If you’re one of the millions of cannabis consumers who are concerned about the potentially negative health effects of smoking or vaping cannabis, you’ve likely been advised to try edibles at one point or another. No one could have prepared you for the experience of eating a small, THC-infused gummi candy and then blasting off into the stratosphere for a few hours while you wrestled with your ego. The form of THC that edibles deliver is much more psychedelic than the form that is produced when cannabis is smoked.

For most users even the smallest dose of edible THC is enough to send them to the moon. But for a very small portion of the population, a genetic variation prevents them from being affected by edibles at all.

How Edibles Work

When cannabis is smoked or vaped, THCA, a cannabinoid acid, is converted into Delta-9 THC, the compound we all know and love as the cannabinoid that makes us feel high. This is done through the process of decarboxylation—when the plant matter is heated. The Delta-9 THC is then absorbed through the lungs and deposited into the bloodstream. The reaction is immediate, and the effects last between 10 minutes and an hour.

When a consumer eats an edible, however, the THCA has already been converted into Delta-9 THC during the preparation process. The compound then travels through the gastrointestinal tract and the liver, where the Delta-9 THC is broken down into a metabolic byproduct called 11-hydroxy THC. This form of THC is much more potent than Delta-9 THC and produces a different experience than smoking altogether. Because it has to be digested, it can take up to 90 minute or longer for an edible to start working, and the effects can last for hours instead of minutes. Users report that edible cannabis also produces more psychedelic effects than the smoked variety.

An enzyme called cytochrome P2C9 (CYP2C9) in the liver and GI tract is responsible for breaking down Delta-9 THC. This enzyme is used as part of the first steps of your body’s metabolizing process. It also breaks down other drugs and hormones. The amount of time it takes to break down THC metabolites is totally dependent on the performance of CYP2C9, and it appears that an individual’s CYP2C9 performance is based on which version of a specific gene they carry.

For some unlucky individuals of a certain genetic subtype, their GI tract produces an enzyme that breaks down THC faster than in others, totally preventing them from feeling the effects of edibles.

Genetic Party Pooper

“I was at a party in my early 20s and someone brought pot brownies,” says Ted Rodriguez, a patient enrolled in the New Mexico Medical Cannabis Program. “An hour into it, everyone was acting like they were having a good time—giggling, acting funny. I didn’t feel anything. Another hour went by and I had already eaten three times the amount of everyone else. I finally had to say ‘Stop, I’m just wasting these.’ ”

Rodriguez says he’s tried edibles a number of times over the years with the same results. “I quit trying after eating a 500 milligram [THC] cookie in Colorado. It was getting too expensive.” To put it in perspective: A normal recommended starting dose for edibles is between 5 and 10 milligrams.

Rodriguez’s tolerance to edibles doesn’t seem to translate over to smoked or vaped cannabis, which appear normal for his level of consumption. Every expert in the field that he’s approached about the problem has been puzzled. Thanks to the federal ban on cannabis and a general lack of awareness around the issue, there just isn’t much in the way of research on the topic.

In 2005 researchers found that a certain CYP2C9 variant metabolized 30 percent less THC than another in the same amount of time. The study was conducted using enzymes in a lab.

But there’s also been at least one clinical study conducted with human participants. It was published in the journal Clinical Pharmacology & Therapeutics in 2009 and found that CYP2C9 efficiency is higher for carriers of a certain genetic variant. The study measured THC and metabolites 11-OH-THC and THC-COOH over time in 43 volunteers who were given 15 milligrams of oral THC. For those whose variant produced a more efficient enzyme, the effects and presence of THC deteriorated much more quickly.

The study had a very small sample size, indicating that there could be many other variants out there with differing levels of CYP2C9 efficiency. All signs point to the likelihood that there is at least one rare CPY2C9 genetic subtype out there that produces an enzyme that processes THC so fast that it doesn’t have time to produce any psychoactive effects.

The Bad News

If you’re one of those sad few who have this genetic edible-destroyer in your makeup, there doesn’t seem to be any way around it: You’ll probably never enjoy the pleasures of an edible-fueled romp through the land of mind alteration.

But there is some good news. First off, you’re not crazy—you’re not the only one having this experience. Second: You can stop buying bigger and more expensive edibles. It will never be worth it.

Most important, though, is that current research around cannabis’ therapeutic benefits has shown repeatedly that the most medically beneficial way to consume cannabis is by smoking raw flower. There is much more to the plant than THC and CBD. There are hundreds of other cannabinoids found in marijuana, and they all have their own unique health benefits. Cannabis extracts and edibles strip away much of these compounds and leave much to be desired.

Written by