Muscle Injury, Pain Relief, Recovery
Conditions
Brief summary
We aim to determine the efficacy of a controlled short-term trial of CBD ingestion for reducing symptomatic response and facilitating recovery following induced muscle injury. We will assess, in serial fashion, symptomatic response, functional limitations and recovery of the quadriceps muscle following induced injury in which CBD oil (or placebo) will be delivered using a sublingual route of administration during a 15-day pre-injury consumption and post-injury recovery phase. A double-blind, randomized, two-arm study design will be used and participants will be randomly assigned to either an active dose (n=15) or vehicle control group (n=15). The clinical outcomes include measures of muscular pain and disability along with measures of pain-related fear and anxiety.
Detailed description
Current research has shown evidence that phytocannabinoids may have a promising therapeutic potential in a variety of physical and psychological ailments, and cannabidiol (CBD) is of particular interest due to its positive safety profile, non-intoxicating effects and widespread capabilities in a number of musculoskeletal diseases. Three primary reasons people consume CBD on a global basis, in addition to the fact that it is non-intoxicating, are for symptomatic (pain) relief, anxiety reduction, and improved sleep quality. Very little is known about CBD and how it functions in the body from both an efficacy and mechanistic perspective, especially in humans. There is a large consumer base for this product that will be expanding exponentially in the next few years. Most of the evidence available is anecdotal from the personal testimony of consumers. We aim to determine the efficacy of a controlled short-term trial of CBD ingestion for reducing symptomatic response and facilitating recovery following induced muscle injury. We will assess, in serial fashion, symptomatic response, functional limitations and recovery of the quadriceps muscle following induced injury in which selected doses of CBD oil (or placebo) will be delivered using a sublingual route of administration during a 15-day pre-injury consumption and post-injury recovery phase. A double-blind, randomized, two-arm study design will be used and participants will be randomly assigned to either an active dose (n=15) or vehicle control group (n=15). Our clinical outcomes include measures of muscular pain and disability along with measures of pain-related fear and anxiety. Our laboratory-based study design is desirable and advantageous because it is a controlled method of tracking individuals using an experimental model of injury that is translatable to clinical populations. This exploratory study will provide preliminary data needed to support the hypotheses of a planned larger scale application.
Interventions
DRUGActive CBD
Participants will be provided a viscous liquid in a bottle with a syringe dropper containing CBD-extract oil at concentrations of 2000mg/30mL (high).
DRUGVehicle Control (Placebo)
Participants will be provided a viscous liquid in a bottle with a syringe dropper containing placebo containing no CBD oil (0mg/30 mL).
Sponsors
Consortium for Medical Marijuana Clinical Outcomes Research
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
a) male and female adults between the ages of 18-35 years and b) English speaking, and c) both female and male subjects must be currently practicing acceptable methods of birth control, such as abstinence, and methods of contraception (barriers, oral, patch or other prophylactic methods).
Exclusion criteria
a) current use of cannabis products on a regular basis or positive urine test for cannabis, b) current use of tobacco or nicotine containing products on a regular basis, c) currently taking prescription medication for management of anxiety disorders, depression, or ADHD, d) current use of nutritional or dietary supplements on a daily basis (e.g. ephedra, yohimbine, pro-hormones, creatine or anabolics), e) current use of OTC anti-inflammatory medications (e.g. Advil, Aleve, Aspirin) on a regular basis, f) history of seizure disorder, family history of seizure disorder, current or history of head trauma, liver disease, renal (kidney) disease, cardiovascular disease (including, but not limited to: hypotension, hypertension, tachycardia, and syncope), g) current medical condition that would prevent the participant from performing strenuous resistance exercise, h) weight lifting for the lower extremities (legs) more than twice a week, i) currently experiencing pain in the hips, leg, or knee region, j) pregnancy, lactating or positive urine pregnancy test, k) known allergy to CBD or coconut/sesame oil, l) an allergy to tree nuts (coconut).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Self-report Ratings of Muscle Soreness | Baseline (Day 1) | A muscle soreness inventory will be used to self-report the level of soreness. The muscle soreness inventory consists of rating soreness on a visual analog scale (VAS). A 10cm line is drawn with 0 (no soreness) on the left pole and 10 (extreme soreness) on the right pole. |
| Self-report Ratings of Disability | Baseline (Day 1) | Disability will be measured using the Lower Extremity Functional Scale (LEFS). LEFS score = SUM (points for all 20 activities) Interpretation: Minimum score: 0 Maximum score: 80 The lower the score the greater the disability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Catastrophizing Scale (PCS) | Baseline (Day 1) | 13-item, 5-point rating scale used to assess different thoughts that may be associated with experiencing pain. The PCS total score is computed by summing responses to all 13 items. PCS total scores range from 0 - 52. The PCS subscales are computed by summing the responses to the following items: Rumination: Sum of items 8, 9, 10, 11; Magnification: Sum of items 6, 7, 13; and Helplessness: Sum of items 1, 2, 3, 4, 5, 12; higher scores indicate worse outcome. |
| Pain Anxiety Symptom Scale - 20 (PASS-20) | Pre-exercise (Day 10) | 20 item, 5-point rating scale that assesses 4 theoretically distinct components of pain-related anxiety including cognitive anxiety (items 1 to 5), fear of pain (items 6 to 10), escape/avoidance behavior (items 11 to 15), and physiological anxiety (items 16 to 20). Each subscale is worth 20 points. Subscales are combined to compute total score. The total scale ranges from 0 to 100; higher scores indicate worse outcome. |
| Maximal Voluntary Isometric Contraction (MVIC) | Pre-exercise (Day 10) | maximum voluntary force produced during a static muscle contraction |
| Fear of Pain Questionnaire (FPQ-9) | Baseline (Day 1) | 9-item, 5-point rating scale to quantify fear of specific situations that normally produce pain. Each subscale contains 3 items, so the possible range of scores for each subscale is 3 through 15. Subscales are combined to compute total score. The Total score has a range of 9 through 45; higher scores indicate worse outcome. |
| Pain Anxiety Symptom Scale (PASS-20) | Post-exercise (Day 15) | 20 item, 5-point rating scale that assesses 4 theoretically distinct components of pain-related anxiety including cognitive anxiety (items 1 to 5), fear of pain (items 6 to 10), escape/avoidance behavior (items 11 to 15), and physiological anxiety (items 16 to 20). Each subscale is worth 20 points. Subscales are combined to compute total score. The total scale ranges from 0 to 100; higher scores indicate worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active CBD-extract Active Dose (2000mg/30mL hemp extract = 67.5mg/day)
Active CBD: Participants will be provided a viscous liquid in a bottle with a syringe dropper containing CBD-extract oil at concentrations of 2000mg/30mL (high). | 15 |
| Vehicle-Control (Placebo) (0mg/30mL hemp extract = no hemp extract)
Vehicle Control (Placebo): Participants will be provided a viscous liquid in a bottle with a syringe dropper containing placebo containing no CBD oil (0mg/30 mL). | 14 |
| Total | 29 |
Baseline characteristics
| Characteristic | Active CBD-extract | Vehicle-Control (Placebo) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 14 Participants | 29 Participants |
| Age, Continuous | 20.1 years STANDARD_DEVIATION 1.4 | 19.8 years STANDARD_DEVIATION 1.6 | 20.0 years STANDARD_DEVIATION 1.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 13 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment United States | 15 participants | 14 participants | 29 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 0 / 15 | 0 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 |
Outcome results
Primary
Self-report Ratings of Disability
Disability will be measured using the Lower Extremity Functional Scale (LEFS). LEFS score = SUM (points for all 20 activities) Interpretation: Minimum score: 0 Maximum score: 80 The lower the score the greater the disability.
Time frame: Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Self-report Ratings of Disability | 77.2 score on a scale | Standard Deviation 5.4 |
| Vehicle-Control (Placebo) | Self-report Ratings of Disability | 76.7 score on a scale | Standard Deviation 4.6 |
Primary
Self-report Ratings of Disability
Disability will be measured using the Lower Extremity Functional Scale (LEFS). LEFS score = SUM (points for all 20 activities) Interpretation: Minimum score: 0 Maximum score: 80 The lower the score the greater the disability.
Time frame: Pre-exercise (Day 10)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Self-report Ratings of Disability | 77.1 score on a scale | Standard Deviation 4.8 |
| Vehicle-Control (Placebo) | Self-report Ratings of Disability | 75.9 score on a scale | Standard Deviation 5.4 |
Primary
Self-report Ratings of Disability
Disability will be measured using the Lower Extremity Functional Scale (LEFS). LEFS score = SUM (points for all 20 activities) Interpretation: Minimum score: 0 Maximum score: 80 The lower the score the greater the disability.
Time frame: Post-exercise (Day 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Self-report Ratings of Disability | 67.7 score on a scale | Standard Deviation 13.2 |
| Vehicle-Control (Placebo) | Self-report Ratings of Disability | 60.1 score on a scale | Standard Deviation 27.4 |
Primary
Self-report Ratings of Muscle Soreness
A muscle soreness inventory will be used to self-report the level of soreness. The muscle soreness inventory consists of rating soreness on a visual analog scale (VAS). A 10cm line is drawn with 0 (no soreness) on the left pole and 10 (extreme soreness) on the right pole.
Time frame: Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Self-report Ratings of Muscle Soreness | 0.0 score on a scale | Standard Deviation 0 |
| Vehicle-Control (Placebo) | Self-report Ratings of Muscle Soreness | 0.0 score on a scale | Standard Deviation 0 |
Primary
Self-report Ratings of Muscle Soreness
A muscle soreness inventory will be used to self-report the level of soreness. The muscle soreness inventory consists of rating soreness on a visual analog scale (VAS). A 10cm line is drawn with 0 (no soreness) on the left pole and 10 (extreme soreness) on the right pole.
Time frame: Pre-exercise (Day 10)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Self-report Ratings of Muscle Soreness | 4.0 score on a scale | Standard Deviation 7.4 |
| Vehicle-Control (Placebo) | Self-report Ratings of Muscle Soreness | 2.3 score on a scale | Standard Deviation 5.9 |
Primary
Self-report Ratings of Muscle Soreness
A muscle soreness inventory will be used to self-report the level of soreness. The muscle soreness inventory consists of rating soreness on a visual analog scale (VAS). A 100mm line is drawn with 0 (no soreness) on the left pole and 100 (extreme soreness) on the right pole.
Time frame: Post-exercise (Day 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Self-report Ratings of Muscle Soreness | 47.8 score on a scale | Standard Deviation 27.3 |
| Vehicle-Control (Placebo) | Self-report Ratings of Muscle Soreness | 61.6 score on a scale | Standard Deviation 22.3 |
Secondary
Fear of Pain Questionnaire (FPQ-9)
9-item, 5-point rating scale to quantify fear of specific situations that normally produce pain. Each subscale contains 3 items, so the possible range of scores for each subscale is 3 through 15. Subscales are combined to compute total score. The Total score has a range of 9 through 45; higher scores indicate worse outcome.
Time frame: Pre-exercise (Day 10)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Fear of Pain Questionnaire (FPQ-9) | 21.5 score on a scale | Standard Deviation 5 |
| Vehicle-Control (Placebo) | Fear of Pain Questionnaire (FPQ-9) | 18.8 score on a scale | Standard Deviation 7.1 |
Secondary
Fear of Pain Questionnaire (FPQ-9)
9-item, 5-point rating scale to quantify fear of specific situations that normally produce pain. Each subscale contains 3 items, so the possible range of scores for each subscale is 3 through 15. Subscales are combined to compute total score. The Total score has a range of 9 through 45; higher scores indicate worse outcome.
Time frame: Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Fear of Pain Questionnaire (FPQ-9) | 23.8 score on a scale | Standard Deviation 5.4 |
| Vehicle-Control (Placebo) | Fear of Pain Questionnaire (FPQ-9) | 21.3 score on a scale | Standard Deviation 5.7 |
Secondary
Maximal Voluntary Isometric Contraction (MVIC)
maximum voluntary force produced during a static muscle contraction measured as Newton-meters.
Time frame: Post-exercise (Day 15)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Maximal Voluntary Isometric Contraction (MVIC) | 128.4 force output in Newton-meters | Standard Deviation 50.2 |
| Vehicle-Control (Placebo) | Maximal Voluntary Isometric Contraction (MVIC) | 121.0 force output in Newton-meters | Standard Deviation 44.7 |
Secondary
Maximal Voluntary Isometric Contraction (MVIC)
maximum voluntary force produced during a static muscle contraction
Time frame: Pre-exercise (Day 10)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Maximal Voluntary Isometric Contraction (MVIC) | 138.5 Newton-meters | Standard Deviation 23.3 |
| Vehicle-Control (Placebo) | Maximal Voluntary Isometric Contraction (MVIC) | 129.3 Newton-meters | Standard Deviation 42.1 |
Secondary
Maximal Voluntary Isometric Contraction (MVIC)
maximum voluntary force produced during a static muscle contraction measured in Newton-meters.
Time frame: Post-exercise (Day 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Maximal Voluntary Isometric Contraction (MVIC) | 122.4 force output in Newton-meters | Standard Deviation 41.2 |
| Vehicle-Control (Placebo) | Maximal Voluntary Isometric Contraction (MVIC) | 102.4 force output in Newton-meters | Standard Deviation 32.6 |
Secondary
Pain Anxiety Symptom Scale - 20 (PASS-20)
20 item, 5-point rating scale that assesses 4 theoretically distinct components of pain-related anxiety including cognitive anxiety (items 1 to 5), fear of pain (items 6 to 10), escape/avoidance behavior (items 11 to 15), and physiological anxiety (items 16 to 20). Each subscale is worth 20 points. Subscales are combined to compute total score. The total scale ranges from 0 to 100; higher scores indicate worse outcome.
Time frame: Pre-exercise (Day 10)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Pain Anxiety Symptom Scale - 20 (PASS-20) | 39.5 score on a scale | Standard Deviation 15.4 |
| Vehicle-Control (Placebo) | Pain Anxiety Symptom Scale - 20 (PASS-20) | 49.9 score on a scale | Standard Deviation 22.1 |
Secondary
Pain Anxiety Symptom Scale (PASS-20)
20 item, 5-point rating scale that assesses 4 theoretically distinct components of pain-related anxiety including cognitive anxiety (items 1 to 5), fear of pain (items 6 to 10), escape/avoidance behavior (items 11 to 15), and physiological anxiety (items 16 to 20). Each subscale is worth 20 points. Subscales are combined to compute total score. The total scale ranges from 0 to 100; higher scores indicate worse outcome.
Time frame: Post-exercise (Day 15)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Pain Anxiety Symptom Scale (PASS-20) | 39.1 score on a scale | Standard Deviation 16.9 |
| Vehicle-Control (Placebo) | Pain Anxiety Symptom Scale (PASS-20) | 47.9 score on a scale | Standard Deviation 21.4 |
Secondary
Pain Catastrophizing Scale (PCS)
13-item, 5-point rating scale used to assess different thoughts that may be associated with experiencing pain. The PCS total score is computed by summing responses to all 13 items. PCS total scores range from 0 - 52. The PCS subscales are computed by summing the responses to the following items: Rumination: Sum of items 8, 9, 10, 11; Magnification: Sum of items 6, 7, 13; and Helplessness: Sum of items 1, 2, 3, 4, 5, 12; higher scores indicate worse outcome.
Time frame: Baseline (Day 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Pain Catastrophizing Scale (PCS) | 21.1 score on a scale | Standard Deviation 6.5 |
| Vehicle-Control (Placebo) | Pain Catastrophizing Scale (PCS) | 26.4 score on a scale | Standard Deviation 11.7 |
Secondary
Pain Catastrophizing Scale (PCS)
13-item, 5-point rating scale used to assess different thoughts that may be associated with experiencing pain. The PCS total score is computed by summing responses to all 13 items. PCS total scores range from 0 - 52. The PCS subscales are computed by summing the responses to the following items: Rumination: Sum of items 8, 9, 10, 11; Magnification: Sum of items 6, 7, 13; and Helplessness: Sum of items 1, 2, 3, 4, 5, 12; higher scores indicate worse outcome.
Time frame: Pre-exercise (Day 10)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Pain Catastrophizing Scale (PCS) | 21.3 score on a scale | Standard Deviation 7.5 |
| Vehicle-Control (Placebo) | Pain Catastrophizing Scale (PCS) | 25.4 score on a scale | Standard Deviation 11.2 |
Secondary
Pain Catastrophizing Scale (PCS)
13-item, 5-point rating scale used to assess different thoughts that may be associated with experiencing pain. The PCS total score is computed by summing responses to all 13 items. PCS total scores range from 0 - 52. The PCS subscales are computed by summing the responses to the following items: Rumination: Sum of items 8, 9, 10, 11; Magnification: Sum of items 6, 7, 13; and Helplessness: Sum of items 1, 2, 3, 4, 5, 12; higher scores indicate worse outcome.
Time frame: Post-exercise (Day 15)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CBD-extract | Pain Catastrophizing Scale (PCS) | 21.4 score on a scale | Standard Deviation 10.1 |
| Vehicle-Control (Placebo) | Pain Catastrophizing Scale (PCS) | 23.9 score on a scale | Standard Deviation 10.3 |