Bioavailability of cannabinoids – transdermal (5/6)

Bioavailability of cannabinoids – transdermal (5/6)

Transdermal delivery of cannabinoids is a little researched topic, although such intake method is a potentially interesting solution, as it would allow for the cannabinoids to slowly infiltrate directly into the bloodstream, when administred, for instance, in the form of patches [1]. Preliminary studies have shown that properly prepared patches are able to provide stable and long-lasting (at least 48h) release of into the bloodstream [2]. On the other hand, though, it is also known, that cannabinoids are generally strongly apolar, so they would tend to accumulate in the outer layers of the skin hardly penetrating its deeper layers.

As the folk stories have it, one of the traditional (and very spectacular) methods of obtaining hashish was to run through blossoming fields of marijuana, allowing the particles of resin and pollen to stick to the skin and clothes. The resin collected in this way was then scraped off the skin surface. The fact that despite such an intense contact with cannabinoids-rich resin no stories report the itoxicated collectors, confirms that the ability of THC in its natural to penetrate the skin is minimal at best [3]. This also points to the possible solution – that an appropriate formulation would be needed to increase the absorption of active substances [4,5]. It has been proven, for example, that the addition of increases the absorption of <delta?>-8-THC. In turn, satisfactory levels of absorption and therapeutic effects in treating multiple sclerosis in mice were obtained by mixing crystalline CBD in propylene glycol with a conventional O / W <(oil / water)> cream base [6]. It has also been found that the addition of ethyl alcohol significantly increases the absorption of such cannabinoids as CBD and ?-8-THC [1].

In addition to the need for supplements to enhance skin penetration, significant differences in the absorption of particular cannabinoids have also been observed. For example, CBD and CBN skin <permeability?> were found to be 10 times higher than the permeability of ?-8-THC and ?-9-THC, possibly due to differences in their lipophilicity (ability to dissolve in fats, oils and other non-polar solvents) [1].

Na tym przykładzie doskonale widać, jak mylące może być porównywanie wyników badań różniących się choćby jednym czynnikiem, takim jak w tym przypadku obiekt doświadczeń.

As a curious fact, the study of the absorption of ?-8-THC by the skin of rats and humans has shown that rats’ skin is 13 times more permeable to this substance than human skin [7]. This case clearly demonstrates how misleading can be comparing the results of research that differ in just one factor, such as the subject of experiment in this case.

PhD, Eng. Beata Plutowska

References:

[1] Stinchcomb A.L., Valiveti S., Hammel D.C., Ramsey D.R. Human skin permeation of ?8-tetrahydrocannabinol, cannabidiol and cannabinol. Journal of Pharmacy and Pharmacology 56 (2004) 291-297.
[2] Valiveti S., Hammel D.C., Earles D.C., Stinchcomb A.L. In vitro/in vivo correlation studies for transdermal ?8-THC development. Journal of Pharmaceutical Sciences 93 (2004) 1154-1164.
[3] Whittle B.A., Guy G.W., Robson P. Prospects for new Cannabis-based prescription medicines. Journal of Cannabis Therapeutics 1 (2001) 183-205.
[4] Lodzki M., Godin B., Rakou L., Mechoulam R., Gallily R., Touitou E. Cannabidiol – transdermal delivery and anti-inflammatory effect in a murine model. Journal of Controlled Release 93 (2003) 377-387.
[5] Paudel K.S., Hammell D.C., Agu R.U., Valiveti S., Stinchcomb A.L. Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers. Drug Development and Industrial Pharmacy 36 (2010) 1088-1097.
[6] Giacoppo S., Galuppo M., Pollastro F., Grassi G., Bramanti P., Mazzon E. A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. DARU Journal of pharmaceutical sciences (2015) 23-48.
[7] Touitou E., Fabin B., Dany S., Almog S. Transdermal delivery of thetrahydrocannabinol. International Journal of Pharmaceutics 43 (1988) 9-15.