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The Psychedelic Solution

Drug taboos may block a potential treatment for cluster headaches, one of the most painful
conditions known.

By Russ Jusskalian | Newsweek Web Exclusive

Oct 14, 2009

"I had a gun sitting on top of the computer monitor," says Bill McConnell. "And I typed 'suicide' plus
'headache' into the search bar to leave an explanation for what I was about to do."

McConnell, who is 39-years-old and wears a blue and

white baseball cap, is commiserating with fellow
sufferers of cluster headaches—a condition some
doctors call the most painful known to medical
science, and one that numerous sufferers say nearly
drove them to take their own lives—in a room at the
Hyatt Regency O'Hare on the outskirts of Chicago. He,
like the rest, arrived a day early for the annual cluster
headache conference organized by a group called
Cluster Busters.

Though they look like ordinary people, and could

easily be your neighbors or colleagues, clusterheads,
as they jokingly refer to one another, have excruciating
and extraordinary life stories. Their condition is well
documented, poorly understood—and devastatingly painful. The medications they use to treat or at least
reduce the suffering are sometimes life-threatening, often physically damaging, and usually psychologically
and emotionally debilitating. ("The disease won't kill you," says McConnell, "but the treatments might.") As a
rule, they've gone mis- or undiagnosed for years, been called hysterical by general practitioners and
neurologists unfamiliar with the condition, and endured countless failed attempts at a cure. Now, thanks to
an active online community, and organizations like Cluster Busters, some sufferers are finding relief in an
unlikely treatment: the serotonergic psychedelic drugs LSD and psilocybin, two chemicals that helped fuel
the psychedelic revelry of the 1960s. Anecdotal reports of the drugs' effectiveness against cluster headaches
have even begun to attract the attention of major research universities.

Many cluster headache sufferers believe the term "headache" is a misnomer that doesn't convey the
sensation, or underlying cause, of an attack. McConnell says an attack is like having a hot ice pick pushed
into the corner of his eye and out through the back of his skull; others at the conference used the metaphor of
a demon crushing one's head and jamming his finger into one's eye socket—an order of magnitude worse

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than a severe migraine. "I would rather give birth without a painkiller than get 'hit,' " says Becky Ulissi,
referring to a cluster headache attack, of which she has up to eight each day.

The most common form of the condition is said to be episodic because sufferers are free from the headaches
for most of the year. But during two-to three-month episodes, the headaches hit up to 10 times per day, and
generally last anywhere from 45 minutes to three hours. Like clockwork, the episodes almost always start
and end around the same time each year, and the headaches often come at the same times each day.

Nobody is certain what actually causes cluster headaches. Theories have ranged from defects in the
trigeminal nerve, which branches out across the jaw, face, and forehead, to the irregular swelling of major
cranial veins. Recent fMRI studies suggest that these theories are incorrect, and instead point to structural
changes in the hypothamalus—the part of the brain responsible for circadian rhythms and other life-
sustaining functions. Traditional treatments focus on aborting a headache that has started by self-injecting
drugs like sumatriptan or dihydroergotamine, which both share chemical and biological similarities with the
neurotransmitter serotonin, or preventing attacks altogether with calcium channel blockers like verapamil
and steroids like prednisone. Pure oxygen is often effective at aborting an attack that has just started, but it
must be administered almost immediately, and requires the correct type of oxygen mask and tank to be
nearby. Unfortunately, long-term, heavy use of most traditional treatments can cause terrible side effects,
including poor circulation, organ fibrosis, blood pressure and cardiac disturbances, type 2 diabetes,
osteoperosis, anxiety, and other biological and psychological disorders.

Bob Wold, the president of Cluster Busters, has a story like many of the group's members. His headaches
went misdiagnosed for four years (he even had a few teeth pulled because his dentist suspected hidden
cavities were causing the pain—a common, and unproductive treatment among wrongly diagnosed cluster
headache sufferers). When he was properly diagnosed, none of the 75 medications he tried gave him lasting
relief. During a particularly painful episode in which he began to consider a radical, and mostly unproven,
surgical treatment that would have involved severing his trigeminal nerves and killing all sensation in his
face, Wold came across an online discussion about using LSD or psilocybin to treat cluster headaches. He
was hesitant, but 45 minutes after his first dose of psilocybin, he could tell that something remarkable was
happening: "My head was clearer than it had felt in 20 years."

But in his quest for a treatment, Wold had also broken the law. According to the Controlled Substances Act,
LSD and psilocybin fall under Schedule 1, the most restricted class of drugs in the United States. Unlike all
other drugs, those in Schedule 1 cannot be prescribed for any reason, and people caught in possession of
them are subject to serious jail time no matter their medical condition. (Cocaine and methamphetamine, by
comparison, can be prescribed by a doctor, and are listed in Schedule 2.) These drugs are so restricted by the
DEA that researchers at the country's top universities find it almost impossible to get the permission and
funding necessary to study the substances in humans. LSD, which is hard to make, is particularly difficult for
cluster headache sufferers to find. But a legal gray area—and a little help from mother nature—makes
psilocybin much more available. That's because while "magic mushrooms" contain psilocybin, their spores
do not—and the online trade in psychedelic mushroom spores is brisk, and legal, in most states. (Actually
growing those spores into mushrooms is considered the illegal manufacture of a controlled substance, so the
legal loophole only makes the mushrooms easier to find. Possession is still illegal.) In addition, the legality of
collecting wild-grown mushrooms containing psilocybin is murky.

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On the Cluster Busters Web site, the group warns that mushrooms can vary in potency, but 1 to 1.5 grams of
"cracker dry" P. cubensis mushrooms—a dose that Wold says is effective for many cluster headache
sufferers—produces a mild stoning effect and the sensation of slightly brighter colors. Wold told me it was
about as intoxicating as one or two glasses of wine. McConnell says that the wildest part of his first
experience was noticing that the lights on the Christmas tree seemed a little brighter and more saturated
than usual. At these levels, hallucinations and far-out magical thinking are avoided, though some cluster
headache sufferers require large enough amounts to induce a full psychedelic trip.

As I spent time at the Cluster Busters conference in Chicago, those suffering with this horrible condition kept
pulling me aside, wanting to share the same message: that all this talk about LSD and psilocybin was not
about getting high, but about treatment. They all told similar stories about being afraid of trying something
illegal for the first time; about painstakingly adjusting doses to find the right amount for relief while
preventing or at least limiting psychedelic experiences; and about the incredible relief of ending a cluster
period, or averting the next one from coming.

In the six years since he founded Cluster Busters, Wold has collected a cache of survey-based data on cluster
headache sufferers who have tried LSD or psilocybin. A normal approach to the novel treatment involves
taking one to three doses of either substance (Wold says LSD usually works as a single dose, whereas
psilocybin often requires three doses spread over a few days) to abort a cluster headache episode that has
already started, and twice-yearly maintenance doses to prevent new episodes from coming. (Users are left to
figure out what a "dose" actually amounts to, since tabs of LSD vary in strength, and some batches of
mushrooms have more psilocybin than others. And because they're both illegal, one doesn't get active dose
information and measurements from a dealer like one would from a registered pharmacist—though Wold
insists that both are usually taken in small enough amounts that the "doses" remain subpsychedelic.) Wold
says that he has documented more than 500 cases of people using this approach, and that roughly 75 percent
of those who have tried it have had significant reductions of their symptoms.

Self-reported treatments should always be viewed with skepticism, says Dr. John Halpern, director of the
Laboratory for Integrative Psychiatry, Division of Alcohol and Drug Abuse at McLean Hospital, and assistant
professor of psychiatry at Harvard Medical School, who attended the Cluster Busters conference. But the
strength of Wold's anecdotal evidence warranted further investigation. So in 2006, Halpern and colleagues
Andrew Sewell and Harrison Pope Jr. published an analysis of interviews with 53 subjects who had tried LSD
or psilocybin for their cluster headaches. What they found was astounding: 41 percent of those who took
psilocybin during a cluster episode (which can last for months) reported a decreased intensity or frequency of
headaches, and an additional 52 percent said the episode ended altogether; 95 percent of those who took
psilocybin between episodes said their next episode was delayed or totally averted. The study was
preliminary, unblinded, and uncontrolled, but convincing enough to prompt more methodical research.
McLean Hospital and Harvard Medical School are currently reviewing a prospective study using psilocybin
to treat cluster headaches in a controlled environment.

But Halpern was puzzled by something he saw in the survey data that members of Cluster Busters already
knew: many of those interviewed found relief from a nonpsychedelic doses. Was it possible that something
else was helping the cluster headaches, rather than the hallucinogenic experience itself? Could the two be
separated? After all, psilocybin and LSD are chemically similar to the neurotransmitter serotonin, which
plays an important role in the part of the brain linked to the headaches, and to some of the drugs used as
traditional treatments. With support from McLean Hospital, Harvard Medical School, and Medizinische

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Hoschule Hannover in Germany, Halpern and a team have begun a pilot study treating cluster headache
patients with BOL (also know as 2-Bromo-LSD), a substance almost identical to LSD yet not psychedelic.
Halpern presented a preliminary round of results earlier this year at the International Headache Congress,
and though only a few subjects have gone through the study, each as had a strong measure of improvement.

The early success of BOL gives sufferers hope for a legal, low-side-effect therapy. But it takes years to get a
new drug on the market, and there are no promises that BOL will continue to perform so well if it makes it to
later-stage clinical trials. In the meantime, some clusterheads—who euphemistically refer to their writhing,
rocking, hair-pulling, wall-punching, head-crushing, crying, screaming attacks as "dancing"—will do what
they have to do to relieve their pain. Even if it means breaking the law.

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