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Director's Report to the National Advisory Council on Drug Abuse - May, 2010



Research Findings - Research on Pharmacotherapies for Drug Abuse

Maternal Buprenorphine Dose, Placenta Buprenorphine, and Metabolite Concentrations and Neonatal Outcomes

Buprenorphine is approved as pharmacotherapy for opioid dependence in nonpregnant patients in multiple countries and is currently under investigation for pregnant women in the United States and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in five term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships among maternal buprenorphine dose, placenta concentrations, and neonatal outcomes after controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue, except for buprenorphine in three placentas. Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations than in meconium. Statistically significant correlations were observed for a) mean maternal daily dose from enrollment to delivery, b) placenta buprenorphine-glucuronide concentration, c) norbuprenorphine-glucuronide concentrations, d) time to neonatal abstinence syndrome onset and duration, e) norbuprenorphine/norbuprenorphine-glucuronide ratio f) maximum neonatal abstinence syndrome score and g) newborn length. Analysis of buprenorphine and metabolites in this alternative matrix may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. Concheiro M, Jones HE, Johnson RE, Choo R, Shakleya DM, Huestis MA. Maternal buprenorphine dose, placenta buprenorphine, and metabolite, concentrations and neonatal outcomes. Ther Drug Monit. 2010 Mar 4.

Clinical Characteristics of Central European and North American Samples of Pregnant Women Screened for Opioid Agonist Treatment

Little comparable information is available regarding clinical characteristics of opioid-dependent women from different countries. In the present study, women from the USA, Canada and a Central European country, Austria, were screened for participation in the Maternal Opioid Treatment Human Experimental Research (MOTHER) study, were compared with respect to their demographic and addiction histories. Pregnant women (n = 1,074) were screened for study participation using uniformed clinical criteria and instruments. The screening results were compared with regard to exclusion, demographics, drug use, and psychosocial and treatment histories. Compared to the screened US and Canadian women, Austrian women were more likely to be younger (p < 0.001), white (p < 0.001), had significantly lower levels of educational attainment (p < 0.001), were less likely to use opioids daily (p < 0.001) and more likely to have been prescribed buprenorphine (p < 0.001). Compared to both rural and urban US groups, the Austrian group was less likely to have legal issues (p < 0.001) and was younger when first prescribed agonist medication (p < 0.001). The differences between North American and European groups may offer unique insights concerning treatment and pregnancy outcomes for opioid-dependent pregnant women. Unger AS, Martin PR, Kaltenbach K, Stine SM, Heil SH, Jones, HE, Arria AM, Coyle MG, Selby P, Fischer G. Clinical characteristics of central European and North American samples of pregnant women screened for opioid agonist treatment. Eur Addict Res. 2010 Feb 17; 16(2):99-107.

Concurrent Validation of the Clinical Opiate Withdrawal Scale (COWS) and Single-item Indices Against the Clinical Institute Narcotic Assessment (CINA) Opioid Withdrawal Instrument

The Clinical Opiate Withdrawal Scale (COWS) is an 11-item clinician-administered scale assessing opioid withdrawal. Though commonly used in clinical practice, it has not been systematically evaluated. This study validates the COWS in comparison to the validated Clinical Institute Narcotic Assessment (CINA) scale. Forty-six out-of-treatment opiate-dependent volunteers were enrolled in a residential trial and stabilized on morphine 30 mg given subcutaneously 4 times daily. Subjects then underwent double-blind, randomized challenges of intramuscularly administered placebo and naloxone (0.4 mg) on separate days, during which the COWS, CINA, and visual analog scale (VAS) assessments were concurrently obtained. Correlations between mean peak COWS and CINA scores as well as self-report VAS questions were calculated. Placebo was not associated with any significant elevation of COWS, CINA, or VAS scores. Internal consistency of COWS was high. The COWS and CINA followed comparable trajectories for the time course of opioid withdrawal. The study showed that the COWS is a valid instrument with sufficient sensitivity to detect mild opiate withdrawal; it would therefore be expected to detect moderate to severe withdrawal. Tompkins DA, Bigelow GE, Harrison JA, Johnson RE, Fudula PJ, Strain EC. Concurrent validation of the Clinical Opiate Withdrawal Scale (COWS) and single-item indices against the Clinical Institute Narcotic Assessment (CINA) opioid withdrawal scale. Drug and Alcohol Dep. 2009; 105: 154-159.

Agonist-like Pharmacotherapy for Stimulant Dependence: Preclinical, Human Laboratory, and Clinical Studies

A variety of natural and synthetic agents have long been used for stimulant properties, with nontherapeutic use producing multiple waves of stimulant abuse and dependence. The multitude of effects of stimulants exist on a continuum, and accordingly, this project characterizes stimulant abuse/dependence and candidate pharmacotherapies in this manner. Behavioral therapy and medications have been investigated for treatment of stimulant abuse/dependence. Effectiveness of some behavioral interventions has been demonstrated. Most medications studied have been found to lack efficacy. However, an expanding literature supports use of agonist-like medications to treat stimulant abuse/dependence, a strategy effective for nicotine and opiate dependence. The agonist-like conceptualization for stimulant dependence posits that medications with properties similar to that of the abused drug, but possessing lesser abuse liability, will normalize neurochemistry and stabilize behavior, thus reducing drug use. Data suggest use of a range of medications, from l-dopa/carbidopa to amphetamine preparations, depending on the severity of use. This report reviews preclinical, human laboratory, and clinical trial data supporting the agonist-like approach, including risks and benefits. Future directions for development of agonist-like medications are also discussed. Herin DV, Rush CR, Grabowski J. Agonist-like pharmacotherapy for stimulant dependence: preclinical, human laboratory, and clinical studies. Ann NY Acad Sci. 2010 Feb; 1187: 76-100.

Randomized, Double-blind, Placebo-controlled Trial of Modafinil for the Treatment of Methamphetamine Dependence

A 12-week, randomized, placebo-controlled Phase II clinical trial comparing the efficacy of 400 mg modafinil (once daily) to placebo was carried out in 71 treatment-seeking methamphetamine dependent participants. There were no statistically significant effects for modafinil on methamphetamine use, retention, depressive symptoms, or craving. In this study, modafinil was no more effective than placebo at 400 mg daily in a general sample of methamphetamine users. Heinzerling KG, Swanson A, Kim S., Cederblon L, Moe A, Ling W, Shoptaw S. Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence. Drug and Alcohol Dep. 2009 (e-publication ahead of print).

The Cardiovascular and Subjective Effects of Methamphetamine Combinded With γ-Vinyl-γ-Aminobutyric Acid (GVG) in Non-treatment Seeking Methamphetamine-dependent Volunteers

γ-Vinyl-γ-aminobutyric acid (GVG) elevates central nervous system γ-aminobutyric acid (GABA) levels by irreversibly inhibiting GABA transaminase. An open-label clinical trial in humans suggested that GVG may reduce cocaine and methamphetamine use. A double-blind, placebo-controlled parallel group study of GVG interaction with the cardiovascular and subjective effects produced by methamphetamine was carried out to test safety and obtain preliminary data on efficacy of GVG for treating methamphetamine dependence in non-treatment seeking methamphetamine dependent volunteers. Subjects received either GVG (n=8) or placebo (n=9) by random assignment. GVG treatment was initiated at 1 g/day and increased to 5 g/day. After reaching the target dose of 5 g/day, participants received methamphetamine (15 + 30 mg iv) and cardiovascular and subjective effects were assessed. No serious adverse events were noted. No significant differences were detected between the groups for systolic or diastolic blood pressure, or heart rate, following methamphetamine exposure. Methamphetamine-induced subjective effects were statistically similar between GVG and placebo treatment groups. The data indicate that GVG treatment is generally well tolerated but not efficacious in attenuating the positive subjective effects of methamphetamine in a human laboratory setting. De La Garza II R, Zorick T, Heinzerling KG, Nusinowitz S, London ED, Shoptaw S, Moody DE, Newton TF. The cardiovascular and subjective effects of methamphetamine combined with γ-vinyl-γ-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers. Pharmacology, Biochemistry and Behavior. 2009 94: 186-193.

Methamphetamine and Paranoia: the Methamphetamine Experience Questionnaire

Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, this project created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA-induced paranoia. They administered the MEQ to 274 MA-dependent subjects. Of the total subjects, 45% (123) first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA-induced paranoia, respectively). Test-retest and inter-rater reliability for MA-induced paranoia showed substantial agreement (kappa = .77, p < .05 and kappa = .80, p < .05, respectively). First episodes of paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the Brief Symptom Inventory (BSI) paranoid ideation scale (rho = .27, p < .05). As expected, there was a poor correlation between paranoia on the MEQ and the BSI depression scale (rho = .14, p = .07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use. Leamon MH, Flower K, Salo RE, Nordahl TE, Kranzier HR, Galloway GP. Methamphetamine and paranoia: the methamphetamine experience questionnaire. Am J Addict. 2010 Mar 1; 19(2): 155-168.

Human Sex Differences in d-Amphetamine Self-administration

Women and men may respond differently to the effects of stimulants such as amphetamine and cocaine. In order to assess potential sex differences in the reinforcing effects of d-amphetamine, a retrospective-analysis was conducted on data collected from three studies that employed similar d-amphetamine self-administration procedures and used identical subject-rated drug-effect measures. Data from 10 women and 15 men were included in the analysis. In all studies, participants sampled placebo, low (8-10 mg) or high (16-20 mg) dose oral d-amphetamine. Following sampling sessions, participants worked for capsules containing one eighth of the previously sampled dose on a modified progressive-ratio schedule of reinforcement. The authors hypothesized that women and men would be differentially sensitive to the reinforcing effects of d-amphetamine. A two-way mixed-model analysis of variance (sex and dose) and planned comparisons were used in the statistical analyses. The low dose of d-amphetamine functioned as a reinforcer in women, but not men, whereas the high dose of d-amphetamine functioned as a reinforcer in men, but not women. Men self-administered significantly more capsules under the high dose condition than women. The results of this study suggest that men are more sensitive to the reinforcing effects of a high dose of d-amphetamine than women. Future research is needed that determines prospectively the reinforcing effects of weight-adjusted doses of d-amphetamine in women and men while controlling for menstrual cycle phase. Vansickel AR, Stoops WW, Rush CR. Addiction. 2010 Feb 9. [Epub ahead of print].

Working Memory fMRI Activation in Cocaine-dependent Subjects: Association with Treatment Response

Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared with non-drug-using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alterations of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections. Moeller FG, Steinberg JL, Schmitz JM, Ma L, Liu S, Kjome KL, Rathnayaka N, Kramer LA, Narayana PA. Psychiatry Res. 2010 Mar 30; 181(3):174-182.

Randomized Trial of Continuing Care Enhancements for Cocaine-dependent Patients Following Initial Engagement

The effects of cognitive-behavioral relapse prevention (RP), contingency management (CM), and their combination (CM + RP) were evaluated in a randomized trial with 100 cocaine-dependent patients (58% female, 89% African American) who were engaged in treatment for at least 2 weeks and had an average of 44 days of abstinence at baseline. The participants were from intensive outpatient programs, which provide 10 hr per week of group counseling. The CM protocol provided gift certificates (maximum value $1,150; mean received = $740) for cocaine-free urines over 12 weeks on an escalating reinforcement schedule, and weekly individual RP sessions were offered for up to 20 weeks. Average number of RP sessions attended was 3 in RP and 13 in CM + RP. Generalizing estimation equation analyses over 18 months postrandomization showed significant effects for CM (but not RP) on urine toxicology and self-reported cocaine use (p = .05), with no significant CM x RP interactions. Secondary analyses indicated CM + RP produced better cocaine urine toxicology outcomes at 6 months than treatment as usual, odds ratio [OR] = 3.96 (1.33, 11.80), p < .01, and RP, OR = 4.89 (1.51, 15.86), p < .01, and produced better cocaine urine toxicology outcomes at 9 months than treatment as usual, OR = 4.21 (1.37, 12.88), p < .01, and RP, OR = 4.24 (1.32, 13.65), p < .01. Trends also favored CM + RP over CM at 6 months, OR = 2.93 (0.94, 9.07), p = .06, and 9 months, OR = 2.93 (0.94, 9.10), p = .06. Differences between the conditions were not significant after 9 months. These results suggest CM can improve outcomes in cocaine-dependent patients in intensive outpatient programs who have achieved initial engagement, particularly when it is combined with RP. McKay JR, Lynch KG, Coviello D, Morrison R, Cary MS, Skalina L, Plebani J. J Randomized Trial of Continuing Care Enhancements for Cocaine-dependent Patients Following Initial Engagement. Consult Clin Psychol. 2010 Feb; 78(1): 111-120.

Lower Levels of Endogenous Dopamine in Patients with Cocaine Dependence: Findings from PET Imaging of D2/D3 Receptors Following Acute Dopamine Depletion

Previous PET imaging studies have demonstrated that cocaine dependence is associated with a decrease in dopamine type 2 and 3 receptor binding in cocaine individuals relative to healthy comparison subjects. Given the nature of PET imaging, it is possible that the measured decrease in radiotracer binding results from an increase in baseline dopamine levels. The purpose of this study was to measure D2/D3 receptors following acute dopamine depletion in cocaine-dependent volunteers relative to healthy comparison subjects. Fifteen cocaine-dependent volunteers and 15 healthy matched comparison subjects were scanned using PET, with the dopamine receptor radiotracer [11C]raclopride, at baseline and again following acute depletion of endogenous dopamine via α-methyl-para-tyrosine (AMPT) administration. Changes in radiotracer binding were measured in the subdivisions of the striatum (caudate, putamen, and ventral striatum) in addition to the striatum as a whole. Findings revealed that cocaine dependent volunteers exhibited lower levels of endogenous dopamine relative to comparison subjects, which was measured as an increase in [11C]raclopride[11C]raclopride binding following AMPT administration. The increase in [11C]raclopride binding in the striatum was 11.1% (SD=4.4%) in healthy comparison subjects and 5.7% (SD=5.9%) in cocaine-dependent volunteers. Similar differences were seen in the subdivisions of the striatum. The results of the study indicate that cocaine dependence is associated with a decrease in the levels of striatal dopamine, and support a series of findings from previous studies that cocaine dependence is associated with a decrease in dopamine transmission in the striatum. This imaging study shows that cocaine dependence is associated with a reduction in endogenous dopamine. Martinez D, Greene K, Broft A, Kumar D, Liu F, Narendran R, Slifstein M, Van Heertum R, Kleber, HD. Lower levels of endogenous dopamine in patients with cocaine dependence: findings from PET imaging of D2/D3 receptors following acute dopamine depletion. Am J Psychiatry. 2009; 166: 1170-1177.

Monetary Alternative Reinforcers More Effectively Decrease Intranasal Cocaine Choice than Food Alternative Reinforcers

Cocaine dependence continues to be a significant public health concern. Contingency management, wherein alternative reinforcers are made available upon cocaine abstinence, has shown promise for decreasing cocaine use. Other research has modeled this effect and demonstrated that alternative reinforcers also reduce cocaine self-administration in the laboratory. Results from both clinical and laboratory studies suggest that the type and value of alternative reinforcers influences their ability to decrease drug choice. The purpose of the present experiment was to determine the effect of money or food alternative reinforcers, valued at $0.01, 0.25, 0.50 and 1.00, on intranasal cocaine (4 [placebo] and 30 mg) choice. Cocaine was chosen to a greater extent than placebo across alternative reinforcer types and values, but the monetary alternative reinforcer suppressed drug choice to a greater degree than the food reinforcer. These results are concordant with previous findings and suggest that money may be a more effective alternative reinforcer for decreasing cocaine use. Future research should determine the sensitivity of this model to specific behavioral aspects of contingency management and whether food could compete with drugs as reinforcers in humans under laboratory conditions. Stoops WW, Lile JA, Rush CR. Monetary Alternative Reinforcers More Effectively Decrease Intranasal Cocaine Choice than Food Alternative Reinforcers. Pharmacol Biochem Behav. 2010 Apr; 95(2): 187-191.

Reactivity to Laboratory Stress Provocation Predicts Relapse to Cocaine

Cocaine dependence is a chronic relapsing disorder characterized by periods of abstinence and high rates of return to drug using behavior. Elevated levels of stress have been associated with relapse to cocaine; however, the nature of this association is not well understood. The relationship between reactivity to three human laboratory provocations and relapse to cocaine was investigated. Participants were 53 cocaine-dependent individuals who were admitted for a 2-day inpatient stay during which a psychosocial provocation (i.e., the Trier Social Stress Task), a pharmacological provocation (i.e., administration of 1 microg/kg corticotrophin releasing hormone; CRH), and a drug cue exposure paradigm were completed. Adrenocorticotrophic hormone (ACTH), cortisol, heart rate, and subjective cocaine craving and stress were assessed at baseline and at multiple time points post-task. Participants' cocaine use was monitored for approximately 1 month following testing. The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving and stress were significant predictors of cocaine use during follow-up. In response to the Trier, attenuated neuroendocrine responses were significant predictors of cocaine use. The findings provide further evidence of the ability of laboratory paradigms to predict relapse. The observed associations between stress reactivity and subsequent cocaine use highlight the clinical importance of the findings. Predictors of relapse may vary based on the type of provocation utilized. Interventions aimed at normalizing stress response, as measured using laboratory paradigms, may prove useful in relapse prevention. Back SE, Hartwell K, DeSantis SM, Saladin M, McRae-Clark AL, Price KL, Moran-Santa Maria MM, Baker NL, Spratt E, Kreek MJ, Brady KT. Reactivity to Laboratory Stress Provocation Predicts Relapse to Cocaine. Drug Alcohol Depend. 2010 Jan 1; 106(1): 21-27.

Cognitive Enhancement as a Pharmacotherapy Target for Stimulant Addiction

No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha(2)-adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction. Sofuoglu M. Cognitive enhancement as a pharmacotherapy target for stimulant addiction. Addiction. 2010 Jan; 105(1): 38-48.

Cocaine Abuse Versus Cocaine Dependence: Cocaine Self-administration and Pharmacodynamic Response in the Human Laboratory

Cocaine has high abuse liability but only a subset of individuals who experiment with it develop dependence. The DSM-IV (APA. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-R. American Psychiatric Association, Washington, DC, 2000) provides criteria for diagnosing cocaine abuse and cocaine dependence as distinct disorders- the latter characterized by additional symptoms related to loss of control over drug use. In this study, two groups of cocaine users (n=8/group), matched on demographic factors and length of cocaine use history and meeting criteria for either cocaine abuse (CocAb) or cocaine dependence (CocDep), were compared on (1) measures related to impulsivity and sensation seeking, (2) response to experimenter-administered cocaine (0, 12.5, 25 and 50mg/70 kg, i.v.), and (3) cocaine self-administration using a Relapse Choice and a Progressive Ratio Procedure (0, 12.5 and 25mg/70 kg, i.v.). Groups did not differ on impulsivity or sensation seeking scores. After experimenter-administered cocaine, the CocAb group reported feeling more suspicious and observers rated them significantly higher on unpleasant effects (e.g., irritability, difficulty concentrating). In contrast, the CocDep group reported significantly greater desire for cocaine, which was sustained over the course of the study, and gave higher street value estimates for cocaine (p<0.05). While cocaine self-administration was dose-related and generally comparable across the two procedures, the CocDep users chose to take significantly more cocaine than the CocAb users. These data suggest that, while regular long-term users of cocaine with cocaine abuse or dependence diagnoses cannot be distinguished by trait measures related to impulsivity, they do exhibit significant differences with regard to cocaine-directed behavior and response to cocaine administration. Walsh SL, Donny EC, Nuzzo PA, Umbricht A, Bigelow GE. Cocaine Abuse Versus Cocaine Dependence: Cocaine self-administration and pharmacodynamic response in the human laboratory. Drug Alcohol Depend. 2010 Jan 1; 106(1): 28-37.

Delta9-tetrahydrocannabivarin Testing May Not Have the Sensitivity to Detect Marijuana use Among Individuals Ingesting Dronabinol

The purpose of this study was to determine whether Delta(9)-tetrahydrocannabivarin (THCV), a plant cannabinoid, is a sensitive measure to detect recent marijuana use in cannabis dependent patients. It has been purported that smoking an illicit plant cannabis product will result in a positive THCV urinalysis, whereas the oral ingestion of therapeutic THC such as dronabinol will result in a negative THCV urinalysis, allowing for discrimination between pharmaceutical THC products and illicit marijuana products. In a double-blind placebo-controlled trial to determine the efficacy of dronabinol in cannabis dependence, all 117 patients produced a positive urine for the marijuana metabolite 11-nor-Delta(9)-THC-9-carboxylic acid; THC-COOH, but 50% had an undetectable (<1 ng/ml) THCV-COOH test. This suggests that THCV may not be a sensitive enough measure to detect recent marijuana use in all heavy marijuana users or that its absence may not discriminate between illicit marijuana use and oral ingestion of THC products such as dronabinol. The investigators propose that the lack of THCV detection may be due to the variability of available cannabis strains smoked by marijuana users in community settings. Levin FR, Mariani JJ, Brooks DJ, Xie S, Murray KA. Delta9-tetrahydrocannabivarin testing may not have the sensitivity to detect marijuana use among individuals ingesting dronabinol. Drug Alcohol Depend. 2010 Jan 1; 106(1): 65-68.

A Double-blind, Placebo-controlled, Randomized Clinical Trial of Oral Selegiline Hydrochloride for Smoking Cessation in Nicotine-dependent Cigarette Smokers

The primary aim of this study was to determine the safety and efficacy of the monoamine oxidase-B (MAO-B) inhibitor selegiline hydrochloride (SEL, l-Deprenyl; Eldepryl) as an aid for smoking cessation in cigarette smokers. One hundred and one nicotine-dependent adult cigarette smokers without current psychiatric or substance use disorders participated in this 8-week randomized, double-blind, placebo-controlled trial. Participants received either SEL (5mg bid, n=51) or placebo (PLO, n=50), in combination with brief (<10 min) manualized smoking cessation counseling. The main smoking outcome measures were 7-day point prevalence abstinence at end of trial (EOT), 4-week continuous smoking abstinence at end of trial (CA), and 7-day point prevalence abstinence at 6-month follow-up (6MFU). Abstinence was determined by an absence of self-reported cigarette smoking and biochemically verified by expired breath carbon monoxide and plasma cotinine levels. Rates of smoking abstinence did not differ by medication group (EOT: SEL=16%, PLO=20%, p=0.57; CA: SEL=14%, PLO=18%, p=0.56; 6MFU: SEL=12%, PLO=16%, p=0.54). Adverse events were modest and comparable between medication groups. Participants receiving SEL were more likely than those receiving PLO to report dry mouth (25.5% versus 8.2%, p<0.05). Results suggest that SEL was safe and well-tolerated by adult cigarette smokers, but did not improve smoking abstinence rates compared to PLO. Weinberger AH, Reutenauer EL, Jatlow PI, O'Malley SS, Potenza MN, George TP. A double-blind, placebo-controlled, randomized clinical trial of oral selegiline hydrochloride for smoking cessation in nicotine-dependent cigarette smokers. Drug Alcohol Depend. 2010 Mar 1; 107(2-3): 188-195.

Smoking in Pregnant Women Screened for an Opioid Agonist Medication Study Compared to Related Pregnant and Non-pregnant Patient Samples

Little is known about the prevalence and severity of smoking in pregnant opioid dependent patients. To first characterize the prevalence and severity of smoking in pregnant patients screened for a randomized controlled trial, Maternal Opioid Treatment: Human Experimental Research (MOTHER), comparing two agonist medications; and second, to compare the MOTHER screening sample to published samples of other pregnant and/or patients with substances use disorders. Pregnant women (N = 108) screened for entry into an agonist medication comparison study were retrospectively compared on smoking variables to samples of pregnant methadone-maintained patients (N = 50), pregnant opioid or cocaine dependent patients (N = 240), non-pregnant methadone-maintained women (N = 75), and pregnant non-drug-addicted patients (N = 1,516). Of screened patients, 88% (n = 95) smoked for a mean of 140 months (SD = 79.0) starting at a mean age of 14 (SD = 3.5). This rate was similar to substance use disordered patients and significantly higher compared to general pregnant patients (88% vs. 22%, p < .001). Aggressive efforts are needed to reduce/eliminate smoking in substance-abusing pregnant women. Jones HE, Heil SH, O'Grady KE, Martin PR, Kaltenbach K, Coyle MG, Stine SM, Selby P, Arria AM, Fischer G. Smoking in pregnant women screened for an opioid agonist medication study compared to related pregnant and non-pregnant patient samples. Am J Drug Alcohol Abuse. 2009; 35(5): 375-380.

Provision of Ancillary Medications During Buprenorphine Detoxification Does Not Improve Treatment Outcomes

For individuals dependent on opioids, recovery efforts begin with a period of withdrawal that typically includes discomfort from symptoms, possibly precipitating a return to drug use. This study investigated potential associations between provision of ancillary medications for opioid withdrawal symptoms and treatment outcomes in 139 participants receiving buprenorphine in a 13-day detoxification trial. Outcome measures include the number of opioid-free urine samples collected and retention in treatment. Ancillary medications were provided to 70% of participants: 59% received medication for insomnia, 45% for anxiety, 40% for bone pain, 35% for nausea, and 28% for diarrhea. Findings indicate no difference in the number of opioid-free urine samples between the group receiving ancillary medication and the group who did not. Tests of specific ancillary medications indicate that those who received diarrhea medication had fewer opioid-free urines than those who did not (P = .004). Results also indicate that participants attended fewer days of treatment if they received anxiety, nausea, or diarrhea medication compared to no medication (all P values <.05). Hillhouse M, Domier CP, Chim D, Ling W. J Addict Dis. 2010 Feb: 29(1): 23-29.

A Method to Diagnose Opioid Dependence Resulting from Heroin versus Prescription Opioids using the Composite International Diagnostic Interview

Treatment research with opioid-dependent populations has not traditionally distinguished between those dependent on prescription opioids versus dependent upon heroin. Evidence suggests there is a substantial subpopulation of individuals with opioid dependence resulting largely or exclusively from prescription opioid use. Because this subpopulation may respond to treatment differently from heroin users, a method for discriminating DSM-IV opioid dependence due to prescription opioid use would provide more precision when examining this population. This paper describes an innovative method using a currently available diagnostic instrument, to diagnose DSM-IV opioid dependence and distinguish between dependence resulting from prescription opioids versus dependence upon heroin. This method employs the CIDI in an enhanced format to differentiate these populations. This format includes expanded listing of drugs for reference, a change in the interview to differentiate the type of opioid and special training for staff. Eight hundred CIDI administrations have been accomplished; staff reports that the enhanced CIDI is practicable and that participants are able to make a distinction between their heroin use and other opioid use. Potter JS, Prather K, Kropp F, Byrne M, Sullivan CR, Mohamedi N, Copersino ML, Weiss RD. Contemp Clin Trials. 2010 Mar; 31(2):185-188. Epub 2010 Jan 14.


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