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The purposes of this study are 1) to determine if the administration of different low doses of CBD (5 mg, 20 mg, 50 mg and 100 mg) result in detectable subjective pleasant drug effect compared to placebo and 2) to qualitatively explore whether low dose CBD is associated with effects that are not detected with the available research tools.
Cannabis contains over 100 cannabinoids, the two most prominent being Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A growing body of evidence exists surrounding the effects of both THC and CBD, however, less is known about the specific effects of CBD concentrations alone. Most existing data regarding the effects of CBD come from studies where this compound is administered in high doses in a therapeutic context, and where the subject can be administered either CBD, THC or both together. These contexts are not representative of the current use by many consumers. Indeed, several available products contain CBD at much lower doses. The overall objective of this study is to evaluate the acute behavioral and biological effects of low doses of CBD (between 5-100mg) and placebo in occasional cannabis users. Potential outcomes not detected with usual assessment tools designed to evaluate THC-induced effects will also be explored.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CBD (Group 1) | Experimental | Group will receive four CBD doses (5 mg, 20 mg, 50 mg and 100 mg), and placebo (0 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence |
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| CBD (Group 2) | Experimental | Group will receive four CBD doses (5 mg, 20 mg, 50 mg and 100 mg), and placebo (0 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence |
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| CBD (Group 3) | Experimental | Group will receive four CBD doses (5 mg, 20 mg, 50 mg and 100 mg), and placebo (0 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. |
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| CBD (Group 4) | Experimental | Group will receive four CBD doses (5 mg, 20 mg, 50 mg and 100 mg), and placebo (0 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cannabis, placebo | Drug | Eligible participant will be randomize 1:1:1:1:1 to receive placebo, CBD (5mg, 20mg, 50mg and 100mg). Only one research product will be inhaled for each visit. The sequence will depend on the assigned randomization group. |
| Measure | Description | Time Frame |
|---|---|---|
| Pleasant drug effect | Pleasant drug effect will be assessed using a single item, visual analog scale, administered following administration of the study product at each study visit. It is rated on a continuous scale ranging from 0 (not at all) to 100 (extremely). | T1(10 minutes after inhalation) |
| Pleasant drug effect | Pleasant drug effect will be assessed using a single item, visual analog scale, administered following administration of the study product at each study visit. It is rated on a continuous scale ranging from 0 (not at all) to 100 (extremely). | T2 (80 minutes after inhalation) |
| Pleasant drug effect | Pleasant drug effect will be assessed using a single item, visual analog scale, administered following administration of the study product at each study visit. It is rated on a continuous scale ranging from 0 (not at all) to 100 (extremely). | T3 (140 minutes after inhalation) |
| Measure | Description | Time Frame |
|---|---|---|
| Drug Effects associated with cannabis administration | Drug Effects Questionnaire (twenty-three-item) will be use to assess participant's physical signs, symptoms associated with cannabis administration and desire to use cannabis. The Drug Effects Questionnaire uses visual analogue scale, ranging from 0 (not at all) to 100 (extremely). | T1 (10 minutes after inhalation) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in plasma concentration of CBD | Plasma levels of CBD will be determined by high performance liquid chromatography-tandem mass spectrometry at baseline and after inhalation. | Baseline and after inhalation at ( 5 minutes, 15 minutes, 80 minutes, 110 minutes, 140 minutes) |
| Change in plasma concentration of 7-Hydroxycannabidiol |
Inclusion Criteria:
Between 21 and 49 years of age, inclusively;
Have used cannabis at least once in lifetime AND have used cannabis three days or less in the 28 days prior to enrollment;
Be able to provide a signed informed consent;
Willing to comply with study procedures and requirements as per protocol, including to abstain from using other cannabis products or any drugs (except alcohol or nicotine) 7 days prior to study visits;
Have a forced expiratory volume in first second (FEV) sup 90 %;
Able to communicate and understand English or French language;
For female participants:
a. Without childbearing potential, defined as: i. postmenopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age); or ii. Documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or
b. With childbearing potential: i. Must have negative pregnancy test result at screening and at subsequent visits.
ii. AND have no pregnancy plan while on the trial iii. AND must agree to use a medically accepted method of birth control throughout the study.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pamela Lachance, PhD | Contact | 514-890-8000 | 30938 | pamela.lachance-touchette.chum@ssss.gouv.qc.ca |
| François-Olivier Hébert, PhD | Contact | 581-741-4941 | francois-olivier.hebert.chum@ssss.gouv.qc.ca |
| Name | Affiliation | Role |
|---|---|---|
| Didier Jutras-Aswad, MD,MS | Centre hospitalier de l'Université de Montréal (CHUM) | Principal Investigator |
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| ID | Term |
|---|---|
| D002189 | Marijuana Abuse |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C587251 | nabiximols |
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In this crossover design, participants will be administered both dosages of CBD and placebo during participation in the study. Participant will be randomly assigned to one of ten pre-determined sequences with a CBD or placebo product at 5 dosages (0 mg, 5 mg, 20 mg, 50 mg and 100 mg). Participants will be randomized based on a completely balanced 5 by 5 latin square
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| CBD (Group 5) | Experimental | Group will receive four CBD doses (5 mg, 20 mg, 50 mg and 100 mg), and placebo (0 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. |
|
| Drug Effects associated with cannabis administration | Drug Effects Questionnaire (twenty-three-item) will be use to assess participant's physical signs, symptoms associated with cannabis administration and desire to use cannabis. The Drug Effects Questionnaire uses visual analogue scale, ranging from 0 (not at all) to 100 (extremely). | T2 (80 minutes after inhalation) |
| Drug Effects associated with cannabis administration | Drug Effects Questionnaire (twenty-three-item) will be use to assess participant's physical signs, symptoms associated with cannabis administration and desire to use cannabis. The Drug Effects Questionnaire uses visual analogue scale, ranging from 0 (not at all) to 100 (extremely). | T3 (140 minutes after inhalation) |
| Change in dissociation | Dissociation will be assessed using the Clinician Administered Dissociative States Scale (CADSS) administered at Baseline (T0) and following administration of the study product (T1- 10 minutes, T2-60 minutes) at each study visit. The CADSS, a 28-items validated instrument, includes 5 observer items and 23 participant self-report items rated on a 5-point scale, ranging from 0 (not at all) to 4 (extremely). Minimum score :0 not at all; Maximum score 72 extremely dissociate. | Baseline and after inhalation at (10 minutes, 80 minutes) |
| Cannabis-Specific Subjective Effects | Subjective effects of cannabis will be assessed using both the positive and negative subscales of the Cannabis Experience Questionnaire administered following administration study product. Each item is rated on a 5-point scale, ranging from 1 (not at all) to 5 (severely).The positive subscale includes16 items related to euphoric experiences (maximum 90 and minimum 16). The negative subscale includes 25 items related to paranoid-dysphoric experiences (Maximum 125 and minimum 25). | T3 (140 minutes after inhalation) |
| Change in Affect | Affect will be measured using the Positive and Negative Affect Schedule administered at Baseline (T0) and following administration of the study product at each study visit. The Positive and Negative Affect Schedule is a 20-item validated questionnaire divided into subscales of positive (10 items) and negative affect (10 items). Each item is rated on a 5-point scale ranging from 1 (not at all) to 5 (extremely). For each subscale minimum is 10 and maximum 50. | Baseline and after inhalation at (10 minutes, 80 minutes, 140 minutes) |
| Change in Anxiety Symptoms | Symptoms of anxiety will be assessed using the States-Trait-Anxiety-Inventory, a 20-item validated self-report scale that measures the severity of anxiety in adults.. Each symptom is rated on a 4-point scale ranging from 1 (not at all) to 4 (very much). | Baseline and after inhalation at (10 minutes, 80 minutes and 140 minutes) |
| Change in Safety | Adverse events will be collected prior to administration of the study product (T0) and following administration of the study product (T1, T2 and T3) | Baseline and after inhalation at (10 minutes, 80 minutes, 140 minutes) |
| Change on cognition | The Cambridge Neuropsychological Test Automated Battery tests will be used for the rapid assessment of multiple cognitive components. | Baseline and after inhalation at T2 (80 minutes). |
| Visit Intoxication Assessment | Signs of intoxication will be assess using the modified Standardized Field Sobriety Test. | End of the visit, approximatively 180 minutes after inhalation |
Plasma levels of CBD will be determined by high performance liquid chromatography-tandem mass spectrometry at baseline and after inhalation. |
| Baseline and after inhalation at ( 5 minutes, 15 minutes, 80 minutes, 110 minutes, 140 minutes) |
| Change in plasma concentration of 7-Carboxy-Cannabidiol | Plasma levels of CBD will be determined by high performance liquid chromatography-tandem mass spectrometry at baseline and after inhalation. | Baseline and after inhalation at ( 5 minutes, 15 minutes, 80 minutes, 110 minutes, 140 minutes) |
| Change in plasma concentration of Anandamide | Plasma levels of CBD will be determined by high performance liquid chromatography-tandem mass spectrometry at baseline and after inhalation. | Baseline and after inhalation at ( 5 minutes, 15 minutes, 80 minutes, 110 minutes, 140 minutes) |