A limited number of pharmacological classes are widely recognized for being associated with abuse potential and these are typically regulated under the Controlled Substances Act before marketing. However, drugs from non-prototype pharmacological classes may be abused after introduction into the market posing new public health challenges and prompting a need for evaluation after marketing.
The aim of this project is to evaluate and characterize the risks associated with two agents, quetiapine and gabapentin, both of which are marketed, widely prescribed off-label, unscheduled, and for which clear signals of abuse and misuse have emerged in the U.S. and abroad. Two studies employing randomized, placebo-controlled, inpatient, within- subject designs will be conducted with otherwise healthy recreational drug abusing volunteers who report a history of recreational sedative use. Participants will undergo a qualification test session during which the response to a test dose of triazolam is determined. Study 1 will examine a range of doses of quetiapine (50, 100 and 200 mg, p.o.) in comparison to triazolam and placebo, Study 2 will examine a range of gabapentin doses (600, 1200, 1800 mg, p.o.) compared to triazolam, oxycodone and placebo. For each drug condition, experimental sessions will include 1) a Sample Session, during which standard abuse liability, safety and simulated driving data will be collected to capture the pharmacodynamic profile and time-action curve for each drug condition, and 2) a Self-Administration Session during which the reinforcing efficacy of each drug will be directly assessed using a progressive ratio procedure. One innovative feature of these studies is that driving simulation testing in the laboratory will be incorporated into the experimental design to evaluate psychomotor effects as they relate to impaired or drugged driving- a national public health concern that has been identified as a priority by the National Institute on Drug Abuse and the White House Office of National Drug Control Policy. These studies will provide important new information on the abuse liability characteristics of two widely prescribed agents, quetiapine and gabapentin, that may inform regulatory decision making and will provide important public health information regarding the risks related to impairment after use of these commonly prescribed and abused drugs.
This research will provide important information regarding the abuse potential of two widely used drugs, quetiapine and gabapentin, which are not presently controlled by the Drug Enforcement Agency but for which signals of abuse have emerged. Moreover, the risks of using these drugs and others (triazolam, oxycodone) on driving will be assessed and will inform prescribing practices and public safety.
