Grants and Contracts Details
Description
Opioid misuse, including prescription opioids, heroin and fentanyl, is epidemic in the United States and
is associated with high morbidity and mortality. The current National Survey on Drug Use and Health estimates
that at least 2.6 million people met criteria for an opioid use disorder (including prescription opioids and heroin).
Opioid-related overdose deaths continue to climb with nearly 30,000 deaths reported in 2014. Toxicological
evidence from post-mortem studies reveals that polypharmacy is a very common finding in opioid-related
deaths, and it is especially common to find co-occurring substances with sedative properties. Despite the
widespread acknowledgment that non-opioid sedatives may enhance the risk of death from an opioid
overdose, few controlled data exist on the pharmacodynamic effects of opioids in combination with these
agents and their co-prescription by providers is common. These studies aim to fill this critical knowledge gap
by assessing agents with sedative properties that commonly are 1) prescribed with opioids (i.e.,
benzodiazepines, gabapentin), 2) abused in combination with opioids, and 3) found in combination at autopsy
(benzodiazepines, alcohol and gabapentin). Three inpatient human laboratory studies will be conducted that
employ rigorous controlled experimental procedures to characterize the pharmacological interaction between
oxycodone when taken in combination with either alprazolam (Experiment 1), alcohol (Experiment 2) or
gabapentin (Experiment 3). Individuals with appropriate recreational drug use histories, who are otherwise
healthy, will be enrolled. An initial dose finding phase will precede each study to ensure subject safety and
scientific rigor before proceeding to a robust randomized controlled design. The three studies will employ
randomized, placebo-controlled, within-subject, double-blind crossover designs and will be conducted in a
controlled hospital setting where appropriate medical supervision is available. Key safety outcomes, including
expired CO2 and other respiratory function indices, pharmacodynamic measures related to abuse potential,
and cognitive/psychomotor performance will be thoroughly examined over a range of doses for all drugs alone.
Pharmacokinetic data (Exp. 1) will also be collected to assess the potential pharmacokinetic interaction as an
underlying mechanism of action, and experimental analgesia/algesia data will be collected in Exp. 3 as
gabapentin is commonly co-prescribed for pain relief with opioids. The analytic approach will include traditional
statistics and modified isobolographic analyses to further elucidate the nature of the pharmacodynamic
interactions. The findings from these studies may directly inform prescribing practices and inform clinical
guidelines for physicians and other providers, regulatory decision-making, and may provide new information for
targeted interventions to reduce the harms of polysubstance prescribing and misuse.
Status | Active |
---|---|
Effective start/end date | 9/30/18 → 7/31/25 |
Funding
- National Institute on Drug Abuse: $3,029,574.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.