Odontalgia, Toothache
Conditions
Keywords
Cannabidiol (CBD), Opioid, Dose, Dental, Pain, Epidiolex, CBD
Brief summary
The purpose of this study is to evaulate CBD as a therapeutic approach for dental pain. Eligible subjects presented with emergency dental pain will be give a single dose of Epidiolex (FDA-approved CBD) or placebo and will be monitored for 3 hours for pain symptoms and psychologic effects.
Detailed description
CBD is a non-psychoactive, non-addictive compound of cannabis that has shown analgesic and anti-inflammatory properties. Epidiolex is the only FDA-approved oral CBD solution and will be the drug of choice in this study.
Interventions
Cannabidiol (CBD): is the primary non-psychoactive and non-addictive compound in cannabis, has already shown potential in treating pain such as arthritis, neuropathic, cancer and chronic pain
DRUGPlacebo
Placebo drug will be a solution with the same taste, texture and color as the drug.
Sponsors
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients who satisfy eligibility criteria and provide written informed consent will be randomly assigned to either 1) CBD 10mg/kg single dose (drug: Epidiolex 100mg/ml solution) or 2) CBD 20mg/kg single dose, or 3) Placebo group (drug: placebo)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Healthy adults 18-75 years old, ASA I or II * permanent tooth with moderate to severe odontogenic pain, i.e. ≥30 on a 100mm VAS, * clinical pulpal diagnosis of irreversible pulpitis or pulpal necrosis, and periapical diagnosis of symptomatic apical periodontitis * test negative for recent cannabis use and/or other drugs of abuse including alcohol (urine tests collected at screening visit), and participant * able to understand the forms (English or Spanish) and provide informed written consent.
Exclusion criteria
* ASA Class III or IV * patients with hepatic impairment * pregnant or lactating women * Patients on drugs metabolized by enzymes that also metabolize CBD (e.g. clobazam, diazepam, topiramate, warfarin) * self-reported prior experience inhaling cannabis (either via smoking or vaporization), use of opioids in the month prior to screening/treatment visit, and/or NSAIDS or acetaminophen 6 hours prior to treatment * unwilling to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intra-group VAS Pain Intensity and Maximum Pain Relief | Baseline to 180 minutes | Patients will report their pain level using a 100mm Visual Analogue Scale at baseline, measured at baseline and 180 minutes. Score is measured on a 100mm scale, scored 0-100, with a lower score indicating less pain. |
| Bite Force Measurement | Baseline, 90 minutes and 180 minutes | Bite force is measured by biting down on the Bite Fork at various times to measure change in value. The digital bite transducer is a previously validated instrument used to assess changes in the bite forces (N) before and after the intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 3 hours and 7 Days | Included: Psychoactive effects, mood changes, and report other side effects after single dose of Epidiolex |
Countries
United States
Participant flow
Recruitment details
The study population consisted of adult patients 18 to 75 y old, presenting at the UT Health School of Dentistry, San Antonio, Texas, with moderate to severe odontogenic pain, defined as ≥30 mm on a 100-mm visual analog scale (VAS)
Participants by arm
| Arm | Count |
|---|---|
| Epidiolex 10mg/kg Single Dose After drug administration, subjects will be monitored for 3 hours, and pain intensity and safety data will be collected at various time points. Ibuprofen 600mg (or acetaminophen/codeine 650/60mg, if a contraindication for ibuprofen exists) will be provided in the 3-hour observation period as rescue medication if needed. Subjects will be encouraged to wait at least 60min after administration of the drug study before consuming the rescue medication. It will be given at the patient's request. If rescue medication was required, the study drug will still be dosed as per protocol, and time-to -rescue analysis will be performed. Then, the recommended root canal therapy will be performed the same or the next day.
Epidiolex 100 mg/mL Oral Solution: Cannabidiol (CBD): is the primary non-psychoactive and non-addictive compound in cannabis, has already shown potential in treating pain such as arthritis, neuropathic, cancer and chronic pain | 20 |
| Epidiolex 20mg/kg Single Dose The 20mg/kg dose is the maximum recommended daily dose from the manufacturer. After drug administration, subjects will be monitored for 3 hours, and pain intensity and safety data will be collected at various time points. Ibuprofen 600mg (or acetaminophen/codeine 650/60mg, if a contraindication for ibuprofen exists) will be provided in the 3-hour observation period as rescue medication if needed. Subjects will be encouraged to wait at least 60min after administration of the drug study before consuming the rescue medication. It will be given at the patient's request. If rescue medication was required, the study drug will still be dosed as per protocol, and time-to -rescue analysis will be performed. Then, the recommended root canal therapy will be performed the same or the next day.
Epidiolex 100 mg/mL Oral Solution: Cannabidiol (CBD): is the primary non-psychoactive and non-addictive compound in cannabis, has already shown potential in treating pain such as arthritis, neuropathic, cancer and chronic pain | 20 |
| Placebo Group Placebo drug will be a solution with the same taste, texture and color as the drug. After drug administration, subjects will be monitored for 3 hours, and pain intensity and safety data will be collected at various time points. Ibuprofen 600mg (or acetaminophen/codeine 650/60mg, if a contraindication for ibuprofen exists) will be provided in the 3-hour observation period as rescue medication if needed. Subjects will be encouraged to wait at least 60min after administration of the drug study before consuming the rescue medication. It will be given at the patient's request. If rescue medication was required, the study drug will still be dosed as per protocol, and time-to -rescue analysis will be performed. Then, the recommended root canal therapy will be performed the same or the next day.
Placebo: Placebo drug will be a solution with the same taste, texture and color as the drug. | 21 |
| Total | 61 |
Baseline characteristics
| Characteristic | Epidiolex 10mg/kg Single Dose | Epidiolex 20mg/kg Single Dose | Placebo Group | Total |
|---|---|---|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 12.66 | 44.75 years STANDARD_DEVIATION 11.61 | 43.1 years STANDARD_DEVIATION 16.78 | 44.15 years STANDARD_DEVIATION 13.68 |
| Body Mass Index (BMI) | 33.5 kg/m^2 STANDARD_DEVIATION 6.42 | 33.32 kg/m^2 STANDARD_DEVIATION 6.63 | 32.32 kg/m^2 STANDARD_DEVIATION 5.5 | 33.04 kg/m^2 STANDARD_DEVIATION 6.18 |
| Race/Ethnicity, Customized Black | 4 Participants | 2 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic | 11 Participants | 16 Participants | 16 Participants | 43 Participants |
| Race/Ethnicity, Customized Hispanic/Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 2 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 21 participants | 61 participants |
| Sex: Female, Male Female | 13 Participants | 16 Participants | 11 Participants | 40 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 10 Participants | 21 Participants |
| Weight | 94.37 Kg STANDARD_DEVIATION 21.04 | 87.71 Kg STANDARD_DEVIATION 22.21 | 92.43 Kg STANDARD_DEVIATION 22.7 | 91.50 Kg STANDARD_DEVIATION 21.98 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 | 0 / 23 |
| other Total, other adverse events | 10 / 21 | 10 / 20 | 5 / 23 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 23 |
Outcome results
Primary
Bite Force Measurement
Bite force is measured by biting down on the Bite Fork at various times to measure change in value. The digital bite transducer is a previously validated instrument used to assess changes in the bite forces (N) before and after the intervention.
Time frame: Baseline, 90 minutes and 180 minutes
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Epidiolex 10mg/kg Single Dose | Bite Force Measurement | 90 minutes | 86 Newtons |
| Epidiolex 10mg/kg Single Dose | Bite Force Measurement | Baseline | 61 Newtons |
| Epidiolex 10mg/kg Single Dose | Bite Force Measurement | 180 minutes | 80 Newtons |
| Epidiolex 20mg/kg Single Dose | Bite Force Measurement | 90 minutes | 59 Newtons |
| Epidiolex 20mg/kg Single Dose | Bite Force Measurement | Baseline | 53 Newtons |
| Epidiolex 20mg/kg Single Dose | Bite Force Measurement | 180 minutes | 66 Newtons |
| Placebo Group | Bite Force Measurement | Baseline | 54 Newtons |
| Placebo Group | Bite Force Measurement | 180 minutes | 65 Newtons |
| Placebo Group | Bite Force Measurement | 90 minutes | 66 Newtons |
Primary
Intra-group VAS Pain Intensity and Maximum Pain Relief
Patients will report their pain level using a 100mm Visual Analogue Scale at baseline, measured at baseline and 180 minutes. Score is measured on a 100mm scale, scored 0-100, with a lower score indicating less pain.
Time frame: Baseline to 180 minutes
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Epidiolex 10mg/kg Single Dose | Intra-group VAS Pain Intensity and Maximum Pain Relief | Baseline | 63 score on a scale |
| Epidiolex 10mg/kg Single Dose | Intra-group VAS Pain Intensity and Maximum Pain Relief | 180 minutes | 21 score on a scale |
| Epidiolex 20mg/kg Single Dose | Intra-group VAS Pain Intensity and Maximum Pain Relief | Baseline | 69 score on a scale |
| Epidiolex 20mg/kg Single Dose | Intra-group VAS Pain Intensity and Maximum Pain Relief | 180 minutes | 20 score on a scale |
| Placebo Group | Intra-group VAS Pain Intensity and Maximum Pain Relief | Baseline | 63 score on a scale |
| Placebo Group | Intra-group VAS Pain Intensity and Maximum Pain Relief | 180 minutes | 48 score on a scale |
Secondary
Number of Participants With Adverse Events
Included: Psychoactive effects, mood changes, and report other side effects after single dose of Epidiolex
Time frame: 3 hours and 7 Days
Population: All subjects enrolled, regardless of whether they completed the study. Adverse effects were self reported. Some subjects were lost to follow up for the 7 day self assessment, so did not complete the self assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epidiolex 10mg/kg Single Dose | Number of Participants With Adverse Events | 3 hour | 9 Participants |
| Epidiolex 10mg/kg Single Dose | Number of Participants With Adverse Events | 7 day | 2 Participants |
| Epidiolex 20mg/kg Single Dose | Number of Participants With Adverse Events | 3 hour | 6 Participants |
| Epidiolex 20mg/kg Single Dose | Number of Participants With Adverse Events | 7 day | 0 Participants |
| Placebo Group | Number of Participants With Adverse Events | 3 hour | 1 Participants |
| Placebo Group | Number of Participants With Adverse Events | 7 day | 2 Participants |