Biomedical subjects

Kevin G Lynch

Publications and source records attributed to Kevin G Lynch.

At least 19 recordsLinked to original sources

PubMed2006

Selective strengthening of conditioned behaviors that occur during periods of amphetamine exposure.

Exposure to psychomotor stimulants, during conditioning sessions, can lead to a persistent increase in the strength of conditioned behaviors and the effects of conditioned stimuli, which can be detected in subsequent drug-free periods. It is possible that the effects are selective for the behaviors and stimuli conditioned during drug exposure. The present study was designed to test this prediction. Animals were trained to discriminate two sets of stimuli. For each set, lever pressing during the presentation of one stimulus (S+) was reinforced and responding during the presentation of the other stimulus (S-) had no programmed consequences. Following an initial acquisition phase, training with one set of stimuli continued during sessions of amphetamine exposure, whereas training with the second set continued during saline exposure (20 intermixed sessions). The findings of subsequent drug-free choice tests showed that the drug history selectively enhanced the propensity of animals to engage in the drug-assigned behavior relative to the saline-assigned behavior. This change in behavior was evident in S+, but not S- trials and was potentially mediated by an acute effect of amphetamine on stimulus conditioning. The findings provide novel evidence that the facilitative effects of coincident conditioning and acute psychomotor stimulant exposure can be selective for the stimuli and behaviors conditioned during the drug exposure. These findings are relevant to hypotheses regarding the etiology of drug addiction.

Amphetamine↗

PubMed2006

Developing adaptive treatment strategies in substance abuse research.

For many individuals, substance abuse possesses characteristics of chronic disorders in that individuals experience repeated cycles of cessation and relapse; hence viewing drug dependence as a chronic, relapsing disorder is increasingly accepted. The development of a treatment for a chronic disorder requires consideration of the ordering of treatments, the timing of changes in treatment, and the use of measures of response, burden and adherence collected during treatment to make further treatment decisions. Adaptive treatment strategies provide a vehicle through which these issues can be addressed and thus provide a means toward improving and informing the clinical management of chronic substance abuse disorders. The sequential multiple assignment randomized trial (SMART) is particularly useful in developing adaptive treatment strategies. Simple analyses that can be used with the SMART design are described. Furthermore, the SMART design is compared with standard experimental designs.

Algorithms↗

PubMed2006

Initial evidence for the reliability and validity of a "Lite" version of the Addiction Severity Index.

PURPOSE: To evaluate the psychometric properties of a shortened version of the baseline ASI-5, the ASI-L-VA. METHOD: Two samples were recruited from intensive outpatient treatment and a methadone maintenance clinic. For Sample A (n=145), two versions of the Addiction Severity Index (i.e., ASI-5 and ASI-L-VA) were administered several days apart in counterbalanced order by different interviewers. Sample B (n=50) was similarly administered the standard ASI-5 twice. RESULTS: For Sample A, the internal consistency (coefficient alphas) of 11 of 19 summary scores derived from the ASI-5 were good, 4 fair, and 4 unacceptable. The results for the ASI-L-VA summary scores indicated that eight were good, six fair, and five unacceptable. The correlations between ASI problem areas were generally low for both versions (supporting the independence of the ASI areas), and none of the t-tests comparing corresponding correlations between the ASI-5 and ASI-L-VA approached statistical significance. The Sample A intraclass correlation coefficient (ICC) results evaluating agreement of the summary scores derived from the ASI-5 at one timepoint and those derived from ASI-L-VA at another point (i.e., concurrent validity) revealed at least fair agreement in all but one instance. Additionally, a comparison of the ICC results for Samples A and B (i.e., ASI-L-VA/ASI-5 versus ASI-5/ASI-5, respectively) revealed that in 13 of 26 cases the ICCs were at the same level of agreement. When level of agreement was discordant, in nine cases the ICCs comparing the ASI-5 and ASI-L-VA exhibited greater agreement and in four cases the ICCs comparing two ASI-5 administrations exhibited greater agreement. CONCLUSIONS: The ASI-L-VA, a reduced item set from the ASI-5, yielded similar information on problem severity as the standard ASI-5.

Adult↗

PubMed2006

Accumbal neurons that are activated during cocaine self-administration are spared from inhibitory effects of repeated cocaine self-administration.

Hypoactivity of the accumbens is induced by repeated cocaine exposure and is hypothesized to play a role in cocaine addiction. However, it is difficult to understand how a general hypoactivity of the accumbens, which facilitates multiple types of motivated behaviors, could contribute to the selective increase in drug-directed behavior that defines addiction. Electrophysiological recordings, made during sessions in which rats self-administer cocaine, show that most accumbal neurons that encode events related to drug-directed behavior achieve and maintain higher firing rates during the period of cocaine exposure (Task-Activated neurons) than do other accumbal neurons (Task-Non-Activated neurons). We have hypothesized that this difference in activity makes the neurons that facilitate drug-directed behavior less susceptible than other neurons to the chronic inhibitory effects of cocaine. A sparing of neurons that facilitate drug-directed behavior from chronic hypoactivity might lead to a relative increase in the transmission of neuronal signals that facilitate drug-directed behavior through accumbal circuits and thereby contribute to changes in behavior that characterize addiction (ie differential inhibition hypothesis). A prediction of the hypothesis is that neurons that are activated in relation to task events during cocaine self-administration sessions will show less of a decrease in firing across repeated self-administration sessions than will other neurons. To test this prediction, rats were exposed to 30 daily (6 h/day) cocaine self-administration sessions. Chronic extracellular recordings of single accumbal neurons were made during the second to third session and the 30th session. Between-session comparisons showed that decreases in firing were exhibited by Task-Non-Activated, but not by Task-Activated, neurons. During the day 30 session, the magnitude of the difference in firing rate between the two groups of neurons was positively related to the propensity of animals to seek and take cocaine. The findings of the present study are consistent with a basic prediction of the differential inhibition hypothesis and may be relevant to understanding cocaine addiction.

Action Potentials↗

PubMed2006

A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms.

BACKGROUND: This trial evaluated the efficacy of amantadine, propranolol and their combination in cocaine dependent patients with severe cocaine withdrawal symptoms. METHODS: Cocaine withdrawal symptom severity was measured by the cocaine selective severity assessment (CSSA). One hundred and ninety-nine patients with high scores on the CSSA participated in a 10-week double-blind trial. Patients were randomly assigned to receive amantadine (300 mg/day), propranolol (100mg/day), a combination of amantadine (300 mg/day) and propranolol (100mg/day) or matching placebo capsules. The primary outcome measure was cocaine abstinence. RESULTS: In the intent-to-treat sample, there were no significant differences between the four medication groups in treatment retention. The odds of cocaine abstinence showed a marginally significant increase over time in the propranolol group (p=0.06) but not in the other three groups. In highly medication-adherent patients, treatment retention was significantly better in the propranolol group compared to the placebo group (p=0.01) and the odds of cocaine abstinence increased significantly over time in the propranolol group but not in the other three groups. CONCLUSION: In the intent-to-treat sample, none of the three active treatments (propranolol, amantadine or their combination) was significantly more effective than placebo in promoting abstinence from cocaine among patients who entered treatment with more severe cocaine withdrawal symptoms. Among patients highly adherent to study medication, propranolol treatment was associated with better treatment retention and higher rates of cocaine abstinence compared to placebo.

Adrenergic beta-Antagonists↗

PubMed2006

Genetic correlations between smoking initiation and smoking behaviors in a twin sample.

Early exposure to cigarettes is connected to increasing rate of regular use later in life. We examine genetic correlation between the age of first cigarette and later smoking related behaviors. The sample consisted of twin ages 25 to 75. Biometrical analysis was used to evaluate the heritabilities and a second analyses based on Cholesky decomposition determined the shared variance. The genetic variance ranged from 48% to 69%. Models comparing age of first cigarette to and smoking persistence, cessation, and number of cigarettes during year smoked most individually indicated a very small proportion of shared genetic variance (ranging from 0.004 to 0.056). These findings support separate genetic and unshared environmental processes for the age of first cigarette as compared to three other smoking related phenotypes. Research in substance abuse risk and prevention literature suggests that delaying initial exposure is a critical step reducing in the risk of later regular use. The interventional implications of the findings support the importance of a tailored approach to preventing smoking behavior and reducing harm in smokers.

Adult↗

PubMed2006

A randomized trial of audio computer and in-person interview to assess HIV risk among drug and alcohol users in Rio De Janeiro, Brazil.

This study compares drug patterns and prevalence of risk behaviors in a randomized trial using two methods of administration, Audio Computer-Assisted Self-Interview (ACASI) and Interviewer-Administered Questionnaire (IAQ), among drug users seeking treatment in a drug treatment center. We randomized 735 participants: 367 to ACASI and 368 to IAQ. No significant difference in sociodemographic variables were found between subjects in the two arms of the study. Those interviewed by ACASI were more likely to report use on 7 of 10 substances assessed. Rates of reporting of sexual risk behaviors (male-to-male and commercial sex) were higher among participants in the ACASI arm. ACASI seems to be a key resource in improving the reporting of sensitive data in Brazil, as it has been in prior international studies.

Adolescent↗

PubMed2006

Acceptability of audio computer-assisted self-interview (ACASI) among substance abusers seeking treatment in Rio de Janeiro, Brazil.

This study aimed to determine the acceptability of the ACASI approach to risk assessment and the impact of personal preference regarding mode of interview on reporting risk behaviors among drug users entering treatment in Rio de Janeiro, Brazil. We assessed 268 substance users who completed the ACASI arm in a randomized trial comparing the ACASI with the Interviewer-Administered Questionnaire (IAQ). The vast majority of interviewees (90.7%) reported no problem using the computer, and 37.3% felt that their privacy was best protected by the ACASI (vs. 16.4% who preferred the IAQ). Nearly half (45.5%) reported that the computer interview would produce more "honest" answers, whereas 30.6% selected the IAQ. In the adjusted regression analysis, problems using the computer were associated only with lower educational level (p<0.05). We found no evidence that preference had an impact on reporting risk behaviors or drug use. Our study showed both good feasibility and acceptability of the ACASI for interviewing drug users in Brazil. The findings extend our understanding of the role of the ACASI method by suggesting the utility of this approach in assessing HIV risk among low-to middle-income drug users in a cultural setting quite different from previous studies.

Adolescent↗

PubMed2006

The availability of web sites offering to sell opioid medications without prescriptions.

OBJECTIVE: This study was designed to determine the availability of web sites offering to sell opioid medications without prescriptions. METHOD: Forty-seven Internet searches were conducted with a variety of opioid medication terms, including "codeine," "no prescription Vicodin," and "OxyContin." Two independent raters examined the links generated in each search and resolved any coding disagreements. The resulting links were coded as "no prescription web sites" (NPWs) if they offered to sell opioid medications without prescriptions. RESULTS: In searches with terms such as "no prescription codeine" and "Vicodin," over 50% of the links obtained were coded as "NPWs." The proportion of links yielding NPWs was greater when the phrase "no prescription" was added to the opioid term. More than 300 opioid NPWs were identified and entered into a database. CONCLUSIONS: Three national drug-use monitoring studies have cited significant increases in prescription opioid use over the past 5 years, particularly among young people. The emergence of NPWs introduces a new vector for unregulated access to opioids. Research is needed to determine the effect of NPWs on prescription opioid use initiation, misuse, and dependence.

Acetaminophen↗

PubMed2005

Conceptual, methodological, and analytical issues in the study of relapse.

This article examines conceptual, methodological, and analytic issues in research on relapse to alcohol and other drug use. The review notes the continued move in relapse research from a primary reliance on retrospective assessment of factors surrounding the onset of relapse episodes to an increased focus on the use of new technologies to obtain "near real time" data on proximal factors in relapses. Recent advances in neurobiology have yielded important gains in our understanding of vulnerability to relapse in alcohol and other drug abusers. New statistical techniques are also available to analyze data on relapse. From a theoretical standpoint, there has been an increasing appreciation for the complicated and dynamic interplay of distal and proximal factors in the relapse process. At this point, the strongest and most detailed data on factors in the onset and course of relapse have been generated by studies of smoking relapses that have made use of Ecological Momentary Assessment (EMA) technology. However, there is still limited "near real" time data on proximal factors in alcohol and other drug relapses, and no such data on factors that influence the course of these relapses, once they have begun. Nevertheless, important methodological advances have been and continue to be made in the study of relapse, and our knowledge about the nature and process of relapse has increased considerably over the past 10 years.

Alcoholism↗

PubMed2005

Sexual and physical victimization as predictors of HIV risk among felony drug offenders.

Injection and other drug use and high-risk sexual behaviors put criminal offenders at increased risk for HIV infection. Studies in other populations, especially females, have found that a history of sexual or physical victimization increases engagement in HIV-risk behaviors, and drug-involved offenders have high rates of such prior victimization. However, there has been little research among male offenders. In a sample of 247 male felony drug offenders in New York City, prior sexual victimization was related to a higher number of sex partners and lower proportion of protected sex acts in the 30 days before arrest. Prior physical abuse was related to cocaine injection, but not heroin injection or high-risk sex behaviors. These results suggest a complex relationship between sexual and physical abuse and HIV risk among male offenders. Assessing for specific prior abuse histories of offenders and providing targeted interventions may be useful for developing more effective primary and secondary HIV prevention services for this high-risk population.

Adult↗

PubMed2005

Multidimensional assessment of nicotine dependence in adolescents.

Despite the critical importance of adolescent smoking, the assessment of nicotine dependence during this developmental period has been the subject of relatively little research. In this study, 301 adolescents (ages 12 through 18 years) reporting daily smoking were recruited for a project on alcohol use disorders (AUDs). The sample included 140 females and 161 males, 251 subjects from clinical and 50 from community sources, and 176 subjects with AUDs at the baseline assessment. Subjects were evaluated with the Nicotine Dependence Syndrome Scale (NDSS), the Fagerstrom Test for Nicotine Dependence (FTND) and a determination of average number of cigarettes per day (cigarettes/day). A varimax factor analysis of 27 NDSS items revealed four factors: (1) Drive/Tolerance (13 items; Cronbach alpha = 0.91); (2) Continuity (five items; Cronbach alpha = 0.67); (3) Priority (three items; Cronbach alpha = 0.64); (4) Stereotypy (five items; Cronbach alpha = 0.66). The NDSS total score, refined by the removal of four items, was also examined (23 items; Cronbach alpha = 0.90). Predicting cigarettes/day at follow-up, initial smoking rate was the best predictor, with the FTND and NDSS Total score showing significant and similar predictive validity. The NDSS Total showed incremental validity in the prediction of smoking progression in a model including demographic characteristics, initial smoking rate and FTND. The findings suggest that the NDSS has acceptable psychometric properties when applied to adolescents, complementing smoking rate and FTND in a multidimensional smoking assessment.

Adolescent↗

PubMed2005

Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm.

RATIONALE: Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated. OBJECTIVE: This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = "denicotinized") cigarettes. METHODS: In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette. RESULTS: The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices. CONCLUSIONS: These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies.

Adolescent↗

PubMed2005

The effectiveness of telephone-based continuing care for alcohol and cocaine dependence: 24-month outcomes.

CONTEXT: Telephone-based disease management protocols have shown promise in improving outcomes in a number of medical and psychiatric disorders, but this approach to continuing care has received little study in alcohol- and drug-dependent individuals. OBJECTIVE: To compare telephone-based continuing care with 2 more intensive face-to-face continuing care interventions. DESIGN: A randomized 3-group clinical trial with a 2-year follow-up. SETTING: Two outpatient substance abuse treatment programs, one community-based and the other at a Veterans Affairs medical center facility. PATIENTS: Alcohol- and/or cocaine-dependent patients (N = 359) who had completed 4-week intensive outpatient programs. INTERVENTIONS: Three 12-week continuing care treatments: weekly telephone-based monitoring and brief counseling contacts combined with weekly supportive group sessions in the first 4 weeks (TEL), twice-weekly cognitive-behavioral relapse prevention (RP), and twice-weekly standard group counseling (STND). MAIN OUTCOME MEASURES: Percentage of days abstinent from alcohol and cocaine, total abstinence from alcohol and cocaine, negative consequences of substance use, cocaine urine toxicological results, and gamma-glutamyltransferase. RESULTS: Participants in TEL had higher rates of total abstinence over the follow-up than those in STND (P<.05). In alcohol-dependent participants, 24-month gamma-glutamyltransferase levels were lower in TEL than in RP (P = .005). In cocaine-dependent participants, there was a significant group x time interaction (P = .03) in which the rate of cocaine-positive urine samples increased more rapidly in RP as compared with TEL. On percentage of days abstinent or negative consequences of substance use, TEL did not differ from RP or STND. Participants with high scores on a composite risk indicator, based on co-occurring alcohol and cocaine dependence and poor progress toward achieving intensive outpatient program goals, had better total abstinence outcomes up to 21 months if they received STND rather than TEL, whereas those with lower scores had higher abstinence rates in TEL than in STND (P = .04). CONCLUSIONS: Telephone-based continuing care appears to be an effective form of step-down treatment for most patients with alcohol and cocaine dependence who complete an initial stabilization treatment, compared with more intensive face-to-face interventions. However, high-risk patients may have better outcomes if they first receive group counseling continuing care after completing intensive outpatient programs.

Aftercare↗

PubMed2005

A double-blind, placebo-controlled trial of modafinil for cocaine dependence.

Despite years of active research, there are still no approved medications for the treatment of cocaine dependence. Modafinil is a glutamate-enhancing agent that blunts cocaine euphoria under controlled conditions, and the current study assessed whether modafinil would improve clinical outcome in cocaine-dependent patients receiving standardized psychosocial treatment. This was a randomized, double-blind, placebo-controlled trial conducted at a university outpatient center (from 2002 to 2003) on a consecutive sample of 62 (predominantly African American) cocaine-dependent patients (aged 25-63) free of significant medical and psychiatric conditions. After screening, eligible patients were randomized to a single morning dose of modafinil (400 mg), or matching placebo tablets, for 8 weeks while receiving manual-guided, twice-weekly cognitive behavioral therapy. The primary efficacy measure was cocaine abstinence based on urine benzoylecgonine levels. Secondary measures were craving, cocaine withdrawal, retention, and adverse events. Modafinil-treated patients provided significantly more BE-negative urine samples (p=0.03) over the 8-week trial when compared to placebos, and were more likely to achieve a protracted period (> or =3 weeks) of cocaine abstinence (p=0.05). There were no serious adverse events, and none of the patients failed to complete the study as a result of adverse events. This study provides preliminary evidence, which should be confirmed by a larger study, that modafinil improves clinical outcome when combined with psychosocial treatment for cocaine dependence.

Adult↗

PubMed2005

Do patient characteristics and initial progress in treatment moderate the effectiveness of telephone-based continuing care for substance use disorders?

AIMS: To determine whether substance use severity, psychiatric severity, social support, self-help attendance or motivation moderated substance use outcomes in a telephone-based continuing care intervention. DESIGN: A randomized study comparing three 12-week continuing care interventions: weekly telephone monitoring and counseling combined with a support group in the first 4 weeks (TEL), twice-weekly individualized relapse prevention (RP) and twice-weekly standard group counseling (STND). METHODS: Following completion of 4-week intensive out-patient programs (IOP), 359 patients with alcohol and/or cocaine dependence were assigned randomly to a continuing care condition and followed quarterly for 12 months. Ten potential moderator variables were examined in separate analyses. Two of these variables reflected pretreatment status, whereas the other variables were focused on performance while in the IOP. A composite risk measure was also constructed from dichotomized versions of seven of these variables, with higher scores indicating greater potential for relapse. The dependent measures were total abstinence and percentage of days abstinent from alcohol and cocaine in each quarter. FINDINGS: Of 40 interaction contrasts that were examined with individual risk indicator measures, only one reached the 0.05 level of significance. Patients with any alcohol use in IOP had a higher percentage of days abstinence in STND than in TEL. In addition, high scores on the composite risk indicator predicted higher total abstinence rates in STND than in TEL, whereas low to moderate scores predicted higher abstinence rates in TEL than in STND. CONCLUSION: For most graduates of IOPs, the combination of brief weekly telephone therapeutic contacts and a support group in the first month produced outcomes that are as good as those obtained in more intensive face-to-face continuing care interventions. However, patients with current dependence on both alcohol and cocaine who make little progress towards achieving the central goals of IOP may have better outcomes if they receive twice-weekly group counseling following IOP.

Adult↗

PubMed2005

Selective serotonin re-uptake inhibitors and the risk of bleeding.

Despite their safety, selective serotonin re-uptake inhibitors (SSRIs) are associated with bleeding. The authors critically reviewed the medical literature on SSRIs to identify subgroups of patients at risk of bleeding complications. The authors performed a literature search using MEDLINE from 1966 to 1st September 2004 using; 'haemorrhage, serotonin uptake inhibitors and antidepressive agents' as search terms and followed up on citations in each paper that was relevant to SSRI associated bleeding. The authors reviewed 7 retrospective analytical studies and 24 case reports of bleeding in 43 different people. Analytical studies support an association between SSRI consumption and upper gastrointestinal (GI) bleeding and perioperative bleeding. Little evidence links SSRI use with intracerebral haemorrhage. The risk of GI bleeding appeared to be highest among patients consuming SSRIs with NSAIDs. Combining aspirin or NSAIDs with SSRIs may further increase the risk of bleeding. Clinicians should caution patients about combining SSRIs with aspirin or NSAIDs. Pharmacotherapy to reduce the risk of GI bleeding should be considered in high risk patients.

Adult↗

PubMed2005

Effects of an intensive street-level police intervention on syringe exchange program use in Philadelphia, PA.

Repeated measurements and mixed-effects models were used to analyze the effects of an intensive long-term street-level police intervention on syringe exchange program use. Utilization data for 9 months before and after the beginning of the intervention were analyzed. Use fell across all categories and time periods studied, with significant declines in use among total participants, male participants, and Black participants. Declines in use among Black and male participants were much more pronounced than decreases among White and female participants.

Acquired Immunodeficiency Syndrome↗