And why cannabis taken orally can feel more psychoactive than inhalation
Medicinal action of cannabinoids don’t depend on psychoactivity although many people enjoy psychoactivity, hence widespread “recreational” use of cannabis. In my 16 years of working with medical cannabis patients, a subset of patients can consume larger than anticipated quantities of THC without psychoactivity. I was surprised to hear of consuming >100mg THC without psychoactivity, but as I continued to see patients with this experience over the years, I suspected liver function was involved. Science is slowly providing details to why a subset of people have this experience.
When you eat a product containing THC, your liver converts THC into 11-hydroxy-THC. 11-hydroxy-THC (11-OH-THC) is the main active metabolite of THC. 11-hydroxy THC may be particularly effective for people suffering from chronic pain and low appetite. The body’s absorption rates of 11-hydroxy-THC are relatively low, and the compound is not easy to stabilize without using solvents, unlike many other cannabinoids, the cannabis market has not found a way to use it directly in formulations. The primary way to utilize 11-hydroxy THC is through your body’s conversion from orally administered THC.
What is 11-hydroxy-THC?
Hold on tight, this is a bit science heavy so bear with me while I explain.
11-hydroxy-THC is the third iteration of a chemical found in raw cannabis. This chemical starts as THCA (tetrahydrocannabinolic acid) in fresh cannabis, and is converted into Δ9-THC after aging and heating. When consumed, Δ9-THCis metabolized by the liver into 11-hydroxy-THC and finally into 11-nor-9-carboxy-THC.
Δ9-THC is the main cannabinoid you get from heated/cured cannabis. Regardless of how you intake cannabis, your liver will metabolize Δ9-THC into 11-hydroxy-THC. The difference is in how quickly this happens. Anything you consume orally is absorbed through the gut and passes through the portal vein system before entering your body’s circulatory system. As a result, the metabolism of Δ9-THC to 11-hydroxy-THC happens much more rapidly after digestion and absorption. By contrast, when you inhale cannabis, Δ9-THC enters your bloodstream directly from your lungs, causing a quick increase in Δ9-THC blood levels. As only a little bit of circulatory blood goes through the liver at a time, the conversion to 11-hydroxy-THC is relatively slow.
Eating Δ9-THC-infused edibles increases the amount of 11-hydroxy-THC available in the blood (when compared to inhalation) because oral consumption requires Δ9-THC to pass through the liver first. This is called the “first-pass effect” or “first-pass metabolism.” The liver enzyme CYP2C9 is responsible for metabolizing Δ9-THC into 11-hydroxy-THC.
As with all liver enzymes, different people have different levels of activity in their liver enzyme. Based on my experience with patients, I anticipate that future research will find that a subset of patient’s have lower activity of CYP2C9 activity, thus converting less Δ9-THC to 11-hydroxy-THC. This subset of patients will notice less psychoactivity from their cannabis edibles. It is also possible that some persons have liver functioning that converts Δ9-THC preferrentially into other cannabinoids that are less psychoactive than 11-hydroxy-THC.
Other possibilities that may contribute to decreased psychoactivity for some people are differences in digestion. It’s important to understand that digestion and absorption vary between individuals, so some will notice an effect from an edible in as little as 30 minutes while others may need hours. If you digest fats poorly, you will not absorb as many cannabinoids from your edibles, leading to decreased effectiveness. Patients with certain digestive disorders may prefer to use inhalation based methods for this reason.
Interestingly, when cannabis is consumed, less Δ9-THC makes its way around the body, and more Δ9-THC is excreted. However, as the THC passes through the liver first, it is more readily converted into 11-hydroxy-THC. 1 mg of Δ9-THC consumed orally and converted into 11-hydroxy-THC can feel more potent than 1 mg of inhaled Δ9-THC.
Inhalation means Δ9-THC goes through the lungs and straight into the blood, slowing the conversion from Δ9-THC into 11-hydroxy-THC.
How It Impacts the Human Body
11-hydroxy-THC may be 2-3 times more potent than Δ9-THC and have significantly more psychoactive effects. In my experience, most patients report psychoactivity from oral Δ9-THC in 1-2 hours although the range is 30 minutes-4 hours. The delay between consumption and psychoactivity highlights the importance of appropriate dosing. I counsel patients who are new to cannabis to use a dosing schedule that starts with a low daily of Δ9-THC with gradual increases until an effective dose is noted. A dose that effectively treats a medical condition can be below the psychoactive threshold.
There is little research into how 11-hydroxy-THC affects the brain and the body. The increased duration of time edibles have an effect for and the potentially greater psychoactivity of 11-hydroxy THC suggests that it could help treat long-duration conditions like chronic pain and insomnia. Evidence also suggests that 11-hydroxy-THC may be responsible for “the munchies” or increased appetite after cannabis use. Most patients report that increased appetite occurs with a delay after inhalation, after the body has had time to convert Δ9-THC to 11-hydroxy-THC.
How to Avoid Consuming Too Much
I use a conservative dosage system, individualized for patients. A common approach in my practice is to recommend a low starting dose of 1-2mg Δ9-THC used daily, likely in concert with other cannabinoids, with a small increase every 2-3 days until noticing a beneficial effect. Your doctor may recommend a different starting dose. If a dose seems mildly beneficial, stay with that dose for up to a week before making the decision to increase. Once an appropriate dose is determined, we may add additional daily doses. This approach has served thousands of patients well over the years, reducing adverse events from Δ9-THC. An appropriate dose may be anywhere from 1mg Δ9-THC to 100mg Δ9-THC, thus an individualized approach is warranted to avoid over dosage in sensitive individuals.
It is common to think, “This edible isn’t having any effect on me,” after an hour and take more. Don’t be duped! The fact that so many edibles are sweet treats makes eating them all at once particularly enticing. I’ve occasionally had cannabis naive patients do so- typically before establishing care with me- leading to a negative experience, or even an unnecessary trip to the ER. I’ll never forget my elderly patient waving her hand my direction, stating “i know my grandson told me to eat only one per day when he gave me these gummy bears. I ignored him because who eats ONLY ONE gummy bear!?”
If you’re a person who can’t eat “just one”, have a non-cannabis option available to satisfy your appetite after having your cannabis dose or choose a product that is less likely to lead to overconsumption like a tincture or a capsule.
If you’re seeking a doctor to help guide you through finding the right dose of THC for you, we’re here to help! Qwibil’s doctors are the leading experts in cannabis care in the Tacoma, WA area.