Growing up in San Francisco in the 1970s, Jennifer Mitchell saw the psychological scars of war firsthand. Vietnam veterans flooded her hometown, often finding an outlet for their trauma in drugs and alcohol. Their suffering, and society’s response — to ignore it — had a lasting impact. “[We all] understand the importance of people who can point and kill,” she says, but “we have to be willing to pick up the pieces when it’s over.”
Mitchell, now an adjunct associate professor of neurology and psychiatry at UCSF, is doing her part to pick up the pieces by finding treatments for people suffering both post-traumatic stress disorder (PTSD) and alcohol use disorder. People with PTSD are two to four times more likely than those without to meet criteria for a substance use disorder — yet today’s medications treat one disorder or the other. Mitchell believes a solution could come in the form of oxytocin, nicknamed “the love hormone” because it promotes pair bonding and social attachment. Now, she’s recruiting participants for a clinical trial testing whether oxytocin could treat PTSD and alcohol use disorder in military personnel.
Her work is part of a growing interest in the potential of oxytocin to treat autism, depression, schizophrenia and other psychiatric and neurodevelopmental disorders. Studies have shown that oxytocin — released during intercourse, childbirth and breastfeeding — is important for pairbonding, which is typically a challenge for those with anxiety, alcohol and substance use disorders. Plus, it has few side effects and is available in a nasal spray, making it easy to administer.
Why do some people thrive in spite of trauma, while others crumble and self-medicate with drugs and alcohol?
When I meet Mitchell, 47, at the Henry H. Wheeler Jr. Brain Imaging Center at UC Berkeley, she’s dressed in all black, fitting for someone who’s made the neuroscience of suffering her life’s work. She has large amber eyes, speaks fast and describes growing up the child of artist parents in the wake of the “Summer of Love.” As a student at Reed College in Portland, Oregon, she found she could predict which classmates would struggle with alcohol and substance use disorders: They were either impulsive, life-of-the-party types, or had suffered a form of trauma. It made her wonder: Why do some people thrive in spite of trauma, while others crumble and self-medicate with drugs and alcohol?
Mitchell looked to the brain for answers, majoring in psychology and studying how people perceive pain. In 1999, she earned a Ph.D. in neuroscience from UCSF, where she also finished a postdoctoral fellowship. Howard Fields, Mitchell’s mentor at UCSF, recalls her “combination of enthusiasm and discipline … which is very characteristic of any scientist that becomes very successful.”
Mitchell had become aware of research suggesting that people with alcohol use disorder often have poor social skills, similar to those with autism. Both groups tend to perform poorly on tests of their ability to recognize people’s emotions, but giving oxytocin to people with autism improved their test performance. Might oxytocin boost social skills in people with alcohol use disorder too? What’s more, other studies — most involving animals and some in humans — showed oxytocin can curb the intake of alcohol and other drugs. Drugs like Antabuse and Campral already help people with alcohol use disorder to drink less, but oxytocin may have the added benefit of addressing the underlying social anxiety that spurs them to reach for the bottle in the first place. “Perhaps this would be a multipronged therapeutic,” Mitchell says.
She set out to test her hypothesis. In a 2016 study of people with alcohol use disorder, she found that oxytocin improved social perception — and reduced alcohol cravings in those with high levels of anxiety surrounding relationships with others. Dutch researchers had earlier reported that in PTSD patients, oxytocin made the amygdala — the brain region associated with strong emotions — less reactive to emotional facial expressions. It makes sense, then, that oxytocin might help the many who struggle with PTSD and alcohol use disorder, both of which are marked by anxiety and social withdrawal.
To find out, Mitchell is leading a clinical trial at an Army medical center at Fort Gordon in Georgia. Around 65 active military personnel will receive a dose of intranasal oxytocin or a placebo and then deliver a speech and perform arithmetic before a panel of judges. Afterward, Mitchell’s team will measure participants’ stress levels. Mitchell is also director of the Institute for Translational Neuroscience at UCSF, which, besides the Fort Gordon trial, is funding two similar trials with slightly different populations and doses to understand how treatment might look for different people and contexts.
If proven to work, oxytocin could become an affordable, accessible treatment for those suffering from PTSD and alcohol and substance use disorders — beyond the military. “You’re talking about the potential to help a substantial amount of people,” says Gary Wynn, of the Uniformed Services University of the Health Sciences. Jessica Peirce of Johns Hopkins University School of Medicine notes that people with PTSD and substance abuse issues have difficulty seeking and staying in treatment. Both disorders carry heavy stigmas, and therapy can require confronting painful memories, as well as making drastic lifestyle changes. Oxytocin may help ease the process, perhaps through promoting bonding with a therapist.
But, Peirce notes, the tasks in Mitchell’s trial — though widely used in stress studies — don’t necessarily reflect the stressors afflicting people with PTSD and alcohol use disorder. Participants’ responses to video footage of war or people drinking at a bar might better predict how they cope with stress. Still, “it’s promising,” Peirce says of Mitchell’s research. “It’s a good first step.”
Mitchell is prepared to play the long game, saying her “stubbornness and curiosity” keep her going. She fingers a silver, steampunk-y ring adorned with a giant moth, which reminds her of the moths outside her childhood home. “They were so attracted to the light, they couldn’t stop themselves,” she says. “They would bang their little heads … until they died in a huge puddle below.” Dark, yes, but finding help for people in pain may require stepping into the shadows.
