Geographic and Racial/Ethnic Differences in Access to Methamphetamine Detoxification Services, United States, 2021.

INTRODUCTION: Methamphetamine detoxification before entering formal and longer term treatment may have a positive impact on treatment retention and success. Understanding geographic distribution of methamphetamine specialty detox services and differential access by race/ethnicity is critical for establishing policies that ensure equitable access across populations. METHODS: We used the Mental health and Addiction Treatment Tracking Repository to identify treatment facilities that offered any substance use detoxification in 2021 (N=2346) as well as the census block group in which they were located. We sourced data from the US Census Bureau to identify the percentage of a census block group that was White, Black, and Hispanic. We used logistic regression to model the availability of methamphetamine-specific detox, predicted by the percentage of a block group that was Black and Hispanic. We adjusted for relevant covariates and defined state as a random effect. We calculated model-based predicted probabilities. RESULTS: Over half (60%) of detox facilities offered additional detox services specifically for methamphetamine. Sixteen states had <10 methamphetamine-specific detox facilities. The predicted probability of methamphetamine-specific detox availability was 60% in census block groups with 0%-9% Black residents versus only 46% in census block groups with 90%-100% Black residents, and was 61% in census block groups with 0%-9% Hispanic residents versus 30% in census block groups with 90%-100% Hispanic residents. CONCLUSIONS: During an unprecedented national methamphetamine crisis, access to a critical health care service was disproportionately lower in communities that were predominately Black and Hispanic. We orient our findings around a discussion of health disparities, residential segregation, and the upstream causes of the systematic exclusion of minoritized communities from health care.

Impact of state and trait anxiety severity on retention and phase advancement in an outpatient buprenorphine treatment program.

BACKGROUND AND OBJECTIVES: Comorbid anxiety is common among buprenorphine patients and may lead to poorer outcomes. This study aimed to examine the prevalence and impact of anxiety severity, measured by the State-Trait Anxiety Inventory (STAI) form Y-1 & Y2 scale, on treatment outcomes (retention and phase advancement) among outpatient buprenorphine-treated patients. METHODS: A retrospective chart review of 94 patients admitted to an outpatient buprenorphine treatment program was conducted. Patients were dichotomized into high and low severity groups based upon an STAI State Anxiety (S-Anxiety) and STAI Trait Anxiety (T-Anxiety) score ≥60 and <60, respectively. Associations of anxiety severity on successful phase advancement and retention during the first 90 days of treatment were assessed. RESULTS: Twenty-one of 94 (22%) participants reported high S-Anxiety and had a significantly greater likelihood of phase advancement (OR = 12.80, 95% CI = [1.19, 136.71]) than those with low S-Anxiety. No significant associations were found between either S-Anxiety or T-Anxiety and treatment retention. Current alcohol use and UDS negative test results for THC or amphetamines were each associated with phase advancement. THC negative UDS test results were associated with 90-day treatment retention. DISCUSSION AND CONCLUSIONS: Contrary to prior reports, buprenorphine patients with higher state anxiety severity demonstrated similar retention and more rapid phase advancement than those with lower state anxiety severity. SCIENTIFIC SIGNIFICANCE: To our knowledge, this is the first study to quantify current anxiety severity using the STAI scale and evaluate its impact on treatment outcomes among buprenorphine-treated patients.

Development and validation of a rapid liquid chromatography/tandem mass spectrometry method to quantitate gabapentin and buprenorphine in human serum.

RATIONALE: Gabapentin has shown initial promise as an opioid-sparing medication in pain patients as well as a treatment for opioid withdrawal and liquid chriomatography/tandem mass spectrometry (LC/MS/MS) is often used for clinical monitoring. Despite reports of validated tandem mass spectrometric methods for the determination of gabapentin and buprenorphine, mechanisms for the collision-induced fragmentation have not been adequetely described. METHODS: A rapid analytical method has been developed to determine gabapentinoid, gabapentin, and the partial opioid agonist, buprenorphine, in 20 µL of human serum using LC/MS/MS with a chromatographic run time of 2 min. A simplified sample cleanup procedure using methanol precipitation of serum proteins/lipids followed by evaporation and reconstitution in mobile phase was demonstrated. Gabapentin and buprenorphine were detected following positive ion electrospray ionization using multiple-reaction monitoring. The internal standard approach was used for quantitation with labeled gabapentin-D10 and buprenorphine-D4 serving as internal standards. Using organic reaction principals and stable isotope labels, collision-induced fragmentation mechanisms for both gabapentin and buprenorphine are proposed. The method was validated according to the FDA Guidance for Industry - Bioanalytical Method Validation. RESULTS: Accuracy was demonstrated by error values ≤15% for buprenorphine and ≤6% for gabapentin. The inter-day precision was ≤4.88% and 15.59% for gabapentin and buprenorphine and the intra-day precision was ≤5.20% and 11.65% for gabapentin and buprenorphine. The lower limit of quantitation corresponded to 10 ng/mL for gabapentin and 1 ng/mL for buprenorphine in serum. Recoveries were 104 ± 2.55% and 85 ± 2.03% for gabapentin and buprenorphine, respectively. CONCLUSIONS: Concentrations of gabapentin and buprenorphine were determined for five authentic human serum samples to further validate the utility of the method and applicable to therapeutic drug monitoring beyond its use as a drug screening assay. Furthermore, new mechanisms for the collision-induced dissociation of gabapentin and buprenorphine have been proposed.

Clearance of buprenorphine during pregnancy and neonatal outcomes.

Buprenorphine is emerging as the preferred pharmacologic treatment for opioid use disorder during pregnancy. We examined the relative plasma clearance of buprenorphine (BUP) across pregnancy. Pregnant women with opioid use disorder participating in a prospective, observational study from 2013 to 2016 on stress in pregnancy who were receiving BUP for opioid use disorder were included. Women with an active eating disorder or suicidal ideation were excluded. Research visits occurred at 4-6-week intervals across pregnancy and the early postpartum period and included medication exposure history and blood samples. All assays for BUP serum concentrations at steady state were completed. Relative weight-adjusted clearance (Cl) was calculated using Cl = (daily dose [mg]/ body weight [kg])/serum concentration [ng/ml]. We collected 112 maternal blood samples from 29 women throughout pregnancy and the postpartum period. Serum concentrations for BUP ranged from < 0.2 to 15.8 ng/ml. Eleven women, with greater than three collected samples, increased their daily dose of BUP during pregnancy; however, there were no significant differences in relative clearance of BUP across this same period. This data suggests that women with opioid use disorder receiving BUP did not demonstrate a significant increase in BUP clearance across pregnancy despite increase in dosages during pregnancy. When selecting an appropriate BUP dosage for management of perinatal opioid use disorder, gestational stage appears not to be an important covariate and should be based on an individualized approach.

The utility of a statewide prescription drug-monitoring database vs the Current Opioid Misuse Measure for identifying drug-aberrant behaviors in emergency department patients already on opioids.

BACKGROUND: The most recent guidelines on prescribing opioids from the United States Centers for Disease Control recommend that clinicians not prescribe opioids as first-line therapy for chronic non-cancer pain. If an opioid prescription is considered for a patient already on opioids, prescribers are encouraged to check the statewide prescription drug monitoring database (PDMP). Some additional guidelines recommend screening tools such as the Current Opioid Misuse Measure (COMM) which may also help identify drug-aberrant behaviors. OBJECTIVE: To compare the PDMP and the Current Opioid Misuse Measure (COMM), a commonly-recommended screening tool for patients on opioids, in detecting drug-aberrant behaviors in patients already taking opioids at the time of ED presentation. METHODS: Patients on opioids were enrolled prospectively in a mixed urban-suburban ED seeing approximately 65,000 patients per year. The sensitivity, specificity, likelihood ratios, and diagnostic odds ratios of the PDMP and COMM were compared against objective criteria of drug-aberrant behaviors as documented in the electronic medical record (EMR) and medical examiner databases. RESULTS: Compared to the COMM, the PDMP had similar sensitivity (36% vs 45%) and similar specificity (79% vs 55%), but better positive predictive value, better negative predictive value, and better diagnostic odds ratio. The combination of the PDMP and the COMM did not improve the detection of drug-aberrant behaviors. CONCLUSIONS: The PDMP alone is a more useful as a screening instrument than either the COMM or the combination of the PDMP plus COMM in patients already taking opioids at time of ED presentation. However, the PDMP misses a majority of patients with documented drug-aberrant behaviors in the EMR, and should not be used in isolation to justify whether a particular opioid prescription is appropriate.

Moderators of response to sertraline versus placebo among recently abstinent, cocaine dependent patients: A retrospective analysis of two clinical trials.

BACKGROUND AND OBJECTIVES: Moderators of treatment response to serotonin reuptake inhibitor sertraline (SRT) for cocaine dependence were assessed in two randomized, double blind, placebo-controlled clinical trials. METHODS: Generalized estimating equation modeling was performed on data from cocaine-dependent volunteers randomized to receive SRT or placebo (N = 126) who completed >2-week drug-free residential portions of the 12-week trials, in which subsequent outpatient treatment (weeks 3-12) included weekly cognitive behavioral therapy and thrice-weekly supervised urine toxicology. PRIMARY OUTCOME MEASURE: Relapse (2 consecutive cocaine-positive or missing urines) following residential stay. Potential moderators included treatment, sex, age, race, depression measures, baseline cocaine urine result, and alcohol dependence diagnosis (ADDx). RESULTS: Odds ratios (OR) for relapse showed placebo-treated participants were significantly more likely to relapse than SRT participants. Regardless of treatment condition, participants more likely to relapse were male, and those with lower Hamilton depression ratings, or baseline cocaine-negative urines. Older subjects or those with current ADDx had higher relapse risk than those without ADDx; however, treating older or ADDx participants with SRT reduced cocaine relapse more than placebo. DISCUSSION AND CONCLUSIONS: Women or those with more severe cocaine use or depressive symptoms may have fewer cocaine relapses regardless of medication treatment. SRT at 200 mg reduced cocaine relapse more than placebo, especially in older participants or in those with comorbid ADDx. SCIENTIFIC SIGNIFICANCE: SRT may be efficacious to support relapse prevention among cocaine-dependent patients in the context of brief residential followed by outpatient treatment, especially in older participants or those with comorbid alcohol/cocaine dependence. (Am J Addict 2017;26:807-814).

Impact of early childhood trauma on retention and phase advancement in an outpatient buprenorphine treatment program.

BACKGROUND: Early adverse life events such as childhood trauma have been linked to development of substance use disorders. The prevalence and impact on treatment of early childhood trauma in opioid-dependent individuals has received limited research attention. The present study examined reported childhood trauma and its relation to retention and adherence in an outpatient buprenorphine treatment program. METHODS: Medical records of individuals who completed childhood trauma questionnaire (CTQ) were reviewed to extract baseline data and demographics (N = 113). Total and subscale CTQ scores were dichotomized to low versus moderate-severe levels of trauma. Treatment course evaluation was based on successful phase advancement and retention in treatment during the first 90 days. Logistic regression models were used to examine associations between CTQ subscales and total score and the two outcomes adjusting for covariates. RESULTS: Moderate-severe trauma defined by total CTQ score was present in 16% of participants. Logistic regression models showed significant associations between physical and emotional neglect and drop out after adjusting for covariates. Individuals who had never married and those with positive admission urine drug screen for opiates associated significantly with drop out. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The results from a convenience sample participating in a university-based buprenorphine treatment program demonstrated significant association between self-reported early childhood trauma and retention during the first 90 days. These findings suggest that addressing early trauma could potentially improve adherence rates leading to reduced disease burden. This study extends the knowledge base on potential predictive factors associated with successful participation in outpatient buprenorphine treatment. (Am J Addict 2016;25:542-548).

Clinical efficacy of sertraline alone and augmented with gabapentin in recently abstinent cocaine-dependent patients with depressive symptoms.

BACKGROUND: Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study's aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. METHODS: Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3-12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. RESULTS: Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. CONCLUSIONS: Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy.

Sadness, suicide, and drug misuse in Arkansas: results from the Youth Risk Behavior Survey 2011.

Exposure to drugs is unfortunately common among high school students and its use has been linked to depression and suicide risk. We used the 2011 Arkansas Youth Risk Behavior Survey to estimate the prevalence of drug abuse and to measure its association with teen suicidality. Three types of substance misuse were reported by more than 10% of Arkansas high school students: cannabis (33.3% ever use). inhalants (18.7% ever use). and prescription drugs without a prescription (13.2% ever use). We found in all suicide outcomes a stronger association with prescription drug abuse, followed by inhalant abuse, then cannabis abuse.

Characteristics of patients undergoing medication-assisted -treatment for opioid use disorder and their interest in Tai Chi practice.

OBJECTIVES: (1) To explore the characteristics of patients with opioid use disorder (OUD) maintained on either methadone or buprenorphine and (2) to determine the relative acceptability of integrating Tai Chi (TC) practice into an ongoing medication-assisted treatment for opioid use disorder (MOUD) program. DESIGN: Survey study. SETTING: The University of Arkansas for Medical Sciences Center for Addiction Services and Treatment Program. PATIENTS: 97 patients receiving MOUD treatment. MAIN OUTCOMES: Drug use history, treatment status, physical limitation, mental health, pain, and whether participants were interested in using TC to improve health outcomes. RESULTS: At least 30.9 percent of the sample reported moderate or higher level of limitation in performing rigorous physical activities, pain intensity, and pain interference. Between 37.1 and 61.5 percent of the sample reported various psychiatric symptoms. Methadone patients reported higher levels of physical limitations, especially in rigorous activities (p = .012), climbing several flights of stairs (p = .001), and walking more than a mile (p = .011), but similar levels of pain (ps = .664-.689) and psychiatric symptoms (ps = .262-.879) relative to buprenorphine patients. At least 40.2 percent of participants expressed moderate or higher level of interest in TC for improving health outcomes, with methadone patients more interested in participating to ease mental and sleep problems (p = .005) and improve physical fitness (p = .015) compared to buprenorphine patients. CONCLUSIONS: High prevalence of physical limitation, pain, and psychiatric comorbidities were found in OUD patients. Since patients were interested in TC to improve their health outcomes, this low-cost intervention, if proven effective, can be integrated into ongoing MOUD programs to improve health in this population.

Smartphone intervention to optimize medication assisted treatment outcomes for opioid use disorder: study protocol for a randomized controlled trial.

Background: Opioids accounted for 75% of drug overdoses in the United States in 2020, with rural states particularly impacted by the opioid crisis. While medication assisted treatment (MAT) with Suboxone remains one of the more efficacious treatments for opioid use disorder (OUD), approximately 40% of people receiving Suboxone for outpatient MAT for OUD (MOUD) relapse within the first 6 months of treatment. We developed the smartphone app-based intervention OptiMAT as an adjunctive intervention to improve MOUD outcomes. The aims of this study are to (1) evaluate the efficacy of adjunctive OptiMAT use in reducing opioid misuse among people receiving MOUD; and (2) evaluate the role of specific OpitMAT features in reducing opioid misuse, including the use of GPS-driven just-in-time intervention. Methods: We will conduct a two-arm, single-blind, randomized controlled trial of adults receiving outpatient MOUD in the greater Little Rock AR area. Participants are English-speaking adults ages 18 or older recently enrolled in outpatient MOUD at one of our participating study clinics. Participants will be allocated via 1:1 randomized block design to (1) MOUD with adjunctive use of OptiMAT (MOUD+OptiMAT) or (2) MOUD without OptiMAT (MOUD-only). Our blinded research statistician will evaluate differences between the two groups in opioid misuse (as determined by quantitative urinalysis conducted by clinical lab staff blinded to group membership) during the 6-months following study enrolment. Secondary analyses will evaluate if OptiMAT-usage patterns within the MOUD+OptiMAT group predict opioid misuse or continued abstinence. Discussion: This study will test if adjunctive use of OptiMAT improve MOUD outcomes. Study findings could lead to expansion of OptiMAT into rural clinical settings, and the identification of OptiMAT features which best predict positive clinical outcome could lead to refinement of this and similar smartphone appbased interventions. Trial registration: ClinicalTrials.gov identifier: NCT05336188, registered March 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05336188.

Smartphone intervention to optimize medication-assisted treatment outcomes for opioid use disorder: study protocol for a randomized controlled trial.

BACKGROUND: Opioids accounted for 75% of drug overdoses in the USA in 2020, with rural states particularly impacted by the opioid crisis. While medication-assisted treatment (MAT) with Suboxone remains one of the more efficacious treatments for opioid use disorder (OUD), approximately 40% of people receiving Suboxone for outpatient MAT for OUD (MOUD) relapse within the first 6 months of treatment. We developed the smartphone app-based intervention OptiMAT as an adjunctive intervention to improve MOUD outcomes. The aims of this study are to (1) evaluate the efficacy of adjunctive OptiMAT use in reducing opioid misuse among people receiving MOUD and (2) evaluate the role of specific OptiMAT features in reducing opioid misuse, including the use of GPS-driven just-in-time intervention. METHODS: We will conduct a two-arm, single-blind, randomized controlled trial of adults receiving outpatient MOUD in the greater Little Rock AR area. Participants are English-speaking adults ages 18 or older recently enrolled in outpatient MOUD at one of our participating study clinics. Participants will be allocated via 1:1 randomized block design to (1) MOUD with adjunctive use of OptiMAT (MOUD+OptiMAT) or (2) MOUD without OptiMAT (MOUD-only). Our blinded research statistician will evaluate differences between the two groups in opioid misuse (as determined by quantitative urinalysis conducted by clinical lab staff blinded to group membership) during the 6-months following study enrolment. Secondary analyses will evaluate if OptiMAT-usage patterns within the MOUD+OptiMAT group predict opioid misuse or continued abstinence. DISCUSSION: This study will test if adjunctive use of OptiMAT improve MOUD outcomes. Study findings could lead to expansion of OptiMAT into rural clinical settings, and the identification of OptiMAT features which best predict positive clinical outcome could lead to refinement of this and similar smartphone app-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05336188 , registered March 21, 2022.

Characterizing methamphetamine withdrawal in recently abstinent methamphetamine users: a pilot field study.

BACKGROUND: Methamphetamine dependence has become a significant problem, but methamphetamine withdrawal symptoms have not been well studied. METHODS: This prospective observational pilot study was designed to examine withdrawal symptoms, mood, anxiety, cognitive function, and subjective measures of sleep over a 4-week period in six patients entering residential treatment for methamphetamine dependence. RESULTS: Methamphetamine withdrawal symptoms, mood, and anxiety symptoms all resolve fairly quickly within 2 weeks of cessation of methamphetamine. Sleep was disrupted over the course of the 4-week study. No clinically significant alterations in blood pressure or heart rate were identified. This study did not demonstrate any alterations in cognitive function over the 4 weeks of the residential stay. CONCLUSIONS: This pilot study points toward the need for a double-blind, placebo-controlled amphetamine withdrawal paradigm in humans where changes in sleep, cognitive function, and withdrawal measures can be explored more fully. SCIENTIFIC SIGNIFICANCE: This study extends the literature by pointing toward a methamphetamine withdrawal syndrome that includes alterations in measures of sleep quality and refreshed sleep, early improvement in depression and anxiety symptoms, most striking during the first week, but persisting into the second week.

Utility of a controlled amphetamine withdrawal paradigm among adults who use methamphetamine: A pilot clinical trial.

BACKGROUND: The continued increase in prevalence of methamphetamine use in the United States has resulted in a significant increase in the number of patients entering treatment for methamphetamine use. However, no robustly efficacious pharmacologic treatment for methamphetamine use or withdrawal has been identified to date after stopping methamphetamine use. AIMS: Given the association between methamphetamine withdrawal and relapse during early treatment, this study tested a controlled d-amphetamine withdrawal paradigm among methamphetamine-using individuals. METHODS: Treatment-seeking adults who used methamphetamine (N = 34; 47% female; 100% white) were enrolled in a 4-week, randomized, double-blind, placebo-controlled trial in a residential setting, in which all participants were maintained on d-amphetamine (30 mg BID) during week 1, then half were switched to placebo during weeks 2-3. All participants received placebo during week 4. Outcomes included vital signs, withdrawal, cravings for methamphetamine, mood, and cognition. Bivariate analyses tested treatment group differences on baseline demographic and outcome variables. Repeated measures models examined main and interaction effects of treatment over time. RESULTS/OUTCOMES: Participants were successfully randomized and safely stabilized on d-amphetamine. Craving for methamphetamine increased during weeks 2-3 in the placebo group relative to those on d-amphetamine. Interactions with age and heart rate were noted. CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first double-blind, placebo-controlled trial measuring pharmacologic effects of abruptly stopping controlled d-amphetamine administration in adults who use methamphetamine. Results support the potential of this withdrawal paradigm to further examine the efficacy of pharmacologic agents in ameliorating methamphetamine withdrawal symptoms.

Effect of PTSD diagnosis and contingency management procedures on cocaine use in dually cocaine- and opioid-dependent individuals maintained on LAAM: a retrospective analysis.

This randomized clinical trial retrospectively examined the effect of post-traumatic stress disorder (PTSD) and contingency management (CM) on cocaine use in opioid and cocaine dependent individuals maintained on high or low-dose LAAM randomly assigned to CM or a yoked-control condition. Cocaine-positive urines decreased more rapidly over time in those without PTSD versus those with PTSD in the noncontingency condition. In participants with PTSD, CM resulted in fewer cocaine-positive urines compared to the noncontingent condition. This suggests that CM may help improve the potentially worse outcomes in opioid- and cocaine-dependent individuals with PTSD compared to those without PTSD. (Am J Addict 2010;00:1-9).

Predictors of attrition from a national sample of methadone maintenance patients.

BACKGROUND: Methadone substitution therapy is an effective harm reduction treatment method for opioid dependent persons. Ability to retain patients in methadone treatment is an accepted predictor of treatment outcomes. OBJECTIVES: The current study evaluates the roles of psychiatric comorbidity, medical comorbidity, and sociodemographic characteristics as predictors of retention in methadone treatment utilizing retrospective analysis of data from a nationwide sample of patients in methadone treatment in the VA. METHODS: Data were gathered using the VA's national health services use database. A cohort of veterans with a new episode of "opiate substitution" in fiscal year 1999 was identified, and their continuous service use was tracked through fiscal year 2002. The sample included a total of 2,363 patients in 23 VA medical centers. Survival analysis was used to explore factors associated with retention in methadone treatment. RESULTS: Younger age, having a serious mental illness, being African American, or having race recorded as unknown were associated with lower rates of retention in methadone treatment programs in this population of veterans (controlling for site). CONCLUSION: Given that extended methadone treatment is associated with improved outcomes while patients remain in treatment, more longitudinal studies using primary data collection are needed to fully explore factors related to retention. For the VA population specifically, further research is necessary to fully understand the relationship between race/ethnicity and treatment retention. SCIENTIFIC SIGNIFICANCE: This is the first retention study the authors are aware of that utilizes data from a nationwide, multisite, population of participants in methadone treatment.

Feasibility and Preliminary Efficacy of Isradipine During Outpatient Buprenorphine Stabilization and Detoxification: A Pilot Randomized, Placebo-Controlled Trial.

BACKGROUND: Given the immense burden of the widespread use of opioids around the world, exploring treatments that improve drug use outcomes, and craving and withdrawal measures in individuals with opioid use disorder is crucial. This pilot study examined the feasibility and preliminary efficacy of the L-type calcium-channel blocker isradipine (ISR) to improve drug use outcomes, and craving and withdrawal measures during buprenorphine (BUP)/ISR stabilization and subsequent taper in opioid-dependent individuals. METHODS: Participants were stabilized on BUP sublingual tablets within the first 2 days of week 1, were then randomized and inducted on either ISR or placebo, gradually increasing the dose over the next 2 weeks, followed by a 10-day BUP taper during weeks 5-6, and ISR/placebo taper during weeks 7 to 8. Assessments included thrice-weekly measures of craving and withdrawal, as well as vital signs and urine drug screens. Medication compliance was assessed by monitoring number of missed clinic visit days. RESULTS: Baseline characteristics of participants (n = 25; 60% male, 96% Caucasian, 48% employed, mean age 32.8 years) did not differ significantly between treatment groups (isradipine, n = 11; placebo, n = 14). During the stabilization phase (n = 19), ISR participants had significantly lower rates of illicit opioid-positive urines (treatment × visit: t = -2.16, P = 0.03), as well as reduction in craving intensity (t = -2.50, P = 0.01), frequency (t = -3.43, P < 0.01) and duration (t = -2.51, P = 0.01). ISR was well tolerated with mild adverse effects. CONCLUSIONS: This study was likely underpowered due to being a pilot trial. Although preliminary results suggest ISR may improve BUP-assisted treatment outcomes, concerns about high number of exclusions (n = 11 during taper phase) based on cardiovascular measures as well as ISR-induced changes in vital signs with the immediate release formulation may limit the feasibility of this approach. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01895270. Registered 10 July 2013, https://clinicaltrials.gov/ct2/show/NCT01895270?id=NCT01895270&draw=2&rank=1.

Open-label pilot study of modafinil for methamphetamine dependence.

Methamphetamine has become a major public health issue globally, particularly in the United States. Despite this, no effective pharmacotherapy for methamphetamine abuse has been developed to date. This 6-week, open-label pilot clinical trial examined the safety and tolerability of modafinil up to 400 mg/d in 8 methamphetamine-dependent individuals. Subjects were inducted onto modafinil at 400 mg/d for more than 3 days and remained on 400 mg/d for 4.5 weeks. Participants received weekly blister packs and underwent weekly individual cognitive behavioral therapy. Adjunctive contingency management procedures were used to enhance retention. Vital signs and supervised urine samples were obtained thrice weekly, and self-reported drug use and Hamilton anxiety and depression ratings were completed once weekly. Eight subjects (50% female, 100% white, aged 35-52 years) were enrolled. Four completed the 6-week study, 3 completed a portion, and 1 withdrew consent before completing intake. Results showed that systolic blood pressure (t = 1.09, P = 0.28), diastolic blood pressure, (t = 1.18, P = 0.24), and heart rate (t = 1.55, P = 0.13) did not change over time. Scores on the modafinil side effects checklist (t = -2.63, P = 0.01), Hamilton anxiety scale (t = -2.50, P = 0.018), and Hamilton depression scale (t = -3.25, P = 0.003) all decreased over time. The proportion of urine positive for amphetamines did not change over time (t = -0.52, P = 0.61), whereas self-reported methamphetamine use did (t = -2.86, P < 0.005). These results suggest that modafinil at 400 mg/d is safe and tolerable for methamphetamine-dependent individuals.

Sex and opioid maintenance dose influence response to naloxone in opioid-dependent humans: a retrospective analysis.

Pooled self-report and physiological data from 32 male and 15 female methadone or levo-alpha-acetyl methadol (LAAM) maintained volunteers were retrospectively analyzed for individual differences in response to naloxone (0.15 mg/70 kg, IM) and placebo at 20 and 40 min post-injection. Males and females were each divided by the median splitmethadone maintenance dose (MMD, in mg/kg body weight) into high and low MMD groups and MMD was used as a factor in the analyses, along with sex, drug, and time post-drug. Females in the low but not high, MMD group showed naloxone-induced increases in ratings on the Antagonist and Mixed-Action sub-scales of the Adjective Rating Scale, and the Lysergic acid diethyl amine (LSD) sub-scale of the Addiction Research Center Inventory at 20 min post-injection. Males in the high MMD group showed significant naloxone-induced increases in scores of these measures at both post-injection time-points. In addition, low MMD subjects showed more short-lived naloxone-induced increases on Visual Analogue Scale (VAS) Bad and Any drug effects ratings than high MMD subjects. These results suggest that those on a lower MMD, especially women, experience a more intense, but short-lived, response to naloxone, whereas those on a higher MMD experience a more modest, but longer-lasting effect.

Survey of Treatment Preferences for Opioid Use Disorder.

OBJECTIVES: This study gathered preliminary information on the initial feasibility of using injection Naltrexone (NTX) therapy in opioid users. METHODS: One hundred opioid users (36% female, 8% minorities, mean age 34.5±11.4 yrs.) undergoing a health screen to determine initial eligibility for an ongoing study completed the survey. RESULTS: Of the 100 respondents, 26, 16, 16, 1 and 0 reported prior treatment episodes of opioid detoxification, buprenorphine (BUP), methadone (MTD), oral NTX and injection NTX, respectively. Ninety and 71% were interested in participating in a study involving oral and/or injection NTX treatment, respectively. Reasons for not wanting to try injection NTX included fear of needles (n=13), side effects (n=7), lack of pain relief (n=12) and cost (n=3). A significantly higher percentage of those interested in injection NTX had episodes of prior opioid agonist maintenance treatment relative to those uninterested (32.4% vs 10.3%; Chi2=5.2, p<0.03). Those preferring injection NTX therapy showed a higher level of interest in this therapy (3.08±1.01 vs 1.62±1.35; Rank Sum p<0.0001) and a lower degree of interest in BUP treatment (2.96±0.93 vs 3.38±0.90; Rank Sum p< 0.03) than those not preferring injection NTX. CONCLUSIONS: These preliminary results suggest that those with prior, failed experience with opioid agonist maintenance treatment are more likely to consider injection NTX therapy, suggesting it may be optimal as a second-line treatment for OUD.