Psychedelic drugs could inspire new medications to treat depression and anxiety

Drugs like LSD help neurons reach out to each other, a promising path for pharmaceutical development.

In a new study, researchers looked at a range of psychedelic drugs and their effects on neurons in the petri dish and tested one drug in rats. They found that these drugs help neurons branch out and communicate with each other. This plasticity could alleviate symptoms of depression, anxiety, and other related conditions.

Previous studies and clinical trials had already shown promise in treating mood and anxiety disorders with psychedelics. What we didn’t understand was how it worked. These new findings now may make it possible to develop new drugs that treat neurological disorders without the hallucinogenic effects.

Psychedelic drugs help neurons communicate


The researchers found that psychedelic drugs caused root-like structures on neurons, called neurites, to grow. David E. Olson, a researcher at the University of California, Davis, led the study. He explains: “Neurites are the branches of neurons that allow them to touch one another, which is key for communication. In depression and related disorders, the neurites in the prefrontal cortex—a part of the brain responsible for regulating anxiety and reward—tend to atrophy. Compounds capable of re-growing these neurites might have great therapeutic value.”

 

This figure shows the effects of three psychedelics and one control (VEH) on cortical neurons. Credit: Ly et al.

 

Olson and his coauthors tested well-known psychedelic drugs—LSD, psilocin, and MDMA—as well as some lesser known ones—DMT, DOI, and noribogaine. All of them caused neurites to grow on cortical neurons in the petri dish. Later, DMT was tested in rats to determine whether it would have the same effect in a living organism. It did. “The effects on neuronal structure and function mirrored those of the fast-acting antidepressant ketamine,” says Olson.

While it’s too early to know for sure, Olson is optimistic his findings will apply to humans as well. One reason is that neurite growth from psychedelics has been demonstrated not only in rats, but also flies. When the same effect is seen in different species, it’s more likely to involve an evolutionarily conserved mechanism that would also be seen in humans. Psychedelics are also known to have long-lasting effects on human brain function, which these structural changes would explain.

A path to new medications


Even if psychedelic drugs are found to stimulate neurite growth in humans, it’s unlikely doctors will be prescribing psychedelics to treat depression and anxiety in the future. Clinical studies of the psychedelic drug psilocybin demonstrate why: “While psilocybin has shown a lot of promise in clinical studies, it needs to be administered in a hospital setting for safety reasons,” says Olson. “What we really need is a safe drug that people can take home with them.” The psychedelic drugs have too many unwanted side effects. Instead, the goal is to develop new pharmaceutical drugs that reproduce the neurite-stimulating effect.

Ketamine-like drugs are already in development


For medications inspired by another recreational drug, ketamine, that process is already underway. Ketamine also stimulates neurite growth, and both ketamine and psychedelics activate the enzyme mTOR to do so. “However, the principal targets of ketamine and psychedelics are different—NMDA receptors for ketamine, and 5-HT2A receptors for psychedelics,” explains Olson, “This might indicate that ketamine and psychedelics initiate neuronal growth in different ways, but that their ultimate effects are similar.” Pharmaceutical companies like Allergan, Johnson and Johnson, and VistaGen are already pursuing ketamine-like drugs to treat depression.

Should future research with psychedelic drugs prove fruitful, they might offer another means to the same end. The next step will be to determine whether the psychedelics’ ability to stimulate growth is linked to their hallucinogenic properties. “Our ultimate goal is to engineer a drug that side steps the hallucinations while still producing the desired effects on neural plasticity,” says Olson.

If they can do so, the medical community will one day have another avenue to treat depression and related conditions. “Mood and anxiety disorders are some of the leading causes of disability worldwide,” says Olson. “We need to use every tool at our disposal—including psychedelics—to better understand the fundamental neurobiology of these diseases, so we can help those who are suffering.”

Featured image courtesy of MR McGill.