Conditions: Narcotic Abuse
Keywords: opioid oxycodone NK1 antagonist aprepitant intranasal abuse
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 9
Healthy volunteers: yes

Brief summary:
Addressing the issue of opioid dependence and tolerance has public health implications for the treatment of opioid abuse (both heroin as well as pharmaceutical opioids) and for the treatment of pain. Recent preclinical data suggest a role for Substance P (NK-1) receptors in modulating both the acute and chronic response to opioids. The objective of this study is to determine whether pretreatment with aprepitant, a selective neurokinin-1 (NK-1) antagonist can reduce the direct response to an opioid agonist (oxycodone) on measures related to abuse liability and reinforcing effects.

Detailed description:
Healthy adult volunteers with histories of illicit opioid use by the intranasal and oral routes will be admitted to this 6-week inpatient, crossover study. They will participate in 15 experimental test sessions, each lasting approximately 6.5 hours, during which they will receive a range of acute doses of aprepitant, including placebo, followed by challenge with oxycodone or placebo (given intranasally or orally). Multi-dimensional outcomes, including physiological (blood pressure, oxygen saturation, pupil diameter), subjective (questionnaires related to mood, abuse liability) and observer ratings will be collected repeatedly throughout each session. Data will be analyzed using parametric approaches to within-subject designs.

Arms:
arm 1: Placebo aprepitant/Placebo oxycodone IN/PO arm 2: Placebo aprepitant/ oxycodone 15 IN 0 PO arm 3: Placebo aprepitant/ oxycodone 30 IN 0 PO arm 4: Placebo aprepitant/ oxycodone 0 IN 20 PO arm 5: Placebo aprepitant/ oxycodone 0 IN 40 PO arm 6: Aprepitant 40 mg/ oxycodone 0 IN 0 PO arm 7: Aprepitant 40 mg/ oxycodone 0 IN 20 PO arm 8: Aprepitant 40 mg/ oxycodone 0 IN 40 PO arm 9: Aprepitant 40 mg/ oxycodone 15 IN 0 PO arm 10: Aprepitant 40 mg/ oxycodone 30 IN 0 PO arm 11: Aprepitant 200 mg/ oxycodone 0 IN 0 PO arm 12: Aprepitant 200 mg/ oxycodone 0 IN 20 PO arm 13: Aprepitant 200 mg/ oxycodone 0 IN 40 PO arm 14: Aprepitant 200 mg/ oxycodone 15 IN 0 PO arm 15: Aprepitant 200 mg/ oxycodone 30 IN 0 PO

Interventions: intervention 1: Aprepitant 0mg intervention 2: Aprepitant 40mg intervention 3: Aprepitant 200mg intervention 4: Oxycodone 0mg, p.o. intervention 5: Oxycodone 20mg, p.o. intervention 6: Oxycodone 40mg, p.o. intervention 7: Oxycodone 0mg, IN intervention 8: Oxycodone 15mg, IN intervention 9: Oxycodone 30mg, IN
Intervention descriptions: intervention 1: Aprepitant 0mg, p.o. pretreatment intervention 2: Aprepitant 40mg, p.o. pretreatment intervention 3: Aprepitant 200mg, p.o. pretreatment intervention 4: Oxycodone 0mg, p.o. intervention 5: Oxycodone 20mg, p.o. intervention 6: Oxycodone 40mg, p.o. intervention 7: Oxycodone 0mg, IN intervention 8: Oxycodone 15mg, IN intervention 9: Oxycodone 30mg, IN

Protocol document: