Exploring the performance of during-treatment substance use outcome measures in predicting longer-term psychosocial functioning and post-treatment abstinence.

BACKGROUND: The selection of appropriate efficacy endpoints in clinical trials has been a long-standing challenge for the substance use disorder field. Using data from a large, multi-site National Drug Abuse Treatment Clinical Trials Network trial (CTN-0044; n=474), this secondary data analysis aimed to explore whether specific proximal (during-treatment) substance use outcome measures predict longer-term improvements in psychosocial functioning and post-treatment abstinence, and whether predictions vary depending on the specific substance (cannabis, cocaine/stimulants, opioids, and alcohol). METHODS: Generalized linear mixed models examined associations between six during-treatment substance use outcome measures and social functioning impairment (Social Adjustment Scale Self-Report) and severity of psychiatric symptoms (Brief Symptom Inventory-18) at end-of-treatment, and 3- and 6-months after treatment as well as post-treatment abstinence. RESULTS: Maximum days of consecutive abstinence, proportion of days abstinent, ≥3 weeks of continuous abstinence, and the proportion of urine specimens negative for the primary substance were associated with post-treatment psychiatric and social functioning improvement and abstinence. However, only the effects of abstinence during the last 4 weeks of the treatment period on all three post-treatment outcomes was stable over time and did not differ between primary substance groups. In contrast, complete abstinence during the 12-week treatment period was not consistently associated with functioning improvements. CONCLUSIONS: Substance use outcome measures capturing the duration of primary substance abstinence during treatment are suitable predictors of post-treatment abstinence and longer-term psychosocial functioning improvement. Binary outcomes, such as end-of-treatment abstinence, may be particularly stable predictors and attractive given their ease of computation and straightforward clinical interpretability.

Safety and efficacy of a digital therapeutic for substance use disorder: Secondary analysis of data from a NIDA clinical trials network study.

Background: Traditional treatments for substance use disorders (SUDs) rely heavily on face-to-face interactions, which pose substantial limitations for patients. A clinical trial of a digital therapeutic (DT), delivering behavioral therapy demonstrated safety and efficacy in a population including patients with opioid use disorder (OUD) not treated with buprenorphine, which is not a guideline-recommended approach. This study re-analyzed the data excluding patients with OUD to more closely approximate real-world patient populations. Methods: Secondary analysis of patients with substance use disorders related to alcohol, cannabis, cocaine, or other stimulants (n = 399, patients with OUD excluded) from a previously-published randomized controlled trial. Patients received 12-weeks of outpatient treatment-as-usual (TAU; n = 193) or TAU with reduced counseling plus a DT (n = 206) providing computerized cognitive behavioral therapy and contingency management. Primary outcomes were abstinence in weeks 9-12 and retention in treatment. Results: The 399 patients in this analysis (206 in the DT group and 193 in the TAU group) reported substance use disorders related to alcohol, cannabis, cocaine, or other stimulants (e.g., methamphetamines). Demographic and baseline characteristics including age, sex, race, education, and reported primary substance use disorder were balanced between treatment groups. Abstinence was significantly higher in the DT group compared to TAU (40.3 vs. 17.6%; p < 0.001) as was retention in therapy (76.2 vs. 63.2%, p = 0.004). Intergroup adverse event rates were not significantly different (p = 0.68). Conclusions: The results demonstrate that use of a DT safely increased abstinence (reduced substance use) and retention in treatment among patients with substance use disorders related to alcohol, cannabis, cocaine, or other stimulants (including methamphetamines).

Engagement patterns with a digital therapeutic for substance use disorders: Correlations with abstinence outcomes.

INTRODUCTION: Patient engagement may play a key role in the success or failure of treatments for substance use disorder (SUD). This exploratory analysis of data from a large, multisite effectiveness trial (NCT01104805) sought to determine how patient engagement with a digital therapeutic for SUD delivered at clinics was associated with abstinence outcomes. METHODS: The study evaluated engagement for 206 participants enrolled in a treatment program for SUDs related to cocaine, alcohol, cannabis, or other stimulants who were randomized to receive treatment as usual (TAU) or reduced TAU plus the digital Therapeutic Education System (TES) for 12 weeks. Participants were eligible for contingency management incentives for module completion (modules cover Community Reinforcement Approach topic areas) and negative urine drug screens. Analyses examined the association of module completion with end-of-treatment abstinence. RESULTS: Participants completed a mean of 38.8 (range 0-72) TES modules over 12 weeks of treatment. Study completers (n = 157) completed a mean of 45.5 (range 9-72) TES modules, whereas study noncompleters (n = 49) completed a mean of 17.4 (range 0-45) TES modules. The study observed a strong positive correlation between TES engagement (i.e., total number of modules completed) and the probability of abstinence during weeks 9-12 of treatment among 157 study completers (OR = 1.11; 95% CI 1.08-1.14). Each module completed increased the odds of abstinence during weeks 9-12 by approximately 11% for study completers and 9% for the full sample. The study observed a similar, but weaker, association between engagement and abstinence among 49 patients who did not complete the study (OR = 1.02; 95% CI 0.98-1.07). CONCLUSIONS: Greater engagement with a digital therapeutic for patients with SUD (i.e., number of modules completed over time) was strongly associated with the probability of abstinence in the last four weeks of treatment among those who completed the recommended 12-week treatment. TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT01104805.

Design and methods of a multi-site randomized controlled trial of an integrated care model of long-acting injectable buprenorphine with infectious disease treatment among persons hospitalized with infections and opioid use disorder.

BACKGROUND: Hospitalization with co-occurring opioid use disorder (OUD) and infections presents a critical time to intervene to improve outcomes for these intertwined epidemics that are typically managed separately. A surge in life-threatening infectious diseases associated with injection drug use, including bacterial and fungal infections, HIV, and HCV accounts for substantial healthcare utilization, morbidity, and mortality. Infectious Disease (ID) specialists manage severe infections that require hospitalization and are a logical resource to engage patients in medication treatment for OUD (MOUD). An injectable long-acting monthly formulation of buprenorphine (LAB) has a potential advantage for initiating MOUD within hospital settings and bridging to treatment after discharge. METHODS: A randomized multi-site trial tests a new model of care (ID/LAB) in which OUD and infections are managed by ID specialists and hospitalists using LAB coupled with referrals to community resources for long-term MOUD. A sample of 200 adults admitted to three U.S. hospitals for OUD and infections are randomly assigned 1:1 to ID/LAB or treatment as usual (TAU). The primary outcome measure is the proportion of patients enrolled in effective MOUD at 12 weeks after randomization. Secondary outcomes include relapse to opioid use, adherence to infectious disease treatment, infection morbidity and mortality, and drug overdose. RESULTS: We describe the design, procedures, statistical analysis, and early implementation issues of this randomized trial. CONCLUSIONS: Study findings will provide insight into the feasibility and effectiveness of integrated treatment of OUD and serious infections and have the potential to reduce morbidity and mortality in this vulnerable population.

Quetiapine treatment for cannabis use disorder.

BACKROUND: Pharmacotherapy for cannabis use disorder (CUD) is an important unmet public health need. METHODS: In a 12-week randomized double-blind placebo-controlled trial, the efficacy of quetiapine (300 mg nightly) for the treatment of CUD was tested in 130 outpatients. Weekly cannabis use was categorized into three groups: heavy use (5-7 days), moderate use (2-4 days) and light use (0-1 days). RESULTS: At baseline both groups were considered heavy users (using days per week: median = 7.0; interquartile range (IQR): 6.5-7.0; daily dollar value: median = $121.4; IQR: 73.8-206.3). The week-by-treatment interaction was marginally significant (χ2(2) = 5.56, P = .06). With each week, the odds of moderate compared to heavy use significantly increased in the quetiapine group (OR=1.17, P < .0001), but not significantly in the placebo group (OR=1.05, P = .16). The odds of light versus heavy use did not significantly differ over time (P = .12). Treatment was also associated with reduced cannabis withdrawal symptoms by 10.4% each week (95% CI: 8.9-11.8). No serious adverse events occurred during the study and no evidence of development of a movement disorder was detected. Adverse effects were not significantly different between the quetiapine and placebo treatment arms. CONCLUSIONS: The use of quetiapine to treat CUD was associated with an increased likelihood of heavy frequency use transitioning to moderate use, but not light use. The clinical significance of reductions in cannabis use, short of abstinence warrants further study.

Exploring gender differences among treatment-seekers who use opioids versus alcohol and other drugs.

Identifying clinical differences between opioid users (OU) and alcohol and other drug users (AOD) may help to tailor treatment to OU, particularly among the majority of OU who are not on opioid agonist treatments. Given the dearth of research on these differences, this study explored gender differences in demographic and clinical characteristics between OU and AOD. Participants (N = 506) were from a multisite, randomized controlled clinical trial of an Internet-delivered psychosocial intervention conducted in 2010-2011. Logistic regression models explored differences in demographic and clinical characteristics by substance use category within and between women and men. Women OU were more likely to be younger, White, employed, benzodiazepine users, and less likely to have children or use cocaine and cannabis than women AOD. Men OU, compared to men AOD, were more likely to be younger, White, younger at first abuse/dependence, benzodiazepine users, and reported greater psychological distress, but were less likely to be involved in criminal justice or use stimulants. Interactions by gender and substance use were also detected for age of first abuse/dependence, employment, and criminal justice involvement. These findings provide a nuanced understanding of gender differences within substance use groups to inform providers for OU seeking treatment.

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial.

OBJECTIVE: Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. METHODS: Fifty-five cocaine-dependent individuals were randomly assigned to receive a 40-minute intravenous infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) during a 5-day inpatient stay, during which they also initiated a 5-week course of mindfulness-based relapse prevention. Cocaine use was assessed through self-report and urine toxicology. The primary outcomes were end-of-study abstinence and time to relapse (defined as first use or dropout). RESULTS: Overall, 48.2% of individuals in the ketamine group maintained abstinence over the last 2 weeks of the trial, compared with 10.7% in the midazolam group (intent-to-treat analysis). The ketamine group was 53% less likely (hazard ratio=0.47; 95% CI=0.24, 0.92) to relapse (dropout or use cocaine) compared with the midazolam group, and craving scores were 58.1% lower in the ketamine group throughout the trial (95% CI=18.6, 78.6); both differences were statistically significant. Infusions were well tolerated, and no participants were removed from the study as a result of adverse events. CONCLUSIONS: A single ketamine infusion improved a range of important treatment outcomes in cocaine-dependent adults engaged in mindfulness-based behavioral modification, including promoting abstinence, diminishing craving, and reducing risk of relapse. Further research is needed to replicate these promising results in a larger sample.

Neurocognitive Profiling of Adult Treatment Seekers Enrolled in a Clinical Trial of a Web-delivered Intervention for Substance Use Disorders.

OBJECTIVE: This study is a secondary descriptive analysis that explores and compares the cognitive profiles of adults entering treatment at geographically diverse community-based substance use disorder treatment facilities. METHODS: Performance on cognitive measures at baseline was compared across 5 primary substance subgroups of individuals (alcohol = 104; cocaine = 102; stimulants = 69; opioids = 108; marijuana = 114) enrolled in a web-based psychosocial treatment study conducted within the National Drug Abuse Treatment Clinical Trials Network. MicroCog subtests were used to assess cognitive domains of attention and mental control, reasoning and cognitive flexibility, and spatial processing. RESULTS: The average age of onset for a substance use disorder was early to mid-20s, with marijuana users reporting the earliest age of onset (mean 19.9, SD 7.5) and stimulant users reporting the latest (mean 25.2, SD 9.9). Among the total sample, half (49.7%) demonstrated impairment in cognitive flexibility and reasoning, and over one-third (37.3%) had impairment in verbal learning and memory. Stimulant (37.68%) and cocaine (34.31%) users showed significantly greater clinical impairment in attention and mental control compared with alcohol users (17.31%) and opioid (21.30%) users (stimulant subgroup only) (χ [4] = 10.97, P = 0.027). Cocaine users showed the greatest overall impairment across total and proficiency subtest scores, although these were not statistically different from other subgroups. CONCLUSIONS: These findings confirmed previous studies, indicating a high prevalence of significant cognitive dysfunction across all substance use categories among treatment-seeking adults, and found that cocaine use appears to be associated with the most impairment. Increasing knowledge of similarities and differences between primary substance subgroups can help guide substance use disorder treatment planning.

New Directions in Medication-Facilitated Behavioral Treatment for Substance Use Disorders.

A promising approach to addressing substance use disorders is to integrate pharmacotherapy with a behavioral treatment with which synergy is possible. In this review, we focus on recent research suggesting that this approach may be effective for cocaine and cannabis use disorders, both of which currently lack efficacious medications. We summarize potential targets of pharmacotherapy of particular relevance to combined medication-behavioral treatment and examine preliminary evidence of clinical efficacy. Common to these promising medications is a hypothesized mechanism of action predicated on reversing drug-related neural adaptations, such as high reactivity to stress or drug cues, that might undermine fruitful engagement with behavioral treatment. We also review emerging medications, such as certain glutamatergic and serotonergic agents, which may be feasibly integrated with existing treatments. We conclude with an outline of future directions for research.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

The effects of dronabinol during detoxification and the initiation of treatment with extended release naltrexone.

BACKGROUND: Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). METHODS: Opioid dependent participants were randomized to receive dronabinol 30mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. RESULTS: The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. CONCLUSION: Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment.

Web-based treatment for substance use disorders: differential effects by primary substance.

INTRODUCTION: This secondary analysis of data from a large, multi-site effectiveness trial (NCT01104805) sought to determine whether effects of a web-based behavioral treatment (Therapeutic Education System [TES]) differed by participants' self-identified primary drug of abuse. METHODS: The all-comers sample of individuals entering outpatient psychosocial counseling treatment for substance abuse (N=497) cited cannabis (22.9%; n=114), stimulants (34.4%, n=171), opioids (21.7%, n=108), or alcohol (20.9%, n=104) as their primary substance of abuse. Participants were randomly assigned to receive treatment-as-usual (TAU) with or without TES substituted for approximately 2h of usual counseling. Multivariate analyses of abstinence outcomes examined interactions of treatment effects with primary substance. RESULTS: Adjusted odds ratios (AORs) demonstrated that primary stimulant users receiving TES were more likely to be abstinent in the final four weeks of treatment compared to stimulant users receiving TAU (AOR=3.59, 95% CI=1.25-10.27). Adjusted odds ratios for alcohol (AOR=3.15, 95% CI=0.85-11.65) and cannabis (AOR=2.64, 95% CI=0.73-9.52) also were of similar magnitude to stimulants but did not reach significance. Abstinence among primary opioid users was not improved by the TES intervention (AOR=0.35, 95% CI=0.09-1.47). CONCLUSIONS: This study supports the TES web-delivered treatment as a viable intervention for the majority of substance users entering outpatient counseling treatment, with demonstrated effectiveness among stimulant users and promising effects in alcohol and cannabis users but little or no effect in primary opioid users. Web-delivered treatments hold promise for expanding the availability of effective behavioral interventions for the majority of substance use disorders.

Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

BACKGROUND AND AIMS: Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. METHODS: We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. RESULTS: The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. CONCLUSIONS: Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use.

Open-label pilot study of quetiapine treatment for cannabis dependence.

BACKGROUND: There are no efficacious pharmacotherapies for cannabis dependence. The effects of quetiapine are well matched to the symptoms of cannabis withdrawal and could be useful in the treatment of cannabis dependence. OBJECTIVES: To evaluate quetiapine for the treatment of cannabis dependence and determine the optimal dosing. METHODS: In an eight-week open-label outpatient pilot trial, we evaluated the feasibility of quetiapine treatment for cannabis dependence in 15 outpatients. Quetiapine was gradually titrated to 600 mg or the maximum tolerated dose. RESULTS: The mean study retention was 6.5 weeks (±2.3), with 67% of participants completing all eight weeks of the trial. The mean maximum dose achieved was 197 mg/day (range: 25-600 mg/day). Only two of the 15 participants were able to achieve the target dose of 600 mg daily. There were no serious adverse events and no participants were discontinued from the trial due to adverse effects. The most common reported adverse effects were fatigue (80% of participants) and somnolence (47%). From baseline to week 8, the modeled overall decrease in daily dollar value of marijuana was 76.3% (CI: 63.4%, 84.7%). Over the eight weeks of the study, there was a 46.9% (CI: 11%, 68.3%) decrease in urine tetrahydrocannabinol-9-carboxylic acid (THCOOH) levels. CONCLUSIONS: These preliminary results are promising in that quetiapine treatment was tolerated by cannabis-dependent patients and associated with decreased cannabis use. The recommended maximum target dose for cannabis-dependent patients is 300 mg daily. These preliminary data support further evaluation of quetiapine as a treatment for cannabis dependence.

Clinically relevant characteristics associated with early treatment drug use versus abstinence.

BACKGROUND: This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. METHODS: We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. RESULTS: Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. CONCLUSIONS: Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. TRIAL REGISTRATION: NCT01104805.

Characteristics of an outpatient treatment sample by primary substance of abuse.

OBJECTIVE: This study examines sociodemographic and clinical characteristics, as a function of primary substance of abuse, among clients approached, screened, and assessed for eligibility in a 10-site effectiveness trial of a Web-based psychosocial intervention for substance use disorders. Consistent with the design of effectiveness trials, eligibility criteria were broad and exclusion criteria minimal; thus, the recruited sample may be viewed as relatively representative of patients seeking treatment throughout the United States. METHODS: χ tests for categorical variables and F tests for continuous variables were used to analyze demographic, substance use, physical and mental health, and sexual risk data collected at screening and baseline; pairwise comparisons between primary substance subgroups for baseline data were conducted if the test statistic P value was 0.01 or less. RESULTS: Few participants expressed disinterest in the study at screening because of the computer-assisted intervention. A diverse sample of substance users completed baseline and were enrolled: 22.9% marijuana; 21.7% opiates; 20.9% alcohol; 20.5% cocaine; and 13.9% stimulants users. Marijuana users demonstrated the greatest differences across primary substances: they were younger, less likely to be married or attend 12-step meetings, and more likely to be in treatment as a result of criminal justice involvement. All patients, even marijuana users, reported comparable rates of co-occurring mental health disorders and sexual risk and substantial rates of polysubstance use disorders. CONCLUSIONS: Primary substance of abuse may be a less important indicator of overall severity compared with co-occurring disorders and other factors common across treatment seekers, further demonstrating the need for integrated treatment services and care and comprehensive pretreatment assessment.

Demographic and clinical characteristics of middle-aged versus younger adults enrolled in a clinical trial of a web-delivered psychosocial treatment for substance use disorders.

OBJECTIVE: Evidence suggests that substance abuse is becoming more prevalent in middle-aged adults. The objective of this secondary analysis was to add to the growing empirical literature on the unique features of middle-aged substance abuse populations. METHODS: We descriptively compared baseline demographic and clinical characteristics of middle-aged (age 45-62 years, n = 111) and younger (age 18-44 years, n = 395) substance abusers entering a Web-based psychosocial treatment study as part of the National Institute on Drug Abuse Clinical Trials Network. RESULTS: A significantly greater percentage of middle-aged adults were nonwhite and had a marital status other than single/never married. There was a significant association between frequency of Internet use and the age group. Forty-six percent of middle-aged adults versus 21% of younger adults reported no Internet use in the prior 90 days. A significantly greater percentage of middle-aged adults used cocaine, and a significantly greater percentage of younger adults used marijuana and opioids. Clinically significant cognitive impairment (z < -1.0) was found for the average participant in both groups on logical association of familiar concepts. CONCLUSIONS: This secondary analysis of a National Institute on Drug Abuse Clinical Trials Network study provides additional information on the unique features of middle-aged substance abusers. Increasing knowledge of similarities and differences between younger and middle-aged substance abusers can help with potential age-specific substance abuse treatment planning.

A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p< .005). Cannabis dependence was highly associated with independent depression (p< .001), while cocaine dependence was highly associated with substance-induced depression (p< .05). Independent depression was associated with higher Hamilton depression scale scores (16 vs. 10, p< .005), and was more highly associated with the comorbid diagnosis of posttraumatic stress disorder (p< .05). Cannabis dependence (p< .001) and female gender (p< .05) were highly significant predictors of major depression specifically. Gender, cannabis dependence, psychiatric severity, and psychiatric comorbidity have variable, statistically significant associations with independent and substance-induced depression, and may be helpful in guiding the diagnostic process.

Comparison of clinical trial recruitment populations: treatment-seeking characteristics of opioid-, cocaine-, and cannabis-using participants.

This study examined the treatment history and intention to seek treatment among 489 individuals interested in substance use disorder clinical trial participation. Opioid and cocaine users were more likely than cannabis users to report having received treatment for substance use in the past and more likely than cannabis users to report planning to seek treatment for substance use before exposure to recruitment advertising. Free cost was the aspect of clinical trial participation that most influenced the decision to make an intake evaluation appointment for opioid-dependent patients as compared with cocaine- and cannabis-dependent participants, and the availability of individual psychotherapy most influenced those who were cannabis dependent. Cannabis-dependent individuals evaluated for clinical trial participation reported that recruitment advertising was an important factor in leading them to seek treatment. These results have implications for clinical trial recruitment and public health efforts directed at encouraging cannabis-dependent individuals to seek treatment.

Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial.

Cannabis dependence is a substantial public health problem. Behavioral treatments have shown promise, but there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence. 156 cannabis-dependent adults were enrolled in a randomized, double-blind, placebo-controlled, 12-week trial. After a 1-week placebo lead-in phase, participants were randomized to receive dronabinol 20mg twice a day or placebo. Doses were maintained until the end of week 8 and then tapered off over 2 weeks. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow back method. There was no significant difference between treatment groups in the proportion of participants who achieved 2 weeks of abstinence at the end of the maintenance phase (dronabinol: 17.7%; placebo: 15.6%). Although both groups showed a reduction in marijuana use over time, there were no differences between the groups. Treatment retention was significantly higher at the end of the maintenance phase on dronabinol (77%), compared to placebo (61%) (P=.02), and withdrawal symptoms were significantly lower on dronabinol than placebo (P=.02). This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms. Future trials might test higher doses, combinations of dronabinol with other medications with complementary mechanisms, or with more potent behavioral interventions.