Medicinal Cannabis for Endometriosis: The Gut Microbiome

This trial will be testing one medicinal cannabis oil product (a CBD full spectrum oil) that is potentially effective for the treatment of endometriosis-associated symptoms, compared to a placebo. The medication (in oil form) will be manufactured and supplied in the same high-quality form, composition and dosage as currently permissible under this category. A dose-finding period will be performed during the first 10 days of the intervention phase to determine the lowest dosage for market, if clinical benefit is observed. All randomized arms will undergo the same dosage finding process to maintain blinding. This occurs during the first 10 days – dose-finding phase – of the intervention phase. Arm 1: CBD oil; Arm 2: placebo oil. 1. Begin with 2 x 0.20mL of oral oil per day (one dose in the morning and one dose at night). a. Arm 1 total starting dosage: 4mg of THC and 4mg of CBD per day b. Arm 2 total starting dosage: 40mg of CBD per day c. Arm 3 total starting dosage: no active ingredients 2. Increase total consumption by 0.2ml (an additional 0.1ml per dose) every two days until participants report any of the following: a. Adverse psychoactive effects are reported that are bothersome to the participant, or b. The maximum dosage of 100mg of CBD per day (Arm 1) is reached. In Arm 1 the maximum amount of THC per day at the maximum dose is no more than 10mg in total. c. Maximum amount of Arm 2 is 1ml per day. If adverse psychoactive effects are reported during dosage finding, participants will be asked to reduce their dosage until these effects are either no longer bothersome or no longer occur. Participants will be offered to undergo a ‘challenge’ test where they can increase their dosage again to see if the adverse effects no longer occur. This is optional and designed to allow participants time to adjust to any psychoactive or bothersome effects. Once the daily dosage has been determined participants will use this as their maximum dosage per day. This means that depending on the presenting symptom severity and other personal factors, participants are able to take a dosage each day that is equal to or less than the daily dosage, but not to exceed this. To measure symptom improvement during the dose-finding phase, the following question will be asked each day: “Thinking of the last 24 hours, do you think that your endometriosis symptoms (pelvic pain, fatigue, gastrointestinal symptoms, nausea) have improved compared to before you started on the trial? Y/N” Intervention drugs and doses: Elan oil (100mg/mL CBD): up to 1mL per day Mode and duration of administration: Oral oil for 3 months Strategies to monitor compliance: Participants will self-administer the study intervention at home and compliance with study intervention will be actively monitored. Compliance will be assessed by asking participants to return the empty bottle(s) in all treatment arms via paid postage. Final study drug reconciliation will be performed at the End of Treatment or after Early Termination. Any discrepancies will be thoroughly explained on the accountability form. Intervention start and stop dates, including dates for intervention delays and/or dose reductions will also be recorded. Participants will only be supplied with enough IMP to complete their treatment course. Returned study drug may not be administered to another subject. Each subject must be counselled on the importance of compliance with the dosing schedule. Compliance is defined as taking 75% of the maximum daily dosage per day on average for each dispensing period and will be determined by: a) confirmation of dosage the dosage taken each day via reminders from REDCap, and b) weighing returned study treatment bottles at the two reconciliation timepoints to determine the average daily dosage.