Everywhere you look-science magazines, medical journals, even Netflix and Hulu-you will see fungi sprouting. Mushrooms are having their moment in science, pop culture, and alt culture.

Now, with momentum from data about the controlled investigational use of lysergic acid diethylamide (LSD) and psilocybin in mental health treatment, scientists are studying the use of psychedelic drugs in the treatment of pain. A series of articles over the last year in Scientific American magazine describes the growing interest in research on psychedelics in mental health and, now, pain management.

Improvements in anxiety and post-traumatic stress disorder have been shown after medication with psychedelic substances. Based on anecdotal reports, drugs such as LSD or psilocybin might also decrease pain. Both LSD and psilocybin are illegal under federal law, although medical studies on them are now being officially cleared with increasing frequency.1,2

Various types of pain, notably cluster headaches, chronic pain, fibromyalgia, and even phantom limb pain, have been shown to benefit from these agents. In May of 2021, a New York City-based, multimillion-dollar psychedelic start-up called Mind Medicine (MindMed) announced Project Angie-a series of studies using LSD and an undisclosed drug to treat chronic pain.1

Dan Karlin, MindMed's chief medical officer, noted that science does not yet know how these drugs work on pain or any other illnesses, but that "... there is compelling preclinical evidence that they work ... via psychological mechanisms ... but also may have some direct effects on descending pain pathways."1

In July 2021, Tryp Therapeutics, a California-based psychedelic start-up, announced that it has partnered with the University of Michigan to study how these drugs might treat fibromyalgia.3 Tryp Therapeutics is exploring chronic pain relief using psilocybin and another psilocybin-based drug (TRP-8803).1

Tryp will conduct a phase 2a clinical trial with the Chronic Pain & Fatigue Research Center in the Department of Anesthesiology at the University of Michigan Medical School.

"The open-label Phase 2a clinical trial will evaluate the efficacy of TRYP-8802, an oral formulation of synthetic psilocybin, in tandem with psychotherapy for treating fibromyalgia. The treatment is designed to target nociplastic pain originating in the central nervous system through the neuroplasticity benefits of psilocybin," according to the release posted on Yahoo Finance.3

The principal investigator for the trial will be Kevin Boehnke, PhD, research investigator at the University of Michigan's Department of Anesthesiology.

"Tryp will seek to identify a response in patients to the treatment to inform the design of a Phase 2b clinical trial for fibromyalgia that will use the company's proprietary, psilocybin-based drug product, TRP-8803, that includes a novel formulation and unique method of delivery," according to the release.

Yale University announced a trial using psilocybin for cluster headaches. In August 2021, the Oxford, England-based pharmaceutical start-up Beckley Psytech raised $80 million for psychedelic research. Part of this will fund a phase 1b safety trial investigating low-dose psilocybin to treat short-lasting unilateral neuralgiform headache attack.1

All these studies are in very early stages. There are skeptics who argue that the evidence for psychedelics relieving pain is weak and that because these drugs are so powerful, they should be used only in psychotherapy-if at all. If psychedelics can relieve physical pain, it remains to be studied whether they are any better at it than other tools that are widely available.1

Any off-target effects of psychedelics need to be carefully monitored. Abuse liability needs to be very closely considered, making sure that there are not unexpected psychiatric effects, especially in populations that are at risk.

Popular media has been on the case, as well. On Netflix, the documentary "Fantastic Fungi" shows a growing number of scientists, physicians, and botanists studying therapeutic uses for psychedelic mushrooms and the environmental role played by fungi. It is an impressive and beautifully filmed documentary, featuring several scientists from Johns Hopkins University and other major research institutions.

On the more low-brow end, but probably more likely to be seen by regular people, the Hulu limited series, "Nine Perfect Strangers," is fiction, but an all-star cast ensures its popularity. It is based on the novel by best-selling author Liane Moriarty. The story centers on a spa owner using psychedelics to cure a character who became addicted to opioids after suffering a bone-shattering injury on the football field.

No, the spa owner, played by Nicole Kidman, is not a licensed health care practitioner, although she refers frequently to the "protocols." So bona fide pain practitioners should be prepared to cringe at the dicey protocols, which the character often overrides anyway.

But practitioners should also be prepared for patients to ask them about mushrooms and other psychedelics as therapy. The first thing to tell them is that it is, of course, illegal in the United States even for medical use, unless it is in a clinical trial.

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