Psychedelic Science Feature: Psilocybin For Headaches

This article by Alexa Julianne was originally published on Psychedelic Spotlight and appears here with permission.

With mounting evidence to support the use of psychedelics in treating serious disorders like PTSD, depression, and anxiety — the sector is now beginning to focus on more highly specialized conditions like headaches.

Psychedelics such as psilocybin “truly have the potential to revolutionize how we treat several neuropsychiatric diseases, including headaches,” said one neuropharmacologist at the annual meeting of the American Headache Society.  Due to the fact that headaches can affect a variety of people, and can range from mild to extremely incapacitating, research is currently ongoing for four different headache types, with psilocybin being the current emphasis

Cluster Headaches

Cluster headaches have been gaining the most attention with psychedelic research because of the severity of symptoms. Cluster headaches can happen up to 8 times per day, are excruciatingly painful, and can last anywhere from 15 minutes to 3 hours. According to the American Migraine Foundation, cluster headaches are named for the manner they occur throughout the day in spontaneous, severe bursts.

One victim of cluster headaches explicitly stated, “I came pretty close to ending my life over it,” resulting in the nickname “suicide headaches.” Cluster headaches dominate the list of the most painful headache types. Cluster headaches were compared to other painful conditions and circumstances, including gunshot wounds, pancreatitis, and stab wounds in a significant international study. With an average pain score of 9.7 on a 10-point scale, cluster headaches were rated as the most painful condition, with labor pain coming in second at 7.2. As the headaches affect 0.1 percent of the population, it is not a rare condition, according to the vice president of the cluster headache non-profit organization, Clusterbusters.

For the treatment of cluster headaches, no specific pharmaceuticals have yet been discovered. However, three treatment modalities are typically used: quick attack-freezing abortive treatment, transitional treatment, and preventive treatment.

• Effective abortive therapies: sumatriptan, high-flow oxygen, and occasionally intranasal triptans.
• Preventive treatment: Verapamil and lithium are prescribed as preventive drugs. However, due to their potential negative effects on the heart, kidney, and liver, verapamil and lithium are frequently ineffective and even cannot be prescribed or stopped utilizing. The succeeding option is topiramate. Doctors may choose melatonin, clomiphene, dihydroergotamine, pizotifen, etc. if these medications don’t work.
• Transitional treatments: these are frequently preferred because the effects of preventative medications may take several weeks to manifest. The most successful transitional therapy involves higher doses of prednisone, greater occipital nerve injection, and frovatriptan.

However, none of the above treatments work for everyone or very consistently. Surveys have shown that out of desperation for relief, people are trying many alternative treatments on their own, including psychedelics.

One of the first of these surveys was conducted in 2006 by Dr. Halpern and colleagues after someone contacted Halpern claiming that psychedelic drugs had completely cured his cluster headaches. He said he had been diagnosed with cluster headaches and that after taking LSD recreationally, he completely recovered from all symptoms.

Halpern’s survey results from 53 respondents showed that psilocybin and LSD both held the potential to have a significant impact on the frequency and severity of cluster headaches. Of the 29 people who used psilocybin in the middle of a cluster period, 27 (93 percent) said it was effective. To elaborate, 52 percent of those said it completely stopped the attack, while 41 percent said it reduced the attack’s intensity or frequency. For 18 of 19 psilocybin users and 4 of 5 LSD users, psychedelics also increased remission time.

A small study in Denmark led by Dr. Gitte Knudsen, a medical doctor at Copenhagen University Hospital Rigshospitalet and a professor at the University of Copenhagen, and her colleagues discovered that psilocybin may increase life satisfaction and quality of life for people with chronic cluster headache even though the burden of persistent headaches might not change. Despite having an overall acceptable safety profile, Dr. Knudsen advised the patients against using psychedelics for self-medication. He also stated that additional clinical studies are required to demonstrate the safety and preventative efficiency of psilocybin.

Based on Halpern’s survey and this encouraging research, studies using psilocybin for cluster headaches have now begun at Yale University. Along with her colleagues, Dr. Emmanuelle Schindler, Medical Director at Headache Center of Excellence and Assistant Professor at Yale found further reports that psychedelics were more effective at treating cluster headache than conventional medications in a qualitative study with almost 500 participants. The survey showed Dr. Schindler that, “Cluster headache sufferers have been using psychedelics to treat their condition for over 20 years” and that they have already “uncovered a lot of anecdotal evidence for the therapeutic potential of [psychedelics].” Now she and her colleagues are initiating controlled studies to look at psilocybin’s effects and mechanisms of action in cluster headaches.

One measurement in the study will compare the effects of a high dose and a low dose (i.e., a microdose, or non-hallucinogenic dose). This is because some of Schindler’s participants reported infrequent use and very low doses while even Halpern and researchers had found that 42% of participants claimed their headaches were partially or completely relieved by taking “subhallucinogenic doses” of psilocybin or LSD. This is particularly intriguing because typical psychedelic research has shown that the more intense or mystical the experience, the better the outcome and the greater the likelihood that results will last a long time. This is true for studies using psilocybin for depression, anxiety, etc. That doesn’t appear to be the case based on headache qualitative data so far.

The investigation is finished, and the findings are ready for publication where we’ll find out what impact three sessions of low or high doses of psilocybin have on frequency, length, or intensity of attacks. According to Schindler, “There appears to be a mechanism of action that is not related to acute psychedelic effects, though more study is needed to uncover what this mechanism might be, which might also be different for different headache disorders.”

This is the justification behind the two additional headache studies Dr. Schindler is conducting at Yale on migraines and post-concussive headaches.

Migraines

Migraines are much more prevalent having less severe pain than cluster headaches and affecting more than 10% of the world’s population. Extreme burning sensation or pulsing pain caused by migraine usually affects one side of the head. Nausea, vomiting, and sensitivity to bright lights and loud noises are typical migraine symptoms. The duration of a migraine attack can be anywhere from a few hours to several days, and the pain may be so severe that it is challenging to carry out daily activities. Prodrome, aura, headache, and postdrome are the four stages through which migraines can progress. However, not everyone with migraines necessarily goes through each stage. According to Schindler, “New treatment therapies are always needed because migraine is a common disease and the primary reason for disability in people under 50 worldwide.”

Analgesics like aspirin, paracetamol, ibuprofen, naproxen, diclofenac, phenazone, and triptans are some of the most popular migraine treatments. Complementary and alternative medicine is frequently used as a result of dissatisfaction with conventional treatments and their terrible side effects.

A 2017 qualitative study from Sweden offered an alternative treatment option when psilocybin was described as “highly effective for both cluster headaches and migraines” by accumulated user reports.

Now, a psilocybin study for migraine headaches is currently enrolling at Yale by Dr. Schindler and colleagues. This is a follow-up study to a small randomized, placebo-controlled exploratory study in which they found that a single dose of low-dose psilocybin reduced the frequency of migraine attacks by 25% over a period of two weeks. The effects that a single dose had on migraines in a short period of time stands in stark contrast to typical migraine medications, which must be taken daily.

In trying to understand this difference, Dr. Schindler explains, “One of the most interesting things is that psychedelics are chemically and pharmacologically similar to conventional migraine medications. Unlike these conventional medications, however, psilocybin appears to have a lasting effect after a single dose; this effect is what distinguishes psychedelics from traditional treatment.”

The rationale for the next study is to “investigate the effects of a repeated dose of psilocybin compared to a single dose to see whether this pulse method of dosing might have a longer therapeutic effect.”

This new study will add to the growing body of research that may support the use of psilocybin as a migraine treatment.

Post-Concussive Headaches

Post-traumatic headaches, another name for post-concussion headaches, are associated with a variety of other concurrent and/or severe situations. There is still a lot to discover about their underlying causes and mechanisms. The symptoms can resemble any primary headache disorder type and are comparable to migraine without ambiance (e.g., cluster headache, tension-type headache). After a traumatic brain injury (TBI), post-concussion headaches typically appear seven days later and resolve within three months.

The FDA has not approved any medications to treat post-traumatic headaches. A primary care physician or the patient frequently starts a patient’s medication regimen. Most patients use NSAIDs as their main form of treatment. However, post-concussive headaches more frequently do not respond to medication, so other treatment modalities are frequently recommended to control them.

Clinical studies to investigate the effects of psilocybin on post-concussive headaches have been started by Deepak D’Souza, MD, and Dr. Schindler and are currently enrolling at Yale. A placebo, low, or high dose of psilocybin will be administered to volunteers on two test days, spaced about two weeks apart. Their headache frequency, intensity, and any other related symptoms will all be evaluated. Throughout the study, blood samples will be drawn at different times to measure inflammatory peptides as well.

SUNHA

Short-term Unilateral Neuralgiform Headache Attacks, or SUNHA, is a rare and crippling type of headache. The headaches are very painful, and can be set off by touching the face or scalp, bathing, washing one’s hair, shaving, eating, talking, coughing, exercising, or any plethora of other common activities. Attacks from SUNHA last between one second and ten minutes, it typically affects men and has an average onset age of 48 years. In the US and Europe, SUNHA is likely to affect 40,000 patients.

What is most striking about this headache according to Cosmo Fielding Mellen, CEO of Beckley Psytech is that, “People can have up to 100 headaches a day and there’s no approved treatment at the moment.”

Beckley Psytech is a privately held independent non-profit that was founded to address neurological and psychiatric disorders through the creative use of psychedelic drugs. They have already begun an early-stage clinical trial evaluating the effects of psilocybin for the treatment of SUNHA. They will test, “if [they] can use low dose psilocybin to improve the symptoms and reduce the frequency of headaches for these patients.”

At the National Hospital for Neurology and Neurosurgery, Manjit Matharu, a consultant neurologist and clinical director of the headache group, says, “I have been involved with research into SUNHA for 22 years and have personally seen the devastating effect this condition can have on so many patients.”

Mellen explains, “The potential medical advantages of psychedelic agents, such as psilocybin, could be transformational to the quality of life for those affected by this disease.” He adds that, “We are very excited to initiate this world-first clinical trial”. For Beckley Psytech and the patients who might gain from this treatment, this marks a significant turning point.

People living with various headache conditions now have a reason for hope owing to psilocybin. The world is still awaiting this research to demonstrate its safety and effectiveness. In the upcoming trial results, we’ll soon find out to what degree the effects psilocybin has on these varying headache conditions.