Ediblocked: Why Can’t Some People Get High From Edibles?

Have you ever shared some edibles between friends, only to discover that one of you is feeling nothing at all? Well, Al McDonald has. The Boston Globe presented Al McDonald’s story as an example of a situation where a group of friends shared “a strong batch of pot-infused cookies” but he got absolutely nothing from them. McDonald even stated that he sat there like “aww man… everybody’s Hoverboard works except for mine.” McDonald represents the group of people who have a hard time getting high from edibles, which seems to have stumped scientists. 

People Who Are ‘Ediblocked’ Are Unaffected by Edibles

McDonald forms part of an “unknown portion of the population that appears to be functionally ‘immune’ to edibles, or at least has exceptionally high tolerances.” The Boston Globe describes this group of people as being “ediblocked” but also explains that when they smoke cannabis, they experience it as normal. Persons who are classified as ediblocked are said to be able to consume quantities of cannabis that would send the majority of people on an intense trip, while they experience nothing.

McDonald was reported to have engaged in a rather “reckless experiment” where he consumed hash tea and only began to feel something at around 700 milligrams of THC. To put that in perspective, 700 milligrams is 140 times the standard serving in Massachusetts of 5 milligrams. Additionally, it is recommended that consumers of cannabis begin with 1-2.5mg of THC as well as capping it at 10mg under normal circumstances in order to minimize adverse effects associated with high THC potency. Cannabis should contain around 10% or less THC to be considered effective, low-potency, and a lower risk of adverse effects such as increased anxiety. 

The Boston Globe goes on to explain that researchers and medical professionals are aware of and acknowledge the phenomenon of being ediblocked but are not able to definitively explain it. They also explain that this can have “serious implications for dosing in medical marijuana treatment” as well as arousing questions on the validity of the blood tests which indicate cannabis-related impairment. 

Researchers Hypothesize That the Answer Might Be in the Liver

The director of the Marijuana Investigations for Neuroscientific Discovery programs at the McLean Hospital, Dr. Staci Gruber, stated that “we’re only just now starting to understand the cannabinoid system” and that “it’s already clear that it’s not just about what and how much you’re using; it’s about how you’re wired.” 

Currently, there is limited research on people with ultra-high tolerances to marijuana edibles, however, Dr. Gruber and other researchers have a compelling hypothesis. The hypothesis is that those who are ediblocked have an unusual variation of a “key liver enzyme” which could “essentially be too efficient at processing ingested THC, turning the compound into its ‘active’ high-inducing metabolite and then its inactive waste product before the active form can enter the bloodstream or brain.”

However, there is another similar possibility which includes being “unusually inefficient at performing this process, with little THC getting metabolized in the first place.” Dr. Gurber explains that “it’s almost as if they’re skipping the intermediate step.” She also explains that the people with the uncommon CYP2C9 gene are breaking down the cannabinoid so fast that “it doesn’t have an opportunity to create the psychoactive effect.” 

What Is The CYP2C9 Gene and How Does it Impact THC Levels in the Body?

MedlinePlus explains that the CYP2C9 gene “provides instructions for making an enzyme that is found in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport.” They go on to explain that the CYP2C9 enzyme plays an important role in the metabolism and breaking down of drugs including warfarin and ibuprofen. The Boston Globe also explains that it also “encodes the enzyme that shepherds THC through its three-step metabolic transformation.” While Dr. Gruber adds that the individuals with the gene are “breaking it down so fast it doesn’t have an opportunity to create the psychoactive effect.” 

A 2020 study found that the levels of THC metabolites found in the consumer’s blood varied drastically “depending on which variant of the enzyme they had.” The research from this study “casts doubt on biological marijuana tests widely used by researchers, doctors, police, and employers.” These tests do not account for the “apparently vast and hard-wired variations in metabolic rate between individuals.” Dr. Gruber explains that “it underscores the need to understand people’s genetic profile, and that there are a lot of variables people haven’t considered” such as whether one has the uncommon CYP2C9 enzyme. 

The Problem With Being Ediblocked

Being ediblocked poses a problem for those who wish to medicate with cannabis by means of oral ingestion as opposed to inhalational methods. When one is unable to feel the effects of edibles or cannabis which is swallowed, they may experience ‘social FOMO’ or the inability to benefit from the pain-relieving and other medicinal properties which cannabis contains.  Edibles make for a great alternative means of cannabis consumption when smoking is not an option. 

When CYP2C9 acts on THC in the liver, the active intermediate is 11-OH-Δ9-THC – which is four times more psychoactive than THC. After this step, the 11-OH-Δ9-THC is inactivated by CYP2C-MALDO. Therefore, the secret of the ediblocked theory could lie in one or both of these steps. This ultimately means ediblocked people are unfortunately missing out on a stronger, more discrete, and cost-effective medical use altogether (1). The Boston Globe states that these ‘ediblocked’ individuals could benefit from the relief of cannabis through edibles if they took a “high enough dose, or if a supplement could be developed that slows their enzyme action”. 

While there is not enough research to support the hypothesis at the moment, the study and the researchers make valid points. Hopefully, research can be conducted to support the suggestions and findings so that we can find solutions for those individuals as well as for improving the means by which we measure cannabis impairment.