The Most Current Information on CBD Pharmacokinetics, Including Therapeutic Benefits, Bioavailability, Drug-Drug Interactions, and Adverse Effects
Canada has legalized marijuana for recreational use, as have more than a few US states. More than half of US states have legalized medical marijuana. In addition, the US legalized the growth and use of industrial hemp in late 2018. When people think of cannabis, they think of a substance that makes people “high,” but there’s much more to it than that. With legalization, serious clinical studies on the plant have begun to fully understand how it works. One of the most important discoveries has been that cannabis has two main cannabinoids, naturally-occurring chemicals in cannabis. They are tetrahydrocannabinol, also known as delta-9-THC, also known as THC, and cannabidiol, or CBD. THC is the part that gets you high. CBD does not, but it does have a slew of non-intoxicating effects. Another important fact to note is that both marijuana and hemp are two kinds of cannabis, though they are the same species of plant. The only notable difference is that marijuana produces much more THC and hemp produces much more CBD and will never have more than a .3 percent concentration of THC.
CBD has become of interest to the general population because of the fact that it is non-intoxicating and research has shown that CBD may have powerful therapeutic benefits. These range from treating epilepsy, anxiety, sleep disorders, depression, chronic pain, inflammation, skin diseases, cancer, glaucoma, and more.
The more popular CBD gets, the more need there is for guidance on how to use it. The specific ways CBD interacts with the body to produce its therapeutic benefits are still the subject of clinical studies, though every day, researchers discover more about how it works. We know CBD interacts with various receptors throughout the entire body, not just by binding to them, but also preventing the binding and re-uptake of other chemicals and processes as well. While studies on the use of CBD have demonstrated no serious side effects to date, other concerns include precise dosing and drug interactions, neither of which should be overlooked when taking CBD for medical reasons or otherwise.
CBD Pharmacokinetics
The human body’s endocannabinoid system is responsible for how cannabinoids interact with the body to produce certain effects. To date, scientists have discovered two specific endocannabinoids in the body, CB-1 and CB-2, though many other receptors, enzymes, and transporters also play a significant role in how a cannabinoid like CBD works when we consume it. The system is complex and still under intense clinical study to fully understand the therapeutic role CBD can have in our lives.
One subject of specific interest has to do with the pharmacokinetics of cannabis and how to use that information to maximize medical benefits while minimizing behavioral and cognitive effects. Another point of interest involves the fact that cannabis’ therapeutic effects may be more powerful when certain combinations of its cannabinoids are delivered simultaneously rather than isolated.
CBD Absorption
CBD absorption depends on the method of consumption, and even within those methods, there is variance. Smoking or vaping CBD produces a rapid onset of effects, within a couple of minutes, though the full-strength effects generally don’t begin until after 30 minutes. The effects tend to last between two and three hours, but can last shorter or longer. Vaping effects typically last up to six hours. Absorption of CBD when smoked or vaped can depend on many factors. These include how intensely and often it is inhaled in onesitting, the concentration of the CBD particles being inhaled, individual lung metabolic rate, deposits in the respiratory system, how much of the substance escapes during the process of inhalation, the method of inhalation, if the temperature of vaporization is sustained, the plant variety, and thermal decomposition. When a person inhales CBD, its mean bioavailability is 31 percent. (Aggarwal, 2013) (Lucas, 2018) (Grant, 2012) (Hazekamp, 2006) (Abrams, 2011)
Absorption seems to be much less or at least more erratic when taking CBD orally, only at about six percent. This is because the liver metabolizes much of the CBD before it gets the chance to enter and absorb into the bloodstream. In addition, because CBD is lipophilic (it loves fat), CBD that has been dissolved in food can increase its bioavailability and allow it to be absorbed better by the human body. Consuming CBD orally has a slower onset and longer-lasting effects, anywhere from four to twelve hours. It’s hard to measure how much absorption happens per dose in CBD edibles if the concentration is not known. Also, if the CBD has been cooked, that can impact absorption. (Alexander, 2016) (Schrot & Hubbard, 2016)
Sublingual consumption of CBD has quicker and more effective absorption than when it is digested. (National Academy of Sciences, 2017)
Distribution
Scientists know that once THC gets into the bloodstream it goes to the liver, brain, heart, and lungs. It is distributed throughout these areas shortly after being absorbed. THC behaves this way in the body because, like CBD, it is lipophilic. Less is known about CBD distribution into the body, but since it is also lipophilic, it may behave similarly. Continuous CBD use does not seem to cause the accumulation of CBD’s plasma levels. However, tissue accumulation is not out of the question.
Metabolism
CBD, like THC, undergoes an intense first-pass effect when consumed orally; it is heavily metabolized by the liver before it gets the chance to enter the bloodstream, reducing its bioavailability. That being said, metabolizing CBD is unlike THC in that much of the dose is expelled in its original form in feces. CBD is also metabolized in the intestines.
CBD impacts how THC is metabolized, though without greatly impacting how much gets passed and distributed.
Elimination
CBD has an elimination half-life of anywhere between 18 and 32 hours, though for daily users, it can be anywhere from three to five days. The method of consumption causes CBD’s elimination half-life to vary significantly.
Animal studies have indicated that a large percentage of a CBD dosage is excreted intact.
Routes of CBD Administration
The method of consuming CBD greatly impacts its pharmacokinetics. Variability in how it affects the human body is common.
A common route of CBD administration is inhalation, particularly by way of a vaporizer. Using a vaporizer is a healthier method than smoking because it will have less negative impact on the lungs. Inhaling CBD allows for the highest bioavailability and the quickest onset, within a matter of minutes. This rapid onset allows for nearly immediate therapeutic benefits, such as in situations of intense pain, nausea, or panic. Plus, it’s mean bioavailability is high, at 31 percent. Inhaling CBD does have a high incidence of variability, as the quantity consumed, the depth and length of inhalation, and the temperature of vaporization all can impact its effect. The effects are short-lived, so use for anything chronic may not be as effective. Plus, it can be hard to take a consistent dose inhaling CBD.
Oral CBD administration has also become popular. CBD edibles, oil, and capsules are all options. While the effects don’t begin until upwards of 20 minutes after consumption, they are much longer lasting than consuming CBD by way of inhaling. Dosing is also much more consistent with oral administration, and it is easy to keep continuously high levels of CBD in the body this way, helpful for treating chronic conditions. The CBD is absorbed slowly and can have an impact for as long as eight hours. Oral CBD consumption leads to a much lower bioavailability, however, as low as six percent. There is also much more variance in effects between individuals through oral CBD administration.
Sublingual CBD administration means it absorbs directly into the bloodstream from under the tongue, avoiding first-pass metabolism and thus increasing both speed of onset and bioavailability. Rectal CBD administration also allows for reducing first-pass metabolism and has become an increasingly popular method of consumption. This method practically doubles the CBD’s bioavailability from oral consumption. Not much research has been done on rectal CBD administration at this point.
CBD also comes in the form of creams, salves, and balms meant for topical use. It is absorbed into the skin directly, never entering the bloodstream. Though, cannabinoids in general are hydrophobic, which can be diffusing CBD into the skin more difficult. Topical application of CBD allows for greater bioavailability than oral delivery. Another topical method of CBD administration is through a transdermal patch, allowing the CBD to bypass first-pass metabolism, again allowing for greater bioavailability. Many patients have used transdermal CBD patches for alleviating chemotherapy symptoms like nausea and vomiting. Keeping the patch on for consecutive days at a time can also help to increase appetite and reduce inflammation more consistently.
Individual Titration Dosing and Prescribing Guidelines
Certified, accurate titration dosing of CBD will require more clinical research, though the trial-and-error method has proven effective thus far without causing safety concerns. Without the data to concretely determine dosing guidelines, medical professionals have mostly opted to start low and slow and gradually up the dose until finding one that works for each individual patient. Experts consider a low dose as under 5 mg, a medium does up to 15 mg, and a high dose up to 30 mg. Higher dosages make side effects and tolerance more probable without necessarily increasing therapeutic benefits.
Research on CBD has indicated its potential to treat many different conditions. These include epilepsy and epileptic seizures, anxiety, stress, depression, chronic pain, sleep disorders, skin disorders, inflammation, glaucoma, psychotic disorders, addiction (including opiate addiction), cancer treatment symptoms. It may also prevent neurodegenerative diseases and cancer. Specific dosing and routes of administration for individual conditions have not been determined, though sticking with a low dose initially and gradually increasing seems to be the best option regardless. The condition, the intensity of the condition, and the individual’s personal attributes, such as weight and metabolism, can help determine the starting dosage more accurately.
In 2018, the FDA approved a CBD-based drug called Epidiolex to treat rare forms of epilepsy. Dosing starts low until achieving the desired results, much the same as using CBD to treat other conditions.
Adverse Effects
Almost half of CBD users have reported adverse drug events, often related to their response to a higher dose. None are serious, but they should be noted regardless. Adverse drug events associated with CBD include sedation, anemia, appetite fluctuations, diarrhea, infection, trouble staying asleep, and transaminase elevations. Most studies into CBD’s side effects have been observed when treating epilepsy and psychotic disorders. Other drugs used to treat these conditions had worse or more serious side effects, making it more likely for patients to follow-through with treatment using CBD.
Due to the limited research available about CBD’s potential adverse effects plus the fact that it is used alongside other treatment plans, more clinical research needs to be done to determine CBD’s solitary adverse effects.
Tolerance
CBD tolerance is speculative at this point, as not enough clinical studies are available. That being said, a number of studies have reportedly found that CBD does not create tolerance. This is in contrast to its cousin cannabinoid THC, which does cause tolerance.
Addiction
Current data shows no evidence that CBD causes abuse, potential for dependence, or withdrawal symptoms. It does not cause cravings nor lead to the abuse of hard drugs. The only relationship it seems to have to addiction comes from research showing that it seems to provide positive results in helping to treat the abuse of other substances, such as opiates, tobacco, THC, and cocaine.
Potential Drug Interactions
Interactions between CBD and other drugs may be caused by CBD’s absorption, metabolism, and elimination. In fact, the potential for CBD to interact with other drugs is high. CBD may interact with enzyme substrates, inducers, or inhibitors by increasing the risk of side and adverse effects and decreasing CBD’s effectiveness. CBD may also interact with secondary metabolism or transport proteins by increasing the risk of side and adverse effects. The research on this is not conclusive yet, but these potential drug-drug interactions are worth noting.
Evolving Future
As peer-reviewed clinical research continues to emerge about CBD, more conclusive guidelines for therapeutic uses, dosages, adverse effects and potential drug interactions will become clear. In the meantime, the fact that it does appear safe and effective to use is promising. Prescribe CBD with caution, nonetheless. Pay special attention to potential drug interactions, as CBD’s biological behavior seems to suggest it will impact how other drugs interact with the body and vice versa.
Disclaimer: Use OneCBD products as directed on the label. Pregnant and nursing mothers should never use OneCBD without first consulting their doctor. The same goes for anyone with a serious medical condition or those taking prescription medications, as CBD presents a high potential for drug-drug interactions. Because of the legal status of cannabis on a national level, OneCBD products have not been approved by the FDA. While research indicates the potential for CBD products to prevent and treat many illnesses, nothing OneCBD produces, manufactures, markets, or distributes is intended for those purposes.
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Jess Lakritz 