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Letting the Sun Shine In?

“Let the sun shine, let the sun shine in, the sun shine in,

Let the sun shine, let the sun shine in, the sun shine in”

From “The Age of Aquarius” by the 5th Dimension.

Yes – psychedelics, of all things, are now being trialed in fibromyalgia (FM) and chronic pain. If taking psychedelics to improve your FM sounds fanciful, weird, or fringy, think again. While it’s not clear these drugs may help, they are being taken seriously by academia. Some researchers even believe psychedelics like psilocybin and NMDA are just a few years away from FDA approval. Let the sun shine in, indeed.

In fact, as Michael Pollan points out in his fascinating book, “How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence“, studying psilocybin and other psychedelics is not a new thing at all. More than a thousand papers were published in scientific journals before the backlash to Timothy Leary, the Sixties, and the CIA’s shenanigans essentially drove the drug underground.

The psychedelic boom all started, oddly enough, in a scientific setting in the late 1930s when a young Swiss chemist employed by Sandoz laboratories was tasked with plowing through the plant compounds found in a fungus called ergot. Ergot is a fungus that infects grains which can cause some people to appear to go mad, but it was ergot’s use as a labor inducer and bleeding stauncher that had captured Sandoz’s attention.

LSD-brain

The discoverer of LSD – a chemist named Albert Hoffman – described seeing the world as if newly created. (Image by Gordon Johnson of Pixabay)

Hoffman’s efforts were to no avail until – and here’s where it takes gets a little woo-woo – five years later Hoffman, uncharacteristically, decided to return to a compound he’d discarded. Later stating that there was something he liked about its chemical structure, Hoffman returned to lysergic acid diethylamide (LSD-25) and retested it.

Hoffman knew that ergot could make people go a little crazy, so he was careful, but he must have slipped up somewhere and absorbed some LSD through his skin because he started feeling some unusual sensations which quickly evolved into a full-blown trip consisting of “fantastic pictures, (and an) extraordinary kaleidoscopic play of colors”.

Intrigued, Hoffman returned a couple of days later to conduct a little experiment – on himself – something that researchers often did back then. After taking what he thought was a minuscule dose of the drug (.25 mg in a glass of water) he descended into the first bad LSD trip ever recorded. As he watched familiar objects assume “grotesque forms”, the outer world “disintegrate” and his ego wash away, Hoffman worried that he was going insane. When he came down, though, he entered into a different world where “everything glistened and sparkled in a fresh light”. The world was, he said, “as if newly created”.

Hoffman was changed forever by his experience. The hard-bitten chemist became, as Pollan notes, “something of a mystic, preaching a gospel of spiritual renewal and reconnection with nature”.

Sandoz saw a different opportunity entirely. Noting how incredibly potent the drug was, Sandoz provided LSD (they called it “Delysid) free of charge from around 1950 to 1966 to thousands of research efforts at institutions like Harvard, Cambridge, and UCLA. Studies touted LSD’s effectiveness at relieving depression, alcoholism, anxiety, and obsessive-compulsive disorder. By the mid-sixties, LSD was being commonly used by psychiatrists in LA and London.

Articles appearing in Time and Life magazines in the 1950s made psychedelics a mainstream topic. It was a J.P. Morgan Vice President, no less, named R. Gordon Wasson, whose 1957 Life magazine article, “Seeking the Magic Mushroom“, ignited the masses.  Wasson’s described experiencing harmonious visions in “vivid color” “that seemed more real to me than anything I had ever seen with my own eyes” during his trip on mushrooms in the mountains of Oaxaca, Mexico. (Albert Hoffman would later isolate the two psychoactive compounds responsible for Wasson’s trip – psilocybin and psilocin.)

The psychedelic/academia connection got snipped in 1966 when Sandoz – startled at the controversy the drug had elicited – withdrew the drug from circulation. After the US government banned LSD in 1967, and declared it a schedule I substance “with a high potential for abuse and no recognized medical use” in 1970, the drug went underground. Funding by the National Institutes of Health continued until the late 1970s, though, until the backlash from a Rockefeller Commission report which found that the CIA had been dosing both employees and civilians without their permission, shut down academic psychedelic research for decades.

A revival began in 1998 when Roland Griffiths at Johns Hopkins University was able to wend a psilocybin grant application past a boatload of concerned reviewers. Since then, Griffiths has co-authored dozens of studies on psychedelics and runs the Johns Hopkins Center for Psychedelic Research that’s staffed by about a dozen PhDs and MDs. In 2008 guidelines for safely studying hallucinogens were published. Since then, psilocybin and psychedelic research has gone quietly mainstream with hundreds of studies published this year.

Besides attempting to figure out how infinitesimally small amounts of a substance could have such mind-altering effects, most clinical trials are focused on attempts to relieve diseases like depression, anxiety, alcoholism, and PTSD. Some, however, are reaching further and attempting to alleviate symptoms in diseases like post-concussion syndrome, Parkinson’s Disease, cluster headache, and fibromyalgia.

A Chronic Pain Connection?

The fact that minute amounts of these drugs can produce such potent effects has sparked much interest in using them to understand how the brain works. We now know that these drugs and serotonin all have a tryptamine structure and that the compounds attach to serotonin receptors – particularly the 5HT-2A receptor. In fact, psilocybin attaches more effectively to the body’s 5HT-2A receptor than serotonin does.

Your brain on psilocybin

A more connected brain on psilocybin. (From Wikimedia Commons).

We also know psychedelics affect the serotonergic neurons that impact parts of the brain that are involved in pain perception. Some believe that next-generation serotonergic drugs will be helpful in pain disorders like FM where the descending serotonergic inhibitory pain pathways are not working well.

In “Chronic pain and psychedelics: a review and proposed mechanism of action“, Joel Castellanos, a Scripps anesthesiologist, explained how psychedelics might be able to bring relief to pain sufferers, as well. One idea is that small doses of psilocybin might function as potent anti-inflammatories for the brain.

It’s a possible increase in neural plasticity, though, that psilocybin and similar drugs may bring which gets the most attention. Studies that characterize the transition from acute to chronic pain suggest that as neural plasticity declines some brain pathways kind of get stuck in a pain mode. Studies have found, for instance, altered activity in pain-associated networks involving the insula and anterior cingulate cortex in both fibromyalgia and ME/CFS.

Moving Beyond Your Past? Turning off the Default Mode Network.

Default Mode Network Connectivity (cropped)

The default mode network keeps a clamp on the brain’s activities. Drugs like psilocybin temporarily release that clamp allowing new connections to be made. (Image from Wikimedia Commons.)

The default mode network (DMN) in the brain, though, may be the key. Several studies have suggested that something has gone wrong with the DMN in ME/CFS and fibromyalgia.

Studies have revealed that psychedelics temporarily break the hold the DMN has on the brain. The rumination center of the brain, the DMN lights up when our attention wanes. It also orchestrates and organizes brain functioning, and, perhaps most importantly for people with FM and ME/CFS or any difficult chronic disease, the DMN uses our past experiences to chart out our futures.

The ability of psychedelics to release the hold the DMN has on the brain may be what allows for the extraordinary experience that can occur. At the same time these drugs are reducing blood flows to the DMN they’re increasing blood flows to other regions of the brain. Meditation, interestingly, produces a similar reduction in DMN activity.

Because psychedelics have the potential to, as one researcher rather colorfully put it, ‘disintegrate’ existing brain networks and then open up new, more productive ones, they may be able to help get chronic pain patients’ brains out of their pain ruts.  Another researcher proposed that psychedelics may provide the opportunity for brain network “resetting” and another suggested they may be able “lubricate cognition” in ways that enhance well-being.

Psychedelics, then, might be one way of increasing neuroplasticity. Neuroplasticity’s core thesis is that neurons that wire together fire together. The more pain neurons fire together, the stronger the connections they produce, and the more pain a person experiences. The process can be visualized as a river carving out deeper and deeper channels that take up more and more of the brain’s resources which become harder and harder to alter over time.

Not only does that process cause one’s pain to intensify, but it can cause pain to spread. Arthritis patients who later come down with fibromyalgia may be suffering from an amplification of their pain-producing brain networks.

Rewiring the Brain to Get Out of Pain: the Moskowitz Approach

By breaking down old and unhealthy brain pathways and opening up new connections, psychedelics may be able to do more quickly what neural plasticity programs like the Amygdala and Insula Retraining Program, Dynamic Neural Retraining System, and Dr. Moskowitz’s approach accomplish.

In fact, one wonders if psychedelics done judiciously could boost the efficacy of these neural plasticity programs and vice versa. Engaging in neuroplasticity programs and practices like meditation might even prove critical in maintaining the new connections formed during the psychedelic experience. Meditation practices are often used in psychedelic retreats and studies to amplify and support the psychedelic experience.

The Future

The impact psychedelics may have on pain is mostly speculation at this point. Study evidence dating back to the 1950s suggests that psychedelics may be quite helpful in pain, but only a few modern studies have been done.

Tryp therapeutics

Tryp therapeutics is funding a psilocybin trial in fibromyalgia.

Several chronic pain psychedelic studies are, however, underway. (Note that these studies use standardized techniques to ensure that a safe experience occurs.) Tryp Therapeutics is partnering with one of the largest FM research centers in the country Daniel Clauw’s Chronic Pain & Fatigue Research Center in a synthetic psilocybin study.

Stating that “existing treatment options for fibromyalgia are often ineffective and show significant side effects,” Clauw well knows how ineffective the current treatment options are for FM. A longtime FM researcher, Clauw has stated that he would welcome cannabis studies if the federal government wouldn’t put up so many roadblocks. Now, his Center has signed on to a psilocybin study. Find out more about the study here.

Another study at the University of Alabama at Birmingham will use .36 mg/kg of psilocybin in the expectation that the participants will have “a full mystical-type experience”. (A series of preparatory sessions will ready the participants for their experience). Johannes Ramaekers of Maastricht University is also reportedly developing a fibromyalgia psychedelic pain study.

A Stanford Neuroscience Newsletter reported that a psychedelic-inspired start-up called Mind Medicine (MindMed) has begun “Project Angie” which will involve a series of studies using LSD (and an undisclosed drug) to treat pain. The company stated that “preliminary evidence” suggested that psychedelics may offer “an entirely novel mechanism of action for treating pain”.

Yale University is also trialing psilocybin in cluster headaches – one of the most painful diseases known. These headaches have been described as being more painful than childbirth, getting shot, or passing a kidney stone. Yale reportedly got interested in psilocybin after a cluster headache sufferer at the end of his rope found relief when microdosing with psilocybin. Other cluster headache patients have found microdosing helpful as well.

Outside Academia

Of course, people outside academia are experimenting…

Microdosing – No Tripping Required

If a full-blown, mind-altering experience isn’t your cup of tea, microdosing might be a possibility. Microdosing involves using doses of psilocybin low enough to increase one’s awareness, alertness, energy, and calmness but without causing one to trip.

Microdosing apparently took off a couple of years ago when Tim Ferris, the author of The Four Hour Workweek, interviewed Dr. James Fadiman, Ph.D. on his podcast. (Check out the podcast here – Episode #66: The Psychedelic Explorer’s Guide- Risks, Micro-Dosing, Ibogaine, and More).

Fadiman is the author of the 2011 book, “The Psychedelic Explorer’s Guide: Safe, Therapeutic, and Sacred Journeys“. Fadiman apparently uses microdosing for “problem-solving purposes”, but others use it to feel more relaxed, to be more “in the flow”, to increase their alertness and energy levels, etc. A microdosing study at Imperial College, London, is reportedly underway.

A recent study found that LSD given at doses below those which produce profound mind-altering effects reduced pain levels to a similar extent as drugs like oxycontin. A 2019 review, “Microdosing psychedelics: More questions than answers? An overview and suggestions for future research“, though, emphasized how little we know about the health effects of microdosing.

  • Check out microdosing websites here, here, and here.
  • You also might want to check out Nicole Kidman in the Nine Perfect Strangers series for a fictionalized account of a Wellness Institute called Tranquillum that employed psychedelics (without informing its clients first).

Psychedelic Retreats

Other groups offer curated psychedelic experiences at retreats. Eleusinia, for instance, which caters to those with painful illnesses, uses virtual reality headsets and meditation in its four-day “psilo retreats” off the coast of Mexico. At the end of the course, the participants are given instructions on how to grow their own mushrooms. Many others are available.

Find out more about psychedelic retreats here and here.

Conclusion

It will take some time to know if psychedelics like psilocybin offer a novel and new approach to chronic pain conditions like fibromyalgia and ME/CFS. Much remains to be learned about dosing, long-term effects, etc., but the research community is engaged and studies are underway. Some researchers believe it’s just a matter of time before some psychedelics get FDA approval. Let the sunshine in, indeed.

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