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

Abstract

Purpose Cannabichromene (CBC) is a phytocannabinoid commonly found in cannabis, yet its acute post-dose pharmacokinetics (PK) have not been examined in humans. This is a secondary data analysis from a trial investigating Spectrum Yellow oil, an oral cannabis product used for medical purposes that contained 20 mg cannabidiol (CBD), 0.9 mg Δ9-tetrahydrocannabinol (THC), and 1.1 mg CBC, per 1 mL of oil. Methods Participants (N = 43) were randomized to one of 5 groups: 120 mg CBD, 5.4 mg THC, and 6.6 mg CBC daily; 240 mg CBD, 10.8 mg THC, and 13.2 mg CBC daily; 360 mg CBD, 16.2 mg THC, and 19.8 mg CBC daily; 480 mg CBD, 21.6 mg THC, and 26.4 mg CBC daily; or placebo. Study medication was administered every 12 h for 7 days. Plasma CBC concentrations were analyzed by a validated two-dimensional high-performance liquid chromatography–tandem mass spectrometry assay. Results After a single dose and after the final dose, the Cmax of CBC increased by 1.3–1.8-fold for each twofold increase in dose; the tmax range was 1.6–4.3 h. Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC0–t of CBD was only 6.6–9.8-fold higher than the AUC0–t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC. Conclusions CBC may have preferential absorption over CBD and THC when administered together. Trial Registration: Australian New Zealand Clinical Trials Registry #ACTRN12619001450101, registered 18 October 2019.

Physiologically based pharmacokinetic modeling and simulation of cannabinoids in human plasma and tissues

“…For example, a recent survey of the U.S. marketplace indicated that the total cannabinoid content in hemp‐derived products ranged from lower than detection limit to 143 mg per serving, with a median of 16.7 mg per serving (Dubrow et al, 2021). In addition, similar oral doses have been administered in the clinical studies for cannabinoids (Hobbs et al, 2020; Peters et al, 2022). Since the hemp‐derived products have been commonly manufactured using formulations such as liquid and capsule, an immediate release suspension (capsule yielded same results) was selected for the PBPK simulations.…”

Natural Cannabichromene (CBC) Shows Distinct Scalemicity Grades and Enantiomeric Dominance in Cannabis sativa Strains

“…All solvents used for UHPLC analyses were HPLC grade and were purchased from Merck Life Science (Milan, Italy) and Carlo Erba Reagents (Milan, Italy). Cannabinoid reference standards dissolved in methanol, namely, cannabidivarin (CBDV, 1 mg/mL), cannabidiolic acid (CBDA, 1 mg/mL), cannabigerol (CBG, 1 mg/mL), cannabidiol (CBD, 1 mg/mL), cannabinol (CBN, 1 mg/mL), (−)-Δ 9 tetrahydrocannabinol [(−)-Δ 9 -THC, 1 mg/mL], (−)-Δ 8 -tetrahydrocannabinol [(−)-Δ 8 -THC, 1 mg/mL], cannabichromene (CBC, 1 mg/mL), and (−)-Δ 9 -tetrahydrocannabinolic acid ((−)-Δ 9 -THCA, 1 mg/mL) with a purity of ≥99%, were purchased from Merck Life Science (Milan, Italy). Preparative TLC plates UV 254 nm (surface 20 × 20 cm, thickness 500 μm), used for the purification of CBC, were purchased from Merck (Darmstadt, Germany).…”

“…4 This synthetic material was used in the bioactivity studies that led to the discovery that CBC is a potent and selective CB2 5 and TRPA1 6 agonist, providing a mechanistic basis for its powerful anti-inflammatory activity, 7 while a remarkable antiepileptic activity was also reported. 8 The observation that CBC has a better oral absorption compared to CBD (2) and Δ 9 -THC (3) 9 provided an additional incentive for clinical studies, which are so far ongoing only with combination products. 9 CBC (1a) is chiral and was originally isolated in 1966 in an optically active form, 10,11 as was its acidic precursor (cannabichromenic acid, CBCA, 1b).…”

“…8 The observation that CBC has a better oral absorption compared to CBD (2) and Δ 9 -THC (3) 9 provided an additional incentive for clinical studies, which are so far ongoing only with combination products. 9 CBC (1a) is chiral and was originally isolated in 1966 in an optically active form, 10,11 as was its acidic precursor (cannabichromenic acid, CBCA, 1b). 12 However, later studies concluded that CBC is racemic, with any residual optical activity and with positivity in the dog ataxia test being due presumably to the presence of impurities.…”

“…Cannabinoid Content (% w/w) in Cannabis Strains Characterized by Different Concentrations of CBD (2), CBG (4), CBN (5), Δ9 -THC (3), and CBC (1a) a…”