The Curious Connection Between Psychedelics and Longevity

Psychedelics are to the mind what longevity drugs are to the body

I hope you don’t mind that I’ve taken a detour from the stated theme of this blog to explore what increasingly appears to be an adjacent area that I think will prove interesting and relevant to Trip Report readers—Longevity science.

The Fountain of Youth Lucas Cranach the Elder

---

I have been exploring the overlap between the two buzzy fields of psychedelic science and longevity science, and I am coming to recognize some profound similarities.

My ideas have matured sufficiently to share, though you should consider this a conceptual introduction, and if you want to dive in deeper, I’ve included some links to additional reading at the end. 

This should be enough to get the wheels turning for readers unfamiliar with the longevity space that may have heard rumblings of one sort or another of a forthcoming renaissance in longevity and life extension. 

Furthermore, I think there is fertile ground to explore between these two areas and perhaps some practical intermingling because of the paradigm shifts they portend in treating mental illness and chronic, age-related diseases.

Here are the similarities between the two fields we’ll explore

• Cultural Narratives

• Funding Roadblocks

• True Believers

• Massive Unmet Need

• Are Longevity Drugs the Psychedelics of the Immune System?

Ok, let’s dive in.

Cultural Narratives

Both psychedelics and longevity as fields of serious scientific inquiry are fighting uphill battles from two sides of a cultural baggage phenomenon. On the one hand, each has their "True Believers," and on the other, we have antagonists of "the sky is falling!" variety.

True believers in both camps invoke a salvation narrative as enthusiastic proponents envision a world transformed and saved through their adoption.

The psychedelic version of this reformed society results from the truths one receives from transformative experiences that unveil the interconnectedness and interdependence of all things in an experience often described as “more real than reality.”

The longevity version is a modern-day recapitulation of the quest for immortality, a theme that has found feverish devotees across the history of humanity.

The second trope is along the lines of flying too close to the sun.

The decades-long narrative of psychedelics as psychosis-inducing agents has been a powerful method of keeping them stigmatized and transmitting the message that anyone engaging with them is playing with fire.

Similarly, ideas of extending life span are countered with "natural order" arguments that push back against the idea that the field is “messing with nature,” and the consequences are sure to be catastrophic. 

However, both domains appear to offer something practical if you look past the overzealous and the cantankerous and explore the really compelling science that points to the potential of less human suffering.

In the case of psychedelics, for the treatment of stubborn mental illness and longevity, an approach to the common sources that lead to age-related Alzheimer's, cardiovascular diseas, and metabolic disease.

Furthermore, both point to a transdiagnostic approach to a broad category of diseases in an increasingly fragmented healthcare system that obscures common origins such as early life adversity, systemic inflammation, and a synthetic food environment.

Funding Roadblocks

To further the similarities, both psychedelics and longevity research have had unique funding barriers that have held back scientific progress for decades.

As Schedule I substances, psychedelics have relied on philanthropic funding until only recently when the commercial interest took hold.

But federal funding is still absent and philanthropic support is light compared to other domains.

Second, it was only recently that psychedelic science pivoted from a stigmatized, career-ending field to a hot new area of research, thus pushing many promising researchers away from the field.

For longevity, the field has been stymied because "aging" is not a recognized diagnosable disease and thus not amenable to investment for pharmaceutical development. So the field has been languishing in the preclinical stage with inspiring and promising results in animals, while advocates lobby for the recognition of aging as a disease.

This has forced many projects into the supplement market, which cannot command investment and valuations that even come close to the pharmaceutical industry. It has also perpetuated the appearance that the field is less rigorous.

Community of True Believers

Against the backdrop of pejorative cultural narratives and lack of funding, both domains have maintained enthusiastic niches and subcommunities, including strong bases of DIY citizen scientists, consciousness explorers, biohackers, and self experimenters kept the light from going out on these lines of inquiry.

Countercultural use of psychedelics has persisted with a robust network operating in the illicit market, underground therapists, guides, and sitters, plus the more recent proliferation of retreats has all kept the psychedelic candle burning.

Biohacking, quantified self and other niche communities have been tinkering with supplementation and self-experimentation while the academic field of gerontology has morphed into longevity and life extension.

Massive Unmet Need

If upcoming pivotal trials of psychedelics can retain some of the efficacy and promise that we see in the small trials; and if the results of longevity research from animal studies showing signs of age reversal, inflammation reduction, and tissue regeneration can translate into humans— both will present a radically different paradigm for the treatment of mental illness, chronic and age-related disease.

These areas of healthcare makeup 90% of annual healthcare expenditure in the US¹ and are completely lacking in cures and treatments that go beyond the mere management of symptoms.

One way of looking at the dominant approach to healthcare is to imagine it as palliative care that begins in middle age. 

Chronic, age-related diseases like cardiovascular disease, neurodegenerative disorders, respiratory conditions, and others are not treated, per se, but managed.

Mental health, too. Often current medications are intended to be taken for months and years, if not indefinitely.

The contemporary approach to these conditions is not unlike morphine to make terminal patients comfortable as they die.

Both psychedelics and potential longevity therapeutics present the idea of addressing the underlying “root causes'' of disease rather than managing the symptoms.

So even if psychedelics, as pharmacotherapy goes bust, and aging as a disease is never established, and life extension turns out to be a myth— at the very least, they are presenting an alternative paradigm that applies evolutionary pressure on the current systems and methods of treatment that virtually everyone finds unacceptable.

Plasticity Based Approaches to Systems, Not Diseases

Finally, and where I am most interested but also pushing against the edge of my understanding, there appears to be a mechanistic common ground between psychedelics and longevity that is worthy of exploration.

The aging process is understood as the progressive accumulation of molecular damage and the decline of the body's Defense, Repair, and Maintenance (DRM) processes.

The science of longevity and life extension is predicated on upregulating these DRM processes and reversing the damage that has been done.

Interestingly, long-standing health practices that date back to antiquity like exercise, fasting & caloric restriction, cold and heat exposure, breathwork and certain herbal/plant medicines all upregulate the body’s DRM processes.

And all of these ancient health practices operate by the principle of that which doesn't kill me makes me stronger— it is the idea that a stressor at a high enough dose would be harmful, is actually beneficial at a smaller dose because it activates the genes that code for an organism’s DRM processes without actually damaging the organism.

Cutting-edge longevity research is the science of exploring ways to upregulate these same processes through genetic modification without the need to apply external stressors.

David Sinclair, probably the world’s most known longevity researcher, put it this way on Twitter:

“To be the best version of yourself, mentally & physically, activate your body’s defenses against aging and other diseases…

Trick your body into thinking its survival is at stake: skip meals, lift heavy things, avoid overeating & snacking, experience hot and cold, do aerobic exercise until you’re out of breath & take supplements proven to mimic them”

What’s this have to do with plasticity?

"Similarly, neuroplasticity – such a fashionable term nowadays – really is amazing, but the nervous system is not the only system that has a remarkable capacity to change in response to demand." —Lorimer Moseley

I think it is reasonable to say we can understand biological plasticity through at least two distinct "flavors":

• Induced Malleability

• Adaptation to Imposed Demand.

Psychedelics might be thought of as inducing the malleability of neural circuitry, thus making them more plastic. This is the chief explanatory model that supports theories of how they work in treating mental health conditions and the cause of the transient, consciousness-altering experiences they create. From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

"Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them."

On the longevity side, molecular damage to tissue, cells, and DNA occurs from toxins in the environment and foods but also the very biological processes that sustain life.

Paradoxically, as we just touched on, the most well-studied components in the longevity arsenal work by activating these DRM processes by imposing short-term exposure to increased levels of stress that drive adaptive, beneficial changes. These imposed demands upregulate the DRM processes in the same way that bicep curls upregulate muscle growth through biological plasticity.

I put the following out to Twitter a few weeks ago looking for answers:

The idea of neuroplasticity seems accepted as capable of producing positive therapeutic outcomes even if the more precise application and specifics of mechanism aren’t fully realized.

But do immunology and endocrinology think about modulation and plasticity similarly?

I think these two fields in particular because of their involvement in everything (mental health, infection, metabolic crises, growth, development, decay, decline etc) and but I don’t know how quantifying and interpreting plasticity/plastogenisis of these systems is done.

In neuro there is structural and functional connectivity, what is the equivalent in these fields?  And what are the reliable means of modulating these systems via plastic changes?

This seems like the interface btw psychedelics and longevity, another scientific growth area

Here’s what I am wondering:

Are Longevity Drugs the Psychedelics of the Immune System?

Is it reasonable to think of the “universal, intrinsic, progressive accumulation of deleterious changes in cells and tissues that increases morbidity and leads to death” as analogous to the faulty circuits we find in the brains of individuals who have a mental illness? 

And thus, should any forthcoming longevity drugs that resolve this accumulation be seen as an immunological analog to the effect that psychedelics have on the brain? 

After all, long-term oxidation-inflammation that contributes to the aging process is primarily mediated by the immune system, just as the neural circuitry modulated by psychedelics is primarily in the purview of the nervous system. 

Just as practices like meditation, therapy, neurofeedback leverage the brain’s innate capacity for modulation and can thus alter traits, mood and behavior, can’t we view psychedelics as merely adding leverage to these processes?

And just as practices like fasting/caloric restriction, cold & heat exposure, and exercise leverage the body’s innate DRM systems, won’t any forthcoming longevity therapeutics simply be leveraging these innate processes and thus adding leverage?

So, the hypothesis I am putting forward is that the drugs we may eventually see come out of longevity science will be accelerants of DRM processes in the same way that psychedelics are accelerants of neuroplastic changes.

In this way, longevity drugs are to the immune system what psychedelics are to the brain.

---

I hope you enjoyed this. Let me know what you think.

Additional Resources

Laura Deming’s Beginner’s Guide to Longevity Research

The Longevity FAQ from Nintil.com

David Sinclair on the Lex Fridman Podcast 

Inconvenient Truths About Human Longevity

Longevity @ Science Direct

1. Health and Economic Costs of Chronic Diseases)