We showed recently that elevated brain levels of the chemokine stromal cell-derived growth factor-1α (SDF-1α/CXCL12, a ligand for the human immunodeficiency virus [HIV] co-receptor CXCR4) diminish the antinociceptive effect of morphine, but failed to influence buprenorphine-induced antinociception.
Because the HIV-1 coat protein, glycoprotein 120 (gp120) T-tropic strain, binds to the same receptor as SDF-1α/CXCL12, the present experiments were designed to investigate the consequence of administering gp120 to rat brain on buprenorphine-induced antinociception in the 54° C hot plate test. For comparative purposes, the effect of gp120 on an equi-antinociceptive dose of methadone was also examined.
A sterilized stainless-steel C313G guide cannula was implanted into the periaqueductal grey (PAG), a brain region critical for the processing of pain signals, and a primary site of action of many analgesics. Rats were pretreated with gp120, administered into the PAG.
The subsequent antinociception associated with methadone was diminished whereas buprenorphine-induced antinociception was unaffected. Buprenorphine thus appears to be a more effective analgesic than methadone in the presence of gp120 in the brain, a condition that is associated with HIV-related pain and infection.
Buprenorphine; HIV; gp120; antinociception; PAG; chemokine
Excessive alcohol consumption in college students is associated with impulsivity and with overestimating levels of others’ drinking; however, females’ and males’ drinking may be differently impacted by their overestimations. We examined whether moderate drinkers discount alcohol rewards differently from money rewards and whether their estimate of others’ drinking is more closely associated with own-drinking for males than females.
College students completed two delay discounting tasks in which they chose between money rewards and between alcohol rewards, varying in amount and delay to receipt. Participants also completed questionnaires about their own and others’ drinking.
Area under the delay-subjective value curve (AUC) was smaller for alcohol than money rewards, implying steeper discounting of alcohol rewards. Regression analyses showed that females’ number of drinks per sitting was related only to AUC for money, while males’ drinks per sitting was related to their estimate of others’ drinks.
The relationship between alcohol consumption and discounting was replicated. This study also indicated that social norms play a larger role in determining males’ drinking than females’.
delay discounting; alcohol; college students; peer influence; gender; social norms
The present study examined the efficacy of various specific lifestyle and situation-specific coping skills by determining the relationship of each of these strategies to drinking outcomes.
Patients with alcohol dependence in intensive day treatment were participating in a randomized trial naltrexone versus placebo and adjunctive communication and coping skills training or a control treatment. The alcohol version of the Urge-Specific Strategies (USS) questionnaire and the General Strategies for Alcoholics (GSA) were administered early in treatment. The USS assesses 16 situation-specific strategies taught in cue exposure treatment, communication skills training, or relaxation/meditation training to cope with experiencing an urge to drink (e.g., think of positive and negative consequences of drinking, use mastery messages, engage in an alternative behavior); the 21-item GSA assesses lifestyle change strategies taught in communication skills training and in the general treatment program (e.g., keep busy, exercise regularly, attend 12-Step meetings, avoid high-risk situations). Alcohol use and frequency of use of the skills were assessed 6 and 12 months following treatment.
Many specific behavioral and cognitive coping strategies were significantly related to drinking outcomes, including 13 urge-specific and 18 general lifestyle strategies, while other strategies were unrelated.
Since some strategies taught in treatment are more effective in preventing relapse than others, treatment may be improved by focusing on these specific strategies. Since results may be limited to this population, replication is needed in more diverse settings and without medication.
Coping skills; alcohol dependence; alcohol treatment; urge to drink
Previous research has demonstrated that depression and family history of illicit substance use disorders (ISUDs) are risk factors for the development of ISUDs. However, no study to date has examined whether these risk factors interact to predict onset. In addition, history of parental and sibling ISUDs have been identified as risk factors almost exclusively in healthy individuals and thus, it is unknown whether they confer unique risk among adolescents with a history of depression.
The current study examined these questions using data from the Oregon Adolescent Depression Project (OADP). DSM diagnoses of probands were assessed during 4-waves, first in adolescence (ages 14–18) and subsequently up until age 30. Lifetime DSM diagnoses of ISUDs in biological mothers, fathers, and siblings were obtained.
Proportional hazards model analyses indicated that there was a significant depression by parental ISUDs interaction. Among probands with parental ISUDs (and not among those without parental ISUDs), depression in adolescence was significantly associated with a shorter time to develop an ISUD. Sibling ISUDs were not associated with onset and did not interact with adolescent depression.
Prevention and intervention efforts targeted at this particularly at-risk group may be effective.
illicit substance use disorder; major depressive disorder; family history
Despite elevated rates of posttraumatic stress disorder (PTSD) among substance use disorder (SUD) patients, as well as the clinical relevance of this co-occurrence, few studies have examined psychological factors associated with a PTSD-SUD diagnosis. Two factors worth investigating are emotion dysregulation and impulsivity, both of which are associated with PTSD and SUDs. Therefore, this study examined associations between PTSD and facets of emotion dysregulation and impulsivity within a sample of trauma-exposed SUD inpatients.
Participants were an ethnically diverse sample of 205 SUD patients in residential substance abuse treatment. Patients were administered diagnostic interviews and completed a series of questionnaires.
Patients with PTSD (n = 58) reported significantly higher levels of negative urgency (i.e., the tendency to engage in impulsive behaviors when experiencing negative affect) and lower sensation seeking, as well as higher levels of emotion dysregulation and the specific dimensions of lack of emotional acceptance, difficulties engaging in goal-directed behavior when upset, difficulties controlling impulsive behaviors when distressed, limited access to effective emotion regulation strategies, and lack of emotional clarity. Further, overall emotion dysregulation emerged as a significant predictor of PTSD status, accounting for unique variance in PTSD status above and beyond facets of impulsivity (as well as other relevant covariates).
Results suggest that emotion dysregulation may contribute to the development, maintenance, and/or exacerbation of PTSD and highlight the potential clinical utility of targeting emotion dysregulation among SUD patients with PTSD.
emotion; emotion regulation; impulsivity; posttraumatic stress disorder; traumatic exposure; substance use disorders
Parental substance use disorder (SUD) is associated with a range of negative offspring outcomes and psychopathology, but the clustering of these outcomes into subtypes has seldom been examined, nor have the familial and environmental contexts of these subtypes been reported. The present study examines the clustering of offspring lifetime substance use and psychiatric disorders into subtypes and characterizes them in terms of familial and non-familial influences using an offspring-of-twins design.
Telephone-administered diagnostic interviews were used to collect data on psychiatric disorders and SUD from 488 twin fathers, 420 biological mothers and 831 offspring. Latent class analysis (LCA) was used to derive subtypes of lifetime comorbidity in offspring. Familial risk and environmental variables associated with each subtype (i.e. parenting, childhood physical or sexual abuse, perceived sibling and peer substance use) were identified using multinomial logistic regression.
Four classes identified by LCA were characterized as 1) unaffected, 2) alcohol abuse/dependence, 3) alcohol abuse/dependence comorbid with anxiety and depression, and 4) alcohol, cannabis abuse/dependence and nicotine dependence comorbid with conduct disorder. Inconsistent parenting, childhood physical/sexual abuse, and perceived sibling and peer substance use were significantly associated with profiles of offspring comorbidity after adjusting for familial vulnerability. Some associations were specific (i.e. perceived peer alcohol use to the AUD class), while others were general (peer smoking to all 3 comorbidity classes).
We observed distinct subtypes of psychiatric and SUD comorbidity in adolescents and young adults. Subtypes of offspring psychopathology have varied associations with parental psychopathology, family environment, and sibling and peer behaviors.
substance use disorder; anxiety; depression; twin; comorbid
This study examines whether residential neighborhood characteristics influence the initiation of marijuana use and binge drinking, and if these neighborhood factors heighten or dampen peer influences on substance use.
Predictors of marijuana (N = 6,516) and binge drinking (N = 6,630) initiation over a one-year period were identified using data from the National Longitudinal Study of Adolescent Health. Participants were ages 12–19 years at baseline. The main predictor variables were neighborhood characteristics, using both objective (proportion of households below the poverty line and female-headed, unemployment rate, residential stability) and subjective (perceived cohesion and safety) measures. Binge drinking was defined as 5 or more drinks in a row.
Initiation occurred for 12.9% of adolescents in the case of marijuana and 16.4% for binge drinking. Marijuana initiation was more likely among adolescents who lived in neighborhoods with a higher unemployment rate, and binge drinking initiation was more likely among those who perceived greater safety in their neighborhood, after adjusting for other neighborhood characteristics, demographics, friend characteristics, and behavioral and family risk factors. There was no evidence that neighborhood context moderates the associations of peer factors on initiation.
Select neighborhood characteristics appear relevant to the initiation of marijuana use and binge drinking, although the mechanisms appear to be distinct for each substance. If these results are found to be robust, future research will help better understand how neighborhood context influences the initiation of adolescent substance use in order to inform prevention efforts.
Adolescent; neighborhood; peer; marijuana; binge drinking
Although the incidence of cannabis abuse/dependence in Americans is rising, the neurobiology of cannabis addiction is not well understood. Imaging studies have demonstrated deficits in striatal D2/D3 receptor availability in several substance-dependent populations. However, this has not been studied in currently-using chronic cannabis users.
The purpose of this study was to compare striatal D2/D3 receptor availability between currently-using chronic cannabis users and healthy controls.
Eighteen right-handed males age 18–34 were studied. Ten subjects were chronic cannabis users; eight were demographically matched controls. Subjects underwent a [11C] raclopride (RAC) PET scan. Striatal RAC binding potential (BPND) was calculated on a voxel-wise basis. Prior to scanning, urine samples were obtained from cannabis users for quantification of urine Δ-9-tetrahydrocannabinol (THC) and THC metabolites (11-nor-Δ-9-THC-9-carboxylic acid; THC-COOH and 11-hydroxy-THC;OH-THC).
There were no differences in D2/D3 receptor availability between cannabis users and controls. Voxel-wise analyses revealed that RAC BPND values were negatively associated with both urine levels of cannabis metabolites and self-report of recent cannabis consumption.
In this sample, current cannabis use was not associated with deficits in striatal D2/D3 receptor availability. There was an inverse relationship between chronic cannabis use and striatal RAC BPND. Additional studies are needed to identify the neurochemical consequences of chronic cannabis use on the dopamine system.
dopamine; raclopride; positron emission tomography; cannabis; marijuana; D2 receptor
A brief screen requiring 3–4 minutes administration time was developed to detect adolescents qualifying for current substance use disorder (SUD) and those who will subsequently manifest SUD by early adulthood.
The revised Drug Use Screening Inventory (DUSI-R; Tarter, 1990) was administered to 329 boys on three occasions (ages 12–14, 15–17 and 18–19 years of age). Principal components analysis yielded a core set of items to form three age-specific versions of the DUSI-R Quick Screen (DQS), consisting of the Substance Involvement Index and Problems Severity Index
Construct, concurrent and predictive validity of the DQS were in the good to excellent range. Sensitivity of the DQS at ages 12–14, 15–17 and 18–19 for detecting current SUD was 100%, 93% and 93%. The DQS at these ages predicted SUD by age 22 with 73%, 77% and 83% accuracy. Replication in another sample revealed sensitivity of 71% and 75% in 15–17 and 18–20 year old males.
The true positive rate of detecting current and future SUD suggests that the DQS is an efficient screen for identifying youths requiring treatment or secondary prevention.
(3–6) Assessment; drug abuse; adolescence; addiction; substance use disorder; Drug Use Screening Inventory; Drug Use Screening Inventory-Revised; DUSI
Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants.
This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met “evaluable” criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified.
Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants.
This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury.
Liver function; buprenorphine; methadone; treatment outcome
This analysis explored the prevalence and correlates of pain in patients enrolled in methadone maintenance treatment (MMT).
Patients in two MMT programs starting a hepatitis care coordination randomized controlled trial completed the Brief Pain Inventory Short-Form and other questionnaires. Associations between clinically significant pain (average daily pain ≥ 5 or mean pain interference ≥ 5 during the past week) and sociodemographic data, medical status, depressive symptoms, and health-related quality of life, and current substance use were evaluated in multivariate analyses.
The 489 patients included 31.8% women; 30.3% Hispanics, 29.4% non-Hispanic blacks, and 36.0% non-Hispanic whites; 60.1% had hepatitis C, 10.6% had HIV, and 46.8% had moderate or severe depressive symptomatology. Mean methadone dose was 95.7 mg (SD 48.9) and urine drug screening (UDS) was positive for opiates, cocaine, and amphetamines in 32.9%, 40.1%, and 2.9%, respectively. Overall, 237 (48.5%) reported clinically significant pain. Pain treatments included prescribed opioids (38.8%) and non-opioids (48.9%), and self-management approaches (60.8%), including prayer (33.8%), vitamins (29.5%), and distraction (12.7%). Pain was associated with higher methadone dose, more medical comorbidities, prescribed opioid therapy, and more severe depressive symptomatology; it was not associated with UDS or self-reported substance use.
Clinically significant pain was reported by almost half of the patients in MMT programs and was associated with medical and psychological comorbidity. Pain was often treated with opioids and was not associated with measures of drug use. Studies are needed to further clarify these associations and determine their importance for pain treatment strategies.
pain; epidemiology; methadone maintenance; addiction; pain management
The President’s National HIV/AIDS Strategy calls for coupling HIV screening and prevention services with substance abuse treatment programs. Fewer than half of US community-based substance abuse treatment programs make HIV testing available on-site or through referral.
We measured the cost-effectiveness of three HIV testing strategies evaluated in a randomized trial conducted in 12 community-based substance abuse treatment programs in 2009: off-site testing referral, on-site rapid testing with information only, on-site rapid testing with risk reduction counseling. Data from the trial included patient demographics, prior testing history, test acceptance and receipt of results, undiagnosed HIV prevalence (0.4%) and program costs. The Cost Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model was used to project life expectancy, lifetime costs, and quality-adjusted life years (QALYs) for HIV-infected individuals. Incremental cost-effectiveness ratios (2009 US $/QALY) were calculated after adding costs of testing HIV-uninfected individuals; costs and QALYs were discounted at 3% annually.
Referral for off-site testing is less efficient (dominated) compared to offering on-site testing with information only. The cost-effectiveness ratio for on-site testing with information is $60,300/QALY in the base case, or $76,300/QALY with 0.1% undiagnosed HIV prevalence. HIV risk-reduction counseling costs $36 per person more without additional benefit.
A strategy of on-site rapid HIV testing offer with information only in substance abuse treatment programs increases life expectancy at a cost-effectiveness ratio <$100,000/QALY. Policymakers and substance abuse treatment leaders should seek funding to implement on-site rapid HIV testing in substance abuse treatment programs for those not recently tested.
Rapid HIV testing; substance use; cost-effectiveness
Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders.
Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120 mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked 5 puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad-libitum cannabis use.
Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120 mg doses.
Dronabinol’s ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg per day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted.
Cannabis; Marijuana; THC; Dronabinol; Withdrawal; Pharmacotherapy
Differences in fronto-striatal connectivity in problem substance users have suggested reduced influence of cognitive regions on reward-salience regions. Youth with a family history of alcoholism (FH+) have disrupted ventral striatal processing compared with controls with no familial risk (FH−). As sensation-seeking represents an additional vulnerability factor, we hypothesized that functional connectivity during reward anticipation would differ by family history, and would mediate the relationship between sensation-seeking and drinking in high-risk subjects.
Seventy 18–22 year olds (49 FH+/21 FH−) performed a monetary incentive delay task during functional magnetic resonance imaging. Group connectivity differences for incentive (reward/loss) vs. neutral conditions were evaluated with psychophysiological interaction (PPI) analysis, seeded in nucleus accumbens (NAcc). Indirect effects of sensation-seeking on drinking volume through accumbens connectivity were tested.
NAcc connectivity with paracentral lobule/precuneus and sensorimotor areas was decreased for FH− versus increased for FH+ during incentive anticipation. In FH+, task-related functional coupling between left NAcc and supplementary sensorimotor area (SSMA) and right precuneus correlated positively with sensation-seeking and drinking volume and mediated their relationship. In FH−, left NAcc-SSMA connectivity correlated negatively with sensation-seeking but was not related to drinking.
These results suggest preexisting differences in accumbens reward-related functional connectivity in high-risk subjects. NAcc coupling with SSMA, involved in attention and motor networks, and precuneus, a default mode structure, appear to mediate sensation-seeking’s effect on drinking in those most at-risk. Differences in accumbens connectivity with attention/motor/default networks, rather than control systems, may influence the reward system’s role in vulnerability for substance abuse.
Adolescent; alcoholism; functional connectivity; nucleus accumbens; reward; substance use
It is well established that individual difference factors modulate aggression under the acute effects of alcohol. In this investigation, we tested the hypothesis that one core dimension of psychopathy, Impulsive Antisociality, would modulate intoxicated aggression, whereas another dimension, Fearless Dominance, would not.
Participants were 516 young social drinkers (253 men and 263 women). Psychopathy was measured using the Psychopathic Personality Inventory (PPI; Lilienfeld and Andrews, 1996). Following the consumption of either an alcohol or a placebo beverage, aggression was measured with a task in which participants administered and received electric shocks to/from a fictitious opponent under the guise of a competitive reaction-time task.
Hierarchical regression analyses supported our hypothesis: Impulsive Antisociality predicted aggression under alcohol, whereas Fearless Dominance did not.
Persons who tend to endorse antisocial and impulsive externalizing behaviors appear to be at greater risk for aggression under the acute influence of alcohol.
Alcohol; Fearless Dominance; Impulsive Antisociality; Physical Aggression
In a prior study, we found changing tobacco use was more complex than previously thought, with users often transitioning between intending to quit and not intending to quit, and among typical use, abstinence, and reduction, on multiple occasions. The current study attempted to replicate those results.
A convenience sample of 40 tobacco smokers who intended to quit within the next 3 months called in nightly for 28 days to an Interactive Voice Response system to report cigs/day and daily intentions to smoke or not for the next day. We provided no treatment.
Within the month of the study, 32% of smokers had multiple episodes of intentions to not smoke, and 64% transitioned among smoking as usual, abstinence, and reduction status on multiple occasions. When participants reported they intended to not smoke the next day, 56% of the time they did not make a quit attempt the next day. Just under half (44%) of quit attempts occurred on days with no intentions to quit the night before. Most quit attempts (69%) lasted less than a day. Reduction in cigs/day was as common as abstinence.
Our prospective results replicated retrospective findings that most attempts to stop smoking result in a complex pattern of changes in smoking. These results suggest future research on treatments that can accommodate a) multiple quit attempts over a short period, b) reduction episodes, c) unplanned quit attempts, and d) immediate relapse.
smoking cessation; tobacco; relapse; harm reduction
People with psychiatric disorders are more likely to smoke and smoke more heavily than the general population, and they suffer disproportionally from smoking-related illnesses. However, little is known about how quitting versus continuing to smoke affects mental health and the likelihood of developing a psychiatric diagnosis. This study used data from a large prospective clinical trial to examine the relations of smoking cessation success with psychiatric diagnoses 1 and 3 years after the target quit day.
This study enrolled 1504 smokers (83.9% white; 58.2% female) in a cessation trial that involved the completion of the Composite International Diagnostic Interview to assess psychiatric diagnoses and biochemical confirmation of point-prevalence abstinence at Baseline and Years 1 and 3.
Regression analyses showed that, after controlling for pre-quit (past-year) diagnoses, participants who were smoking at the Year 3 follow-up were more likely to have developed and maintained a substance use or major depressive disorder by that time than were individuals who were abstinent at Year 3.
Quitting smoking does not appear to negatively influence mental health in the long-term and may be protective with respect to depression and substance use diagnoses; this should encourage smokers to make quit attempts and encourage clinicians to provide cessation treatment.
Smoking; Psychiatric diagnosis; Smoking cessation; Longitudinal; Mental health
Reductions in drinking among individuals randomised to control groups in brief alcohol intervention trials are common and suggest that asking study participants about their drinking may itself cause them to reduce their consumption. We sought to test the hypothesis that the statistical artefact regression to the mean (RTM) explains part of the reduction in such studies.
967 participants in a cohort study of alcohol consumption in New Zealand provided data at baseline and again six months later. We use graphical methods and apply thresholds of 8, 12, 16 and 20 in AUDIT scores to explore RTM.
There was a negative association between baseline AUDIT scores and change in AUDIT scores from baseline to six months, which in the absence of bias and confounding, is RTM. Students with lower baseline scores tended to have higher follow-up scores and conversely, those with higher baseline scores tended to have lower follow-up scores. When a threshold score of 8 was used to select a subgroup, the observed mean change was approximately half of that observed without a threshold. The application of higher thresholds produced greater apparent reductions in alcohol consumption.
Part of the reduction seen in the control groups of brief alcohol intervention trials is likely to be due to RTM and the amount of change is likely to be greater as the threshold for entry to the trial increases. Quantification of RTM warrants further study and should assist understanding assessment and other research participation effects.
Regression to the mean; Brief intervention; Alcohol; Student; Research participation
A national smoking cessation campaign based on behaviour change theory and operating through both traditional and new media was launched across England during late 2012 (‘Stoptober’). In addition to attempting to start a movement in which smokers would quit at the same time in response to a positive mass quitting trigger, the campaign set smokers the goal of being smoke-free for October and embodied other psychological principles in a range of tools and communications.
Data on quit attempts were obtained from 31,566 past-year smokers during nationally representative household surveys conducted monthly between 2007 and 2012. The effectiveness of the campaign was assessed by the increase in national quit attempt rate in October relative to other months in 2012 vs. 2007–2011.
Relative to other months in the year, more people tried to quit in October in 2012 compared with 2007–2011 (OR = 1.79, 95%CI = 1.20–2.68). In 2012 there was an approximately 50% increase in quitting during October compared with other months of the same year (9.6% vs. 6.6%; OR = 1.50, 95%CI = 1.05–2.15), whereas in 2007–2011 the rate in October was non-significantly less than in other months of the same period (6.4% vs. 7.5%; OR = 0.84, 95%CI = 0.70–1.00). Stoptober is estimated to have generated an additional 350,000 quit attempts and saved 10,400 discounted life years (DLY) at less than £415 per DLY in the modal age group.
Designing a national public health campaign with a clear behavioural target (making a serious quit attempt) using key psychological principles can yield substantial behaviour change and public health impact.
Smoking; Cessation; Quitting; Mass media; Cost-effectiveness; Stoptober
To prepare for DSM-V, the structure of DSM-IV alcohol dependence and abuse criteria and a proposed additional criterion, at-risk drinking, require study in countries with low per-capita consumption, and comparison of current and lifetime results within the same sample. We investigated DSM-IV Alcohol Use Disorder (AUD) criteria in Israel, where per-capita alcohol consumption is low.
Household residents selected from the Israeli population register (N=1,338) were interviewed with the AUDADIS. Item Response Theory analyses were conducted using MPlus, and diagnostic thresholds examined with the kappa statistic.
Dependence and abuse criteria fit a unidimensional model interspersed across the severity continuum, for both current and lifetime timeframes. Legal problems were rare and did not improve model fit. Weekly at-risk drinking reflected greater severity than in U.S. samples. When dependence and abuse criteria were combined, a diagnostic threshold of ≥3 criteria produced the best agreement with DSM-IV diagnoses (kappa>0.80).
Consistent with other studies, alcohol dependence and abuse criteria reflected a latent variable representing a single AUD. Results suggested little effect in removing legal problems and little gained by adding weekly at-risk drinking. Results contribute to knowledge about AUD criteria by examining them in a low-consumption country.
Item Response Theory; alcohol use disorders; alcohol abuse; alcohol dependence; at-risk drinking; DSM-IV; DSM-V; diagnostic criteria; Israel
Nicotine dependence (ND) and major depression (MD) are highly prevalent disorders that frequently co-occur. Less is known about which aspects of ND are most strongly associated with MD. The present study was designed to determine if subtypes of smokers exist and differ in their risk of MD and lifetime MD symptoms. Latent class analysis was used to identify profiles of DSM-IV ND criteria for 8,842 daily smokers drawn from the larger 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). We found evidence for 4 distinct subtypes of smokers mainly characterized by increasing levels of ND severity, by number of criteria endorsed. We found a dose–response relationship between classes by increasing ND severity and odds of past-year MD and lifetime depression criteria. Class 2 was characterized by higher symptom endorsement probabilities (SEPs) for wider range of ND criteria and a higher odds of MD (OR = 3.66) compared to class 3, which was characterized by higher SEPs for physiological ND criteria, higher prevalence of ND (class 2, 71.50% vs. class 3, 81.57%), and a lower odds of MD (OR = 2.15). A post hoc contrast showed these two distinct classes of respondents with mild to moderate ND significantly differed in their likelihood of MD comorbidity (F = 12.25, 1 df, p = 0.0008). ND severity mainly characterized the classes, but unique differences may exist between smokers with mild to moderate ND. Individuals with symptom profiles not characterized by physiological dependence endorse wider range of ND criteria and have a higher likelihood of MD.
Latent class analysis; Co-occurring disorders; Nicotine dependence; Major depression; Psychiatric epidemiology
Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans.
Outpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300 mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6 mg IM in ascending order at 1-hr intervals [up to 13.5 mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) Visual Analog Scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade.
Blockade of the VAS “any drug effect” response to 3 mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150 and 300 mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300 mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing.
These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment.
naltrexone; opioid blockade; opioid challenge; extended-release naltrexone; depot naltrexone; injectable naltrexone; Vivitrol; hydromorphone
The relationship between serious drug involvement and risk for unemployment is well recognized, but few studies have prospectively examined this relationship among college students. This study used longitudinal data to examine the association between drug use patterns during college and the likelihood of employment post-college, holding constant sociodemographic variables and personality characteristics. Second, we estimate the prevalence of alcohol and other drug use disorders among employed individuals.
Data were derived from the College Life Study. Participants entered college as traditional students and were assessed annually for six years, regardless of continued college attendance. Analyses were restricted to 620 individuals no longer enrolled in school by Year 6.
Using multinomial regression modeling, persistent drug users [i.e., used illicit drugs (other than marijuana) and/or nonmedical prescription drugs every year they were assessed during the first four years of study] were significantly more likely than non-users to be unemployed vs. employed full-time post-college. Persistent drug users and infrequent marijuana users were also more likely than non-users to be unemployed vs. employed part-time. In Year 6, 13.2% of individuals employed full-time and 23.7% of individuals employed part-time met DSM-IV criteria for drug abuse or dependence during the past year.
If confirmed, the results of this study suggest that persistent drug use among academically-achieving young adults might increase risk for post-college unemployment. More research is needed to understand the processes underlying this association. Further attention should be directed at managing substance use problems among recent college graduates who have secured employment.
College students; drug and alcohol use; employment; longitudinal study
Frontal systems dysfunction is present in stimulant-dependent patients. However, it is unclear whether this dysfunction is a pre-morbid risk factor or stimulant-induced, is severe enough to be clinically relevant, and if it is relevant to treatment response. These questions were addressed using the Frontal Systems Behavior Scale (FrSBe), a reliable and valid self-report assessment of three neurobehavioral domains associated with frontal systems functioning (Apathy, Disinhibition, and Executive Dysfunction, summed for a Total), that assesses both pre- and post- morbid functioning, and has a specific cutoff for defining clinically significant abnormalities.
Six sites evaluating 12-step facilitation for stimulant abusers obtained the FrSBe from 180 methamphetamine- and/or cocaine-dependent participants. Dichotomous treatment response measures included self-reported stimulant use, stimulant urine drug screens, and treatment completion.
A substantial percentage of participants retrospectively reported clinically significant neurobehavioral abnormalities prior to lifetime stimulant abuse initiation (e.g., 67.5% on FrSBe-Total) with a significant increase in the proportion reporting such abnormalities for current functioning (86% on FrSBe-Total; p<0.0001). Treatment response was significantly worse for participants with, relative to those without, clinically significant Disinhibition as measured by treatment non-completion (31.6% vs. 15.6%, OR=2.51) and self-reported stimulant use during treatment (40.5% vs. 16.7%, OR=3.40).
These findings suggest that frontal systems dysfunction is present prior to stimulant-abuse onset and worsens with stimulant use. Disinhibition may be a prime target for intervention in stimulant-dependent individuals.
cocaine; methamphetamine; stimulant; prefrontal cortex dysfunction; FrSBe
Recently, the NIH called for additional research on the topic of viral and host factors contributing to impaired cognitive and neural function in HIV/AIDS patients and their response to antiretroviral treatment. This investigation responds to that call by examining a host factor, a family history of substance dependence, often overlooked in cognitive and neuroimaging studies of HIV/AIDS.
We categorized 146 HIV-1 seropositive patients receiving antiretroviral treatment (ART) and 92 seronegative volunteers by the presence or absence of alcohol, cocaine, or heroin dependence affecting a biological parent. Seropositive patients were further categorized by the estimated ability of their individual ART regimens to penetrate the CNS. The indicator of brain function was a 3–7 Hz oscillatory electroencephalographic response (theta ERO) evoked by target stimuli presented during a simple selective attention task.
The analysis revealed that the presence of a family history of substance dependence obscured the reduction in frontal theta ERO power accompanying the presence of HIV-1 as well as the improvement in frontal theta ERO power accompanying treatment with ART agents estimated to have greater (n=41) versus lesser (n=105) CNS penetrance. Secondary analyses employing sLORETA source localization techniques revealed that the source of the theta ERO response was similarly reduced by the presence of either HIV-1 or a family history of substance dependence.
We conclude that a family history of substance dependence complicates and obscures the subtle neurophysiological changes which typically accompany HIV/AIDS and ART. Studies of new therapeutic agents for HIV-1-associated cognitive and neurophysiological impairments must consider this complication and exclude or control it.
HIV; Substance Use Disorder; Family History; Event Related Potentials; AIDS; Antiretroviral Treatment