabant, 30 or 90 mg, before marijuana smoking experienced symptomatic hypotension. The 7 subjects who experienced symptomatic hypotension had significantly higher mean (SD) peak plasma THC concentrations (181.6 +/- 80.2) than did the 33 subjects who did not (109.0 +/- 62.6). Rimonabant by itself had no effects on BP and did not alter THC pharmacokinetics. CONCLUSIONS: These findings indicate that CB1 receptors play a role in mediating effects of cannabis smoking on BP in humans.

Adult↗
PubMed2006

Assessment of agonist and antagonist effects of tramadol in opioid-dependent humans.

The subjective, behavioral, and physiologic effects of racemic tramadol, an analgesic with low abuse liability and dual mu-opioid agonist and monoamine reuptake actions, were evaluated in 2 clinical pharmacology studies in dependent opioid abusers. In the withdrawal precipitation study, participants (N = 8) were maintained on methadone 60 mg/day orally and challenged with intramuscular tramadol, hydromorphone, naloxone, and placebo 20 hr after methadone administration. In the withdrawal suppression study, participants (N = 6) were maintained on hydromorphone given orally 10 mg 4 times daily, and spontaneous opioid withdrawal was produced by withholding doses for 23 hr. During the experimentally induced withdrawal, oral tramadol, hydromorphone, naltrexone, and placebo were given. In both studies a comprehensive panel of participant-rated, observer-rated, and physiologic measures were collected. In both studies, naloxone and naltrexone significantly increased measures of opioid withdrawal, whereas tramadol showed no discernible antagonist effects. In contrast, tramadol's pattern of effects was more similar to that of hydromorphone and suggestive of mild opioid-agonist effects (withdrawal suppression), though not to a statistically significant degree.

Adult↗
PubMed2005

Changes in HIV risk behaviors among patients receiving combined pharmacological and behavioral interventions for heroin and cocaine dependence.

Cocaine use is associated with injecting and sexual HIV risk behaviors. This study was a randomized controlled trial of behavioral interventions for cocaine dependence and HIV risk behaviors among dually (cocaine and heroin) dependent outpatients. Methadone maintenance was augmented with cognitive-behavioral therapy (CBT), contingency management (CM), both (CBT+CM), or neither. The study sample (n=81) was 52% female, 70% African American, and 37.9+/-7.0 years old. Proportions reporting HIV risk behaviors at intake were: 96.3% (78/81) injection drug use, 56.8% (46/81) sharing needles, 30.9% (25/81) unprotected sex, 28.4% (23/81) trading sex for money or drugs. Proportions who no longer reported behaviors at study exit were: 51.3% (40/78) injection drug use, 91.3% (42/46) sharing needles, 88% (22/25) unprotected sex, 91.3% (21/23) trading sex for money or drugs. Participants receiving CBT+CM were more likely to report cessation of unprotected sex relative to control (OR=5.44, 95% CI 1.14-26.0, p=0.034) but this effect was no longer significant after adjusting for drug-negative urines. These results suggest broad beneficial effects of methadone maintenance augmented with behavioral interventions for reducing HIV risk behaviors.

Adult↗
PubMed2005

Determination of total and free concentrations of the enantiomers of methadone and its metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine) in human plasma by enantioselective liquid chromatography with mass spectrometric detection.

A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection (LC-MS) has been validated for the determination of total and free plasma concentrations of (R)- and (S)-methadone (Met) and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP, the primary metabolite of Met), using their respective deuterium-labeled compounds as internal standards [(R,S)-d3-Met and (R,S)-d3-EDDP]. For total drug determinations, 1 ml human plasma was extracted, using a cation-exchange solid-phase extraction cartridge; the eluate was evaporated, reconstituted in the mobile phase, and injected into the LC-MS system. The free fractions of Met and EDDP were determined, using 500 microl of plasma, which were placed in an ultrafiltration device and centrifuged at 2000 x g until 250 microl of filtrate was collected. The filtrate was extracted as described above and analyzed. Enantioselective separations were achieved using an alpha1-acid glycoprotein chiral stationary phase, a mobile phase composed of acetonitrile-ammonium acetate buffer [10 mM, pH 7.0] (18:82, v/v), a flow rate of 0.9 ml/min at 25 degrees C. Under these conditions, enantioselective separations were observed for Met (alpha = 1.30) and EDDP (alpha = 1.17) within 15 min. Met, EDDP, [2H3]-Met and [2H3]-EDDP were detected using selected ion monitoring at m/z 310.30, 278.20, 313.30, and 281.20, respectively. Linear relationships between peak height ratio and drug-enantiomer concentrations were obtained for Met in the range 1.0-300.0 ng/ml, and for EDDP from 0.1 to 25.0 ng/ml with correlation coefficients greater than 0.999, where the lower limit of quantification (LLOQ) was 1 ng/ml for Met and 0.1 ng/ml for EDDP. The relative standard deviation (R.S.D.) expressed as R.S.D. for the intra- and inter-day precision of the method were < 5.3% and the R.S.D. for accuracy was < 5.0%. The method was used to analyze plasma samples obtained from patients enrolled in a Met-maintenance program.

Calibration↗
PubMed2005

Adverse events among patients in a behavioral treatment trial for heroin and cocaine dependence: effects of age, race, and gender.

Safety monitoring is a critical element of clinical trials evaluating treatment for substance dependence, but is complicated by participants' high levels of medical and psychiatric comorbidity. This paper describes AEs reported in a large (N = 286), 29-week outpatient study of behavioral interventions for heroin and cocaine dependence in methadone-maintained outpatients. A total of 884 AEs were reported (3.1 per patient, 0.12 per patient-week), the most common being infections (26.8%), gastrointestinal (20.5%), musculoskeletal (12.3%), and general (10%) disorders. Serious AEs were uncommon (1.6% of total). Female participants reported significantly higher rates of AEs (incidence density ratio, IDR = 1.38, p < 0.0001); lower rates of AEs were reported by African Americans (IDR = 0.73, p<0.0001) and participants over age 40 reported lower rates of AEs (IDR = 0.84, p = 0.0095). AE incidence was not associated with the study intervention or with psychiatric comorbidity. Further work is needed to adapt AE coding systems for behavioral trials for substance dependence; the standard Medical Dictionary for Regulatory Activities, International Federation of Pharmaceutical Manufacturers Associations (MedDRA) coding system used in this report did not contain a separate category for one of the most common types of AE, dental problems. Nonetheless, the data reported here should help provide a context in which investigators and IRBs can interpret the patterns of AEs they encounter.

Administration, Oral↗
PubMed2005

Influence of psychotherapy attendance on buprenorphine treatment outcome.

We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p=0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p=0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence.

Administration, Sublingual↗
PubMed2005

Menstrual cycle length during methadone maintenance.

AIMS: While the menstrual disruption of heroin has been demonstrated, there are few published data concerning methadone maintenance and menstrual function. This study was conducted to evaluate whether cycle length was more regular during methadone maintenance. SETTINGS: An out-patient research treatment program in Baltimore, Maryland, USA. PARTICIPANTS: A total of 191 heroin and cocaine-using women from two clinical trials, lasting 25-29 weeks; each woman was maintained on 70-100 mg of methadone. MEASUREMENTS: Start/end dates of each menses were collected. DESIGN: Menstrual patterns were classified as regular, irregular, transient amenorrhea, persistent amenorrhea or cycle restart. Repeated-measures regression modeling determined correlates of cycle length and predictors of long cycles (> 40 days) and short cycles (< 20 days). Bleeding episodes were defined as 1 or more bleeding days, bound by at least 2 non-bleeding days. Correlates/predictors examined were body mass index, drug use, methadone dose and race. FINDINGS: In the 133 women for whom menstrual patterns could be determined, cycle-length irregularity was common: irregular, 62 (46.7%); regular, 37 (27.8%); cycle restart, 16 (12%); persistent amenorrhea, 11 (8.3%); transient amenorrhea, seven (5.3%). Each additional week on methadone maintenance was associated with decreased risk of long (OR = 0.96, P < 0.01 and short (OR = 0.92, P < 0.01) cycles. Of 27 women with secondary amenorrhea pre-study, 16 (59%) restarted menses. Positivity for opioids or cocaine was not significantly associated with short or long cycles. CONCLUSIONS: Cycle length begins to normalize during methadone maintenance. Menses resumption may occur. Methadone maintenance, despite interfering with menstrual function in an absolute sense, may interfere less than illicit heroin abuse.

Adult↗
PubMed2005

A high-level specification for adaptive ecological momentary assessment: real-time assessment of drug craving, use and abstinence.

In psychological research, efforts to capture day-to-day human experience traditionally relied on pen-and-paper diaries and questionnaires. Some current studies, however, incorporate handheld computers, which provide researchers with many options and advantages in addition to providing more reliable data. One advantage of using handheld computers is the programmability of the electronic diary, which, compared to old-fashioned paper diaries, affords the researchers with a wealth of possibilities. An important possibility is to construct a built-in mechanism in the computer-administered questionnaires that would allow transparent branching, in which question presentation is contingent on participants' answers to previous questions. The major hurdle in implementing such an approach is the limitations of the platform used for such assessments: inexpensive "low-end" handheld devices. We propose a high-level specification which enables non-programming researchers to "branch" their questionnaires without modifications to the source code in a highly user-friendly fashion, with backtracking capability and very modest hardware requirements. A finite state automaton approach was implemented, we believe for the first time, to create an auto-trigger mechanism for the real-time evaluation of the conditions. This solution provides our investigators with the capacity to administer efficient assessments that are dynamically customized to reflect participants' behaviors without the need for any post-production programming.

Behavioral Research↗
PubMed2004

Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence.

BACKGROUND: Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. METHODS: Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. RESULTS: The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. CONCLUSIONS: A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.

Administration, Sublingual↗
PubMed2004

A laboratory study of hydromorphone and cyclazocine on smoking behavior in residential polydrug users.

The effects of cyclazocine and hydromorphone on spontaneous and laboratory cigarette smoking were compared in a double-blind, placebo-controlled, crossover study. Participants (seven men, one woman) received oral doses of placebo, cyclazocine (0.2, 0.4, and 0.8 mg) and hydromorphone (5 and 15 mg) in a randomized order on experimental days. Spontaneous smoking was recorded during two intervals on the experimental days: a 3-h period 5-8 h after drug administration (Interval 1), and the rest of the day (Interval 2). Measures of smoking topography and subjective and physiologic effects of a single cigarette were obtained on the experimental days. Neither hydromorphone nor cyclazocine significantly changed spontaneous smoking when compared to the placebo condition; however, compared to hydromorphone (5 mg), cyclazocine (0.4 and 0.8 mg) decreased spontaneous smoking during Interval 1. Hydromorphone (5 and 15 mg) and cyclazocine (0.4 and 0.8 mg) diminished smoking-induced increases in heart rate. Compared to the placebo condition, cyclazocine (0.2 and 0.4 mg) reduced exhaled carbon monoxide (CO) boost, a measure of smoke exposure. Further studies of the effects of kappa opioid agonists on smoking behavior may lead to a better understanding of the role of opiates in smoking behavior.

Adult↗
PubMed2004

Effects of high-dose intravenous buprenorphine in experienced opioid abusers.

Sublingual buprenorphine, a long-acting, partial mu-opioid agonist, is as effective as methadone in the treatment of heroin dependence, with a better safety profile due to its antagonist activity. However, the safety of therapeutic doses (8 to 16 mg) that might be diverted for intravenous (i.v.) use has not been demonstrated. To evaluate the safety and possible ceiling effects of buprenorphine administered i.v. to experienced opioid users, buprenorphine was administered to 6 nondependent opioid abusers residing on a research unit; the doses tested, in separate sessions, were 12 mg buprenorphine sublingual, i.v./sublingual placebo, and escalating i.v. buprenorphine (2, 4, 8, 12, and 16 mg). Physiologic and subjective measures were collected for 72 hours post-drug administration. Buprenorphine minimally but significantly increased systolic blood pressure. Changes in heart rate or oxygen saturation among the 7 drug conditions were not statistically significant. The mean maximum decrease in oxygen saturation from baseline was greatest for the 8-mg i.v. dose. Buprenorphine produced positive mood effects, although with substantial variability among participants. Onset and peak effects occurred earlier following i.v. administration: peak i.v. effects occurred between 0.25 and 3 hours; peak sublingual effects occurred at 3 to 7 hours. Duration of effects varied among the outcome measures. The dose-response curves were flat for most parameters, particularly subjective measures. Side effects were mild except in one participant who experienced severe nausea and vomiting after the 12-mg i.v. dose. Buprenorphine appears to have a ceiling for cardiorespiratory and subjective effects and a high safety margin even when taken by the i.v. route.

Administration, Sublingual↗
PubMed2003

Quantitative determination of the enantiomers of methadone and its metabolite (EDDP) in human saliva by enantioselective liquid chromatography with mass spectrometric detection.

A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection (LC-MS) has been developed and validated for the simultaneous determination of saliva concentrations of (R)- and (S)-methadone (Met) and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (EDDP, a primary metabolite of Met). Saliva specimens were collected using Salivette devices (Sarsedt), and centrifuged; collected saliva was then spiked with deuterated internal standards, D3-Met and D3-EDDP, and directly injected into the LC-MS. Enantioselective separations were achieved on a liquid chromatographic chiral stationary phase (CSP) based upon immobilized alpha(1)-acid glycoprotein (AGP) using a mobile phase composed of acetonitrile: ammonium acetate buffer (10mM, pH 7.0) in a ratio of 18:82 (v/v), a flow rate of 0.9 ml/min and a temperature of 25 degrees C. Under these conditions, enantioselective separations were observed for methadone (alpha=1.30) and EDDP (alpha=1.17) within 15 min. Met, EDDP, D3-Met and D3-EDDP were detected using selected ion monitoring at m/z 310.20, 278.20, 313.20 and 281.20, respectively. Linear relationships between peak height ratio and drug-enantiomer concentrations were obtained for methadone in the range of 5.0-600.0 ng/ml, and for EDDP from 0.5 to 15.0 ng/ml per enantiomer with correlation coefficients better than 0.9994, where lower limit of quantification (LLOQ) for Met was 5 ng/ml and for EDDP 0.5 ng/ml. Acceptable intra- and inter-day precision of the method (CVs<4.0%) and accuracy (CVs<4.0%) were obtained. These findings demonstrate the accuracy and precision of the method used to successfully analyze saliva obtained from patients enrolled in a methadone-maintenance program.

Chromatography, Liquid↗
PubMed2003

The reinstatement model and relapse prevention: a clinical perspective.

OBJECTIVES: This commentary assesses the degree to which the reinstatement model is homologous to the human experience of relapse. RESULTS: A review of the literature suggests that the relationship is less clear than is often assumed, largely due to a lack of prospective data on the precipitants and process of relapse (especially relapse to heroin or cocaine abuse). However, reinstatement does not need to resemble relapse to have immediate clinical value; predictive validity as a medication screen would be sufficient. Whether the model has predictive validity is unknown, because, to date, very few clinical trials have tested medications that are effective in the reinstatement model, and even fewer have used designs comparable to those of reinstatement experiments. A clinical trial comparable to a reinstatement experiment would enroll participants who are already abstinent, and its main outcome measure would be propensity to undergo a specific type of relapse (e.g., relapse induced by stress or cues). CONCLUSIONS: Until clinical and preclinical work are more comparable, criticisms of the reinstatement model's presumed shortcomings are premature.

Animals↗