Funded Projects

Effective medications for opioid use disorder (MOUD) are approved by the Food and Drug Administration for the treatment of people with opioid use disorder; however, only a small fraction of patients who would benefit from these medications actually use them. Several reasons contribute to low MOUD use, including lack of insurance; lack of knowledge about the medications, both among patients and providers; stigma associated with MOUD; and social norms. Innovative methods are needed to help increase MOUD use. One such option is peer-led interventions that might increase patients’ interest in MOUD. One existing peer-led intervention is the Harnessing Online Peer Education (HOPE) online community intervention that has been designed to reduce stigma and increase health behavior change among stigmatized populations, such as people living with HIV. This project will investigate whether and how HOPE can be adapted for people with opioid use disorder. It will assess whether HOPE can effectively increase MOUD requests, MOUD uptake, and sustained adherence to MOUD as well as reduce overdose rates.  

Some chemotherapy treatments damage nerves outside the brain and spinal cord. This condition, chemotherapy-induced peripheral neuropathy, involves tingling, burning, weakness, or numbness in hands and/or feet and affects nearly 70% of cancer patients receiving chemotherapy. Common pain medications, including opioids, can relieve pain for short intervals but are not suitable for long-term therapy. This project will develop and test a new type of treatment (reduced size cyclic analogs) for this condition. The research will evaluate the ability of this therapy to reduce inflammation and pain, as well as to repair nerve damage.

Approximately 20% of patients who undergo surgery develop chronic Postsurgical Pain, which is linked with slow recovery, persistent opioid use and dependence. This project supports a scientist from a group underrepresented in biomedicine to expand ongoing research testing ketamine during and/or after surgery to prevent post-mastectomy pain syndrome. Ketamine is a low-risk treatment option that is easy to implement in a wide range of clinical settings.

Social determinants of heath may affect breast cancer diagnosis and disease staging at time of mastectomy. It is unclear if socioeconomic factors such as annual income, marital status/single parent household, number of children, distance from the hospital, and other life stressors facing individuals from under-resourced populations affect development of postmastectomy pain syndrome or response to the drug ketamine. This research will analyze these factors toward mitigating post-mastectomy pain. This analysis will also serve as the basis for further research to define pathways that minimize health disparities plays in the development of chronic, post-surgical pain. The ultimate goal of this research is to normalize risk for chronic pain after breast surgery.

Pain Coping Skills Training (PCST) uses a cognitive behavioral therapy (CBT) approach to teach patients cognitive and behavioral coping skills shown to reduce pain and pain interference (e.g., relaxation, distraction, cognitive restructuring, activity pacing). Randomized controlled trials show that PCST and similar CBT-based interventions, when delivered in a traditional in-person format, can improve pain and functioning in people with cancer and other conditions. Yet these interventions are underused in clinical care due to barriers such as high resource costs, a shortage of therapists trained to deliver them, and travel requirements for patients. This trial aims to deliver evidence-based behavioral pain interventions such as PCST with methods capable of overcoming barriers currently limiting patient access. This will be investigated using a two-arm trial comparing pain relief with the following interventions: painTRAINER in clinic with eight web-based follow-up sessions; enhanced usual care.

Cancer remains a leading cause of death among Hispanic/Latino populations in the United States. Compared with non-Hispanic Whites, Hispanic/Latino cancer patients are more likely to experience poor quality of life and inadequate cancer-related care, including less effective pain relief and poor patient‒provider communication. Additionally, Hispanic/Latino populations often have inadequate access to pain treatment, due to both social disparities and language barriers. However, most behavioral and psychosocial oncology research continues to focus on non-Hispanic Whites, and empirically validated and effective treatment interventions, particularly psychosocial interventions, are often not available in Spanish. This project will generate a Spanish-language version of the painTRAINER internet-based coping skills training program that is both linguistically and culturally sensitive and will evaluate its feasibility and acceptability in Hispanic/Latino patients with persistent cancer-related pain.

More than half of children and adolescents diagnosed with a type of cancer called bone sarcoma experience pain that interferes with daily life. This project will adapt an evidence-based cognitive behavioral therapy mobile app for use with Black and Hispanic adolescents who disproportionately experience pain from this cancer, putting them at risk for opioid misuse. Once fully adapted, this therapy will be paired with a remotely delivered brain stimulation treatment (transcranial direct current stimulation). This research will also examine the impact of patient-reported conditions such as depression, anxiety, and sleep problems, as well as of various social determinants of health, on pain.

The widespread misuse of opioids has underscored the need to develop nonaddicting pain medications. Chronic pain is a major factor contributing to insomnia, and sleep disruption due to chronic pain causes patients to seek relief, exacerbating the drive for prescription opioids. In opioid use disorder, withdrawal from opiates induces insomnia, posing an additional challenge for successful abstinence. This study aims to determine whether treatment of opioid withdrawal-induced insomnia with nociceptin/orphanin FQ receptor (NOPR) agonists will mitigate the drive for opiate use. A major component of the arousal/withdrawal circuitries resides in the locus coeruleus (LC), which expresses MOPRs. The study will determine whether and how the NOPR system engages LC circuits to reduce arousal and insomnia-related phenotypes and assess the hypotheses that 1) the NOPR system is a component of the endogenous sleep/wake regulatory system and 2) NOPR agonists can act as therapeutic interventions to reduce opiate use.

For individuals with moderate to severe opioid use disorder (OUD), medication-assisted treatments (MATs) such as oral methadone and extended-release naltrexone (XR-NTX) are the gold standard in initiating and maintaining long-term recovery. Still, many patients struggle with persistent sleep disturbance and stress reactivity in the early stages of recovery, which drive relapse behaviors. This proposal constitutes a novel mechanistic approach to understanding the role of the orexin system in sleep disturbance and circadian rhythms of stress in OUD patients who are maintained on MATs and are early in recovery. This study will determine whether the FDA-approved sleep medication suvorexant (SUVO) improves sleep continuity and decreases diurnal measures of stress, and whether improvement of sleep/stress processes translates to improved OUD treatment outcomes. Its findings will fill critical gaps in our understanding of the role of the orexin system in sleep disturbance and circadian rhythms of stress that impact OUD recovery.

FDA-approved medications for treating opioid use disorder are effective, but there is a significant unmet need for alternatives, especially relapse prevention. NIDA and the FDA have encouraged investigators to expand the range of therapeutic outcomes, beyond measurement of abstinence. Insomnia is a clinically significant, but understudied, correlate/predictor of relapse to substance use. Yet most medications for treating insomnia have limited efficacy and can produce side effects. The orexin (OX) system plays a key role in sleep and substance use, offering a promising avenue for study. This project will address whether OX-1/2 antagonism is a mechanism that can directly improve outpatient opioid abstinence, or whether OX antagonism corrects sleep deficiencies and indirectly improves opioid abstinence. Specific aims are to determine whether nightly treatment with the OX-1/2 antagonist suvorexant, relative to placebo, 1) increases outpatient opioid abstinence and 2) improves sleep efficiency on the residential detoxification unit. The study will also determine 3) whether improved sleep efficiency predicts greater opioid abstinence (regardless of group assignment).

Opioid use disorder (OUD) is a chronic and relapsing brain disease that affects over 2 million Americans. Despite effective evidence-based treatments in the form of behavioral interventions and FDA-approved medication for addiction treatment (MAT), relapse rates are high. The Collaboration Linking Opioid Use Disorder and Sleep Study will investigate patients on MAT to elucidate potential causal mechanisms between sleep deficiency and OUD. The aims of this study are to 1) test whether there are different neurocognitive connectivity patterns between patients with adequate vs. deficient sleep in brain systems involved in addiction and assess the extent to which these “neural fingerprints” predict ongoing opioid use; 2) evaluate the potential biologic, psychiatric, and pharmacologic mechanisms that explain the causal pathway between sleep deficiency and opioid use; and 3) test ecologic factors such as psychosocial, family, and neighborhood contextual factors associated with OUD and their contribution to sleep deficiency among patients in MAT.

Repetitive drug use forms powerful memories associating drug-evoked experiences with its proximal environmental cues. Memories are major obstacles for successfully treating addiction, since even after a prolonged period of abstinence, reexposure to such cues often triggers craving that promotes relapse. A polysynaptic pathway from the paraventricular nucleus of the thalamus (PVT) to the lateral hypothalamus (LH) has been shown to play a role in the maintenance of the opioid-associated memories. Hypocretin (Hcrt) neurons in the LH strongly innervate the PVT, required for maintaining wakefulness and involved in drug seeking. These factors may link sleep disorders in opioid addicts with their long-lasting drug-associated memories. This study will (1) determine whether Hcrt neurons in the LH are the major target; (2) examine whether manipulating the LH (Hcrt)-PVT pathway can effectively prevent relapse; and (3) test whether sleep intervention could be an effective strategy to prevent relapse.