How Cannabinoids Work: Part I – Paths Into the Body | Marijuana

How Cannabinoids Work: Part I – Paths Into the Body


Researchers have made great strides in discovering how medical cannabis works in the body, but individual patients may still wonder how it can help them, and in what form and what dose. The journey to figuring out the answer can be frustrating, as even experienced medical cannabis consumers often don’t know the specifics when it comes to questions of what, how, when, and how much.

The answer has to do with bioavailability, the fraction of an active ingredient that gets to the target cells after the body metabolizes it and breaks it down.

For example, if you take a single 500 milligram tablet of acetaminophen, it goes into your stomach, where the active ingredient is digested. It goes through the liver, where it interacts with enzymes and some of it is deactivated, or destroyed. By the time it reaches the bloodstream, only about 315 mg, or 63 percent, is left to do the job.

Companies take this into account when coming up with dosing guides, and medical professionals come out of school armed with reference books telling them how bioavailable various drugs will be. To confuse matters more, the amount left after metabolism can change based on how large the dose is, what else the liver is doing, and other body-specific factors.

Cannabinoids, of course, are not listed in these reference works, but the body of evidence in modern research serves as a helpful guide.  

In general, cannabinoids act as signaling messengers that enter the body and bind to cellular receptors. From there, they set off a chain of events, including changes in protein concentrations and metabolite levels, and ultimately create physiological changes in the body. Those are the desired effects, as well as the side effects.

How big those effects are depends on the number and “fit” of the signaling molecules.

When a cannabis product is labeled, for example, 5 percent THC, we would like to know how much of that 5 percent interacts with its target in the body — in this case, the cannabinoid-binding receptors. Knowing the bioavailability, or fraction of a drug that gets absorbed, helps us to predict the expected effects, such as reduced pain or improved sleep.

To more accurately gauge the effects of cannabis, it’s important to understand two basic concepts. First, we’ll look at how the various paths cannabis can take into the body impact its bioavailability.  In a follow-up column, we’ll discuss how cannabis moves through the body, and what happens to it there.

Paths Into the Body

Traditional pharmaceuticals are listed by dosage type: oral, intravenous, intramuscular, and so on. Cannabinoids are available in several different forms, delivery methods, and combinations of the two that affect their path into the body.

In terms of active ingredients, we can classify cannabis products into three types:

  • Single-molecule, or pure, products, such as those containing only THC or CBD
  • Mixtures, with more than one known molecule, such as THC/CBD/terpene blends, provided at a specific ratio
  • Flower, which contains hundreds of molecules, some of which may or may not be specified

We do not expect a product with 20 percent pure THC, a product with 20 percent THC in a THC/CBD mixture, and a flower labeled as 20 percent THC to produce the same results in the body, because these products do not have the same bioequivalence, a pharmaceutical term indicating products with identical effects. The single-molecule product will interact with a specific type of receptor in the body, while the mixture and flower will have an “entourage effect” in which multiple molecules or the whole plant work together to create a different response from that of the purified active ingredient, according to research from neurologist and cannabis researcher Dr. Ethan Russo.  

The form of the product and the delivery method both affect bioequivalence, meaning they both raise the question of “how much?” For example, flower labeled 20 percent THC may also contain significant amounts of THCA, the cannabinoid acid form that must be converted to THC by heat, which increases the total THC concentration delivered to the body to as much as 25 percent.

Another challenge for determining how much is inaccurate potency labeling. A 2017 study led by Dr. Marcel O. Bonn-Miller  found that only one-third of the CBD extracts sold online are accurately labeled, with large numbers of products containing either significantly more or significantly less CBD than stated on the label. This study indicated that vaporization liquid is the most frequently mislabeled product.

As states roll out rules and regulations for lab testing, many are discovering variances in labeling, lab procedures and allowable levels of contaminants that led to significant failure rates. A report from NBC’s San Francisco Bay Area affiliate KNTV-TV showed that identical samples tested in two independent labs could result in a 23 percent difference in content, which shows a lack of testing reproducibility among labs.

For comparison, pharmaceutical companies report a maximum of 5 percent variation of active ingredient content among products from the same batch.

Standardization of production processes and testing, as well as increased regulation, should lead to greater accuracy.

About Author

Itzhak Kurek is the CEO and co-founder of Cannformatics Inc, a startup that matches medical cannabis patients to the most effective cannabis strain, product and dosage, based on saliva biomarkers. He has 25 years of experience in biochemistry and molecular biology, specializing in plant photosynthesis, yield enhancement, metabolism and cellulose biosynthesis. He received his Ph.D. in plant sciences from Tel Aviv University in Israel and completed his postdoctoral research at the University of California, Davis. He has also conducted research at the Technical University of Munich in Germany; John Innes Center in Norwich, England; the National Center for Scientific Research (CNRS) in Bordeaux, France; and the Lawrence Berkeley National Laboratories in California. He has published 20 peer-reviewed scientific papers and more than 10 granted US and international patents.


  1. I’m quite certain that the proper combination of tincture CBD around 80- 90% and THC will alleviate crippling neuropathic pain without making me sleepy but at advanced age don’t want to experiment considering all my other meds. As the Feds take on Pharma pricing and more states legalize cannabis the FDA will eventually cave and we’ll get some medically approved clinical trials and drop the seven veils. Flying medically blind on something so obvious as non-hemp medicinal cannabis is like getting rid of prohibition and absurd. Trouble is that the eventual legalization will be primarily for the highs, not the pain relief.

    • It’s funny to me that an adult male cannot comprehend the connection between addiction, seeking out highs, and pain. Whether it be your neuropathic pain, or pain from depression and anxiety, or any other disorder that causes physical pain to manifest itself within our bodies. We all go through pain, why do you think it is okay for you or anyone else to say who gets to medicate themselves with some of the most naturally effective medications on earth. Medicinal marijuana is not just for patients that experience physical pain, it is for patients with a whole lot of other symptoms like trouble focusing, depression, insomnia, etc.

  2. How would I get in touch with Dr. Kurek to obtain his services? I have an intractable pain condition that I’m attempting to treat with CBD oil (full spectrum, lab tested), but I have no idea what my specific needs are or which entourage effect combinations would be most beneficial for me.

    Please contact me using the email address I’ve provided when filling out this form.

  3. CBDA (cannabidiolic acid) decarboxylates when heated at 230 degrees F to become CBD, which evaporates around 356 degrees F. Once it is converted, the molecule is CBD with the same effect you expect from CBD.
    I hope this helps.

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