Despite the value of 12-step meetings, few studies have examined factors associated with attendance among those living with HIV/AIDS, such as the impact of HIV disease severity and demographics.
This study examines predisposing characteristics, enabling resources and need on attendance at Alcoholic Anonymous (AA) and Narcotics Anonymous (NA) meetings among those living with HIV/AIDS and alcohol problems.
Secondary analysis of prospective data from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study, a cohort of 400 adults living with HIV/AIDS and alcohol problems. Factors associated with AA/NA attendance were identified using the Anderson model for vulnerable populations. Generalized estimating equation logistic regression models were fit to identify factors associated with self-reported AA/NA attendance.
At study entry, subjects were 75% male, 12% met diagnostic criteria for alcohol dependence, 43% had drug dependence and 56% reported attending one or more AA/NA meetings (past six months). In the adjusted model, female gender negatively associated with attendance, as were social support systems that use alcohol and/or drugs, while presence of HCV antibody, drug dependence diagnosis, and homelessness associated with higher odds of attendance.
Non-substance abuse related barriers to AA/NA group attendance exist for those living with HIV/AIDS, including females and social support systems that use alcohol and/or drugs. Positive associations of homelessness, HCV infection and current drug dependence were identified. These findings provide implications for policy makers and treatment professionals who wish to encourage attendance at 12-step meetings for those living with HIV/AIDS and alcohol or other substance use problems.
HIV-infection; alcohol addiction disorder; substance-related disorders; 12 step groups; HIV/AIDS
Two competing concepts address the development of involvement with psychoactive substances: the “gateway hypothesis” (GH) and common liability to addiction (CLA).
The literature on theoretical foundations and empirical findings related to both concepts is reviewed.
The data suggest that drug use initiation sequencing, the core GH element, is variable and opportunistic rather than uniform and developmentally deterministic. The association between risks for use of different substances, if any, can be more readily explained by common underpinnings than by specific staging. In contrast, the CLA concept is grounded in genetic theory and supported by data identifying common sources of variation in the risk for specific addictions. This commonality has identifiable neurobiological substrate and plausible evolutionary explanations.
Whereas the “gateway” hypothesis does not specify mechanistic connections between “stages”, and does not extend to the risks for addictions, the concept of common liability to addictions incorporates sequencing of drug use initiation as well as extends to related addictions and their severity, provides a parsimonious explanation of substance use and addiction co-occurrence, and establishes a theoretical and empirical foundation to research in etiology, quantitative risk and severity measurement, as well as targeted non-drug-specific prevention and early intervention.
Drug dependence; Drug abuse; Genetics; Phenotype; Evolution
Contingency management (CM) is a widely recognized empirically-supported addiction treatment; however, dissemination and adoption of CM into routine clinical practice has been slow. Assessment of beliefs about CM may highlight key barriers and facilitators of adoption and inform dissemination efforts. In the present study, we developed a 35-item questionnaire (Contingency Management Beliefs Questionnaire; CMBQ) assessing CM beliefs and examined the relation of these beliefs to clinician characteristics and clinical practices.
The web-based study was completed by 617 substance abuse treatment providers. We examined the factor structure using exploratory factor analysis (EFA) in a randomly selected half-sample (n =318) and evaluated the generalizability of the solution using confirmatory factor analysis (CFA) in the second half-sample (n = 299).
EFA results suggested a 3-factor solution with 32 items retained; factors represented general barriers, training-related barriers, and pro-CM items. CFA results supported the solution, and reliability was good within each half-sample (α = .88 and 0.90). Therapeutic approach, years experience in addictions field, perception of CM’s research support, prior CM training, and CM adoption interest were significantly associated with the factors.
Overall, participants viewed CM favorably yet endorsed barriers, indicating a need for more extensive and targeted response to the most common misperceptions in dissemination efforts.
contingency management; treatment barriers; dissemination; adoption; technology transfer
Young adulthood represents a key developmental period for the onset of substance use disorder (SUD). While the number of young adults entering treatment has increased, little is known about the mechanisms of change and early recovery processes in this important clinical population. This study investigated during-treatment change in key therapeutic processes (psychological distress, motivation, self-efficacy, coping skills, and commitment to AA/NA), and tested their relation to outcome at 3 months post-treatment.
Young adults undergoing residential treatment (N=303; age 18–24; 26% female; 95% Caucasian) were enrolled in a naturalistic prospective study and assessed at intake, mid-treatment, discharge, and 3 months following discharge. Repeated-measures and regression analyses modeled during-treatment change in process variables and impact on outcome.
Statistically significant medium to large effect sizes were observed for changes in most processes during treatment, with the exception of motivation, which was high at treatment intake and underwent smaller, but still significant, change. In turn, these during-treatment changes all individually predicted 3-month abstinence to varying degrees, with self-efficacy emerging as the sole predictor in a simultaneous regression.
Findings help to clarify the mechanisms through which treatment confers recovery-related benefit among young adults. At treatment intake, high levels of abstinence motivation but lower coping, self-efficacy, and commitment to AA/NA, suggests many entering treatment may be “ready and willing” to change, but “unable” to do so without help. Treatment appears to work, in part, by helping to maintain motivation while conferring greater ability and confidence to enact such change.
mechanisms of change; treatment process; repeated measures; young adults; Minnesota Model; Alcoholics Anonymous; 12 step
The present study examines whether general and alcohol-specific peer risk factors from age 10 to 18 are associated with longitudinal patterns of adult alcohol abuse disorder symptoms from age 21 to 33.
Using growth mixture modeling, trajectory groups of alcohol abuse disorder symptoms from age 21 to 33 were identified. We then examined the relationships between the identified trajectory groups of alcohol abuse disorder symptoms and respondents' own , a general negative peer factor, and an alcohol-specific peer factor (having drinking peers) in adolescence using pseudo-class Wald chi-square tests and multinomial logistic regressions.
Four different trajectory groups of alcohol abuse disorder symptoms were identified: persistor group (3%), decreaser group (23%), escalator group (3%), and a no-disorder group (71%). Bivariate Wald chi-square tests indicated that adolescent binge drinking behavior and general and alcohol-specific peer factors differentiated the adult alcohol abuse trajectory groups. Multivariate multinomial logistic regression showed that the general negative peer factors distinguished those who later persisted in alcohol abuse from those who desisted (i.e., persistor group vs. decreaser group) during young adulthood, even after adjusting for respondents' adolescent binge drinking. On the other hand, associating with drinking peers did not distinguish these trajectories.
Alcohol-specific peer influences appear to influence alcohol abuse disorder symptoms in the early 20s, while general negative peer exposure in adolescence increases in importance as a risk factor for alcohol abuse disorder symptom persistence in the late 20s and the early 30s.
Alcohol abuse disorder symptoms; Young Adulthood; Adolescent peer factors; Conceptualizing general and outcome specific peer measures
Herkinorin is the first μ opioid (MOP) selective agonist derived from salvinorin A, a hallucinogenic natural product. Previous work has shown that, unlike other opioids, herkinorin does not promote the recruitment of β-arrestin-2 to the MOP receptor and does not lead to receptor internalization. This paper presents the first in vivo evaluation of herkinorin’s antinociceptive effects in rats, using the formalin test as a model of tonic inflammatory pain. Herkinorin was found to produce a dose-dependent decrease in the number of flinches evoked by formalin. These antinociceptive effects were substantially blocked by pretreatment with the nonselective antagonist naloxone, indicating that the antinociception is mediated by opioid receptors. Contralateral administration of herkinorin did not attenuate the number of flinches evoked by formalin, indicating that its effects are peripherally restricted to the site of injection. Following chronic administration (5-day), herkinorin maintained antinociceptive efficacy in both phases of the formalin test. Furthermore, unlike morphine, herkinorin was still able to inhibit flinching in both phases of the formalin test in animals made tolerant to chronic systemic morphine treatment. Collectively, these results suggest that herkinorin may produce peripheral antinociception with decreased tolerance liability and thereby represents a promising template for the development of agents for the treatment of a variety of pain states.
MOP receptors; herkinorin; β-arrestin-2; morphine; tolerance; formalin
Morphine and other opiates are among the most widely prescribed and clinically useful medications for the treatment of chronic pain. However, the applicability of these compounds has been severely hampered by the rapid development of tolerance and physical dependence that typically accompanies their repeated use. A growing body of evidence has implicated the regulated functioning of μ-δ opioid receptor heteromers in both the modulation of morphine-mediated antinociception, and in the limitation of undesirable side effects resulting from chronic opiate exposure. Moreover, μ-δ heteromers exhibit unique ligand binding characteristics and signaling properties, indicating that pharmacological targeting of the μ-δ heteromer may represent a novel therapeutic approach for the management of chronic pain and addiction disorders. Therefore, the present review will attempt to summarize the latest relevant findings regarding the regulation and functional characteristics of the μ-δ heteromer both in vitro and in vivo.
Opiate receptor; endorphin; G protein coupled receptor; heterodimer; oligomerization; opiate addiction; opiate tolerance; opiate dependence
Mu-opioid receptors (MOR) are the therapeutic target for opiate analgesic drugs and also mediate many of the side-effects and addiction liability of these compounds. MOR is a seven-transmembrane domain receptor that couples to intracellular signaling molecules by activating heterotrimeric G proteins. However, the receptor and G protein do not function in isolation but their activities are moderated by several accessory and scaffolding proteins. One important group of accessory proteins is the regulator of G protein signaling (RGS) protein family, a large family of more than thirty members which bind to the activated Gα subunit of the heterotrimeric G protein and serve to accelerate signal termination. This action negatively modulates receptor signaling and subsequent behavior. Several members of this family, in particular RGS4 and RGS9-2 have been demonstrated to influence MOR signaling and morphine-induced behaviors, including reward. Moreover, this interaction is not unidirectional since morphine has been demonstrated to modulate expression levels of RGS proteins, especially RGS4 and RGS9-2, in a tissue and time dependent manner. In this article, I will discuss our work on the regulation of MOR signaling by RGS protein activity in cultured cell systems in the context of other in vitro and behavioral studies. In addition I will consider implications of the bi-directional interaction between MOR receptor activation and RGS protein activity and whether RGS proteins might provide a suitable and novel target for medications to manage addictive behaviors.
RGS proteins; mu-opioid receptors; G-proteins; morphine
Noncompliance with medications may have major impacts on outcomes measured in research, potentially distorting the validity of controlled clinical trials. Riboflavin is frequently used in trials as a marker of adherence. It can be combined with study medication and is excreted in urine where it fluoresces under UV light. This study compares qualitative visual inspection of fluorescence to quantitative fluorometric analysis of riboflavin concentration in its ability to detect the presence of riboflavin in urine.
Twenty-four volunteers received 0 mg, 25 mg, and 50 mg doses of riboflavin under single-blind conditions, with 20 also receiving a 100 mg dose. Five serial urine samples were collected over the following 36 hours. Quantitative measurement of riboflavin by fluorometric analysis and qualitative assessment of each sample using visual inspection were performed.
The overall false positive rate for qualitative assessment was 53%. For quantitative assessment, a riboflavin concentration of 900 ng/mL was established to classify positive samples. More than 80% of samples were positive 2 to 24 hours following ingestion of 25 mg and 50 mg, and less than 80% were positive at 36 hours. At least 95% of observations for the 100 mg dose were above 900 ng/mL at all timepoints.
Quantitative fluorometric assessment is superior to qualitative visual inspection alone in determining medication adherence. The combination of 25–50 mg of daily riboflavin and a cut-off level of 900 ng/mL allows for the acceptable sensitivity of missing detection of non-compliant participants while preserving a high level of power to detect all cases of medication compliance.
adherence; quantitative; qualitative; riboflavin; tracer
Methadone plasma concentrations are decreased by nelfinavir. Methadone clearance and the drug interactions have been attributed to CYP3A4, but actual mechanisms of methadone clearance and the nelfinavir interaction are unknown. We assessed nelfinavir effects on methadone pharmacokinetics and pharmacodynamics, intestinal and hepatic CYP3A4/5 activity, and intestinal P-glycoprotein transport activity. CYP3A4/5 and transporters were assessed using alfentanil and fexofenadine, respectively.
Twelve healthy HIV-negative volunteers underwent a sequential crossover. On three consecutive days they received oral alfentanil plus fexofenadine, intravenous alfentanil, and intravenous plus oral methadone. This was repeated after nelfinavir. Plasma and urine analytes were measured by mass spectrometry. Opioid effects were measured by pupil diameter change (miosis).
Nelfinavir decreased intravenous and oral methadone plasma concentrations 40-50%. Systemic clearance, hepatic clearance, and hepatic extraction all increased 1.6- and 2-fold, respectively, for R- and S-methadone; apparent oral clearance increased 1.7- and 1.9-fold. Nelfinavir stereoselectively increased (S>R) methadone metabolism and metabolite formation clearance, and methadone renal clearance. Methadone bioavailability and P-glycoprotein activity were minimally affected. Nelfinavir decreased alfentanil systemic and apparent oral clearances 50% and 76%, respectively. Nelfinavir appeared to shift the methadone plasma concentration-effect (miosis) curve leftward and upward.
Nelfinavir induced methadone clearance by increasing renal clearance, and more so by stereoselectively increasing hepatic metabolism, extraction and clearance. Induction occurred despite 50% inhibition of hepatic CYP3A4/5 activity and more than 75% inhibition of first-pass CYP3A4/5 activity, suggesting little or no role for CYP3A in clinical methadone disposition. Nelfinavir may alter methadone pharmacodynamics, increasing clinical effects.
methadone; nelfinavir; CYP3A; CYP2B6; HIV; drug interactions
Unemployment is associated with negative outcomes both during and after drug abuse treatment. Interventions designed to increase rates of employment may also improve drug abuse treatment outcomes. The purpose of this multi-site clinical trial was to evaluate the Job Seekers’ Workshop (JSW), a three session, manualized program designed to train patients in the skills needed to find and secure a job.
Study participants were recruited through the NIDA Clinical Trials Network (CTN) from six psychosocial counseling (n=327) and five methadone maintenance (n=301) drug treatment programs. Participants were randomly assigned to either standard care (program-specific services plus brochure with local employment resources) (SC) or standard care plus JSW. Three 4-hr small group JSW sessions were offered weekly by trained JSW facilitators with ongoing fidelity monitoring.
JSW and SC participants had similar 12- and 24-week results for the primary outcome measure (i.e., obtaining a new taxed job or enrollment in a training program), Specifically, one-fifth of participants at 12 weeks (20.1 – 24.3%) and nearly one-third at 24 weeks (31.4–31.9%) had positive outcomes, with “obtaining a new taxed job” accounting for the majority of cases.
JSW group participants did not have higher rates of employment/training than SC controls. Rates of job acquisition were modest for both groups, suggesting more intensive interventions may be needed. Alternate targets (e.g., enhancing patient motivation, training in job-specific skills) warrant further study as well.
Substance Use Disorders; Vocational Rehabilitation; Treatment; Translational Research; Employment
To examine the population prevalence, patterns of onset, and important demographic covariates for dual (co-occurring) diagnoses of substance and non-substance mental disorders.
A nationally representative sample of U.S. Latino adults was interviewed face-to-face.
Estimates were made using data from the National Latino and Asian Services Survey (NLAAS) using the World Health Organization CIDI, DSM-IV criteria, for case ascertainment.
U.S. born Latinos are much more likely to report a dual diagnoses than are foreign born Latinos in both sexes; 16.88% vs. 5.02% for males (p<0.000), and 7.48% vs. 0.58% for women (p<.000). Total dual diagnoses prevalence was 6.79%, with non-substance mental disorder occurring first 70% of the time, with an earlier age of onset for U.S. Latinos. Immigrants were less likely to be positive for dual diagnoses (OR= 0.234, p=<0.0001), or any substance disorder diagnosis (OR=0.261, p=<.0001), if they reported lifetime substance use when compared to U.S. born Latinos.
Latino adults residing in the U.S. have one-fourth the risk of dual diagnoses compared to the U.S. population. Most of this difference is accounted for by lower rates of substance and non-substance disorders and a lower propensity for progression from substance use to substance use disorders, combined with a later age of onset for mental disorders among immigrants. Immigrant women rarely reported dual diagnoses. We recommend bio-behavioral models and transnational studies to identify life course factors contributing dual diagnoses among U.S. born Latinos.
epidemiology; minority groups; comorbidity; immigration
Male mice from 14 standard inbred strains were exposed to morphine in a sustained released preparation injected subcutaneously. Five hours later withdrawal was precipitated by intraperitoneal injection of naloxone. Mice were tested from 0 to 15 minutes after naloxone for withdrawal jumping behavior, and then from minute 15–16 for other signs, including boli count, presence of soft stool, lacrimation, “wet dog” shakes, and air chewing. They were also assessed for change in body temperature 17 minutes after naloxone. Strains differed markedly in the severity of withdrawal for jumping, change in body temperature, and number of fecal boli. Strains also differed in percentage of animals displaying soft stool and air chewing behavior. The other two signs were seen at too low frequency for analysis. Correlations of strain mean withdrawal severity with other responses to morphine and other abused drugs showed that high morphine withdrawal jumping and low change in body temperature were both genetically related to high morphine consumption, but not generally to other measures of morphine withdrawal or morphine sensitivity.
inbred mouse strains; pharmacogenetics; dependence; morphine; precipitated withdrawal; jumping
A typical approach to categorizing substance users for epidemiologic purposes or to identify substance use problems at treatment admission is by indicating the primary substance used and/or for which treatment is sought. But does such singular focus on the primary drug limit the validity of conclusions from longitudinal analysis of drug use patterns over time? This analysis combined data from five longitudinal studies conducted in California and examined 10-year patterns of heroin, cocaine, methamphetamine (meth), marijuana, and alcohol use for primary users of heroin (n=629), cocaine (n=694), and meth (n=474). Results suggest relatively low levels of use of non-primary heroin, cocaine, and meth, but moderate levels of alcohol and marijuana use. Growth models showed declining primary drug levels for heroin and meth users and relatively consistent levels over 10 years for cocaine users, while levels of non-primary drugs remained at consistently low levels or declined in tandem with the primary drug. Results indicate that group descriptions of primary heroin, cocaine, or meth use trajectories over time may present valid information about drug use patterns in general.
epidemiology; poly-drug abuse; trajectories; trends; growth models
Some epidemiological and cessation studies suggest physical exercise attenuates or prevents recreational drug use in humans. Preclinical studies indicate wheel activity reduces cocaine self-administration in rats; this may, however, require the establishment of compulsive wheel activity.
Effects of concurrent wheel activity on intravenous d-methamphetamine (METH) self-administration were examined in male Wistar and Sprague Dawley rats with negligible prior wheel experience. Wistar rats self-administered METH (0.05 mg/kg/inf) under a fixed-ratio 1 (FR1) schedule with concurrent access to an activity wheel during sessions 1–14, 8–21 or 15–21. Control rats which did not self-administer METH had access to an activity wheel during sessions 1–14, 8–21 or 15–28. Sprague Dawley rats self-administered METH (0.1 mg/kg/inf) under FR1 for 14 sessions with either concurrent access to a locked or an unlocked activity wheel.
METH self-administration was lower when the wheel was available concurrently from the start of self-administration training in both strains, even though Sprague Dawley rats self-administered twice as many METH infusions and ran one-sixth as much on the wheel compared to Wistar rats. Wheel access initiated after 7 or 14 days had no effect on METH self-administration in Wistar rats. Wheel activity was significantly reduced in these groups compared with the group with concurrent wheel and METH access for the first 14 sessions.
These data show METH self-administration is reduced by exercise if initiated from the start of self-administration and that prior METH self-administration experience interferes with the value of exercise as a reinforcer.
d-methamphetamine; self-administration; running; rats
Relapse to drug use after a period of abstinence is a persistent problem in the treatment of cocaine dependence. Physical activity decreases cocaine self-administration in laboratory animals and is associated with a positive prognosis in human substance-abusing populations. The purpose of this study was to examine the effects of long-term access to a running wheel on drug-primed and cue-induced reinstatement of cocaine-seeking behavior in male and female rats.
Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) and exercising (access to wheel) groups for the duration of the study. After 6 weeks, rats were implanted with intravenous catheters and trained to self-administer cocaine for 14 days. After training, saline was substituted for cocaine and responding was allowed to extinguish, after which cocaine-primed reinstatement was examined in both groups. Following this test, cocaine self-administration was re-established in both groups for a 5-day period. Next, a second period of abstinence occurred in which both cocaine and the cocaine-associated cues were withheld. After 5 days of abstinence, cue-induced reinstatement was examined in both groups.
Sedentary and exercising rats exhibited similar levels of cocaine self-administration, but exercising rats responded less than sedentary rats during extinction. In tests of cocaine-primed and cue-induced reinstatement, exercising rats responded less than sedentary rats, and this effect was apparent in both males and females.
These data indicate that long-term access to a running wheel decreases drug-primed and cue-induced reinstatement, and that physical activity may be effective at preventing relapse in substance-abusing populations.
cocaine; exercise; extinction; reinstatement; self-administration; sex differences
Research is increasingly focusing on identifying factors distinguishing patients who complete versus dropout of residential substance abuse treatment. One potentially relevant factor that has received relatively little attention is borderline personality disorder (BPD).
This study sought to examine the effect of BPD on residential substance abuse treatment dropout within a sample of 159 male patients with substance use disorders – a population often understudied with regard to BPD and at high-risk for treatment dropout. Patients were administered a structured diagnostic interview to establish BPD diagnoses. Patients were then followed throughout the course of residential substance abuse treatment to identify those who completed treatment and those who prematurely dropped out of treatment.
Patients with BPD were significantly more likely to prematurely dropout of treatment, and this finding remained even when taking into account relevant covariates (i.e., court-ordered treatment status, contract duration, and major depressive disorder). Further, patients with BPD were more likely to experience center-initiated dropout as opposed to voluntary withdrawal from treatment.
These findings add to the literature on BPD-SUD co-occurrence, suggesting that the presence of co-occurring BPD among male SUD patients may increase the risk for dropout from residential substance abuse treatment, necessitating targeted interventions focused on decreasing dropout within this patient subgroup.
Borderline Personality Disorder; Comorbidity; Personality Disorders; Substance Abuse Treatment; Substance Use Disorder; Treatment Retention
Cannabis is the most widely used illicit substance and has been associated with cognitive impairment. It is unclear whether such impairment can occur in the absence of potential confounding influences of co-morbid axis-I disorders and use of other illicit substances.
Young adult volunteers (18–29 years) were recruited from the general community on the basis of having no axis-I disorders or history of illicit substance use other than cannabis use. Subjects were then grouped according to presence or absence of cannabis use (>1 time/week over past 12 months). Cognition was compared between groups using selected paradigms from the CANTAB.
Cannabis users (n=16) and controls (n=214) did not differ significantly on salient demographic characteristics. Compared to controls, cannabis users showed significant impairments on quality of decision-making (Cambridge Gamble task), and executive planning (One Touch Stockings of Cambridge task). Response inhibition, spatial working memory, and sustained attention were intact.
This study identified cognitive deficits in cannabis users even in the absence of axis-I disorders and a history of using other illicit drugs. Future work should use longitudinal designs to track whether these deficits predate cannabis use or are due to its consumption.
Addiction; Cognition; Cannabis; Impulsivity
Previous research with non-drug reinforcers has shown that simultaneously presenting (compounding) an extinguished cue with another cue formerly associated with the same reinforcer can increase rates of cue-controlled behavior. The present study investigated whether an extinguished cocaine cue would energize cocaine seeking when presented simultaneously with another cocaine cue. This study also investigated whether extinction could be enhanced by subjecting an extinguished cocaine cue to further extinction after administration of reinstating injections of cocaine.
Rats were first trained to self-administer cocaine in the presence of three different cues. Then, one of the cues was subjected to the standard extinction treatment. Another cue was subjected to a modified extinction treatment where additional extinction sessions were preceded by non-contingent cocaine injections. The third cue was not extinguished.
The cue subjected to standard extinction ceased to control cocaine seeking when presented alone, but significantly increased cocaine seeking when compounded with the non-extinguished cocaine cue. The cocaine cue subjected to the modified extinction treatment also significantly increased cocaine seeking occasioned by the non-extinguished cocaine cue.
Extending results of previous studies involving non-drug stimuli, the present study showed that extinguished cocaine cues can enhance cocaine seeking when compounded with other cocaine cues. These results illustrate the persistence of drug cues in controlling behavior despite extinction and highlight the need for developing treatments that eliminate this residual energizing capacity that survives extinction.
extinction; drug cues; cocaine; self-administration; cue exposure; stimulus compounding; rats
Ten early onset problem behaviors were used to prospectively predict alcohol, tobacco, cannabis, and cocaine disorders in young adulthood (mean age=28.6 yrs.) for a U.S. community sample of 671 participants.
Data from a longitudinal study of participants who were recruited from high schools during adolescence and followed into young adulthood were used to evaluate prospective associations. The relationship between early onset problem behaviors, reported when participants were age 16 years, and psychiatric diagnoses assessed in young adulthood was tested. Structural equation models were used to evaluate both generality and specificity hypotheses regarding relationships between early onset problem behaviors and young adult disorders.
Findings supported the specificity hypothesis in that “like” early onset problem behaviors significantly predicted “like” young adult outcomes (e.g., early cocaine use predicted cocaine disorders). Furthermore, eliminating such “like” predictors in regression equations resulted in a 36% reduction in the amount of variance accounted for by the equation. The generality hypothesis was also supported in that a larger number of early onset problem behaviors strengthened the prediction of young adult disorders beyond the “like” attribute, and a dose-response pattern indicated that additional early onset problem behaviors increased the probable occurrence of a young adult disorder.
A comprehensive framework relating early onset problem behaviors to young adult substance disorders will require the integration of both generality and specificity hypotheses, and a developmental orientation focused on the unfolding of mediating and moderating processes. Early screening of multiple, rather than single, early onset problems is also discussed.
early-onset; young adulthood; problem behaviors; substance use disorders
Respondent-driven sampling (RDS) has been promoted as a superior method in recruiting hard-to-reach and hidden populations. Although its application has expanded enormously, there remains a need for empirical data evaluating the performance of RDS in different settings. This study describes the application of RDS to recruit a community sample (N=396) of young adults (18–23 years old) into a natural history study of non-medical pharmaceutical opioid use. Since recruitment targeted non-dependent pharmaceutical opioid users, and applied other eligibility restrictions, several modifications had to be made to make RDS work with this narrowly-defined target population. RDS recruitment was less efficient than expected, and produced greater numbers of African American recruits than anticipated. Although the sampling quota was met, sample analysis revealed a lack of equilibrium in terms of ethnic composition and very strong in-group recruitment tendencies among White and African American respondents. This study contributes potentially helpful insights into the strengths and limitations of using RDS which may benefit future studies.
sampling; respondent driven sampling; hidden populations; illicit use of pharmaceutical opioids; young adults
The abuse-related behavioral effects of inhalant vapors are poorly understood but probably involve multiple neurotransmitter receptor mechanisms. The present study examined the receptor systems responsible for transducing the discriminative stimulus of the abused chlorinated hydrocarbon 1,1,1-trichloroethane (TCE) in mice.
Thirty mice were trained to discriminate 10 min of 12000 ppm TCE vapor exposure from air using an operant procedure. Substitution tests were then conduced with positive GABAA receptor modulators and/or NMDA receptor antagonists.
The nonselective benzodiazepines midazolam and diazepam produced 62% and 61% and the barbiturate pentobarbital produced 68% TCE-lever selection. Zaleplon, an alpha1 subunit-preferring positive GABAA receptor benzodiazepine-site positive modulator resulted in 29% TCE-lever selection. The direct extrasynaptic GABAA agonist gaboxodol (THIP) and the GABA reuptake inhibitor tiagabine failed to substitute for TCE. No substitution was elicited by a competitive (CGS-19755), noncompetitive (dizocilpine) or glycine-site (L701,324) NMDA antagonist. The mixed benzodiazepine/noncompetitive NMDA antagonist anesthetic Telazol and the anticonvulsant valproic acid exhibited low levels of partial substitution for TCE (38% and 39% respectively). Ethanol and nitrous oxide failed to substitute for TCE.
The results suggest that the discriminative stimulus effects of TCE are fairly selectively mediated by positive modulation of GABAA receptors. The failure of gaboxadol to substitute and the poor substitution by zaleplon suggests that extrasynaptic GABAA receptors as well as GABAA receptors containing alpha 1 subunits and are not involved in transducing the discriminative stimulus of TCE. Studies with additional GABAA benzodiazepine-site positive modulators will be necessary to confirm and extend these findings.
inhalants; drug discrimination; 1,1,1-trichloroethane; solvents
Although there are significant differences in prevalence of substance use between African-American and White adolescents, few studies have examined racial differences in developmental patterns of substance use, especially during the important developmental transition from adolescence to young adulthood. This study examines racial differences in trajectories of heavy drinking and regular marijuana use from adolescence into young adulthood.
A community-based sample of non-Hispanic African-American (n = 276) and non-Hispanic White (n = 211) males was analyzed to identify trajectories from ages 13 through 24.
Initial analyses indicated race differences in heavy drinking and regular marijuana use trajectories. African Americans were more likely than Whites to be members of the nonheavy drinkers/nondrinkers group and less likely to be members of the early-onset heavy drinkers group. The former were also more likely than the latter to be members of the late-onset regular marijuana use group. Separate analyses by race indicated differences in heavy drinking for African Americans and Whites. A 2-group model for heavy drinking fit best for African Americans, whereas a 4-group solution fit best for Whites. For regular marijuana use, a similar 4-group solution fit for both races, although group proportions differed.
Within-race analyses indicated that there were clear race differences in the long-term patterns of alcohol use; regular marijuana use patterns were more similar. Extended follow ups are needed to examine differences and similarities in maturation processes for African-American and White males. For both races, prevention and intervention efforts are necessary into young adulthood.
developmental trajectories; heavy drinking; regular marijuana use; racial differences; transition to adulthood
Extensive evidence demonstrates that current cocaine abusers show hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond poorly relative to drug-naïve controls on tests of executive function. Relatively little is known about the cognitive sequalae of long-term abstinence in cocaine addicts.
Here, we use a GO-NOGO task in which successful performance necessitated withholding a prepotent response to assay cognitive control in short-and long-term abstinent cocaine users (1-5 weeks and 40-102 weeks, respectively).
We report significantly greater activity in prefrontal, cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for both successful response inhibitions and errors of commission. Moreover, this relative hyperactivity was present in both abstinent groups, which, in the presence of comparable behavioral performance, suggests a functional compensation.
Differences between the short- and long-abstinence groups in the patterns of functional recruitment suggest different cognitive control demands at different stages in abstinence. Short-term abstinence showed increased inhibition-related dorsolateral and inferior frontal activity indicative of the need for increased inhibitory control while long-term abstinence showed increased error-related ACC activity indicative of heightened behavioral monitoring. The results suggest that the integrity of prefrontal systems that underlie cognitive control functions may be an important characteristic of successful long-term abstinence.
Cocaine addiction; abstinence; cognitive control; response inhibition
Cocaine use, abuse and dependence remains a pressing public health problem. Based on its mechanism of action, varenicline, an alpha4 beta2 partial agonist seemed to be a likely candidate for treating cocaine dependence.
Cocaine dependent participants (n = 37) were enrolled in a 9-week double-blind placebo controlled clinical trial. Varenicline was titrated up to a target dose of 1 mg BID during the first week of medication.
Varenicline was associated with lower odds of cocaine use than placebo (OR = 2.02, p=0.08), as measured by thrice-weekly urinalysis results. Compared to placebo-treated participants, varenicline treated participants had significantly decreased rates of cocaine reward, as measured by the Multiple Choice Procedure (MCP) (p = .02).
Varenicline appears to decrease cocaine use and reward, suggesting that further investigation of varenicline may be warranted.
cocaine; treatment; pharmacotherapy; contingency management