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The Stimulant Selective Severity Assessment: A replication and exploratory extension of the Cocaine Selective Severity Assessment.

ABSTRACT: BACKGROUND:Cocaine and methamphetamine have similar withdrawal symptoms and many individuals concurrently use both substances; however, no measures concurrently assess withdrawal from multiple stimulants. OBJECTIVES:This study's aim was to explore the Stimulant Selective Severity Assessment (SSSA), a modified version of the Cocaine Selective Severity Assessment (CSSA), in a sample of stimulant users to determine if it can assess withdrawal symptoms in users of one or more stimulants. METHODS:Baseline data were analyzed from the STimulant Reduction Intervention using Dosed Exercise trial, a multisite randomized clinical trial that evaluated exercise versus health education on drug use outcomes in individuals with stimulant use disorders. Data were analyzed for internal consistency, construct validity, and scale dimensionality. RESULTS:Internal consistency for the full sample was good (??=?0.81; N?=?302), with similar alphas in Cocaine (0.81; n?=?177) and Cocaine/Other Stimulant (0.82; n?=?92) groups, but with much lower alpha for the group without cocaine use (Other Stimulant, i.e., primarily methamphetamine, ??=?0.66; n?=?32). Support for construct validity was evidenced by significant positive correlations (r?=?0.17 to 0.67) with measures of stimulant craving, depressive symptoms, and pain. Four factors were revealed. Conclusions/Importance: The Stimulant Selective Severity Assessment is a new measure that can be used to assess withdrawal symptoms in users of cocaine or cocaine plus methamphetamine, but it should not be administered to users of methamphetamine only.

SUBMITTER: Walker R

PROVIDER: S-EPMC6438747 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Stimulant Selective Severity Assessment: A replication and exploratory extension of the Cocaine Selective Severity Assessment.

Walker Robrina R Northrup Thomas F TF Tillitski John J Bernstein Ira I Greer Tracy L TL Trivedi Madhukar H MH

Substance use & misuse 20190118 3

<h4>Background</h4>Cocaine and methamphetamine have similar withdrawal symptoms and many individuals concurrently use both substances; however, no measures concurrently assess withdrawal from multiple stimulants.<h4>Objectives</h4>This study's aim was to explore the Stimulant Selective Severity Assessment (SSSA), a modified version of the Cocaine Selective Severity Assessment (CSSA), in a sample of stimulant users to determine if it can assess withdrawal symptoms in users of one or more stimulan ...[more]

PMID: 30657406

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Project description:ImportanceUse of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of cardiovascular (CV) events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk.ObjectiveTo evaluate the association between stimulant use and risk of CV events among older adults.Design, setting, and participantsThis propensity score-matched cohort study, with 4 nonusers per 1 user, was conducted from July 1, 2017, to June 27, 2019, using data from population-based health care databases from Ontario, Canada, from January 1, 2002, to December 31, 2016. Included individuals were outpatients aged 66 years or older.ExposuresInitiation of a prescription stimulant.Main outcomes and measuresThe primary outcome was a CV event, defined as a composite of emergency department visit or hospitalization for myocardial infarction, stroke or transient ischemic attack (TIA), or ventricular arrhythmia. Risk of CV event was assessed at 30 days, 180 days, and 365 days after initiation of stimulants from Cox proportional hazard models. A secondary analysis assessed each component of the primary outcome separately.ResultsAmong 6457 older adults who initiated a prescription stimulant (ie, the exposed group) and 24 853 older adults who did not initiate such treatment (ie, the unexposed group), the distribution of baseline patient characteristics was well balanced after matching (sex: 3173 [49.1%] men vs 12 112 [48.7%] men; standardized difference, 0.01; median [IQR] age: 74 [69-80] years vs 74 [69-80] years; standardized difference, 0.01). Within this cohort, there were 932 CV events during the 365-day follow-up (5.11 events per 100 person-years among individuals who initiated stimulants). In the primary analysis, stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or TIA (HR, 1.6; 95% CI, 1.1-2.1) at 30 days.Conclusions and relevanceThis cohort study found that stimulant use was associated with an early increase in CV events among older adults with no association for long-term use.

Project description:Modafinil is a mild psychostimulant with pro-cognitive and antidepressant effects. Unlike many conventional stimulants, modafinil has little appreciable potential for abuse, making it a promising therapeutic agent for cocaine addiction. The chief molecular target of modafinil is the dopamine transporter (DAT); however, the mechanistic details underlying modafinil's unique effects remain unknown. Recent studies suggest that the conformational effects of a given DAT ligand influence the magnitude of the ligand's reinforcing properties. For example, the atypical DAT inhibitors benztropine and GBR12909 do not share cocaine's notorious addictive liability, despite having greater binding affinity. Here, we show that the binding mechanism of modafinil is different than cocaine and similar to other atypical inhibitors. We previously established two mutations (W84L and D313N) that increase the likelihood that the DAT will adopt an outward-facing conformational state--these mutations increase the affinity of cocaine-like inhibitors considerably, but have little or opposite effect on atypical inhibitor binding. Thus, a compound's WT/mutant affinity ratio can indicate whether the compound preferentially interacts with a more outward- or inward-facing conformational state. Modafinil displayed affinity ratios similar to those of benztropine, GBR12909 and bupropion (which lack cocaine-like effects in humans), but far different than those of cocaine, ?-CFT or methylphenidate. Whereas treatment with zinc (known to stabilize an outward-facing transporter state) increased the affinity of cocaine and methylphenidate two-fold, it had little or no effect on the binding of modafinil, benztropine, bupropion or GBR12909. Additionally, computational modeling of inhibitor binding indicated that while ?-CFT and methylphenidate stabilize an "open-to-out" conformation, binding of either modafinil or bupropion gives rise to a more closed conformation. Our findings highlight a mechanistic difference between modafinil and cocaine-like stimulants and further demonstrate that the conformational effects of a given DAT inhibitor influence its phenomenological effects.

Dataset Information

The Stimulant Selective Severity Assessment: A replication and exploratory extension of the Cocaine Selective Severity Assessment.

Publications

The Stimulant Selective Severity Assessment: A replication and exploratory extension of the Cocaine Selective Severity Assessment.

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