#66: 🍄 Psychedelics As Potential Longevity Therapeutics
Exploring the Link Between Psychedelics and Neurodegenerative Diseases
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🍄 Psychedelics As Potential Longevity Therapeutics
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#66: 🍄 Psychedelics As Potential Longevity Therapeutics
Psychedelics have applications beyond mental health. These "psychoplastogens," are gaining attention for their ability to promote neuroplasticity, and are stepping into the longevity arena, with potential applications in targeting issues like inflammation, oxidative stress, and blood-brain barrier disruption.
🍄 Psychedelics As Potential Longevity Therapeutics
Psychedelics are substances that can alter perception, mood, and various cognitive processes. They include substances like LSD, psilocybin, DMT, and MDMA among others.
Some psychedelics, such as LSD, DMT and ibogaine, are potent “psychoplastogens,” which are small molecules capable of rapid structural and functional growth and changes in neurons. This growth and formation of new connections between neurons is called neuroplasticity, which can lead to beneficial therapeutic effects in mental health disorders and potentially in neurodegenerative disease.
While there is ongoing research into the potential therapeutic benefits of psychedelics for mental health, their impact on longevity has not been a primary focus of scientific investigation.
One company taking a look at psychedelics for longevity is Terran Biosciences.
They are a cutting-edge central nervous system (CNS)-focused biotech platform company with a mission to transform the way we treat neurological and psychiatric disease.
Terran Biosciences has one of the largest psychedelics development programs in the industry. Their game-changing novel drug, Idazoxan, can be used to treat schizophrenia and Alzheimer’s and comes as an extended-release version for once-daily dosing.
They have a number of compounds that have a direct application in the longevity space, including psychedelics with a long history of human use, such as psilocybin, LSD, DOM, MDMA and MDMA-derivatives, and 2-CB (read more about 2-CB in Nina’s Notes #38).
Terran has also developed novel psychedelic drugs without the hallucinogenic trip.
Taking the Trip Out of Psychedelics
While psychedelics have demonstrated therapeutic potential across several health indications, their hallucinogenic effects drastically limit their clinical scalability.
Psychedelic therapy often requires a supervised multi-hour psychedelic trip, with a trained psychotherapist, a proper set-and-setting, preparation meetings, follow-ups and integration sessions.
Even with all of these precautions in place, psychedelic therapy still comes with the risk of a bad trip.
For a lot of people the idea of hallucinating for hours and the risk of a bad trip is a non-starter.
To solve this problem, researchers from the University of California, Davis, and start-ups such as Terran Biosciences, Delix Therapeutics, Onsero, and EmpathBio are working to decouple the trip from the healing properties of psychedelics.
Terran is taking an interesting approach to increase the potential of psychedelics for broader clinical use and expand access for many patients.
They are combining psychedelics with serotonin (5-HT) receptor blockers, and specifically blocking the 5-HT2B receptor.
The team at Terran saw in the literature that psychedelic hallucinations presented in a DMT trip are directly linked with only one receptor in the brain, the 5-HT2B receptor.
So the team asked the question, if we give the psychedelic along with a 5-HT2B blocker, could we eliminate the hallucination trip but retain the therapeutic benefits?
They now have drug combinations in development which combine 5-HT2B blockers with classic psychedelics, but we will have to wait for the preclinical and clinical results of their studies with these novel drug combinations to determine the success rate.
If psychedelics did not have the hallucinogenic effect, then these therapeutics could be given to a patient to take at home, without supervision. This opens up the possibility of treatment and prevention of disorders which require on-demand care, such as pain management, or for disorders which require on-going care such as traumatic brain injuries and neurodegenerative diseases.
Psychedelic-Longevity Crossover
The brain is deeply connected with our healthspan and longevity. A healthy brain supports cognitive function, helping individuals make better life choices and adapt to our environment.
Conversely, neurodegenerative diseases, chronic stress and mental health issues can impact longevity and healthspan by affecting overall health and well-being.
Maintaining brain health and addressing related conditions are crucial for healthy aging.
Psychedelics stimulate the growth of new neurons in the adult brain, and reopen critical windows of synaptic plasticity, which were once thought to be exclusive to childhood and infancy.
Given their ability to promote the regeneration and restructuring of brain connections, these psychoplastogens may have the potential to stop some of the neurodegeneration that occurs with aging.
In neurodegenerative disorders, several problems such as inflammation, blood-brain barrier disruption and oxidative stress occur in the brain which psychedelics might be able to target and slow down, especially if they are used early on.
Inflammation
Psychedelics could protect the brain from stress and inflammation associated with neurodegeneration, as psychedelics are known to reduce levels of proinflammatory biomarkers like interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in neurons.
This theory emerged because reducing inflammation was also recently proposed as an antidepressant strategy, since a large percentage of depressed individuals have elevated inflammatory biomarkers.
It has been successfully shown that the single administration of a psychedelic can produce long-term therapeutic effects for depression. However the mechanism behind how this is occurring remains unknown.
Scientists, Dr. Thomas Flanagan and Dr. Charles Nichols, proposed a theory that this anti-inflammatory effect may occur because of psychedelic induced anti-inflammatory responses whereby the psychedelic reduces neuroinflammation associated with major depressive disorder, which could otherwise facilitate a person’s relapse back into a depressed state.
Blood-Brain Barrier Disruption
The brain is protected by the blood-brain barrier (BBB) whose job it is to keep harmful substances from getting into the brain and causing damage. A breakdown of this system is associated with brain-specific damage, such as stroke or traumatic brain injury, and neurodegeneration.
Psychedelics could potentially prevent the breakdown of the BBB.
To investigate this concept, researchers used a rat model of stroke and treated the rats with DMT which decreased proinflammatory biomarkers.
Most interestingly, the DMT treated rats demonstrated improved motor skills post-stroke.
This promotion of motor skill recovery post-stroke by psychedelics is very promising for the use of psychedelics to prevent or repair neurodegeneration.
Oxidative Stress
Oxidative cell damage is a common issue in neurodegenerative diseases. This damage occurs when there’s an imbalance between harmful molecules, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), and protective molecules like antioxidants, such as superoxide dismutases (SOD), and glutathione peroxidases (GPX).
In a healthy brain and body, the reactive species play important roles in cellular processes like apoptosis (programmed cell death) and cellular signaling.
However, when there are too many reactive molecules and not enough antioxidants to neutralize them, they can harm various parts of the cells which are essential for healthy cellular function. Overtime, this can lead to the degradation of cells, organs and tissues.
Chemical reactions in the body called redox reactions generate ROS and RNS, and disruption of the balance of redox reactions occur in Parkinson's disease (PD) and Alzheimer's disease (AD).
In the psychedelic brew ayahuasca, there are two components, harmine and harmaline, that have antioxidant properties and can inhibit monoamine oxidase, an enzyme that catalyzes oxidative stress.
Additionally, ayahuasca, harmine and harmaline have the potential to stimulate the creation of new glial cells and the migration of neural progenitor cells, which are specialized cells in the brain that have the potential to develop into different types of neurons or glial cells. This suggests that psychedelics may have the capacity to support brain repair and regeneration.
Psilocybin and DMT might also provide antioxidant effects by activating the serotonin 5-HT1A receptor, which can lead to the expression of antioxidative factors. This activation has been shown to reduce oxidative stress damage in retinal cells and in mice models of macular degeneration.
Psychedelics as disease-modifying therapeutics
Psychedelics are promising for the treatment of neurodegenerative and movement disorders due to their ability to stimulate neurogenesis, reduce inflammation and reduce oxidative stress.
They have the potential to not only provide symptomatic relief but to actually treat and prevent diseases, indicating their potential as breakthrough therapies.
Several clinical trials have demonstrated both safety and efficacy for MDMA-assisted therapy and psilocybin-assisted therapy with profound and persistently positive results in PTSD and major depressive disorder.
While studies with psychedelics for neurodegenerative disease are only now getting started, preclinical research in cells and animal models show promise for the future prospect of applications in neurodegenerative diseases and longevity.
📚 Book of the Week
Mister Magic by Kiersten White
Rating: ★★★☆☆
Mister Magic is a suspenseful and thrilling mystery novel about a group of castmates from a children’s show that was canceled after a tragic accident stopped production. No records of the show exist but a cult following of fans remembers the show, and the life lessons taught by the host, Mister Magic.
Who is Mister Magic?
What happened to the 6th member of the Circle of Friends and who has brought the friends back together suddenly after 30 years?
It’s not a horror novel, but is a little scary at times, with a very creepy and eerie theme song for the show.
I had a hard time connecting the dots in the book sometimes, with unreliable memories from the characters and some mind-bending scenes. Overall, I liked the book, finding it both bizarre and hair-raising.
⚡️ Check This Out
Wearable exosuits to help warehouse workers avoid back injuries, help people with spinal cord injuries to stand and walk, assist soldiers and help you run faster.
Verve Motion, a Massachusetts-based startup, has created a battery-powered exosuit to solve the workplace injury problem. The wearable robotic looks like a backpack and is strong enough to help workers avoid back injuries while lifting merchandise. Verve Motion has sold 1000+ exosuits, and they are being used in grocery store chains like Wegmans and Albertsons.
ReWalk Robotics makes products that help people with spinal cord injuries to stand, walk and climb stairs. Their eWalk product is the first exoskeleton to receive FDA clearance for personal and rehabilitation use in the USA.
HeroWear, a Nashville-based company worked with Vanderbilt University and the US Army to create a wearable device called the Soldier Assistive Bionic Exosuit for Resupply (SABER) which is meant to assist soldiers with lifting and reducing back strain during logistics operations.
A research group at Chung-Ang University in Seoul, South Korea has built a lightweight exosuit to help you run faster. With steel cables powered by electrical motors attached to the runner’s thighs, the motors pull the cables, mimicking the contraction of muscles, and helps people run faster by assisting their hip extension, the powerful motion that propels a runner forward.
The research group published a study with the exosuit in Science Robotics in September 2023. On average, the participants in the study (none of whom were considered to be elite athletes) managed to sprint 200 meters 0.97 seconds faster while wearing the suit than without it.
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Edited by Wright Time Publishing
This is fantastic, Nina, thank you 🙏🏼
I’m so glad I found you. ☺️