Cannabinoids for the Treatment of Anxiety Disorders: An 8-Week Pilot Study

NCT04569760 | Withdrawn Phase 3

• 1 other identifier: CBD_ANX_2
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This proposed study aims to evaluate the efficacy of a daily oral cannabinoid oil preparation 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 cannabinoids using biological markers as well as examine the neuro-cognitive effects of cannabinoid treatment.

Conditions

Generalized Anxiety Disorder; Social Anxiety Disorder; Panic Disorder; Agoraphobia

Keywords

Anxiety Disorders; Cannabinoids; Cannabis; Cannabidiol

Outcome Measures

Primary Outcomes (1)

• 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.

  Change from baseline to week 8

Secondary Outcomes (19)

• Clinical Global Impression - Severity (CGI-S)

  Change from baseline to week 8

• Clinical Global Impression - Improvement (CGI-I)

  Change from baseline to week 8

• Generalized Anxiety Disorder-7 (GAD-7)

  Change from baseline to week 8

• Liebowitz Social Anxiety Scale- Self Report (LSAS-SR)

  Change from baseline to week 8

• Panic and Agoraphobia Scale (PAS)

  Change from baseline to week 8

Study Arms (2)

Cannabinoid Oil - Oral Preparation

EXPERIMENTAL

50mg CBD: 2mg of THC in each 1ml drop in MCT Oil, flexibly dosed at 200-800 mg per day. Dosing will start at 2 mls twice a day for one week and be titrated to 4 mls twice/daily for one week. At the end of Week 2, dose may be titrated to 6 mls twice a day ; then at the end of Week 4, dose may be titrated to 8 mls twice daily (the maximum of 800 mg/day total dose of High CBD). The dose will be titrated in increments of 200 mg (4 mls)/day/week if participants are tolerating their current dose, are experiencing no adverse events and have not fully responded so that they may potentially reach 800 mg/day/week by Week 4.

Drug: 50:2 mg(CBD:THC)/ml - Cannabinoid Oil Oral Preparation- titrated as tolerated up to a maximum 8mls twice daily (200 mg- 800 mg total dose)

Placebo Oil - Oral Preparation

PLACEBO COMPARATOR

MCT Oil Dosing will start at 2 mls twice a day for one week and be titrated to 4 mls twice/daily for one week. At the end of Week 2, dose may be titrated to 6 mls twice a day ; then at the end of Week 4, dose may be titrated to 8 mls twice daily (a volume equivalent to the maximum of 800 mg/day total dose of High CBD). The dose will be titrated in incremental volumes equivalent to 200 mg of active product (4 mls)/day/week if participants are tolerating their current dose, are experiencing no adverse events and have not fully responded so that they may potentially reach the volume equivalent to 800 mg/day/week by Week 4.

Drug: Placebo Oil

Interventions

50:2 mg(CBD:THC)/ml - Cannabinoid Oil Oral Preparation- titrated as tolerated up to a maximum 8mls twice daily (200 mg- 800 mg total dose) DRUG

Oral cannabinoid oil preparation dosed in 1ml increments

Also known as: Active

Cannabinoid Oil - Oral Preparation

Placebo Oil DRUG

Oral MCT Oil Preparation - No cannabinoids- titrated as tolerated up to a maximum of 8mls twice daily (equivalent to 200 mg- 800 mg total dose of the active product)

Also known as: Placebo

Placebo Oil - Oral Preparation

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 greater than or equal to 22.
• Physical exam and laboratory findings without clinically significant abnormalities. Screening bloodwork values for hematology and chemistry are to be Within Normal Limits.
• 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, benzodiazepines, and stimulants)

You may not qualify if:

• 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.
• Participants currently using medications that are CYP3A4, CYP2C19 or CYP2D6 inhibitors or inducers which includes but is not limited to: tricyclic antidepressants, topiramate, clobazam, amitriptyline, fentanyl, the related opioids sufentanil and alfentanil, codeine, oxycodone, macrolides, calcium channel blockers, cyclosporine, sildenafil, tadalafil, antihistamines, antiretrovirals, atorvastatin and simvastatin, warfarin and valproate or other anti-epileptics.
• 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-MADRS28≥ 25). Patients with significant suicidal ideation (MADRS item 10 score \> 3) or who have enacted suicidal behaviors 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.
• Participants who have severe cardiovascular, immunological, liver, or kidney disease, arrhythmia or a history of arrhythmias will be excluded.

Sponsors & Collaborators

• McMaster University: lead
• MediPharm Labs Corp: collaborator

Study Sites (1)

MacAnxiety Research Centre

Hamilton, Ontario, L8S 1B7, Canada

Location

MeSH Terms

Conditions

Generalized Anxiety Disorder; Phobia, Social; Panic Disorder; Agoraphobia; Anxiety Disorders; Marijuana Abuse

Interventions

Exercise

Condition Hierarchy (Ancestors)

Mental Disorders; Phobic Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Michael Van Ameringen, MD, FRCPC

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: September 30, 2020
• Study Start: April 1, 2021
• Primary Completion: April 1, 2023
• Study Completion: June 1, 2023
• Last Updated: March 24, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)