Why don’t cannabis edibles work for me?

Lorena Cupcake, voted “Chicago’s Best Budtender” in 2019, has answered hundreds of questions from cannabis buyers and patients during her time as a budtender. And now they’re turning that experience into a monthly advice column, Ask a budget tender. Have a question for cupcake? Send your questions to askabudtender@weedmaps.com.

Hello cupcake,

I never get any real effect from consuming edibles. It’s like my body doesn’t recognize if I don’t inhale real smoke or steam.

I’ve tried a number of different strains, both homemade and medicinal grade, to no avail!

Any suggestions?

Signed,

This rubber is just a rubber, what is it?

Dear rubber,

There are endless factors that influence our individual cannabis experience. While a batch of brownies can bake an entire party, it’s likely that each person’s high will have a unique intensity and length due to their height, tolerance, and other factors. However, if you are feeling cold sober while your friends keep giggling, it makes sense to wonder what is different about your body and the way you metabolize cannabis.

During my time as a budtender, I have seen this complaint enough times to theorize the most likely causes.

Gastrointestinal diseases and cannabis

When someone says, “Edibles don’t really work for me,” the first question I ask is whether they have a gastrointestinal problem. Inflammatory bowel disease, malabsorption syndrome, and irritable bowel syndrome can affect the uptake of nutrients, water, and drugs by the small intestine.

In my experience, the vast majority of people who do not experience any effects from edibles confirm that their bodies are also having difficulty digesting food. After looking into the author of this month’s question, I was able to rule out this simple explanation – which led me to a more complex possible explanation.

Slow metabolizers versus fast metabolizers

Cytochrome P450 enzymes, sometimes called CYP enzymes (“sip”), help your liver metabolize most drugs. Although there are over 50 CYP enzymes, six of them do most of the work and often work together to get the job done.

Each CYP enzyme is correlated to a specific gene that acts as a guide and tells your body how to build the enzyme step by step. Each gene has a number of possible different versions known as alleles. The allele most commonly carried by most people is known as the “wild type”. If you inherit the wild-type allele from both parents, your body will metabolize the drugs as expected.

Usually, when a parent passes on a less common “variant” allele, that gene encodes enzymes that don’t work as well, which means you metabolize drugs a little more slowly. This decreased enzyme effectiveness means you do slow metabolizer.

According to the website of Lobo Genetics, a company that offers genetic testing for cannabis users, “these ‘slow metabolizers’ should be more careful when consuming THC as they are likely to experience longer duration and intensity of intoxication, especially when ingesting the THC oral form. “Slow metabolisers can accumulate THC levels up to 300% higher than those with standard metabolism, leading to unpleasant consequences from excessive intoxication.

This is where things get interesting. If you inherit multiple copies of the wild-type allele – this is the most common, “normal” version of the gene that usually leads to healthy drug metabolism – your system will be too good at clearing drugs from your bloodstream. As an ultra-fast metabolizer, you may not even get a chance to feel the desired effects of THC before it has been converted to an inactive metabolite.

Dr. Staci Gruber, director of Marijuana Investigations for Neuroscientific Discovery (MIND) at McLean Hospital, recently explained the phenomenon to the Boston Globe. “You break it down so quickly that it has no way of producing the psychoactive effect,” she told Globe staff, adding that variables like the rate at which your body is consuming fat also play a role.

CYP2C9 and CYP2C19, the two genes most associated with cannabis metabolism, each have over 30 variants in addition to the standard wild type. “There is no ultrafast metabolizer genotype for THC and the CYP2C9 metabolic gene; only normal and slow metabolisers, ”a representative from Lobo Genetics told me. “For … the metabolic gene CYP2C19 there are both ultra-fast metabolisers (CYP2C19 * 17) and slow metabolisers (CYP2C19 * 2, * 3).”

The Lobo Gene CBD test might confirm my suspicions that you are a fast metabolizer, Gummy. If you know how to interpret the data, you could even find the relevant genes in test results from companies that don’t specifically market to cannabis users, like AncestryDNA or 23andMe.

Would you like to skip the swab? You could just ask your family members. Since it is an inherited trait, there is a significant chance that one of your siblings, birth parents, or other blood relatives will experience the same reaction to cannabis use.

Alternatives to edibles

As I said earlier, the best way to get high is the one that works for you. It sounds like smoking and vaping are both viable options for you, which makes sense; These methods are preferred by many cannabis users who appreciate the quick onset of action. Our lungs quickly absorb cannabinoids into our system, avoiding the waiting and guesswork associated with edibles.

However, most of us will have to stop taking an inhalation at some point, be it a permanent change or just a short break. Illness, surgery, and travel can all be valid reasons to change your intake method, and having limited options can be frustrating.

Fortunately, I have a few suggestions that will avoid both inhalation and digestion. The first is transdermal, or transcutaneous absorption, in which a medical patch releases cannabinoids into the blood vessels just below our skin.

You could try too sublingual or buccal Drug delivery. Latin for “under the tongue” and “cheek”, these methods are based on the absorbent lining of your mouth. The usual method is to hold tincture, mouth drops, or spray under your tongue, or rub RSO between your gums and cheek. Hold the product in your mouth for 2-3 minutes, or “past the point where it feels gross,” as I heard from another budtender.

Cannabinoids should circulate rapidly through your system without undergoing first-pass metabolism by CYP enzymes. A similar biological process explains the success some people find with cannabis suppositories. Solidified, infused oil is formed into a ball that is then inserted vaginally or anally. Since the suppository melts inside, it should have a long-lasting analgesic effect comparable to a fast-acting edible.

Genetic testing to predict your response to cannabis

An influential study of cannabis metabolism in 2013 recommended that “more prospective studies with clinical endpoints are needed before the paradigm of personalized medicine based on the variants can be established”. Since then, a number of studies have examined the relationship between our genetic makeup and our experiences with cannabis.

Last year, the Journal of Cannabis Research published a small study in which pharmacists provided personalized consultations based on results from Lobo Genetics. “Our results suggest that patients greatly appreciated the pharmacist’s advice and the ability to use personalized genetic information to make decisions about future cannabis use,” the researchers wrote.

As pharmacogenetic tests become more widely available from companies like PillCheck, they are likely to become more integrated into the cannabis counseling process. Imagine a futuristic pharmacy where a scanner marks you as a fast metabolizer and a computerized advisor suggests suppositories instead of gummy bears. It seems like science fiction, but it might be closer than we think.

Do you need advice on how to incorporate cannabis into your lifestyle? Write cupcake to askabudtender@weedmaps.com

Featured image by Gina Coleman / Weedmaps