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Are Cannabinoids and Hallucinogens Viable Treatment Options for Headache Relief?

Neurology Reviews. 2014 May;22(5):22-23.

SAN FRANCISCO—Within the headache community, desperate patients have tried just about everything for relief. Patients have been using cannabis for headache for several decades, and more recently it has been suggested that hallucinogens may induce remission of cluster headache. At the Headache Cooperative of the Pacific’s Seventh Annual Winter Conference, Brian E. McGeeney, MD, MPH, discussed the use of cannabinoids and hallucinogens for headache. Dr. McGeeney is an Assistant Professor of Neurology at Boston University School of Medicine.

Marijuana for Migraine

Patient testimonials may abound, but as far as evidence-based medicine goes, “there are no blinded studies for the use of cannabinoids for headache,” Dr. McGeeney pointed out. The use of cannabinoids for pain started in the 1970s. A short paper in the early 1970s in Headache described what was essentially a withdrawal headache, “which you can certainly get, especially with the daily use of cannabis.”

Goadsby et al demonstrated that the endogenous cannabinoid receptor ligand anandamide, which is the most well-known endogenous cannabinoid, is able to inhibit dural blood vessel dilation from electrical stimulation, administration of calcitonin gene-related peptide and nitrous oxide, or capsaicin administration. This inhibition is reversible. “This goes in some way toward providing a theory of how this [drug] may work for headache or migraine,” Dr. McGeeney said. “Cannabinoid receptors—CB1 and CB2—are located throughout the CNS and even in the peripheral nervous system. Cannabinoid receptors are 10 times more prevalent than opioid receptors.”

In the brain, cannabinoid receptors are found not just in the cortex, but in deep brain structures as well. “And if you think it’s going to work in headache, it is probably going to have a role in particular in the brainstem,” said Dr. McGeeney.

One theory is that the transmission of the trigeminal impulse of the first- and second-order neurons can be modulated by descending influences that can be either excitatory or inhibitory. Some evidence suggests that cannabinoid agonists may affect transmission along the trigeminal nerve. “And that is a plausible theory as to why it may work in headache,” Dr. McGeeney said. “Patients tell me that Cannabis indica is more likely to give them headache relief than other types.”

Hallucinogens and Headache

“There is some truth to claims that psilocybin works to abort a cluster headache,” Dr. McGeeney said. “But generally, the use of psilocybin in cluster headache patients is more to induce a remission of repeated attacks, not to treat an acute attack.” The reason why psilocybin may be helpful is its similarity to serotonin. The indole ring is a key part of the serotonin agonist, and the chemical structures of serotonin, tryptophan, and most hallucinogenic compounds are similar.

Hallucinogenic compounds that cluster patients may be using include lysergic acid amine (LSA)–containing seeds, the psilocybin mushroom, and lysergic acid diethylamide (LSD), which is much more difficult to obtain.

The connection between hallucinogens and cluster headache began in 1998 when a Scottish man posted a provocative comment on a cluster headache website. He said, “I’ve been getting cluster headaches for many years, and I missed my fall cycle. And the only thing I’ve done differently is the recreational use of LSD. I wonder whether that has something to do with it.” This was met with skepticism in the cluster community. But gradually, more people started to pursue hallucinogens to see whether they made a difference.

The first things they used were seeds—Rivea corymbosa, Hawaiian baby woodrose, and certain strains of morning glory seeds—which have hallucinogenic alkaloids in them. “It is perfectly legal in the United States to buy these seeds, to sell them, and to cultivate them, but it is not legal to ingest them or to soak them in water and then drink the water, which is rather disgusting and easily induces nausea and vomiting,” said Dr. McGeeney. Cluster patients are using these seeds to try to induce a remission. Albert Hoffman, of LSD fame, analyzed the ergot in those seeds—ergine and isoergine.

The use of hallucinogens among cluster headache patients came to light with a 2006 paper by Sewell et al in Neurology. The authors surveyed 53 cluster patients, 21 of whom had chronic cluster headache. Half of those who used psilocybin said that it completely eliminated their attacks. “In speaking to many of these patients over the years, that elimination can be anywhere from days to months. But it is not rare to come across someone who says that psilocybin will eliminate their attacks for a couple of months,” Dr. McGeeney said.

Patients are worried about arrest when they take these substances. Possession of psilocybin mushrooms is illegal everywhere. Psilocybin is a Schedule 1 drug. Fortunately for patients, buying the spores is legal in most states. Several vendors operate online. In California, Georgia, and Idaho, however, it is illegal to buy the spores.

“I go every year to ClusterBusters meetings and meet these patients,” Dr. McGeeney said. ClusterBusters is a support meeting for patients who have cluster headache. “They talk about treatment, and that does include alternative treatments, but not solely,” he noted. “It is not necessarily everybody or even most people who are pursuing that option.”

LSD has been around since the 1940s. “In practice, this is a much more difficult hallucinogen for patients to get,” Dr. McGeeney said. “These are ordinary people. Where are they going to get LSD? It is practically impossible.”

Nonhallucinogenic Hallucinogens

According to Dr. McGeeney, the evidence suggests that to gain the cluster–abortive benefits of hallucinogens, patients do not have to hallucinate. “You can take an LSD molecule and brominate it,” he said. “And you turn it into brominated LSD, which is nonhallucinogenic.”

Is this method useful for cluster headache? That question started to be answered a few years ago. A 2010 study published in Cephalalgia described five patients, four of whom had chronic cluster headache. They were administered brominated LSD, and they did not hallucinate. At baseline, the number of attacks per week in the five patients was 40, 40, 35, 30, and 25. After treatment, all patients had close to zero attacks.

One of the authors of the original 2006 survey in Neurology, John Halpern, is trying to bring brominated LSD to market in the United States. The regulations and red tape have been daunting despite herculean efforts by Dt. Halpern. “But we’re hoping that this may be an option in the near future,” Dr. McGeeney said.

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John Halpern, is trying to bring brominated LSD to market in the United States. The regulations and red tape have been daunting despite herculean efforts by Dt. Halpern. “But weÂ’re hoping that this may be an option in the near future,” Dr. McGeeney said. 
  I can't help asking -- Is Dr. M hoping for BOL in the near future on the basis of some new information, or is he just "hoping" like the rest of us?  I have to admit that I have always understood that before the regulations and red tape, funding was what was holding back Entheogen (and from Dr. Halpern's presentation at the last conference, I felt very pessimistic about that).  If there's any reason for optimism (as opposed to hope), I'd be thrilled to hear it.


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