Heat Exposure ofCannabis sativaExtracts Affects the Pharmacokinetic and Metabolic Profile in Healthy Male Subjects

Abstract

The most important psychoactive constituent of CANNABIS SATIVA L. is Δ (9)-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC. In natural plant extracts of C. SATIVA, large amounts of THC and CBD appear in the form of THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompanied with a lower rate of adverse effects. Therefore, in the present study, the pharmacokinetics and metabolic profiles of two different C. SATIVA extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dronabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacokinetics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC (24 h) than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH-THC, THC-COOH, CBN) plasma AUC (24 h) was higher for the heated than for the unheated extract. The median CBD plasma AUC (24 h) was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pattern and possibly better tolerability.

Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects

“…Preparations taken orally (capsules, oral‐mucosal sprays and imbued food/liquid consumables) have a much lower peak THC plasma concentration compared to inhalation and a longer lag to peak concentration ( t max ) of between 60 and 120 minutes . They are subject to both gastric hydrochloric acid degradation and extensive first pass metabolism resulting in a much lower systematic bioavailability of THC compared with inhaled preparations . A large number of studies have examined the gastrointestinal bioavailability of oral intake heavy metals through food, drinking water and complementary medicine.…”

<p>Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements</p>

“…[12][13][14] Notes: a COA results that were based on dry materials used in preparation of final product; these products were not used in final calculations of percentage of company COA. Company reported COA bolded numbers represent COA analysis from the same company we utilized in this study (#11, 18,25). Label claim % numbers bolded and italicized were products that only contained a CBD label claim as the primary cannabinoid and no total cannabinoid claims for comparative purposes.…”

“…20,22 It is likely that this is intentional as CBDA has been associated with an antiinflammatory effect and is thought to be involved in improved bioavailability of cannabinoids. [23][24][25] The remainder of the products and the two higher CBDA products also contained CBD as the primary cannabinoids with a range of 0-54 mg/mL or gram and a median of 10 mg/mL or gram. In fact, there are few products that have over 20 mg/mL or gram (6/29) or 50 mg/mL (3/29) or gram of CBD or total cannabinoids.…”

“…[30][31][32][33] In general, the milligram quantity of total terpenes across products ranges from 0.015-6.7 mg/ mL or gram with only 6 products with over 1 mg/mL or gram of total terpenes. Further examination for any single terpene at concentrations higher than 1 mg/mL leaves only three products (#18, 19,25) that have a single terpene at that level. Overall, total terpenes for most products would be similar in concentrations to some of the minor cannabinoids observed, making it difficult to elucidate exactly whether alternate cannabinoids and/or terpenes are exhibiting some of the synergy observed as the "entourage effect" discussed in the literature.…”

Constituyentes psicoactivos del cannabis y sus implicaciones clínicas: una revisión sistemática

“…In order to avoid conflicting pharmacological reports, several authors have indicated that other plant cannabinoids need to be considered when evaluating cannabis effects (Eichler et al, 2012;Mechoulam, 2005;Turner, 1974). Our review shows that in most occasions other psychoactive cannabinoids are not even analyzed.…”