New dimensions in longevity

Ahead of Wonderland, Max Unfried discusses the role psychedelics have to play in longevity medicine, mental health and geroscience research.

It’s not long to go, now, until Wonderland, the world’s leading psychedelics conference that sees researchers, clinicians and investors flock to Miami, Florida; this year the event is including a longevity focus for the first time and boasts a raft of top speakers including Bryan Johnson and Aubrey de Grey.

Longevity.Technology: Longevity and psychedelics are increasingly sharing the same space, so it is no wonder that Wonderland is set to consider the relationship and interplay between the two in a series of keynotes, discussions and open mic sessions.

One of the speakers is Max Unfried of VitaDAO and the National University of Singapore, where he is a longevity scientist specializing in the systems biology and biomarkers of aging, and the role of psychedelics in longevity medicine. We sat down with Unfried to expand our consciousness and find out more about the role psychedelics can play in longevity medicine.

Some natural psychedelic compounds have been dubbed breakthrough therapies by the FDA, and while FDA approval can give these compounds perceived legitimacy as medicines, Unfried says that many longevity physicians are rather sceptical about psychedelics, a scepticism he attributes to a lack of knowledge and unawareness of the vast amount of literature available.

“Longevity physicians often claim that general practitioners are ignorant of longevity medicine while being ignorant of psychedelic medicine,” he explains.

“While the effect size of psychedelics for mental health is rather strong, their effect on longevity has yet to be proven out – and when I talk about longevity here, I mean the stalling of age-related decline, or even reversing aging.”

While there are some indications that psychedelics could help with neuroplasticity and neurogenesis as well as improvements of the immune system, Unfried says, conducting psychedelic research can still have many hurdles, even preclinically. FDA approval or not, geography matters, as different regulators have different views.

The cognitive benefits of psychedelics have been well documented, but we do not yet know yet if psychedelics can directly prevent physical decline. However, Unfried makes the point that we should consider the argument that they are indeed able to help through mentally induced second order effects – that is, that every action has a consequence, and each consequence has another consequence.

Personality changes with age, explains Unfried, citing that Openness to Experience is particularly in decline.

“This means that elderly are less likely to pick up new hobbies or try out new things that might keep them physically active,” he says. “This, combined with anxiety disorders such as irrational fears of specific situations, and an aversion to open or public spaces, can lead to many people just not getting the daily movement they need to keep the body well-functioning.

All this leads to what Unfried describes as a “death spiral, where physical decline leads to more physical decline”.

But there is light at the end of the tunnel. Unfried says that multiple studies have shown that psychedelics can significantly increase the personality trait “Openness”, which in practice should result in people trying out new things and having an improved outlook on life.

“Moreover, psilocybin, LSD, DMT, MDMA and Ketamine have shown anxiolytic properties,” he adds. “Hence, psychedelic therapy at a certain age might help people engage more again in life and keep their bodies moving.”

Diving deeper, Unfried explains that on a molecular level, many physical disease states involve inflammation. “This is very much true for many age-related diseases such as CVD, diabetes, malignancy, auto-immune disease, arthritis, etc, where inflammation plays a significant role,” he says, adding that inflammaging is a risk factor for bad health status such as sarcopenia and frailty.

“Getting control of inflammation through the anti-inflammatory effects of psychedelics could help alleviate these physical decline. While this is still an active area of research it seems psychedelics interact with established inflammatory and immune response pathways including the serotonergic system, sigma-1 receptor as well as cytokine regulation.”

While psychedelics are often trumpeted as improving mental health, the truth, as so often with longevity science, is more nuanced than that.

When it comes to reflecting on their relationship, Unfried says there is a lot to unpack.

“Anxiety disorders and affective disorders such as various forms of depression are amongst the most common mental health issues in the elderly. We know that people with depression have a shorter life expectancy and depression is associated with accelerated aging. Studies applying aging clocks have shown that people with depression have accelerated epigenetic and metabolic age. The question is why?”

Max Unfried, longevity scientist and speaker at Wonderland

Unfried explains that given that various studies show that psychedelics improve anxiety and depression, one can speculate that psychedelics could decelerate epigenetic and metabolomic aging. While studies would have to be conducted to show this, Unfried points to studies in mice that demonstrate epigenetic remodelling can occur as part of LSD-induced neuroplasticity increases.

“What is of interest with regard to longevity, is if psychedelics have geroprotective effects and if the mechanisms that are geroprotective are also the reason psychedelics are helping with mental health.

“We know that neuroplasticity and neurogenesis play vital roles in preserving cognitive sharpness and adaptability, but they tend to decrease as we age. This age-dependent reduction in neuroplasticity is further emphasized by diminishing levels of Brain-Derived Neurotrophic Factor (BDNF), and BDNF is directly connected to brain aging… And this is where psychedelics come into play: numerous psychedelics show the ability to enhance neuroplasticity and stimulate neurogenesis by increasing the production of BDNF.”

Within the extensive realm of longevity studies, psychedelics stand out for Unfried as potential game-changers that could challenge traditional notions of brain aging.

“Their capacity to restore neuroplasticity and neurogenesis, especially by influencing key molecules such as BDNF, marks them as potential foundational tools in our quest for sustained cognitive vitality,” he says.

The field of psychedelics is not without its disadvantages – to mention it in conversation is often to be met with questions about tripping hippies turning on, tuning in and dropping out. Does Unfried feel that the stigma attached to the use of psychedelics in medicine is finally breaking down?

“For the past fifty years various governments of the world have done their best to give psychedelics a bad reputation and added stigma,” he says. “An entire generation has been indoctrinated and raised with the belief that psychedelics are dangerous.

“It is breaking down rather slowly – it’s a generational shift, where young scientists pave the way, and we might just have to endure until the scientific gerontocracy is retired.”

But perhaps now the times, they are a-changin’, with events such as Wonderland playing a significant part in bringing the use of psychedelics to the fore. And for Unfried, while community is key in this, more must still be done.

“I’m a big believer in community driven change, and what Wonderland provides is the gathering of a big part of the psychedelic community,” he explains. “However, it’s also a echo chamber, where people are preaching to the converted – this might just be the sign of a still young industry. Similar to longevity it is important to get people speaking about psychedelics at non-psychedelic conferences.”

The field of psychedelics is often viewed as non-mainstream and a little bit ‘out there’ – but longevity research can often benefit from left field thinking.

“There is not much originality in the field and most scientists are conservative-thinking – yielding to incremental improvements but not much radical innovation. Radical new ideas in the last few years can be counted on one hand.”

Unfried cites the Impetus Grants as one of the lights at the end of the tunnel.

“They are doing a great job of attracting more unconventional ideas – and actually funding them,” he says. “At least this also gives scientists reasons to have crazy ideas again and put mental resources towards them. Given that we still don’t really know what aging is, or how to control it, there is a lot of room and crazy hypotheses to be tested out.

“I do think that psychedelics could offer fluent cross disciplinary modes of thinking, and make scientists dream big again, coming up with new hypotheses to test, as often a scientist’s mind is confined to their subject matter expertise.”

Unfried points to Nobel laureate Kary Mullis, who claimed his discovery of polymerase chain reaction had been fuelled by LSD consumption.

“Who knows what LSD could unleash if every five to ten years, every scientist took a trip to other dimensions?”

Interested in attending Wonderland? Access tickets and speaker/sponsorship/exhibitor opportunities here.

Photo credit: Marek Piotrowski