CBD Oil for Reducing Emotional Impact of COVID-19 (CBDOIL)

• ClinicalTrials.gov Identifier: NCT04603781
• Recruitment Status: Recruiting
• First Posted: October 27, 2020
• Last Update Posted: February 26, 2021
• Sponsor: University of Texas at Austin
• Collaborators: Way West Hemp Inc.; SunFlora.Inc
• Information provided by (Responsible Party): Michael J. Telch, University of Texas at Austin

Study Description

Brief Summary:

The overarching objective of the proposed project is to test the relative clinical efficacy of CBD isolate, full-spectrum CBD oil, and placebo in in reducing COVID-Induced stress, anxiety, depression, anger, and sleep disturbance.

Condition or disease	Intervention/treatment	Phase
Anxiety Depression; Alcohol Abuse; Substance Abuse; Anger; Sleep Disturbance; Stress Reaction	Dietary Supplement: CBD Isolate; Dietary Supplement: Full Spectrum CBD Oil; Dietary Supplement: Broad-Spectrum CBD Oil; Dietary Supplement: Placebo Oil	Phase 2; Phase 3

Detailed Description:

Background and Significance of the Proposed Project

The COVID-19 pandemic has hit us like a ton of bricks creating unimaginable levels of unanticipated death, financial hardship, and dramatic changes in nearly every facet of our life including school, work, shopping, social and family life. Sadly, the physical, mental, economic, and health burden of COVID-19 disproportionately affects the poor, the elderly, and people of color.

The stress-induced by these changes as well as the lack of control we have over them, increases risk for new onset of mental health problems such as anxiety, depression, substance abuse, sleep disturbance, and family violence as well as exacerbation of symptoms among those with pre-existing psychiatric conditions. Although many people will successfully manage the increased stress from COVID-19 on their own or with the support from family and friends, others may need extra help to cope. Consequently, there is an urgent need for developing cost-effective strategies for managing the stress-induced psychological consequences of COVID-19.

There's been considerable excitement in the press over the potential therapeutic use of cannabidiol (CBD) products in the treatment of a variety of physical and mental health problems. Delta-9-tetrahydrocannabinol (delta-9 THC) is still illegal in most states because of its psychoactive abuse potential. In contrast, cannabidiol (CBD) does not convert to THC in the body and has negligible side effects relative to main-stream psychiatric drugs (benzodiazepines and antidepressants) commonly prescribed for the treatment of stress-related disorders such as anxiety, depression, and insomnia. Mounting evidence from studies with rodents suggests that CBD may confer significant promising health-related benefits including anti-inflammatory, pain-relieving, anti-cancer, memory enhancement, and facilitation of fear extinction (see White for a recent review).

The biggest success story for CBD use in humans to date comes from placebo-controlled randomized clinical trials demonstrating a 50% or more reduction in previously intractable seizures in children suffering from Dravet syndrome and Lennox-Gastaut syndrome. Moreover, several controlled clinical trials have shown promising findings in reducing psychotic symptoms among patients with schizophrenia and among young adults displaying THC-induced psychosis.

Preliminary Evidence that CBD may offer promise in the treatment of stress-related disorders has started to emerge. A small pilot trial with 24 patients presenting with social anxiety disorder found that relative to placebo, a single dose of 100 mg of CBD oil led to lower levels of anxiety, cognitive impairment, and discomfort in their actual speech performance as well as their anxiety before the speech. An uncontrolled case series of 11 PTSD patients receiving 8 weeks of CBD, reported a 28% reduction in PTSD symptom scores. In a small 4-week placebo-controlled study of 37 young Japanese adults with social anxiety disorder, Masataka found a significant advantage of CBD over placebo in reducing subjects' scores on two widely used measures of social anxiety symptoms.

Why Compare CBD-Isolate with Broad-Spectrum and Full-Spectrum CBD? CBD isolate is the purest form of CBD. It is made by extracting it from its natural environment - either hemp which is legal and recognized as generally safe in all states because of its low THC content (less than .3%), or the marijuana plant which has high levels of THC (up to 30%) and remains a Schedule 1 controlled substance under the Controlled Substances Act of 1970.

Unlike hemp-derived CBD Isolate, hemp-derived full-spectrum CBD contains all the hundreds of phytochemicals naturally found in the cannabis plant, including CBD, trace cannabinoids including Cannabinol (CBN), Cannabichromene (CBC), Cannabigerol (CBDA) and Cannabidivarin (CBDV), and more than 200 different terpenes, essential oils, and negligible THC content (less than 0.3%).

Research demonstrating the wide-ranging therapeutic effects of CBD oil including anti-emetic, anti-inflammatory, anxiolytic, and anti-psychotic effects were based on studies using pure doses of CBD Isolate. However, more recently it has been shown that the therapeutic effects of purified CBD display a bell-shaped dose-response curve suggesting a limited dose range, with no beneficial effects achieved at either lower or higher doses. This narrow therapeutic window presents a challenge for using CBD isolate clinically.

Based on recent research with rodents and humans, administration of a full spectrum cannabis extract containing mostly CBD but also containing other minor phytocannabinoids and non-cannabinoids exerted a synergistic effect with CBD that was both more effective than CBD Isolate without the unwanted bell-shaped dose-response curve. This finding has been named the entourage effect. However, to date, there are no human trials for any physical or mental health problem comparing the gold standard CBD isolate with a full-spectrum CBD formulation, despite the fact that both forms of CBD are widely available without a prescription in stores all across the United States. The proposed project will provide important data to determine whether a full-spectrum CBD formulation offers any advantages over CBD isolate in reducing COVID-19 stress-induced symptoms.

Specific Aims and Hypotheses:

1. Compare the efficacy of a 4-week daily regimen of hemp-derived CBD isolate (300 mg/day), broad-spectrum CBD oil, full spectrum CBD oil (300 mg/day), or placebo oil in reducing patient-rated symptoms of stress, anxiety, depression, and sleep disturbance. It is predicted that patients receiving and of the three active CBD oil formulations (pure isolate, broad-spectrum, or full spectrum CBD oil) will show significantly greater reduction in emotional distress and sleep disturbance relative to those receiving placebo oil. It is also predicted that broad-spectrum and full-spectrum CBD oil will outperform CBD isolate in reducing COVID-19 stress-induced symptoms of stress, anxiety, depression, anger, and sleep disturbance.
2. Examine predictors of patients' clinical response to the 3 treatments. It is expected that the superiority of broad-spectrum and full-spectrum CBD oil relative to CBD isolate or placebo will be more pronounced for patients showing more severe COVID-19 stress-induced symptoms at baseline.
3. Examine the perceived acceptability and side effects profile of 4 weeks of daily CBD/Placebo oil ingestion. It is expected that each of the three CBD formulations (CBD isolate, Broad-spectrum or Full spectrum CBD oil) will show minimal side effects that will not exceed the level of side effects for those ingesting placebo oil with the possible exception of somnolence.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 4-arm double-blind placebo-controlled trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Use of CBD Oil for Reducing the Negative Emotional Impact of COVID-19: A Randomized Placebo-Controlled Clinical Trial
• Actual Study Start Date: December 4, 2020
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: CBD-Isolate 300 mg.; Nightly administration of 300 mg. of CBD-Isolate for 28 consecutive days	Dietary Supplement: CBD Isolate; 300 mg. daily dose of CBD Isolate Oil; Other Name: Pure CBD oil
Active Comparator: Full-Spectrum CBD Oil 300 mg.; Nightly administration of 300 mg. of Full Spectrum CBD Oil for 28 consecutive days	Dietary Supplement: Full Spectrum CBD Oil; 300 mg. daily dose of CBD with full spectrum of other cannabinoids found in the hemp plant
Active Comparator: Broad-Spectrum CBD oil 300 mg.; Nightly administration of 300 mg. of Broad-Spectrum CBD Oil for 28 consecutive days	Dietary Supplement: Broad-Spectrum CBD Oil; 300 mg. daily dose of CBD with a selected spectrum of other cannabinoids found in the hemp plant
Placebo Comparator: Placebo Oil; Nightly administration of 300 mg. of Placebo Oil for 28 consecutive days	Dietary Supplement: Placebo Oil; MCT Oil with mint flavoring

Outcome Measures

Primary Outcome Measures :

1. PROMIS Emotional Distress Index [ Time Frame: Week 0-Baseline ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
2. PROMIS Emotional Distress Index [ Time Frame: Week 1-Treatment ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
3. PROMIS Emotional Distress Index [ Time Frame: Week 2-Treatment ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
4. PROMIS Emotional Distress Index [ Time Frame: Week 3-Treatment ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
5. PROMIS Emotional Distress Index [ Time Frame: Weeks 4-Treatment ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
6. PROMIS Emotional Distress Index [ Time Frame: Week 5-Treatment ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
7. PROMIS Emotional Distress Index [ Time Frame: Week 6-Treatment ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
8. PROMIS Emotional Distress Index [ Time Frame: Week 7-Follow-up ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
9. PROMIS Emotional Distress Index [ Time Frame: Week 8-Follow-up ]
   This measure is a 23-item patient-rated emotional distress symptom scale consisting of 3 sub-factors (Depression, Anxiety, and Anger). Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).

Secondary Outcome Measures :

1. PROMIS Depression Scale [ Time Frame: Week 0-Baseline ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
2. PROMIS Depression Scale [ Time Frame: Week 1-Treatment ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
3. PROMIS Depression Scale [ Time Frame: Week 2-Treatment ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
4. PROMIS Depression Scale [ Time Frame: Week 3-Treatment ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
5. PROMIS Depression Scale [ Time Frame: Week 4-Treatment ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
6. PROMIS Depression Scale [ Time Frame: Week 5-Follow-up ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
7. PROMIS Depression Scale [ Time Frame: Week 6-Follow-up ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
8. PROMIS Anxiety Scale [ Time Frame: Week 0 Baseline ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
9. PROMIS Anxiety Scale [ Time Frame: Week 1-Treatment ]
   This measure is an 8-item patient-rated depression symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
10. PROMIS Anxiety Scale [ Time Frame: Week 2-Treatment ]
    This measure is a 7-item patient-rated anxiety symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
11. PROMIS Anxiety Scale [ Time Frame: Week 3-Treatment ]
    This measure is a 7-item patient-rated anxiety symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
12. PROMIS Anxiety Scale [ Time Frame: Week 4-Treatment ]
    This measure is a 7-item patient-rated anxiety symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
13. PROMIS Anxiety Scale [ Time Frame: Week 5-Follow-up ]
    This measure is a 7-item patient-rated anxiety symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
14. PROMIS Anxiety Scale [ Time Frame: Week 6-Follow-up ]
    This measure is a 7-item patient-rated anxiety symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
15. PROMIS Anger Scale [ Time Frame: Week 0 Baseline ]
    This measure is an 8-item patient-rated anger symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
16. PROMIS Anger Scale [ Time Frame: Week 1 Treatment ]
    This measure is an 8-item patient-rated anger symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
17. PROMIS Anger Scale [ Time Frame: Week 2 Treatment ]
    This measure is an 8-item patient-rated anger symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
18. PROMIS Anger Scale [ Time Frame: Week 3 Treatment ]
    This measure is an 8-item patient-rated anger symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
19. PROMIS Anger Scale [ Time Frame: Week 4 Treatment ]
    This measure is an 8-item patient-rated anger symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
20. PROMIS Anger Scale [ Time Frame: Week 5 Follow-up ]
    This measure is an 8-item patient-rated anger symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
21. PROMIS Anger Scale [ Time Frame: Week 6 Follow-up ]
    This measure is an 8-item patient-rated anger symptom scale. Each symptom is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
22. PROMIS Alcohol Negative Consequences Scale [ Time Frame: Week 0 Baseline ]
    This measure is an 8-item patient-rated index of alcohol-related problems. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
23. PROMIS Alcohol Negative Consequences Scale [ Time Frame: Week 1 Treatment ]
    This measure is an 8-item patient-rated index of alcohol-related problems. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
24. PROMIS Alcohol Negative Consequences Scale [ Time Frame: Week 2 Treatment ]
    This measure is an 8-item patient-rated index of alcohol-related problems. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
25. PROMIS Alcohol Negative Consequences Scale [ Time Frame: Week 3 Treatment ]
    This measure is an 8-item patient-rated index of alcohol-related problems. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Never) to 5 (Always).
26. PROMIS Alcohol Negative Consequences Scale [ Time Frame: Week 4 Treatment ]
    This measure is an 8-item patient-rated index of substance use severity. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Almost Always).
27. PROMIS Alcohol Negative Consequences Scale [ Time Frame: Week 5 Follow-up ]
    This measure is an 8-item patient-rated index of substance use severity. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Almost Always).
28. PROMIS Alcohol Negative Consequences Scale [ Time Frame: Week 6 Follow-up ]
    This measure is an 8-item patient-rated index of substance use severity. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Almost Always).
29. PROMIS Sleep Disturbance Scale [ Time Frame: Week 0 Baseline ]
    This measure is an 8-item patient-rated index of sleep disturbance. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Very Much).
30. PROMIS Sleep Disturbance Scale [ Time Frame: Week 1 Treatment ]
    This measure is an 8-item patient-rated index of sleep disturbance. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Very Much).
31. PROMIS Sleep Disturbance Scale [ Time Frame: Week 2 Treatment ]
    This measure is an 8-item patient-rated index of sleep disturbance. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Very Much).
32. PROMIS Sleep Disturbance Scale [ Time Frame: Week 3 Treatment ]
    This measure is an 8-item patient-rated index of sleep disturbance. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Very Much).
33. PROMIS Sleep Disturbance Scale [ Time Frame: Week 4 Treatment ]
    This measure is an 8-item patient-rated index of sleep disturbance. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Very Much).
34. PROMIS Sleep Disturbance Scale [ Time Frame: Week 5 Follow-up ]
    This measure is an 8-item patient-rated index of sleep disturbance. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Very Much).
35. PROMIS Sleep Disturbance Scale [ Time Frame: Week 6 Follow-up ]
    This measure is an 8-item patient-rated index of sleep disturbance. Each item is rated over a 7-day period on a 5-point scale ranging from 1 (Not at all) to 5 (Very Much).
36. COVID-19 Coping Self-Efficacy [ Time Frame: Week 0 Baseline ]
    This measure is a 12-item author-constructed patient-rated index of COVID-19 Coping Self-Efficacy
37. COVID-19 Coping Self-Efficacy [ Time Frame: Week 1 Treatment ]
    This measure is a 12-item author-constructed patient-rated index of COVID-19 Coping Self-Efficacy
38. COVID-19 Coping Self-Efficacy [ Time Frame: Week 2 Treatment ]
    This measure is a 12-item author-constructed patient-rated index of COVID-19 Coping Self-Efficacy
39. COVID-19 Coping Self-Efficacy [ Time Frame: Week 3 Treatment ]
    This measure is a 12-item author-constructed patient-rated index of COVID-19 Coping Self-Efficacy
40. COVID-19 Coping Self-Efficacy [ Time Frame: Week 4 Treatment ]
    This measure is a 12-item author-constructed patient-rated index of COVID-19 Coping Self-Efficacy
41. COVID-19 Coping Self-Efficacy [ Time Frame: Week 5 Follow-up ]
    This measure is a 12-item author-constructed patient-rated index of COVID-19 Coping Self-Efficacy
42. COVID-19 Coping Self-Efficacy [ Time Frame: Week 6 Follow-up ]
    This measure is a 12-item author-constructed patient-rated index of COVID-19 Coping Self-Efficacy

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

INCLUSION CRITERIA:

• Displays elevated symptom scores on one or more of the following established assessment instruments for depression (PROMIS-Depression), anxiety (PROMIS-Anxiety), Anger (PROMIS-Anger), sleep disturbance (PROMIS-Sleep); or Alcohol/Substance (PROMIS-Alcohol; PROMIS- Substance Use)
• Age between 18 to 70;
• Fluent in English;
• Has home access to the Internet;
• Willingness to provide signed informed consent;
• Willingness to refrain from all non-study CBD products during the 6-week study period;
• Willing to complete a brief pre-study 7-day online symptom monitoring log;

EXCLUSION CRITERIA:

• History of a suicide attempt in the past 6 months;
• Current medical problems that would preclude participating in the study;
• Pregnant or plan to become pregnant within the next 6 weeks;
• Currently taking blood thinners such as Warfarin or anti-seizure medications such as valproic acid;
• Hx of adverse reactions to CBD Oil;
• Allergic to coconut oil.

Contacts and Locations

Contacts

Contact: Michael J Telch, Ph.D.; (512) 814-5480; Telch@austin.utexas.edu

Contact: Cate Fischer, B.A.; (703) 343-0533‬; Cmfischer@utexas.edu

Locations

United States, Texas

University of Texas at Austin, Laboratory for the Study of Anxiety Disorders; Recruiting

Austin, Texas, United States, 78712

Contact: Michael J Telch, Ph.D. 512-814-5480 Telch@austin.utexas.edu

Contact: Cate Fischer, BA (703) 343-0533‬ cmfischer@utexas.edu

Principal Investigator: Michael J Telch, Ph.D.

Sponsors and Collaborators

University of Texas at Austin

Way West Hemp Inc.

SunFlora.Inc

Investigators

• Principal Investigator: Michael J Telch, Ph.D.; University of Texas at Austin

More Information

Publications:

Cowger TL, Davis BA, Etkins OS, Makofane K, Lawrence JA, Bassett MT, Krieger N. Comparison of Weighted and Unweighted Population Data to Assess Inequities in Coronavirus Disease 2019 Deaths by Race/Ethnicity Reported by the US Centers for Disease Control and Prevention. JAMA Netw Open. 2020 Jul 1;3(7):e2016933. doi: 10.1001/jamanetworkopen.2020.16933. Erratum in: JAMA Netw Open. 2020 Aug 3;3(8):e2019768.

Mazza C, Ricci E, Biondi S, Colasanti M, Ferracuti S, Napoli C, Roma P. A Nationwide Survey of Psychological Distress among Italian People during the COVID-19 Pandemic: Immediate Psychological Responses and Associated Factors. Int J Environ Res Public Health. 2020 May 2;17(9). pii: E3165. doi: 10.3390/ijerph17093165.

White CM. A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential. J Clin Pharmacol. 2019 Jul;59(7):923-934. doi: 10.1002/jcph.1387. Epub 2019 Feb 7. Review.

Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S; Cannabidiol in Dravet Syndrome Study Group. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.

Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631.

McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry. 2018 Mar 1;175(3):225-231. doi: 10.1176/appi.ajp.2017.17030325. Epub 2017 Dec 15.

Zuardi AW, Hallak JE, Dursun SM, Morais SL, Sanches RF, Musty RE, Crippa JA. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006 Sep;20(5):683-6. Epub 2006 Jan 9.

Morgan CJ, Curran HV. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiatry. 2008 Apr;192(4):306-7. doi: 10.1192/bjp.bp.107.046649.

Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, Quevedo J, Roesler R, Schröder N, Nardi AE, Martín-Santos R, Hallak JE, Zuardi AW, Crippa JA. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011 May;36(6):1219-26. doi: 10.1038/npp.2011.6. Epub 2011 Feb 9.

Elms L, Shannon S, Hughes S, Lewis N. Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. J Altern Complement Med. 2019 Apr;25(4):392-397. doi: 10.1089/acm.2018.0437. Epub 2018 Dec 13.

Masataka N. Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers With Social Anxiety Disorders. Front Psychol. 2019 Nov 8;10:2466. doi: 10.3389/fpsyg.2019.02466. eCollection 2019.

Linares IM, Zuardi AW, Pereira LC, Queiroz RH, Mechoulam R, Guimarães FS, Crippa JA. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Braz J Psychiatry. 2019 Jan-Feb;41(1):9-14. doi: 10.1590/1516-4446-2017-0015. Epub 2018 Oct 11.

Linares I, Zuardi AW, Pereira LCG, et al. Cannabidiol presents an inverted U-shaped dose-response curve in the simulated public speaking test. Eur Neuropsychopharm. 2016;26:S617. doi:10.1016/s0924-977x(16)31702-3

Gallily R, Yekhtin Z, Hanuš LO. Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using <i>Cannabis</i> Extract Enriched in Cannabidiol. Pharmacol Amp Pharm. 2015;06(02):75-85. doi:10.4236/pp.2015.62010

Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011 Aug;163(7):1344-64. doi: 10.1111/j.1476-5381.2011.01238.x. Review.

• Responsible Party: Michael J. Telch, Principal Investigator, University of Texas at Austin
• ClinicalTrials.gov Identifier: NCT04603781
• Other Study ID Numbers: 2020-07-0138
• First Posted: October 27, 2020
• Last Update Posted: February 26, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael J. Telch, University of Texas at Austin:

CBD Oil; CBD Isolate; COVID-19; stress symptoms; RCT

Additional relevant MeSH terms:

COVID-19; Dyssomnias; Parasomnias; Substance-Related Disorders; Alcoholism; Fractures, Stress; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Chemically-Induced Disorders; Mental Disorders; Sleep Wake Disorders; Nervous System Diseases; Alcohol-Related Disorders; Fractures, Bone; Wounds and Injuries