11-OH-Tetrahydrocannabinol



   While the topic is phytocannabinoids, those cannabinoids produced by plants, we will be looking at a bit further at ∆-9-THC and how it is metabolized, or changed from one chemical form to another for elimination by the body. The phytocannabinoid ∆-9-THC is metabolized by the liver into another active cannabinoid: 11-OH-THC. An understanding of how this "self-made" THC metabolite (product of metabolism) interacts with the endocannabinoid system is necessary when choosing optimal treatment for your conditions.

Cannabinoid: 11-hydroxy-tetrahydrocannabinol (11-OH-THC), an active metabolite of phytocannabinoid ∆-9-THC

After decarboxylation (by application of heat, UV light or aging) of THCA to ∆-9-THC, the phytocannabinoid is "activated" and ready to work on the endocannabinoid system; however, the activity of ∆-9-THC is only part of the tetrahydrocannabinol story. 11-OH- THC is the first product of ∆-9-THC produced by the liver as the body metabolizes it for removal from the body. Interestingly, this metabolite is not only active and interacts with the endocannabinoid system much as ∆-9-THC, it is much more potent and longer lasting. Knowing this and how to game your body and endocannabinoid system can make your treatment with medical cannabis more effective, less costly and decrease the possibility of dosing errors.

Making Some 11-OH-THC

∆-9-THC is first changed into 11-OH-THC by the liver and goes into the circulatory system which distributes it throughout the body where it then interacts with the endocannabinoid system. Most of the final elimination of THC is through the GI tract in feces. When 11-OH-THC passes through the liver, it is further metabolized to the inactive metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). From there, the inactive THC-COOH passes into circulation, accumulates in fatty tissues being slowly released into circulation and is then removed by the kidneys being excreted in urine. This is the metabolite of THC which urine drug screens detect and can be present for weeks after last cannabis use.

When cannabis is administered by the inhalation route, ∆-9-THC is very quickly absorbed into the bloodstream to exert its effects on the endocannabinoid system. The ∆-9-THC which is not picked up ends up circulating through the liver and is then converted to 11-OH-THC. The 11-OH-THC produced is either eliminated in the GI tract or released into circulation. The levels of 11-OH-THC measured are much lower, but present longer, in comparison to ∆-9-THC levels seen in subjects using smoked cannabis. Most of the effects of THC on the endocannabinoid system using inhalation administration are from ∆-9-THC.

Making More 11-OH-THC

For patients with around the clock symptoms or high dose requirements of THC to control symptoms, the 11-OH-THC version of tetrahydrocannabinol should be considered. Being more potent and longer lasting, it can provide more a more adequate response with lower and less frequent dosing. By virtue of being more potent and providing a longer duration of action, it can also be more cost effective.

Oral cannabis administration is the way to produce a much higher fraction of ∆-9-THC conversion to 11-OH-THC compared to the inhalation route. The THC is adsorbed through the gut and enters the liver first before entering circulation. Much more ∆-9-THC is available for metabolism to 11-OH-THC, some of which is eliminated via the gut with the rest released by the liver to interact with the endocannabinoid system resulting in more profound and longer lived effects than ∆-9-THC.

With these pluses over inhalation administration, the oral route seems the way to go for many patients; however, the advantages are indeed but one edge of the sword. For patients needing rapid symptom relief, the quite variable 30 minute to 4+ hour onset of action (activation time) is inadequate. Patients with intermittent symptoms, those that last a relatively short time or are of moderate intensity not requiring much THC for symptom control may over treat. Because of being more potent and longer lasting, having a variable activation time and other factors, it is much easier to exceed the therapeutic dose (that required to improve symptoms) and experience side effects of high dose THC which can persist for hours.

The amount of 11-OH-THC produced in an individual is, of course, quite variable. There are many factors to consider when using oral cannabis such as conditions effecting gastric emptying (e.g. diabetes) or gut absorption, timing of last meal, amount of fat content in ingested foods, individual metabolism determined by genetics, etc. Correct dosing is a bit tricky.

Back to the Big Picture

Tetrahydrocannabinol is only one piece, but is a big piece, of the cannabinoid puzzle. Understanding the characteristics and differences of the several species identified will allow you to optimize you use of medical cannabis and obtain the best possible results. Increasing the fraction of 11-OH-THC produced can be a better "fit" in the puzzle for many patients.

Determining the appropriate dose for an individual patient always comes down to titration, which is the administration of small standardized doses at specified time intervals until an endpoint of symptom control is achieved. I will cover titrations in more detail in another article, but here are the pearls.