Back to resultsCannabidiol for the Treatment of Anxiety Disorders: An 8-Week Pilot Study
Primary Purpose
Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder
Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Cannabidiol (CBD) Oil Capsules
Sunflower Lecithin Oil in Capsule
Sponsored by
About this trial
This is an interventional treatment trial for Generalized Anxiety Disorder focused on measuring Anxiety Disorders, Cannabidiol, Cannabis
Eligibility Criteria
Inclusion Criteria:
- Male or female outpatients 21-65 years of age with a primary psychiatric diagnosis of either GAD, SAD, PD or agoraphobia as defined by DSM-5 criteria and a HAM-A score of ≥ 22.
- Physical exam and laboratory findings without clinically significant abnormalities.
- Participants must agree to abstain from recreational cannabis use for the duration of the study.
- Concomitant psychotropic medication use will be allowed provided that the dose has been stable for 8 weeks prior to randomization. (including antidepressants, anti-psychotics, anti-convulsants, benzodiazepines, stimulants, mood stabilizers)
- The ability to comprehend and satisfactorily comply with protocol requirements.
- Written informed consent given prior to entering the baseline period of the study.
Exclusion Criteria:
- Current recreational or medicinal use of cannabis within 4 weeks of study initiation.
- Participants with a lifetime history of cannabis use disorder or other substance use disorders (except tobacco use disorder)will be excluded.
- Participants with a lifetime history of daily cannabis use will be excluded.
- Dose changes of concomitant medication will not be permitted during the study period.
- Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months), or women who are planning on becoming pregnant.
- Diagnosis of any of the following mental disorders as defined by the DSM-5: a lifetime history of schizophrenia or any other psychosis, mental retardation, organic medical disorders, bipolar disorder. Entry of patients with obsessive compulsive disorder or posttraumatic stress disorder will be permitted if the anxiety disorder is judged to be the predominant disorder, in order to increase accrual of a clinically relevant sample.
- Major depression will be allowed if not severe (Montgomery Asberg Depression Rating Scale-MADRS ≥ 25). Patients with significant suicidal ideation (MADRS item 10 score > 3) or who have enacted suicidal behaviours within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
- Participants with a family history of psychosis will be excluded.
- Participants who have a history of adverse reactions to cannabis will be excluded.
Sites / Locations
- MacAnxiety Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cannabidiol (CBD) Oil Capsules
Sunflower Lecithin Oil in Capsule
Arm Description
Pure CBD in sunflower lecithin oil, flexibly dosed at 200-800 mg per day
1-4 capsules daily
Outcomes
Primary Outcome Measures
Hamilton Anxiety Rating Scale (HAM-A)
The 14-item HAM-A was developed to assess general anxiety symptoms in a clinical population and has proven sensitive to change with treatment. It is a clinician-rated measure and will be administered at each visit by a trained, blinded rater, using the Structured Interview Guide for the HAM-A. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) are summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.
Secondary Outcome Measures
Clinical Global Impression - Severity (CGI-S)
The CGI-S is a clinician-rated instrument used to assess global severity of symptoms. The CGI-S ranges from 1 (normal, not ill) to 7 (among the most severely ill).
Clinical Global Impression - Improvement (CGI-I)
The CGI-I is a clinician-rated instrument used to assess overall improvement of illness. The CGI-I ranges from 1 (very much improved) to 7 (very much worse).
Generalized Anxiety Disorder-7 (GAD-7)
The GAD-7 is a self-reported questionnaire that measures the severity of various signs of GAD. It contains seven items with a 4-point scale (range: 0 to 3). The total possible score is ranged from 0 to 21, with higher scores representing greater severity of GAD.
Liebowitz Social Anxiety Scale- Self Report (LSAS-SR)
The LSAS-SR is a 24 item scale that provides separate scores for fear and avoidance in social and performance situations with higher scores representing increased social anxiety. The LSAS-SR contains three total scores 1) total fear score (0-72), 2) total avoidance score (0-72) and total overall score (0-144).
Panic and Agoraphobia Scale (PAS)
The PAS is a measure of the severity of illness in patients with panic disorder (with or without agoraphobia). It has 13 items with a 5-point scale (range: 0-4). The total possible score is ranged from 0 to 52, with higher scores representing increased severity of illness. It contains 5 sub-scales: panic attacks, agoraphobic avoidance, anticipatory anxiety, disability, and functional avoidance (health concerns).
Quick Inventory of Depressive Symptomology (QIDS)
The QIDS is a self-report measure of depression. It contains 16 items with a 4-point scale (range: 0 to 3) which assess the severity of the nine diagnostic symptom criteria used in the DSM: Sleep disturbance, sad mood, decrease/increase in appetite/weight, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, and psychomotor agitation/retardation. The total possible score is ranged from 0 to 27, with higher scores representing greater severity of depression.
Sheehan Disability Scale (SDS)
The SDS is a 3 question instrument designed to assess functional impairment associated with mental disorders in three domains: work impairment, social impairment, and impairment of family life or home responsibilities. Each sub-scale score ranges from 0 to 10 and a total disability score, calculated as the sum of scores for each question ranges from 0 to 30. Higher scores reflect greater impairment.
World Health Organization Disability Assessment Scale (WHODAS 2.0)
The WHODAS 2.0 is a 36-item self-administered questionnaire that covers 6 domains of functioning, including: Cognition, mobility, self-care, getting along with people, life activities, participation. Each question ranges from 'none' to 'extreme or cannot do'. The scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3) and "extreme" (4) - are summed to give a total score that ranges from 0 to 144, with higher scores representing a greater degree of functional limitation.
Insomnia Severity Index (ISI)
The ISI has 7 questions with a 5-point score (range: 0 to 4). The total possible score is ranged from 0 to 28, with higher scores reflecting greater severity of sleep difficulty.
Marijuana Craving Questionnaire
The Marijuana Craving Questionnaire is a 47-item self-report instrument that assesses marijuana craving along four dimensions: compulsivity, emotionality, expectancy, and purposefulness. Each item is answered with a 7-point scale from 1 (strongly disagree) to 7 (strongly agree).
Obsessive Compulsive Inventory-Revised (OCI-R)
The OCI-R is a self-report scale for assessing symptoms of Obsessive-Compulsive Disorder (OCD). It consists of 18 questions with a 5-point scale (range: 0 to 4). The possible range of scores is 0 to 72, with higher scores indicating a greater likelihood of the presence of OCD.
PTSD Checklist (PCL-5)
The PCL-5 is a 20 item self-report measure that assesses symptoms of PTSD. Each item is rated on a 5-point scale from 0 (not at all) to 4 (extremely). The possible range of scores is 0 to 80, with higher scores indicating greater severity of PTSD.
Drug Effects Questionnaire (DEQ)
The DEQ assesses the extent to which participants 1) feel any substance effect(s), 2) feel high, 3) like the effects, 4) dislike the effects, and 5) want more of the substance using 100mm Visual Analog Scales.
Marijuana Withdrawal Checklist
The Marijuana Withdrawal Checklist has 22 items that assess mood, behavioural, and physical symptoms associated with marijuana withdrawal. Each item is rated on a 4-point scale from 0 (none) to 3 (severe). A total score is obtained by summing each of the item totals (range 0 to 66). Higher scores indicated more severe symptoms associated with marijuana withdrawal.
Shipley II: Verbal
Measures verbal intelligence quotient (IQ) - crystallized intelligence
Shipley II: Abstraction
Measures abstract intelligence quotient (IQ) - fluid intelligence
Digits Forward Test
Measures attention
Digits Backward Test
Measures working memory
Go/No-Go Test
Measures behavioural inhibition
Monetary Choice Questionnaire
Measures impulsive decision making
Probabilistic Choice Questionnaire
Measures risky decision making
Trails A and B Task
Measures visual attention and switching
Rey Auditory Verbal Learning Test
Measures short-term auditory-verbal memory
Simple Visual Reaction Time Task
Measures reaction time
Sustained Attention to Response Task
Measures sustained attention
Experimental Drug Purchase Task
Measures drug abuse liability
Inflammatory Markers
Serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α and IFN-γ
Full Information
NCT ID
NCT03549819
First Posted
May 15, 2018
Last Updated
February 10, 2023
Sponsor
McMaster University
Collaborators
Tilray
1. Study Identification
Unique Protocol Identification Number
NCT03549819
Brief Title
Cannabidiol for the Treatment of Anxiety Disorders: An 8-Week Pilot Study
Official Title
Cannabidiol for the Treatment of Anxiety Disorders: An 8-Week Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2021 (Actual)
Primary Completion Date
December 15, 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
McMaster University
Collaborators
Tilray
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This proposed study aims to evaluate the efficacy of daily Cannabidiol (CBD) Oil Capsules in treating symptoms of DSM-5 anxiety disorders, using a two-arm, 8-week randomized, placebo-controlled trial in adults aged 21-65 years. The study will also evaluate the relationship between inflammation, anxiety and CBD using biological markers as well as examine the neuro-cognitive effects of CBD treatment.
Detailed Description
The study will be a randomized, double-blind, placebo-controlled parallel design comparing the efficacy and safety of flexibly dosed CBD Oil capsules versus placebo for the treatment of adults, aged 21 to 65 years with a primary Diagnostic and Statistical Manual 5 (DSM-5) anxiety disorder: Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), Panic Disorder (PD), or agoraphobia. A total 50 participants (n=25/cell) who meet the inclusion criteria will be randomized to receive 1 of 2 treatments in a 1:1 ratio: CBD Oil Capsules or matching placebo, with the possibility of dose titration during this 8-week period. The outcomes of this research will make a significant contribution to enhance our current understanding of the effects of cannabis in anxiety disorders.
To be involved in this study, the study doctor will first check that the participant is qualified. This is called screening, and will involve a clinical assessment, physical exam and urine tests. This visit may take up to 3 hours to complete.
If the participant successfully completes screening the participant will start treatment in one of the two assigned treatment groups. Treatment is 8 weeks. Participants will come to the study clinic 6 times during the treatment phase of the study. Each visit will last 1 to 2 hours. Each visit will involve reporting any side effects that the participant may have experienced, completing questionnaires about mood and anxiety symptoms, sleep, overall functioning and alcohol and drug use. Participants will also be assessed by the study doctor. The first and last visits will also involve blood work and completing a number of tasks on the computer, which measure focus, attention and memory.
Each participant will be involved in the study for a maximum of 10 weeks. This includes the screening visit and follow-up visit.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia
Keywords
Anxiety Disorders, Cannabidiol, Cannabis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cannabidiol (CBD) Oil Capsules
Arm Type
Experimental
Arm Description
Pure CBD in sunflower lecithin oil, flexibly dosed at 200-800 mg per day
Arm Title
Sunflower Lecithin Oil in Capsule
Arm Type
Placebo Comparator
Arm Description
1-4 capsules daily
Intervention Type
Drug
Intervention Name(s)
Cannabidiol (CBD) Oil Capsules
Intervention Description
200 mg CBD- titrated as tolerated up to a maximum 2 capsules twice daily (200 mg- 800 mg total dose)
Start at 1 capsule/day (at bedtime) for one week and be titrated to 1 capsule twice/daily for one week. At the end of Week 2, dose may be titrated to 1 capsule in the morning and 2 capsules at bedtime; then at the end of Week 4, dose may be titrated to 2 capsules twice daily (the maximum of 800 mg/day total dose)
Intervention Type
Drug
Intervention Name(s)
Sunflower Lecithin Oil in Capsule
Intervention Description
Start at 1 capsule/day (at bedtime) for one week and be titrated to 1 capsule twice/daily for one week. At the end of Week 2, dose may be titrated to 1 capsule in the morning and 2 capsules at bedtime; then at the end of Week 4, dose may be titrated to 2 capsules twice daily (the maximum of 800 mg/day total dose)
Primary Outcome Measure Information:
Title
Hamilton Anxiety Rating Scale (HAM-A)
Description
The 14-item HAM-A was developed to assess general anxiety symptoms in a clinical population and has proven sensitive to change with treatment. It is a clinician-rated measure and will be administered at each visit by a trained, blinded rater, using the Structured Interview Guide for the HAM-A. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) are summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.
Time Frame
Change from baseline to week 8
Secondary Outcome Measure Information:
Title
Clinical Global Impression - Severity (CGI-S)
Description
The CGI-S is a clinician-rated instrument used to assess global severity of symptoms. The CGI-S ranges from 1 (normal, not ill) to 7 (among the most severely ill).
Time Frame
Change from baseline to week 8
Title
Clinical Global Impression - Improvement (CGI-I)
Description
The CGI-I is a clinician-rated instrument used to assess overall improvement of illness. The CGI-I ranges from 1 (very much improved) to 7 (very much worse).
Time Frame
Change from baseline to week 8
Title
Generalized Anxiety Disorder-7 (GAD-7)
Description
The GAD-7 is a self-reported questionnaire that measures the severity of various signs of GAD. It contains seven items with a 4-point scale (range: 0 to 3). The total possible score is ranged from 0 to 21, with higher scores representing greater severity of GAD.
Time Frame
Change from baseline to week 8
Title
Liebowitz Social Anxiety Scale- Self Report (LSAS-SR)
Description
The LSAS-SR is a 24 item scale that provides separate scores for fear and avoidance in social and performance situations with higher scores representing increased social anxiety. The LSAS-SR contains three total scores 1) total fear score (0-72), 2) total avoidance score (0-72) and total overall score (0-144).
Time Frame
Change from baseline to week 8
Title
Panic and Agoraphobia Scale (PAS)
Description
The PAS is a measure of the severity of illness in patients with panic disorder (with or without agoraphobia). It has 13 items with a 5-point scale (range: 0-4). The total possible score is ranged from 0 to 52, with higher scores representing increased severity of illness. It contains 5 sub-scales: panic attacks, agoraphobic avoidance, anticipatory anxiety, disability, and functional avoidance (health concerns).
Time Frame
Change from baseline to week 8
Title
Quick Inventory of Depressive Symptomology (QIDS)
Description
The QIDS is a self-report measure of depression. It contains 16 items with a 4-point scale (range: 0 to 3) which assess the severity of the nine diagnostic symptom criteria used in the DSM: Sleep disturbance, sad mood, decrease/increase in appetite/weight, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, and psychomotor agitation/retardation. The total possible score is ranged from 0 to 27, with higher scores representing greater severity of depression.
Time Frame
Change from baseline to week 8
Title
Sheehan Disability Scale (SDS)
Description
The SDS is a 3 question instrument designed to assess functional impairment associated with mental disorders in three domains: work impairment, social impairment, and impairment of family life or home responsibilities. Each sub-scale score ranges from 0 to 10 and a total disability score, calculated as the sum of scores for each question ranges from 0 to 30. Higher scores reflect greater impairment.
Time Frame
Change from baseline to week 8
Title
World Health Organization Disability Assessment Scale (WHODAS 2.0)
Description
The WHODAS 2.0 is a 36-item self-administered questionnaire that covers 6 domains of functioning, including: Cognition, mobility, self-care, getting along with people, life activities, participation. Each question ranges from 'none' to 'extreme or cannot do'. The scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3) and "extreme" (4) - are summed to give a total score that ranges from 0 to 144, with higher scores representing a greater degree of functional limitation.
Time Frame
Change from baseline to week 8
Title
Insomnia Severity Index (ISI)
Description
The ISI has 7 questions with a 5-point score (range: 0 to 4). The total possible score is ranged from 0 to 28, with higher scores reflecting greater severity of sleep difficulty.
Time Frame
Change from baseline to week 8
Title
Marijuana Craving Questionnaire
Description
The Marijuana Craving Questionnaire is a 47-item self-report instrument that assesses marijuana craving along four dimensions: compulsivity, emotionality, expectancy, and purposefulness. Each item is answered with a 7-point scale from 1 (strongly disagree) to 7 (strongly agree).
Time Frame
Change from baseline to week 8
Title
Obsessive Compulsive Inventory-Revised (OCI-R)
Description
The OCI-R is a self-report scale for assessing symptoms of Obsessive-Compulsive Disorder (OCD). It consists of 18 questions with a 5-point scale (range: 0 to 4). The possible range of scores is 0 to 72, with higher scores indicating a greater likelihood of the presence of OCD.
Time Frame
Change from baseline to week 8
Title
PTSD Checklist (PCL-5)
Description
The PCL-5 is a 20 item self-report measure that assesses symptoms of PTSD. Each item is rated on a 5-point scale from 0 (not at all) to 4 (extremely). The possible range of scores is 0 to 80, with higher scores indicating greater severity of PTSD.
Time Frame
Change from baseline to week 8
Title
Drug Effects Questionnaire (DEQ)
Description
The DEQ assesses the extent to which participants 1) feel any substance effect(s), 2) feel high, 3) like the effects, 4) dislike the effects, and 5) want more of the substance using 100mm Visual Analog Scales.
Time Frame
Change from baseline to week 8
Title
Marijuana Withdrawal Checklist
Description
The Marijuana Withdrawal Checklist has 22 items that assess mood, behavioural, and physical symptoms associated with marijuana withdrawal. Each item is rated on a 4-point scale from 0 (none) to 3 (severe). A total score is obtained by summing each of the item totals (range 0 to 66). Higher scores indicated more severe symptoms associated with marijuana withdrawal.
Time Frame
Change from baseline to week 8
Title
Shipley II: Verbal
Description
Measures verbal intelligence quotient (IQ) - crystallized intelligence
Time Frame
Baseline
Title
Shipley II: Abstraction
Description
Measures abstract intelligence quotient (IQ) - fluid intelligence
Time Frame
Baseline
Title
Digits Forward Test
Description
Measures attention
Time Frame
Change from baseline to week 8
Title
Digits Backward Test
Description
Measures working memory
Time Frame
Change from baseline to week 8
Title
Go/No-Go Test
Description
Measures behavioural inhibition
Time Frame
Change from baseline to week 8
Title
Monetary Choice Questionnaire
Description
Measures impulsive decision making
Time Frame
Change from baseline to week 8
Title
Probabilistic Choice Questionnaire
Description
Measures risky decision making
Time Frame
Change from baseline to week 8
Title
Trails A and B Task
Description
Measures visual attention and switching
Time Frame
Change from baseline to week 8
Title
Rey Auditory Verbal Learning Test
Description
Measures short-term auditory-verbal memory
Time Frame
Change from baseline to week 8
Title
Simple Visual Reaction Time Task
Description
Measures reaction time
Time Frame
Change from baseline to week 8
Title
Sustained Attention to Response Task
Description
Measures sustained attention
Time Frame
Change from baseline to week 8
Title
Experimental Drug Purchase Task
Description
Measures drug abuse liability
Time Frame
Week 8
Title
Inflammatory Markers
Description
Serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α and IFN-γ
Time Frame
Change from baseline to week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female outpatients 21-65 years of age with a primary psychiatric diagnosis of either GAD, SAD, PD or agoraphobia as defined by DSM-5 criteria and a HAM-A score of ≥ 22.
Physical exam and laboratory findings without clinically significant abnormalities.
Participants must agree to abstain from recreational cannabis use for the duration of the study.
Concomitant psychotropic medication use will be allowed provided that the dose has been stable for 8 weeks prior to randomization. (including antidepressants, anti-psychotics, anti-convulsants, benzodiazepines, stimulants, mood stabilizers)
The ability to comprehend and satisfactorily comply with protocol requirements.
Written informed consent given prior to entering the baseline period of the study.
Exclusion Criteria:
Current recreational or medicinal use of cannabis within 4 weeks of study initiation.
Participants with a lifetime history of cannabis use disorder or other substance use disorders (except tobacco use disorder)will be excluded.
Participants with a lifetime history of daily cannabis use will be excluded.
Dose changes of concomitant medication will not be permitted during the study period.
Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months), or women who are planning on becoming pregnant.
Diagnosis of any of the following mental disorders as defined by the DSM-5: a lifetime history of schizophrenia or any other psychosis, mental retardation, organic medical disorders, bipolar disorder. Entry of patients with obsessive compulsive disorder or posttraumatic stress disorder will be permitted if the anxiety disorder is judged to be the predominant disorder, in order to increase accrual of a clinically relevant sample.
Major depression will be allowed if not severe (Montgomery Asberg Depression Rating Scale-MADRS ≥ 25). Patients with significant suicidal ideation (MADRS item 10 score > 3) or who have enacted suicidal behaviours within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
Participants with a family history of psychosis will be excluded.
Participants who have a history of adverse reactions to cannabis will be excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Van Ameringen, MD, FRCPC
Organizational Affiliation
Hamilton Health Sciences Corporation
Official's Role
Principal Investigator
Facility Information:
Facility Name
MacAnxiety Research Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 1B7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beth Patterson, MSc
Phone
905-921-7644
Email
bpatter@mcmaster.ca
First Name & Middle Initial & Last Name & Degree
Michael Van Ameringen, MD, FRCPC
First Name & Middle Initial & Last Name & Degree
James MacKillop, PhD
First Name & Middle Initial & Last Name & Degree
Emily MacKillop, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Cannabidiol for the Treatment of Anxiety Disorders: An 8-Week Pilot Study
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