Past CAPPI Pilot Grant Awardees

Pilot study of medical and institutional mistrust among people who use drugs and people in treatment for opioid use disorder.

Health-related mistrust is largely associated with poorer outcomes across myriad health behaviors and conditions, including preventive cancer screenings and HIV. Although many studies have examined the impacts of mistrust on the health of Black communities, particularly Black men living with HIV, very little is known about how mistrust may manifest among people who use drugs (PWUD). As a population, this group is socio-demographically diverse, but addiction does in fact discriminate; higher overdose risk and worse treatment access outcomes fall along known fault lines of inequity. Specifically, structural racism and classism continue to enforce barriers to care for minoritized populations, including communities of color and low-income people.

This mixed method project will explore how people who use drugs and people in OUD treatment experience mistrust related to their health, including medical treatments (e.g., medications for opioid use disorder), healthcare (e.g., hospital systems, insurance, healthcare providers), the correctional/carceral system, and other social and economic systems that shape people’s daily lives. This pilot will provide preliminary data for an R-series submission. The overarching purpose of this line of research is to inform the implementation of strategies, policies, and processes to increase availability of evidence-based harm reduction strategies, and to increase uptake of treatment for opioid use disorder among people most in need of care.

Assessment of knowledge, beliefs, and perceptions about pain management: A study with adults living with sickle cell disease

Sickle cell disease (SCD) is the most common inherited blood disease in the US that disproportionately affects African Americans. Pain is a hallmark feature of SCD due to acute vaso-occlusive episodes (also called pain crisis) of varying severity and location. As individuals age, they develop high rates of chronic pain, intensifying the effects of SCD and its negative impact across many areas of life and functioning. There are no targeted disease-specific methods for managing SCD-related pain. As a result, aggressive opioid management is often used for the treatment of acute pain. However, the benefits of long-term opioid therapy for chronic pain management are negligible, raising the need to explore additional pain management options. While psychosocial treatments are recommended for chronic pain management in other populations, these have been underutilized in SCD. Though barriers to optimal pain management treatment are multifaceted and require system-level changes, it is also crucial to examine factors operating at the patient level that may impact the implementation and adoption of psychosocial treatments for pain management. The proposed project will examine to what extent individuals living with SCD are aware of psychosocial treatment options or willing to engage in psychosocial treatments for pain management. Finding from this study will inform intervention development to enhance patient engagement to participate and benefit from non-pharmacological chronic pain management options in the future.

Scholars Profile

Uncovering New Potential Therapeutic Targets for the Treatment of Psychostimulant Abuse

Amphetamines (AMPHs) are highly effective psychostimulants commonly used for the treatment of neuropsychiatric disorders such as attention deficit hyperactivity disorder. AMPHs are also commonly abused, leading to devastating medical and societal effects. Nonmedical use of Adderall (racemic mixture of AMPH) increased 67%, and hospital emergency room visits increased 156% from 2006-2011. In 2017, AMPHs were the drugs most frequently involved in deaths in four regions that include 19 states west of the Mississippi (geographic breakdown of deaths by drug; C.D.C. 2019.) Recent studies suggest that imbalances in the gut microbiome (dysbiosis) participate in the pathogenesis of drug abuse. Microbial products such as short-chain fatty acids are suspected to play a fundamental role in this process. This proposal will investigate the molecular mechanisms by which the microbiome alters AMPH-induced responses, focusing on regulation of central dopamine neurotransmission and reward processes. We will use the molecular discoveries generated with the support of this pilot award as preliminary data for an NIH R01 application. The goal of this work is to uncover new potential therapeutic targets for the treatment of psychostimulant abuse.

Scholars Profile

Feasibility and Acceptability of Psilocybin to Treat Fibromyalgia
Drs. Hendricks and Younger will be collaborating on a novel pilot study designed to test the feasibility and potential efficacy of psilocybin in the treatment of fibromyalgia. In this study, participants with fibromyalgia will receive two preparatory counseling sessions, and will then be randomly assigned to receive either psilocybin or the placebo comparator dextromethorphan. Follow-up counseling sessions will take place one day and one week after drug administration. Fibromyalgia symptoms will be monitored daily for 6 weeks after drug administration, allowing for an estimation of the longer-term effects of psilocybin on fibromyalgia.

Scholars Profile  Peter Hendricks, Ph.D.   Jarred Younger, Ph.D.

Determining DNA Methylation Links to Obesity and Chronic Pain

Chronic pain and obesity are highly prevalent in the United States and disproportionately affects African Americans (AA). Specifically, AA are 15% more likely to suffer from obesity than Whites, 7 out of 10 AA ages 18 to 64 are overweight or obese, and AA report more experimental pain sensitivity and more severe and disabling chronic pain than whites. The exact cause of the high prevalence of obesity and chronic pain in AAs remains unknown. Cumulative evidence suggests that the relationship between obesity and chronic pain is multifactorial (involving the interaction of genetic and environmental factors) and multidirectional (obesity increases pain, pain increases obesity, and chronic pain and obesity are comorbid conditions). Epigenetics is one mechanism that links environmental factors to gene expression without altering the DNA sequence. For instance, DNA methylation (DNAm) is a reversible epigenetic mechanism by which environmental factors alter which genes are turned-on or turned-off without changing the DNA sequence. Thus, we hypothesize that the DNAm of genes that regulate metabolism and inflammatory processes play a critical role in the development of obesity and increase pain sensitivity. To test this hypothesis, we will explore the role of DNAm in the obesity-pain link in 50 (25 obese and 25 non-obese) AAs, which is an essential step in understanding the underlying mechanism. The next critical step is to show that the observed DNAm changes result in alterations in gene expression. Thus, we propose to examine the transcriptome to identify expressed genes and their role in the obesity-pain relationship. Given that the epigenome is subject to change and can be modified, we expect that our findings would provide a basis for the development of targeted interventions to treat obesity and pain.

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 Understanding the Molecular and Genetic Associations between Chronic Pain and Opioid Euphoria

Many individuals suffering from opioid abuse disorder first encounter opioids in a clinical setting related to a long-lasting pain state (e.g., surgery). However, although chronic pain influences the desire to take drugs of abuse, we know very little about how pain states alter the molecular response to opioids in brain circuits that mediate the transition to drug addiction. This pilot proposal will foster a collaboration between two laboratories with unique expertise in pain (Dr. Sorge) and molecular mechanisms of addiction (Dr. Day) to help define how chronic pain alters the molecular and genetic signatures in key brain regions that contribute to the euphoric effects of opioids. Using an animal model, this proposal will combine opioid drug exposure in chronic pain states with cutting-edge single-cell molecular profiling approaches, yielding a novel cellular atlas for discovery-based identification of new cellular and molecular targets for therapeutic intervention.

Scholars Profile