Scientists give psychedelic drugs to tiny brains in petri dishes
Using organoids allows researchers to circumvent legal and ethical barriers to valuable research. Tim Wallace reports.
Naturally occurring psychedelic compounds such as psilocybin, produced in mushrooms, and dimethyltryptamine (DMT), produced in many plants and animals, are of great interest to medical researchers as potentially effective treatments for conditions such as depression and drug addiction.
Investigating their effects and potential benefits through human trials, however, is a legal and ethical minefield.
Now research from Brazilian scientists shows a way to avoid the need to conduct risky tests on humans, through measuring the effects of such compounds using cerebral organoids – cultures of neural cells that mimic a developing human brain, grown in petri dishes.
Using these mini-brains or organoids, which can develop cell structures similar to those found in real brain areas such as the cerebral cortex, ventral forebrain and hippocampus, offers “an exciting new range of opportunities to investigate the molecular responses of human neural tissue to psychoactive substances,” the scientists write in the journal Scientific Reports.
The research, led by Vanja Dakic of the D'Or Institute for Research and Education (IDOR) in Rio de Janeiro, involved dosing mini-brains with the psychedelic compound 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). They report that a single treatment produced noticeable anti-inflammatory effect on brain cells, increased the synaptic mechanisms considered crucial to learning and memory, and reduced the effects of a neural receptor (mGluR5) associated with the rewarding effects of addictive substances such as cocaine.
5-MeO-DMT is related to but pharmacologically different in its effects to DMT (or to be precise N,N-DMT), the better-known psychoactive agent in the traditional South American shamanic herbal brew known as ayahuasca. Whereas DMT occurs naturally in many plants and animals including human, 5-MeO-DMT is produced in just a few plants and one known animal species, the Bufo alvarius toad. Is it used in some shamanic ceremonies, taken as a snuff known as 'yopo’, and is regarded as more intense, and less pleasant, than ayahuasca.
Dakic’s colleague and co-author Stevens Rehen, the head of research at IDOR, says the study is the first time scientists have been able to describe “psychedelic-related changes in the molecular functioning of human neural tissue".
Fellow co-author Sidarta Ribeiro, of the Brain Institute at the Federal University of Rio Grande do Norte in Natal, says the study reinforces the clinical potential of substances “that are under legal restrictions but which deserve attention of medical and scientific communities".