Funded Projects

Currently there are no effective treatments approved by the U.S. Food and Drug Administration for cocaine use disorder. This project will explore the use of a novel class of small molecules that selectively block the molecule phosphodiesterase 7 (PDE7). Past research suggests that the PDE7 class of compounds helps restore normal functions of the dopamine reward system altered by chronic exposure to cocaine. This research will use both preclinical and clinical research studies to develop and test a PDE7 blocker, toward development of the first oral treatment for cocaine use disorder. 

The opioid antagonist naltrexone (NTX) is a proven treatment for opioid use disorder (OUD); however, lack of adherence is a serious limitation that has prevented NTX from reaching its maximum therapeutic potential. To address this limitation, BioCorRx is developing BICX102, a subcutaneous solid depot pellet of NTX, a single implantation of which can provide continual blockade of opioid receptors for up to 3 months. This can prevent patients from being adversely affected by almost any opioid relapse event, while improving efficacy and adherence to behavioral programs that support long-term management and recovery. This proposal comprises the steps required to achieve FDA approval. Successful development of BICX102 would result in a safe and effective 3-month subcutaneous depot pellet/implant containing NTX (1,000 mg) that would be far less reliant on patient compliance.

Extended-release naltrexone (XR-NTX) reduces overdose risk; however, transitioning to XR-NTX requires detoxification, which is a major hurdle. Non-opioid detoxification with an alpha-2 adrenergic receptor agonist, such as lofexidine, may shorten detoxification time, but it does not reduce the subjective effects of withdrawal. Pregabalin potentiates the activity of glutamic acid decarboxylase, inhibits calcium influx and release of excitatory neurotransmitters, raises GABA levels, and is approved for neuropathic pain, for fibromyalgia, and as an adjunctive therapy for adults with partial onset seizures. The study will test whether pregabalin can be combined with lofexidine to better reduce the subjective effects of opioid withdrawal than lofexidine alone and increase the proportion of patients that transition to XR-NTX. Such a dosing combination could lower the detoxification hurdle for patients who are interested in antagonist treatment or who are in settings where it is unavailable or difficult to access.

Opioids have been significantly over-prescribed and are associated with numerous deaths, resulting in the nation’s current opioid crisis. The FDA recently approved the ?2 adrenergic agonist lofexidine as a non-addictive, non-opioid treatment for opioid use disorder (OUD), but there is a continued, urgent need to develop additional pharmacological alternatives to address both pain and OUD. The psychoactive, natural product, Mitragyna speciosa (kratom), has triggered significant interest in this space because Mitragynine, its main alkaloid, can interact with both mu opioid and ?2 receptors, offering a totally new approach for treating OUD. This project involves the synthesis and research of a series of Mitragynine analogs to better understand the pharmacological mechanisms that underlie Mitragynine’s opioid and adrenergic activities. If successful, this project will result in templates for the design of novel opioid receptor ligands. This advance would greatly improve the knowledge of interactions of these structurally novel compounds with opioid receptors and facilitate the development of these ligands as treatments for OUD.

There are no FDA-approved medications for stimulant use disorders, and therapies for opioid use disorders remain suboptimal in ways that are now a focus of national attention. Thus, there is a clear need to identify new targets and explore new approaches for addiction medication development. Several lines of evidence suggest that PTPRD (receptor type protein tyrosine phosphatase D) may be a promising target for development of pharmacotherapeutics to treat not only stimulant use disorders but opioid use disorders as well. This research will focus on improving existing PTPRD ligands, identifying their effects on the dopamine and opioid systems, and moving the best novel, patentable PTPRD ligands toward human studies. If successful, this project will generate novel, well-tolerated, and bioavailable PTPRD ligands that display in vitro potency, selectivity and stability, and in vivo modulation of both cocaine and opioid-mediated reward at doses that present no significant toxicity.

Opioids can be effective analgesics but can also be fatal due to opioid-induced respiratory depression after overdose. This project will use cutting-edge molecular, physiological, behavioral, and imaging techniques to better understand and distinguish opioid-induced respiratory depression and opioid-mediated analgesia. Nerve cell-specific, single-cell transcriptomic analysis will be used to identify functional markers expressed in nerve cells that play a specific role in opioid-induced respiratory depression, but not opioid analgesia. This research study will help to identify novel therapeutic targets that could selectively rescue opioid-induced respiratory depression while maintaining the beneficial pain-relieving effects of opioids. 

Buprenorphine is used for treatment of opioid use disorder (OUD), and patients often take it for many years by slowly dissolving it in the mouth. In 2022, the U.S. Food and Drug Administration warned about possible oral complications from buprenorphine use, including tooth decay, oral infections, and tooth loss. However, this warning was largely based on small studies with no comparison group and no assessment of other risk factors such as limited dental care. This project will follow two groups of individuals with OUD who take either sublingual buprenorphine or methadone, to compare their oral health and understand barriers and facilitators of dental care. The results will be used to plan an intervention for preventing and treating oral diseases in this patient group.

Recently, concerns have been voiced that medications to treat opioid use disorder (OUD) may contribute to dental problems, including cavities and tooth loss. These concerns may contribute to barriers preventing use of these medications. A better understanding of the effects of these medications on oral complications is critical. This project will use national databases to link dental, medical, and pharmacy claims data for Medicaid- or commercially-insured new users of various medications for OUD to determine and compare oral health outcomes. The project will also examine the perspectives and experiences of people with OUD on oral health.