HOW PSILOCYBIN, THE PSYCHEDELIC IN MUSHROOMS, REWIRES THE BRAIN TO EASE DEPRESSION, ANXIETY AND MORE
“Let’s be adults about this. These are no longer ‘shrooms.’ These are no longer party drugs for young people,” Stamets told CNN. “Psilocybin mushrooms are nonaddictive, life-changing substances.”
Small clinical trials have shown that one or two doses of psilocybin, given in a therapeutic setting, can make dramatic and long-lasting changes in people suffering from treatment-resistant major depressive disorder, which typically does not respond to traditional antidepressants.
Based on this research, the US Food and Drug Administration has described psilocybin as a breakthrough medicine, “which is phenomenal,” Stamets said.
Psilocybin, which the intestines convert into psilocin, a chemical with psychoactive properties, is also showing promise in combating cluster headaches, anxiety, anorexia, obsessive-compulsive disorder and various forms of substance abuse.
“The data are strong from depression to PTSD to cluster headaches, which is one of the most painful conditions I’m aware of,” said neurologist Richard Isaacson, director of the Alzheimer’s Prevention Clinic in the Center for Brain Health at Florida Atlantic University.
“I’m excited about the future of psychedelics because of the relatively good safety profile and because these agents can now be studied in rigorous double-blinded clinical trials,” Isaacson said. “Then we can move from anecdotal reports of ‘I tripped on this and felt better’ to ‘Try this and you will be statistically, significantly better.’ “
WHAT ABOUT MICRODOSING?
Stamets, who over the last 40 years has discovered four new species of psychedelic mushrooms and written seven books on the topic, said he believes microdosing is a solution. That’s the practice of taking tiny amounts of a psilocybin mushroom several times a week to maintain brain health and a creative perspective on life.
A typical microdose is 0.1 to 0.3 grams of dried psilocybin mushrooms, as compared with the 25-milligram pill of psilocybin that creates the full-blown psychedelic experience.
Stamets practices microdosing and has focused on a process called “stacking” in which a microdose of mushrooms is taken with additional substances believed to boost the fungi’s benefits. His famous “Stamets Stack” includes niacin, or vitamin B3, and the mycelium, or rootlike structure, of an unusual mushroom called Lion’s mane.
Surveys of microdosers obtained on his website have shown significantly positive benefits from the practice of taking small doses.
“These are self-reported citizen scientists’ projects, and we have now around 14,000 people in our app where you register yourself and report your microdose,” Stamets told an audience at the 2022 Life Itself conference, a health and wellness event presented in partnership with CNN.
“I’m going to say something provocative, but I believe it to my core: Psilocybin makes nicer people,” Stamets told the audience. “Psilocybin will make us more intelligent and better citizens.”
Scientific studies so far have failed to find any benefits from microdosing, leaving many researchers skeptical. “People like being on it, but that doesn’t validate the claims of microdosing,” Johnson said. “People like being on a little bit of cocaine, too.”
Experimental psychologist Harriet de Wit, a professor of psychiatry and behavioral science at the University of Chicago, was excited to study microdosing because it solves a key problem of scientific research in the field – it’s hard to blind people to what they are taking if they begin to trip. Microdosing solves that problem because people don’t feel an effect from the tiny dose.
De Wit specializes in determining whether a drug’s impact is due to the drug or what scientists call the “placebo effect,” a positive expectation that can cause improvement without the drug.
She published a study in 2022 that mimicked real-world microdosing of LSD, except neither the participants nor researchers knew what was in the pills the subjects took.
“We measured all kinds of different behavioral and psychological responses, and the only thing we saw is that LSD at very low doses produced some stimulant-like effects at first, which then faded,” de Wit said.
The placebo effect is powerful, she added, which might explain why the few additional studies done on it have also failed to find any positive results.
“I suspect microdosing may have an effect on mood, and over time it might build up resilience or improve well-being,” Nutt said. “But I don’t think it will rapidly fragment depression like macrodosing and going on a trip.”
ARE SHROOMS GOOD FOR YOU?
There’s more. Researchers say psychedelic drugs help neurons in the brain sprout new dendrites, which look like branches on a tree, to increase communication between cells.
“These drugs can increase neuronal outgrowth, they can increase this branching of neurons, they can increase synapses. That’s called neuroplasticity,” Nutt said.
That’s different from neurogenesis, which is the development of brand-new brain cells, typically from stem cells in the body. The growth of dendrites helps build and then solidify new circuits in the brain, allowing us to, for example, lay down more positive pathways as we practice gratitude.
“Now our current thinking is this neuronal outgrowth probably doesn’t contribute to the increased connectivity in the brain, but it almost certainly helps people who have insights into their depression while on psilocybin maintain those insights,” Nutt said.
“You shake up the brain, you see things in a more positive way, and then you lay down those positive circuits with the neuroplasticity,” he added. “It’s a double whammy.”
Interestingly, SSRIs also increase neuroplasticity, a fact that science has known for some time. But in a 2022 double-blind phase 2 randomized controlled trial comparing psilocybin to escitalopram, a traditional SSRI, Nutt found the latter didn’t spark the same magic.
“The SSRI did not increase brain connectivity, and it actually did not improve well-being as much as psilocybin,” Nutt said. “Now for the first time you’ve got the brain science lining up with what patients say after a trip: ‘I feel more connected. I can think more freely. I can escape from negative thoughts, and I don’t get trapped in them.’ “
Taking a psychedelic doesn’t work for everyone, Johnson stressed, “but when it works really well it’s like, ‘Oh my god, it’s a cure for PTSD or for depression.’ If people really have changed the way their brain is automatically hardwired to respond to triggers for anxiety, depression, smoking — that’s a real thing.”
How long do results last? In studies where patients were given just one dose of a psychedelic “a couple of people were better eight years later, but for the majority of those with chronic depression it creeps back after four or five months,” Nutt said.
“What we do with those people is unknown,” he added. “One possibility is to give another dose of the psychedelic — we don’t know if that would work or not, but it might. Or we could put them on an SSRI as soon as they’ve got their mood improved and see if that can hold the depression at bay.
“There are all sorts of ways we could try to address that question,” Nutt said, “but we just don’t know the answer yet.”
Additionally
Beneficial effects of microdosing may include:
Heightened focus, creativity, productivity, and energy.
Decreased anxiety, depression, or stress.
Less social anxiety.
Reduced menstrual pain.
Emotional openness.
Increased spiritual awareness.
Reduced cravings for addictive substances.
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