Human skin permeation of Δ8-tetrahydrocannabinol, cannabidiol and cannabinol

Abstract

The purpose of this study was to quantify the in-vitro human skin transdermal flux of Delta8-tetrahydrocannabinol (Delta8-THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal analysis and in-vitro diffusion studies with human tissue were completed for the compounds. Heats of fusion, melting points and relative thermodynamic activities were determined for the crystalline compounds, CBD and CBN. Flux, permeability, tissue concentration and lag times were measured in the diffusion experiments. CBN had a lower heat of fusion and corresponding higher calculated relative thermodynamic activity than CBD. Ethanol concentrations of 30 to 33% significantly increased the transdermal flux of Delta8-THC and CBD. Tissue concentrations of Delta8-THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for Delta8-THC. Combinations of these cannabinoids with ethanol will be further studied in transdermal patch formulations in vitro and in vivo, as significant flux levels of all the drugs were obtained. CBD, the most polar of the three drugs, and other more polar cannabinoids will also be the focus of future drug design studies for improved transdermal delivery rates.

Deposition of cannabinoids in hair after long-term use of cannabis

“…Besides deposition from the environment, drug findings in hair from controlled studies also indicated a deposition from sebum and sweat or via the skin [4,41,42]. In in vitro studies, the horny layer exhibited some resistance to the diffusion of cannabinoids across human skin in the following order: THC < CBN < CBD [43,44]. The passage of a lipid-soluble compound from blood to other body fluids being dependent on the substance's pK a and pH, THC is not expected to accumulate in sweat.…”

Human Cannabinoid Pharmacokinetics

“…Transcutaneous-Another route of cannabinoid exposure that avoids first-pass metabolism and improves THC bioavailability is topical administration [43]. Cannabinoids are highly hydrophobic, making transport across the aqueous layer of the skin the rate-limiting step in the diffusion process [44] [45].…”

“…Cannabinoids are highly hydrophobic, making transport across the aqueous layer of the skin the rate-limiting step in the diffusion process [44] [45]. In vitro diffusion studies may underestimate in vivo transdermal flux [43]. After application of a dermal patch, mean steady-state plasma concentration of Δ 8 -THC was 4.4 ng/ml within 1.4 h, and was maintained for at least 48 h. Permeabilities of CBD and CBN were found to be 10-fold higher than for Δ 8 -THC.…”

Does cannabidiol have a role in the treatment of schizophrenia?

“…These results need to be considered carefully when conducting clinical trials where it is not ethically possible to cease pharmacotherapy of drugs metabolised by CYP enzymes. However, a novel route worth considering and which avoids the hepatic first pass is transdermal delivery (Stinchcomb et al, 2004).…”