NIDA 41020

Design of the NIDA clinical trials network validation study of tobacco, alcohol, prescription medications, and substance use/misuse (TAPS) tool.[Pubmed:27444426]

Contemp Clin Trials. 2016 Sep;50:90-7.

BACKGROUND: Substance use and its associated use disorders are under-detected and under-treated in primary care. There is a need for a clinically useful brief screening and assessment instrument to identify primary care patients with substance use, sub-threshold substance use disorder (SUD), and SUD to facilitate brief intervention and treatment. METHODS: We describe the design of the recently completed National Drug Abuse Treatment Clinical Trials Network's tobacco, alcohol, prescription medications, and substance use/misuse screen and brief assessment tool validation study. Study aims included to: develop a 2-stage screening and brief assessment tool (TAPS Tool) to detect substance use, problem use, and SUD among adult primary care patients; examine the validity of both the screen component and the TAPS Tool by comparing them to reference standard screening and assessment measures of no use, problem use, and SUD; and determine the feasibility and acceptability of the self-administration and interviewer-administration of the tool. The design included a pilot testing phase (n=30) and the main study of 2000 adult primary care participants who were randomly assigned in counter-balanced order to have the interviewer-administration or the self-administration of the TAPS Tool followed by the other administration format. Participants' views of feasibility, acceptability and preference for format of self-administration versus interviewer-administration of the TAPS Tool were assessed. Criterion measures of use and DSM-5 SUDs were administered. DISCUSSION: The TAPS Tool study builds on prior work to develop a 2-stage clinical tool for facilitating the adoption of screening, brief assessment and treatment for SUDs in primary care.

Coping strategies as a mediator of internet-delivered psychosocial treatment: Secondary analysis from a NIDA CTN multisite effectiveness trial.[Pubmed:27776269]

Addict Behav. 2017 Feb;65:74-80.

OBJECTIVE: Coping strategies are a predictor of abstinence among patients with substance use disorders. However, little is known regarding the role of coping strategies in the effectiveness of the Community Reinforcement Approach (CRA). Using data from a 12week randomized control trial assessing the effectiveness of the Therapeutic Education System (TES), an internet-delivered version of the CRA combined with contingency management, we tested the role of coping strategies as a mediator of treatment effectiveness. METHODS: 507 participants entering 10 outpatient addiction treatment programs received either treatment-as-usual (TAU), a counselor-delivered treatment (Arm 1), or reduced TAU plus TES wherein 2h of TAU per week were replaced by TES (Arm 2). Abstinence from drugs and alcohol was evaluated using urine toxicology and self-report. Coping strategies were measured using the Coping Strategies Scale-Brief Version. Mediation analyses were done following Baron and Kenny's and path analysis approaches. RESULTS: The average baseline coping strategies scores were not significantly different between the two treatment arms. Overall, TES intervention was significantly associated with higher coping strategies scores when accounting for baseline scores (F1,1342=8.3, p=0.004). Additionally, higher coping strategies scores at week 12 were associated with an increased likelihood of abstinence during the last 4weeks of the treatment, while accounting for treatment assignment and baseline abstinence. The effect of TES intervention on abstinence was no longer significant after controlling for coping strategies scores at week 12. CONCLUSION: Our results support the importance of coping skills as a partial mediator of the effectiveness of an internet-version of the CRA combined with contingency management.

NIDA Clinical Trials Network CTN-0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT): Study design and rationale.[Pubmed:27521809]

Contemp Clin Trials. 2016 Sep;50:253-64.

INTRODUCTION: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. METHODS: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. RESULTS: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. CONCLUSIONS: XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. CLINICAL TRIAL REGISTRATION: NCT02032433.

Analogs of SR-141716A (Rimonabant) alter d-amphetamine-evoked [3H] dopamine overflow from preloaded striatal slices and amphetamine-induced hyperactivity.[Pubmed:17532007]

Life Sci. 2007 Jun 13;81(1):63-71.

The CB(1) cannabinoid receptor antagonist SR-141716A (Rimonabant) markedly diminishes the behavioral effects of opiates and nicotine and has been an important tool to ascertain the role of cannabinoid receptors in drug addiction. The present goal was to determine the less-explored interaction of SR-141716A and d-amphetamine in neurochemical and behavioral assays. Additionally, the effect of the substituents and substitution patterns on the phenyl ring located at the 5 position of SR-141716A (4-chlorophenyl), and of the CB(1)/CB(2) cannabinoid receptor agonist WIN-55,212-2, was determined. SR-141716A, AM-251 (4-iodophenyl) and NIDA-41020 (4-methoxyphenyl) did not alter amphetamine-evoked [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine. MRI-8273-30-1 (4-fluorophenyl; 0.1-10 microM) attenuated amphetamine (3 microM)-evoked [(3)H]overflow, and MRI-8273-59 (3,4-dichlorphenyl; 0.01-10 microM) augmented amphetamine (0.3-3 microM)-evoked [(3)H]overflow. WIN-55,212-2 was without effect. In a locomotor activity experiment, SR-141716A and MRI-8273-30-1 did not alter amphetamine-induced hyperactivity. However, MRI-8273-59 (1-3 mg/kg) dose-dependently attenuated amphetamine (1 mg/kg)-induced hyperactivity. The present results suggest that SR-141716A is less efficacious to alter amphetamine effects than its reported efficacy to diminish the effects of opiates and nicotine. Modification of the 5-phenyl position of SR-141716A affords compounds that do interact with amphetamine in vitro and in vivo.

Synthesis, structure-activity relationship, and evaluation of SR141716 analogues: development of central cannabinoid receptor ligands with lower lipophilicity.[Pubmed:12570386]

J Med Chem. 2003 Feb 13;46(4):642-5.

Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.