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Research

The Bioavailability of Cannabis Through Various Delivery Methods

Ashley Priest

by Ashley Priest

August 12, 2024 02:47 pm ET Estimated Read Time: 11 Minutes
Fact checked by Kymberly Drapcho Medically reviewed by Dr. Abraham Benavides
The Bioavailability of Cannabis Through Various Delivery Methods

Different methods for consuming cannabis will provide the body with varying amounts of cannabinoids. There’s a difference between smoking a joint, bowl, bong, or blunt, vs. eating an edible, or taking a bit of tincture. The same applies when you do a dab or consume cannabis concentrates, use transdermal patches, creams, lotions, or other topicals.

When you consume a cannabis product, whether it be Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD), how much of it is your body actually taking in? If a product says it contains 100 mg of CBD and you take all of it, you presume that you consumed 100 mg of CBD correct? You may have taken 100 mg of CBD, but that doesn’t mean your body is receiving or utilizing all 100 mg of CBD (8).

The bioavailability of the CBD you consume will determine how much of that 100 mg your body actually gets to use. When someone consumes 100 mg of CBD with a given bioavailability rate, they may only take in as little as 30% or 30 mg of the 100 mg of CBD they just ingested. The rest is thought to be discarded as waste by the body, but some cannabinoids and their metabolites will bioaccumulate in the body depending on frequency and metabolic factors (8). The long-term effects and tissue distribution of this bioaccumulation are yet to be determined but so far have not shown serious adverse effects nor serious drug interactions. This is why knowing the bioavailability of different consumption methods can be very valuable for a patient trying to pinpoint the right regimen for their needs.

Bioavailability Of Cannabis

What Is Bioavailability?

Per Merriam Webster Dictionary, bioavailability is described as “the degree and rate at which a substance (such as a drug) is absorbed into a living system or is made available at the site of physiological activity.” This means that if a product has a high bioavailability rate, you are getting more out of it versus one with a low bioavailability rate. There are several complex metabolic factors that influence different methods’ bioavailabilities. Sometimes these factors vary based on the metabolism and enzyme levels a specific person has in their body compared to others.

What Is Nano-Availability?

Nano refers to the size, in this case, super microscopic. Nano-availability is a relatively new area of medicine delivery with great promise. This process allows medications to be more efficiently absorbed. The use of nanomedicine, though it is a recent pharmacological advancement, has been used to target a variety of site-specific diseases (6). Some of the targets have been used to advance chemotherapeutic and immunotherapeutic medications along with improving the efficacy of many existing medications. 

According to researchers “Initially, the use of nanotechnology was largely based on enhancing the solubility, absorption, bioavailability, and controlled-release of drugs (6).” 

The exciting thing about this is that it can also be applied to cannabis products to increase bioavailability and medicinal effects. In fact, some companies are already using this technology such as Boulder, Colo. based Wana brands to increase bioavailability and absorption speed. Their line of tinctures and fast-acting edible products use their own proprietary nano-liposomal emulsion technology (9). 

Different Consumption Methods & Bioavailability 

The five main consumption methods include inhalation, sublingual, oral, transdermal, via suppositories, and transdermal. As you may or may not know, many people have different preferences on what delivery method they prefer. Some people may prefer smoking or vaporizing while others prefer faster absorption routes like using sublingual tinctures. Keeping all of this in mind, let’s take a look at five delivery methods for consuming cannabis and see how the bioavailability rates vary.

Inhalation

Within inhalation methods such as smoking a joint or vaping, the THC bioavailability averages about 31% per a 2018 systematic review (8). Additionally, it is suggested that the bioavailability and blood plasma levels vary based on how large of a puff is inhaled and how deep the cannabis smoke has been inhaled into the lungs (5).

When it comes to joints, they typically contain .5 to .8 grams of cannabis that usually is about 8% THC. Experts believe that between 20-70% of the THC enters your lungs, with about 30% of that becoming bioavailable after entering your bloodstream. The THC peaks in your bloodstream in 3 to 10 minutes and is no longer bioavailable in about 3 hours via smoking. 

In earlier studies, when a 3.55% THC cigarette was consumed, the participant reached a peak plasma level of 152±86.3 ng/mL approximately 10 min after inhalation. However, this study concluded that “Bioavailability following the smoking route was reported as 2−56%, due in part to intra- and inter-subject variability in smoking dynamics, which contributes to uncertainty in dose delivery (5).” – Marilyn A. Heustis, 2007

Smoking cannabis with a bong is said to remove higher levels of tar, but one study found that it actually removes higher THC levels out of the cannabis as opposed to the tar (2). A bong, however, does remove gas-phase intoxicants out of marijuana smoke including carbon dioxide, ammonia, and nitrosamines.

Many people assume that inhaling cannabis, whether smoking or vaporizing gives your body the same amount of THC, but this simply is not true. Vaporizing cannabis actually delivers cannabis more efficiently into the lungs while a smaller amount of tar is inhaled. This is typically a 1:10 cannabinoid to tar ratio, as opposed to 1:27 for smoking cigarettes and an average of 1:27 for smoking cannabis out of pipes (2).

It is important to note that various cannabis strain CBD and THC concentrations have increased over the years and that now cannabis may contain equal portions of CBD and THC (5). Depending on the levels of CBD compared to THC, the sensation of being “high” may change as well as the medicinal effects from marijuana.

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Sublingual

Many consider the sublingual intake of cannabinoids to be very comparable to that of inhalation in terms of bioavailability simply because they utilize similar mucous membranes for absorption into the bloodstream (5). Basically, sublingual or oral-mucosal cannabinoids are a mixed delivery method mostly involving absorption through mouth mucous membranes and some are digested. The onset is faster and usually reaches higher concentrations than edible (oral) cannabis. 

According to studies on Sativex, a 1:1 CBD: THC oromucosal prescription spray, bioavailability was estimated between 92-98% (7). Sativex (nabiximols) is a prescription-only mouth spray that is currently in trial phases for approval by the FDA but it is available in Canada, the United Kingdom, and some European countries. It is intended to alleviate neuropathy, spasticity, and overactive bladder symptoms for use in patients with multiple sclerosis (MS)

Oral

According to a respected cannabinoid pharmacokinetics review, it was found that oral bioavailability ranges from 4-20% with peak THC concentrations ranging from 4.4-11ng/ml roughly 2-4 hours after the ingestion of a 20mg THC cookie. 

Dr. Huestis adds that “variable absorption, degradation of [the] drug in the stomach, and significant first-pass metabolism to active [11-hydroxy tetrahydrocannabinol] 11-OH-THC and inactive metabolites in the liver” could be the underlying cause as to why this consumption method offers such a low bioavailability rate. When cannabis is orally and undergoes first-pass metabolism, 50% of the THC that is being metabolized gets broken down into 11-OH-THC before it circulates into the bloodstream, which is a factor in why the bioavailability is decreased in this form (2). Some researchers believe that 11-OH-THC contributes to 4-times the psychoactive effects of THC on its own, which might explain why people tend to experience a more intense ‘high’ feeling while taking cannabis orally. 

Despite the lower bioavailability of edibles, tinctures, and oral capsules, these products typically last longer than other methods of consumption. This is seen by the fact that cannabis blood concentrations hit peak plasma levels between one to six hours and have been shown to have a half-life of 20-30 hours (2). 

It is important to remember that everyone digests food at different rates and has different levels of digestive enzymes in their system. This means that oral cannabis consumption effects will vary from person to person. One dose that works great for a friend may be too large or small for you because of this.

Suppositories

There are several different CBD and THC suppositories on the market. One may wonder what these are used for. Research suggests that rectal administration could be very valuable for those suffering from GI-related issues, severe nausea, cachexia, altered mental status, speech/swallow disorders, and the elderly (5). 

Keep in mind, using a suppository gives you local pain relief, as opposed to other delivery methods where THC passes into the blood (3). Thus overall bioavailability of THC used as a suppository has no rectal bioavailability. In fact, a 1985 study focusing on rectal use in rhesus monkeys found that THC was not bioavailable after testing blood plasma levels (10). This was compared to oral and intravenous, and intramuscular cannabis delivery methods. 

One study focused on administering Marinol rectally. Marinol, a synthetic THC medication, has been approved by the FDA and is primarily used for uncontrolled nausea during chemotherapy in cancer patients. This study on Marinol for spasticity concluded that rectal administration of 2.5−5 mg of THC produced maximum plasma concentrations of 1.1−4.1 ng/ml within 2−8 h (5). Researchers found that rectal bioavailability of the was approximately twice that of using Marinol orally. Rectal use was shown to absorb in the body quicker and bioavailability was higher because it was absorbed rectally at higher levels and had a lower first-pass metabolism. and lower first-pass metabolism. Lower first-pass metabolism is important because more of the medication is bioavailable for the body to use. It is important to note that this could be due to the fact that Marinol is not real THC, just synthetic.

Additional studies show that like Marinol, a chemically modified version of THC called THC-hemisuccinate (THC-HS) is bioavailable in the rectum (3). THC-HS rectal use can result in improvements in spasticity, rigidity, and pain while producing any other measurable signs of intoxication. A 2018 study published in Medical Cannabis and Cannabinoids found that after rectal administration of THC-HS Δ9-THC levels were about 70%-80% bioavailable. This bioavailability measurement was two-and-a-half times higher than levels after an orally ingested THC capsule. 

It is important to again reiterate, that THC has no bioavailability when used rectally unless it has been altered. We also do not know how bioavailable THC or CBD is when used in suppositories vaginally, though there are studies underway to change that knowledge (3). Despite this, many women are opting to use cannabis-based suppositories for a variety of women’s health concerns including vulvodynia, endometriosis, pelvic floor dysfunction disorders, and painful sexual intercourse. 

Topical and Transdermal

Topical and transdermal products work to help relieve pain and inflammation transcutaneously, or through the skin (5). This is because they are repelled easily by water, which allows them to transport easily across the aqueous layer of the skin. 

While there have been no human-based studies on the bioavailability of cannabinoids through a topical or transdermal application, the preclinical animal studies are promising. These application methods avoid a first-pass metabolism effect and through slow-release, they offer dosing over a longer period of time in comparison to other delivery methods. They are also likely not well absorbed into the rest of the body beyond the application site, meaning not well “systemically” absorbed (4). It is unlikely to feel psychoactive effects of cannabis when applying it to the skin. More research is needed on determining the true bioavailability of topical products.

Available cannabis-based topicals include (2):

  • Creams (equal portions of oil and water)
  • Ointments (oil and water in an 80%:20% ratio)
  • Herbal poultices
  • Transdermal patches (contain 10 mg of THC mixed in a polymer matrix and extracted from cannabis using ethanol)

A 2016 study evaluated the efficacy of transdermal CBD for reducing pain and inflammation in arthritic rat models. Researchers applied CBD gel doses of 3.1, 6.2, and 62.3 mg a day, and analyzed blood plasma levels along with evaluating synovial joint tissue thickening. They found that topical CBD gel in the larger doses improved arthritic symptoms in the rats and that it has a strong therapeutic potential for humans suffering from similar issues (4).

When it comes to using transdermal patches, researchers hope that it can reduce the negative side effects of cannabis use seen while smoking. They also believe that transdermal patches bypass the first-pass metabolism of cannabinoids which can help improve the effectiveness of the transdermal patch being used (5). Anecdotally many users experience stronger and longer-lasting joint and muscle pain relief while using transdermal patches over topical products, but also this may depend on the amounts of THC and CBD in each of the products.

1. Absorption – a complete guide. Cannify. (2021). Retrieved December 7, 2021, from https://www.cannify.us/education/cannabis-and-the-body/cannabinoid-clinical-pharmacology/what-your-body-does-to-cannabis-pharmacokinetics/thc-absorption/

2. Fugh-Berman, A., Wood, S., Kogan, M., Abrams, D., Mathre, M. L., Robie, A., Raveendran, J., Onumah, K., Mehta, R. S., White, S., Kasimu-Graham, J., & D’Antonio, P. (n.d.). An Introduction to the Biochemistry & Pharmacology of Medical Cannabis. Washington DC; Department of Health. https://doh.dc.gov/sites/default/files/dc/sites/doh/publication/attachments/Medical%20Cannabis%20An%20Introduction%20to%20the%20Biochemistry%20and%20Pharmacology.pdf

3. Grove, J. (2020, January 14). Do cannabis suppositories work? Project CBD. Retrieved December 7, 2021, from https://www.projectcbd.org/medicine/do-cannabis-suppositories-work

4. Hammell, D. C., Zhang, L. P., Ma, F., Abshire, S. M., McIlwrath, S. L., Stinchcomb, A. L., & Westlund, K. N. (2016). Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. European journal of pain (London, England), 20(6), 936–948. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/ 

5. Huestis M. A. (2007). Human cannabinoid pharmacokinetics. Chemistry & biodiversity, 4(8), 1770–1804. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/ 

6. Patra, J. K., Das, G., Fraceto, L. F., Campos, E., Rodriguez-Torres, M., Acosta-Torres, L. S., Diaz-Torres, L. A., Grillo, R., Swamy, M. K., Sharma, S., Habtemariam, S., & Shin, H. S. (2018). Nano based drug delivery systems: recent developments and future prospects. Journal of nanobiotechnology, 16(1), 71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145203/

7. Karschner, E. L., Darwin, W. D., Goodwin, R. S., Wright, S., & Huestis, M. A. (2011). Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clinical chemistry, 57(1), 66–75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717338/ 

8. Millar, S. A., Stone, N. L., Yates, A. S., & O’Sullivan, S. E. (2018). A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Frontiers in pharmacology, 9, 1365. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275223/

9. Wana Quick Fast-Acting Tincture’s innovative nano-liposomal emulsion technology transforms cannabis consumption. Quicksilver Scientific. (2020, December 1). Retrieved April 7, 202 from https://www.quicksilverscientific.com/wana-quick-fast-acting-tinctures-innovative-nano-liposomal-emulsion-technology-transforms-cannabis-consumption/ 

10. Perlin, E., Smith, C. G., Nichols, A. I., Almirez, R., Flora, K. P., Cradock, J. C., & Peck, C. C. (1985). Disposition and bioavailability of various formulations of tetrahydrocannabinol in the rhesus monkey. Journal of pharmaceutical sciences, 74(2), 171–174. https://pubmed.ncbi.nlm.nih.gov/2985774/

Post Your Comments

  • Raynee Holland says:

    August 18, 2022 at 10:46 am

    Hello, my name is Raynee Holland. I recently just got my medical marijuana card. So, I am 19 my doctor did tell me before I got the card that FL doesn’t really allow flower if you’re under 21. I was allowed “inhalation” on my medical marijuana, does concentrate include for that? Or is that against the 21 law.

    Reply
  • Judges Carter says:

    November 17, 2022 at 10:44 am

    Absolutely grand information here. Thank you. I have made suppositories for years.

    Reply
  • Ryan says:

    April 22, 2023 at 12:27 pm

    “Within inhalation methods such as smoking a joint or vaping, the THC bioavailability averages about 31% per a 2018 systematic review (8).” This is for CBD, not THC, as the article states.

    Reply

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