Bioavailability of cannabinoids – inhalation (2/6)

Bioavailability of cannabinoids – inhalation (2/6)

Inhalation, epecially smoking, is the most common way of cannabinoids intake. This administration method allows the cannabinoids to directly enter the bloodstream. If the inhalation is carried out in high temperature (as in the smoking of <vaporization> (vaping?)process), the user absorps practically only the <phenolic> (neutral) forms of cannabinpids – such as CBD, THC, CBG, etc., as all their acidic forms (CBDA, THCA, CBGA, etc.) are instantly <decarboxylated> due to the high temperature.

So far, the studies on absorption have focussed primarily on smoking cannabis in form of cigarettes and suggest that the relative bioavailability of THC, CBD and CBN (defined as the concentration of substance in blood plasma in comparison to that following the IV application referred to as 100%) falls within very wide ranges of respectively: 10-35%, 15-45% and 10-65% [1]. The divergency in results is not caused by the poor absorption in the lungs, but by such factors as: thermal degradation of cannabinoids (up to 30%), residues left in cigarette butts, losses in lateral fumes <boczne strumienie dymu?> During smoking most cannabinoids just do not get to the lungs. About 50% of the THC contained in the dried mass is inhaled into the lungs, while up to 50% of the inhaled amount is being exhaled back, and the part remaining in the lungs is instantly metabolised locally[2]. Other factors that affect the absorption are: depth of inhalation, its duration and holding breath.

Therefore, it can be safely assumed that the significant increase in bioavailability can be achieved by optimizing the process of inhalation itself; for example it has been proven that even switching from smoking cigarettes to a pipe (which produces less smoke) has increased the amount of THC to enter the lungs [1]. Very good results can be also achieved with the use of vaporizer [3-5], the crucial factor here being the vaporization temperature and the amount of raw material in the chamber [6]. Generally speaking, the higher the temperature, the more cannabinoids are vaporized (especially since some of them boil in very high temperatures – like CBG that requires over 200° C to vaporize). Of course the rise in temperature also speeds up the degradation processes, but as the degradation curve rises slower than the level of cannabinoids effectively vaporized, the rule of thumb remains: the higher the temperature, the better. The higher the temperature, the better.
Efficiency-wise, it is also worth noting that the efficiency of vaporization per gram is the higher the less raw material is in the filling chamber in the beginning.

A nebulizer allowing the inhalation in the lower temperatures would also be a good alternative, if not for the fact thatthis method requires the active substances to be water-soluble, which in the case of cannabinoids necessitates their appropriate pharmaceutical modification [7]. Either way, both vaporization and nebulization allow to avoid inhaling toxic products of plant material’s <pyrolysis>.

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There are just few papers setting out to examine the inhalation of cannabis extracts. In fact, the only study available is the nebulization study conducted by GW Pharmaceuticals on the occasion of the introduction of Sativex, et although it is an extract-based product, it also containis ethanol, propylene glycol and mint oil [8]. Studies have indeed shown high absorption of cannabinoids with this method of administation, but the reported side effects such as cough, hoarseness and throat irritation have caused the subjects to favour the other administration methods tested, such as sublingual drops and oral spray.

The undoubted advantage of inhalation is that it allows for the very rapid (in minutes or even seconds) appearance of cannabinoids in the blood stream and their equally fast distribution in the body. In the case of THC, its maximum concentration in the blood occurs as soon as already during the inhalation (!), although in just a few minutes after it, the level of its unmetabolized form plummets and after just about half an hour it is already lower than the concentration of its metabolites that start to appear on an equally rapid rate [9]. Compared to oral administration, the duration of the psychoactive effects following inhalation is shorter, the same applies to the effect on the body – the so-called pharmacodynamic effect. To simplify this – inhalation grants the faster effect, yet for a shorter time, while the oral administation takes more time, but the effects last longer [10]. This happens because oral absorption is much slower and THC is continuously distributed in small doses throughout the body (for example – to the <adipose> tissue, from where it is then released back to the bloodstream long after the intake) [11], whereas the inhalation works rather on the “first come, first served (and first to leave)” principle.

PhD, Eng. Beata Plutowska
Translation: Robert Kania

References:

[1] Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics 42 (2003) 327-360.
[2] Borgelt L.M., Franson K.L., Nussbaum A.M., Wang G.S. The pharmacologic and clinical effects of medical Cannabis. Pharmacotherapy 33(2013) 195-209.
[3] Abrams D.I., Vizoso H.P., Shade S.B., Jay C., Kelly M.E., Benowitz M.L. Vaporization as a smokeless Cannabis delivery system: A pilot study. Clinical Pharmacology & Therapeutics (2007) 1-7.
[4] Gieringer D., St Laurent J., Goodrich S. Cannabis vaporizer combines efficient delivery of THC with effective suppression of pyrolytic compounds. Journal of Cannabis Therapeutics. 4 (2004) 7-27.
[5] Hazekamp A., Ruhaak R., Zuurman L., van Gerven J., Verpoorte R. Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. Journal of Pharmaceutical Sciences 95 (2006) 1308-1317.
[6] Pomahacova B., Van der Kooy F., Verpoorte R. Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhalation Toxicol0gy 21 (2009) 1108-1112.
[7] Naf M. Pharmacokinetics and analgesic potency of ?-9- tetrahydrocannabinol (THC). Inauguraldissertation zur Erlangung der Würde einer Doktorin der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel (2004) Luzern.
[8] Guy G.W., Flint M.E. A single centre, placebo-controlled, four period, crossover, tolerability study assesing, pharmacodynamic effects, pharmacokinetic characteristics and cognitive profiles of a single dose of three formulations of Cannabis Based Medicine Extracts (CBMEs) (GWPD9901), plus a two period tolerability study comparing pharmacodynamic effects and pharmacokinetic characteristics of a single dose of Cannabis Based Medicine Extract given via two administration routes (GWPD9901 EXT). The Haworth Press, Inc. 2003
[9] Huestis M.A., Henningfield J.E., Cone E.J. Blood cannabinoids. I. Absorption of THC and formation of 11-OH- THC and THCCOOH during and after smoking Marijuana 16 (1992) 276-282.
[10] Information for health care professionals: Cannabis (marihuana, marijuana) and the cannabinoids (February 2013) Health Canada
[11] Public Information Report on Sativex Oromucosal Spray UK/H/961/01/DC