Are psychedelics a treatment for long COVID? Researchers probing this mystery don't have answers yet

Are psychedelics a treatment for long COVID? Researchers probing this mystery don't have answers yet.

By Rich Haridy, 22nd December 2023

Salon

It was March 2020 and Ash was the healthiest she’d been in 15 years. She had just started an exciting new job and COVID was still a nameless “novel coronavirus” mainly appearing on cruise ships. One evening, after getting home from the gym, Ash was suddenly struck with a wave of feverish delirium. She passed out and eventually came to a couple of hours later on the kitchen floor with her dog staring down at her.

The next two weeks were a blur, but eventually Ash started to feel better. About a month after the initial illness she had pretty much recovered. And then things started getting strange. She had this feeling her teeth were rotting. A painful pressure began building in her head.

“And it just took over my nerves,” Ash explained in a conversation with Salon. “About six weeks after COVID, I started losing the use of my hands.”

Everything from opening a ziploc bag to using scissors became profoundly difficult. Multiple GPs, dentists, clinical specialists and even a Chinese acupuncturist all had no idea what was going on. By the end of 2020 Ash had stopped working altogether. Alongside the neuropathic problems all the now common neurological long COVID issues had become entrenched: Brain fog, dissociation, extreme fatigue, memory troubles.

Alienated by mainstream medicine’s denial of her condition, Ash became her own guinea pig for the next couple of years. With a deep knowledge of science and a pool of friends in the entheogenic community Ash tried anything and everything to overcome her debilitating symptoms. Steroids, low-dose naltrexone, melatonin, lecithin, goldenseal, sceletium and a whole world of anti-inflammatory botanical ferments like kefir. Some helped temporarily, some didn’t help at all. Ash kept a detailed treatment diary, tracking the effects of everything she consumed.

“People were just sending me random obscure stuff. And I'm like, yep, that doesn't work. That works. That doesn't work. Oh, that doesn't work for more than three days.”

Then in early 2023, Ash tried something completely different. Something she described as a game-changer for her condition: A powerful hallucinogenic plant called iboga that originates from Africa. It's active ingredient is known as ibogaine and it's being explored for addiction treatment. It's not clear yet if it will really help — but even more questions remain about its potential for alleviating long COVID.

The serotonin hypothesis
It has been estimated that at least 65 million people have, or have had, long COVID. The illness encompasses hundreds of different symptoms and researchers are still struggling to find a way to easily define it. Some of the more universal symptoms — fatigue, post-exertional malaise, brain fog or memory loss — resemble what has previously been seen in other post-viral chronic illnesses, such as influenza or Epstein-Barr. But the sheer scale and heterogeneity of long COVID has made it challenging to study.

A number of different, compelling hypotheses have emerged to try and describe the pathology underlying long COVID. Some have suggested the condition is caused by a persistent viral reservoir of SARS-CoV-2 viruses, the microbes that cause COVID, hiding out somewhere in the body. Others argue the acute illness triggers a chain reaction of immune dysregulation, which ultimately leads to persistent chronic symptoms. It’s also been proposed that SARS-CoV-2 could alter one’s gut microbiome in ways that cause broader systemic inflammation. And then there’s all the ways COVID can impair normal functions of the brainstem and vagus nerve.

In October a study was published in the journal Cell that turned the world of long COVID research upside down. The study, led by a team from Perelman School of Medicine at the University of Pennsylvania, presented a kind of grand-unifying hypothesis attempting to tie together all prior ideas surrounding long COVID.

The researchers first reviewed metabolite profiles from several previously published long COVID studies. A pattern quickly emerged. Those patients with long-term symptoms consistently showed lower levels of circulating serotonin. In fact, the pattern was so reliable the researchers could distinguish long COVID patients from fully recovered patients just by measuring plasma serotonin levels.

Subsequent animal tests revealed SARS-CoV-2 infections did indeed reduce circulating serotonin — so the researchers then wondered how this was happening. Because the vast majority of serotonin in our body is produced in the gastrointestinal tract, all attention turned to the gut.

Across a series of impressive animal and organoid experiments the researchers discovered SARS-CoV-2 infections induced a kind of inflammatory response that disrupted the gut’s ability to absorb the amino acid tryptophan. Without an effective source of tryptophan the GI tract is unable to effectively produce serotonin, and this is potentially how serotonin depletion could be a defining trait of long COVID.

The final piece of the puzzle was understanding how this viral-induced serotonin depletion could lead to the neurocognitive problems commonly seen in long COVID. After all, serotonin produced in the gut does not cross the blood-brain barrier. While circulating serotonin levels looked to be directly depleted by viral inflammation, levels of serotonin in the brain remained unaffected.

Here the researchers turned to the vagus nerve — a crucial communication superhighway that travels from the brainstem to the gut. It was discovered serotonin depletion in the gut dampened vagal nerve signalling to the brain, specifically the hippocampus. When vagal nerve activity was reduced, hippocampal neuron activity declined, and this led to cognitive impairments such as memory problems.

The masterstroke in the new research was its exploration into how serotonin interacts with vagal nerve neurons. Elaborate animal and cell tests revealed serotonin signalling via 5HT3 receptors on vagal nerve neurons was responsible for this whole chain reaction. And, perhaps most significantly, when 5HT3 receptors on the vagal nerve were artificially stimulated with a drug, animals suffering long COVID-like impairments showed notable cognitive improvements.

What psychedelic compound is known to stimulate 5HT3 receptors? Ibogaine.

No magic bullet
Ash was fastidious about maintaining a treatment diary. “Start low, go slow”, she’d say in reference to bringing any new compound into her larger regime. In the merry-go-round of self-experiments she looked to a homegrown iboga tincture. Maybe, in low doses, it could help give her the motivation to exercise, she thought.

“Some people are extremely responsive to iboga,” Ash said. “It has adverse effects when I take a drop of the homemade tincture without diluting it down.”

These minidoses of iboga did help Ash start exercising regularly again. They weren’t traditional microdoses but something closer to a psychedelic dose. The psychological boost from this motivational bounce sent positive ripples throughout the rest of his life, but the iboga was no panacea. The brain fog and sense of disconnectedness was still devastating. Ash would regularly spend hours just staring into space.

Some time passed and a colleague offered Ash a magic mushroom extract. It was an unpleasant-tasting homemade concoction but being the psychonaut scientist she is, Ash gave it a shot. She took a minidose of the extract. The result was a deep healing sleep and Ash was excited. She took another small dose the very next day but it frustratingly did nothing.

She called her colleague with the news about the inconsistent results. “No, no, no,” the colleague said. “You can only take this once or twice a week.”

“So I eyeballed a dose twice a week,” Ash said. “And the mental clarity started to come back. And they kind of feed off each other. So if you've got enough physical energy to do something, then you can exercise, you can go outside, you can have a shower, wash your clothes, you can hang them up. And you can do that best if you've had a deep night's sleep, which I hadn't had for a long time.”

The magic mushroom extract helped Ash regain a substantial volume of mental clarity and connectedness. Like any chronic disease, improvements were gradual with frequent relapses. Two steps forward, one step back, as they say.

“[But there] was still a feeling of derealization, depersonalization,” Ash said. “Things aren't connected to each other, like being hungry and having food in the house are two completely separate issues. [And] it can take you an hour to connect.”

So Ash began experimenting with DMT. Just once or twice a month in a smokable blend commonly known as changa. Much like Ash’s prior psychedelic experiments, the DMT was imbibed in low doses.

“I wasn't out to discover the meaning of life. I just wanted to get far enough in that I could access reality on a step by step basis. You can't afford to be that far gone if you're not processing things properly. If you can't remember how to put a meal together, the last thing you want to be is crawling around the floor.”

The psilocybiome
“The gut microbial system, at the interface between the individual and the environment, is important for healthy homeostasis,” explained John Kelly, a psychiatrist and neuroscientist from Trinity College Dublin. “Gut microbes communicate with the brain via the gut-brain axis, including tryptophan-kynurenine, immune, hypothalamic pituitary adrenal axis, and vagus nerve pathways.”

Kelly has worked on several psychedelic therapy clinical trials, including last year’s landmark phase 2 human study exploring the effect of single psilocybin doses on treatment-resistant depression. However, one of his personal areas of interest looks to bring together two different nascent scientific fields — psychedelic medicine and the microbiome.

Continued here https://www.salon.com/2023/12/07/are-psychedelics-a-treatment-for-long-covid-researchers-probing-this-mystery-dont-have-answers-yet/