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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 Δ8‐tetrahydrocannabinol (Δ8‐THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal ana...

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Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2004-03, Vol.56 (3), p.291-297
Main Authors: Stinchcomb, Audra L., Valiveti, Satyanarayana, Hammell, Dana C., Ramsey, Diana R.
Format: Article
Language:English
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Summary:ABSTRACT The purpose of this study was to quantify the in‐vitro human skin transdermal flux of Δ8‐tetrahydrocannabinol (Δ8‐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 Δ8‐THC and CBD. Tissue concentrations of Δ8‐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 Δ8‐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.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357022791