Residual next-day effects of alprazolam on psychomotor performance and simulated driving in healthy normal adults.

The prevalence of drugged driving has increased in the United States. Some drugged driving may be unintentional as prescription medications used as sleeping aids, like zolpidem, cause impairment after the predicted duration of therapeutic action has elapsed. The aim of this study was to determine if nighttime administration of alprazolam, a drug commonly prescribed off-label as a sleeping aid, impacts driving performance the following day.

Evaluation of tradipitant, a selective NK1 antagonist, on response to oxycodone in humans.

Rationale: Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans.

Objective: To explore the potential for a selective NK1 antagonist, tradipitant, to attenuate the abuse liability and reinforcing and analgesic effects of oxycodone in opioid-experienced individuals.

Acute administration of oxycodone, alcohol, and their combination on simulated driving-preliminary outcomes in healthy adults.

Rationale: Epidemiological data indicate that drivers testing positive for an opioid drug are twice as likely to cause a fatal car crash; however, there are limited controlled data available.

Objectives: The primary aim of this study was to assess the effects of a therapeutic dose range of oxycodone alone and in combination with alcohol on simulated driving performance.

Methods: Healthy participants (n = 10) completed this within-subject, double-blind, placebo-controlled, randomized outpatient study.

Buprenorphine Induction in Persons With Opioid Use Disorder Hospitalized with Acute Hepatitis A.

Background: It is not known whether buprenorphine/naloxone (bup/nx) can be safely initiated in hospitalized patients with acute hepatitis A infection. We assessed liver function and tolerability of bup/nx induction in patients with acute Hepatitis A Virus (HAV).

Methods: Retrospective review of patients (N = 31) admitted to a tertiary care facility for acute HAV who were evaluated by an addiction medicine consultant.

Outpatient Parenteral Antimicrobial Therapy Plus Buprenorphine for Opioid Use Disorder and Severe Injection-related Infections.

Unlabelled: In a pilot randomized trial in persons with opioid use disorder hospitalized with injection-related infections, an innovative care model combining outpatient parenteral antimicrobial therapy with buprenorphine treatment had similar clinical and drug use outcomes to usual care (inpatient intravenous antibiotic completion) and shortened hospital length of stay by 23.5 days.

Clinical Trials Registration: NCT03048643.

Cannabinoid modulation of opioid analgesia and subjective drug effects in healthy humans.

Rationale: Dozens of preclinical studies have reported cannabinoid agonist potentiation of the analgesic effects of μ-opioid agonists.

Objectives: The aim of this study was to determine if a cannabinoid agonist could potentiate opioid analgesia in humans using several laboratory pain models.

Methods: Healthy participants (n = 10) with/out current drug use/pain conditions completed this within-subject, double-blind, placebo-controlled, randomized outpatient study.

In-hospital illicit drug use, substance use disorders, and acceptance of residential treatment in a prospective pilot needs assessment of hospitalized adults with severe infections from injecting drugs.

Objective: To conduct a pilot needs assessment of underlying substance use disorders (SUD), motivation for SUD treatment, and willingness to enter residential SUD treatment in hospitalized adults who inject drugs with complex infections requiring intravenous (IV) antibiotics, and to assess the presence of in-hospital illicit substance use.

Patients And Methods: From March 8, 2016 through August 25, 2016 hospitalized, English-speaking, adult patients not currently in SUD treatment with a history of injection drug use and a current infection requiring treatment with IV antibiotics, were prospectively enrolled. Participants were followed weekly during the hospitalization and for 60 days after discharge via interview and medical record review.

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation.

Objective: To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD.

Randomized controlled trial of a computerized opioid overdose education intervention.

Background: Opioid overdose (OD) has become a significant public health problem in need of effective interventions. The majority of existing educational interventions target provision of naloxone and are conducted in-person; these elements present logistical barriers that may limit wide-spread implementation. This study developed and evaluated an easily disseminated opioid OD educational intervention and compared computerized versus pamphlet delivery METHODS: Participants (N=76) undergoing opioid detoxification were randomly assigned to receive OD education via a Pamphlet (N=25), Computer (N=24), or Computer+Mastery (N=27) with identical content for all delivery modalities.

Effects of Short-Term Oxycodone Maintenance on Experimental Pain Responses in Physically Dependent Opioid Abusers.

Unlabelled: A common clinical problem with opioid analgesics is the loss of analgesic efficacy after repeated dosing; when this occurs, it is not clear what principles should guide providing effective analgesia among opioid-dependent individuals. This within-subject inpatient study aimed to determine if physically dependent opioid abusers (n = 11) experience changes in oxycodone-induced analgesia during 2 oxycodone maintenance (30 mg orally 4 times per day) phases: initial stabilization (days 1-3) and after 6 weeks of chronic dosing. Six sessions (3 each phase), measured threshold, tolerance, and pain ratings for a Pressure Pain Test and Cold Pressor Test after a single double-blind dose of oxycodone 30 mg (initial stabilization) and 0, 30, and 60 mg (chronic dosing) given in place of a scheduled maintenance dose.

A Pharmacokinetic Study Examining Acetazolamide as a Novel Adherence Marker for Clinical Trials.

Rationale: Accurate assessment of medication adherence is critical for determination of medication efficacy in clinical trials, but most current methods have significant limitations. This study tests a subtherapeutic (microdose) of acetazolamide as a medication ingestion marker because acetazolamide is rapidly absorbed and excreted without metabolism in urine and can be noninvasively sampled.

Methods: In a double-blind, placebo-controlled, residential study, 10 volunteers received 15 mg oral acetazolamide for 4 consecutive days.

Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

Background: The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal.

Methods: Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study.

Intranasal buprenorphine alone and in combination with naloxone: Abuse liability and reinforcing efficacy in physically dependent opioid abusers.

Background: Buprenorphine can be abused by the intranasal route. This study sought to examine the relative abuse liability and reinforcing efficacy of intranasal buprenorphine compared to intranasal buprenorphine/naloxone in opioid-dependent individuals.

Methods: Eleven healthy male and female volunteers physically dependent on short-acting opioids resided as inpatients during participation in this double blind, within subject, placebo-controlled study.

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis.

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ(9)-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown.

Safety of oral dronabinol during opioid withdrawal in humans.

Background: Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal.

Quinine as a potential tracer for medication adherence: A pharmacokinetic and pharmacodynamic assessment of quinine alone and in combination with oxycodone in humans.

Effective strategies to monitor pharmacotherapy adherence are necessary, and sensitive biological markers are lacking. This study examined a subtherapeutic dose of quinine as a potential adherence tracer. Primary aims included examination of the plasma and urinary pharmacokinetic profile of once-daily quinine; secondary aims assessed pharmacokinetic/pharmacodynamic interactions with oxycodone (a CYP3A and CYP2D substrate).

Characterizing opioid withdrawal during double-blind buprenorphine detoxification.

Background: Prescription opioid (PO) abuse has become an urgent public health issue in the United States. Detoxification is one important treatment option, yet relatively little is known about the time course and severity of opioid withdrawal during buprenorphine detoxification.

Methods: This is a secondary analysis of data from a randomized, placebo-controlled, double-blind evaluation of 1, 2, and 4-week outpatient buprenorphine tapers among primary prescription opioid (PO) abusers.

Internet-based group contingency management to promote smoking abstinence.

Internet-based group contingencies have been shown to promote brief periods of abstinence from cigarette smoking. Under a group contingency, small teams of smokers must collectively meet abstinence goals to receive monetary consequences. The present study investigated 2 arrangements, 1 in which all team members had to meet group treatment goals to receive monetary consequences (full group), and 1 in which team members had to meet some group goals and some individual goals to receive these consequences (mixed group).

Employment-based reinforcement of adherence to oral naltrexone in unemployed injection drug users: 12-month outcomes.

Oral naltrexone could be a promising relapse-prevention pharmacotherapy for recently detoxified opioid-dependent patients; however, interventions are often needed to promote adherence with this treatment approach. We recently conducted a study to evaluate a 26-week employment-based reinforcement intervention of oral naltrexone in unemployed injection drug users (Dunn et al., 2013).

Pharmacodynamic effects of oral oxymorphone: abuse liability, analgesic profile and direct physiologic effects in humans.

Oxymorphone is a semisynthetic μ-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of oxymorphone were reintroduced in the United States in 2006 and reports of abuse ensued; however, there are limited data available on its pharmacodynamic effects. The current study aimed to examine the direct physiologic effects, relative abuse liability, analgesic profile and overall pharmacodynamic potency of oxymorphone in comparison with identical doses of oxycodone.

Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans.

Aripiprazole is a partial agonist at dopamine (D2) and serotonin (5-HT1a) receptors and 5-HT2 antagonist. Because cocaine affects dopamine and serotonin, this study assessed whether aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole on ad lib cigarette smoking and with a novel 40-hr smoking abstinence procedure.

Lobeline Effects on Cognitive Performance in Adult ADHD.

Objective: In preclinical studies, lobeline inhibited hyperactivity induced by nicotine and amphetamine, and improved performance and learning in studies utilizing radial-arm maze and spatial-discrimination water maze. This laboratory proof-of-concept study investigated lobeline as a treatment for ADHD symptoms in adults (31.11 ± 7.

Methadone-related overdose deaths in rural Virginia: 1997 to 2003.

Aim: Nonmedical use of prescription drugs and poisoning overdose deaths related to prescription drugs are increasing. This article presents an in-depth description of decedents from rural southwestern Virginia, where methadone was identified on toxicology.

Methods: Cases for this study were derived from a population-based review of 893 drug-related deaths occurring from 1997 to 2003 in the Office of the Medical Examiner, Western District of Virginia.

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

Background: Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal.

Methods: Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial.

Employment-based reinforcement of adherence to oral naltrexone treatment in unemployed injection drug users.

Oral naltrexone has high potential for use as a relapse prevention pharmacotherapy for opiate dependence yet suffers from notoriously poor adherence. This study evaluated whether entry to a therapeutic workplace could reinforce adherence with oral naltrexone. Opiate-dependent and cocaine-using injection drug users were detoxified, inducted onto oral naltrexone, and randomly assigned to a contingency (n = 35) or prescription (n = 32) group for a 26-week period.