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
Cannabinoid: 11-hydroxy-tetrahydrocannabinol (11-OH-THC), an active metabolite of
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
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.
Perform your titration on a day you have no obligations. Although you can not be
poisoned (overdose/death) by cannabis, you can easily be "over served" and
experience sometimes intense intoxication which may last several hours. Be sure you
are somewhat tolerant to cannabis’ side effects by the inhalation route before
beginning an oral trial to minimize the chances of excessive side effects. Have a CBD
source available to treat any too intense euphoric effects if they occur.
You MUST keep a log/diary of the intensity of symptoms to be controlled. You should
hourly evaluate and record symptoms, dose of medication and time of administration
on titration day.
Start with a LOW dose (1.25 - 2.5mg ∆-9-THC).
Administer the SAME dose (1.25 - 2.5mg ∆-9-THC) at the SAME time intervals (about
60 - 120 min for most patients).
When a 50% improvement in symptoms has been reached you have determined your
DOSE (e.g. it took three 2.5mg doses to reach the endpoint, your dose is 7.5mg). If
you experience intolerable side effects at some point in the titration, back down one
"step" on the dose and record that as highest tolerated.
Pay attention to when your symptoms reoccur (keep up with your log hourly). If the
medication lasts eight hours, you have determined your DOSING INTERVAL - the
schedule you take the determined DOSE (e.g. 7.5mg every eight hours).
Brian Nichol MD