Cannabinoid Bioavailability

main-cannabinoids

When cannabinoids are swallowed on an empty stomach surprisingly few avoid “first pass metabolism” by the liver and enter circulation unaltered. Studies indicate swallowed Δ9-tetrahydrocannabinol (THC) has a bioavailability of between 4% to 20%. This low bioavailability is in direct contrast to the strong wave of neuro-activity often felt. The reason for this contradiction is that the metabolism of THC into 11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) produces a molecule many times more neuro-active, but with key medical benefits deactivated. Highly neuro-active metabolites are the reason a cannabis euphoria (high) can have two distinct phases.

first-pass

People mistakenly take an intense high as an indication their medicine has successfully absorbed and so believe they are healing themselves efficiently, but sadly they are often mistaken. Counter intuitively the height of the high a person experiences can be a relatively poor indicator as to the amount of unmetabolised THC circulating and healing the body. Due to the low and varied bioavailability of oral THC formulations, alternative routes of administration, including oromucosal (through the mouth lining), sublingual (under the tongue), vaporisation, inhalation and rectal administration have been developed by pharmaceutical companies to improve the amount of cannabinoids delivered in their products. All medical users should take note of these measures as this is an industry that would much prefer to produce a useable cannabis pill. That they don’t is for good reason.marijuana_tinctures_15

The bioavailability of cannabinoids is lower when taken on an empty stomach, or more accurately, an empty liver. Oils are metabolised mostly in the liver and by eating fat 30 minutes before administering cannabis oil, the liver will be otherwise occupied when the medicine starts to circulate. A tablespoon of coconut oil is widely considered to be a healthy and effective option and other supplements can be taken with or mixed into the coconut oil. The eating of the coconut oil is to otherwise occupy the liver. Easily absorbed by the small intestine and transported to the liver, coconut and cannabis infusions/mixes are particularly inefficient except perhaps for treating a liver problem. Then it would be a very efficient delivery method, but still not always the best as vasodilation might be an issue. Your blood vessels (especially in the digestive system) become larger, allowing for increased blood-flow, which is normally okay. However for people with gall bladder / liver problems, this means immediate inflammation and potential pain, despite any anti-inflammatory effects.

cannabis-coconut-oil

Just because a cannabinoid has found it’s way to the liver does not, however, mean it will remain there to successfully treat disease. The enzymes that metabolise cannabinoids are mainly found in the liver so a cannabinoid entering the liver is more likely to connect with an enzyme and be metabolised rather than connect with a cancerous cell. This makes liver cancer a trickier one to treat without additional supplements. Beneficially, certain plant molecules are metabolised by the same enzymes that metabolise most THC molecules. The enzyme Cytochrome P450 2C9 (CYP2C9, plays a major role in oxidation of xenobiotic [foreign chemical substances] and endogenous compounds) and molecules, apigenin (bioflavonoid found in many fruits and vegetables) and amentoflavone (plant alkaloid found in such as Gingko biloba and St John’s Wort; also a body-building supplement), as well as having additional benefits, will give the enzymes work, keep them busy, allowing cannabinoids a greater opportunity to circulate, connect with and destroy mutated cells in the liver and throughout the body.

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This enzyme busying effect is called competitive inhibition. A well known example is the grapefruit effect. A molecule in grapefruit called bergamottin competitively inhibits an enzyme called Cytochrome P450 3A4 (CYP3A4, which contributes to bile acid detoxification, termination of action of steroid hormones and elimination of phytochemicals in food) that metabolises many pharmaceuticals causing a risk of build-up and overdose. Bergamottin slows drug removal by 50-80% categorising it as a moderate inhibitor. Apigenin and amentoflavone reduces clearance by just under 80%, a strong inhibitor. As one cannot overdose on cannabis, this strong competitive inhibition can be safely harnessed, allowing cannabinoids greater chance to heal and maximise the benefits of an often expensive and limited supply. Amentoflavone is also among the more powerful inhibitors of CYP3A4.

chemistry-of-a-grapefruit

Slowing metabolism does not result in a stronger high. The main metabolite of THC is 11-OH-THC. This metabolite is more neuro-active than THC, the very reason a cannabis high can have two distinct phases. Slowing metabolism of THC to 11-OH-THC means the more neuro-active metabolite’s entry into the body is spread out over a longer period. Consequently a person is less likely to be made uneasy by a strong, more condensed wave of neuro-activity. It’s counter-intuitive but the amount of healing occurring cannot easily be judged by the height of the high. THC will be long gone by the time the effects of the 11-OH-THC have stopped being felt. Additional oil should be administered whilst still feeling the effects of the 11-OH-THC if a constant pressure is to be placed on a disease.

apigenin

To place a disease under constant pressure, cannabis oil should be taken more than a couple of times a day. If apigenin and amentoflavone are being used, perhaps four to five suppositories / doses in 24 hours. 50 mg of apigenin and twice a day 200 mg of amentoflavone, 30-40 minutes before each suppository over a few days. A daily dose of 250 mg of apigenin and 400 mg amentoflavone is not excessive, more might safely be used. Apigenin and amentoflavone will interact with certain pharmaceuticals and interactions are well understood, researched and documented. Their use should be emphasised to, and noted by, any doctors who might be administering pharmaceuticals and any pharmacist can check contra-indications. The effects will last for perhaps a few days after use is discontinued.

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Selaginella tamariscina (amentoflavone)

Apigenin and amentoflavone are also Monoamine Oxidase Inhibitors (MAOI’s). MAOI’s block an enzyme called monoamine oxidase, which breaks down excess tyramine in the body. Blocking this enzyme helps relieve depression. However, tyramine can quickly reach dangerous levels if you eat high tyramine foods, which may cause a spike in blood pressure and require emergency treatment. Tyramine is not tricky to avoid and many people take MAOI’s. Tyramine is naturally found in small amounts in protein-containing foods. As these foods age, the tyramine level increases. Some foods high in tyramine include:

  • Aged Cheddar and Swiss cheeses, Blue cheeses such as Stilton and Gorgonzola, and Camembert. Cheeses made from pasteurised milk are less likely to contain high levels of tyramine, including American, Cottage, Ricotta and Cream cheeses.
  • Cured meats, treated with salt and nitrate or nitrite, such as dry-type sausages, pepperoni and salami
  • Fermented cabbage, such as sauerkraut and kimchee

  • Soy, fish and shrimp sauces

  • Yeast-extract spreads, such as Vegemite and Marmite

  • Broad beans such as Fava beans

  • Improperly stored foods / spoiled foods.

cheeses

Adapted from an article, Cannabinoid Bioavailability, by Dominic Le Prevost


Disclaimer: The above information is not to be taken in lieu of actual medical advice

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