A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History

Abstract

Background: An oral route of administration for tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD) eliminates the harmful effects of smoking and has potential for efficacious cannabis delivery for therapeutic and recreational applications. We investigated the pharmacokinetics of CBD, Δ⁹-THC, 11-OH-THC, and 11-nor-9-carboxy-Δ⁹-THC (THC-COOH) in a novel oral delivery system, Solutech™, compared to medium-chain triglyceride-diluted cannabis oil (MCT-oil) in a healthy population. Materials and Methods: Thirty-two participants were randomized and divided into two study arms employing a comparator-controlled, parallel-study design. To evaluate the pharmacokinetics of Δ⁹-THC, CBD, 11-OH-THC, and THC-COOH, blood was collected at pre-dose (t=0) and 10, 20, 30, and 45, min and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48 h post-dose after a single dose of Solutech (10.0 mg Δ⁹-THC, 9.76 mg CBD) or MCT (10.0 mg Δ⁹-THC, 9.92 mg CBD). Heart rate and blood pressure were measured at 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h. Relationships between cannabis use history, body mass index, sex, and pharmacokinetic parameters were investigated. Safety was assessed before and at 48 h post-acute dose. Results: Acute consumption of Solutech provided a significantly greater maximum concentration (C_max), larger elimination and absorption rate constants, faster time to C_max and lag time, and half-life for all analytes compared to MCT-oil (p<0.001). In addition, cannabis use history had a significant influence on the pharmacokinetic parameters of CBD, Δ⁹-THC, 11-OH-THC, and THC-COOH. On average, participants with later age of first use had higher Δ⁹-THC, CBD, and THC-COOH C_max and later time-to-C_max and half-life for Δ⁹-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032). Those with more years of recreational cannabis use had higher area under the curve for Δ⁹-THC and CBD, C_max for CBD, and longer 11-OH-THC half-life than those with less (p≤0.048). Conclusion: This study demonstrated that consumption of Solutech enhanced most pharmacokinetics parameters measured compared to MCT-oil. Participant's cannabis use history, including their age of first use and number of years using cannabis significantly impacted pharmacokinetic parameters investigated. Acute consumption of both products was found to be safe and well tolerated. The results suggest that Solutech may optimize bioavailability from cannabis formulations.

Trial registration: ClinicalTrials.gov NCT04601207.

Keywords: cannabidiol; novel delivery system; pharmacokinetics; tetrahydrocannabinol.

FIG. 1.

Participant disposition. Seventy-one participants screened for this study and 32 enrolled with 16 in each arm.

FIG. 2.

Plots with the mean (±SD) and individual data points for participants in the Solutech™ and MCT-oil groups are presented for Δ⁹-THC, mean±SD (—), *significance with a p-value <0.05. (A) AUC_0–48h, (B) C_max,0–48h, (C) T_max,0–48h, (D) T_lag, (E) AUC_I, (F) λ, (G) t_1/2, (H) λ_z, (I) t_{1/2, z}, (J) k_a. Δ⁹-THC, tetrahydrocannabinol; λ, elimination rate constant; λ_z, terminal elimination rate constant; AUC_0–48h, area under the curve; AUC_I, area under the curve to infinity; C_max,0–48h, maximum concentration; k_a, absorption rate constant; MCT-oil, medium-chain triglyceride-diluted cannabis oil; SD, standard deviation; t_1/2, half-life; t_{1/2, z}, terminal half-life; T_lag, lag time; T_max,0–48h, time to maximum concentration.

FIG. 3.

Plots with the mean (±SD) and individual data points for participants in the Solutech and MCT-oil groups are presented for CBD, mean±SD (—), *significance with a p-value <0.05. (A) AUC_0–48h, (B) C_max,0–48h, (C) T_max,0–48h, (D) T_lag, (E) AUC_I, (F) λ, (G) t_1/2, (H) λ_z, (I) t_{1/2, z}, (J) k_a. CBD, cannabidiol.

FIG. 4.

Plots with the mean (±SD) and individual data points for participants in the Solutech and MCT-oil groups are presented for 11-OH-THC, mean±SD (—), *significance with a p-value <0.05. (A) AUC_0–48h, (B) C_max,0–48h, (C) T_max,0–48h, (D) T_lag, (E) AUC_I, (F) λ, (G) t_1/2, (H) λ_z, (I) t_{1/2, z}, (J) k_a.

FIG. 5.

Plots with the mean (±SD) and individual data points for participants in the Solutech and MCT-oil groups are presented for THC-COOH, mean±SD (—), *significance with a p-value <0.05. (A) AUC_0–48h, (B) C_max,0–48h, (C) T_max,0–48h, (D) T_lag, (E) AUC_I, (F) λ, (G) t_1/2, (H) λ_z, (I) t_{1/2, z}, (J) k_a. THC-COOH, 11-nor-9-carboxy-Δ⁹-THC.

FIG. 6.

Mean (±SD) concentration-time profile of THC (A), CBD (B), 11-OH-THC (C), and THC-COOH (D) by product over a 48-h blood sampling period. Each point represents the concentration (ng/mL) of their respective metabolite at a specific time post-administration of Solutech (blue ) or MCT-oil (red ). Error bars represent the SD in concentration measurements at each time. All 32 participants (16 per product) are included in this figure.