Monday, February 05, 2018

PAS-18-624: Mechanistic investigations of psychosocial stress effects on opioid use patterns (R01- Clinical Trial Optional)

Psychosocial stress, defined here as socioenvironmental demands that tax the adaptive capacity of the individual (e.g., low socioeconomic status, childhood adversity, bullying), has repeatedly been linked to substance use disorders (SUDs). Neighborhood poverty and social support are shown to influence substance use patterns. Among smokers, multiple psychosocial stressors are associated with relapse, and acute psychosocial stress has been demonstrated to enhance cigarette craving and smoking behavior. Similarly, psychosocial stress has been associated with greater risk of relapse in individuals with alcohol and cocaine use disorders. Recent findings suggest that OUD might also be influenced by psychosocial stress, although the exact relationship and underlying mechanisms remain poorly understood.

In light of the current opioid epidemic in the United States, there is an urgent need to understand how psychosocial stress influences the risk for opioid misuse, abuse, and use disorder. According to the 2014 National Survey on Drug Use and Health (NSDUH), over 4 million Americans engaged in non-medical use of prescription opioids in the previous month, and approximately 1.9 million Americans met criteria for OUD. Further, according to the Center for Disease Control (CDC), deaths from drug overdose in the US exceeded 60,000 last year, surpassing the number of AIDS-related deaths at the height of the HIV/AIDS epidemic. Another recent CDC report indicates that areas with the largest number of filled prescriptions for pain medications also have higher rates of poverty and unemployment, implicating psychosocial stressors as factors that exacerbate opioid use patterns across the country. Notably, relatively few mechanistic studies have investigated the relationship between psychosocial stress and substance use disorders, of which only a fraction pertains to OUDs specifically.

This funding opportunity announcement seeks to address two specific mechanistic pathways via which psychosocial stress may modulate opioid use trajectories.The first pathway is through its effects on cognitive and affective systems that are also altered in OUDs. Stressful environments have been linked to impairments in reasoning, memory, inhibitory and cognitive control, and negative affect. Acute poverty, for example, has been shown to immediately impact performance on tasks measuring intelligence and cognitive control. Relatedly, there is substantial co-morbidity between OUD and stress-related affective disorders, including depression, anxiety and PTSD. Many neurobiological substrates and circuits that are thought to mediate cognitive and affective aspects of addiction are impacted by psychosocial stress. Taken together, these findings suggest that more research is warranted on the role of cognitive and affective systems mediating the effects of psychosocial stress on opioid use trajectories.

Psychosocial stress can also influence opioid use trajectories through its effects on pain processing. Of relevance here, adverse childhood experiences have been associated with an increased prevalence of pain-related medical conditions during adulthood and many individuals with stress-related psychiatric disorders have co-morbid chronic pain syndromes. This may be a consequence of overlapping neural circuits or substrates that are engaged by psychosocial stress and pain and that have been implicated in OUD. Recent estimates suggest that the rates of opioid misuse in patients with chronic pain range from 15-26%. Importantly, and germane to the discussion above, negative affect and the reduced ability to cope with negative emotions in pain appear to increase opioid misuse rates. Further research is needed to understand how the effects of psychosocial impacts on cognitive and affective components of pain may influence the opioid use trajectory. This knowledge may advance prevention and treatment strategies in chronic pain populations.