Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes

Abstract

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of cannabis. The route of administration is important for interpretation of cannabinoid toxicology.

Legal cannabis laws, home cultivation, and use of edible cannabis products: A growing relationship?

“…Edible cannabis products help users avoid the health risks associated with toxins produced by smoking. However, edible cannabis use results in a delayed onset (1-3 hours) of psychoactive effects after consumption (Vandrey, et al, 2017), which, combined with increased product availability and suboptimal regulation of product packaging and content labeling, has led to an increased number of accidental edible-related overdoses and emergency room visits (Cao, Srisuma, Bronstein, & Hoyte, 2016; Ghosh, et al, 2015; MacCoun & Mello, 2015; Vandrey, et al, 2015; Wang, et al, 2014). In recent years, states with legal cannabis laws (LCL) have taken necessary regulatory steps to reduce this risk by requiring edible products to have universal warning symbols; provide consumers with knowledge about proper serving size; limit the amount of THC per serving and the total number of servings per unit; and be sealed in tamper-resistant packaging (Marijuana Enforcement Division, 2017; Oregon Liquor Control Commission, 2016).…”

Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice

“…64 ). Even though the oral route may look safer than inhalation (toxic compounds originated during cannabis combustion, more precise dosing), it may result in more frequent central adverse effects [66][67][68] possibly due to greater proportion of active metabolite 11-OH THC to parent THC (ref. 69,70 ).…”

“…The pharmacokinetics of THC and CBD in oral tablets shows lower absorption rate with THC T max of approx. 0.6 to 2.6 h after ingestion, depending on the dose and drug dosage form 66,73,74 . Interestingly, slower absorption was reported in sublingual (crushed tablet) administration of 5 mg THC than after normal oral use, in study of Klumpers et al 74 .…”

“…3 h) (ref. 66 ) with sustained plasmatic levels, especially in chronic administration 64,77,78 . Overall bioavailability after oral administration varies from 4 to 20% (ref.…”

The potential impact of cannabis legalization on the development of cannabis use disorders

“…Smoking delivers THC to the central nervous system much more quickly than oral ingestion, leading to a more rapid onset of effects, and in some cases a more intense experience (Vandrey et al, 2017). Smoking cannabis, however, involves ingestion of noxious smoke, which produces potentially negative or undesirable sensations, and delivers known carcinogens into the body (Tashkin et al, 2002).…”