Why Some People Can't Handle Their Weed

She had no clue what she was in for, but certainly couldn't have imagined this. Ellie Reid, a 26-year-old graduate student at the University of North Carolina at Chapel Hill, had one of the worst nights of her life—and all she did was eat a weed brownie.

"I had no sense of the time. I was very shaky. It was almost like an out of body experience," recalls Reid, who asked we not use her real name for professional reasons.

Reid had never experienced panic attacks or anxiety before, but felt completely out of control. "Every minute felt like three hours. I felt like I was trapped inside myself," she says. "I was sitting in a bathroom for a while because I just felt so out of control and freaked out."

Reid's experience might seem surprising given that one of the factors driving the widespread consumption of cannabis, which is used by one in eight Americans, is the search for mental relaxation and well-being. But if you're around weed enough, you likely know someone like Reid, a person who loses their shit on pot, or simply can't handle the drug because it makes them paranoid or fills them with anxiety. Why is this?

In research, the association between cannabis and anxiety has received little attention, in spite of the fact that cannabis is the most widely used illicit drug in the world and anxiety is the most prevalent mental disorder. The majority of studies that have been done are based on self-reports, where participants respond to questionnaires that ask about how their use affects their anxiety levels. While some research points to the positive mental health effects of marijuana, there is growing evidence that suggests the popular perception of the drug's ameliorating effects on anxiety and panic aren't the full story.

A 2009 study in the Human Psychopharmacology Clinical and Experimental Journal actually found that anxiety reactions and panic attacks are the acute symptoms most frequently associated with cannabis use. "When talking about brain science and cannabis, it's easy to be swept away by anecdotal evidence and sound bites," says Dr. Ruben Baler, a health scientist at the National Institute on Drug Abuse. But the brain is complex, and the slightest difference in a person's brain chemistry can cause significant differences in how our mind and body respond to cannabis, says Dr. Baler.

When humans consume weed, it stimulates their endocannabinoid system (ECS), which plays a key role in regulating our response to reward, stress and emotions. "What the ECS does is it optimizes our brain between excitation and inhibition," says Dr. Baler. But when chemicals found in weed, such as THC, enter the ECS, they perturb the system's ability to act in synchrony, which can disrupt our ability to regulate our response to stress, potentially causing anxiety.

"Fear stimuli that we can normally cope with can become unmanageable under the effects of marijuana because our fight-or-flight response gets disrupted," says Dr. Baler. "You may not be able to keep those stimuli under control because your ECS is so out of whack because of all the THC in your system," he says.

Chelsea Wind, a 46-year-old caregiver from Anderson, California, has been using medicinal marijuana every day for the past six years for pain management. One night she had a panic attack when she was at her friend's house. "He was encouraging me to smoke more and more and get as high as humanly possible," says Wind. "It felt like I had stopped being able to breath. I was panicking so much and I made him call 9-1-1."

Wind's experience may be related to the quantity of weed she consumed. Dr. Mohini Ranganathan, an assistant professor of psychiatry at Yale University who specializes in cannabinoid research, says people who consume low doses of weed are more likely to experience the anti-anxiety effects. "But as the dose increases, you become more and more likely to experience anxiety and panic," she says.

One reason for this is that THC acts as a partial agonist, meaning that when it binds to a receptor, it only produces some of the drug's effects, making it less potent than synthetic strains of marijuana like Spice and K2, which are full agonists. "But as you increase the dose of cannabis, it starts to look more like these synthetic drugs," says Dr. Ranganathan.

If you consume a large quantity of THC, it makes sense that you might start experiencing some of the psychotic effects people encounter when they take K2 or Spice such as extreme anxiety, paranoia and hallucinations, according to Dr. Ranganathan.

But what about those whose reaction to weed changes over time? According to Dr. Baler, these changing reactions aren't surprising because the plasticity of the brain morphs over time. "Very small differences can lead to huge differences in how the brain responds to cannabis," he says.

Matt Folliot, a 33-year-old comedian and actor in Toronto, started smoking weed when he was 14. "For a long time, it was a relaxing, fun, social thing to do. I had lots of fun times with my friends when I would smoke," he says. But by his mid-20s, this changed. "I've always had trouble with anxiety, and I tend to find if I smoke nowadays, [weed] often contributes to a paranoid, sort of anxious, self conscious feeling, or a feeling of being overwhelmed by having so much to do even though there's nothing to get done," he says, echoing the sentiments of many a former pot smoker.

Environmental factors, such as early traumatic experiences or chronic stress, can change the structure of the brain's fear-processing system. Located in the amygdala and the hippocampus, these areas are particularly sensitive to cannabis, which explains why some people develop contrasting mental responses to marijuana over the life course, says Dr. Ranganathan.

Folliot believes that life experiences had a major impact on the change in his reaction to marijuana. "I had dealt with a lot of family and friends dying. I pretty much watched my Mom pass away and that took years for me to deal with."

Like environmental factors, the strain of pot you smoke can have a major impact on anxiety levels, too.

"When people talk about marijuana, they're not distinguishing between the different components of cannabis," says Dr. Ranganathan. The two main components in cannabis are THC and cannabidiol (CBD). According to the research, these components have contrasting effects on anxiety-levels. "We know very well from animal studies that as THC concentration starts increasing, it's more likely to intensify anxiety," where small doses of CBD has been related to reduced anxiety, she adds.

Wind's experience mimics Dr. Ranganathan's findings. She says strains of Sativas, which have relatively higher doses of THC, exacerbate her social anxiety. "I would have thought everything was fine, but then I'll smoke a Sativa and I'll start ruminating and I'll think of a social situation and I'll get anxiety about it. I'll start thinking, 'I shouldn't have said that, Oh My God!'" Wind says. "I might even get paranoid about what my roommate was thinking about me."

But if it's the right strain, it can have the reverse effect. "I can be more gregarious and relaxed around people if it's an Indica," she says.

Problem is, it's not that simple. There are over 65 cannabinoids found in cannabis, yet substantial data only exists on THC and CBD. "With so little research, it's impossible to fully understand the psychological effects cannabis can have on an individual's anxiety levels," says Dr. Ranganathan.

Folliot agrees. "It's almost like searching through your pill cabinet for the right pill that's gonna make you feel better," he says. "But it's a bit like Russian roulette because you don't know what that pill will do."

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