Opioids

Clinical Research on Opioids

Substantial increases in the abuse of prescription opioids observed recently in the US have resulted in sharp rises in morbidity and opioid-related overdose deaths. While opioid dependence is among the most destructive and lethal of addictions, it also has the most powerfully effective medication treatments. Maintenance with the opioid receptor agonist methadone, the partial agonist buprenorphine, or the opioid antagonist naltrexone is each associated with substantial rates of remission. Our Division is involved in cutting edge research in the area of new medications and behavioral treatments to treat opioid dependence. We have tested various medication strategies to improve outcome of treatment with opioid blocker naltrexone and have worked on improving opioid detoxification. At present we are developing new approaches to conduct an outpatient opioid detoxification and initiation of treatment with long-acting injectable naltrexone. We are also planning to conduct a trial of a long-acting injectable preparation of buprenorphine. We also provide training on reversing opioid overdose and dispense free naloxone kits to all interested individuals.

Faculty conducting clinical opioid research:

• Adam Bisaga, MD
• Edward V. Nunes, MD
• Jeanne Manubay, MD

Laboratory Research on Opioids

The Opioid Laboratory in the Division on Substance Use Disorders is dedicated to conducting studies that are designed to gain a better understanding of the underlying mechanisms of Opioid Use Disorder (OUD), including its antecedents and consequences. We use laboratory models of drug-taking behavior where opioid-experienced participants first sample a dose of an opioid and then are given the opportunity to work for that dose by responding on a computer mouse (making clicks or finger presses on the mouse). Our participants will make hundreds of responses to earn active drug, and they make far fewer responses when inactive drug is available. We and other scientists have demonstrated that methadone, buprenorphine, and naltrexone, which are all currently FDA-approved treatments for OUD, reduce drug-taking behavior in the laboratory. Thus, the model has been validated for these effective treatment medications. We have examined other medications, such ibudilast, a non-selective phosphodiesterase inhibitor and glial cell modulator, minocycline, a broad-spectrum antibiotic and glial cell modulator, gabapentin, a GABA agonist and anticonvulsant, and lorcaserin, a serotonin 5HT2c agonist, as potential MOUDs. We are currently testing a vaccine for treating OUD, and we plan to test monoclonal antibodies that target fentanyl. In addition to developing medications for OUD, we are also conducting studies to examine the potential influence of genetic variables on opioid use, as well as the influence of pain on opioid-mediated effects. We examined both the risks and benefits of prescribing naloxone to drug users as a means of reducing opioid overdose and we will be testing a novel device that stimulates phrenic nerves as a potential treatment for drug overdose. All of these studies are designed to help us understand and treat this serious disorder.

Faculty conducting laboratory opioid research:

• Adam Bisaga, MD
• Sandra Comer, PhD
• Jermaine Jones, PhD
• Jeanne Manubay, MD
• Rachel Luba, PhD
• Felipe Castillo, MD