LSD and DMT Caused the Brain to Form New Connections in Flies and Rats

This story is part of When the Drugs Hit, a Motherboard journey into the science, politics, and culture of today's psychedelic renaissance. Follow along here .

LSD and DMT have long been substances of choice in the psychonaut community, and with good reason. Both of these substances are known to profoundly alter a user’s mental state and and result in vivid hallucinations. Yet due to a decades-long moratorium on psychedelic research in the United States, researchers still don’t have a very good picture of how these mind-altering drugs are actually affecting the brain at a physical level.

In a new study published today in Cell Reports, researchers at the University of California, Davis, administered LSD, DMT, and other psychedelic drugs to flies and rats and found that many of these substances—particularly LSD—resulted in neurons forming more synapse connections in the animals’ brains. These results are particularly encouraging because they suggest that psychedelics, or substances like them, may be quite effective in treating depression, anxiety, and post-traumatic stress disorder.

According to UC Davis biochemist David Olson, one of the main signs of depression is that the parts of a neuron that branch out to form connections with other neurons (collectively known as neurites) tend to “shrivel up” in the prefrontal cortex, an area of the brain that is critical in regulating emotion and anxiety. As such, researchers in molecular psychiatry have focused on finding substances that are able to promote neurite growth, or “neuroplasticity,” to counteract the effects of depression and anxiety on the structure of the brain.

In this respect, Olson and his colleagues write that ketamine has “shown the most promise in recent years” for treating depression and addiction because it works fast and is effective in patients that haven’t had success with other forms of treatment. The downside of ketamine, however, is that it is addictive and thus has a potential for abuse. Since many psychedelics have demonstrated a low addiction potential, yet similar antidepressant properties to ketamine, they seemed like a promising avenue for promoting neurite growth as a way to fight depression, anxiety, and post-traumatic stress.

“We specifically designed these experiments to mimic previous studies of ketamine so that we might directly compare these two compounds,” the UC Davis researchers wrote. “To a first approximation, they appear to be remarkably similar.”

The research team administered DMT, psilocin (one of the psychoactive compounds in magic mushrooms), MDMA, and LSD to flies and rats, and found that they all promoted neurite growth. According to the researchers, however, LSD was especially effective compared to the other substances. Surprisingly, the psychedelic ibogaine, which is gaining currency as an addiction treatment, was “the only psychedelic tested that had absolutely no effect.”

“This was surprising,” the researchers wrote, “because we hypothesized that ibogaine’s long-lasting anti-addictive properties might result from its psychoplastogenic [e.g., the ability to alter brain structure] properties.”

Although these test were only done on fly and rat neurons, the fact that the results were so clear in invertebrate and vertebrate species suggests that the effects of these psychedelics on neurite growth “act through an evolutionarily conserved mechanism.” In other words, it’s not far-fetched to hypothesize that similar effects might be found in human brains. Despite the promising results, Olson doesn’t think that drugs that cause strong hallucinations are likely to be widely used for depression, but acknowledges that “a compound inspired by psychedelics very well could.”

“These are some of the most powerful compounds known to affect brain function, it’s very obvious to me that we should understand how they work,” Olson said in a statement. “If we fully understand the signaling pathways that lead to neural plasticity, we might be able to target critical nodes along those pathways with drugs that are safer than ketamine or psychedelics.”