Interest in the medical and recreational use of has led to increased interest in how to best administer the two most abundant cannabinoids in the plant: THC and .

These two molecules typically represent about 70 percent of all of the known cannabinoids in the unadulterated plant. The manner in which THC and CBD are administered plays a critical role in determining the rate and amount of each molecule that is absorbed by the brain.

, the most popular route of cannabis administration for the past few thousand years, provides a rapid and efficient method of drug delivery from the lungs to the brain. The rapidity of entry of any drug into the brain is directly related to the amount of euphoria a drug produces; thus, inhalation is typically associated with a higher abuse potential as well as a more intensely pleasurable and reinforcing effect. This applies to whether one is inhaling smoke from the burning plant material or from heated oil within a vape pen. The issue of whether is healthier than smoking the burning plant is still, surprisingly, controversial and unresolved.

Sublingual administration refers to holding the drug in the mouth to allow the drug to be absorbed into the well-vascularized mucosa under the tongue. Absorption is fairly rapid and flows directly into the superior vena cava, a large vein that takes the drug first to the heart and then quickly into the brain, thus avoiding what is called “first-pass metabolism” by the liver.

One study compared the sublingual administration of THC and CBD. Despite the administration of equivalent amounts of THC and CBD (25 mg each), lower plasma concentrations of CBD were always observed. Thus, if you are more interested in using THC than CBD, sublingual is probably an optimal method of administration.

Oral administration, such as ingesting THC or CBD extracted into oil and then suspended within food, does not avoid the first-pass metabolism by the liver. However, absorption from the gut can be slightly improved by dissolving these molecules in sesame oil or most other cooking oils. Very little of the THC consumed actually enters the blood circulation, and thus gains access to the brain, following oral administration. The peak THC in the blood occurs about 1−5 hours after the ingestion of 20 mg of THC in a cookie or brownie.

Keep in mind that oral administration of any drug is probably the least efficient way to get a drug into the brain. Only about 6 percent of a 20 mg dose of THC, or about 1.2 mg, actually gets into the blood following oral administration. The problem is that most of the consumed THC or CBD degrades in the stomach or is metabolized by the liver primarily into inactive metabolites. However, if you are determined to eat your drug in a brownie or cookie, the blood levels of CBD, but not THC, are increased when consumed with food or just prior to eating. CBD is a highly fat-soluble, thus the fat in most foods increases its solubility and absorption. Thus, if you are more interested in using CBD than THC, oral administration is probably an optimal method of administration.

Rectal administration is not the administration method likely to be most popular when you are interested in sharing the experience with a friend. However, and this might make you change your mind, the proportion of the THC dose administered that gains access to the blood via the rectal route was twice that of the oral route due to higher absorption and lower first-pass metabolism by the liver. Some dispensaries do offer rectal suppositories; now you know why.

Topical application of THC or CBD is a viable option because this administration method avoids first-pass metabolism by the liver and because these molecules are very fat-soluble. However, they must first penetrate the dead superficial layer of skin and the aqueous layers of the dermis. Some of the early studies of this application method greatly underestimated how much THC could get across the skin. The ability of these molecules to pass through the skin may explain why cannabis was a component of the holy anointing oils described in the Old Testament.

Topical absorption of THC or CBD can be improved if the skin is abraded, burned, or inflamed; obviously, these are not ideal conditions for regular use. Commercially prepared transdermal patches are advantageous because they are designed to enhance the transport of drugs across the skin. When a dose of THC was administered using a transdermal patch, the blood level peaked about 1.5 hours later and remained elevated and stable for at least two days. Transdermal patches are an optimal method of administration for the long-term reduction of .

Now that the drugs are in the body, where are they going and how long do they stay there? THC and CBD are highly fat-soluble and initially taken up by tissues that are highly perfused with blood, such as the lung, heart, brain, and liver. Unfortunately, body fat tends to hang on to THC for a much longer time than does the brain. This is one of the main limiting factors of the duration of the effects of THC in the brain; essentially, the body fat steals THC away from the brain. The ratio of THC in fat to THC in the brain was approximately 21:1 after 7 days of consecutive use, and 64:1 after 27 days of consecutive use. Thus, most of the THC consumed is deposited into body fat. THC not only concentrates in human fat, but it also tends to stay there a very long time by actually binding to the fat molecules.

Ideally, a single dose of between 2 and 22 mg of THC (the ratio of THC to CBD is highly influential but also rather complicated; I will discuss that in a later blog) must be present in a cannabis cigarette, and the entire cigarette must be used by a single person in order to get 0.2−4.4 mg of THC into the blood that is then distributed throughout the entire fat-filled body. Ultimately, only about 4 trillion molecules of THC will successfully penetrate across the blood-brain barrier to distribute themselves within a brain that contains ten billion times as many other molecules. Apparently, this “tiny drop of THC dissolved in an ocean of brain” is sufficient to produce the desired effects.

© Gary L. Wenk, Ph.D. is the author of Your Brain on Food and is a member of the Governor’s Medical Marijuana Advisory Committee for the State of Ohio.