Ask most people about the neurochemical origins of depression and you’ll likely hear how low serotonin levels are the cause. But today’s scientists know depression’s roots are more tangled and complex. One area of interest to them is the brain’s prefrontal cortex, a region responsible for motivational and goal-directed behavior. For those with depression, this region’s neurons are unhealthy, their connections, called synapses, withering like rotten roots.

“If you’re not getting the right growth cues, the prefrontal cortex cannot communicate to other brain regions and you’re going to end up with depression,” said Lindsay Cameron, a neuroscience Ph.D. student. “So by stimulating growth in the prefrontal cortex, you’re strengthening control over these other regions and restoring health.”

Cameron and other researchers at UC Davis are actively exploring drugs capable of spurring such neural growth and restoring health. And some dark horse candidates are psychedelics like LSD, psilocybin and DMT. 

“Psychedelics can increase growth of neurons in the prefrontal cortex and they cause growth rapidly,” said Cameron, who was first author on an ACS Chemical Neuroscience study that showed microdosing rats with DMT can positively affect their mood and anxiety and a co-author on a Cell Reports study that showed psychedelics promote neural plasticity. “Psychedelics are some of the most powerful drugs out there and it’s ridiculous how little we know about them.” 

According to Cameron, popular antidepressants, like SSRIs and SSNRIs, are designed with the serotonin hypothesis of depression in mind and are missing the mark for some patients. Research shows the drugs are about 70 percent effective, tend to lose their potency and can be slow-acting, taking weeks to kick in. 

“We need a fundamentally new way of tackling these diseases,” said Cameron. “That’s what I am hoping to do with my Ph.D.”

“Lindsay is the kind of student that every principal investigator hopes to work with,” said Assistant Professor David Olson, Department of Chemistry. “She has a voracious appetite for knowledge, is intensely curious and is driven to make discoveries that will benefit the world. Students like Lindsay are really the lifeblood of academic research.”    

Opening the doors of scientific perception

At the basis of Cameron’s curiosity is a desire to develop tools that’ll fix the body when its systems go haywire. She traces her interest in physiology back to her parents, who both worked in the healthcare industry.  

While pursuing a degree in pharmacology at McGill University, Cameron learned how various drugs travel through and affect the body. She was particularly drawn to brain-altering drugs, delving into the largely marginalized scientific literature available on psychedelics and their effects on brain chemistry.

Following graduation, Cameron entered the workforce to pay off her bachelor’s degree debt before pursuing graduate school. She worked as a research assistant, an optometric assistant and at a health food store. She wound up at UC Davis after accepting a junior specialist position in the lab of Professor Hwai-Jong Cheng, who holds appointments in the Department of Neurobiology, Physiology and Behavior, Center for Neuroscience and the School of Medicine. 

“Dr. Cheng really helped me figure out how to approach scientific problems,” said Cameron. “By the time I got into grad school and I started, I had a leg up of where I would’ve been right out of undergrad, so I’m really glad I ended up taking those years off.”

Micro-doses, big implications

There’s a trend hitting the coast. Peruse Los Angeles Magazine or The Atlantic and you’ll read about people singing the praises of microdosing.

“It’s people taking really small doses of psychedelics without any hallucination effects every couple of days. People are saying anecdotally that it helps them with depression and anxiety. It’s increasing their sociability and their creativity at work,” said Cameron. “They’re basically saying it’s enhancing cognitive function.”

Such anecdotes led to experiments. Cameron and her Olson Lab colleagues administered microdoses of DMT (N, N-dimethyltryptamine) to rats and measured the molecule’s effects on the rodents’ depression and anxiety behaviors.

To measure the antidepressant properties of psychedelics, the team performed a “swim test,” a staple rodent behavioral test for evaluating antidepressant drugs. During the test, researchers place a rodent in a small, water-filled tank after dosing the animal with either a psychedelic molecule or a placebo for a set period of time. Rodents with depression and anxiety-like symptoms typically just free-float in the water, but rodents dosed with DMT showcased motivational behavior, which in this case is swimming.

“This is one of the main tests generally used in the field and it’s been shown to correlate really well with if a drug will have antidepressant effects in humans or not,” said Cameron.

This is your brain on drugs

The team also tests the effects of psychedelics on the brain through neuronal cultures. Neurons from the prefrontal cortex are placed in a dish and then treated with a psychedelic molecule.

By the time Cameron enrolled in the Neuroscience Graduate Group, psychedelic research had fallen off her radar. She then attended a presentation given by Olson. The Olson Lab specializes in chemical neuroscience, specifically focusing on psychoplastogens, an Olson Lab-coined term that refers to the small molecules like psychedelics that promote neural plasticity. 

“I chased him out of the building and I was like, ‘Are you taking students?’” recalled Cameron.

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About Graduate Studies

Graduate Studies at UC Davis includes over 100 dynamic degree programs and a diverse and interactive student body from around the world. Known for our state-of-the-art research facilities, productive laboratories and progressive spirit – UC Davis offers collaborative and interdisciplinary curricula through graduate groups and designated emphasis options, bringing students and faculty of different academic disciplines together to address real-world challenges.

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