N-acetylcysteine for smoking cessation among dual users of tobacco and cannabis: Protocol and rationale for a randomized controlled trial.

BACKGROUND: Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared environmental cues reinforcing use may make tobacco smoking cessation more difficult. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's potential efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. To date, no RCT has examined NAC for smoking cessation among dual users of tobacco and cannabis. METHOD: In a double-blind, placebo-controlled RCT, we will examine NAC for smoking cessation among dual users of tobacco and cannabis. Sixty adult cigarette-cannabis co-users are randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups receive 8 weekly cognitive behavioral therapy sessions addressing smoking cessation and cannabis reduction. Outcomes are assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette craving, nicotine dependence, and use; and cannabis craving and use. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes. CONCLUSION: Results will inform smoking cessation treatment among dual users of tobacco and cannabis. CLINICALTRIALS: gov Identifier: NCT04627922.

Which Emergent Medication Should I Give Next? Repeated Use of Emergent Medications to Treat Acute Agitation.

Agitation is a common symptom encountered among patients treated in psychiatric emergency settings. While there are many guidelines available for initial management of the acutely agitated patient, there is a notable dearth of guidelines that delineate recommended approaches to the acutely agitated patient in whom an initial medication intervention has failed. This manuscript aims to fill this gap by examining evidence available in the literature and providing clinical algorithms suggested by the authors for sequential medication administration in patients with persistent acute agitation in psychiatric emergency settings. We discuss risk factors for medication-related adverse events and provide options for patients who are able to take oral medications and for patients who require parenteral intervention. We conclude with a discussion of the current need for well-designed studies that examine sequential medication options in patients with persistent acute agitation.

Case Report: Buprenorphine Induction Using Transdermal Buprenorphine in a Veteran With Opioid Use Disorder and Psychosis, Managing Precipitated Withdrawal.

Buprenorphine induction can lead to precipitated opioid withdrawal, even when using novel techniques such as transdermal buprenorphine. Involuntary limb movements are a distressing symptom of precipitated withdrawal that can be difficult to treat. We report a case of a military veteran transitioning from methadone to buprenorphine for the treatment of opioid use disorder (OUD) using small doses of transdermal buprenorphine. Herein, we review the literature associated with opioid withdrawal-related restlessness. Despite the known risk of concurrent benzodiazepine and buprenorphine administration, including decreased respiratory rate and death, we present a clinical presentation in which this medication combination may be necessary while under medical supervision. We suggest a stepwise algorithm for pharmacotherapy in patients experiencing involuntary limb movements associated with precipitated withdrawal. To safeguard the success of medication-assisted treatment (MAT) for opioid addiction, clinicians should be aware of potential clinical challenges when managing precipitated opioid withdrawal in patients with complex psychiatric comorbidities.

Deployment Anxiety Reduction Training: A Pilot Study of Acceptability and Feasibility in Current or Recent Active Duty Service Members.

Objectives: The Deployment Anxiety Reduction Training (DART) is a manualized tool that was developed and piloted with active duty service members and recently deployed veterans regarding their response to potential and experienced acute combat stress reactions. DART is low risk and has high potential to be beneficial. It is a brief, one-session, non-pharmacological approach designed to reduce symptoms of peritraumatic panic and increase resilience in the face of a potentially traumatic stressor. Methods: This study was a mixed-methods pilot study to assess the utility and acceptability of DART during deployment. Results: Self-report and interview responses indicated that participants generally found the DART techniques acceptable and easy to understand. Overall, the techniques were perceived as likely to be helpful with high utility, although there was variation in perceived helpfulness among the different techniques. Participants overwhelmingly positively endorsed delivery of the DART protocol through use of smartphone technology. Conclusions: Results indicate that the DART components were considered highly acceptable and feasible for use in the deployed environment.

Cocaethylene formation following ethanol and cocaine administration by different routes.

Ethanol alters the hepatic biotransformation of cocaine, resulting in transesterification to a novel active metabolite, cocaethylene. Because of first pass metabolism, oral drug administration might be expected to produce relatively larger concentrations of cocaethylene than would intravenous or smoked administration. We, therefore, compared the effects of route of cocaine administration on the formation and elimination of cocaethylene. Six experienced cocaine users were tested in 6 sessions, approximately 1 week apart. Deuterium-labeled cocaine (d5) was administered in all conditions. Oral cocaine-d5 2.0 mg/kg, intravenous cocaine-d5 1.0 mg/kg, and smoked cocaine-d5 (200 mg) were administered after oral ethanol 1.0 g/kg or placebo. A small, intravenous dose of deuterated cocaethylene (d3) also was administered with all conditions for determination of cocaethylene formation. Physiologic and subjective effects were recorded and plasma cocaine-d5, cocaethylene-d5, cocaethylene-d3, and benzoylecgonine-d5 were measured by gas chromatography-mass spectrometry. About 24% (± 11) of intravenous cocaine was converted to cocaethylene. The oral route (34% ± 20) was significantly greater than from the smoked route (18% ± 11) and showed a trend toward significance for greater formation of cocaethylene compared to the intravenous route. Within each route, the cocaine-ethanol combination produced greater increases in heart rate and rate-pressure product than cocaine alone. Global intoxication effects across time after smoking or intravenous administration were significantly greater when cocaine and ethanol were both given. Administration of cocaine by different routes alters the amount of cocaethylene formed through hepatic first-pass effects. Increased cardiovascular and subjective effects might explain the toxicity and popularity of the combined drugs.