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Why don't cannabis edibles ever work for me?

Gastrointestinal disorders and cannabis

When someone says “edibles don't really work for me,” my first question is whether they have a gastrointestinal issue. Inflammatory Bowel Disease, malabsorption syndrome, and Irritable Bowel Syndrome can affect how the small intestine absorbs nutrients, water, and medicine.

In my experience, the vast majority of folks who don't feel effects from edibles confirm that their body also has trouble digesting food. After following up with the author of this month's question, I was able to rule out that simple explanation — leading me to a more complex potential explanation.

Slow metabolizers versus rapid metabolizers

Cytochrome P450 enzymes, sometimes called CYP (“sip”) enzymes, help your liver kickstart the metabolization of most drugs. While there are over 50 CYP enzymes, six of them do the bulk of the work, often tag-teaming to get the job done.

Each CYP enzyme correlates to a specific gene that acts as a book of instructions, telling your body how to construct the enzyme step-by-step. Every gene presents a number of possible different versions known as alleles. The most common allele carried by most people is known as the “wild type.” If you inherit the wild-type allele from both parents, your body will metabolize drugs as expected.

If a parent passes on a less-common “variant” allele, that gene will usually encode enzymes that don't work as well, meaning you'll metabolize drugs a little slower. This diminished enzyme efficacy means you'll be a slow metabolizer.

According to the website for Lobo Genetics, a company that offers genetic testing for cannabis users, “These 'slow metabolizers' should be more cautious when consuming THC, as they will likely experience an increased duration and intensity of intoxication, especially when taking THC in oral form.” Slow metabolizers could accumulate levels of THC up to 300% higher than those with standard metabolisms, leading to unpleasant consequences from over-intoxication.

Here's where things get interesting. If you inherit multiple copies of the wild-type allele — that's the most common, “normal” version of the gene, usually resulting in a healthy drug metabolism — your system will be too good at clearing drugs from your bloodstream. As an ultrarapid metabolizer, you may not even have a chance to feel the desired effects of THC before it's converted into 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're breaking it down so fast it doesn't have an opportunity to create the psychoactive effect,” she told Globe staff, adding that variables like how quickly your body absorbs fat also plays a role.

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

The Lobo Gene CBD test could help confirm my suspicion that you're a rapid 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.

Want to skip the swab? You could just ask your family members. Since this is an inherited trait, there's a significant chance one of your siblings, birth parents, or other blood relatives may experience the same reaction to ingested cannabis.

Alternatives to edibles

As I've said before, the best way to get high is the way that works for you. It sounds like smoking and vaporizing are both viable options for you, which makes sense; those methods are preferred by a large number of cannabis users, who appreciate the rapid onset of effects. Our lungs quickly absorb cannabinoids into our system, avoiding the waiting and guesswork involved with edibles.

However, most of us will need to step back from inhalation eventually, whether it's a permanent change or just a short break. Illness, surgery, and travel can all be valid reasons to switch ingestion methods, and it can be frustrating to have limited options.

Thankfully, I have a few suggestions that avoid both inhalation and digestion. The first is transdermal, or transcutaneous absorption, where a medicated patch delivers cannabinoids to the blood vessels found just underneath our skin.

You could also try sublingual or buccal drug administration. Latin for “under the tongue” and “cheek,” these methods rely on the absorbent mucous membranes of your mouth. The usual method is to hold tincture, oral drops, or oral spray under your tongue, or to rub RSO between your gum and cheek. Hold the product in your mouth for 2 - 3 minutes, or “past the point where it feels gross,” as I've heard a fellow budtender say.

Cannabinoids should begin circulating through your system rapidly, without undergoing first-pass metabolism by CYP enzymes. A similar biological process accounts for the success some people find with cannabis suppositories. Solidified, infused oil is molded into the shape of a bullet, which is then inserted vaginally or anally. As the suppository melts inside, it should create long-lasting analgesic effects comparable to a fast-acting edible.

Genetic testing to predict your response to cannabis

An influential 2013 study into the metabolism of cannabis 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 where pharmacists provided personalized consultations based on results from Lobo Genetics. “Our findings suggest that patients highly valued the pharmacist consultation and being able to use personalized genetic information to make decisions about future cannabis use,” researchers wrote.

As pharmacogenetics testing from companies like PillCheck becomes more widely available, it's likely to become more integrated into the cannabis consultation process. Imagine a futuristic dispensary where a scanner flags you as a rapid metabolizer and a computerized consultant suggests suppositories instead of gummies. It seems like science fiction, but it might be closer than we think.

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