Dextromethorphan, Gabapentin, and Oxycodone to Treat Opioid-Induced Hyperalgesia
Condition: Hyperalgesia; Opioid-Related Disorders
MeSH terms: Hyperalgesia; Opioid-Related Disorders
Study type: Interventional

Summary: 
      Individuals who reduce or stop use of opioid medications are at risk for developing
      hyperalgesia, which is an increased sensitivity to pain. This study will compare the
      effectiveness of dextromethorphan, gabapentin, and oxycodone at reducing hyperalgesia in
      individuals addicted to opioids who are concurrently receiving methadone treatment.
    

Detailed description: 
      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.
    

Intervention name(s): Gabapentin
Intervention type(s): Drug
Intervention description(s): Gabapentin initiated up to a daily dose of 2400mg PO x 5 weeks
Intervention MeSH terms: Gabapentin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Opiate Addiction; Opiate Dependence