Melissa M. Norberg

A Meta-Analysis of D-Cycloserine and the Facilitation of Fear Extinction and Exposure Therapy

BACKGROUND Translational research suggests that D-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist, might facilitate fear extinction and exposure therapy by either enhancing NMDA receptor function during extinction or by reducing NMDA receptor function during fear memory consolidation. This article provides a quantitative review of DCS-augmented fear extinction and exposure therapy literature. METHODS English-language journal articles that examined DCS augmented with fear extinction or exposure therapy were identified through public databases from June 1998 through September 2007, through references of originally identified articles and contact with DCS investigators. Data were extracted for study author, title, and year; trial design; type of subject (animal vs. human; clinical vs. nonclinical); sample size, DCS dose, and timing in relation to extinction/exposure procedures; dependent variable; group means and SDs at post-extinction/exposure; and follow-up outcome. RESULTS D-cycloserine enhances fear extinction/exposure therapy in both animals and anxiety-disordered humans. Gains generally were maintained at follow-up, although some lessening of efficacy was noted. D-cycloserine was more effective when administered a limited number of times and when given immediately before or after extinction training/exposure therapy. CONCLUSIONS This meta-analysis suggests that DCS is a useful target for translational research on augmenting exposure-based treatment via compounds that impact neuroplasticity. D-cycloserine s major contribution to exposure-based therapy might be to increase its speed or efficiency, because the effects of DCS seem to decrease over repeated sessions. This information might guide translational researchers in discovering more selective and/or effective agents that effectively enhance (or reduce) NMDA receptor function.

Categorization and cognitive deficits in compulsive hoarding.

According to the cognitive-behavioural model of compulsive hoarding, information-processing deficits in the areas of attention, memory, decision-making, and categorization contribute to hoarding behaviour. The purpose of the current study was to examine whether individuals with compulsive hoarding exhibited impairment on executive functioning and categorization tasks. Three groups of participants were recruited (N = 60): individuals with compulsive hoarding syndrome, individuals with an Axis I mood or anxiety disorder, and non-clinical control participants. All participants completed self-report measures of cognitive difficulties, neuropsychological tests of executive functioning and decision-making, and four categorization tasks. Results suggested that hoarding participants reported more cognitive failures and more problems with attention and decision-making than non-clinical control participants. In addition, hoarding participants performed worse than both control groups on the Stockings of Cambridge (SOC), a neuropsychological test of planning ability, and were slower and more anxious during a categorization task. These findings suggest that specific deficits in executive functioning may be associated with the difficulties hoarding patients have organizing their possessions.

The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress.

BACKGROUND Rates of treatment seeking for cannabis are increasing, and relapse is common. Management of cannabis withdrawal is an important intervention point. No psychometrically sound measure for cannabis withdrawal exists, and as a result treatment developments cannot be optimally targeted. The aim is to develop and test the psychometrics of the Cannabis Withdrawal Scale and use it to explore predictors of cannabis withdrawal. METHODS A volunteer sample of 49 dependent cannabis users provided daily scores on the Cannabis Withdrawal Scale during a baseline week and 2 weeks of abstinence. RESULTS Internal reliability (Cronbachs alpha=0.91), test-retest stability (average intra-class correlation=0.95) and content validity analysis show that the Cannabis Withdrawal Scale has excellent psychometric properties. Nightmares and/or strange dreams was the most valid item (Wald χ²=105.6, P<0.0001), but caused relatively little associated distress (Wald χ²=25.11, P=0.03). Angry outbursts were considered intense (Wald χ²=73.69, P<0.0001) and caused much associated distress (Wald χ²=45.54, P<0.0001). Trouble getting to sleep was also an intense withdrawal symptom (Wald χ²=42.31, P<0.0001) and caused significant associated distress (Wald χ²=47.76, P<0.0001). Scores on the Severity of Dependence Scale predicted cannabis withdrawal. CONCLUSIONS The Cannabis Withdrawal Scale can be used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required.

Quantifying the Clinical Significance of Cannabis Withdrawal

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal: A Randomized Clinical Trial

IMPORTANCE There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. OBJECTIVE To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. DESIGN, SETTING, AND PARTICIPANTS A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. INTERVENTIONS A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. MAIN OUTCOMES AND MEASURES Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. RESULTS Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of nabiximols over placebo for self-reported cannabis use (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89). CONCLUSIONS AND RELEVANCE In a treatment-seeking cohort, nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12611000398909.

Social Anxiety, Reasons for Drinking, and College Students.

Recent research suggests that social anxiety may be associated with higher rates of alcohol problems in women, yet may be associated with lower levels of drinking in men. The current study investigated putative mechanisms that may underlie potential gender differences in the social anxiety-alcohol relationship. One hundred and eighteen college students (61.0% women) completed an interview assessing drinking behaviors and questionnaires measuring social anxiety, drinking motives, and drinking situations. Although college men and women both reported similar frequencies of drinking in positive situations and to enhance positive emotions, women reported drinking more often in negative situations and to cope with aversive emotions than men. Mediated moderation analyses suggested that women with social anxiety may be at greater risk of encountering adverse consequences because of their likelihood to drink to conform or to cope with the aversive affect they experience in negative situations. Conversely, when men experience high rates of adverse consequences, it may be due to drinking greater quantities of alcohol in positive situations. Highly socially anxious college men may drink less alcohol and experience fewer adverse consequences than their nonanxious or mildly anxious counterparts because they may find themselves in positive situations and drinking to enhance positive feelings less often, potentially due to avoidant behavior. These findings may help to explain why social anxiety serves as a potential risk factor for alcohol-related problems for college women, but a protective factor for college men.

The association between distress tolerance and cannabis use-related problems: the mediating and moderating roles of coping motives and gender.

Recent research has linked distress intolerance to a greater incidence of cannabis use-related problems. Additionally, individuals reporting coping motives for cannabis use might be particularly vulnerable to use-related problems, and tendencies to use coping motives may be influenced by gender. The current study sought to extend the literature by examining the role of distress tolerance on cannabis use-related problems and the potential influences of coping motives for use and gender. Participants were 118 cannabis-using adults (Mage = 29.84). As hypothesized, highly distress intolerant individuals reported more cannabis-use related problems. Further, coping motives mediated the relationship between distress tolerance and cannabis use-related problems, and this effect was more powerful for women than for men. The current study adds to our understanding of the impact of distress tolerance and problematic patterns of cannabis use.

Quality of life and anxiety and depressive disorder comorbidity

The present investigation evaluated the relations among anxiety and depressive disorder comorbidity and quality of life (QOL) by utilizing self-report measures of life satisfaction and functional disability. Participants were 94 individuals who were presented for treatment at an outpatient anxiety disorders clinic and 26 nonclinical participants. Results indicated that participants diagnosed with anxiety disorders reported lower QOL than did nonclinical participants. Anxiety disorder comorbidity did not additionally impact QOL; however, presence of a depressive disorder comorbid with an anxiety disorder did negatively impact QOL as these individuals reported significantly more functional disability and less life satisfaction than did individuals with anxiety disorders alone or those without a psychiatric diagnosis. These results highlight the negative nature of anxiety disorders and improve clarification on the role of diagnostic comorbidity on QOL among those with an anxiety disorder.

Effectiveness of a Self-Guided Web-Based Cannabis Treatment Program: Randomized Controlled Trial

Background Self-help strategies offer a promising way to address problems with access to and stigma associated with face-to-face drug and alcohol treatment, and the Internet provides an excellent delivery mode for such strategies. To date, no study has tested the effectiveness of a fully self-guided web-based treatment for cannabis use and related problems. Objectives The current study was a two-armed randomized controlled trial aimed at testing the effectiveness of Reduce Your Use, a fully self-guided web-based treatment program for cannabis use disorder consisting of 6 modules based on cognitive, motivational, and behavioral principles. Methods 225 individuals who wanted to cease or reduce their cannabis use were recruited using both online and offline advertising methods and were randomly assigned to receive: (1) the web-based intervention, or (2) a control condition consisting of 6 modules of web-based educational information on cannabis. Assessments of cannabis use, dependence symptoms, and abuse symptoms were conducted through online questionnaires at baseline, and at 6-week and 3-month follow-ups. Two sets of data analyses were undertaken—complier average causal effect (CACE) modeling and intention to treat (ITT). Results Two thirds (149) of the participants completed the 6-week postintervention assessment, while 122 (54%) completed the 3-month follow-up assessment. Participants in the intervention group completed an average of 3.5 of the 6 modules. The CACE analysis revealed that at 6 weeks, the experimental group reported significantly fewer days of cannabis use during the past month (P=.02), significantly lower past-month quantity of cannabis use (P=.01), and significantly fewer symptoms of cannabis abuse (P=.047) relative to controls. Cannabis dependence symptoms (number and severity) and past-month abstinence did not differ significantly between groups (Ps>.05). Findings at 3 months were similar, except that the experimental group reported significantly fewer and less severe cannabis dependence symptoms (Ps<.05), and past-month quantity of cannabis consumed no longer differed significantly between groups (P=.16). ITT analyses yielded similar outcomes. Conclusion Findings suggest that web-based interventions may be an effective means of treating uncomplicated cannabis use and related problems and reducing the public health burden of cannabis use disorders. Trial registration ACTRN12609000856213, Australian New Zealand Clinical Trials Registry.

Group cognitive-behavioral therapy for hoarding disorder: An open trial

Although cognitive-behavioral therapy (CBT) appears to be a promising treatment approach for hoarding disorder, treatment to date has been quite labor intensive. The goal of this study, therefore, was to assess the potential effectiveness of group CBT for hoarding, without home visits by the clinician. Forty-five individuals with hoarding disorder enrolled in either a 16 or 20 session program of group CBT; 30 (67%) completed treatment. Using mixed-effects models to account for missing data, we report data from 35 (78%) participants who provided enough data for analysis. Participants demonstrated significant improvements in hoarding symptoms, as well as symptoms of depression and anxiety, and quality of life. Improvements in hoarding symptoms were comparable to two published clinical trials on individual CBT for hoarding disorder. Results of this study suggest that group CBT for hoarding, without home discarding sessions by the clinician, may be an effective treatment option with the potential advantage of increasing treatment access by reducing clinician burden and cost of treatment.