018 and P = .044, respectively) in reducing headache frequency, but only among those that completed the study. In the analysis including all treated patients, treatment groups did not differ significantly during follow-up. Feverfew Feverfew is an herbal preparation that was used for centuries in the treatment of fevers, headache, infertility, toothaches, inflammation and arthritis. Although the feverfew plant was originally native to the Balkan mountains in Eastern Europe, it now grows throughout Europe, North America, and South America. It is commercially available as the dried leaves of the weed plant Tanacetum parthenium,

and its anti-migraine action is probably related to the parthenolides within these leaves. Feverfew may act in migraine prophylaxis by inhibiting platelet aggregation as well as the release of BVD-523 clinical trial serotonin from platelets and white

blood cells. It may also act as an anti-inflammatory agent through the inhibition of prostaglandin synthesis and phospholipase A.68-71 The efficacy selleck screening library of feverfew in migraine prophylaxis has been controversial, as many RCTs72-77 conducted in the past 3 decades have yielded contradictory results. In addition, a 2004 Cochrane review78 of double-blind RCTs assessing the clinical efficacy and safety of feverfew in migraine prevention concluded that there was insufficient evidence to suggest that feverfew is more effective than placebo in migraine prophylaxis. No major safety or tolerability issues were identified, although side effects reported in the RCTs included gastrointestinal disturbances, mouth ulcers,

and a “post-feverfew syndrome” of joint aches. Inconsistent results from the above studies were attributed to wide variations in the strength of the parthenolides79 and differences in the stability of feverfew preparations80 and subsequently, a new, more stable feverfew extract (MIG-99) was created. In an initial RCT involving 147 patients,81 none of the MIG-99 doses were significant Axenfeld syndrome for the primary endpoint, although a subset of high-frequency migraineurs appeared to benefit from treatment. In a follow-up multicenter RCT with 170 subjects82 randomized to 6.25 mg t.i.d. of MIG-99 or placebo, a statistically significant and clinically relevant reduction in migraine frequency in the MIG-99 group compared to placebo was reported. Feverfew should not be used by pregnant women, as it may cause uterine contractions resulting in miscarriage or preterm labor. It can also cause allergic reactions; patients with allergies to other members of the daisy family, including ragweed and chrysanthemums, are more likely to be allergic to feverfew. Recreational Drugs Although controversial, the evidence for the use of recreational drugs such as marijuana, lysergic acid diethylamide (LSD) and psilocybin is worth mentioning for the insight it provides regarding the pathophysiology of migraine and cluster headache.