Research at Wayne State University launched to combat the country’s opioid use epidemic received another boost from the National Institute on Drug Abuse recently, thanks to a new $1.8 million grant to launch phase two of a study led by Mark Greenwald, Ph.D., the Gertrude Levin Endowed Chair in Addiction and Pain Biology and a professor of Psychiatry and Behavioral Neurosciences.

Dr. Greenwald, who also directs the department’s Substance Abuse Research Division, is the principal investigator on grant R33 DA044946, “Opioid/Benzodiazepine Polydrug Abuse: Integrating Research on Mechanisms, Treatment and Policies.”

The project will test the hypothesis that benzodiazepine/opioid polydrug use is maintained by a dual-deficit in affective/hedonic regulation – excess negative and deficient positive emotional states – which is linked to neurocognitive (executive control) and behavioral impairments.

“By translating findings from population and clinical levels to laboratory-based approaches, this project will address the complex and harmful nature of benzodiazepine/opioid polydrug use with the goals of advancing mechanistic understanding, and improving treatment outcomes and policies to reduce risks of overdose, disability and death,” Dr. Greenwald said.

The phase two award was issued based on meeting scientific milestones during a R21 award from NIDA concluding at the end of this month that used epidemiological and clinical interview methods in patients in treatment for opioid + benzodiazepine-use problems.

The three-year project period for this new laboratory-based human psychopharmacology study will begin Sept. 1.

In participants with a history of benzodiazepine/opioid polysubstance use, the study aims to determine whether, at screening, differing use patterns are associated with different profiles on affective, neurocognitive and behavioral phenotypes, including more lifetime drug-use consequences, and greater price-inelasticity for opioid and benzodiazepine drugs using behavioral economic simulation methods; and in the lab, experimental drug administration of alprazolam/morphine (sequential and simultaneous) versus either drug alone or placebo differentially alters affective/hedonic phenotypes in different behavioral choice procedures.

“Although COVID slowed our progress, we met our scientific milestones. Our initial hypotheses were confirmed, even though we haven’t recruited as many patients as anticipated, but we will continue to recruit. We have been approved by NIDA to continue our research program in the present R33 award with participants who are not currently in treatment for their substance use,” Dr. Greenwald said. “We will extensively screen participants in person, so we will be able to compare findings between treatment-involved and non-involved individuals.”

In the new sample they will test, under highly-controlled laboratory conditions, the effects of an opioid drug (morphine) and short-acting benzodiazepine (alprazolam) alone, and in sequential and simultaneous oral administration, relative to placebo, on affective, neurocognitive and behavioral outcome measures.

The study team includes co-principal investigator and Professor of Psychiatry Cynthia Arfken, Ph.D., who is providing biostatistical input and analyses; co-investigator and Associate Professor of Psychiatry Leslie Lundahl, Ph.D., who will oversee clinical screening and neurocognitive testing and assist with safety monitoring; and co-investigator Tim Roehrs, Ph.D., who will assist with measures of sleep, sleepiness and insomnia in the patient population. Dr. Roehrs is director of Research at the Sleep Disorders and Research Center of Henry Ford Health System and a professor in the Department of Psychiatry and Behavioral Neurosciences.

As part of the study, participants will stay overnight at a Henry Ford facility, and Dr. Roehrs will oversee nocturnal polysomnographic (EEG) recordings.

“We will also send participants home after each drug exposure with portable devices that can record sleep activity. That way, we can track whether these experimental drug exposures alter same-night sleep efficiency and REM sleep. This aspect of polydrug use has not been studied under controlled conditions, so the results should be very informative,” Dr. Greenwald added.

The clinical trial is registered at ClinicalTrials.Gov as NCT05006079.