Humans have used psychedelic drugs for hundreds of years, but we still don’t know an awful lot about what LSD, MDMA, DMT, psilocybin, and the whole galaxy of other psychedelic drugs do to our brains. That’s because it’s really hard — and really illegal — to lick toads. It’s also illegal to smoke DMT inside a fMRI machine. Fortunately, scientists have found a way around that problem: Now they can use mini-brains — known more formally as “organoids” — that can show us what happens in real time without having to get anyone high.

In a study published Monday in the journal Scientific Reports, a team of Brazilian scientists dosed mini-brains with 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a chemical similar to DMT that’s secreted by Incilius alvarius toads. They found that a single 24-hour treatment with 5-MeO-DMT downregulated pathways that are associated with inflammation and substance-use disorders, and they also observed how the psychedelic drug creates cellular changes in the brain.

Beyond their actual findings, this research represents an important step for organoid research on drugs.

“For the first time we could describe psychedelic related changes in the molecular functioning of human neural tissue”, says Stevens Rehen, study leader and a professor at the Federal University of Rio de Janeiro and Head of Research at D’Or Institute for Research and Education.

DMT receptors in mini-brain organoids. Dakic et al

Organoids, mini versions of human brain regions, are grown from stem cells and bear a lot of structural similarities to the brains of human fetuses. These organoids are ideal for this type of drug research because they can be grown in a lab and experimented on without the ethical or legal concerns that come along with research on human subjects.

In the 5-MeO-DMT study, scientists used cerebral organoids to explore how the drug affects protein expression which governs brain plasticity and inflammation, among other things. They found that the drug didn’t have any effects on cell growth or death, but they did find that organoid cells express 5-MeO-DMT receptors, meaning that these lab-grown mini-brains seem to be appropriate platforms for testing DMT-type drugs.

The cerebral organoids used in this study contain mature neurons, meaning that scientists can use the organoids to gain insights into how an actual brain in a human body might respond to drugs. Dakic et al

A major weakness of this study is that organoids don’t contain all the different areas of an actual human brain. Therefore, scientists using organoids to study the effects of drugs on the brain can’t see all the complex interactions that typically occur among brain regions when a person uses psychedelic drugs. But this research does provide important first steps as scientists explore why psychedelics like 5-MeO-DMT seem to help protect people’s brains from neurodegeneration.

Abstract:

Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico analysis reinforced previously reported anti-inflammatory actions of 5-MeO-DMT and revealed modulatory effects on proteins associated with long-term potentiation, the formation of dendritic spines, including those involved in cellular protrusion formation, microtubule dynamics, and cytoskeletal reorganization. Our data offer the first insight about molecular alterations caused by 5-MeO-DMT in human cerebral organoids.

Taking LSD can make your brain work more like a child’s. Check out this video to find out more.