5HT3 Antagonists to Treat Opioid Withdrawal and to Prevent the Progression of Physical Dependence

This study will be split into two separate investigations, aim 1 and aim 2. Study aim 1 (Prevention of Opioid Withdrawal) will investigate whether ondansetron, a 5HT3-receptor antagonist, can reduce or prevent withdrawal signs and symptoms in patients physically dependent on opioids to treat chronic back pain. In this aim, study participants will be titrated onto sustained release oral morphine for 30 days after which time they will return to the lab to undergo naloxone-induced withdrawal with either 8 mg ondansetron pre-treatment (30 min prior to naloxone-induced withdrawal) or placebo. Participants will then return to their titrated dose of oral morphine for one week before returning for the second study session in which they will receive the opposite pre-treatment (8 mg ondansetron or placebo) 30 minutes prior to naloxone-induced withdrawal. Objective opioid withdrawal score (OOWS), subjective opioid withdrawal score (SOWS) and Profile of Mood States (POMS) will be assessed at baseline and five or seven times during the study sessions at 30 and 37 days post titration. Beck Depression Inventory, Roland-Morris Questionnaire and State-Trait Anxiety Inventory and VAS Pain Score will be assessed at baseline as well as at both study sessions (30 and 37 days post titration). Study aim 2 (Prevention of Physical Dependence) will investigate whether ondansetron, a 5HT3 receptor antagonist, can prevent physical dependence in patients taking opioids chronically for controlling chronic back pain. Participants will taper onto sustained release oral morphine for 10 days then will maintain the effective dose for twenty days (total of 30 days) while simultaneously taking 8 mg ondansetron or placebo three times daily with morphine dose. After 30 days of morphine plus 8 mg ondansetron or placebo, study participants will return to the lab to undergo naloxone-induced withdrawal. OOWS, SOWS, POMS, pain visual analogue scale (VAS), Beck Depression Inventory and Roland Morris Disability Index will be administered at baseline and at the beginning of each study session (30 days post titration). Furthermore OOWS, SOWS and POMS will be administered twice during the first study session and at least five times during the second study session (Day 30): at the beginning of the session, after IV insertion, and after naloxone-induced opioid withdrawal.