Anebulo Pharmaceuticals, Inc. announced complete results from its randomized, double-blind, placebo-controlled Phase 2 clinical trial evaluating ANEB-001 as a potential treatment for ACI in healthy volunteers challenged with oral delta-9-tetrahydrocannabinol ("THC"). Part B of the study was an adaptive design that included six cohorts of up to 15 healthy adults to examine different doses of THC and ANEB-001, and the impact of delayed dosing of ANEB-001 or placebo. In total, Parts A and B of the Phase 2 study enrolled 134 healthy subjects.

Data from Part A of the study previously showed positive protective effects of a single oral dose of 50 or 100 mg ANEB-001 when co-administered with an oral challenge dose of 10.5 mg THC. In Part B of the study, subjects were challenged with substantially higher oral doses of THC (21, 30, or 40 mg) and treated with lower doses of ANEB-001 (10 or 30 mg) or a matching placebo. Delayed dosing of ANEB-001 was also examined by introducing a one-hour pause between the THC challenge and treatment with the ANEB-001 or placebo.

The final cohort of the study included the administration of a high-fat meal prior to the THC challenge. Based on the final data for Part B of the study, a single low oral dose of ANEB-001 (10 mg) administered 1 hour after a THC challenge rapidly and statistically significantly reversed key psychotropic effects of THC doses as high as 30 mg, including a reduction in the visual analog scale (VAS) for feeling high (p=<0.0001) and improvement in VAS alertness (p=0.0042) and reduced body sway (p=0.0196). In a pre-specified pooled analysis of data for the combined 21 mg or 30 mg THC dose levels, a single 10 mg of ANEB-001 administered one hour after THC achieved statistical significance on all primary outcomes, including a reduction in VAS feeling high (p=<0.0001), improvement in VAS alertness (p=0.0024), reduced body sway (p=0.0014), and reduction in heart rate (p=0.0125).

ANEB-001 also reduced the time required for the THC effects to normalize back to baseline. The Phase 2 study was conducted in the Netherlands by the CHDR. A total of 134 healthy subjects were enrolled. All subjects received oral THC challenge doses.

In total, 91 subjects received single oral doses of ANEB-001. Pharmacodynamic outcomes were assessed by mixed-effect model repeated measures (MMRM) analysis of covariance (ANCOVA) through 8 hours post-ANEB-001 dosing. Safety was assessed by continuous observation through 24 hours and followed up at 7 to 14 days after treatment.

ANEB-001 was well tolerated in this study and there were no serious adverse events. At the 30 mg THC dose, prior to dosing ANEB-001 or placebo, subjects developed mild to moderate THC-related symptoms including moderate euphoria, nausea, and/or vomiting, and mild bradyphrenia, dizziness, paresthesia, and/or feeling emotional. After delayed dosing of 10 mg ANEB-001 or placebo following a 21 mg or 30 mg THC challenge dose, the adverse events considered possibly or probably related to ANEB-001 were mild except for one case of moderate nausea/vomiting at THC doses of 21 mg and 30 mg; the incidence of dizziness and euphoria was greater in the placebo treated subjects.

Administration of a high-fat meal delayed the absorption of THC resulting in blunted effects of a 30 mg THC dose on many of the outcomes. However, delayed dosing of 10 mg ANB-001 still significantly reduced VAS feeling high in fed subjects (p=0.0030).