• Oxidative stress, stroke, and inflammation contribute to changes in the brain as we age, including loss of neurons and decreased neuroplasticity

• These changes cause cognitive declines resulting in inattention, memory loss, and slower processing speeds

• Studies demonstrate that psychedelics promote both neuronal regeneration and neuroplasticity, which may make them useful in slowing or reversing age-related cognitive decline

 

As we age, it becomes more difficult to recall recently-learned information. Attention and executive function suffer, and it becomes more difficult to multitask. Coordination and balance are impaired. 

These declines in cognition adversely affect both quality of life and life expectancy for older adults. They complicate day-to-day functioning and contribute to loss of mobility. 

Many researchers believe that psychedelics show promise in reversing age-related cognitive decline. We’ll take a look at how psychedelics work and what that might mean for treating age-related cognitive decline. 

 

 

 

 

What are psychedelics? 

 

Psychedelics are substances that alter our perception of reality. They fall into a few different categories: serotonergic hallucinogens act directly upon the serotonin pathways. They include psilocybin, LSD, mescaline, and 2,5-dimethoxy-4-iodoamphetamine (DOI). They can cause hallucinations, such as those Hoffman experienced with his first dose of LSD. 

 

 

Psychedelic or dissociative anesthetics include PCP and ketamine. The neurotransmitter glutamate, they induce a sense of dissociation from the body. Hallucinations are not a hallmark effect of these drugs, although they can occur. 

Entactogens include 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphctamine (MDE). They stimulate the hippocampus while deactivating the amygdala and thalamus, producing a sense of serenity in most subjects. They are not strongly associated with hallucination. 

 

A long history of psychedelic use

 

Prehistoric cave art found in Spain and Algeria depict the use of psilocybe, the mushroom species from which the psychedelic psilocybin is extracted. 

In ancient Greece, a drink called kykeon, thought now to contain ergot, fueled the esoteric rites of a sect devoted to Demeter. At least 1,000 years prior to Columbus’ arrival, indigenous peoples in the Americas were using psilocybe, as well as  hallucinogens such as peyote and ayahuasca, in spiritual rites. It is highly probable that our hominid ancestors encountered psychedelic plants and experienced their hallucinogenic effects. 

 

A revolutionary bicycle ride

 

Psychedelics have been used for millennia, but our current study of these substances owes itself to an accidental discovery in Switzerland during World War II.

While trying to stabilize alkaloids produced by the ergot fungus in 1938, Swiss Chemist Albert Hoffman synthesized a new compound. He had hoped to produce a  respiratory stimulant, but the compound was a disappointment and was shelved. 

A few years later, Hoffman decided to look anew at the compound, inadvertently absorbing some of it as he worked. He felt an uncommon sense of intoxication and decided a few days later to investigate these effects more fully. 

On April 19, 1943, he dissolved a small amount of the compound in water and purposely ingested about 250 micrograms–that was the smallest dosage, he reckoned, at which the compound would produce any noticeable effects. He then hopped on his bicycle to ride home.  

His commute soon became nightmarish and confusing, full of sensory distortions and motor disturbances. He feared he might die. Instead, he woke the next day feeling “perfectly healthy” and uncharacteristically serene. 

He realized that his “useless” compound–lysergic acid diethylamide–might have uses far beyond what he had imagined. On his way home from work, Hoffman had unwittingly taken the world’s first-ever LSD trip. 

 

An enthusiastic embrace

 

Hoffman believed that LSD could become a powerful tool in psychiatric treatments, a belief shared by his superiors and colleagues at Sandoz Laboratories. Sandoz began marketing LSD under the name Delysid in 1947. When Hoffman went on to isolate psilocybin in 1958, Sandoz marketed it, as well. 

In the United States, LSD quickly captured the public’s attention.  Psychologists used it to augment psychotherapy. It was heralded as an effective treatment for alcoholism, and the media reported on it frequently and enthusiastically. Between 1950 and 1965, over 1,000 separate studies on LSD were published. 

 

Renewed Interest

 

The Controlled Substances Act of 1971 criminalized LSD, psilocybin, and peyote. A combination of restricted supply and government censure stifled research. 

Interest in psychedelics and their psychiatric applications is exploding once again, though. In the last 10 years, 20 studies on psilocybin alone have been published; more than 90 have been done on psychedelics in general.

A promising study in 2002 found  that a single dose of ketamine significantly reduced treatment-resistant depression within three days–much more quickly than the average antidepressant. 

 

 

How the Brain ages 

 

To understand how psychedelics might benefit older adults, it is helpful to understand how the brain changes as we age. Imaging and post-mortem tissue studies have shown us that age changes the structure and function of the brain in many significant ways. 

 

Loss of gray matter

Gray matter is the neuron-rich tissue of your brain’s outer cortex. It is associated with complex learning, reasoning skills and motor control. Gray matter in the frontal cortex, located in the anterior regions of the frontal lobes, decreases at an average rate of 5% every 10 years in adults over age 65.

There is rising support for the frontal aging hypothesis, which posits that most age-related cognitive changes are due to loss of mass in this region of the brain.
Similar loss of gray matter is noted in the hippocampus, which is responsible for memory consolidation and visuospatial reasoning as well as mood regulation. Atrophy of the hippocampus is associated with memory loss and depression in older adults.

 

 

Loss of white matter

 

White matter gets its name from the myelin sheath that surrounds and insulates axons,  filaments that relay impulses from the neurons to the synapses.  While gray matter is found mostly on the outer surfaces of the brain, white matter is mostly concentrated in areas closer to the center of the brain. 

Age-related decreases in white matter are associated with declines in  cognitive function and motor control, as well as dementia. 

 

Loss of synapses and neurons 

 

In young adulthood, the outer cortex of our brains contains between 14 to 16 billion neurons.

As we age, we lose about 10% of these neurons. This rate of loss may seem negligible, but combined with changes in the structures of remaining neurons, it significantly affects cognition. 

Neurological changes associated with age include loss of synapses, which are junctions between the axon of one neuron and the dendrite of another. When synapses are lost, intercellular communication is complicated. Dendritic spines–tiny, hair-like protrusions that extend from the axons of neurons–are also lost.  

Dendritic spines transmit electrical signals from the synapse to the neuron; they are important for maintaining neuroplasticity,  the brain’s ability to restructure neurons in response to stimuli and injury. 

The loss of neurons, synapses, and dendritic spines forces the existing neurons to work much harder to accomplish simple tasks. This requires a great deal of energy and negatively affects attention and multitasking. It also causes fatigue. 

 

How could psychedelics help?

 

The same properties that make psychedelics useful in treating depression have implications for treating age-related cognitive decline. Psychedelics treat depression by stimulating serotonin pathways in the brain.They have a number of other effects that could also potentially address cognitive decline. 

 

Serotonin and age 

 

The serotonin pathways are implicated in higher cognitive functions, and many of the behavioral and cognitive changes seen with age are rooted in neuron loss in the serotonin pathways.  

By activating these pathways, psychedelics facilitate more efficient communication between neurons. This could minimize some of the effects of neuronal loss and could possibly allow us to preserve cognitive function as we age.  

 

Regeneration of neurons

 

According to a study published in Nature in 2023, psychedelics promote signaling for brain-derived neurotrophic factor (BDNF), a molecule that stimulates the formation of new neurons (neurogenesis), synapses (synaptogenesis), and dendritic spines (spinogenesis). 

In rat studies, dendritic spines nearly doubled in brain tissue exposed to LSD. In addition to increasing the density of dendritic spines, Dimethyltryptamine (DMT) exposure resulted in increased frequency of synaptic impulses. This maximizes communication between nerve cells. 

 

Increased Neuroplasticity

 

In promoting neurogenesis and spinogenesis, psychedelics also promote neuroplasticity. Neuroplasticity is defined by some scientists as “the brain's ability to increase capacity in response to sustained experience.” 

Neuroplasticity gives us a greater ability to learn and absorb new information. It also allows neural pathways to adjust to injury from trauma or strokes. Psychedelics might help older adults preserve neuroplasticity. 

 

 

Risks

 

Psychedelic therapy is not without its risks. No human studies on psychedelic therapies and age-related cognitive decline have been conducted, and parameters for optimal dosing have not been established. . 

Psychedelics can induce psychosis, especially among those with a personal or family history of psychotic disorders. They can also induce extreme anxiety or panic. Hallucinogen Persisting Perception Disorder (HPPD), a state of perceptual disturbances lasting weeks or even years after the initial dose, is a rare adverse effect. Many psychedelics cause rapid heartbeat, fever, and sweats. 

While most researchers believe that most people can take psychedelics safely under a physician’s guidance, there is no way as of now to guarantee their safety for use in the aging population. To complicate the matter, most psychedelics remain illegal in the United States.

 

 

A bright future

 

In the US today, adults over age 65 account for about 15% of the population. That percentage will climb to 21% by 2030. By 2060, one in four Americans will be 65 or older. Age-related cognitive decline therefore stands to become a significant public health concern over the next decades. 

Psychedelics represent tremendous promise in slowing and rolling back these declines. They could radically change treatment options for those over 65, increasing quality of life and  independence. This would be a gain not only for individuals, but for society at large.