LSD, psilocybin, and 2C-B are often classified together as psychedelics—but new brain imaging research in rats shows that each compound produces its own distinct pattern of brain activity.
These differences appeared during both the drugs‘ active effects and in brain scans taken one week later, according to a study published in Nature Communications.
Interest in psychedelic medicine has increased rapidly, with several compounds now being tested in clinical trials for conditions such as depression, PTSD, and addiction. Most previous studies have focused on individual drugs, leaving it unclear how the effects of different psychedelics actually overlap. To address this, researchers at the University of Southern Denmark designed a study to directly compare the effects of different psychedelics side by side.
Different Drugs, Different Fingerprints
Each drug produced its own distinct pattern of brain activity, and only a handful of changes showed up across all three.
“Psychedelic drugs are often discussed as if they work in the same way. But when we look at the brain, the differences are clear,” said Mikael Palner, associate professor at the University of Southern Denmark’s Department of Clinical Research and senior author of the study. “Each drug appears to affect its own networks, and that is new knowledge.”
2C-B and LSD drove the most changes while the drugs were active, but the more striking result showed up after the drugs had worn off. At the one-week mark, 2C-B primarily affected regions of the brain associated with reward, while LSD showed effects in areas involved in habits and motivation. Meanwhile, psilocybin primarily affected regions associated with emotion.
“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,” said Frederik Gudmundsen, the study’s first author, who completed his PhD at the University of Southern Denmark and now works as a postdoc at Aarhus University’s Translational Neuropsychiatry Unit.
Not Better, Just Different: and Still a Long Way From the Clinic
None of this means one drug is better than another, but it does suggest psychedelics may not be one interchangeable category when it comes to developing them for medical practice.
“If the drugs affect the brain differently, it is also possible that they may eventually prove better suited to different disorders,” Palner said. “We do not know that yet, but our study provides a biological starting point for investigating it.”
Despite these intriguing findings, the research does not determine if these distinct patterns of brain activity from different psychedelic substances apply to human patients. The researchers acknowledge this limitation, noting that the results are based on animal models and that further studies in humans are necessary to determine if the same differences apply.
The authors also disclosed that Mikael Palner holds shares in the psychedelic drug companies Compass Pathways and AtaiBeckley, but neither company was involved in the research.
The study still offers a detailed biological picture of how different psychedelic substances alter brain metabolism and network activity and could help researchers investigate whether specific compounds might eventually prove better suited to particular disorders.
For now, researchers have yet to determine whether LSD, psilocybin, and 2C-B will ultimately have distinct roles in medicine or whether the differences between them are less important in humans.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.