By: David Warmflash

david-warmflashLysergic acid diethylamide (LSD) and psilocybin (found in “magic mushrooms”) are currently Schedule 1 drugs, meaning that they have abuse potential and are not considered useful clinically. But researchers actually have been uncovering potential uses for this category of agents, which are called hallucinogenics, because hallucination is one notable effect. These drugs show promise in treating cluster headaches in particular. Additionally, limited evidence suggests a possible role for these agents in treating depression.

Similar to a migraine, a cluster headache is a neurovascular condition where symptoms are related to changes in cerebral blood flow. Whereas migraines affect three times as many women as men, cluster headaches affect mostly men and are much less common overall (male 40 per 10,000; female 8 per 10,000). They strike in clusters; during a symptomatic period lasting days to months, the victim feels severe headaches wax and wane, then disappear until a new cluster period begins. The pain can be so bad that cluster headaches are also called “suicide headaches,” based on some cases of victims actually killing themselves to end the pain.

As with migraine headaches, 100 percent oxygen through a mask is a mainline treatment for an acute cluster headache attack. However, a Cochrane review of 11 studies encompassing 209 participants shows that hyperbaric oxygen therapy (HBOT) offers no benefit over sea level pressure oxygen (normobaric oxygen therapy ). Also similar to oxygen, triptan drugs such as sumatriptan (subcutaneous or intranasal) constitute a gold standard treatment. These are agonists of the 5HT1 serotonin receptor and like oxygen they’re useful in aborting an acute cluster headache attack, as is another commonly used drug called dihydroergotamine.

To prevent headache attacks during a cluster period, the standard treatment is corticosteroids (methylprednisone, methysergide), but there are substantial side effects, including muscle weakness, mood changes, bleeding and bruising, mood changes, ankle and facial swelling, dizziness and nausea, and osteoporosis. Other drugs such as verapamil, valproic acid, lithium, and topiramate, and valproic acid have been used for long-term prevention, but they often don’t work in many patients, plus these too can produce side effects. Another option is occipital nerve block, a procedure that has shown some promise for cluster headache patients according to a 2012 review, but the trial design has been criticized in terms of how patients were selected.shutterstock_341543084

Given the limitations in therapy, some cluster headache victims have used LSD and psilocybin as treatment over the last several decades. This led to a small retrospective study (53 patients) published in the Journal of Neurology in 2006 suggesting a slight effect of LSD and perhaps a greater effect for psilocybin in reducing headache duration and severity. It’s retrospective and patients knew what they were taking, so of course a placebo effect could have been substantial. However, the result does provide a rationale for conducting prospective studies.

Perhaps an even more encouraging was published in The Lancet this past year, showing psilocybin to be effective in alleviating symptoms and signs of depression. Conducted in the U.K. with only 12 patients, the study was even smaller than the cluster headache study described above, but all 12 patients showed improvement. According to the researchers, such a result was in no way dramatic, but it lays the groundwork for larger studies.

As in the U.S., however, U.K. laws classify hallucinogenic as not prescribable. Specifically the British drug category is Class A, which is equivalent to the U.S. Schedule 1. Thus, both here and across the pond, clinical utilization of these drugs would require a substantial policy shift.

David Warmflash, M.D., is an astrobiologist, science writer, and physician. He is principal investigator on a Planetary Society-sponsored investigation of the effects of the space environment on organisms.