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  1. Terrapinzflyer
    The Psychedelic Solution
    Drug taboos may block a potential treatment for cluster headaches, one of the most painful conditions known.

    "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 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.

    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 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.

    By Russ Jusskalian



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