Drug Research Psychedelic Drugs Affect the Brain Differently

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LSD, psilocybin and other psychedelic drugs are often considered as one group. But a new study shows that each drug affects the brain differently. The findings could have implications for the development of future treatments for mental health disorders

In recent years, psychedelic drugs have attracted growing interest as potential treatments for conditions including depression, anxiety and addiction. Although these drugs are often considered as one group, researchers from the University of Southern Denmark have now shown that they affect the brain in markedly different ways. The findings are based on brain scans in rats and suggest that the differences between psychedelic drugs may be greater than previously assumed.

Previous studies have mainly investigated one psychedelic drug at a time. In the new study, the researchers directly compared three drugs: LSD, psilocybin and 2C-B, a synthetic drug with psychedelic properties.

The researchers examined how the drugs changed brain activity, both while the drugs were active and one week later. The results showed that each drug produced its own distinct pattern. Only a few changes were shared across all three drugs.

“Psychedelic drugs are often discussed as if they work in the same way. But when we look at the brain, the differences are clear. Each drug appears to affect its own networks, and that is new knowledge”, says Mikael Palner, Associate Professor at the Department of Clinical Research at the University of Southern Denmark and senior author of the study.

More than one Type of Psychedelic Drug

The researchers found that the three psychedelic drugs changed brain activity in different ways. 2C-B and LSD produced the most changes while the drugs were active, but the researchers also found different effects after the acute effects of the drugs had worn off.

“What is interesting is that the differences do not only appear while the drugs are active. We can also see different traces in the brain afterwards. 2C-B mainly affected areas linked to reward, LSD affected areas linked to habits and motivation, while psilocybin stood out by primarily affecting areas involved in emotions”, says Frederik Gudmundsen, first author of the study. Gudmundsen completed his PhD at the University of Southern Denmark and is now a postdoc at the Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University.

This does not necessarily mean that one drug is better than another. But the findings suggest that psychedelic drugs may not be best understood as a single group when they are being investigated as medicines.

“If the drugs affect the brain differently, it is also possible that they may eventually prove better suited to different disorders. We do not know that yet, but our study provides a biological starting point for investigating it”, explains Mikael Palner.

A Step Towards more Targeted Treatments

Interest in psychedelic medicines has grown considerably in recent years. Several drugs are currently being investigated in clinical trials for conditions including depression, PTSD and addiction.

The new study does not tell us whether the drugs work in patients. But it gives researchers a better understanding of what happens in the brain when different psychedelic drugs are active. This knowledge could become important if future treatments are to be more closely tailored to individual disorders.

The researchers also emphasise that the findings come from experiments in rats. Studies in humans are therefore needed before it is possible to say whether the same differences are also relevant to the treatment of patients.

Original Article: Serotonergic psychedelics induce distinct patterns of metabolic activity and covariance within biologically informed rat brain networks; Nature Communications; DOI:10.1038/s41467-026-75890-0

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