A recent study identifies neural pathways driving anti-anxiety effects associated with psychedelics
By KATELYN BURNS— science@theaggie.org
Psychedelics are a class of hallucinogenic drugs that can cause an altered mental state. While there’s currently very little known about the mechanisms of these drugs and the extent of their effects, there has been interest in their potential therapeutic uses.
Dr. Jessie Muir, a postdoctoral scholar in the Kim Lab at Princeton University, said traditional treatments for anxiety can be ineffective.
“Despite [anxiety and depression’s] prevalence and their burden on the population, traditional treatments for anxiety and depression are ineffective in a large part of the population,” Muir said via email. “Even [for] people in which treatment does work, there is a high risk for recurrence.”
Psychedelics have been found to promote changes in the prefrontal cortex that can have therapeutic effects, and they have shown promise as a non-traditional treatment for anxiety. Of course, in certain situations, psychedelics can have the opposite effect, inducing anxiety.
“When we discuss psychedelics as potential therapeutics, it is important to isolate these therapeutic effects, as it would be beneficial to be able to treat [anxiety] with as little adverse side effects as possible,” Muir said.
In a study published in Science, a peer-reviewed journal in the American Association for the Advancement of Science, in November 2024, mice were used to study the neural pathways driving the therapeutic anti-anxiety effects of psychedelics.
Dr. Christina Kim is an assistant professor of neuroscience and bioengineering at Princeton University and the lead researcher of the Kim Lab.
“If we could isolate distinct neural pathways that just drive potential beneficial behavioral effects, without driving the hallucinogenic effects, these could inform new therapeutics that ultimately could be safer and more precise,” Kim said via email.
In the study, neurons in the medial prefrontal cortex that were active following a psychedelic injection were tagged and reactivated after the drug was no longer affecting the mice. It was noted that the anti-anxiety effects occurred without the hallucinogenic-associated head twitch responses.
“This was also a little unexpected, as we thought that the neurons in the medial prefrontal cortex may also be involved in driving the hallucinogenic-like effects,” Kim said.
The prefrontal cortex has been the focus of a lot of work, including this study, regarding the therapeutic effects of psychedelics.
“The medial prefrontal cortex is one that has been well-studied in rodents; hence we focused on it [in this study],” Kim said.
However, other brain regions like the ventral hippocampus, as noted in a recent paper published in Neuron in November 2024, are also thought to be involved in the therapeutic effects of psychedelics.
“We still do not know exactly how the hallucinogenic effects of these drugs are instantiated in the brain,” Kim said. “It’s possible that it involves many brain areas; this is something that many researchers are actively working on.”
It should be noted that while the study had implications for the therapeutic use of psychedelics without the hallucinations, the specific psychedelic from this study — 2,5-dimethoxy-4-iodoamphetamine (DOI) — wasn’t being evaluated as therapeutic.
“The psychedelic we studied in our paper is not one that is being evaluated as a therapeutic in clinical trials,” Kim said. “Our study was very much a basic research-focused study.”
Regarding future clinical trials and other research-focused studies, new tools and technologies are being developed now that will open new possibilities in psychedelic research.
“We are actively engineering new types of molecular technologies that would allow us to identify specific proteins that may be involved in psychedelic signaling in activated neurons,” Kim said.
The possibilities of expanding research is a source of inspiration for Muir.
“There’s a lot to learn about these drugs and we have more tools now than ever before to study them,” Muir said.
Written by: Katelyn Burns— science@theaggie.org
