Quick Summary: Some people with certain variants in the AKT1 gene may be more prone to more paranoia, anxiety, and disorienting effects of THC. This may supercede the differences between containing strains to a degree. So consider this before you tell someone "you haven't found the right strain."

Do you, a client, or someone you know always seems to get anxious from cannabis? 

Some people are simply more prone to these unwanted effects from THC.

"You just haven’t found the right strain" might not be the right answer...

People with the T allele of rs2494732 might be more prone to anxiety or paranoia with THC use according to a 2016 study published in Translational Psychiatry entitled "AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers"

For a more in depth article on genetic variants or SNPs in general, read this here.

From the abstract "A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis—which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content—and also ±7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms."

The term psychotomimetic means "psychosis mimicking" and the researchers used a standardized scale to assess these aspects of participants high. While this doesn't exactly translate directly 1:1 to paranoia/anxiety alone, it's a parallel trait.

Other studies have found that this variant, along with a variant in DRD2 has an influence on first episode psychosis and cannabis use.

But for the purposes of thinking about who might be more prone to a bad time with THC, this gene likely plays a role.

Below is a graph from the study showing that those with the C allele scored on average 15-20% higher on the intoxicated psychotic symptom score while high.

One of the strengths of this study was that they let the participants bring their own weed in order to account for the way people might self-select strains that work better for them. Despite this, the effect remained. They also measured the CBD and THC content in the strains used and found no impact on the results. 

One of AKT1's roles is a regulatory factor in the brain's dopamine system. It codes for a protein kinase that forms part of the striatal dopamine signaling cascade, which is known to be altered in schizophrenia compared to healthy people.

This variant in AKT1 is not the only things that can impact this of course. There are other genetic factors that influence this and every trait is complex. And, of course set, setting, and strain matter too. But, in certain cases, it seems that some people may be less compatible with THC regardless of the strain. 

So, how to use this information?

First, understand that some people are just wired to respond to weed differently. Some people like it, some people don't. It's time to get over the idea that people's preferences make them "weak" or "not able to handle it."

It's easier to have empathy for people when you can understand genetic differences like this. Shaming people for different responses to the plant doesn't help anyone. 

Cannabis induced anxiety is one of the most common unwanted side effects and is more associated with higher doses of THC. Lower doses may have an anxiolytic (anxiety reducing) effect, but again that may depend on the person. CBD tends to decrease anxiety at most doses, so choosing more balanced strains or products may be helpful.

Additionally, different studies have found a variety of associations with anxiety disorders and chronic cannabis use. Some have suggest a small increase in likelihood, especially for social anxiety issues, but others have found no effect.

Finally, some people do find THC helpful for reducing anxiety. But just because some people find it helpful, keep in mind everyone has a different response and the AKT1 gene likely plays a role.

The Big Picture

Response to cannabinoids has many components. I like to think of it as a combination of:

• Set (Mindset, psychology)
• Setting (Where and when are you using it)
• Genetics (Your baseline tendencies)
• Epigenetics (Your current health status)
• Strain (Combination of cannabinoids and terpenes)
• Method of Ingestion (vaped vs oral vs smoked)
• Dose
• Quality of Product

Some of these factors you may have more control over than others. You can't control your genetics but you can match the right inputs to your genetics.

This means potentially choosing a different food, herb, supplement, or lifestyle choice to create better epigenetic expression.

Having a better understanding of ALL the components listed above can help you optimize you or your client's health in a more strategic, precise way.

If you're curious about analyzing your endocannabinoid genes, send me a message. I helped develop the Apeiron Endocannabinoid Genetic Panel that can give you a better understanding of the dynamics of how you respond to THC, CBD, and naturally create your own endocannabinoids. I look at this and 50+ other variants for a comprehensive look into how to best use cannabinoids.

Or if you're a practitioner and are interested in providing your clients with better answers about cannabinoids, you can learn more about a comprehensive training on precision genetic analysis I've put together with Dan Stickler, MD by clicking here.

The bottom line? Don't be the "yOu JuSt HaVeN't FoUnD tHe RiGht StRaIn YeT" guy. Maybe, but maybe not.