Spinal Cord Diseases, Spinal Cord Injuries
Conditions
Keywords
cannabis, central neuropathic pain, analgesia
Brief summary
This study will demonstrate that vaporized marijuana results in antinociception when compared to placebo in subjects with spinal cord injury. To further evaluate potential benefits and side effects, the effect of different strengths of cannabis on mood, cognition, and psychomotor performance will also be measured.
Detailed description
This study will demonstrate that vaporized cannabis can produce antinociceptive effects compared to placebo in human subjects with spinal cord injury (SCI). A within-subject crossover study of the effects of cannabis versus placebo on spontaneous and evoked pain will be performed. A synopsis of antinociception with mood, cognitive impairment, psychomotor performance, and side effects will be obtained to help evaluate the utility of vaporized marijuana in SCI neuropathic pain. This study will compare the analgesic and side effect profile of low (3.5%) to high dose (7.0%) delta 9-tetrahydrocannabinol in subjects with spinal cord injury pain. It is hypothesized that a low dose will produce a lesser degree of neuropsychological impairment while maintaining a similar degree of pain relief to the higher dose. The use of two different strengths will help determine tolerable dosing for the treatment of SCI neuropathic pain.
Interventions
DRUGVaporization of Cannabis
Randomized, Controlled Crossover Trial of Vaporized Cannabis using different strengths of THC in patients with Central Neuropathic Pain Active Comparator: Vaporized High Dose 6.7% THC Active Comparator: Vaporized High Dose 2.9% THC Placebo Comparator: Vaporized Placebo THC
Sponsors
VA Northern California Health Care System
University of California, San Diego
National Institute on Drug Abuse (NIDA)
Barth Wilsey
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age greater than 18 and less than 70 2. Pain intensity ≥ 4/10 3. Neuropathic pain defined as chronic pain in an area of sensory abnormality corresponding to the spinal cord or nerve root lesion, and the pain should have no primary relation to movement, inflammation or other local tissue damage 4. Leeds Assessment of Neuropathic Symptoms and Signs score greater than or equal to 12 5. Spinal cord injury of 3 or more months duration (to avoid spontaneous recovery obfuscating generalizability)
Exclusion criteria
1. Known concomitant cerebral damage/cognitive impairment (TBI, Alzheimer's Disease Vascular dementia, Parkinson's disease, dementia with Lewy Bodies and Front temporal dementia 2. Clinically significant or unstable medical condition (i.e., cardiac, respiratory, hepatic or renal disease) that, in the opinion of the investigator, would compromise participation in the study 3. Neurologic disorders unrelated to spinal cord injury that may confound the assessment of the central neuropathic pain due to spinal cord injury (hereditary neuropathies; diabetic peripheral neuropathy; traumatic neuropathy; and immune-mediated neuropathies) 4. Active substance abuse within past year using The Substance Abuse Module of Diagnostic Interview Schedule for DSM-IV 5. Pregnancy as ascertained by a self-report and a mandatory commercial pregnancy test 6. Currently on probation or parole. 7. Hx of Schizophrenia, Bipolar Depression with Mania, current suicidal ideation or past history of suicide attempt 8. Severe depression (Patient Health Questionnaire-9 ≥ 15) 9. Current suicidal ideation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving a Reduction in Pain Intensity of 30% or More | hourly pain assessments for 8 hours | Number of participants achieving a reduction of pain intensity of 30% or more, a level believed to be clinically important, was estimated for each treatment dose. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled via recruitment from the UC Davis Medical Center Spinal Cord Injury Clinic, IRB-approved recruitment letters and newspaper advertisements.
Pre-assignment details
Screening for inclusion criteria (e.g., age \> 18 and ≤ 70, pain intensity ≥ 4/10 and Leeds Assessment of Neuropathic Symptoms and Signs, a pain scale based on analysis of sensory description and bedside examination of sensory dysfunction. A threshold of ≥12 on this instrument was utilized to substantiate neuropathic pain.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants received all interventions | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 46.4 years STANDARD_DEVIATION 13.6 |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 38 | 0 / 41 |
| other Total, other adverse events | 0 / 41 | 0 / 38 | 1 / 41 |
| serious Total, serious adverse events | 0 / 41 | 0 / 38 | 0 / 41 |
Outcome results
Primary
Number of Participants Achieving a Reduction in Pain Intensity of 30% or More
Number of participants achieving a reduction of pain intensity of 30% or more, a level believed to be clinically important, was estimated for each treatment dose.
Time frame: hourly pain assessments for 8 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo THC | Number of Participants Achieving a Reduction in Pain Intensity of 30% or More | 18 participants |
| 2.9% THC | Number of Participants Achieving a Reduction in Pain Intensity of 30% or More | 26 participants |
| 6.7% THC | Number of Participants Achieving a Reduction in Pain Intensity of 30% or More | 35 participants |
Comparison: The number needed to treat (NNT) to achieve 30% pain reduction during the 8-hour period was 4 (95% CI: 2.1-25.3) for the lower dose vs. placebo, and 3 (95% CI: 1.6-4.2) for the higher dose versus placebo.p-value: <0.05Mixed Models Analysis