New study cautions marijuana beginners to 26 adverse reactions

Researchers documented the most common negative side effects of smoking weed, and who might be most susceptible.

  • A team of researchers identified a total of 26 possible adverse reactions to cannabis use.
  • Coughing fits, anxiety, and paranoia are among the top three most common adverse reactions to smoking weed.
  • It was the people who smoke on a less frequent basis who were more likely to have had the bad experiences.

"She's fine! She'll be okay." I remember calling down to a concerned pedestrian strolling past my apartment early one evening back in college as my friend gasped and vomited on our porch, brought to her knees by a violent coughing fit after having just huffed a joint of cannabis. And she was okay! (Eventually.) But new research affirms that these types of experiences, which range from unpleasant to deeply distressing, are relatively common for people new to smoking pot.

The most common adverse effects of pot

As it turns out, coughing fits are among the top three most common adverse reactions to cannabis use, along with anxiety and paranoia, according to a new study published in the Journal of Cannabis Research.

Now that weed is legal in the state, a team of researchers at Washington State University sought to document potential negative reactions to cannabis in order to paint a detailed picture of the effects of smoking weed for newbies. The authors surveyed more than 1,500 college students on the specific type and frequency of adverse reactions they had experienced while using pot. Additionally, the students in the study were surveyed about their demographics, personality traits, reasons for using cannabis and their use patterns.

Despite marijuana's numerous benefits, the team identified a total of 26 possible adverse reactions to the drug. More than half of the study participants reported having coughing fits along with anxiety and/or paranoia while using cannabis. The most frequently occuring of these were the coughing fits, along with chest/lung discomfort and body humming. A subset of the study group reported these reactions occurring around 30–40% of the time they were using pot. On the flip side, the three least-commonly reported reactions to cannabis use were fainting, visual hallucinations and cold sweats.

"There's been surprisingly little research on the prevalence or frequency of various adverse reactions to cannabis and almost no research trying to predict who is more likely to experience these types of adverse reactions," said Carrie Cuttler, assistant professor of psychology and an author on the paper, according to WSU News. "With the legalization of cannabis in Washington and 10 other states, we thought it would be important to document some of this information so that more novice users would have a better sense of what types of adverse reactions they may experience if they use cannabis."

The most distressing of the 26 negative reactions were panic attacks, fainting, and vomiting. Yet, the survey data suggested that cannabis users generally do not find even acute adverse reactions to cannabis to be severely distressing.

What causes a bad reaction?

Photo by Add Weed on Unsplash

So, who is most likely to experience the negative reactions? Interestingly, one thing the researchers didn't find to correlate with a bad reaction to cannabis was the quantity of use during a single session. Rather, it was the people who smoke on a less frequent basis who were more likely to have had the bad experiences. Additionally, individuals who reported using cannabis to fit in with their peers, had a history of displaying problematic use of the drug or had anxiety sensitivity—a tendency to catastrophize the bodily sensations that come with anxiety—were more likely to report negative side effects from cannabis use and experience more intense levels of distress. Although, Cuttler noted that these associations were small and nothing was strongly related to these experiences.

One curious correlation Cuttler found after reanalyzing the data was that certain personality traits on the Big Five personality model more frequently experienced one of the more rare reactions to the drug.

"[I] found that the personality traits extraversion and openness to experience predicted the frequency with which people reported experiencing visual hallucinations," she told Big Think. There were, however, no significant predictors of what individuals were more susceptible to experiencing fainting—another rare side effect. In the future, Cuttler thinks it will be important to continue investigations into what other individual difference variables might predict positive vs. negative experiences with cannabis, and to document them at a broader level.

Although the study didn't reveal measures that can be taken to protect against negative effects, Cuttler echoed the common advice given to new users: "Start low and go slow. It's generally a good idea for people to start with lower potency products and to use small amounts at first."

Given its rapid entry into the mainstream over the last few years, it may be time marijuana starts getting treated like other medicinal drugs that come with warning labels. The researchers expressed hope that findings like these will be utilized by doctors and medical cannabis distributors to give users or potential users a clearer idea of the side effects that come with lighting up.

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The surprise reason sleep-deprivation kills lies in the gut

New research establishes an unexpected connection.

Reactive oxygen species (ROS) accumulate in the gut of sleep-deprived fruit flies, one (left), seven (center) and ten (right) days without sleep.

Image source: Vaccaro et al, 2020/Harvard Medical School
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  • When the buildup is neutralized, a normal lifespan is restored.

We don't have to tell you what it feels like when you don't get enough sleep. A night or two of that can be miserable; long-term sleeplessness is out-and-out debilitating. Though we know from personal experience that we need sleep — our cognitive, metabolic, cardiovascular, and immune functioning depend on it — a lack of it does more than just make you feel like you want to die. It can actually kill you, according to study of rats published in 1989. But why?

A new study answers that question, and in an unexpected way. It appears that the sleeplessness/death connection has nothing to do with the brain or nervous system as many have assumed — it happens in your gut. Equally amazing, the study's authors were able to reverse the ill effects with antioxidants.

The study, from researchers at Harvard Medical School (HMS), is published in the journal Cell.

An unexpected culprit

The new research examines the mechanisms at play in sleep-deprived fruit flies and in mice — long-term sleep-deprivation experiments with humans are considered ethically iffy.

What the scientists found is that death from sleep deprivation is always preceded by a buildup of Reactive Oxygen Species (ROS) in the gut. These are not, as their name implies, living organisms. ROS are reactive molecules that are part of the immune system's response to invading microbes, and recent research suggests they're paradoxically key players in normal cell signal transduction and cell cycling as well. However, having an excess of ROS leads to oxidative stress, which is linked to "macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging." To prevent this, cellular defenses typically maintain a balance between ROS production and removal.

"We took an unbiased approach and searched throughout the body for indicators of damage from sleep deprivation," says senior study author Dragana Rogulja, admitting, "We were surprised to find it was the gut that plays a key role in causing death." The accumulation occurred in both sleep-deprived fruit flies and mice.

"Even more surprising," Rogulja recalls, "we found that premature death could be prevented. Each morning, we would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralize ROS in the gut, we could rescue the flies." Fruit flies given any of 11 antioxidant compounds — including melatonin, lipoic acid and NAD — that neutralize ROS buildups remained active and lived a normal length of time in spite of sleep deprivation. (The researchers note that these antioxidants did not extend the lifespans of non-sleep deprived control subjects.)

fly with thought bubble that says "What? I'm awake!"

Image source: Tomasz Klejdysz/Shutterstock/Big Think

The experiments

The study's tests were managed by co-first authors Alexandra Vaccaro and Yosef Kaplan Dor, both research fellows at HMS.

You may wonder how you compel a fruit fly to sleep, or for that matter, how you keep one awake. The researchers ascertained that fruit flies doze off in response to being shaken, and thus were the control subjects induced to snooze in their individual, warmed tubes. Each subject occupied its own 29 °C (84F) tube.

For their sleepless cohort, fruit flies were genetically manipulated to express a heat-sensitive protein in specific neurons. These neurons are known to suppress sleep, and did so — the fruit flies' activity levels, or lack thereof, were tracked using infrared beams.

Starting at Day 10 of sleep deprivation, fruit flies began dying, with all of them dead by Day 20. Control flies lived up to 40 days.

The scientists sought out markers that would indicate cell damage in their sleepless subjects. They saw no difference in brain tissue and elsewhere between the well-rested and sleep-deprived fruit flies, with the exception of one fruit fly.

However, in the guts of sleep-deprived fruit flies was a massive accumulation of ROS, which peaked around Day 10. Says Vaccaro, "We found that sleep-deprived flies were dying at the same pace, every time, and when we looked at markers of cell damage and death, the one tissue that really stood out was the gut." She adds, "I remember when we did the first experiment, you could immediately tell under the microscope that there was a striking difference. That almost never happens in lab research."

The experiments were repeated with mice who were gently kept awake for five days. Again, ROS built up over time in their small and large intestines but nowhere else.

As noted above, the administering of antioxidants alleviated the effect of the ROS buildup. In addition, flies that were modified to overproduce gut antioxidant enzymes were found to be immune to the damaging effects of sleep deprivation.

The research leaves some important questions unanswered. Says Kaplan Dor, "We still don't know why sleep loss causes ROS accumulation in the gut, and why this is lethal." He hypothesizes, "Sleep deprivation could directly affect the gut, but the trigger may also originate in the brain. Similarly, death could be due to damage in the gut or because high levels of ROS have systemic effects, or some combination of these."

The HMS researchers are now investigating the chemical pathways by which sleep-deprivation triggers the ROS buildup, and the means by which the ROS wreak cell havoc.

"We need to understand the biology of how sleep deprivation damages the body so that we can find ways to prevent this harm," says Rogulja.

Referring to the value of this study to humans, she notes,"So many of us are chronically sleep deprived. Even if we know staying up late every night is bad, we still do it. We believe we've identified a central issue that, when eliminated, allows for survival without sleep, at least in fruit flies."

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