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Far out. Analog of LSD (inset) could prove to be a powerful treatment for cluster headaches.

LSD Alleviates 'Suicide Headaches'

Kai is a contributing correspondent for Science magazine based in Berlin, Germany.

BERLIN—Patients suffering from the agony of cluster headaches will take anything to dull the pain, even LSD, it turns out. Results from a pilot study presented here on Saturday at the International Headache Congress reveal that six patients treated with 2-bromo-LSD, a nonhallucinogenic analog of LSD, showed a significant reduction in cluster headaches per day; some were free of the attacks for weeks or months.

"Some of these patients are still reporting significant relief more than a year after they were treated with the compound," says John Halpern, a psychiatrist at Harvard Medical School in Boston and one of the investigators involved in the study. "Nobody has ever reported these kinds of results."

Cluster headaches, sometimes referred to as "suicide headaches" because of the almost unbearable pain they cause sufferers, usually involve just one side of the face; patients often liken the pain to someone trying to pull their eye out for hours. They can occur in bouts lasting many weeks, with several attacks a day.

"What causes these attacks is still not clear," says Peter Goadsby, a headache expert at the University of California, San Francisco, who is not connected with the research. But recent studies suggest that changes in the structure of the hypothalamus are involved. Because that part of the brain is responsible for, among other things, circadian rhythms, the daily cycle of our body that dictates when we sleep but also regulates body temperature and blood pressure, it could explain the periodicity of attacks and why they seem to occur particularly often around the solstices.

Although there is no cure, patients can sometimes cure the headache by inhaling pure oxygen at the onset of an attack. Other treatments include blocking calcium channels with the drug verapamil—which is used for cardiac arrhythmia—or taking triptans, also used for migraines. Some patients have also reported finding relief in hallucinogenic drugs such as LSD and psilocybin.

Those reports intrigued Torsten Passie, a psychiatrist at the Hannover Medical School in Germany and an expert on LSD. So he, Halpern, and colleagues decided to test 2-bromo-LSD (BOL), which was developed by Sandoz, the Swiss company that discovered the psychedelic effects of LSD and marketed it as a drug for some time, as a kind of placebo compound in LSD trials.

At the conference, Halpern and Passie presented the data of six patients with severe cluster headache who were given BOL once every 5 days for a total of three doses. All patients reported a reduction in frequency of attacks, and five patients reported having no attacks for months afterward.

"There seems to be a long-term prophylactic effect that we cannot explain," Halpern says. The team has since treated a seventh patient with similar results. "Compared to what these headache sufferers currently have available to them, this is quite remarkable. It could lead to a near-cure-like treatment", Halpern says. He and Passie have founded a company called Entheogen Corp. to fund further research and are hoping to start a phase II clinical trial with 50 patients later this year.

Goadsby points to shortcomings in the research, however. "These are just a few patients in a completely unblinded study; you would certainly expect some placebo effect," he says. Indeed, Goadsby has done a double-blind study comparing pure oxygen and air in the treatment of cluster headache. Twenty percent of the patients treated with air, the placebo, reported pain reduction. Because cluster headaches can occur in episodes and then vanish again for months or years, it is also difficult to distinguish a drug's long-term effect from normal attack patterns, Goadsby cautions. "Still," he says, "this is an interesting study, and it certainly warrants further investigation."

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