The numerous benefits of hemp administration for humans and animals are due to their rich supply of biologically active compounds, among which Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are assigned the largest roles.
Of the two main active compounds of hemp, THC is responsible for more of the plant’s psychoactive properties. The bioavailability levels of THC, CBD and their derivatives depends on the route of administration of these compounds.
Oral administration directs these substances into the bloodstream via the portal circulatory system. After their absorption, they go to the liver, where they are metabolised via liver enzymes (CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2B6, and CYP2C19).
THC is converted into the psychoactive compound 11-COOH-THC and then into 11-OH-THC, which has no psychoactive activity. CBD is hydroxylated to 7-COOH derivatives, which are excreted unchanged or as glucuronide conjugates.
But in vitro studies have demonstrated that under acidic conditions, CBD is converted to THC. Therefore, it is crucial to understand the bioavailability and stability of CBD and THC in oral administration.
Typically, oil compounds are commonly used as carriers for most lipophilic drugs. It is suggested that non-ionic compounds such as Cremophor, which have hydrophilic properties, may emulsify and dissolve lipophilic molecules by forming micelles to enclose the lipophilic molecules.
In order to investigate the impact of different carrier oil compounds on CBD bioavailability, the current study assessed the stability and bioavailability of an extract of Cannabis sativa, referred to as “THC-reduced hemp extract” (CBD:THC = 16/1), when administrated orally in two different solvents.
They found one of the solvents led to a higher bioavailability of both components with some of the CBD being converted to THC in the body.
The authors conclude: "Oral administration of the Cannabis sativa extract with a decreased THC content leads to much higher concentrations of CBD than THC in the whole-blood and brain for both solvent formulations (Rapae oleum and Cremophor). The total bioavailability of both CBD and THC was higher for Rapae oleum than for Cremophor. Since some of the CBD is converted into THC in the body, this should be considered when using Cannabis sativa for medical purposes. This THC-reduced hemp extract is a promising candidate for medical applications."
The hemp variety KC Dora, a Hungarian variety of fibrous monoecious hemp bred at Agromag Kft, was used in this study, with the following extract composition:
This extract was used to prepare preparations in both solvents, namely, Rapae oleum and in a mixture of Cremophor/ethyl alcohol 96%/NaCl 0.9%, in the ratio 1:1:18.
Rapae oleum is a mixture of fatty acids: oleic acid, linoleic acid, linolenic acid, palmitic acid, stearic acid, eicosenoic acid and erucic acid .Cremophor is a mixture of polyoxyethylated triglycerides, made by reacting castor oil.
The experiment used Cannabis sativa extracts with a concentration of 216 mg of pure cannabidiol (CBD) in 1 g of extract.
Each of the 48 male Wistar rats were randomly assigned to receive a single dose of the extract dissolved in either Rapae oleum or Cremophor/ethanol/NaCl mixture at a dose of 30 mg/kg of rat body-weight. Blood samples from 0.5, 1, 2, 4, 6 and 24 h post administration and, after sacrifice, the whole brain of the rats were analysed by mass spectrometry.
For the Cannabis sativa extract with a decreased THC content, there were much higher levels of CBD than THC in both the blood and brain, a phenomenon observed for both formulations.
However, there were some differences in the bioavailability of both CBD and THC depending on the solvent, with higher CBD concentrations in the whole-blood and brain observed for the Rapae oleum formulation compared to Cremophor, whereas, in the case of THC, the differences were less noticeable.
The report states: "Whether the enhanced CBD concentration in whole-blood administered in Rapae oleum was due to heightened solubility in gastrointestinal fluids or increased drug permeability remains uncertain. The presence of co-solvents (such as ethanol in Cremophor) may indeed modulate gastric and intestinal drug absorption (and thus their pharmacokinetics) depending on the drugs’ concentration and chemistry. Indeed, Cremophor may lower the surface tension and improve the dissolution of lipophilic drugs in an aqueous medium by forming micelles to entrap the drugs."