*2.3. Study Intervention*

Oral capsules, manufactured by Tilray Brands, Inc. (New York City, NY, USA), consisted of highly purified (>98%) cannabinoids in oil. Formulations included TN-TC11M2, a THC:CBD combination in a 1:1 ratio (2.5 mg/2.5 mg), and TN-C200M2, consisting CBD only (200 mg). Capsules were of interest given the potential of orally administered cannabinoids to reduce gut-associated inflammation [35]. Due to person-to-person variability in metabolism and tolerability [36], participants up-titrated cannabinoid doses as tolerated (Table 1), a method which has proven successful in other clinical trials [37]. Dosage ranges for both the THC/CBD combination (2.5 to 15 mg/day) and the CBD-only formulation (200 to 800 mg/day) have been determined based on other clinical trials demonstrating safety, tolerability, and the efficacy of these doses for the managemen<sup>t</sup> of other pathologies such as chronic pain, epilepsy, schizophrenia, or even multiple sclerosis [38–41].

**Table 1.** Recommended up-titration schedule for TN-TC11M2 and TN-C200M2 regimens.


\* Original titration schedule for arm 2: this titration schedule has been revised because of possible hepatotoxicity of high dose of CBD (800 mg per day); # Revised titration schedule for arm 2.
