Opioid Use, Sedative Use
Conditions
Keywords
opioid, sedative, opiate
Brief summary
This study will examine the effects of doses of opioid/placebo and doses of sedative/placebo, alone and in combination. The primary outcomes are related to pharmacodynamic measures (subjective ratings of drug liking and other abuse-related effects; physiological outcomes) to determine the interaction effects of these compounds.
Detailed description
Gabapentin and oxycodone are commonly used in combination for the treatment of chronic pain. Gabapentin is now widely misused/abused with studies indicating that gabapentin abuse is especially common among individuals with opioid misuse. The nature of gabapentin's abuse-related effects have been described in case reports and online as sedative-like and opioid-like, with descriptive reports including sedation, euphoria, talkativeness and increased energy. Despite their widespread co-administration both for licit and illicit purposes, no controlled psychopharmacological studies to our knowledge have directly examined the effects of oxycodone (or another opioid agonist) and gabapentin in combination. This study's objective is to characterize the subjective effect profile of gabapentin, examine the interaction between gabapentin and oxycodone, and assess the acute analgesic response to gabapentin and oxycodone, alone and in combination, across a range of doses for each drug.
Interventions
DRUGOpioid Agonist
Abuse liability evaluation.
DRUGSedatives
Abuse liability evaluation.
Sponsors
National Institute on Drug Abuse (NIDA)
Sharon Walsh
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a randomized, double-blind, double-dummy, placebo- controlled design
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Healthy adults, ages 18-55 * Current non-medical use of opioids and sedatives
Exclusion criteria
* Physical dependence on opioids, alcohol, or benzodiazepines/sedatives/hypnotics * Seeking treatment for drug use * Significant medical problems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | This outcome was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session). | Participants rated their subjective drug liking on a standardized VAS scale (0 to 100). Raw data transformed to peak scores. Higher scores indicate greater drug effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | This outcome was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session). | Participants rated their subjective drug effect on a standardized VAS scale (0 to 100). Raw data transformed to peak scores. Higher scores indicate greater drug effects. |
| Change in Respiration Rate | Respiration rate was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session). | Respiration rate (number of breaths per minute). Raw data transformed to trough scores. Lower scores indicate greater impairment. |
| Change in End-tidal Carbon Dioxide (EtCO2) | EtCO2 recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session). | EtCO2 collected via capnograph monitored throughout each session. Raw data transformed to peak scores. Higher scores indicate greater impairment. |
| Change in Oxygen Saturation | Oxygen saturation recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session). | Oxygen saturation (measured as a percentage through pulse ox) monitored throughout each session. Raw data transformed to trough scores. Lower scores indicate greater impairment. |
Countries
United States
Participant flow
Pre-assignment details
This is a crossover study with 9 conditions tested in random order in each completing subject.
Participants by arm
| Arm | Count |
|---|---|
| Completing Participants Subjects who completed the full study (i.e., completed all dose conditions) Participants will receive non-therapeutic experimental doses of gabapentin (600 and 1200 mg, p.o.), alone and in combination with oxycodone (20 and 40 mg, p.o.). The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for gabapentin ≈ 2.5 hr; oxycodone ≈ 1.5 hr). Therefore, oxycodone will be administered 1 hr after gabapentin to align peak responses.
Opioid Agonist: Active opioid agonist or placebo, administered orally
Sedatives: Active sedative or placebo, administered orally | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Non-responsive to drug conditions. | 1 |
Baseline characteristics
| Characteristic | Completing Participants |
|---|---|
| Age, Continuous | 36.80 years STANDARD_DEVIATION 8.11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 5 / 11 | 5 / 11 | 0 / 11 | 1 / 11 | 0 / 11 | 1 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 1 / 11 | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
Outcome results
Primary
Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking
Participants rated their subjective drug liking on a standardized VAS scale (0 to 100). Raw data transformed to peak scores. Higher scores indicate greater drug effects.
Time frame: This outcome was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session).
Population: Per Protocol population, defined as participants completing the 9 experimental drug conditions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo / Placebo | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 7.40 Score on a scale | Standard Error 2.39 |
| Placebo / Oxycodone 20mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 39.00 Score on a scale | Standard Error 7.19 |
| Placebo / Oxycodone 40mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 40.80 Score on a scale | Standard Error 9.14 |
| Gabapentin 600mg / Placebo | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 24.50 Score on a scale | Standard Error 8.54 |
| Gabapentin 1200mg / Placebo | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 15.00 Score on a scale | Standard Error 8.7 |
| Gabapentin 600mg / Oxycodone 20mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 40.70 Score on a scale | Standard Error 9.1 |
| Gabapentin 1200mg / Oxycodone 20mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 34.50 Score on a scale | Standard Error 8.26 |
| Gabapentin 600mg / Oxycodone 40mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 56.50 Score on a scale | Standard Error 6.85 |
| Gabapentin 1200mg / Oxycodone 40mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking | 44.90 Score on a scale | Standard Error 8.29 |
Comparison: Peak scores were calculated for individual participants within each dose condition and analyzed in a one-factor model (drug condition) with a compound symmetry covariance structure.p-value: <0.0001Mixed Models Analysis
Secondary
Change in End-tidal Carbon Dioxide (EtCO2)
EtCO2 collected via capnograph monitored throughout each session. Raw data transformed to peak scores. Higher scores indicate greater impairment.
Time frame: EtCO2 recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session).
Population: Per Protocol population, defined as participants completing the 9 experimental drug conditions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo / Placebo | Change in End-tidal Carbon Dioxide (EtCO2) | 39.60 mm Hg (unit of pressure) | Standard Error 1.01 |
| Placebo / Oxycodone 20mg | Change in End-tidal Carbon Dioxide (EtCO2) | 41.20 mm Hg (unit of pressure) | Standard Error 0.87 |
| Placebo / Oxycodone 40mg | Change in End-tidal Carbon Dioxide (EtCO2) | 42.90 mm Hg (unit of pressure) | Standard Error 1.08 |
| Gabapentin 600mg / Placebo | Change in End-tidal Carbon Dioxide (EtCO2) | 39.10 mm Hg (unit of pressure) | Standard Error 0.64 |
| Gabapentin 1200mg / Placebo | Change in End-tidal Carbon Dioxide (EtCO2) | 38.40 mm Hg (unit of pressure) | Standard Error 0.48 |
| Gabapentin 600mg / Oxycodone 20mg | Change in End-tidal Carbon Dioxide (EtCO2) | 42.00 mm Hg (unit of pressure) | Standard Error 0.75 |
| Gabapentin 1200mg / Oxycodone 20mg | Change in End-tidal Carbon Dioxide (EtCO2) | 41.90 mm Hg (unit of pressure) | Standard Error 0.59 |
| Gabapentin 600mg / Oxycodone 40mg | Change in End-tidal Carbon Dioxide (EtCO2) | 44.80 mm Hg (unit of pressure) | Standard Error 0.68 |
| Gabapentin 1200mg / Oxycodone 40mg | Change in End-tidal Carbon Dioxide (EtCO2) | 43.90 mm Hg (unit of pressure) | Standard Error 0.9 |
Comparison: Peak scores were calculated for individual participants within each dose condition and analyzed in a one-factor model (drug condition) with a compound symmetry covariance structure.p-value: <0.0001Mixed Models Analysis
Secondary
Change in Oxygen Saturation
Oxygen saturation (measured as a percentage through pulse ox) monitored throughout each session. Raw data transformed to trough scores. Lower scores indicate greater impairment.
Time frame: Oxygen saturation recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session).
Population: Per Protocol population, defined as participants completing the 9 experimental drug conditions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo / Placebo | Change in Oxygen Saturation | 96.77 Percentage of oxygen in blood | Standard Error 0.4 |
| Placebo / Oxycodone 20mg | Change in Oxygen Saturation | 96.29 Percentage of oxygen in blood | Standard Error 0.25 |
| Placebo / Oxycodone 40mg | Change in Oxygen Saturation | 95.72 Percentage of oxygen in blood | Standard Error 0.53 |
| Gabapentin 600mg / Placebo | Change in Oxygen Saturation | 96.86 Percentage of oxygen in blood | Standard Error 0.58 |
| Gabapentin 1200mg / Placebo | Change in Oxygen Saturation | 96.87 Percentage of oxygen in blood | Standard Error 0.32 |
| Gabapentin 600mg / Oxycodone 20mg | Change in Oxygen Saturation | 96.59 Percentage of oxygen in blood | Standard Error 0.19 |
| Gabapentin 1200mg / Oxycodone 20mg | Change in Oxygen Saturation | 96.29 Percentage of oxygen in blood | Standard Error 0.28 |
| Gabapentin 600mg / Oxycodone 40mg | Change in Oxygen Saturation | 95.80 Percentage of oxygen in blood | Standard Error 0.45 |
| Gabapentin 1200mg / Oxycodone 40mg | Change in Oxygen Saturation | 95.61 Percentage of oxygen in blood | Standard Error 0.41 |
Comparison: Trough scores were calculated for individual participants within each dose condition and analyzed in a one-factor model (drug condition) with a compound symmetry covariance structure.p-value: 0.0002Mixed Models Analysis
Secondary
Change in Respiration Rate
Respiration rate (number of breaths per minute). Raw data transformed to trough scores. Lower scores indicate greater impairment.
Time frame: Respiration rate was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session).
Population: Per Protocol population, defined as participants completing the 9 experimental drug conditions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo / Placebo | Change in Respiration Rate | 12.70 Number of breaths per minute | Standard Error 0.68 |
| Placebo / Oxycodone 20mg | Change in Respiration Rate | 12.00 Number of breaths per minute | Standard Error 0.42 |
| Placebo / Oxycodone 40mg | Change in Respiration Rate | 11.50 Number of breaths per minute | Standard Error 0.54 |
| Gabapentin 600mg / Placebo | Change in Respiration Rate | 12.10 Number of breaths per minute | Standard Error 0.41 |
| Gabapentin 1200mg / Placebo | Change in Respiration Rate | 12.90 Number of breaths per minute | Standard Error 0.66 |
| Gabapentin 600mg / Oxycodone 20mg | Change in Respiration Rate | 11.80 Number of breaths per minute | Standard Error 0.51 |
| Gabapentin 1200mg / Oxycodone 20mg | Change in Respiration Rate | 12.10 Number of breaths per minute | Standard Error 0.59 |
| Gabapentin 600mg / Oxycodone 40mg | Change in Respiration Rate | 11.30 Number of breaths per minute | Standard Error 0.47 |
| Gabapentin 1200mg / Oxycodone 40mg | Change in Respiration Rate | 11.90 Number of breaths per minute | Standard Error 0.57 |
Comparison: Trough scores were calculated for individual participants within each dose condition and analyzed in a one-factor model (drug condition) with a compound symmetry covariance structure.p-value: 0.138Mixed Models Analysis
Secondary
Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect
Participants rated their subjective drug effect on a standardized VAS scale (0 to 100). Raw data transformed to peak scores. Higher scores indicate greater drug effects.
Time frame: This outcome was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 8 hours per session).
Population: Per Protocol population, defined as participants completing the 9 experimental drug conditions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo / Placebo | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 10.70 Score on a scale | Standard Error 2.94 |
| Placebo / Oxycodone 20mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 39.30 Score on a scale | Standard Error 6.32 |
| Placebo / Oxycodone 40mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 39.70 Score on a scale | Standard Error 8.05 |
| Gabapentin 600mg / Placebo | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 25.00 Score on a scale | Standard Error 7.43 |
| Gabapentin 1200mg / Placebo | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 21.50 Score on a scale | Standard Error 9.93 |
| Gabapentin 600mg / Oxycodone 20mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 39.10 Score on a scale | Standard Error 7.37 |
| Gabapentin 1200mg / Oxycodone 20mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 37.50 Score on a scale | Standard Error 7.73 |
| Gabapentin 600mg / Oxycodone 40mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 52.30 Score on a scale | Standard Error 8.36 |
| Gabapentin 1200mg / Oxycodone 40mg | Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect | 44.40 Score on a scale | Standard Error 8.51 |
Comparison: Peak scores were calculated for individual participants within each dose condition and analyzed in a one-factor model (drug condition) with a compound symmetry covariance structure.p-value: <0.0001Mixed Models Analysis