Trippy Hearing Aids: Psychedelics Spur New Synapses in Mouse Ear Cells

Growing old is a bittersweet experience. While it brings with it many joys of life, it also carries the baggage of undesirable changes to the body. One such hallmark of aging is the loss of synapses—the connections between neurons—which is a key driving force for many neurodegenerative disorders. This phenomenon, called synaptopathy, can affect synapses across the board, causing detrimental changes to memory, such as in Alzheimer’s disease, or diminish sensory perception, as in age-related hearing loss. The burden of hearing loss is twofold. Not only does it affect more than 50 percent of the population, but it also associated with a two to three times greater risk of age-related dementia.¹ “If you have age-related hearing loss, you have a higher chance of also having dementia or cognitive decline,” said Uri Manor, a cell biologist at the University of California, San Diego, who studies the mechanisms of hearing loss.

Uri Manor is a cell biologist at the University of California, San Diego, who studies the molecular mechanisms underlying hearing loss.

Candace Manor

Currently, there are no approved treatments for synaptopathy, but researchers have been looking into an interesting candidate: psychedelics. A leisurely afternoon of reading during the pandemic left Manor amazed that psychedelics could potentially treat a range of mental health diseases like post-traumatic stress disorder, depression, and anxiety. “It’s like a silver bullet,” he said. At the same time, emerging reports showed that the drugs could induce plasticity in neurons.² On digging a little deeper, Manor found a conference report from the 1960s that showed enhanced hearing in people after they consumed LSD.³ Curious to find out if these effects stemmed from structural changes, Manor and his group studied the effects of psychedelics on mouse ear neurons and found that psychedelics induce the formation of new synapses in the cochlea, the hearing organ present in the inner ear. “This is the first time someone has reported an effect [of psychedelics] on neurons outside the brain,” said Manor, about their preliminary findings, presented at the Association for Research in Otolaryngology’s annual meeting on February 24, 2025. He hopes these data could pave the way for new treatments for hearing loss and other peripheral neuronal defects.

Many psychedelics act by binding to serotonin receptor 2. Manor and his team found that these receptors are expressed in the mouse cochlea as early as one month after birth, suggesting that psychedelics could influence cochlear neurons. So, they obtained cochlear samples from adult mice that had normal hearing and were either exposed to psilocin or left untreated and labeled the synapses between cochlear hair cells and auditory sensory neurons using antibodies. A single dose of psilocin was sufficient to cause a significant increase in the number of cochlear synapses, as compared to animals that were not exposed to the hallucinogens. A synapse function test revealed that the new synapses also led to an increase in signal transmission between the cells. The effects lasted for a month after a single treatment.

A major drawback of psychedelics as therapeutics is their strong hallucinogenic effect. To combat this, Manor collaborated with David Olson, a chemical neuroscientist at the University of California, Davis who has developed non-hallucinogenic psychoplastogens.⁴ When Manor and his colleagues tested the effects of these modified compounds on the cochlear neurons, they observed the formation of new synapses, as well as growth of new neuronal protrusions.

The group has previously reported that synaptopathy and age-related hearing loss precedes cognitive decline in several Alzheimer’s disease mouse models.¹ Based on these observations, Manor thinks of the cochlea as the canary in the coalmine, serving as an early sign of neurodegeneration in the brain. “It's a harbinger. It's a notification that neurons are degenerating,” he said. His team has begun experiments to test if the stimulatory impact of psychedelics on peripheral synapse formation has therapeutic potential to treat disorders such as hearing loss and neuropathies.