Safety, Pharmacokinetics and Pharmacodynamics of Spectrum Yellow Oil in Healthy Participants

Abstract

Due to a lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, decision-making surrounding appropriate dosing of cannabis used for medical purposes is limited. This multiple-dose study evaluated the safety, tolerability, PK, and PD of Spectrum Yellow oil [20 mg/mL cannabidiol (CBD)/<1 mg/mL ∆9-tetrahydrocannabinol (THC)]. Participants (N=43) were randomized to one of five groups: 120 mg CBD and 5.4 mg THC daily, 240 mg CBD and 10.8 mg THC daily, 360 mg CBD and 16.2 mg THC daily, 480 mg CBD and 21.6 mg THC daily, or placebo. Study medication was administered every 12 hours for seven consecutive days. Treatment-emergent adverse events (TEAEs); plasma and urine concentrations of THC, CBD, and metabolites; and self-reported subjective effects were collected. Nearly all TEAEs (44/45) were of mild or moderate severity; none was serious. The highest incidence of TEAEs (67%) was in the two higher-dose treatment groups. The highest number of TEAEs (17/45) occurred on the first treatment day. Steady-state plasma CBD concentrations were reached by Day 7. On Day 7, CBD exposure showed dose-proportionality (AUC0-t slope=1.03 [0.70, 1.36], Cmax slope=0.92 [0.53, 1.31]). Most plasma THC concentrations were below the limit of quantification. Across Days 1 and 7, there were no consistent differences in subjective effects between placebo and active study medication. A prudent approach to improve tolerability with Spectrum Yellow oil might involve initial doses no higher than 240 mg total CBD and 10.8 mg total THC daily in divided doses, with titration upwards over time as needed based on tolerability.

Medicinal cannabis in the treatment of chronic pain

“…In clinical trials, treatment-emergent side effects of typical oral THC doses (approximately 5-20 mg) tend to be mild or moderate in severity and more prominent on the first day of dosing. 51,52 Patients using nabiximols generally report few adverse reactions, other than mild increases in appetite and some dizziness, nausea, fatigue and dysgeusia. Inhaled cannabis will produce more immediate and pronounced feelings of intoxication than oral THC products.…”

Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ9-tetrahydrocannabinol: a pilot study

“…Future research evaluating the therapeutic potential of CBC may wish to study higher doses, and may need to collect data on safety at such doses. Plasma concentrations of CBC were generally higher and more consistently quantifiable than those of CBD and THC at the same lower limit of quantification [24], relative to the dose administered. More specifically, while the dose of CBD was 18 times higher than the dose of CBC, the AUC 0-t of CBD was only 6.6-9.8 fold higher than the AUC 0-t of CBC (in Treatment D, where CBC was quantifiable in most samples); while the dose of THC was similar to the dose of CBC, THC was quantifiable in fewer plasma samples than CBC [24].…”

“…Results on participant characteristics, safety and tolerability of Spectrum Yellow oil, and PK of CBD and THC in Spectrum Yellow oil are presented in the parent publication [24]. The overall conclusion was that Spectrum Yellow oil was safe and well-tolerated.…”

“…A major finding of the parent study was that Spectrum Yellow oil was well-tolerated in healthy participants at daily doses up to 480 mg CBD and 20 mg THC [24]. Because Spectrum Yellow oil also contained 1.1 mg/mL CBC, it can thus be inferred that, in the presence of CBD and THC, CBC is well-tolerated up to daily doses of 26.4 mg.…”

“…The parent study was a Phase 1, randomized, double-blind, placebo-controlled, multiple-dose trial in 43 healthy participants to assess the safety, tolerability, PK, and PD of Spectrum Yellow oil [24]. The study was conducted in accordance with consensus ethics principles, International Conference on Harmonization Good Clinical Practice guidelines, the Declaration of Helsinki, and local Australian laws and regulations.…”