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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. Electronic supplementary material The online version of this article (10.1186/s13063-019-3225-7) contains supplementary material, which is available to authorized users.

Veterans with mental health problems and a history of interpersonal and military trauma exposure are at increased risk for chronic homelessness. Although studies have examined posttraumatic stress disorder (PTSD) as a predictor of homelessness, there is limited understanding of specific mechanisms related to cumulative trauma exposure. We sought to elucidate how cumulative interpersonal and military trauma exposure may be linked to homelessness chronicity by examining the role of factors that influence trauma recovery and functional impairment. Specifically, we examined the indirect association of cumulative trauma exposure with homelessness chronicity through distress and responses to trauma-related intrusions and emotion regulation problems in a sample of 239 veterans in community-based homeless programs. Participants completed measures of trauma exposure, responses to intrusions, intrusion distress, difficulties with emotion regulation, and duration and episodes of homelessness. Structural equation modeling was used to test a serial indirect effect model in which cumulative trauma exposure was indirectly associated with homelessness chronicity through distress from and responses to intrusions as well as emotion regulation problems. The results supported the hypothesized sequential indirect effect for episodes of homelessness, indirect effect odds ratio (IE ORs) = 1.12-1.13, but not for current episode duration, IE OR = 1.05. Overall, the present findings elucidate specific trauma-related factors that may be particularly relevant to episodic patterns of homelessness and interfere with efforts to remain housed. These findings represent an important step toward shaping policy and program development to better meet mental health care needs and improve housing outcomes among homeless veterans.