Bioavailability

The true bioavailability of cannabinoids is not absolute or consistent among different people. There are MANY variables that affect the percentage of the consumed cannabinoids that actually make it into the human bloodstream, where they are made available to the areas of the body that need them.

There is a lot of debate on the actual percentages, however for the average patient or consumer, that percentage isn't as important as knowing the relative differences based on different administration methods, or ways to take them. Here is a quick reference chart we developed based on the best information we could find:

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The simplified bioavailability graphic above is meant to demonstrate the differences in the main methods to take cannabis products. Research in this area is not robust, but the relative differences are generally accepted common knowledge among most practitioners and experts. We checked in with several.

Below we list the sources we have found that seem to help shed light on this very important aspect of cannabis & hemp products. If you are aware of other sources, whether from experts, research studies, or "conventional wisdom", please let us know.

They are organized by the 5 main administration methods used by patients and consumers today: smoke, vapor, edible, tincture, and emulsion such as nano-emulsions and micro-emulsions. We included a quote from each source, as well as link addresses to the published paper or abstract (many are behind paywalls unfortunately). This is certainly not a complete list, and we welcome new information from research, practitioners, and experts. Please let us know!

Bioavailability is mostly determined by the blood plasma concentration levels over time. The pharmacokinetics (PK) variables measured when determining the bioavailability of a drug include:

AUC (area under the curve) - gives an idea of the drug's concentration in blood plasma over time.
C(max) - the maximum concentration achieved
t(max) - the time it takes to reach the maximum concentration
t(1/2) - 'terminal half life' is the time it takes for the plasma concentration level to fall to one half of the maximum concentration

The chart below shows a typical dose-response graph over time. The AUC is the area shaded blue.

An example blood plasma concentration over time curve showing AUC, Cmax, tmax, C(1/2), and t(1/2)

As you will see, the overall results vary widely, and perhaps even more importantly, the results among people within the same study varied widely. Everyone has a unique condition or goal and a unique biochemistry. So, everyone really HAS to do their own research by trial and error to find out what works best for their unique needs and biochemistry. As always, guidance from experienced cannabis professionals is the best way to start the process.

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The good news is there have been zero confirmed cannabis overdose deaths that we know of. But as more and more products are processed, concentrated, extracted, distilled, and mixed with solvents and additives, we need to be very careful. As we said, there are no absolute rules when it comes to cannabis these days. It is a very personal product and each of us must find out what works best for our goals. There are hundreds of active ingredients made by cannabis and hemp plants, and it's up to everyone to find the best blend of those ingredients for their unique needs, and the best way to take them.

Edibles seem to have very low bioavailability, but that's misleading. Edibles are more highly processed by the liver. That leads to higher concentrations of new, liver-created cannabinoids (11-OH-THC is one) that the other ingestion methods don't usually create because the cannabinoids are absorbed BEFORE they get to the liver. It's why the effects of edibles last MUCH longer than the effects of the other methods of consumption.

Many people report that the effects they experience from edibles (or anything swallowed) are very different from the effects they experience from other consumption methods (inhaling or tinctures, for example). Some people even say they simply don't feel ANY effects from edibles, like they are immune. How YOU experience cannabis will be unique, and will take some trial and error to find out what works best.

Be patient, and always START LOW (dose) and GO SLOW (when increasing your starting dose) until you find what works well for you.

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References sorted by: Method of Consumption, then date of publication or quote.

Methods of Consumption:

Smoke
Edible
Emulsions, Nanoemulsions
Vapor (vaporizers & dabs)
Tincture

General

"The biochemical transformations of cannabinoids in the human body depend on the delivery route used (e.g., oral, inhalation, or transdermal), which impacts their bioavailability and bioactivity"

McClements, D. J., Enhancing Efficacy, Performance, and Reliability of Cannabis Edibles: Insights from Lipid Bioavailability Studies, Annual Review of Food Science and Technology, Vol. 11: 45-70, 2020, https://www.annualreviews.org/doi/10.1146/annurev-food-032519-051837

"Regardless of what any marketing campaign might say, no one knows for sure what the exact rate is. What we do know is that different methods of CBD consumption will produce different rates of bioavailability."

Georgia Smith & Dr. Ted Valley, CBD Bioavailability: The Complete Guide to This Complex Term, Way of Leaf, https://wayofleaf.com/cbd/101/cbd-bioavailability1. Smoke

1. Smoke

"Between 18% and 50% of cannabinoids is bioavailable by smoking"

McClements, D. J. Enhancing Efficacy, Performance, and Reliability of Cannabis Edibles: Insights from Lipid Bioavailability Studies, Annual Review of Food Science and Technology, Vol. 11:45-70 (Volume publication date March 2020), https://www.annualreviews.org/doi/10.1146/annurev-food-032519-051834

"Bioavailability following smoking [a CBD-dominant cannabis cigarette] was 31%"

Millar Sophie A., Stone Nicole L., Yates Andrew S., O'Sullivan Saoirse E. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Frontiers in Pharmacology 2018; 9-1365, https://pubmed.ncbi.nlm.nih.gov/30534073/

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"In five individuals each smoking a single cigarette containing ∼19 mg CBD, the average peak blood plasma level of CBD was 110 ng/mL (range: 42–191 ng/mL) recorded at 3 min postdose; the mean half-life was 31±4 h and the average systemic availability was 31% (range: 11–45%)"

Ujváry I, Hanuš L. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy. Cannabis Cannabinoid Res. 2016;1(1):90-101. Published 2016 Mar 1. doi:10.1089/can.2015.0012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576600/

"The mean bioavailability of THC in smoked cannabis is about 25%"

Goullé JP, Guerbet M. Les grands traits de la pharmacocinétique du delta-9-tétrahydrocannabinol (THC); les nouveaux cannabinoïdes de synthèse; le cannabis et la sécurité routière [Tetrahydrocannabinol pharmacokinetics; new synthetic cannabinoids; road safety and cannabis]. Bull Acad Natl Med. 2014 Mar;198(3):541-56; discussion 556-7. French. PMID: 26427296. https://pubmed.ncbi.nlm.nih.gov/26427296/

"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. The number, duration, and spacing of puffs, hold time, and inhalation volume, or smoking topography, greatly influences the degree of drug exposure"

Huestis, M. A., Human Cannabinoid Pharmacokinetics, Chemistry and Drug Metabolism, National Institute on Drug Abuse, NIH, Chem Biodivers. 2007 August ; 4(8): 1770–1804. doi:10.1002/cbdv.200790152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/

"Average bioavailability by the smoked route was 3.1 to 13% in five subjects, with a fourfold difference in availability noted"

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"They determined that 2−22 mg of THC must be present in a cannabis cigarette to deliver 0.2−4.4 mg of THC, based on 10−25% bioavailability for smoked THC"

"Despite a computer-paced smoking procedure that controlled the number of puffs, length of inhalation, hold time, and time between puffs, there were large inter-subject differences in plasma THC concentrations due to differences in the depth of inhalation, as participants titrated their THC dose"

Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-1804. doi:10.1002/cbdv.200790152, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/#R6

"THC bioavailability averages 30% [from smoking]"

McGilveray IJ. Pharmacokinetics of cannabinoids. Pain Res Manag. 2005 Autumn;10 Suppl A:15A-22A. doi: 10.1155/2005/242516. PMID: 16237477. https://pubmed.ncbi.nlm.nih.gov/16237477/

"The systemic availability after inhalation calculated from the area under curve values was in the range of 27 +/- 10% [24% to 30%] for the heavy users and 14 +/- 1% for the light users. Thus, it seems likely that the statistically significant difference in systemic availability of smoked delta 9-tetrahydrocannabinol was due to a more efficient smoking by the heavy users."

Ohlsson A, Lindgren JE, Wahlén A, Agurell S, Hollister LE, Gillespie HK. Single dose kinetics of deuterium labelled delta 1-tetrahydrocannabinol in heavy and light cannabis users. Biomed Mass Spectrom. 1982 Jan;9(1):6-10. doi: 10.1002/bms.1200090103. PMID: 6277407. https://pubmed.ncbi.nlm.nih.gov/6277407/

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2. Edible

"At present, however, there is a poor understanding of how cannabis edibles behave within the human body after ingestion"

"Studies with other types of hydrophobic bioactives, such as nutraceuticals and vitamins, have shown that food composition and structure have a major impact on their bioaccessibility, transformation, and absorption within the GIT, thereby influencing their bioavailability and bioactivity"

"6–20% [of cannabinoids] is bioavailable after oral ingestion. This is, however, likely to be highly dependent on the nature of the food or beverage consumed"

"Both molecules [THC & CBD] are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%"

Cherniakov, Izgeloz, Domb & Hoffman, The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model, July 2017, European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 109, DOI:10.1016/j.ejps.2017.07.005, https://pubmed.ncbi.nlm.nih.gov/28736128/

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"For example, the oral bioavailability of CBD is roughly 15 percent. That means for every 100 milligrams of CBD that you eat, only 15 milligrams will actually reach your bloodstream"

Andrew Pham, Lead Scientist at CV Sciences, Inc. Formerly Lead Scientist at SC Laboratories. Executive member of the Cannabis Chemistry Subdivision (CANN) of the American Chemical Society. https://www.leafly.com/news/health/vaping-cbd-oil-vs-ingesting

"Oral THC bioavailability was reported to be 10−20% by Wall et al. Participants were dosed with either 15 mg (women) or 20 mg (men) of THC dissolved in sesame oil and contained in gelatin capsules. THC Plasma concentrations peaked ca. 4−6 h after ingestion of 15−20 mg of THC in sesame oil"

"The peak THC concentrations ranged from 4.4 to 11 ng/ml, occurring 1−5 h following ingestion of 20 mg of THC in a chocolate cookie; the oral bioavailability was estimated to be 6%. Slow rates of absorption and low THC concentrations occur after oral administration of THC or cannabis. Several factors may account for the low oral bioavailability of 4−20% (as compared to intravenous drug administration), including variable absorption, degradation of drug in the stomach, and significant first-pass metabolism to active 11-OH-THC and inactive metabolites in the liver"

"Glycocholate and sesame oil improved the bioavailability of oral THC; however, there was considerable variability in peak concentrations and rates of absorption, even when the drug was administered in the same vehicle"

Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-1804. doi:10.1002/cbdv.200790152, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/#R6

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"Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable"

McGilveray IJ. Pharmacokinetics of cannabinoids. Pain Res Manag. 2005 Autumn;10 Suppl A:15A-22A. doi: 10.1155/2005/242516. PMID: 16237477. https://pubmed.ncbi.nlm.nih.gov/16237477/

"CBD has similar oral absorption and bioavailability to THC"

"A comparison of the results for AUC/dose (delta 9-THC) after oral dosing with comparable data from intravenous administration indicated bioavailability of the order of 10% to 20% for both sexes"

Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther. 1983 Sep;34(3):352-63. doi: 10.1038/clpt.1983.179. PMID: 6309462. https://pubmed.ncbi.nlm.nih.gov/6309462/

"THC bioavailability was 6% when orally administered"

Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9- tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther 1980;28: 409 –16

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3. Nanoemulsions & Emulsions

"There have been major advances in the formulation, characterization, and utilization of edible nanoemulsions over the past decade or so." The paper describes 5 different types of nanoemulsion technology that can affect bioavailability: 1) Lipid phase solidification, 2) Interfacial engineering, 3) Lipid droplet clustering, 4) Particle coating, & 5) Microgel encapsulation.

McClements, D. J., Advances in edible nanoemulsions: Digestion, bioavailability, and potential toxicity, Progress in Lipid Research, Vol. 81, January 2021, 101081 https://www.sciencedirect.com/science/article/abs/pii/S0163782720300618?dgcid=rss_sd_all

"There is accumulating evidence from in vitro and in vivo studies showing that nanoemulsions are highly effective at increasing the bioavailability and bioactivity of orally administered hydrophobic bioactives, such as nutraceuticals, vitamins, healthy lipids, and pharmaceuticals"

McClements, D. J., Advances in edible nanoemulsions: Digestion, bioavailability, and potential toxicity, Progress in Lipid Research, Vol. 81, January 2021, 101081, https://www.sciencedirect.com/science/article/abs/pii/S0163782720300618?dgcid=rss_sd_all

"The smaller size of the oil droplets in nanoemulsions means that they are digested more rapidly and fully in the gastrointestinal tract, which can increase the bioavailability of encapsulated hydrophobic bioactives"

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"Researchers concluded that vesicles and lipid droplets, which are often removed when samples are centrifuged to measure bioaccessibility, are effective at solubizing hydrophobic drugs, which may lead to an underestimation of the true bioaccessibility"

Peng, S., & McClements, D. J., Current Status in our understanding of physiochemical basis of bioaccessibity, Current Opinion in Food Science, Vol. 31: 57-62, 2020, https://www.sciencedirect.com/science/article/abs/pii/S221479931930089X

"Both in vitro and in vivo studies have shown that the oral bioavailability of lipophilic nutraceuticals can be increased substantially using nanoemulsion technology"

Choi, S.J., McClements, D.J. Nanoemulsions as delivery systems for lipophilic nutraceuticals: strategies for improving their formulation, stability, functionality and bioavailability. Food Sci Biotechnol 29, 149–168 (2020). https://doi.org/10.1007/s10068-019-00731-4

"These novel formulations use nanotechnology to offer up to 100% bioavailability"

Dr. Patricia Frye, a member of the Society of Cannabis Clinicians and chief medical officer at Hello MD, (2019) https://www.leafly.com/news/health/most-thc-cbd-oil-waste-in-body

"Considering a future clinical study, where the present CBD-NE [nanoemulsion] formulation is orally administered and its pharmacokinetic profile is compared with a conventional oil solution in humans, we could expect the increment of the CBD bioavailability by nanoemulsification to be higher than that observed in the present study (65%). Because the basal bioavailability of CBD in an oil formulation in humans is so low (due to poor absorption and extensive first-pass metabolism), the bioavailability-enhancing effect of NE formulations could be more greatly pronounced than in rats"

Nakano Y., Tajima M., Sugiyama E.,Sato V.H., Sato H., Development of a Novel Nanoemulsion Formulation to Improve Intestinal Absorption of Cannabidiol, Med Cannabis Cannabinoids 2019;2:35–42, https://doi.org/10.1159/000497361

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"In vivo pharmacokinetics analysis on mice confirmed that the oral bioavailability of curcumin in the nanoemulsion was increased by 9-fold compared with unformulated curcumin"

Yu, H. & Huang, Q, Improving the Oral Bioavailability of Curcumin Using Novel Organogel-Based Nanoemulsions, J. Agric. Food Chem. 2012, 60, 21, 5373–5379, https://doi.org/10.1021/jf300609p

"Oral administration of CBD-piperine-PNL resulted in 6-fold in AUC compared to CBD solution"

"Pharmacokinetic experiments of THC-piperine-PNL with resulted in a 9.3-fold increase in AUC as compared to THC solution"

"There was wide inter- and intra-subject variability in pharmacokinetic parameters with up to 10-fold differences in THC (3.5- to 4- fold for CBD) AUC between subjects and even greater differences in Cmax. The variability appeared to be greater for THC than for CBD. The bioavailability of THC appears to be greater than that of CBD"

Guy & Robson, A Phase I, Double Blind, Three-Way Crossover Study to Assess the Pharmacokinetic Profile of Cannabis Based Medicine Extract (CBME) Administered Sublingually in Variant Cannabinoid Ratios in Normal Healthy Male Volunteers, (2003), http://www.cannabis-med.org/data/pdf/2003-03-04-5.pdf

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4. Vapor (vaporizers & dabs)

"The mean inh [inhaled] bioavailability (calculated vs. iv) was 55 ± 37% and 59 ± 47% for THC and CBD, respectively" (range: 31% to 86% for CBD)

Meyer P, Langos M, Brenneisen R. Human Pharmacokinetics and Adverse Effects of Pulmonary and Intravenous THC-CBD Formulations. Med Cannabis Cannabinoids. 2018 Jun 12;1(1):36-43. doi: 10.1159/000489034. PMID: 34676320; PMCID: PMC8489341. https://pubmed.ncbi.nlm.nih.gov/34676320/

"During vaporization, CBD enters your lungs and diffuses directly into your bloodstream rather than passing through your gut and liver. This avoids the first-pass effect altogether, allowing nearly four times as much CBD to enter your circulation for a maximum bioavailability of roughly 50 to 60 percent"

"Recoveries of THC_tot and CBD_tot in the vapor of 4 electrically-driven vaporizers were 58.4 and 51.4%, 66.8 and 56.1%, 82.7 and 70.0% and 54.6 and 56.7% for Volcano Medic^®, Plenty Vaporizer^®, Arizer Solo^® and DaVinci Vaporizer^®, respectively."

Lanz C, Mattsson J, Soydaner U, Brenneisen R. Medicinal Cannabis: In Vitro Validation of Vaporizers for the Smoke-Free Inhalation of Cannabis. PLoS One. 2016;11(1):e0147286. Published 2016 Jan 19. doi:10.1371/journal.pone.0147286, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718604/

Methods of Consumption:

Smoke

Edible

Emulsions, Nanoemulsions

Vapor (vaporizers & dabs)

Tincture

General

1. Smoke

2. Edible

3. Nanoemulsions & Emulsions

4. Vapor (vaporizers & dabs)

5. Tinctures