Multiple Sclerosis, Neuropathic Pain, Peripheral Neuropathy, Post-herpetic Neuralgia, Reflex Sympathetic Dystrophy, Spinal Cord Injury
Conditions
Keywords
cannabis, marijuana, neuropathy, antinociception, mood, cognition, neuropathic pain
Brief summary
This study theorized that a low dose of vaporized cannabis could alleviate nerve injury pain.
Detailed description
We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated.
Interventions
DRUGMild dose cannabis
3.53% THC by weight
DRUGLow dose cannabis
1.29% THC by weight
DRUGCannabis
0.00% THC by weight
Sponsors
Center for Medicinal Cannabis Research
VA Northern California Health Care System
University of California, Davis
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
* Age greater than 18 and less than 70 * Visual Analogue Scale (VAS pain intensity) greater than 3/10 * A negative urine drug screening test, i.e., no evidence of IV drug abuse * Neuropathic pain due to reflex sympathetic dystrophy, peripheral neuropathy, post-herpetic neuralgia, post-stroke pain, multiple sclerosis or spinal cord injury
Exclusion criteria
* Presence of another painful condition of greater severity than the neuropathic pain condition which is being studied. * Subjects with moderate-severe major depression, bipolar/mania, bipolar II/hypomania and schizophrenia or schizoaffective disorder. * Unstable Type 1 or 2 diabetes defined as blood glucose more than 156 mg/dl * History of traumatic brain injury * Uncontrolled medical condition, including coronary artery disease, hypertension, cerebrovascular disease, asthma, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), opportunistic infection, malignancy requiring active treatment, active substance abuse (alcohol or injection drugs). * Current use of marijuana (e.g., within 30 days of randomization) * Pregnancy as ascertained by a self-report and a mandatory commercial pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With 30% or Greater Reduction in Pain Intensity | baseline to six hours | The primary outcome variable, VAS Pain Intensity, was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).An assessment was performed before the administration of vaporized cannabis or placebo and hourly thereafter for six hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | baseline to six hours | The pain intensity scores for all of the time points (i.e., baseline prior to administration and up to 5 hours following administration of cannabis). VAS Pain Intensity was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain). |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at the UCDMC and VA Northern California Pain clinics,UCDMC Spinal Cord Injury Clinic, and newspaper advertisements. Between December 2009 and March 2011, 59 patients were consented to enroll in the study.
Pre-assignment details
Twenty subjects did not receive study medication: 9 withdrew for various reasons and 11 were disqualified following a medical evaluation with subsequent disclosure of exclusionary criteria on a physical exam or laboratory finding.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who were randomized | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age, Continuous | 50 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 36 | 0 / 37 | 0 / 38 |
| serious Total, serious adverse events | 0 / 36 | 0 / 37 | 0 / 38 |
Outcome results
Primary
Participants With 30% or Greater Reduction in Pain Intensity
The primary outcome variable, VAS Pain Intensity, was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).An assessment was performed before the administration of vaporized cannabis or placebo and hourly thereafter for six hours.
Time frame: baseline to six hours
Population: This was a cross over study. Ten of the 38 subjects who were exposed to placebo had a 30% reduction in pain intensity as compared to 21 of the 37 exposed to the low dose and 22 of the 36 receiving the medium dose of cannabis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mild Dose Cannabis | Participants With 30% or Greater Reduction in Pain Intensity | 61 percentage of participants |
| Low Dose Cannabis | Participants With 30% or Greater Reduction in Pain Intensity | 57 percentage of participants |
| Placebo Cannabis | Participants With 30% or Greater Reduction in Pain Intensity | 26 percentage of participants |
Secondary
Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis
The pain intensity scores for all of the time points (i.e., baseline prior to administration and up to 5 hours following administration of cannabis). VAS Pain Intensity was assessed by asking participants to indicate the intensity of their current pain on a 100-mm visual analog scale (VAS) between 0 (no pain) and 100 (worst possible pain).
Time frame: baseline to six hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mild Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Baseline prior to Administration of Cannabis | 57.3 units on a scale | Standard Deviation 24.1 |
| Mild Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 1 after Administration of Cannabis | 51.8 units on a scale | Standard Deviation 22.1 |
| Mild Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 2 after Administration of Cannabis | 44.3 units on a scale | Standard Deviation 26.8 |
| Mild Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 3 after Administration of Cannabis | 39.7 units on a scale | Standard Deviation 25.8 |
| Mild Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 4 after Administration of Cannabis | 40.4 units on a scale | Standard Deviation 26.9 |
| Mild Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 5 after Administration of Cannabis | 41.7 units on a scale | Standard Deviation 25.5 |
| Low Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 5 after Administration of Cannabis | 40.7 units on a scale | Standard Deviation 27.2 |
| Low Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Baseline prior to Administration of Cannabis | 54.4 units on a scale | Standard Deviation 23.4 |
| Low Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 3 after Administration of Cannabis | 38.2 units on a scale | Standard Deviation 27.1 |
| Low Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 4 after Administration of Cannabis | 39.5 units on a scale | Standard Deviation 27.2 |
| Low Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 1 after Administration of Cannabis | 49.8 units on a scale | Standard Deviation 25.7 |
| Low Dose Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 2 after Administration of Cannabis | 45.8 units on a scale | Standard Deviation 26.4 |
| Placebo Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 1 after Administration of Cannabis | 56.5 units on a scale | Standard Deviation 24.1 |
| Placebo Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 2 after Administration of Cannabis | 55.4 units on a scale | Standard Deviation 25.1 |
| Placebo Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 5 after Administration of Cannabis | 51.8 units on a scale | Standard Deviation 25.1 |
| Placebo Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 3 after Administration of Cannabis | 50.7 units on a scale | Standard Deviation 25 |
| Placebo Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Baseline prior to Administration of Cannabis | 57.5 units on a scale | Standard Deviation 22.8 |
| Placebo Cannabis | Visual Analogue Scale Pain Intensity Scores for Baseline and up to 5 Hours Following Administration of Vaporized Cannabis | Hour 4 after Administration of Cannabis | 48.1 units on a scale | Standard Deviation 25.6 |
Comparison: Hour 1 after Administration of Cannabisp-value: >0.05Mixed Models Analysis
Comparison: Hour 2 after Administration of Cannabisp-value: =0.0002Mixed Models Analysis
Comparison: Hour 3 after Administration of Cannabis (after the second inhalation of cannabis)p-value: <0.0001Mixed Models Analysis
Comparison: Hour 4 after Administration of Cannabisp-value: =0.0004Mixed Models Analysis
Comparison: Hour 5 after Administration of Cannabisp-value: =0.0018Mixed Models Analysis