The Washington PostDemocracy Dies in Darkness

A new treatment may halt cluster headaches. But some say psychedelic drugs are the real answer.

(Jose David Morales for The Washington Post)
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Imagine a hot poker inside your brain, pressing hard on the back of your eye.

That’s how Bob Wold describes a “cluster headache”: a rare and poorly understood disorder he has suffered for the past 40 years.

The hour-long attacks — four or more a day — occur in “clusters” that drag on for up to three months. Wold has seen neurologists, chiropractors and acupuncturists, tried more than 70 drugs, had teeth removed and root canals, and considered brain surgery.

Nothing helped for the first 20 years, until the day the strait-laced, middle-aged construction contractor tried psilocybin — the active ingredient in “magic mushrooms” — an illegal drug he had previously thought “was just for people who fried their brains.” Ever since, Wold, now 65, has relied on periodic low doses of “’shrooms” to keep his excruciating headaches at bay.

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Cluster-headache sufferers are renowned among headache doctors for their desperation. "You'll eat shoe polish if you think it will help," one respondent wrote in a survey. Patients call the headaches more painful than childbirth, gunshot wounds and kidney stones. They also commit suicide at about three times the rate of the general population, University of West Georgia psychologist and researcher Larry Schor said.

“The pain is so intense that I’ve had some seemingly psychotic thoughts during attacks,” said Schor, who has suffered from the disorder since 1983. “Like maybe if I could take a pliers and start pulling out molars, or if I hammered in the smallest drill bit near my eye, that could relieve the pressure.”

On average cluster headache sufferers wait more than five years before they are properly diagnosed, after which prescribed drugs often fail and may also have serious side effects, including rebound headaches, which can worsen headache pain, due to medication overuse.

Yet “clusterheads,” as some patients call themselves, today have new reasons to take heart — because of the dogged efforts of Wold and Clusterbusters, an activist group he founded in 2002. The organization has a mailing list with more than 11,000 members and a website with advice on everything from suicide prevention to how to sign up for new clinical trials to how to get discounts on new medications to how to obtain, store and grow magic mushrooms for treatment.

Clusterbusters’ out-of-the-box efforts on behalf of its pain-wracked members are “the stuff of movies,” said Rutgers University sociologist Joanna Kempner, who is writing a book on the group. She compares the clusterheads to the 1980s HIV activists who also boldly experimented with unapproved drugs.

“Medicine has ignored these patients for so long that they live in a wild west of treatments,” Kempner said. “They saw the gap in research and did their own research on their own bodies.”

In the process, Clusterbusters has won the hearts — and help — of key allies in academia and the pharmaceutical industry.

Wold and colleagues helped pave the way for the Food and Drug Administration’s 2019 approval of Emgality, an injectable drug that is the first pharmaceutical treatment that can be prescribed to prevent cluster headaches.

The medication deploys a monoclonal antibody to block a protein — calcitonin gene-related peptide (CGRP) — that inflames nerve endings. Eli Lilly originally designed the medication for migraines but devised a higher dose for cluster headaches after interviewing Clusterbusters members, some of whom also participated in its clinical trial, Wold said.

The Clusterbusters’ website hails the Emgality advance as “historical,” but Wold is more excited about new research he hopes will soon confirm his belief that psychedelic drugs can shorten a cluster siege. Later this year, Yale University neurologist Emmanuelle Schindler expects to finish one of the first placebo-controlled studies involving a form of psilocybin to treat cluster headaches.

Schindler not only relied on Clusterbusters to recruit patients for her study but also used key parts of their dosing protocol. After years of self-experiments, many group members believe they have shortened, or “busted,” their clusters with three sub-hallucinogenic amounts of mushrooms spaced five days apart. Schindler is using synthetic psilocybin on a similar schedule, at just 10 milligrams per dose. She said she expects her results to show that “patients know a lot more about their condition and how to treat it than they’re usually given credit for.”

In the patient survey, conducted by Clusterbusters and involving 493 patients recruited from clinics and websites, more than 35 percent of respondents mentioned using “illicit substances.” Based on their responses, Schindler and colleagues suggested that psilocybin and LSD “were comparable to or more efficacious than most conventional medications.”

To cope with headaches in real time, many cluster headache patients use high-flow oxygen therapy, from tanks in their home. Small studies support its safety and effectiveness, and the Mayo Clinic, the American Headache Society and the American Migraine Foundation endorse its use for cluster headaches.

In 2010, however, the Centers for Medicare and Medicaid Services said the evidence for oxygen therapy was “promising” but insufficient to support reimbursement. Clusterbusters and other headache advocacy groups have been lobbying the CMS ever since. Wold said the federal agency’s refusal to cover oxygen for Medicare and Medicaid patients has had ripple effects, in that many private insurers are unwilling to reimburse it and doctors are less eager to prescribe it.

Yet he added that the CMS has promised to rule on the advocates’ latest appeal and that he hoped for a breakthrough.

“A lot of things are finally coming together, and it’s really an exciting time,” he said.

Up to 1 in 1,000 people, among them more than 300,000 Americans, endure cluster headaches. That’s close to the number of people with multiple sclerosis, a much more familiar disorder. Cluster headache cases include the British “Harry Potter” actor Daniel Radcliffe and former NFL defensive tackle Terrance “Pot Roast” Knighton, who played for the Washington football team in 2015.

Cluster headaches are sometimes confused with migraines, but there are some important differences. Migraines are about 120 times more common and almost always much less severe. Migraine pain can vary in location, but cluster headaches typically involve just one side of the head. And whereas migraines are three times as common in women as men, cluster headaches are as much as six times more common in men.

Brain scans suggest cluster headaches affect the hypothalamus, trigeminal nerve and autonomic nervous system. The hypothalamus controls your internal clock, so its role may help explain why the headaches usually strike at the same time of day, often as a nasty wake-up call. Scientists suspect the involvement of the hypothalamus may also explain why chronic cluster headache sufferers tend to have more frequent attacks when the days are longest, in July and August, and shortest, in January and February.

The pain itself is caused by dilated blood vessels pressing on the trigeminal nerve. But no one knows what causes the vessels to swell, and doctors are often helpless to offer safe, effective remedies.

Even as some patients hail Emgality, the new preventive drug, as “a godsend” and “life saver,” others complain of an array of downsides including weight gain, hair loss, faintness, joint pain, brain fog and limited benefit.

The psychedelics certainly also have drawbacks.

They don’t work for everyone, and even at low doses shouldn’t be used by people with problems including heart trouble, schizophrenia and bipolar disorder, Schindler said. The Mayo Clinic warns that LSD can cause “permanent mental changes in perception, rapid heart rate and high blood pressure, tremors, [and] flashbacks, a re-experience of the hallucination — even years later.”

Scientists call magic mushrooms some of the least-toxic and less-addictive recreational drugs, yet some users have reported frightening bad trips, panic, seizures and hospitalizations.

U.S. agencies classify psilocybin and LSD, along with marijuana and heroin, as Schedule I substances, considered to have “high potential for abuse, no currently accepted medical use . . . and a lack of accepted safety for use under medical supervision.”

Despite their risks, however, these drugs, when carefully administered, can help cluster headache patients when nothing else works, some experts said. “LSD and psilocybin are the best we have to offer, although legally we can’t offer them,” psychiatrist John Halpern said.

In 2004, Halpern, then working at Harvard University, was one of the nation’s few researchers studying the medical use of psychedelic drugs. Wold showed him and his colleagues a video of a Clusterbusters member who Wold says was involuntarily committed to a mental hospital because a doctor refused to believe he wasn’t faking his pain.

Halpern decided to help after learning that two staff workers at McLean Hospital, a Harvard-affiliated psychiatric facility, had committed suicide after suffering cluster headaches.

“I wanted to demonstrate that these aren’t drug-seeking individuals but construction workers, lawyers, people from all walks of life yet affiliated in the unluckiest guild of all,” he said. Two years later, he co-wrote a study in Neurology based on interviews with 53 cluster-headache patients who had used psychedelic drugs. Twenty-five of 48 who had used psilocybin and seven of eight who had used LSD reported that the drugs stopped a cluster in its tracks.

Wold’s odyssey in search of relief is familiar to many clusterheads. He was a healthy, 20-something professional, playing football with his young son when he suddenly felt as if his head might explode. The pain vanished after an hour but returned each day over the next few weeks.

For the next 20 years, Wold endured his cycles amid fruitless visits to doctors, until he happened to read an online message by a cluster-headache patient calling himself “Flash” who said he had found relief with LSD. Shortly thereafter, Wold and a few other people he knew began their private experiments with psilocybin.

Today, Wold keeps his headaches under control mainly with oxygen he pays for out-of-pocket and mushrooms he grows with spores ordered online. The Clusterbusters website describes a “medicinal dose” as one gram or less of dried mushrooms, amounting to half of a mild recreational dose. Wold said it feels like he has had a couple of beers.

He added that he is always happy to hear from others helped by Clusterbusters.

“We’re constantly getting thank-you notes from as far away as Romania, saying things like ‘I’ve been using psilocybin for 15 years and it saved my life,’ ” he said. “But we don’t really care what people find that’s going to help them. Whatever path they choose, we’re just trying to make it easier and safer.”

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The battle over psychedelic treatments

Researchers who study cluster headaches face daunting obstacles. The disorder is so rare that patients are hard to track down, particularly during an attack, while the pain may deter them from traveling to research sites.

Add psychedelic treatments to the mix and recruiting is even harder because many people are unwilling to try even low doses of these drugs. (In the lab, risks are minimized, Yale University neurologist Emmanuelle Schindler said, because patients are carefully screened, prepared and observed. If such treatments ever become legal, doctors presumably would take on these tasks.)

Yet another obstacle for researchers investigating psychedelics is the lack of ready money from pharmaceutical firms, funders of most modern drug studies.

“No one wants to pay for something you can grow in your basement,” one scientist said.

In recent years, however, private philanthropists have come to the rescue.

Schindler’s study of a form of psilocybin to treat cluster headache was largely supported by Carey Turnbull, a New York-based philanthropist and former financial services entrepreneur.

In an interview, Turnbull estimated that he has donated roughly $10 million for research into psychedelic drugs, calling them “the most astonishing probes of mood and cognition, which not only lead to mystical experiences but help alleviate terribly disabling neurological problems.”

Scientists running experiments with psychedelic drugs must register with the Drug Enforcement Administration, in addition to getting approval from the Food and Drug Administration. They’ve also faced considerable stigma, although that is starting to change.

Research on psilocybin and other hallucinogens is in a renaissance following a four-decade lull. Many among the 127 studies of psilocybin published in 2020 suggest promise in treating mental disorders, such as anxiety, depression and anorexia nervosa.

Laws are also starting to change.

The use, sale and possession of the drug remains illegal under federal law. Yet in recent years, the cities of Denver, Oakland and Santa Cruz, Calif., and Somerville, Mass., have decriminalized it. Last November, Oregon became the first state, by referendum, to make psilocybin legal for therapeutic use. Oregon has also decriminalized psilocybin and LSD, although LSD remains illegal under both federal and state law everywhere else.

Purveyors and consumers of “magic mushrooms” have found ways to get around the restrictions. Internet sites sell spores in syringes to grow at home. And in Oakland, the Zide Door Church of Entheogenic Plants allegedly sold magic mushrooms to thousands of “parishioners,” even after a police raid last September.