Sublingual Cannabidiol for Anxiety

Tracking Information
First Submitted Date ICMJE	September 4, 2015
First Posted Date ICMJE	September 14, 2015
Last Update Posted Date	December 18, 2017
Estimated Study Start Date ICMJE	March 2018
Estimated Primary Completion Date	March 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 14, 2017)	Change from Baseline in Self-Reported Anxiety as Assessed by the Beck Anxiety Inventory (BAI) [ Time Frame: Week 1, Week 2, Week 3, Week 4 ]; The BAI is a 21-item self-report measure used to rate subjective, somatic, and panic-related symptoms of anxiety on a scale of 0 to 3, and will be given to participants on a weekly basis.
Original Primary Outcome Measures ICMJE; (submitted: September 10, 2015)	Change from Baseline in Self-Reported Anxiety as Assessed by the Beck Anxiety Inventory (BAI) [ Time Frame: One week ]; The BAI is a 21-item self-report measure used to rate subjective, somatic, and panic-related symptoms of anxiety on a scale of 0 to 3, and will be given to participants on a weekly basis.
Change History	Complete list of historical versions of study NCT02548559 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 14, 2017)	Change from Baseline in Anxiety Assessed by the Hamilton Anxiety Scale (HAM-A) [ Time Frame: Week 1, Week 2, Week 3, Week 4 ]The HAM-A is an administered measure of anxiety that will be given on a weekly basis; a variety of symptoms are rated on a scale of 0 to 4.; Change from Baseline in Self-Reported Anxiety Assessed by the State-Trait Anxiety Inventory (STAI) [ Time Frame: Week 1, Week 2, Week 3, Week 4 ]This self-report measure is comprised of two 20-item scales, with a range of four possible responses from 1 to 4, and differentiates between the more temporary condition of "state" anxiety and the more general quality of "trait" anxiety. It will be given on a weekly basis.
Original Secondary Outcome Measures ICMJE; (submitted: September 10, 2015)	Hamilton Anxiety Scale (HAM-A) [ Time Frame: One week ]The HAM-A is an administered measure of anxiety that will be given on a weekly basis; a variety of symptoms are rated on a scale of 0 to 4.; State-Trait Anxiety Inventory (STAI) [ Time Frame: One week ]This self-report measure is comprised of two 20-item scales, with a range of four possible responses from 1 to 4, and differentiates between the more temporary condition of "state" anxiety and the more general quality of "trait" anxiety. It will be given on a weekly basis.; Beck Depression Inventory (BDI) [ Time Frame: One week ]The BDI is a 21-item self-report measure used to assess the severity of depression; each item relates to a symptom of depression and is rated on a 0-3 scale. It will be given on a weekly basis.; Profile of Mood States (POMS) [ Time Frame: One week ]The POMS will be given weekly. It includes ratings of 0 to 4 of 65 adjectives relating to how the participant generally feels.; Positive and Negative Affect Scale (PANAS) [ Time Frame: One week ]The PANAS is a 20-item scale in which mood variables are rated on a 1-5 scale; ten items are summed to create a positive affect score, and ten items are summed to create a negative affect score. It will be completed weekly.; Beck Hopelessness Scale (BHS) [ Time Frame: Four weeks ]The BHS is a 20-item self-report questionnaire measuring feelings of hopelessness on a true/false scale. It will be completed at the baseline and final visits.; Beck Scale for Suicide Ideation (BSS) [ Time Frame: Four weeks ]The BSS will be completed at the baseline and final visits. It consists of 21 items designed to query suicidal intentions on a scale of 0 to 2.; World Health Organization Quality of Life BREF (WHOQOL-BREF) [ Time Frame: Four weeks ]The WHOQOL-BREF will be completed at the baseline and final visits, and consists of 26 items assessing physical, psychological, social and environment factors related to quality of life on a scale of 1 to 5.; 36-Item Short Form (SF-36) [ Time Frame: Four weeks ]The SF-36 contains 36 items that give an 8-scale profile of health and well-being scores. It will be completed at the baseline and final visits.; Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Four weeks ]The PSQI contains 19 questions assessing sleep quality and disturbance over the previous four weeks. The items yield seven component scores, including sleep latency, sleep duration and daytime dysfunction, which are summed to create a global score.; ActiGraph Device [ Time Frame: One week ]Participants will wear an ActiGraph activity and sleep monitoring device throughout the treatment period. Data from the device, including sleep duration and sleep latency, will be downloaded on a weekly basis.; Letter-Number Sequencing Subtest of the WAIS-R [ Time Frame: Four weeks ]Participants are asked to repeat sequences of alternating letters and number in numerical and alphabetical order. The dependent variable is how many sequences the participant can repeat correctly. This subtest measures working memory, attention, concentration and mental control.; Digit Symbol Substitution Test (DSST) [ Time Frame: Four weeks ]The DSST measures attention, psychomotor speed, visual scanning and information processing. Participants are asked to substitute symbols for numbers following a key, and are given 90 seconds to complete as many items as they can; the number of correct items is the dependent variable.; Rey Auditory Verbal Learning Test (RAVLT) [ Time Frame: Four weeks ]The RAVLT assesses the participant's immediate and delayed recall of a 15-item word list. Results provide an assessment of verbal learning, strength of memory following interfering tasks, proactive interference, accuracy of recognition memory and storage vs. retrieval of newly learned information.; Benton Visual Retention Test (BVRT) [ Time Frame: Four weeks ]The BVRT assesses visual perception, visual memory and constructional abilities. Participants reproduce 10 drawings after looking at each drawing for 10 seconds. Participants are given either full credit or no credit based on the accuracy of their reproduction, yielding a range of scores from 0-10.; Stroop Color-Word Test [ Time Frame: Four weeks ]The Stroop test measures the ability to inhibit inappropriate responses and resist interference. Variables measures are the time to complete each of three sections, as well as total errors of omission and commission per condition.; Trail Making Test [ Time Frame: Four weeks ]This test measures visual conception and visuomotor tracking, as well as maintenance of cognitive set. Time to complete each test and number of errors are the dependent variables.; Controlled Oral Word Association Test (COWAT) [ Time Frame: Four weeks ]Performance on the COWAT is reflective of executive function and verbal memory. One score is compiled for the number of words generated in one minute, and another score is generated by the number of items named in a category in one minute.; Wisconsin Card Sort Test (WCST) [ Time Frame: Four weeks ]The WCST measures executive function by having participants match stimulus cards to key cards without receiving an explanation of the criterion being used to match. Dependent variables include total number of categories correct, perseverative errors and other error types.; Structural Magnetic Resonance (MR) Imaging [ Time Frame: Four weeks ]An anatomic MR scanning protocol will be completed at the baseline and final visits. Structural MRI images will be acquired in the axial and coronal planes, and will be used to ensure regions of interest are visible and localized for correlation with functional data, to ensure participants are free of clinical abnormalities, and for potential morphometric analyses.; Functional MR Imaging [ Time Frame: Four weeks ]Functional MR data will be acquired at the baseline and final visits. Resting state data will be acquired to assess regional interactions in the brain occurring when a participant is not actively performing a task. Functional data will also be acquired during completion of the Multi-Source Interference Task (MSIT), which reliably activates circuitry associated with cognitive and attentional pathways.; Diffusion Tensor Imaging (DTI)/Diffusion Kurtosis Imaging (DKI) [ Time Frame: Four weeks ]DTI/DKI data will be acquired to examine white matter fiber tract integrity at baseline and the final visit.; Barratt Impulsiveness Scales (BIS-11) [ Time Frame: Four weeks ]The BIS-11 is a 30-item questionnaire, with each response rated from 1 to 4, which assesses and scores several dimensions of impulsivity. It will be completed at the baseline and final visits.; Impulsiveness-Venturesomeness-Empathy Scale (IVE) [ Time Frame: Four weeks ]The IVE measures impulsiveness, venturesomeness, and empathy using 63 items with yes/no responses. Scores for each trait will be calculated at baseline and at the final visit.; UPPS Impulsive Behavior Scale (UPPS-P) [ Time Frame: Four weeks ]The UPPS-P is a 59-item scale used to measure impulsivity using a rating scale of 1 to 4. Scores are calculated to represent premeditation, positive urgency, negative urgency, sensation seeking, and perseverance.; Barratt Inhibition System/Barratt Approach System Scale (BIS/BAS) [ Time Frame: Four weeks ]The BIS/BAS is a 24-item scale assessing the motivational systems of approach and inhibition on a scale of 1 to 4.; Fagerstrom Test for Nicotine Dependence (FTND) [ Time Frame: Four weeks ]The FTND is a 6-item questionnaire measuring current and past use of nicotine. Items are scored on a scale of 0 to 3 and are summed to yield a total score accompanied by a classification of dependence.; Alcohol Use Disorders Identification Test (AUDIT) [ Time Frame: Four weeks ]The AUDIT is a 10-item questionnaire that asks a variety of questions about alcohol consumption, rated on a scale of 0 to 4.; Cannabis Use Disorders Identification Test (CUDIT-R) [ Time Frame: Four weeks ]The CUDIT-R is an 8-item self-report measure that provides an assessment of patterns of cannabis use, dependence symptoms and problems related to use.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Sublingual Cannabidiol for Anxiety
Official Title ICMJE	Sublingual Cannabidiol for Anxiety
Brief Summary	This study evaluates the effects of cannabidiol (CBD) for the treatment of anxiety in adults certified for medical marijuana. Participants will use a sublingual (under-the-tongue) tincture of whole plant derived CBD three times daily for four weeks in addition to their normal treatment regimen. Participants' clinical state will be assessed weekly during the treatment period. In addition, cognitive function and measures of quality of life, sleep, general health, and multimodal neuroimaging will be assessed at baseline and the post-treatment final visit.
Detailed Description	Cannabis has been used for medicinal purposes across many cultures for a range of disorders dating as far back as 2700 B.C. The plant is comprised of a variety of components, including phytocannabinoids that act on CB1 and CB2 receptors. Numerous phytocannabinoids are present in cannabis, including the major psychoactive constituent of cannabis, delta-9 tetrahydrocannabinol (THC), which acts as a CB1 receptor agonist. Another phytocannabinoid, cannabidiol (CBD), is a major non-psychoactive constituent of cannabis and is only a partial agonist at CB1 receptors. Increasing evidence indicates that CBD in particular may have significant medicinal properties and benefits; experimental studies in both animals and humans have demonstrated that CBD can act as an anticonvulsant, antipsychotic, and muscle relaxant. CBD is often found in higher levels in products dispensed as medical marijuana relative to strains used primarily for recreational use. Several studies have demonstrated that CBD produces acute anxiolytic effects in animals and humans, although thus far no clinical trials of CBD have been conducted in patients with anxiety. As a growing number of states are legalizing medical marijuana, a gap exists in the scientific literature regarding the effects of CBD on anxiety. This investigation is composed of two phases. Phase 1 is comprised of a four-week, open label clinical trial of a high-CBD containing compound (22:1 CBD:THC) in individuals with anxiety. Participants will be pre-screened by phone in order to evaluate their eligibility for the study. If approved, participants will come to the hospital for a baseline/screening visit, and will complete a structured clinical interview, clinical and quality of life questionnaires, cognitive assessments, and an hour-long MRI scan. Enrolled participants will be given tincture to use for the duration of the study; participants will be instructed to self-administer 2 milliliters (ml) of the tincture under the tongue three times per day for four weeks. Throughout the treatment period, participants will return to the hospital on a weekly basis to complete questionnaires about their mood and quality of life. Participants will also return to the hospital for a final visit after four weeks of treatment to complete additional questionnaires, cognitive assessments, and another hour-long MRI scan. Phase 2 of the study is a double-blind clinical trial of this tincture in patients with anxiety. This double-blind trial will begin after the open-label trial has been completed. In the same manner as the open-label trial, participants will be pre-screened by phone, and approved participants will come to the hospital for a baseline/screening visit to complete a structured clinical interview, questionnaires, and cognitive assessments. Eligible participants will also have the option to complete an hour-long MRI scan at the baseline and final visits. Enrolled participants will receive either CBD tincture or placebo tincture to self-administer throughout the four week treatment period, as described above. Participants will return to the hospital weekly during the treatment period to complete questionnaires about their mood and quality of life. Participants in this phase of the study will also return for a final visit after four weeks of treatment to complete additional questionnaires, cognitive assessments, and an optional hour-long MRI scan.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
Condition ICMJE	Anxiety
Intervention ICMJE	Drug: Cannabidiol; Cannabidiol; total daily dose of 28.08mg.
Study Arms	Experimental: Cannabidiol; 2ml of sublingual cannabidiol tincture (4.68mg/ml CBD) administered three times per day (TID) for four weeks.; Intervention: Drug: Cannabidiol
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Not yet recruiting
Estimated Enrollment ICMJE; (submitted: September 10, 2015)	16
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	March 2019
Estimated Primary Completion Date	March 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 18 or older; Has a certificate for medicinal marijuana for anxiety; Native English speaker or acquired English prior to age 5; Minimum score of 8 on the Beck Anxiety Inventory (BAI) at the screening visit; Provides informed consent Exclusion Criteria: Non-native English speakers; Estimated IQ < 75; No current certificate for medicinal marijuana; Pregnancy; Presence of serious medical illness, including liver or kidney disease, or neurological disorder; Claustrophobia or metal implanted within the body, or body piercings that are not removable; Cardiac pacemakers, metal clips on blood vessels (also called stents), artificial heart valve, artificial arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings (wounded in military combat, sheetmetal workers, welders, and others), other metallic surgical hardware in vital area, certain tattoos with metallic ink, certain transdermal (skin) patches such as NicoDerm (nicotine for tobacco dependence), Transderm Scop (scopolamine for motion sickness), or Ortho Evra (birth control), certain intrauterine devices (IUDs) containing metal; Poor vision, as subjects must have normal or corrected-to normal vision for viewing stimuli during fMRI protocols
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Staci Gruber, PhD. 617-855-2762 gruber@mclean.harvard.edu
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT02548559
Other Study ID Numbers ICMJE	2015P000959
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Not Provided
Responsible Party	Staci Gruber, Ph.D., McLean Hospital
Study Sponsor ICMJE	Staci Gruber, Ph.D.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Mclean Hospital
Verification Date	December 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP