Share on PinterestPsychedelics may be able to strengthen the connection between two brain regions key to treating depression, according to new research in rats. The Washington Post/Getty Images
- With growing interest in using psychedelic drugs to treat mental health disorders, researchers have explored the effects of a psychedelic derivative of amphetamine on rat brains.
- They wanted to see how it affects the brain cells connected to thinking and emotion.
- The researchers found a specific pathway in the brain that psychedelics act on, which they believe contributes to neuroplasticity, or the brain’s ability to form and strengthen new connections.
While many people may consider psychedelics to be solely a recreational drug, research indicates that this drug class can be helpful in treating mental health issues such as depression and addiction.
The researchers in the new study aimed to better understand how psychedelics impact the brain, particularly the neurons involved in thought and emotion. For that, they used the psychedelic DOI (2,5-dimethoxy-4-iodoamphetamine) on rats.
They found that psychedelics influence a brain pathway, suggesting potential to “rewire” the brain and improve treatment for depression and other mental health disorders.
Their findings are published in the journal eNeuro.
Examining 2 brain regions affected by depression
The Centers for Disease Control and Prevention addressed mental health in a 2024 report that shows how widespread depression and anxiety are in the U.S.
The study notes that around 18.2% of U.S. adults reported recently experiencing symptoms of anxiety, and 21.4 % reported recently having symptoms of depression.
There are many treatments for depression and anxiety, including antidepressants such as sertraline (Zoloft) and bupropion (Wellbutrin). Many people with these disorders also go to talk therapy.
Some studies have examined the use of psychedelics in treating mental health conditions and found they offer faster and sometimes longer-lasting relief after just one or a few treatments compared to traditional antidepressants.
Psychedelics act on serotonin receptors in the brain and can trigger deep changes in brain connectivity and emotion processing within hours.
Federally, psychedelics are still considered Schedule I substances. However, a few states have legalized them for therapeutic uses, while others are exploring the same. Oregon, for example, legalized the use of psychedelics to treat anxiety, depression, and addiction.
The researchers in the new psychedelics study hope that exploring and learning more about the neural pathways in which these drugs work will further strengthen the case for using them therapeutically.
The scientists focused on two brain regions in their study: the claustrum and the anterior cingulate cortex (ACC).
The claustrum is significant because it is sensitive to psychedelics, and, according to the researchers, has “the highest 5-HT2A and 5-HT2CR expression in the brain.” These are serotonin receptors, which are significant because they are implicated in depression.
The ACC, which is responsible for processing and controlling emotions, is affected by depression.
How psychedelics may reshape brain functioning
To see how psychedelics impact neuroplasticity, the researchers experimented on male rats. Each rat was housed individually, anesthetized, and then studied to examine brain activity.
The scientists used electrical signals to see how strongly neurons in the claustrum responded, both with and without psychedelics.
Under normal conditions, the stimulation weakened the connections between neurons, causing what the researchers described as “long-term depression.”
However, when the psychedelic DOI was introduced, it had the opposite effect and made those same connections stronger, causing “long-term potentiation.” The psychedelic strengthened synaptic connections and promoted neuroplasticity.
The findings point to the claustrum and the ACC as important areas where psychedelics might reshape brain functioning.
By strengthening communication between these regions, rather than weakening it, psychedelics could help support the lasting improvements seen in people who undergo psychedelic therapy for depression and anxiety.
Overall, the results suggest that psychedelics can quickly and persistently change how brain cells connect and adapt, which may explain their long-term positive effects on mood and thinking.
Psychedelics enhance communication between brain regions
Dustin Hines, PhD, an associate professor of neuroscience at the University of Nevada, Las Vegas, who was not involved in the study, spoke with Medical News Today about the study findings.
“These findings really extend what we already know about how psychedelics affect the brain by showing a concrete cellular mechanism for something we’ve mostly inferred from imaging studies,” said Hines.
Hines noted that existing research points toward psychedelics being able to enhance communication between brain regions, and this study “pinpoints the claustrum.”
Zeroing in on the claustrum
“That’s remarkable because it suggests psychedelics don’t just amplify signaling; they may literally rewrite how certain circuits learn and adapt over time.”
— Dustin Hines, PhD
Rochelle Hines, an assistant professor of neuroscience at the University of Las Vegas, Nevada, who was not involved in the study, also spoke with MNT about the study.
R. Hines explained in more detail how the connection between the claustrum and the ACC plays a key role in how the brain manages attention, emotions, and self-awareness.
“The claustrum acts like a conductor, coordinating activity across brain regions, while the ACC contributes to evaluating emotional salience and guiding adaptive behavior,” explained R. Hines.
“Dysfunction in these circuits has been linked to depression and obsessive rumination. So, demonstrating that psychedelics can shift plasticity in this claustro-cortical pathway offers a plausible substrate for their enduring antidepressant and anti-rigid thinking effects.”
— Rochelle Hines
R. Hines did note that there are some “potential downsides” to the effects psychedelics can have in these areas.
“Excessive or poorly integrated connectivity, especially between sensory integration hubs like the claustrum and emotional evaluators like the ACC, could contribute to overbinding of information, which may manifest as hallucinations, anxiety, or cognitive confusion,” cautioned R. Hines.
