Psilocybin is a plant derived hallucinogen with a long history of use and shorter history of prohibition that suppressed earnest efforts to research its biochemistry. Efforts to guide psilocybin from the state of prohibition into a form of therapy for neurological conditions have been underway for some years now, however. Increased interest in this compound in research and funding circles, alongside the ability to run studies on psilocybin without censure, inevitably leads to new discoveries. In today's open access paper, for example, researchers provide evidence to suggest that psilocybin acts to slow aging.
Mice given monthly doses of psilocybin starting in late life exhibit at 10-15% increase in overall median life span. The researchers conducted cells studies that suggest that psilocybin touches on a few well-studied pathways known to influence mammalian life span, and reduces the burden of cellular senescence. Treated versus untreated mice exhibited a similar body weight, so the animal study results don't appear to be the result of inadvertent calorie restriction. All in all, this is quite interesting, but a great deal more work is needed in order to dig into the mechanisms involved. Additionally, one should bear in mind that most mechanisms shown to slow aging have much larger effects in short-lived species than in long-lived species such as our own.
Psilocybin treatment extends cellular lifespan and improves survival of aged mice
To date, more than 150 clinical studies with psilocybin have been completed or are ongoing for various clinical indications, including psychiatric (anxiety, depression, addiction), neurodegenerative (Alzheimer's), pain, and more. Human studies have demonstrated that a single-dose of psilocybin can improve debilitating physical and psychological symptoms - with durable effects (up to ~5 years). Despite considerable clinical evidence supporting the therapeutic benefits of psilocybin, the molecular mechanisms responsible for these impacts remain enigmatic. Studies with psilocybin have predominantly focused on neurological impacts and/or behavioral outcomes; few studies have evaluated alternative or systemic mechanisms which may also contribute to its beneficial effects.
The "psilocybin-telomere hypothesis" postulates that psilocybin interventions may quantifiably impact telomere length, which offers a potential explanation for its efficacy across a wide range of clinical indications. This hypothesis is based on a large corpus of studies linking mental health to biological aging markers. However, no prior studies have experimentally investigated the direct impact of psilocybin on biological aging.
To evaluate the impact of psilocybin on cellular aging, we employed an in vitro model of replicative senescence. Cells were serially passaged with media containing psilocin or vehicle until they reached replicative senescence. Psilocin treatment (10 μM) resulted in a 29% extension of cellular lifespan. Results were more striking using a higher dose of psilocin in the same cell type (100 μM treatment led to a 57% extension in cellular lifespan). Results were more striking using a higher dose of psilocin in the same cell type (100 μM treatment led to a 57% extension in cellular lifespan. Telomere length was preserved in psilocin-treated age-matched cells. This data suggest that psilocin impacts signaling pathways associated with cellular aging.
To evaluate the impact of psilocybin on longevity in vivo, aged (19 month) female mice were treated with vehicle or psilocybin once/month for 10 months. Mice were initially given a low-dose (5 mg/kg) for the first treatment followed monthly high-dose (15 mg/kg) treatment for a total of 10 treatments. We elected to utilize 19-month old mice, which is roughly equivalent to 60-65 human years, in order to evaluate its therapeutic potential as a clinically-relevant anti-aging intervention. Notably, psilocybin treated mice demonstrated significantly higher survival (80%), compared to vehicle (50%). Although not quantitatively measured, psilocybin-treated mice exhibited phenotypic improvements in overall fur quality, including hair growth and reductions in white hair compared to vehicle-treated mice. In summary, we provide the first experimental evidence demonstrating that psilocybin treatment can enhance survival in aged mice.
View the full article at FightAging
