Psychedelic therapy is imminent. Within six years, the market for this new wave of therapeutics is predicted to reach nearly $7 billion. With advocates and investors like Tim Ferriss leading the way, protocols for implementing psilocybin, MDMA, LSD, and ibogaine into treatments for depression, PTSD, addiction recovery, and existential distress are being crafted right now.
How will psychiatrists adapt to these new substances?
This is no easy question. Unlike antidepressants currently on the market, you cannot visit a psychiatrist or general practitioner and receive a script within 10 minutes—a longstanding issue in modern psychiatry, especially given that antidepressants don't work better than talk therapy (or as this meta-analysis shows, work better in conjunction with psychotherapy) and carry with them many physical risks. One of the most prominent side effects is weight gain, which has the potential to lead to a whole series of further physical and mental health problems.
Psychedelics are also not without risks. Early results from esketamine—this ketamine variant is not actually a psychedelic but has been generally lumped into the same category and provides a cautionary tale—have not been overly encouraging:
"Through an analysis of adverse events reported to the FDA, the authors found several adverse events related to the use of esketamine nasal spray, such as dissociation, sedation, feeling drunk, completed suicide, and especially suicidal and self-injurious ideation."
This isn't to write off the protocol, which has shown efficacy in trials (though not without issues either). Anecdotal reports have been positive for some depression sufferers. More importantly, the emerging ketamine clinics across North America feature robust protocols that run counter to many current antidepressant-driven psychiatric evaluations. We should continue to explore this line of therapeutics, just more carefully.
The future of psychedelic-assisted psychotherapy | Rick Doblin
The Multidisciplinary Association for Psychedelic Studies (MAPS) foresaw the possibility of psychedelic therapy decades ago. The organization's founder, Rick Doblin, argued against the scheduling of MDMA in the mid-80s. The group's training protocols for MDMA, ayahuasca, ibogaine, and LSD are holistic and include screening sessions, pre-treatment meetings, day-long sessions, and post-treatment integration.
You cannot ingest psychedelics and go about your day. Unlike SSRIs and SNRIs, they don't take weeks for you to feel the effects. This is an entirely different model than current psychiatry protocols. If psychedelic therapy is going to be integrated into psychiatry, mental health professionals need training. They'll have to adapt. Cutting corners will be impossible.
Besides overcoming the hurdle of federal regulations (which is quickly happening), psychedelics should be subject to Risk Evaluation and Mitigation Strategies (REMS), writes Paul Tulls in Nature. This means these novel therapies will be administered according to current FDA guidelines.
"The effect would be to bundle the delivery of the drug with the therapy component, and potentially certify practitioners. A source working on one of the trials says that discussions are under way with the FDA over whether therapists who administer the drugs ought to be trained, what that training might involve and whether therapist certification should be required."
Psilocybin-containing mushroom.
Credit: Microgen / Adobe Stock
This will not be without its challenges. As Tullis writes, some therapists have been skirting federal law by offering psychedelic therapy for 30 years, reminiscent of LSD sessions in the 1950s and MDMA therapy in the 1970s. In fact, LSD was subjected to over 1,000 studies before being criminalized, though it's admittedly hard to offer a placebo. (Niacin has worked in some trials.) The comprehensive protocols being developed now have early pioneers to thank.
Psychedelics are also entering an industry with standard practices. Some therapists are likely to remain skeptical; others might not train properly before administering the drugs, which could create problems for the entire industry should some patients experience adverse effects. Psychotherapy will always be necessary before and after administration. In an industry where many are accustomed to writing scripts, not providing in-depth existential explorations with their patients—and many patients are accustomed to quick visits that result in refills—a giant learning curve is necessary.
While many are hopeful that psychedelic therapy will have broad appeal, the more likely result is a slow integration with specialized clinics (such as with ketamine today). There will undoubtedly be players with no history of psychedelics involved only for economic gain; we're already seeing it with tens of millions of dollars pouring into companies. The competing forces of revenue maximization and psychedelic ritual are likely to create friction.
Regardless, this emerging industry requires funding to get off the ground. We just need to temper expectations with the real-world consequences of the psychedelic model—a hard sell in a world accustomed to quick returns. And we'll need therapists willing to explore uncharted territory on its own terrain, not the ground they're accustomed to walking on.
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Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
It's not your imagination, it turns out. Stress can turn a person's hair gray. It's said that if you look at before and after pictures of any eight-year U.S. president the impact of the office on hair color is clear, though in fairness, it may be that candidates dye their hair and then at some point stop doing so. Nonetheless, scientists from Harvard have not only verified the conventional wisdom on our graying noggins, but have also figured out why stress is so brutal to our follicular pigmentation.
The new research from Harvard scientists is published in the journal Nature.
An unusual chance to see stress at work
Image source: Ververidis Vasilis/Evan El-Amin/Vacclav/Shutterstock/Big Think
Senior author of the study Ya-Chieh Hsu, professor of Stem Cell and Regenerative Biology at Harvard, explains what prompted her research:
"Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hair — the only tissues we can see from the outside. We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start with — and besides, we were genuinely curious to see if stress indeed leads to hair graying."
It turns out that stress activates nerves associated with our basic fight-or-flight system, and these nerves permanently damage pigment-regenerating melanocyte stem cells in hair follicles, causing them to cease production of melanin that normal provides color to hair follicles.
Hsu's team studied the issue using mice, and was somewhat stunned at their findings. "When we started to study this, I expected that stress was bad for the body — but the detrimental impact of stress that we discovered was beyond what I imagined," recalls Hsu.
The scientists stressed the mice using a combination of three methods:
- restraint stress — forcibly immobilizing the subject
- chronic unpredictable stress — a "random, intermittent, and unpredictable exposure to a variety of stressors"
- injections of resiniferatoxin (RTX).
Who’s in charge here?
Image source: Helga Lei/Shutterstock
Hsu and her colleagues first suspected an immune system reaction was at the root of graying hairs only to discover that mice without immune systems still turned gray in response to stressors. The next suspect was cortisol produced by the adrenal glands — however, this proved not to be so. "Stress always elevates levels of the hormone cortisol in the body," says Jsu, "so we thought that cortisol might play a role. But surprisingly, when we removed the adrenal gland from the mice so that they couldn't produce cortisol-like hormones, their hair still turned gray under stress."
It’s the sympathetic nervous system
Image source: Judy Blomquist/Harvard University
Finally, the researchers investigate the possibility that the system responding to stressors was the mice's sympathetic nervous systems, the part of the nervous system that kicks into action with the fight-or-flight impulse. The sympathetic nervous system is a vast network of nerves that connects, among other places, to hair follicles in the skin. In response to stress, the system sends a rush of the chemical norepinephrine to the follicles' melanocyte stem cell, causing them to quickly burn through and deplete their stores of pigment.
Say Hsu, "After just a few days, all of the pigment-regenerating stem cells were lost. Once they're gone, you can't regenerate pigments anymore. The damage is permanent." Great for survival, not so good for hair color.
A big hint of a much greater insight
Sympathetic system nerves are magenta above. Melanocyte stem cells are yellow.
Image source: Hsu Laboratory, Harvard University
"Acute stress," says lead author of the study Bing Zhang, "particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animal's survival. But in this case, acute stress causes permanent depletion of stem cells."
The research, done in collaboration with other Harvard researchers, presents a new appreciation of the effect the sympathetic system can have on the body's cells during stress.
One of these collaborators, Harvard immunologist Isaac Chu, notes, "We know that peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells. With this study, we now know that neurons can control stem cells and their function, and can explain how they interact at the cellular and molecular levels to link stress with hair graying."
Given this finding regarding the direct impact of stress on follicular stem cells, the question of what it else it may affect becomes an obvious one. As Hsu sums it up, "By understanding precisely how stress affects stem cells that regenerate pigment, we've laid the groundwork for understanding how stress affects other tissues and organs in the body."
This importance of the study therefore goes way beyond graying heads. "Understanding how our tissues change under stress is the first critical step," says Hsu, "toward eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area."
Are modern societies trying too hard to be clean, at the detriment to public health? Scientists discovered that a microorganism living in dirt can actually be good for us, potentially helping the body to fight off stress. Harnessing its powers can lead to a "stress vaccine".
Researchers at the University of Colorado Boulder found that the fatty 10(Z)-hexadecenoic acid from the soil-residing bacterium Mycobacterium vaccae aids immune cells in blocking pathways that increase inflammation and the ability to combat stress.
The study's senior author and Integrative Physiology Professor Christopher Lowry described this fat as "one of the main ingredients" in the "special sauce" that causes the beneficial effects of the bacterium.
The finding goes hand in hand with the "hygiene hypothesis," initially proposed in 1989 by the British scientist David Strachan. He maintained that our generally sterile modern world prevents children from being exposed to certain microorganisms, resulting in compromised immune systems and greater incidences of asthma and allergies.
Contemporary research fine-tuned the hypothesis, finding that not interacting with so-called "old friends" or helpful microbes in the soil and the environment, rather than the ones that cause illnesses, is what's detrimental. In particular, our mental health could be at stake.
"The idea is that as humans have moved away from farms and an agricultural or hunter-gatherer existence into cities, we have lost contact with organisms that served to regulate our immune system and suppress inappropriate inflammation," explained Lowry. "That has put us at higher risk for inflammatory disease and stress-related psychiatric disorders."
Christopher Lowry
University of Colorado Boulder
This is not the first study on the subject from Lowry, who published previous work showing the connection between being exposed to healthy bacteria and mental health. He found that being raised with animals and dust in a rural environment helps children develop more stress-proof immune systems. Such kids were also likely to be less at risk for mental illnesses than people living in the city without pets.
Lowry's other work also pointed out that the soil-based bacterium Mycobacterium vaccae acts like an antidepressant when injected into rodents. It alters their behavior and has lasting anti-inflammatory effects on the brain, according to the press release from the University of Colorado Boulder. Prolonged inflammation can lead to such stress-related disorders as PTSD.
The new study from Lowry and his team identified why that worked by pinpointing the specific fatty acid responsible. They showed that when the 10(Z)-hexadecenoic acid gets into cells, it works like a lock, attaching itself to the peroxisome proliferator-activated receptor (PPAR). This allows it to block a number of key pathways responsible for inflammation. Pre-treating the cells with the acid (or lipid) made them withstand inflammation better.
Lowry thinks this understanding can lead to creating a "stress vaccine" that can be given to people in high-stress jobs, like first responders or soldiers. The vaccine can prevent the psychological effects of stress.
What's more, this friendly bacterium is not the only potentially helpful organism we can find in soil.
"This is just one strain of one species of one type of bacterium that is found in the soil but there are millions of other strains in soils," said Lowry. "We are just beginning to see the tip of the iceberg in terms of identifying the mechanisms through which they have evolved to keep us healthy. It should inspire awe in all of us."
Check out the study published in the journal Psychopharmacology.
