Why can cannabis feel relaxing for some people, but may make others feel anxious or overwhelmed? A new study from Northwestern University gives us a look at what may be happening in the brain when higher doses of THC increase anxiety.
The short answer: In mice, higher doses of a THC-like compound made fear responses stronger. Lower doses did not. Researchers traced the effect to a specific group of brain cells involved in fear. Because the study was done in mice, it points to a likely mechanism in people rather than proving one.
Ethos Chief Medical Officer Dr. Brooke Worster breaks down what the researchers found and what it means for you.
What the study looked at
Researchers gave mice either a placebo or a synthetic compound that acts like THC, at several different doses. It isn’t the same cannabis you’d find on our shelves, but it works on the same receptors in the brain. Then they exposed the mice to a scent that naturally triggers fear and watched how they reacted.What they found
The higher the dose, the bigger the fear response. Mice paused, froze, and retreated more, which are the behaviors that signal fear in mice. At low doses, researchers didn’t see this effect at all.
That lines up with something people have reported for a long time. A little THC can be anxiolytic, meaning it reduces anxiety. A lot of THC can be anxiogenic, meaning it creates or worsens anxiety. This study helps explain why.
The brain “brake” behind it
The researchers zeroed in on a group of cells called somatostatin neurons, found in a part of the brain that helps process threats. Dr. Worster compares what happens to taking your foot off the brake. At higher doses, THC appears to release a brake in this circuit, so the brain moves into a fear response faster.
What this means for you
Cannabis products keep getting stronger, and high-THC options are easy to find. If any of these sound like you, lower-potency THC products can help you stay in control and lower the chance of feeling too anxious or too high:- You’re new to cannabis
- You’re prone to anxiety
- You’re heading into an unfamiliar or uncertain situation
Pay attention to how you respond and know yourself. If you’re not sure where to start, our team can walk you through lower-THC options.
What this study doesn’t tell us
- It was done in mice. As Dr. Worster puts it, take it with a grain of salt.
- It only tested a THC-like compound. It tells us nothing about CBD or other cannabinoids. CBD is active at receptors on these same neurons, which makes it an intriguing next question.
- The mice had no prior exposure. A “low dose” for someone who uses cannabis regularly looks very different. Dr. Worster suspects regular use may change how active these neurons are, which could explain why a familiar amount can still trigger anxiety sometimes. That idea wasn’t tested here.
The bigger picture
This study adds to our understanding of where cannabinoids may act in the brain. It also points to a possible new target for anxiety treatment in general, especially situational anxiety like the nerves before public speaking. It’s early, but it’s a promising direction for future research.
Learn more
If this is your first research breakdown with Dr. Worster, start with her look at cannabis and brain aging. The two studies share a thread: with cannabis, more isn’t automatically better. In the brain aging study, heavier use showed no extra benefit. In this one, higher doses amplified fear.Let’s make this as simple as we can. This is a very dense basic science paper that looked at mice. They gave the mice either a placebo or a synthetic THC. So not exactly the cannabinoids that you or I are ingesting, but a version of it.
After they exposed the mice to these substances in different concentrations, they gave them what amounts to a fear stimulus: an odor that produces fear. And they saw that with higher concentrations of THC, the mice had a more exaggerated fear response. They paused, they stopped, they retreated. They did the things that indicate more fear in mice.
What that means is exactly what people have been observing for a very long time. Especially when a person is prone to or struggling with anxiety, or it’s an anxiety-inducing situation, higher concentrations and higher doses of THC can exacerbate anxiety.
What it looked like very specifically: there’s this idea in the brain that there are neurons that can slow down or lower your anxiety response to things. In mice, and it translates into humans, they’re called somatostatin neurons. If you give enough THC, you basically inhibit these neurons, and that makes your anxiety response bigger.
With low amounts of THC, they didn’t see this at all. But with higher amounts of THC, they saw a much more exaggerated anxiety response in mice.
What we’ve seen a little in the research, and heard time and time again, is that a little bit of THC can be what we call anxiolytic, reducing the amount of anxiety people feel or experience. But a lot of THC is anxiogenic. It generates anxiety in you and makes it worse. And this gives us the very specific brain mechanism by which it probably happens.
Now, take it with a grain of salt. It was in mice. But it probably happens through this idea of taking your foot off the brake, which is what these somatostatin neurons do. If I take my foot off the brake, I’m going to barrel into anxiety quicker. And that’s the effect THC has on our brain.
As the breadth and potency of cannabis products increases, and you can buy things that have a whole lot of THC, it’s really helpful for consumers to understand this. If you’re new to the space, if you’re prone to anxiety, or if you’re going to be in an uncertain or unknown situation, avoiding high THC concentrations is paramount. It will help you reduce that risk of “I got really anxious” or “I got too high.” You can regulate that a little better by sticking to much lower potency THC products.
Unfortunately, because they looked at a synthetic THC-only product, it doesn’t tell us anything about CBD. Now, we know that CBD is active at the receptors on these somatostatin neurons. So it’s really intriguing to think about what might happen if you put CBD into that same model, looked at these neurons and their functionality, and saw their expressivity under a microscope. That’s probably one of the gaps in this study: we don’t know anything about cannabinoids outside of THC.
The other thing I think has bigger potential: it gives us another mechanism by which humans probably experience anxiety. Could that be a therapeutic target to relieve anxiety or reduce your anxiety response? Think about people who get anxiety with public speaking. It’s a very situationally dependent thing. If you could target that pathway and those neurons specifically, you might have a brand-new mechanism by which to treat anxiety.
It also helps us understand, with more nuance, what happens if you’re using cannabis and you’re prone to anxiety. These are the ways we’re certain THC can trigger anxiety. And most importantly, with the lowest potency THC exposure, the mice did not have that exaggerated anxiety response. So really pay attention to that when you’re using any cannabinoid products, and know yourself. Lower THC really is better if you’re an anxious person. This neuron grouping and pathway is different than we understood.
The other thing this doesn’t tell us: these are naive mice, so to speak. They didn’t have any tolerance to cannabis built up. What a low dose or low concentration looks like in someone with repeated exposure is very different than in someone without it.
What’s also interesting is for people who use cannabis regularly and still have times where it triggers anxiety. What you may be doing is reconfiguring how active these neurons are, or what they look like. So sometimes, with an exposure that’s different than your prior ones, you can still have a stronger brake than you had before. That allows your body to experience more anxiety.
All of these things add to our understanding of where cannabinoids affect our brain and, in the larger sense, what might be therapeutic targets for people experiencing anxiety.
