Cannabis, Opioid Use, Pain
Conditions
Keywords
Clinical Trial, Analgesia, Phase II, 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 cannabidiol (CBD; Epidiolex) would enhance analgesia, subjective reports, and cognitive performance when compared to the FDA-approved opioid hydromorphone (Dilaudid). This is study 2 is a series of studies.
Detailed description
This was a human laboratory systematic examination of whether adding the FDA-approved cannabinoid cannabidiol (CBD; Epidiolex; 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
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Study drug administration will be concealed from all study staff and participants to prevent bias in outcomes.
Intervention model description
Within-subject study
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 or cannabinoid 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 * ALT or AST levels \>3x ULN and/or Bilirubin levels \>2x ULN during Screening * Current (past 60-day) suicidal thoughts or past year history of suicidal behavior * Taking medications contraindicated with hydromorphone or cannabidiol * 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 |
|---|---|---|
| Peak Cold Pressor Tolerance | 8 hour study session | Peak amount of time participant submerged hand in cold pressor (5 degree circulating cold water) laboratory test of pain as a function of double- blinded study medications (range 0 -300). |
| Peak Self-report Rating of Drug Effect (0-100), as Measured by the Visual Analog Rating Scale | 8 hour study session | Peak self-report rating of Drug Effect on a 0 (none at all) to 100 (extremely) visual analog scale as a function of double- blinded study medication, wherein higher values indicate stronger subjectively-experienced drug effects. |
| Peak Number Accurate on Circular Lights | 8 hour study session | Peak number accuracy on the Circular Lights fine motor task as a function of double-blinded study drug administration. Participants were provided 60 seconds to press buttons that are lit in randomized order and displayed automatically on a circular lights wall mounted unit. The primary outcome is the number of lit buttons that were accurately pressed within 60 seconds, which is a metric to assess fine motor impairment. Lower numbers are indicative of greater drug-related impairment. There is no upper limit on the circular lights task. |
Countries
United States
Participant flow
Recruitment details
This is a within-subject study, and all participants (n=31) completed all study conditions. The same 31 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. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 33.3 years STANDARD_DEVIATION 11.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 2 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 | 16 Participants |
| Region of Enrollment United States | 31 Participants |
| Sex: Female, Male Female | 17 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 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 8 / 31 | 20 / 31 | 15 / 31 | 22 / 31 | 20 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 | 0 / 31 |
Outcome results
Primary
Peak Cold Pressor Tolerance
Peak amount of time participant submerged hand in cold pressor (5 degree circulating cold water) laboratory test of pain as a function of double- blinded study medications (range 0 -300).
Time frame: 8 hour study session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo+Placebo | Peak Cold Pressor Tolerance | 118.6 minutes | Standard Error 8.8 |
| Hydromorphone+Placebo | Peak Cold Pressor Tolerance | 130.8 minutes | Standard Error 8.9 |
| Hydromorphone (Oral) 4mg + Cannabidiol 50mg | Peak Cold Pressor Tolerance | 161.1 minutes | Standard Error 10.1 |
| Hydromorphone (Oral) 4mg + Cannabidiol 100mg | Peak Cold Pressor Tolerance | 163.2 minutes | Standard Error 9.9 |
| Hydromorphone (Oral) 4mg + Cannabidiol 200mg | Peak Cold Pressor Tolerance | 154.6 minutes | Standard Error 9.6 |
p-value: 0.195ANOVA
Primary
Peak Number Accurate on Circular Lights
Peak number accuracy on the Circular Lights fine motor task as a function of double-blinded study drug administration. Participants were provided 60 seconds to press buttons that are lit in randomized order and displayed automatically on a circular lights wall mounted unit. The primary outcome is the number of lit buttons that were accurately pressed within 60 seconds, which is a metric to assess fine motor impairment. Lower numbers are indicative of greater drug-related impairment. There is no upper limit on the circular lights task.
Time frame: 8 hour study session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo+Placebo | Peak Number Accurate on Circular Lights | 64.9 correct responses | Standard Error 1 |
| Hydromorphone+Placebo | Peak Number Accurate on Circular Lights | 59.2 correct responses | Standard Error 1 |
| Hydromorphone (Oral) 4mg + Cannabidiol 50mg | Peak Number Accurate on Circular Lights | 64.1 correct responses | Standard Error 1 |
| Hydromorphone (Oral) 4mg + Cannabidiol 100mg | Peak Number Accurate on Circular Lights | 63.6 correct responses | Standard Error 0.9 |
| Hydromorphone (Oral) 4mg + Cannabidiol 200mg | Peak Number Accurate on Circular Lights | 64.3 correct responses | Standard Error 0.9 |
p-value: 0.074ANOVA
Primary
Peak Self-report Rating of Drug Effect (0-100), as Measured by the Visual Analog Rating Scale
Peak self-report rating of Drug Effect on a 0 (none at all) to 100 (extremely) visual analog scale as a function of double- blinded study medication, wherein higher values indicate stronger subjectively-experienced drug effects.
Time frame: 8 hour study session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo+Placebo | Peak Self-report Rating of Drug Effect (0-100), as Measured by the Visual Analog Rating Scale | 4.8 units on a scale | Standard Error 0.7 |
| Hydromorphone+Placebo | Peak Self-report Rating of Drug Effect (0-100), as Measured by the Visual Analog Rating Scale | 12.6 units on a scale | Standard Error 1.4 |
| Hydromorphone (Oral) 4mg + Cannabidiol 50mg | Peak Self-report Rating of Drug Effect (0-100), as Measured by the Visual Analog Rating Scale | 15.7 units on a scale | Standard Error 1.7 |
| Hydromorphone (Oral) 4mg + Cannabidiol 100mg | Peak Self-report Rating of Drug Effect (0-100), as Measured by the Visual Analog Rating Scale | 18.0 units on a scale | Standard Error 1.6 |
| Hydromorphone (Oral) 4mg + Cannabidiol 200mg | Peak Self-report Rating of Drug Effect (0-100), as Measured by the Visual Analog Rating Scale | 17.9 units on a scale | Standard Error 1.6 |
p-value: <0.001ANOVA