Medications Development for the Treatment of Cannabis Related Disorders

Stress (emotional, physical, social) facilitates drug seeking behavior through the
activation of the HPA axis, autonomic nervous system, and brain DA systems. Furthermore,
alterations within several neuropeptide systems (CRF, Substance P, and others) also
contribute to the role of stress in addiction. Central to this project is that anxiety and
stress responses are modulated by substance P and its preferred target, the NK1 receptor.
Therefore the aim of this pilot clinical trial is to determine the safety and efficacy of
aprepitant (a neurokinin 1 (NK1) receptor antagonist). We hypothesize that the NK1 receptor
antagonist, aprepitant, will be safe, tolerable and efficacious at reducing the withdrawal
symptoms, cue craving, and reinforcement value for both cannabis and tobacco resulting from
the cessation of either or both drugs. We will assess this hypothesis in the context of a
carefully controlled human laboratory study in which subjects (N=72) will be randomized in a
3 x 2 factorial design to one of 3 behavioral conditions; a) withdrawn from both substances,
b) withdrawn from tobacco only, or c) withdrawn from cannabis only, and to receive one of 2
medication dose conditions: placebo or aprepitant (160 mg/day). Medication will be
administered for 5 days, followed by a cue challenge, choice procedure, and then a
consequence (i.e., oral cannabis or a cigarette or money) also on day 5.