Literature Collection

Background: As overdose remains a major public health concern in the United States, it is important to understand the experiences people who inject drugs (PWID) have with overdose. Past experiences during such emergencies are an important determinant of future behavior, including help seeking, which can be lifesaving. Methods: We explored experiences with overdose, using data from 21 in-depth interviews collected from PWID in a rural county in West Virginia (Cabell County). We used an iterative, modified constant comparison approach to synthesize resulting interview data. Results: Participants reported pervasive experiences with overdose, including through their own personal overdose experiences, witnessing others overdose, and losing loved ones to overdose fatalities. Experiencing emotional distress when witnessing an overdose was common among our participants. Many participants reported regularly carrying naloxone and using it to reverse overdoses. Multiple participants described believing the myth that people grow immune to naloxone over time. Concerns about the presence of fentanyl in drugs were also common, with many participants attributing their own and others' overdoses to fentanyl. Conclusions: Our findings have important implications for naloxone access and education, as well as policies and practices to encourage help seeking during overdose events among rural PWID. Participant concerns about fentanyl in the drug supply highlight the need for access to drug checking technologies.

The leaves of Mitragyna speciosa (kratom), a plant native to Southeast Asia, are increasingly used as a pain reliever and for attenuation of opioid withdrawal symptoms. Using the tools of natural products chemistry, chemical synthesis, and pharmacology, we provide a detailed in vitro and in vivo pharmacological characterization of the alkaloids in kratom. We report that metabolism of kratom's major alkaloid, mitragynine, in mice leads to formation of (a) a potent mu opioid receptor agonist antinociceptive agent, 7-hydroxymitragynine, through a CYP3A-mediated pathway, which exhibits reinforcing properties, inhibition of gastrointestinal (GI) transit and reduced hyperlocomotion, (b) a multifunctional mu agonist/delta-kappa antagonist, mitragynine pseudoindoxyl, through a CYP3A-mediated skeletal rearrangement, displaying reduced hyperlocomotion, inhibition of GI transit and reinforcing properties, and (c) a potentially toxic metabolite, 3-dehydromitragynine, through a non-CYP oxidation pathway. Our results indicate that the oxidative metabolism of the mitragynine template beyond 7-hydroxymitragynine may have implications in its overall pharmacology in vivo.

BACKGROUND: The prevalence of methamphetamine use disorder (MUD) in the United States has risen dramatically in the past four decades and is concentrated in populations such as men who have sex with men (MSM). Despite the public health consequences of MUD, there are no FDA-approved psychopharmacological treatments. Psychosocial treatment alone has been shown to reduce methamphetamine use, but high attrition rates limit treatment efficacy. Promising findings from animal models of MUD using exogenous oxytocin, a social neuropeptide, have set the stage for translational work. Along with unique anti-addiction effects, oxytocin holds a primary role in enhancing social salience and modulating stress. In humans, oxytocin administration, combined with evidence-based psychosocial interventions, may act synergistically to improve addiction treatment outcomes and improve retention rates in current MUD treatment. METHODS/DESIGN: We are conducting a randomized, double-blind, placebo-controlled trial of oxytocin-enhanced motivational interviewing group therapy (MIGT). Oxytocin or placebo 40 IU is administered intranasally in conjunction with six, weekly MIGT sessions. We will recruit 50 MSM, initiating treatment for MUD from specialized community health programs in San Francisco, CA, USA. Individuals will be randomized (1:1) to receive six, weekly sessions of MIGT with or without oxytocin. Our primary outcome is session attendance. Other outcomes of interest include: measures of group cohesion, anxiety, psychophysiology, and stimulant craving and use. DISCUSSION: This will be the first study of oxytocin's effects in humans with MUD. Findings from this novel protocol will attempt to bridge existing animal data with the need for innovative clinical treatments for MUD, inform the growing field of pharmacologically-enhanced psychotherapy, and help to elucidate mechanisms behind oxytocin's potential anti-addiction effects. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02881177 . Registered on 26 August 2016.