An Anti-Burnout Pill May Now Be Possible, but Scientists Say It's Unethical

When workplace stress becomes all encompassing, it’s easy to feel unmotivated to complete tasks (like writing articles about workplace stress), keep a professional demeanor with coworkers, or even show up for work in the first place. Burnout is real, and as scientists recently explained in the journal Cell, it may have its origins in a group of “giving up” cells in the brain.

"Burnout is an insidious syndrome that becomes apparent after long periods of exposure to stress."

In May, the World Health Organization recognized “burnout” as an “occupational phenomenon,” clarifying that it’s not a medical condition but specifically related to workplace stress. “Burnout is an insidious syndrome that becomes apparent after long periods of exposure to stress,” Michael Musker, Ph.D., a senior research fellow who studies wellbeing and resilience at the South Australian Health and Medical Research Institute, tells Inverse. Burnout can manifest itself in feelings of exhaustion, negativity, cynicism, and low productivity.

Scientists like Musker have learned a lot about how burnout occurs but are only now discovering how and why it begins to manifest in the brain in the first place.

But in a study published in late July in Cell, scientists at University of Washington and Washington University, along with other collaborators, studied the brains of mice to identify what causes them to stop seeking a reward — in essence, what makes them burn out. They were able to trace burnout to a set of cells in the brain that seem to drive the urge to give up.

What Burnout Looks Like in the Brain

At its simplest, burnout is the body’s response to external stress. When the body is under stress for a long period of time, Musker says, it suppresses its response to the stress hormones, like cortisol, and becomes sick and exhausted. These effects then spill over into work life and home life, affecting social as well as professional interactions.

“It is like the coiling of a spring getting tighter over time, giving rise to anxiety, tension, and feelings of dread about going to work,” Musker says. But when you actually enjoy your job, he adds, it’s almost like a dopamine hit — a motivation to keep going back every day.

In the Cell study, the researchers created an experiment that mimicked the struggle to get that hit of enjoyment by first conditioning mice to poke their nose on a button in their cage. When the mice poked in the right spot, a tube would lower and give them sugar water. But as the study progressed, it would take a lot more poking to get the reward — sometimes an impossible amount.

“Every subsequent reward, they have to poke more times in an exponential fashion, so it gets harder and harder and harder for them to get the reward, up to the point where they might have to poke 100 times to get a single reward,” Michael Bruchas, Ph.D., the senior author on this study, tells Inverse. “Eventually, they might say, ‘Okay, I’ve had it. I don’t really want the sugar that much, I’m going to give up.’”

The scientists found that a little-understood neuromodulator, nociceptin, was behind this demotivation loop. Neuromodulators are chemicals in the brain that Bruchas likens to the dimmer on a light switch. “They have the ability to increase activity or dampen activity depending upon where they’re acting and what contexts are acting,” he says. In the case of the frustrated mice, nociceptin’s increasing presence was making it harder for dopamine, a chemical associated with the pleasurable feeling of getting a reward, to do its job.

As the mice sought rewards, their dopamine cells produced more dopamine, motivating them to continue. But as the animals worked harder and harder to get those rewards, their nociceptin cells started producing more nociceptin with each subsequent task. “Essentially, right before the animal gives up is when these neuron’s activity is the highest,” Bruchas says.

He called these nociceptin neurons the “giving up” or “frustration” cells.

And Bruchas found the dopamine cells in the brain that drive motivation have a receptor for this nociceptin peptide. When nociceptin binds to this receptor, dopamine cells slow their roll.

"Burnout is an insidious syndrome that becomes apparent after long periods of exposure to stress."

Nociceptin, Bruchas says, may potentially play a role in addiction. When the mice were still motivated to get their reward, the team observed dopamine surging in the ventral tegmental area — the part of the brain associated with reward, motivation, and addiction — before nociceptin’s activity kicked in. By manipulating nociceptin, researchers may be able to find a way to mitigate addiction and turn off the drive for reward.

Could There Be an Anti-Burnout Pill?

Lique Coolen, Ph.D., a neurobiologist at Kent State University who studies the impact of social experiences on addiction, tells Inverse this paper could have huge implications for neurobiological understanding of the demotivation system, particularly in regards to drug abuse. She says the dopamine system is meant to drive individuals towards food, water, and sex, but drugs of abuse highjack this system.

“Most of the research has been focused on what drives the goal-directed behavior,” she says. “I think this is some of the first evidence that there is this system in place that actively inactivates this [dopamine] system and therefore dampens the motivation.”

Coolen says she thinks this nociceptin system could be explored clinically to help patients struggling with addiction by dampening the activity of dopamine cells. For example, Inverse previously reported on a drug that targets nociceptin receptors and mu opioid receptors to kill pain, without the same euphoric or addictive effects of other opioids.

The dopamine-nociceptin system, Musker says, not only affects simple pleasures, like the drive for food and sex, but also our motivation in professional and social settings.

“These systems affect everything we do, from getting out of bed in the morning to performing complex tasks,” Musker says. “Any changes or tweaks in these amazing biological systems can have everyday implications from anxiety to full-blown depression.”

Why An Anti-Burnout Pill Would Be Unethical

Though a nociceptin-inhibiting drug is currently in clinical trials for major depressive disorder, Bruchas doesn’t know if the same would be possible for an anti-burnout pill.

"“Regulating it in a mental health state seems like it could be appropriate, and regulating it some other kind of state probably isn’t."

“You can imagine a situation where you could say, ‘Hey, we all want to be more motivated and so we’re going to take this thing to stabilize our motivation,’” Bruchas says. “Regulating it in a mental health state seems like it could be appropriate, and regulating it in some other kind of state probably isn’t.”

Cary Cherniss, Ph.D., a professor emeritus of applied psychology at Rutgers University agrees, even going as far as to say that manipulating this system in workers experiencing burnout might be unethical.

Instead of looking for a burnout cure, he suggests targeting workplace environmental factors, including work overload and employee autonomy. “The factor that is probably the most important has to do with the behavior of one’s supervisor or boss,” Cherniss tells Inverse.

While he recognizes that a neurological change to increase motivation may reduce burnout, he says that’s looking at the problem from the wrong direction.

“Any intervention that targets the individual is going to be like paddling upstream,” he says. “Much better to turn the canoe around and head downstream, by looking at the work environment instead.”

By fostering more emotional intelligence in supervisors and allowing employees ample work-life balance, he says some of these burnout symptoms will dissipate.

“Burnout is a strong sense of helplessness and hopelessness,” Cherniss says. “If you can do something to address that helplessness, you’ll have a more proactive worker.”