Safety, Pharmacokinetics and Pharmacodynamics of Spectrum Red Softgels in Healthy Participants

Abstract

Due to a lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, informed physician and patient decision-making surrounding appropriate dosing of cannabis for medical purposes is limited. This Phase 1, multiple-dose study evaluated the safety, tolerability, PK, and PD of Spectrum Red softgels (2.5 mg Δ9-tetrahydrocannabinol (THC) and < 0.25 mg cannabidiol (CBD)). Participants (N = 41) were randomized to one of five groups: 5 mg THC and 0.06 mg CBD daily (Treatment A), 10 mg THC and 0.12 mg CBD daily (Treatment B), 15 mg THC and 0.18 mg CBD daily (Treatment C), 20 mg THC and 0.24 mg CBD daily (Treatment D), or placebo. Study medication was administered in divided doses, every 12 hours, approximately 60 minutes after a standardized meal, for seven consecutive days. All treatment-emergent adverse events (TEAEs) (65/65) were of mild to moderate severety; none was serious. The highest number of TEAEs (30/65) occurred on the first day of treatment. The most common TEAEs included somnolence, lethargy, and headache (reported by 8, 7, and 5 participants, respectively). On Day 7, maximum observed plasma concentration of 11-carboxy-THC increased by 2.0- and 2.5-fold as the dose doubled between Treatments A and B and between Treatments B and D, respectively. Mean peak post-treatment ratings of self-reported subjective effects of “feel any effect” and “dazed” differed between Treatment D and placebo on Days 1, 3, and 7. Over a week of twice-daily dosing of Spectrum Red softgels, daily doses of THC up to 20 mg and of CBD up to 0.24 mg were generally safe and became better tolerated after the first day of treatment. A prudent approach to improve tolerability with Spectrum Red softgels might involve initial daily doses no higher than 10 mg THC and 0.12 mg CBD 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.…”