buprenorphine--naloxone-drug-combination and Cocaine-Related-Disorders

The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP).. Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines.. In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response.. These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine; Cocaine-Related Disorders; Delayed-Action Preparations; Enkephalins; Humans; Injections, Intramuscular; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Protein Precursors

To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.. This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events.. No group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events.. Buprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

Topics: Administration, Oral; Adult; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Treatment Outcome

Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study.. This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates.. This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP.

Topics: Administration, Sublingual; Adolescent; Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome; Young Adult

Despite rising morbidity and mortality from the opioid epidemic and other addictions, people who inject drugs (PWID) remain understudied regarding pain outcomes. Data among PWID regarding chronic pain and drug use, including non-medical use of opioids, is largely unknown. We examined the prevalence of chronic pain and drug use for pain in this population.. Standardized surveys captured self-report of demographics, chronic pain, and non-prescription drug use in 203 PWID in an urban syringe services program between April and November 2016. Chronic pain was defined as self-report of chronic pain diagnosis or persistent pains over the past 6 months.. Overall, 47% (95% CI, 40%-54%) of PWID reported chronic pain, while 35% (95% CI, 29%-42%) reported non-prescription drug use of any type for pain. Among those with chronic pain, drug use to treat pain was commonly reported (76%; 95% CI, 66%-83%). Non-medical opioid use did not differ among PWID with or without chronic pain or drug use for pain. A multivariable logistic regression model showed chronic pain was more likely among non-Hispanic whites and those with arthritis, older age, and homelessness.. Chronic pain serves as an important factor in the persistence of drug use in more than one-third of PWID in this sample. The high prevalence of chronic pain with drug use for pain suggests that proper pain management is likely to be an essential component of preventing or regressing injection drug use in PWID, with data needed on effective interventions for this population.

Topics: Adolescent; Adult; Age Factors; Analgesics, Opioid; Arthritis; Baltimore; Black or African American; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Ill-Housed Persons; Male; Middle Aged; Needle-Exchange Programs; Odds Ratio; Opioid-Related Disorders; Prevalence; Risk Factors; Substance Abuse, Intravenous; White People; Young Adult

Urine adulteration is a concern among patients treated for opioid use disorder. Quantitative urine testing for buprenorphine (B) and norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can facilitate constructive conversations with patients that may lead to modifications in the treatment plan, and strengthening of the patient-provider relationship.. Three cases are presented in which discordant urine B and NB levels were recognized. Each patient was submerging buprenorphine/naloxone strips in their urine to mask ongoing illicit drug use. The authors used an approach to addressing intentional adulteration of urine samples that adheres to the principles of harm-reduction, the centrality of the patient-provider relationship, and the acknowledgment that ongoing illicit drug use and subsequent dishonesty about disclosure may be common among persons with substance use disorders. Each of the three patients ultimately endorsed diluting their urine, which allowed for strengthening of the patient-provider relationship and modifications to their treatment plans. Two of the three patients stabilized and achieved abstinence, while the third was eventually referred to a methadone treatment program.. Providers should routinely monitor B and NB levels, rather than qualitative screening alone, and discordant levels should elicit a timely conversation with the patient. The authors use of a nonjudgmental approach to address urine adulteration, including giving patients an opportunity to reflect on potential solutions, has been effective at helping patients and providers to reestablish a therapeutic alliance and maintain retention in treatment.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Drug Contamination; Female; Humans; Male; Methadone; Middle Aged; Opioid-Related Disorders; Substance Abuse Detection

To test if polysubstance use profiles and drug-related outcomes differ between those receiving and not receiving opioid substitution therapies (OST) among people who inject drugs (PWID).. An annual cross-sectional, sentinel sample of PWID across Australia.. Data came from 3 years (2011-13) of the Illicit Drug Reporting System (IDRS).. A total of 2673 participants who injected drugs from the combined national IDRS samples of 2011 (n = 868), 2012 (n = 922) and 2013 (n = 883).. Latent class analysis (LCA) was used to summarize participants' self-reported use of 18 types of substances, with the resulting polysubstance use profiles then associated with participant experience of a number of drug-related outcomes.. Polysubstance use profiles exhibiting a broad range of substance use were generally at increased risk of negative drug-related outcomes, whether or not participants were receiving OST, including thrombosis among OST receivers [odds ratio (OR) = 2.13, 95% confidence intervals (CI) = 1.09-4.17], injecting with used needles among OST receivers and non-receivers, respectively (OR = 2.78, 95% CI = 1.50-5.13; OR = 2.15, 95% CI = 1.34-3.45) and violent criminal offences among OST receivers and non-receivers, respectively (OR =2.30, 95% CI = 1.16-4.58; OR = 1.87, 95% CI = 1.14-3.07). An important exception was non-fatal overdose which was related specifically to a class of PWID who were not receiving OST and used morphine frequently (OR = 1.83, 95% CI = 1.06-3.17) CONCLUSION: Regardless of opioid substitution therapies usage, people who inject drugs who use a broad-range of substances experience greater levels of injecting-related injuries and poorer health outcomes and are more likely to engage in criminal activity than other groups of people who inject drugs.

Topics: Abscess; Adolescent; Adult; Alcoholism; Amphetamine-Related Disorders; Analgesics, Opioid; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cross-Sectional Studies; Drug Overdose; Female; Heroin Dependence; Humans; Male; Marijuana Abuse; Methadone; Middle Aged; Needle Sharing; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance-Related Disorders; Thrombosis; Violence; Young Adult

Topics: Animals; Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clinical Trials as Topic; Cocaine-Related Disorders; Counseling; Dopamine; Drug Discovery; Drug Industry; Humans; Ibogaine; Lobeline; Molecular Targeted Therapy; Naloxone; Naltrexone; Oligopeptides; Opioid-Related Disorders; Pleasure; Rats; Receptors, Nicotinic; Reward; Substance-Related Disorders; Tobacco Use Disorder; Vaccines; Vesicular Monoamine Transport Proteins

Cocaine use is common in opioid-dependent HIV-infected patients, but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known.. We conducted a prospective study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter. Assessments were conducted at baseline and quarterly for 1 year. We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention, illicit opioid use, antiretroviral adherence, CD4 counts, HIV RNA, and risk behaviors.. Sixty-six percent (197 of 299) of patients reported baseline cocaine use and 65% (173 of 266) of patients with follow-up data reported in-treatment cocaine use. Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention, antiretroviral adherence, CD4 lymphocytes, or HIV risk behaviors. However, baseline cocaine use was associated with a 14.8 (95% confidence interval [CI], 9.0-24.2) times greater likelihood of subsequent cocaine use (95% CI, 9.0-24.2), a 1.4 (95% CI, 1.02-2.00) times greater likelihood of subsequent opioid use, and higher log10 HIV RNA (P < 0.016) over time. In-treatment cocaine use was associated with a 1.4 (95% CI, 1.01-2.00) times greater likelihood of concurrent opioid use.. Given cocaine use negatively impacts opioid and HIV treatment outcomes, interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted.

Topics: Adult; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Risk Factors; Treatment Outcome; Unsafe Sex