Why Do People React Differently to THC?

Paranoid THC
People's reactions to THC, the psychoactive compound in marijuana, can vary significantly, with some experiencing pleasant sensations and others experiencing discomfort or paranoia. This variation was previously attributed to psychological factors, with a 2014 study suggesting that individuals with low self-esteem or high anxiety were more likely to have negative experiences with marijuana. However, recent research from Western University in Ontario, Canada, suggests that biological factors may play a significant role. The study found that when THC was absorbed in the front of the brain, it produced positive effects, but when absorbed in the back of the brain, it led to negative effects, indicating that individual reactions to THC may be more dependent on biology than mental state.
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Most people enjoy the pleasant and soothing sensations of a marijuana high. For recreational users, it’s usually the end goal. Medical marijuana recipients may consider these same feelings to be a fringe benefit of treatment regimes that can provide a wide range of benefits from pain relief to appetite enhancement and stress relief.

In fact, marijuana has been shown to help nine out of ten people control and reduce anxiety levels by more than half. In addition, there are antioxidant, anti-inflammatory, anti-bacterial and neuroprotective properties that make medical marijuana one of the most promising natural remedies in modern pharmacology.

Yet, despite all of its positive qualities, marijuana is also known to affect some people in negative ways that range from a general sense of discomfort and bad thoughts to bouts of short-term paranoia. While THC, a psychoactive compound in marijuana, has long been blamed for triggering everything from euphoria to paranoia, researchers have struggled to submit a good explanation for why a particular strain of marijuana causes different psychological reactions.

Until now.

Do Bad Moods Make Bad Highs?

One explanation that gained early popularity was based on findings from a 2014 study conducted by Oxford University. The study, which looked at 121 people who consumed a THC-solution, came to the conclusion that people suffering from low self-esteem, high levels of anxiety, and unsettled feelings were more likely to have bad experiences with marijuana.

The thinking behind this was that cannabis amplified existing mental states.

As study author, Dr Daniel Freeman, notes:

Thinking we are inferior means we feel vulnerable to harm. Just small differences in our perception can make us feel that something strange and even frightening is going on. Many people have a few paranoid thoughts, and a few people have many paranoid thoughts.

But What About Biology?

In the summer of 2019, a new explanation for the differences in response toTHC and marijuana’s mood-altering properties captured the media’s attention. These groundbreaking findings come from a research group at Western University in Ontario, Canada.

Dr. Steve Laviolette explains what prompted his team to investigate THC:

We know a lot about the long-term and short-term effects of THC, but there is very little known about the specific areas in the brain that are responsible for independently controlling those effects.

What is known is that THC is absorbed by cell membranes known as cannabinoid receptors, which are found throughout the brain. And it is also known that not all receptors will absorb THC evenly. It was the specifics of these variations that the researchers wanted to investigate.

They did so by injecting THC into different areas of the brains of laboratory rats. What they discovered was that when THC was absorbed in the front of the brain, it created rewarding and positive effects. But when THC was injected into the back part of the brain, the rats exhibited negative effects.

This is the first indication that reactions to THC may be based more on biology rather than mental attitude.

Of course, this is just the first step, and the Western University group and others will need to find ways to replicate similar results in human brains.

As Dr. Laviolette states:

We’re starting to unravel some of the more intricate details of how cannabis is affecting the brain.

Once we figure out what molecular pathways are causing those effects in different areas, then in the long-term we can work on modulating THC formulations so they don’t activate those specific pathways.

Future THC Studies

The initial findings of this report open up some fascinating possibilities. Will future research show that an individual’s reaction to marijuana is based on their genetics, or might it reveal that moods can in some way alter the body’s biochemistry, making one area of the brain more receptive to marijuana’s influences?

And as we learn more about the specific chemistry of marijuana, will the medical cannabis industry be able to create new strains and products that produce positive sensations for all people?

It’s a topic we will continue to monitor and provide updates on as more breaking scientific news becomes available!

Updated: March 7, 2024

Pierce Hoover

Pierce Hoover is a career journalist with more than three decades of experience in print, broadcast and online writing, editing and reporting, with more than 5,000 articles published in national and international print media and online. His focus on medical marijuana therapies mirrors his broader interest in science-based alternative medical practices.


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