CBD Oil Half Life


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Click the link to find out how CBD is processed, how long it stays in your system, and what factors affect the cannabinoid’s effects duration and impact. Do you know how long CBD stays in your system? CBD’s metabolism has been scarcely researched, but we’ve done our best to provide you with the most accurate estimates. Background: Cannabidiol is being pursued as a therapeutic treatment for multiple conditions, usually by oral delivery. Animal studies suggest oral bioavailability is low, but literature in humans is not sufficient. The aim of this review was to collate published data in this area. Methods: A systematic search of PubMed and EMBASE (including MEDLINE) was conducted to retrieve all articles reporting pharmacokinetic data of CBD in humans. Results: Of 792 articles retireved, 24 included pharmacokinetic parameters in humans. The half-life of cannabidiol was reported between 1.4-10.9 hours after oromucosal spray, 2-5 days after chronic oral administration, 24 hours after i.v., and 31 hours after smoking. Bioavailability following smoking was 31% however no other studies attempted to report the absolute bioavailability of CBD following other routes in humans, despite i.v formulations being available. The area-under-the-curve and Cmax increase in dose-dependent manners and are reached quicker following smoking/inhalation compared to oral/oromucosal routes. Cmax is increased during fed states and in lipid formulations. Tmax is reached between 0-4 hours. Conclusions: This review highlights the paucity in data and some discrepancy in the pharmacokinetics of cannabidiol, despite its widespread use in humans. Analysis and understanding of properties such as bioavailability and half-life is critical to future therapeutic success, and robust data from a variety of formulations is required.

How Long Does CBD Stay in Your System

CBD is becoming increasingly popular. And with more and more people using CBD supplements, many have questions about how long CBD products remain in the body after consumption. Below we’ll explain how the body processes CBD, what the substance’s half-life is, and much more.


  1. How CBD works
  2. How is CBD processed?
  3. What is half-life?
  4. How long does CBD stay in your system?
  5. What affects the half-life of CBD?
  6. How long does CBD stay in your system—bottom line

How CBD works

CBD works primarily by interacting with the endocannabinoid system, a regulatory network that keeps the body functioning at its best. Unlike other cannabinoids, CBD doesn’t bind directly with the ECS’s receptors, but works behind the scenes to deliver its unique effects.

The situation becomes a little more complicated because you can take CBD in a variety of different ways, with the method of administration playing a pivotal role in how the compound is metabolised (broken down and distributed around the body).

If you take CBD orally, for example, it has to pass through the digestive system before it can take effect. But, when taken sublingually (under the tongue) or inhaled through a vaporizer, CBD can bypass the digestive system and get to work faster.

How is CBD processed?

Once consumed and absorbed, CBD travels to the liver where it’s metabolised into a variety of compounds that your cells can use. This metabolism is carried out by the same group of enzymes responsible for breaking down roughly 60% of all medications available on the market.

From the liver, CBD metabolites move around the body, where they may interact with a wide variety of receptors.

Although that outlines the basic journey of CBD, what we’re interested in is how long the interaction between CBD metabolites and receptors last—how long CBD stays in your system. To understand that, we need to explain the concept of “half-life”.

What is half-life?

Half-life is the term used to measure the amount of time it takes for a compound to be reduced to half its original amount or effectiveness in the body. It’s gauged by measuring blood plasma for metabolites of the compound in question. From the plasma, drug metabolites are either removed from the body or translocated to another type of bodily fluid.

Half-life is typically measured by administering a single dose of a compound, then testing blood plasma for traces of the drug at regular intervals. The amount of the drug in the plasma will usually increase, reach a peak, and then start to decline.

Using the information obtained while measuring CBD’s half-life, scientists can work out how long CBD stays in the body. You cannot do this yourself at home, but we can use their data to provide a general timeframe.

How long does CBD stay in your system?

The exact half-life of CBD isn’t 100% clear, but we can explore some of the existing studies. There’s evidence [1] that suggests that CBD has a half-life of roughly 2–5 days. This is based on a study involving 14 patients with Huntington’s disease. The patients were given doses of around 700mg of CBD per day for 6 weeks. Note that these doses are much higher than a standard recommended dose.

In another study [2] , half-life of CBD was evaluated based on a single dose in the amount of 20mg and 18.8–19.4mg administered intravenously and smoked respectively. The half-life was accordingly estimated at 18–30h and 27–35h.

But, and this is an important but, that timescale will vary from one person to the next. How long CBD stays in your system is also affected by several biological factors, as well as the way you consume it.

As a general rule of thumb, the more efficient the consumption method, the faster CBD is processed, and the quicker it leaves our system. So, back to our earlier example, orally consumed CBD should stay in your system longer, compared to sublingual application or vaping. It’s a delicate balancing act, but one that you’ll need to experiment with to find out what works for you.

What affects the half-life of CBD?

Whenever talking about the metabolism of any compound, it’s essential to realise that everyone’s body is a little different, and several biological factors can influence your ability to process compounds such as CBD.

CBD is fat-soluble, so a small portion may get stored in fat cells. The cannabinoid can stay in your system for a little longer if you have a high body fat percentage.

• Efficiency of your metabolism

Our metabolism is a combination of chemical reactions, one of which includes the conversion of food to energy. The faster your metabolism, the quicker substances (including CBD) are broken down, processed and eliminated.

• Method of consumption

How you consume CBD not only alters the potency but the duration of effects. The method of consumption also goes hand in hand with bioavailability. Generally speaking, administration methods with greater bioavailability will also leave your system faster.

• Amount of CBD consumed

The more CBD you take, the longer it takes for your body to process it. Be careful though, high doses may produce mild side effects, so it’s essential to find what works for you.

• Purity and strength of the oil/supplement you’re using

The higher the concentration of a CBD oil or supplement, the longer it takes your liver to process, and the longer active ingredients stay in your system.

How long does CBD stay in your system—bottom line

CBD is a very unique and complex compound that can affect everyone slightly differently. Unfortunately, studies have not yet been able to pinpoint the exact half-life of cannabidiol. The half-life of CBD can be estimated to be between 18 and 35 hours, while other studies suggest that the half-life of CBD could be up to 5 days.

However, remember that these are ball-park figures. As we mentioned earlier, a lot of different factors can influence the rate at which your body processes and metabolises compounds like CBD. Until further studies look into the half-life of cannabidiol, these figures are the closest we’ve got.

How Long Does CBD Stay In Your System?

As with everything you ingest, especially when it comes to active ingredients in supplements, it’s natural to ask questions about their effects, duration, and metabolism.

While CBD oil doesn’t get you high like marijuana products, it does get stored in your fat tissues. Common drug tests only look for THC metabolites, but some people are still concerned about how long CBD oil will last in their system.

Hemp was just legalized in 2018 under the amended Agricultural Act, and despite the rolling legalization movement (no pun intended here!), scientists are still trying to determine the time the metabolites of cannabis are stored in the user’s system.

This article will explain the time CBD acts in the body, how long it takes to flush CBD out of your system, and why it’s unlikely that it will cause you to fail a drug test.

How Long Does CBD Oil Stay in Your System? (Important Factors)

As much as we’d like to provide you with a universal timeframe for the time CBD oil will stay in your system, it’s easier said than done. Studies are limited in this regard, and different factors can influence the duration.

There are five major variables that determine how long CBD remains in your body:

The Dose of CBD

Usually, it takes about one day for CBD to be flushed out of your system after taking a single dose. However, the higher the dose, the more time your body will need to get rid of it.

How Often You Consume CBD

The frequency of use also determines how long CBD will stay in your system. CBD accumulates in the body over time if you’re a regular user. Most experts suggest taking CBD for at least two weeks to see how it affects your health and whether or not you’re reaping the benefits. For occasional users, the time CBD leaves the system is shorter.

Your Unique Body Chemistry

Everybody is different. People have different diets, lifestyle habits, metabolisms — all of which can affect the way they metabolize CBD. Your fat content, body mass index, and age will also influence the time CBD remains in the body.

Consumption Method

CBD is found in many different formats. The method of administration affects everything from the onset and duration of effects for the time required for the CBD to leave your system.

CBD is available as the following products:

  • CBD oil
  • CBD capsules
  • CBD edibles (e.g. gummies and honey sticks)
  • CBD vapes
  • CBD topicals

The fastest and most efficient way to deliver CBD into your system is through vaporization. Vaping provides quick effects and leaves the body in a similar time manner. CBD oils and tinctures have a slower onset (15–20 minutes), but they last longer (up to 6 hours). Oral products like capsules and edibles need to pass through the digestive system, so their onset may be delayed by as much as 90 minutes. On the other hand, oral forms of CBD provide the longest duration, up to 10 hours. If you’re looking for localized relief from your discomfort, topicals are a good choice. Their absorption rate and duration time may vary depending on the product’s formula, so make sure to carefully read the ingredients list before buying.

Taking CBD on Empty / Full Stomach

How often you eat, how much, and what you eat plays an important role in the metabolism of CBD. If you take CBD on an empty stomach, it will be metabolized and eliminated faster than when you take it along with a meal.

Studies on CBD’s Metabolism: How Long Does It Stay In Your System?

As mentioned, there aren’t many studies investigating the time CBD oil stays in the user’s system. Below we present the most important research to date.

A 1991 study published in the journal Pharmacology, Biochemistry & Behavior examined the levels of CBD in the participants after high doses administered daily. The authors tested a daily dose of 700 mg of CBD on 14 patients with Huntington’s disease. One week after the experiment stopped, the CBD levels were measured at just 1.5 ng/mL. The research team concluded that CBD concentrations were “virtually undetectable.” (1)

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According to a double-blind, randomized placebo-controlled 2005 study from the journal Therapeutic Drug Monitoring, low doses of CBD — 1.35 mg taken with 2.5 mg of THC —disappear from the body after nine hours from ingestion (2).

Finally, a 2018 review of existing CBD studies found that the estimated half-life of CBD from CBD oil was 2–5 days for daily users. Other methods of administration brought varying half-lives (3).

What is the Half-Life of a Substance?

The half-life of a compound is a popular unit in medicine that helps researchers determine the time it takes for half of the initial dose of a substance to leave one’s system (4).

Based on the assumption that the half-life of 10 mg CBD is 3 hours, the timeframe for how long CBD stays in your system works like this:

  • 1 hour after administration – CBD reaches peak blood levels of 10 mg
  • 3 hours (first half-life) – the amount of CBD is reduced to 5 mg
  • 6 hours (second half-life) – there’s 2.5 mg of CBD in the body
  • 9 hours (third half-life) – only 1.25 mg of CBD circulates in the body
  • 12 hours (fourth half-life) – your body is left with 0.62 mg of CBD

As we said, the half-life of CBD depends on the consumption method and how often you take CBD oil.

How Long Do the Effects of CBD Oil Last?

The form of CBD determines how long your body will need for the effects to take hold — and how long they will last. It also affects the bioavailability of cannabidiol (5).

Here’s what to expect:

Sublingual CBD (CBD Oils, Tinctures & Sprays)

Sublingual use is a fairly efficient consumption method because CBD can pass directly into the bloodstream using the tiny capillaries under your tongue. This complex network of blood vessels allows the CBD to avoid the first-pass metabolism in the liver. Sublingual consumption produces its effects within 15–20 minutes after ingestion, lasting between 4–6 hours. The bioavailability of CBD oil — the amount that eventually enters the bloodstream — is measured at 35%.

Oral CBD (Capsules & Edibles)

Oral ingestion is one of the most common consumption methods for CBD products. Taking a capsule or eating a CBD gummy bear is a relatively effective way to reap the benefits of this cannabinoid. However, oral consumption is also the slowest way to deliver the effects of CBD. Since you swallow the product, the CBD needs to be metabolized in the gut before entering the bloodstream. From there, it can reach your endocannabinoid system within 30–90 minutes depending on your metabolism and whether or not you had eaten something before taking CBD.

This phenomenon is referred to as the “first-pass metabolism,” where the liver enzymes decrease the amount of CBD before its remaining dose can start circulating in the body. Although common among on-the-go users and those who dislike the taste of CBD oil, capsules come with the lowest bioavailability. Only up to 20% of swallowed CBD ends up in your bloodstream.

The delayed onset also leads to the gradual release of CBD into the endocannabinoid system, so the effects last longer than with oils — up to 10 hours.

Vaporized CBD

As mentioned earlier, vaporization provides the highest bioavailability of all CBD formats, with up to 56% of inhaled CBD entering your system. When you take a puff from your CBD vape pen or inhale the vapor from a high-CBD flower, the active ingredients enter the bloodstream using the lung tissue. Doing so ensures fast-acting effects; they usually take hold within 5 minutes after inhalation. On the other hand, they provide the shortest duration of all consumption methods; vaporized CBD will last up to 3 hours.

Topical CBD

Topical formulations range from creams to salves to gels, lotions, bath bombs, and other skin care products. This form of CBD is suited for people who want to target localized problems, such as irritation and discomfort. Sportspeople and athletes use CBD topicals to improve post-workout recovery. When you apply CBD to the skin, it reaches the epidermis layer, where the CB2 receptors are located. The activation of these receptors leads to an array of benefits related to skin health. Again, the absorption rates of CBD topicals vary between different formulas. Make sure to check the list of ingredients and look for the type of fats and oils used as the product’s base.

Will CBD Oil Show Up on a Drug Test?

In most cases, CBD won’t show up on a drug test.

The majority of drug tests are designed to look specifically for THC metabolites or other illicit substances. Employers must follow the Substance Abuse and Mental Health Services (SAMHSA) guidelines — and they don’t include detecting CBD.

But since hemp-derived CBD products may contain up to 0.3% of THC, this raises questions about the possibility of THC showing up on a drug test when the subject is a daily user.

The chances of testing false-positive for THC when taking full-spectrum CBD oil are extremely low. You would need to take around 2,000 milligrams daily to risk failing a drug test.

This can be easily avoided by choosing a broad-spectrum product that contains all the non-psychoactive ingredients of hemp, but without traces of THC. If you’re allergic to some of the hemp compounds, CBD isolate will be the safest bet.

How do you ensure that your CBD oil contains 0.3% of THC or less?

Always look for the Certificate of Analysis (CoA) from a third-party laboratory. An independent lab will look at the potency of CBD, the THC content in your CBD oil, and will detect any potential contaminants in the tested sample. Reputable companies share their lab reports with customers either on their websites or on request.

Even if you test false-positive for THC, you can tell your employer that you take full-spectrum CBD oil and ask for another screening.

How Long Is CBD Detectable in Urine?

Studies are limited when it comes to how long CBD stays in a person’s urine. A 2016 study conducted by researchers from Pacific Toxicology Laboratories in California found that CBD needed only 24 hours to flush CBD out of the subjects’ bodies. After two hours from the administration, 14 out of 15 participants still tested positive for CBD metabolites (6).

How Long Is CBD Detectable in the Blood?

Although not as common as urine tests, blood tests can be used to detect THC metabolites from CBD oil. The reason why they’re not the preferred method of drug testing is because of how quickly THC is eliminated from the bloodstream. The time THC and CBD are detectable in your plasma is about five hours after you take it. However, their metabolites can be present for up to a week.

How Long Is CBD Detectable in the Hair?

A hair test can detect drugs for an extended period of time. These tests can detect the THC metabolites from CBD oil for as long as three months post-administration. The time CBD stays in your hair isn’t clear, but hair tests are very uncommon for both cannabinoids.

Does CBD Interact with Medications?

CBD-induced drug interactions are a real thing. CBD may either shorten or prolong the time it takes to flush the active ingredients in medications from the body.

CBD acts as a substrate and inhibitor of CYP450 enzymes, which metabolize the substances in drugs. Therefore, CBD may affect the metabolism of many pharmaceuticals. Depending on the type of interaction, CBD may cause a subtherapeutic effect, or lead to excessive concentrations of the drug in the bloodstream.

If you take any medications, we encourage you to consult a doctor you trust to avoid the said interactions and maximize the health benefits of CBD oil.

Is CBD Toxic for the Liver?

One study on mice has found that extremely high doses of CBD administered acutely can increase the number of liver enzymes and cause toxicity. However, the results haven’t been replicated in humans, not to mention that the CBD dose was exorbitant considering the weight of the mice. Some studies report that CBD is well tolerated in daily doses of up to 1,500 mg. The World Health Organization (WHO) has also acknowledged CBD as a safe substance.

That being said, CBD has a few mild side effects when taken in large doses. These include dry mouth, changes in appetite, dizziness, fatigue, and diarrhea.

The good news is that none of these reactions are life-threatening, not to mention that it’s impossible to fatally overdose on cannabinoids.

CBD and Breastfeeding: Can CBD Pass Into Your Baby’s System?

Doctors suggest that breastfeeding mothers abstain from CBD for at least 1 week before they start breastfeeding. The Food and Drug Administration (FDA) holds a strong stance against the use of CBD during breastfeeding due to the lack of sufficient research on how CBD affects breastfed babies. We only know that some amount of cannabinoid can pass into a baby’s bloodstream with milk.

Until researchers establish the safety of CBD during breastfeeding, it’s safe to avoid it.

So, How Long Does CBD Oil Stay in Your System?

Low-to-moderate doses administered acutely shouldn’t stay in your system for more than 24 hours. Even high doses of CBD should disappear from the body within a week.

However, regular use of CBD may cause it to remain longer in your system. For some people, it takes more than a week to flush CBD completely out of the body. That’s because CBD builds up over time in the fat tissues.

The time CBD oil will stay in your system is determined by several factors, including your age, metabolism, weight, dosage, frequency of use, consumption method, and the use of other medications.

The good news is that drug tests don’t look for CBD, so if you take normal doses of full-spectrum CBD oil, you’re in the clear.

We hope you’ll find this article useful for further research. If you know about any new discoveries in terms of how long CBD stays in one’s system, feel free to leave a comment below! All of our articles are regularly updated according to the latest research.

A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

Background: Cannabidiol is being pursued as a therapeutic treatment for multiple conditions, usually by oral delivery. Animal studies suggest oral bioavailability is low, but literature in humans is not sufficient. The aim of this review was to collate published data in this area.

Methods: A systematic search of PubMed and EMBASE (including MEDLINE) was conducted to retrieve all articles reporting pharmacokinetic data of CBD in humans.

Results: Of 792 articles retireved, 24 included pharmacokinetic parameters in humans. The half-life of cannabidiol was reported between 1.4 and 10.9 h after oromucosal spray, 2–5 days after chronic oral administration, 24 h after i.v., and 31 h after smoking. Bioavailability following smoking was 31% however no other studies attempted to report the absolute bioavailability of CBD following other routes in humans, despite i.v formulations being available. The area-under-the-curve and Cmax increase in dose-dependent manners and are reached quicker following smoking/inhalation compared to oral/oromucosal routes. Cmax is increased during fed states and in lipid formulations. Tmax is reached between 0 and 4 h.

Conclusions: This review highlights the paucity in data and some discrepancy in the pharmacokinetics of cannabidiol, despite its widespread use in humans. Analysis and understanding of properties such as bioavailability and half-life is critical to future therapeutic success, and robust data from a variety of formulations is required.


The Cannabis sativa plant contains more than a hundred phytocannabinoid compounds, including the non-psychotomimetic compound cannabidiol (CBD) (Izzo et al., 2009). CBD has attracted significant interest due to its anti-inflammatory, anti-oxidative and anti-necrotic protective effects, as well as displaying a favorable safety and tolerability profile in humans (Bergamaschi et al., 2011), making it a promising candidate in many therapeutic avenues including epilepsy, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. GW pharmaceuticals have developed an oral solution of pure CBD (Epidiolex ® ) for the treatment of severe, orphan, early-onset, treatment-resistant epilepsy syndromes, showing significant reductions in seizure frequency compared to placebo in several trials (Devinsky et al., 2017, 2018a; Thiele et al., 2018). Epidiolex ® has recently received US Food and Drug Administration (FDA) approval (GW Pharmaceuticals, 2018). CBD is also being pursued in clinical trials in Parkinson’s disease, Crohn’s disease, society anxiety disorder, and schizophrenia (Crippa et al., 2011; Leweke et al., 2012; Chagas et al., 2014; Naftali et al., 2017), showing promise in these areas. Additionally, CBD is widely used as a popular food supplement in a variety of formats for a range of complaints. It is estimated that the CBD market will grow to $2.1 billion in the US market in consumer sales by 2020 (Hemp Business, 2017).

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From previous investigations including animal studies, the oral bioavailability of CBD has been shown to be very low (13–19%) (Mechoulam et al., 2002). It undergoes extensive first pass metabolism and its metabolites are mostly excreted via the kidneys (Huestis, 2007). Plasma and brain concentrations are dose-dependent in animals, and bioavailability is increased with various lipid formulations (Zgair et al., 2016). However, despite the breadth of use of CBD in humans, there is little data on its pharmacokinetics (PK). Analysis and understanding of the PK properties of CBD is critical to its future use as a therapeutic compound in a wide range of clinical settings, particularly regarding dosing regimens and routes of administration. Therefore, the aim of this systematic review was to collate and analyse all available CBD PK data recorded in humans and to highlight gaps in the literature.


Search Strategy

The systematic review was carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (Moher et al., 2009). A systematic search of PubMed and EMBASE (including MEDLINE) was conducted to retrieve all articles reporting pharmacokinetic data of CBD in humans. Search terms included: CBD, cannabidiol, Epidiolex, pharmacokinetics, Cmax, plasma concentrations, plasma levels, half-life, peak concentrations, absorption, bioavailability, AUC, Tmax, Cmin, and apparent volume of distribution. No restrictions were applied to type of study, publication year, or language. The searches were carried out by 14 March 2018 by two independent researchers.

Eligibility Criteria

The titles and abstracts of retrieved studies were examined by two independent researchers, and inappropriate articles were rejected. Inclusion criteria were as follows: an original, peer-reviewed paper that involved administration of CBD to humans, and included at least one pharmacokinetic measurement as listed in the search strategy.

Data Acquisition

The included articles were analyzed, and the following data extracted: sample size, gender, administration route of CBD, source of CBD, dose of CBD, and any pharmacokinetic details. Where available, plasma mean or median Cmax (ng/mL) were plotted against CBD dose (mg). Similarly, mean or median Tmax and range, and mean or median area under the curve (AUC0−t) and SD were plotted against CBD dose (mg). The source/supplier of the CBD was also recorded. No further statistical analysis was possible due to sparsity of data and heterogeneity of populations used. All studies were assessed for quality using an amended version of the National Institute for Health (NIH), National Heart, Lung and Blood Institute, Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group (National Institute for Health, 2014). A sample size of ≤ 10 was considered poor, between 11 and 19 was considered fair, and ≥20 was considered good (Ogungbenro et al., 2006).

Definitions of PK Parameters

Tmax: Time to the maximum measured plasma concentration.

Cmax: Maximum measured plasma concentration over the time span specified.

t1/2: Final time taken for the plasma concentration to be reduced by half.

AUC0−t: The area under the plasma concentration vs. time curve, from time zero to “t.”

AUC0−inf: The area under the plasma concentration vs. time curve from zero to t calculated as AUC0−t plus the extrapolated amount from time t to infinity.

Kel: The first-order final elimination rate constant.


In total, 792 records were retrieved from the database searching, 24 of which met the eligibility criteria (Figure 1). Table 1 summarizes each included study. Routes of administration included intravenous (i.v.) (n = 1), oromucosal spray (n = 21), oral capsules (n = 13), oral drops (n = 2), oral solutions (n = 1), nebuliser (n = 1), aerosol (n = 1), vaporization (n = 1), and smoking (n = 8). CBD was administered on its own in 9 publications, and in combination with THC or within a cannabis extract in the remainder. One study was conducted in children with Dravet syndrome, while the remainder were conducted in healthy adult volunteers (Devinsky et al., 2018b). Overall, the included studies were of good quality (Supplementary Table 1). However, many studies had small sample sizes. Additionally, not all studies included both males and females, and frequent cannabis smokers were included in a number of studies. Thus, interpretation and extrapolation of these results should be done with caution.

Figure 1. Flow chart for study retrieval and selection.

Table 1. Human studies reporting pharmacokinetic (PK) parameters for cannabidiol (CBD).

Cmax, Tmax, and Area Under the Curve

Within the 25 included studies, Cmax was reported on 58 occasions (for example within different volunteer groups or doses in a single study), Tmax on 56 occasions and area under the curve (AUC0−t) on 45 occasions. These data from plasma/blood are presented in Figures 2A–C. The AUC0−t and Cmax of CBD is dose-dependent, and Tmax occurs between 0 and 5 h, but does not appear to be dose-dependent.

Figure 2. (A) Mean or median Tmax (h) and range against CBD dose (mg) (B) mean or median area under the curve (AUC0-t) (h × ng/mL) and SD against CBD dose (mg) and (C) plasma mean or median concentration max (Cmax; ng/mL) against CBD dose (mg). It was not possible to present error bars for Cmax as SD and SEM were both reported in the data. IV, intravenous; SD, standard deviation; SEM, standard error of the mean.

Oromucosal Drops/Spray

A number of trials in humans were conducted by Guy and colleagues to explore administration route efficiency of sprays, an aerosol, and a nebuliser containing CBD or CBD and THC (CBD dose 10 or 20 mg) (Guy and Flint, 2004; Guy and Robson, 2004a,b). Oromucosal spray, either buccal, sublingual, or oropharyngeal administration, resulted in mean Cmax between 2.5 and 3.3 ng/mL and mean Tmax between 1.64 and 4.2 h. Sublingual drops resulted in similar Cmax of 2.05 and 2.58 ng/mL and Tmax of 2.17 and 1.67 h, respectively. Other oromucosal single dose studies reported Cmax and Tmax values within similar ranges (Karschner et al., 2011; Atsmon et al., 2017b).

Minimal evidence of plasma accumulation has been reported by chronic dosing studies over 5–9 days (Sellers et al., 2013; Stott et al., 2013a). Cmax appears to be dose-dependent. A dose of 20 mg/day resulted in a mean Cmax of 1.5 ng/mL and mean AUC0−t of 6.1 h × ng/mL while 60 mg/day equated to a mean Cmax of 4.8 ng/mL and AUC0−t was 38.9 h × ng/mL (Sellers et al., 2013). In another study, Cmax increased dose-dependently from 0.4 to 1.2 and 2.2 ng/mL following 5, 10, and 20 mg single doses, respectively, and from 0.5 to 1.1 and 3.2 ng/mL, respectively following chronic dosing over 9 consecutive days (Stott et al., 2013a). There was a significant increase in time-dependent exposure during the chronic treatment. Mean AUC0−t for the single doses were 0.8, 4.5, 9.9, and 2.5, 6.7, and 20.3 for the chronic dosing schedule, respectively. Tmax does not appear to be dose-dependent, nor affected by acute or chronic dosing schedules.

Stott et al. reported an increase in CBD bioavailability under fed vs. fasted states in 12 men after a single 10 mg dose of CBD administered through an oromucosal spray which also contained THC (Stott et al., 2013a,b). Mean AUC and Cmax were 5- and 3-fold higher during fed conditions compared to fasted (AUC0−t 23.1 vs. 4.5; Cmax 3.7 vs. 1.2 ng/mL). Tmax was also delayed under the fed state (4.0 vs. 1.4 h).

In children, Devinsky et al. reported mean AUC as 70, 241, 722, and 963 h × ng/mL in groups receiving 2.5, 5, 10, and 20 mg/Kg/day of CBD in oral solution (Devinsky et al., 2018b).

Oral Intake

Cmax and AUC following oral administration also appears to be dose dependent. A dose of 10 mg CBD resulted in mean Cmax of 2.47 ng/mL at 1.27 h, and a dose of 400 or 800 mg co-administered with i.v. fentanyl (a highly potent opioid) to examine its safety resulted in a mean Cmax of 181 ng/mL (at 3.0 h) and 114 ng/mL (at 1.5 h) for 400 mg, and 221 ng/mL (at 3.0 h) and 157 ng/mL (at 4.0 h) for 800 mg, in 2 sessions, respectively (Guy and Robson, 2004b; Manini et al., 2015). A dose of 800 mg oral CBD in a study involving 8 male and female cannabis smokers, reported a mean Cmax of 77.9 ng/mL and mean Tmax of 3.0 h (Haney et al., 2016). Although, an increase in dose corresponds with an increase in Cmax, the Cmax between the higher doses of CBD does not greatly differ, suggesting a saturation effect (e.g., between 400 and 800 mg).

One hour after oral capsule administration containing 5.4 mg CBD in males and females, mean Cmax was reported as 0.93 ng/mL (higher for female participants than male) (Nadulski et al., 2005a). A subset (n = 12) consumed a standard breakfast meal 1 h after the capsules, which slightly increased mean Cmax to 1.13 ng/mL. CBD remained detectable for 3–4 h after administration (Nadulski et al., 2005b).

Cherniakov et al. examined the pharmacokinetic differences between an oromucosal spray and an oral capsule with piperine pro-nanolipospheres (PNL) (both 10 mg CBD) in 9 men. The piperine-PNL oral formulation had a 4-fold increase in Cmax (2.1 ng/mL vs. 0.5 ng/mL), and a 2.2-fold increase in AUC0−t (6.9 vs. 3.1 h × ng/mL), while Tmax was decreased (1.0 vs. 3.0 h) compared to the oromucosal spray (Cherniakov et al., 2017a). This group further developed self-emulsifying formulations and reported again an increased bioavailability and increased Cmax within a shorter time compared to a reference spray (Atsmon et al., 2017a,b).

Intravenous Administration

The highest plasma concentrations of CBD were reported by Ohlsson et al. following i.v. administration of 20 mg of deuterium-labeled CBD. Mean plasma CBD concentrations were reported at 686 ng/mL (3 min post-administration), which dropped to 48 ng/mL at 1 h.

Controlled Smoking and Inhalation

After smoking a cigarette containing 19.2 mg of deuterium-labeled CBD, highest plasma concentrations were reported as 110 ng/mL, 3 min post dose, which dropped to 10.2 ng/ml 1 h later (Ohlsson et al., 1986). Average bioavailability by the smoked route was 31% (Ohlsson et al., 1986). A nebuliser resulted in a Cmax of 9.49 ng/mL which occurred at 0.6 h, whereas aerosol administration produced Cmax (2.6 ng/mL) at 2.35 h (Guy and Flint, 2004). In 10 male and female usual, infrequent cannabis smokers, Cmax was 2.0 ng/mL at 0.25 h after smoking a cigarette containing 2 mg of CBD (Schwope et al., 2011). CBD was detected in 60% of whole blood samples and in 80% of plasma samples at observed Cmax, and no longer detected after 1.0 h. A study in 14 male and female cannabis smokers reported 15.4% detection in frequent smokers with no CBD detected in occasional smokers in whole blood analysis (Desrosiers et al., 2014). In plasma however, there was a 53.8 and 9.1% detection in the frequent and occasional groups, with corresponding Cmax of 1.1 ng/mL in the frequent group, and below limits of detection in the occasional group.

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The mean half-life (t1/2) of CBD was reported as 1.1 and 2.4 h following nebuliser and aerosol administration (20 mg) (Guy and Flint, 2004), 1.09 and 1.97 h following single oral administration (10 and 20 mg) (Guy and Flint, 2004; Guy and Robson, 2004b), 2.95 and 3.21 h following 10 mg oral lipid capsules (Atsmon et al., 2017a,b), between 1.44 and 10.86 h after oromucosal spray administration (5–20 mg) (Guy and Robson, 2004b; Sellers et al., 2013; Stott et al., 2013a,b; Atsmon et al., 2017b), 24 h after i.v. infusion, 31 h after smoking (Ohlsson et al., 1986), and 2–5 days after chronic oral administration (Consroe et al., 1991).

Elimination Rate

Mean elimination rate constant (Kel [1/h]) has been reported as 0.148 in fasted state, and 0.155 in fed state after 10 mg CBD was administered in an oromucosal spray also containing THC (Stott et al., 2013a,b). After single doses of 5 and 20 mg CBD, mean Kel (1/h) was reported as 0.173 and 0.123 (Stott et al., 2013a). Following 20 mg CBD administration through a nebuliser and pressurized aerosol, mean Kel was reported as 0.98 and 0.43, respectively, while 20 mg CBD administered as sublingual drops was reported as 0.37 (Guy and Flint, 2004).

Plasma Clearance

Plasma apparent clearance, CL/F (L/h) has been reported to range from 2,546 to 4,741 in a fasted stated following 10 mg CBD administered via oromucosal spray (Stott et al., 2013a,c). This value decreases to 533 following the same concentration in a fed state (Stott et al., 2013b). A plasma apparent clearance of 3,252 and 3,783 was reported following 5 and 20 mg single doses of CBD via oromucosal spray (Stott et al., 2013a). Ohlsson et al. reported plasma apparent clearance as 74.4 L/h following i.v. injection (Ohlsson et al., 1986).

Volume of Distribution

Mean apparent volume of distribution (V/F [L]) was reported as 2,520 L following i.v. administration (Ohlsson et al., 1986). Following single acute doses through oromucosal spray administration, apparent volume of distribution was reported as 26,298, 31,994, and 28,312 L (Stott et al., 2013a).


The aim of this study was to review and analyse all available PK data on CBD in humans. Only 8 publications reported PK parameters after administering CBD on its own, and the others were in combination with THC/cannabis. Only 1 study reported the bioavailability of CBD in humans (31% following smoking). From the analysis of these papers, the following observations were made; peak plasma concentrations and area under the curve (AUC) are dose-dependent and show minimal accumulation; Cmax is increased and reached faster following i.v., smoking or inhalation; Cmax is increased and reached faster after oral administration in a fed state or in a pro-nanoliposphere formulation; Tmax does not appear to be dose-dependent; and half-life depends on dose and route of administration. Overall, considerable variation was observed between studies, although they were very heterogeneous, and further work is warranted.

Human studies administering CBD showed that the AUC0−t and Cmax are dose-dependent, and Tmax mostly occurred between 1 and 4 h. Animal studies in piglets, mice, and rats also all demonstrate a dose-dependent relationship between CBD and both plasma and brain concentrations (Long et al., 2012; Hammell et al., 2016; Garberg et al., 2017), suggesting that human brain concentrations will also be dose-dependent. Ten publications in this review reported the half-life of CBD which ranged from 1 h to 5 days and varies depending on the dose and route of administration. Very limited data was available for detailed analysis on the elimination rate, apparent clearance or distribution of CBD in humans.

Plasma levels of CBD were increased when CBD was administered with food or in a fed state, or when a meal is consumed post-administration. Oral capsules with piperine pro-nanolipospheres also increased AUC and Cmax. This is also demonstrated in animal studies; co-administration of lipids with oral CBD increased systemic availability by almost 3-fold in rats (Zgair et al., 2016) and a pro-nanoliposphere formulation increased oral bioavailability by about 6-fold (Cherniakov et al., 2017b). As CBD is a highly lipophilic molecule, it is logical that CBD may dissolve in the fat content of food, increasing its solubility, and absorption and therefore bioavailability as demonstrated by numerous pharmacological drugs (Winter et al., 2013). Thus, it may be advisable to administer CBD orally in a fed state to allow for optimal absorption.

Only one study used intravenous administration of CBD and reported PK details, which could be a beneficial route of administration in some acute indications. Results from other routes such as rectal, transdermal, or intraperitoneal have also not been published in humans, although transdermal CBD gel and topical creams have been demonstrated to be successful in animal studies (Giacoppo et al., 2015; Hammell et al., 2016). Interestingly, intraperitoneal (i.p.) injection of CBD corresponded to higher plasma and brain concentrations than oral administration in mice, however in rats, similar concentrations were observed for both administration routes, and brain concentrations were in fact higher following oral compared to i.p. route (Deiana et al., 2012). No published data exists on the tissue distribution of CBD in humans. Although plasma levels of CBD do not show accumulation with repeated dosing, it is possible that there may be tissue accumulation.

Only one study in this review was conducted in children (n = 34) (Devinsky et al., 2018b). Children (4–10 years) with Dravet syndrome were administered an oral solution of CBD and AUC was reported to increase dose-dependently. It is important to emphasize the statement that children are not small adults, and there are many differences in their pharmacokinetic and pharmacodynamic profiles. Absorption, excretion, metabolism, and plasma protein binding are generally reduced in children compared to adults, and apparent volume of distribution is generally increased (Fernandez et al., 2011). These parameters need to be explored fully for CBD in order to understand and advise dose adjustments.

Within the adult studies, inter- and intra-subject variability was observed in studies, and it remains to be seen whether i.v. and other routes of administration that by-pass initial metabolism will alleviate this issue. Interestingly, although each of the subject’s weight was taken into account, none of the studies addressed subject fat content as a factor in their exclusion criteria; as muscle can weigh more than the same proportion of fat. It is well-known that cannabinoids are highly lipophilic compounds and accumulate in fatty tissue which can then be released gradually (Gunasekaran et al., 2009). It may be of benefit in future study to either put in place more stringent exclusion criteria and measure subject fat content or assess the possible accumulation of CBD in fatty tissue. Differences in metabolism, distribution and accumulation in fat, and in biliary and renal elimination may be responsible for prolonged elimination half-life and variable pharmacokinetic outcomes. CBD use is widespread and has been recommended for use by the FDA in childhood-onset epilepsy. CBD also displays therapeutic promise in other disorders such as schizophrenia and post-traumatic stress disorder. If we are to understand the actions of CBD in those disorders and increase the success rate for treatment, these groups of patients and their distinct characteristics must be assessed as they may not be comparable to a healthy volunteer population.

A systematic review in 2014 concluded that CBD generally has a low risk of clinically significant drug-interactions (Stout and Cimino, 2014). A few studies in the current review included examination of drug-drug interactions with CBD. GW Pharmaceuticals performed a clinical trial investigating the pharmacokinetic interaction between CBD/THC spray (sativex) and rifampicin (cytochrome P450 inducer), ketoconazole, and omeprazole (cytochrome P450 inhibitors) (Stott et al., 2013c). Authors concluded overall that CBD in combination with the drugs were well-tolerated, but consideration should be noted when co-administering with other drugs using the CYP3A4 pathway. Caution is also advised with concomitant use of CBD and substrates of UDP-glucuronosyltransferases UGT1A9 and UGT2B7, and other drugs metabolized by the CYP2C19 enzyme (Al Saabi et al., 2013; Jiang et al., 2013). Manini et al. co-administered CBD with i.v. fentanyl (a high potency opioid) which was reported as safe and well-tolerated (Manini et al., 2015). In a number of trials with CBD in children with severe epilepsy, clobazam concentrations increased when CBD was co-administered and dosage of clobazam had to be reduced in some patients in one study (Geffrey et al., 2015; Devinsky et al., 2018b). Gaston and colleagues performed a safety study in adults and children in which CBD was administered with commonly-used anti-epileptic drugs (AEDs) (Gaston et al., 2017). Most changes in AED concentrations were within acceptable ranges but abnormal liver function tests were reported in those taking valproate and authors emphasized the importance of continued monitoring of AED concentrations and liver function during treatment with CBD.

Limitations of this review should be acknowledged. Different population types including healthy and patient populations and cannabis naïve or not were all grouped together which may impede generalizability. The proportions of men and women in each study were also not uniform, and it is still being elucidated whether men and women have distinct pharmacokinetic profiles with regards to cannabinoids (Fattore and Fratta, 2010). One study suggested that the PK of CBD was different in their female volunteers (Nadulski et al., 2005a). It should also be mentioned that CBD is currently not an approved product with a pharmacopeia entry so using different sources of CBD that are subject to different polymeric forms, different particle sizes, and different purities may also affect the PK profiles observed. It is important for future work that researchers record the source of the CBD material used so that results have the highest chance of being replicated. Despite a thorough search of the two databases chosen, the addition of more databases may have widened the search to increase the number of results and hence improve the reliability and validity of the findings. However, the review was carried out by two independent reviewers, and searches generated were analyzed separately and then compared.

In conclusion, this review demonstrates the lack of research in this area, particularly in routes of administration other than oral. An absence of studies has led to failure in addressing the bioavailability of CBD despite intravenous formulations being available. This is of critical importance due to the popularity of CBD products and will help interpret other PK values. Standardized and robust formulations of CBD and their PK data are required for both genders, with consideration of other factors such as adiposity, genetic factors that might influence absorption and metabolism, and the effects of disease states.

Author Contributions

SM, SO, and AY: substantial contributions to the conception or design of the work. SM: writing of the manuscript. SM and NS: database searching and data extraction. All authors: the analysis and interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


This work was supported by the Biotechnology and Biological Sciences Research Council [Grant number BB/M008770/1].

Conflict of Interest Statement

AY was employed by company Artelo Biosciences.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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