Cannabis, Opioid Use, Unspecified, Pain
Conditions
Keywords
Clinical Trial, Phase II, Analgesia, Abuse Potential
Brief summary
This is a single-group, within-subject, double-blind, double-dummy, placebo and active-controlled study evaluated whether the FDA-approved cannabinoid dronabinol (Marinol) would enhance analgesia, subjective reports, and cognitive performance when compared to the FDA-approved opioid hydromorphone (Dilaudid).
Detailed description
This was a human laboratory systematic examination of whether adding the FDA-approved cannabinoid dronabinol (Marinol; oral) to the FDA-approved opioid hydromorphone (Dilaudid; oral) would change the experience of hydromorphone as rated by laboratory measures of pain, subjective reports of drug effects, and cognitive performance. Subjects are healthy individuals with no history of drug use disorder. Study subjects and staff were completed blinded to the study drugs and the class of drugs under investigation and were informed that subjects may receive opioids, stimulants, cannabinoids, benzodiazepines, over the counter medications, and/or placebo. All participants completed all sessions. Sessions lasted up to 8-hours and were conducted at least 7 days apart on an outpatient basis. Primary outcomes were collected from participants prior to dosing and at several hour periods post-dosing.
Interventions
Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Each participant completed each of the 5 study conditions (identified here as arms).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18-75 * Urine sample tests negative for common illicit substances of abuse, including cannabis * Medically cleared to take study medications * Are not pregnant or breast feeding * Willing to comply with the study protocol.
Exclusion criteria
* Meet DSM-5 criteria for alcohol/substance use disorder * Taking opioids for pain * Previous adverse reaction to a cannabinoid product * Prescribed and taking stimulants or benzodiazepines * Answer yes to item 1 of the Brief Pain Inventory indicating chronic pain * Self-report any illicit drug use in the past 7 days * Presence of any clinically significant medical/psychiatric illness judged by the investigators to put subject at elevated risk for experiencing an adverse event * History of seizure disorder * Have a known allergy to the study medications or sesame seed oil * Taking medications contraindicated with hydromorphone or dronabinol * Have a history of clinically significant cardiac arrhythmias or vasopastic disease * Have an abnormal and clinically-significant ECG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task | Baseline and time of hand withdrawal from cold pressor, up to 60 seconds | Compare study conditions in seconds to withdraw hand from cold pressor laboratory pain task, where longer time periods reflect higher tolerance to pain. |
| Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale | 8-hour study session | Mean peak of Visual Analog Scale ratings of Drug Effect (0-100) compared across each study condition, with higher ratings reflecting stronger drug effects. |
| Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior | Baseline and 8-hours | Within-subject comparison of study conditions on the Digit Symbol Substitution Test (DSST), a measure of cognitive performance that is sensitive to drug effects, wherein lower percent scores reflect worse performance and suggest greater drug-related impairment. |
Countries
United States
Participant flow
Pre-assignment details
This is a within-subject study, and all participants (n=29) completed all study conditions. The same 29 participants moved from one treatment arm to the next.
Participants by arm
| Arm | Count |
|---|---|
| All Participants This is a within group study and same participants went through all treatment arms. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 30.4 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 29 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 14 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 | 0 / 29 | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 12 / 29 | 22 / 29 | 11 / 29 | 25 / 29 | 21 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 | 0 / 29 | 0 / 29 | 0 / 29 |
Outcome results
Primary
Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior
Within-subject comparison of study conditions on the Digit Symbol Substitution Test (DSST), a measure of cognitive performance that is sensitive to drug effects, wherein lower percent scores reflect worse performance and suggest greater drug-related impairment.
Time frame: Baseline and 8-hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + Placebo Condition | Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior | 10.2 Mean Percent Correct |
| Hydromorphone (Oral) 4mg + Placebo Condition | Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior | 5.1 Mean Percent Correct |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 2.5mg | Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior | 10.1 Mean Percent Correct |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 5.0mg | Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior | 10.3 Mean Percent Correct |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 10mg | Mean Change From Baseline in Maximum Percent Correct on Digit Symbol Substitution Test of Cognitive Behavior | 3.6 Mean Percent Correct |
p-value: 0.51Mixed Models Analysis
Primary
Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task
Compare study conditions in seconds to withdraw hand from cold pressor laboratory pain task, where longer time periods reflect higher tolerance to pain.
Time frame: Baseline and time of hand withdrawal from cold pressor, up to 60 seconds
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Placebo Condition | Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task | 25.4 seconds | Standard Error 12.7 |
| Hydromorphone (Oral) 4mg + Placebo Condition | Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task | 33.9 seconds | Standard Error 15.7 |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 2.5mg | Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task | 31.7 seconds | Standard Error 10.9 |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 5.0mg | Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task | 36.7 seconds | Standard Error 12.6 |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 10mg | Mean Change From Baseline in Seconds to Withdraw Hand From Cold Pressor Laboratory Pain Task | 18.1 seconds | Standard Error 5.4 |
p-value: 0.61Mixed Models Analysis
Primary
Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale
Mean peak of Visual Analog Scale ratings of Drug Effect (0-100) compared across each study condition, with higher ratings reflecting stronger drug effects.
Time frame: 8-hour study session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Placebo Condition | Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale | 10.0 score on a scale | Standard Deviation 10.1 |
| Hydromorphone (Oral) 4mg + Placebo Condition | Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale | 51.1 score on a scale | Standard Deviation 22.9 |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 2.5mg | Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale | 55.7 score on a scale | Standard Deviation 29.4 |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 5.0mg | Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale | 55.7 score on a scale | Standard Deviation 29.3 |
| Hydromorphone (Oral) 4mg + Dronabinol (Oral) 10mg | Mean Peak Rating of Drug Effect (0-100) as Measured by the Visual Analog Rating Scale | 56.9 score on a scale | Standard Deviation 31.7 |
p-value: <0.0001Mixed Models Analysis