Dextromethorphan, Gabapentin, and Oxycodone to Treat Opioid-Induced Hyperalgesia

Opioid medications are frequently used for the treatment of moderate to severe pain;
however, individuals who use opioids have a high risk of becoming addicted. Opioid users who
abruptly stop using opioid drugs may experience withdrawal symptoms, including drug craving,
sweating, sleep disruption, nausea, irritability, and pain. Hyperalgesia, a severe and
excessive sensitivity to pain, is a serious condition that may also occur when opioid use is
reduced or discontinued. Opioid medications affect both the pain inhibitory and facilitatory
systems, meaning that while they are effective at treating pain in many individuals, they
also have the ability to intensify pain and cause hyperalgesia in some opioid users. Three
medications, dextromethorphan, gabapentin, and oxycodone, may alleviate the symptoms of
hyperalgesia and lessen an individual's sensitivity to pain. Further research is needed to
confirm the benefits of these medications for opioid addicts. The purpose of this study is
to compare the effectiveness of dextromethorphan, gabapentin, and oxycodone at reducing
opioid-induced hyperalgesia in methadone-maintained opioid addicts.

This study will involve three separate experiments. Participants in Experiment 1 will be
randomly assigned to receive either dextromethorphan or placebo; in Experiment 2,
participants will be randomly assigned to receive either gabapentin or placebo; and in
Experiment 3, participants will be randomly assigned to receive either oxycodone or placebo.
Each experiment will last 5 weeks. All 3 experiments will begin with a screening session.
Potential participants will undergo a physical exam and an electrocardiogram. Blood and
urine will be collected for laboratory tests and drug screening. Each individual's medical
and drug history will be reviewed and psychological and opiate withdrawal symptoms will be
assessed. Individuals who complete the screening and meet all study requirements will be
permitted to continue in the study.

All participants will be maintained on methadone throughout the study. Participants will
also receive either the study medication (dextromethorphan, gabapentin, or oxycodone) or
placebo four times per day beginning on Day 5. Study visits will take place once a week. At
each visit, medications for the previous week will be accounted for and medications for the
following week will be dispensed. Questionnaires and self-reports will be completed to
assess depression levels and drug use. Urine tests will be used to screen for the presence
of drugs and alcohol. During the study, participants will take part in four pain testing
sessions to measure pain threshold and tolerance; two sessions will take place during Week 1
and another two sessions will occur during Week 5. The pain testing sessions will include a
cold pressor (CP) test and an electrical stimulation (ES) procedure. The CP test will
involve placing an arm in ice water for a short period of time; the ES procedure will
involve stimulating muscle nerve endings via electrodes placed on the skin. Immediately
after the CP and ES sessions, blood will be drawn for laboratory testing. Participants will
again complete questionnaires and self-reports, and urine samples will be collected. Gift
cards will be offered as an incentive for attending study visits and having negative drug
tests.

Inclusion Criteria:

- Be between the ages of 18 and 55 years of age.

- Meets DSM-IV diagnostic criteria for opioid dependence

- Taking a stable dose of methadone for 6 weeks prior to study entry and is compliant
in methadone maintenance treatment

- Is in good physical health or under a physician's care if a medical condition
requires ongoing treatment

Exclusion Criteria:

- Known sensitivity to dextromethorphan, gabapentin, or oxycodone

- Currently dependent on alcohol, benzodiazepine, or any drug (other than nicotine)

- Currently in an acutely psychotic, severely depressed state and in need of inpatient
treatment

- Immediate suicide risk

- Neurological or psychiatric illness (e.g., peripheral neuropathy, schizophrenia,
neuropathic pain, Raynaud's disease, or urticaria)

- Acute medical condition that would make study participation medically dangerous
(e.g., acute hepatitis, unstable cardiovascular disease, liver disease, or kidney
disease)

- Liver enzyme values five times greater than normal

- Currently taking analgesic medication for a painful condition on a regular basis

- Current or past history of high blood pressure, heart disease, or stroke

- Currently using a pacemaker

- Pregnant or breastfeeding