Psychedelic drugs promote neural plasticity in rats and flies

June 12, 2018, Cell Press
The effects of three psychedelics and one control (VEH) on cortical neurons. Credit: Ly et al.

Psychedelic drugs may have mind-altering powers in the physical sense, too. A new study, published June 12 in the journal Cell Reports, found psychedelics, specifically DOI, DMT, and LSD, can change brain cells in rats and flies, making neurons more likely to branch out and connect with one another. The work supports the theory that psychedelics could help to fight depression, anxiety, addiction, and post-traumatic stress disorder.

"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," says senior author David E. Olson, assistant professor in the Department of Chemistry and the Department of Biochemistry & Molecular Medicine at the University of California, Davis.

The idea that depression stems from imbalanced brain chemistry remains popular, but recent studies have revealed evidence that depression manifests as structural changes in brain circuits or atrophy in parts of the brain. This doesn't mean neurons die off during depression, but that neurites retract. Neurites are the sections—either axons or dendrites—of a neuron that project out to bridge the gap between two neurons at the synapse to facilitate communication.

"One of the hallmarks of depression is that the neurites in the prefrontal cortex—a key brain region that regulates emotion, mood, and anxiety—those neurites tend to shrivel up," says Olson. These brain changes also appear in cases of anxiety, addiction, and .

In their paper, Olson and colleagues tested psychedelics from the amphetamine, tryptamine, and ergoline drug classes. In both test tube and animal experiments, the psychedelics showed functional and structural changes like those promoted by ketamine in cortical neurons. Psychedelics increased both the density of dendritic spines and the density of synapses. Some psychedelics tested, including LSD, proved to be more potent and efficacious than ketamine in promoting neurite growth.

The researchers did not do any human experiments, but experiments in both vertebrates and invertebrates showed psychedelics produced similar effects across species. This indicates the biological mechanisms that respond to psychedelics have remained the same across eons of evolution and that psychedelics will likely have the same brain growth (neural plasticity) effects in humans.

Psychedelic drugs such as LSD and ayahuasca change the structure of nerve cells, causing them to sprout more branches and spines, UC Davis researchers have found. This could help in "rewiring" the brain to treat depression and other disorders. In this false-colored image, the rainbow-colored cell was treated with LSD compared to a control cell in blue. Credit: Calvin and Joanne Ly

Olson and colleagues also set out to test how these psychedelics promoted neural plasticity, meaning they explored which biological pathways psychedelics activate that lead to neural growth. Ketamine's neural plasticity effects were previously shown to be dependent on a protein called brain-derived neurotrophic factor (BDNF). When the researchers blocked BDNF signaling, psychedelics lost their ability to promote neurite growth. BDNF binds to a receptor, called TrkB, that is part of a signaling pathway that includes mTOR, which is known to play a key role in the production of proteins necessary for the formation of new synapses. When the researchers experimented by inhibiting mTOR, it also completely blocked the psychedelics' ability to promote neurite growth. Olson thinks identifying the signaling pathways at play in psychedelic-induced changes will help future research identify compounds that could be developed into depression treatments.

"If we fully understand the signaling pathways that lead to , we might be able to target critical nodes along those pathways with drugs that are safer than ketamine or psychedelics," says Olson.

Although most psychedelics aren't considered to be addictive in the same way that cocaine is, they do produce hallucinations. Olson doesn't expect psychedelics to become prescription drugs for . "But a compound inspired by very well could," he says.

Explore further: Psychedelic drug use associated with reduced partner violence in men

More information: Cell Reports, Ly et al.: "Psychedelics Promote Structural and Functional Neural Plasticity." https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30755-1 , DOI: 10.1016/j.celrep.2018.05.022

Related Stories

Psychedelic drug use associated with reduced partner violence in men

June 5, 2018
In a new study published in the Journal of Psychopharmacology, researchers from UBC's Okanagan campus have discovered that men who have used psychedelic drugs in the past have a lower likelihood of engaging in violence against ...

No link between psychedelics and mental health problems

March 5, 2015
The use of psychedelics, such as LSD and magic mushrooms, does not increase a person's risk of developing mental health problems, according to an analysis of information from more than 135,000 randomly chosen people, including ...

Use of psychedelic drugs remains prevalent in the US

April 23, 2013
An article published in F1000Research, and approved for indexing in PubMed and other major bibliographical databases, estimates that there were approximately 32 million users of psychedelic drugs in the United States in 2010.

Mind-altering drugs could treat mental disorders

March 30, 2016
Psychedelic compounds have had a colorful past. Although initially investigated for medical uses, they were banned after cultural and political times changed in the 1960s and 1970s. Now, the compounds are getting another ...

Researchers test psychedelic on cerebral organoids

October 9, 2017
A Brazilian study, published in Scientific Reports on October 09, 2017, has identified changes in signaling pathways associated with neural plasticity, inflammation and neurodegeneration triggered by a compound from the family ...

Rethinking serotonin could lead to a shift in psychiatric care

September 5, 2017
A better understanding of how a key chemical messenger acts in the brain could lead to a radical shift in psychiatric care, according to a new paper.

Recommended for you

Helping amputees feel as though their prosthetic limb belongs to their own body

August 14, 2018
The famous idiom "seeing is believing" is not enough to help amputees with the use of their prosthetic limb. Many amputees opt out of prolonged use of their prosthetic limb because their perception of their missing limb simply ...

Double discovery reveals insights behind brain degeneration

August 13, 2018
Research discoveries revealing the genetic causes of neurological degeneration could be a key to slowing the progression of devastating diseases.

Scientists turn unexpected brain study results into research tool

August 13, 2018
Puzzled by their experimental results, a team of scientists from Baylor College of Medicine and Texas Children's Hospital investigated why a research tool that was expected to suppress neuronal activity actually was stimulating ...

Could nose cells treat spinal cord injuries?

August 13, 2018
Researchers have designed a new way to grow nose cells in the lab heralding hope for sufferers of spinal cord injuries, including those who are wheelchair bound.

Study examines how people adapt to post stroke visual impairments

August 13, 2018
A new University of Liverpool study, published in Wiley Brain and Behaviour, examines the factors that influence how a person adapts to visual field loss following stroke.

Detailed atlas of the nervous system

August 10, 2018
Researchers at Karolinska Institutet have created a systematic and detailed map of the cell types of the mouse nervous system. The map, which can provide new clues about the origin of neurological diseases, is presented in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.