Effects of Experimental Sleep Disturbances on Receptor Function of Study Drug

Subjects are provided an 8-hour sleep opportunity. Two speakers are placed 12 inches from the head of the bed and four remote-activated mechanical vibrators are placed underneath the mattress. EEG microarousals (\>3 s), as defined according to standard criteria, are elicited at a frequency of 30 or more events per hour.

On the third day of the in-patient visit participants will undergo multiple injections of study medication or placebo. This is a double-blind within-subject Phase II trial. As such, study medications must remain blinded. Participants may receive a medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter pain medications, or placebo (saline).

An 8-hour sleep opportunity period starting from lights out is divided into eight, one-hour intervals. One of the intervals is randomly determined to be a 60 minute forced awakening, during which no sleep is permitted. Each of the remaining seven, 60-minute intervals are subdivided into tertiles (20 min. blocks). A 20-min forced awakening (FA) is randomly scheduled to occur in either the 1st, 2nd, or 3rd tertile of each hour. During FAs, staff keep subjects awake, either by voice or gentle shaking.

Subjects sleep normally for an 8 hour period.