Natural cannabinoids bioavailability (1/6)

Natural cannabinoids bioavailability (1/6)

Each compound introduced into our bodies can be tracked and divided into four stages: absoprtion, distribution, metabolism and elimination. As an introduction to this big issue, we take on the first bit – absorption of cannabinoids.

Most studies done so far on different methods of cannabinoids application deal with crystalline THC, and less often CBD. While we can safely assume the results obtained for THC might, to some extent, be replicated on other cannabinoids, the same cannot be said about the use of isolated cannabinoids and natural extracts [1]. Things get even more complicated, once you go into details – each extraction method results in different composition and ingredients of the final product, which all have major influence on absorption. One good example is the oral intake of water insoluble substances (such as cannabinoids) together with lipid-like substance (e.g. vegetable oil) increases bioavailability and increases the rate of transportation of those from intestine directly to circulatory system via lymphatic system (bypassing the liver), allowing for the use of smaller dose [2].

The concept commonly used in the pharmaceutical industry and health sciences is the relative bioavailability, defined as the quantity of unchanged active substance appearing in blood plasma compared with intravenous application (considered to be 100%). It is necessary to determine the stable and unified dose of the specific active ingredient to be applied to all patients suffering from a specific condition. In the case of natural hemp extracts, however, for a number of reasons things get more complicated and such methodology is of limited use [3].

One of the reason for that is the role of metabolites. As will be discussed later, cannabinoids metabolites may still be biologically active (that is one of the reasons why recent studies include the concentration of metabolites in the plasma – this, however, is done only for the few major metabolites, ot of more than a 100 identified for THC and CBD only!). Another, equally important factor, is that we don’t know, whether the relationship between the concentrations of cannabinoids in the blood plasma and its concentration in individual tissues and organs exists and if so, how to measure it – blood plasma is not a destination place for cannabinoids activity or storage [4]. It has been known already since the eighties, that the THC “high” is correlated with low concentration on the plasma – it is the neural tissue of the brain, where it acts on our cannabinoid receptors [5]. It is the brain and other organs that are generally considered as targets for various biologically active substances, not the plasma – and therefore it is safe to assume, that only local measurement of the cannabinoids concentration can provide reliable information about the actual bioavailability and effective therapeutic dose [3].

To make it even more complicated – it is well established, that intake of single cannabinoid has a completely different influence than using a mixture of different, naturally occurring cannabinoids and other compounds found in hemp plant, including terpenoids etc. Those mutually interacting substances have synergies of their own and show significant differences in bioavailability compared to particular isolated cannabinoids. Moreover, as different extracts are available on the market, they provide different ratios of each ingredient. Many manufacturers do not put enough stress on the standardization of the product, leading to significant differences from batch to batch even within a given brand… All the more reason to look out for reliable sources of hemp extracts, with detailed information on each lot cannabinoid profile. Otherwise it is almost futile to engage in discussion on natural hemp extracts bioavailability.

Many people report that they feel significant differences in the effect of particular hemp extracts even when their label suggest similar potency. This most probably results from different ratios of particular cannabinoids, presence of other plant-derived compounds that could positively or negatively affect bioavailability.

All of that suggest, that using standard measurement methods, applied universally for drugs and medicines, cannot be simply copy-pasted for cannabinoids bioavailability analysis. Using oversimplified indicators such as “total percentage bioavailability”, as often seen in the manufacturers’ marketing materials, can lead to drawing false conclusions and potentially harmful and/or wasteful use of hemp extracts. Since our own endocannabinoids are produced locally right where they are needed [6], it seems logical to provide phytocannabinoids as close as possible to where we want them to go. Bloodstream, being non-selective, should not be your first-choice [7]. Choosing the best method of administration (inhalation, sublingual administration, oral administration, transdermal application etc.), therefore, depends on your needs and should be made on a case-by-case basis

Final factor to consider while taking cannabinoids, is the variation between individual organisms, their different conditions, as well as the expectations of users. The spectrum of the observed biological effects of cannabinoids is wide, so the dosage depends on the desired effect. Other dosage can produce analgesic effects and other anticonvulsants. Due to all these factors, the most common method recommended by those skilled the use of hemp and cannabis extracts is known as titration – gradual dose adjustment (starting with the lowest, and then slowly increasing or decreasing) to obtain optimal results. This is the method frequently used in medicine also for commercially available pharmaceutical formulations containing cannabinoids, such as Sativex [8].

Beata Plutowska, PhD

References:

[1] Gallily R.,Yekhtin Z., Hanus L.O. Overcoming the bell-shaped dose-response of cannabidiol by using Cannabis extract enriched in cannabidiol. Pharmacology & Pharmacy 6 (2015) 75-85.
[2] Kalepu S., Manthina M., Padavala V. Oral lipid-based drug delivery systems – an overview. Acta Pharmaceutica Sinica B, 3 (2013) 361-372.
[3] Ginsburg B.C. Toward a comprehensivemodel of delta-(9)- tetrahydrocannabinol pharmacokinetics using a population pharmacokinetics approach. Clinical Pharmacokinetics 54 (2015) 129-131.
[4] 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.
[5] Hollister L.E, Gillespie H.K, Ohlsson A, Agurell S. Do plasma concentrations of Δ9- tetrahydrocannabinol Reflect the degree of intoxication? The Journal of Clinical Pharmacology 21 (1981) 171S-177S.
[6] Wang J., Ueda N. Biology of endocannabinoid system. Prostaglandins & Other Lipid Mediators 89 (2009) 112-119.
[7] Huestis M.A. Human cannabinoid pharmacokinetics. Chemical Biodiversity 4 (2007) 1770-1804.
[8] Public Information Report on Sativex Oromucosal Spray UK/H/961/01/DC