The U.S. Food and Drug Administration (FDA) approved the MACH-19 trials (the acronym for Mushrooms and Chinese Herbs for COVID-19) after researchers applied for approval in April.
The first two phase 1 randomized, double-blind, placebo-controlled trials have begun at UCLA and the University of California San Diego to treat COVID-19 patients quarantining at home with mild to moderate symptoms. A third trial is investigating the use of medicinal mushrooms as an adjuvant to COVID-19 vaccines.
The researchers have also launched a fourth trial testing the mushrooms against placebo as an adjunct to a COVID booster shot. It looks at the effect in people who have comorbidities that would reduce their vaccine response. An article in JAMA described the trials.
The two mushroom varieties being tested — turkey tail and agarikon — are available as over-the-counter supplements, according to the report. They are a separate class from hallucinogenic or “magic” mushrooms being tested for other uses in medicine.
“They are not even as psychoactive as a cup of tea,” Gordon Saxe, MD, PhD, MPH, principal investigator for the MACH-19 trials, told this news organization.
For each of the MACH-19 treatment trials, researchers plan to recruit 66 people who are quarantined at home with mild to moderate COVID-19 symptoms. Participants will be randomly assigned either to receive the mushroom combination, the Chinese herbs, or a placebo for 2 weeks, according to the JAMA paper.
D. Craig Hopp, PhD, deputy director of the division of extramural research at the National Center for Complementary and Integrative Health (NCCIH), told JAMA in an interview that he was “mildly concerned” about using mushrooms to treat people with active SARS-CoV-2 infection.
“We know that a cytokine storm poses the greatest risk of COVID mortality, not the virus itself,” Dr. Hopp said. “The danger is that an immune-stimulating agent like mushrooms might supercharge an individual’s immune response, leading to a cytokine storm.”
Stephen Wilson, PhD, an immunologist who consulted on the trials when he was chief operating officer of the La Jolla Institute for Immunology, says in the JAMA article that a cytokine storm is unlikely for these patients because the mushroom components “don’t mimic inflammatory cytokines.” Dr. Wilson is now chief innovations officer at Statera Biopharma.
“We think the mushrooms increase the number of immunologic opportunities to better see and respond to a specific threat. In the doses used, the mushrooms perturb the immune system in a good way but fall far short of driving hyper or sustained inflammation,” Dr. Wilson said.
Dr. Saxe said the FDA process was extensive and rigorous and FDA investigators also asked about potential cytokine storms before approving the trials. Cytokine storm is not an issue with a healthy response, Dr. Saxe pointed out. It’s a response that’s not balanced or modulated.
“Mushrooms are immunomodulatory,” he said. “In some ways they very specifically enhance immunity. In other ways they calm down overimmunity.” Dr. Saxe noted that they did a sentinel study for the storm potential “and we didn’t see any evidence for it.”