Summary: Researchers are reassessing the therapeutic potential of psychedelics as an antidepressant option for people with depression.
Source: Virginia Commonwealth University
For almost five decades, research on psychedelics was largely sidelined. Now an increasing number of scientists, including Javier González-Maeso, Ph.D., and Mario de la Fuente Revenga, Ph.D., in the Department of Physiology and Biophysics at the Virginia Commonwealth University School of Medicine, are investigating whether psychedelic compounds or related molecules can offer a viable treatment for depression.
Major depressive disorder is among the most common mental health conditions in the United States. The National Institute of Mental Health estimates that about 17.3 million adults are affected. Standard care typically combines psychotherapy and medications, but these treatments can take weeks or months to produce meaningful improvement and often fail to bring adequate relief for many patients.
“Patients with depression often must take antidepressants for weeks or even months before they see the first therapeutic effects. During that time the risk of suicide can increase,” said González-Maeso, an associate professor.
Rapid antidepressant effects
Recent clinical studies in the U.S. and Europe indicate that a single dose of psilocybin—the primary psychoactive compound in so‑called ‘magic mushrooms’—can produce rapid antidepressant effects, sometimes within hours. These improvements also appear to persist longer than the benefits typically seen with conventional antidepressants.
González-Maeso cites research showing that, in one trial, 80 percent of people with terminal cancer and coexisting depression who received a single psilocybin dose maintained improved mood outcomes at six months follow-up.
“This does not mean that the average person feeling down will soon be able to pick up therapeutic mushrooms at a pharmacy,” said de la Fuente, a postdoctoral fellow in González-Maeso’s laboratory.
Interest in psychedelic therapy is tempered by decades of legal restrictions. After the 1950s and 1960s research showed promise for mood and substance use disorders, the Drug Enforcement Administration classified LSD, psilocybin and similar substances under strict controls beginning in 1970. For many years psychedelics were categorized as Schedule I drugs—defined as substances with no accepted medical use and a high potential for abuse. It was not until around 2000 that the Food and Drug Administration allowed psilocybin research to resume, and only recently have positive study results returned psychedelics to public attention.
Because of their legal status, researchers must generate robust, reproducible evidence before psychedelics could be prescribed by clinicians. “It will take rock‑hard scientific evidence before they can be used by physicians,” de la Fuente said.
A central task for scientists now is to understand how psychedelic compounds produce antidepressant effects. González-Maeso and de la Fuente are focused on the biological changes psychedelics trigger in the brain, both at molecular and structural levels.
Rewiring the brain
One promising explanation for the observed antidepressant effects is that psychedelics promote changes in neural circuitry—specifically by encouraging the formation of new synapses. Synapses are the contact points where neurons communicate, and previous studies have found that people with depression often show fewer synaptic connections, particularly in brain regions involved in mood and cognition such as the frontal cortex.
In preclinical work, González-Maeso and de la Fuente report that a single dose of a psychedelic compound reduced depression‑like behaviors in mice and increased the number of synapses in the frontal cortex. These findings were presented at the inaugural meeting of the International Society for Research on Psychedelics in New Orleans.
Relief without the psychedelic ‘trip’
The researchers aim to translate these insights into safer, clinically usable drugs. If the molecular pathways that produce antidepressant benefits can be identified, it may be possible to design compounds that deliver lasting mood improvement without causing hallucinations or psychosis‑like effects.
González-Maeso and de la Fuente have filed provisional U.S. patents on two compounds they intend to test for antidepressant potential. Their long‑term goal is to harness the therapeutic mechanisms of psychedelics while avoiding the hallucinatory experiences that currently accompany these drugs.
“Psychedelics were a banned field for decades,” de la Fuente said. “Now, with renewed scientific openness and modern technologies, researchers can explore a largely untapped area. From a scientific perspective, it’s like entering a promised land that could yield new treatments with real clinical impact.”
Source:
Virginia Commonwealth University
Media Contacts:
Amber Logan – Virginia Commonwealth University
Image Source:
The image is in the public domain.