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Can Cannabinoids Can Prevent Cluster Headaches?

Cluster Headaches

Cluster headache, nicknamed “suicide headache”, is a neurological disease that involves, as its most prominent feature, an immense degree of pain.  “Cluster” refers to the tendency of these headaches to occur periodically, with active periods interrupted by spontaneous remissions.  The cause of the disease is currently unknown.  It affects approximately 0.1% of the population, and men are more commonly affected than women are.
Cluster headaches are excruciating unilateral headaches of extreme intensity.  The duration of the common attack ranges from as short as 15 minutes to three hours or more.  The onset of an attack is rapid, and most often without the preliminary signs that are characteristic of a migraine.  However, some sufferers report preliminary sensations of pain in the general area of attack, often referred to as “shadows”, that may warn them an attack is lurking or imminent.  Though the headaches are almost exclusively unilateral, there are some documented as cases of “side-shifting” between cluster periods, or, even rarer, simultaneously (within the same cluster period) bilateral headache.  Trigeminal neuralgia can also bring on headaches with similar qualities.  However, with trigeminal neuralgia the pain is mostly located around the facial area and is described as being like stabbing electric shocks, burning, pressing, crushing, exploding or shooting pain that becomes intractable.

Pain

The pain may be very sharp, may cause pain around the eye area, and may be a pain within the back of the eye.  The pain of cluster headaches is markedly greater than in other headache conditions, including severe migraines; experts have suggested that it may be the most painful condition known to medical science.  Female patients have reported it as being more severe than childbirth.  Dr. Peter Goadsby, Professor of Clinical Neurology at University College London (now University of California, San Francisco), and a leading researcher on the condition has commented:
“Cluster headache is probably the worst pain that humans experience.”  I know that is quite a strong remark to make, but if you ask a cluster headache patient if they have had a worse experience, they will universally say they have not.  Women with cluster headache will tell you that an attack is worse than giving birth.  Therefore, you can imagine that these people give birth without anesthetic once or twice a day, for six, eight, or ten weeks at a time, and then have a break.
The pain is lancinating or boring/drilling in quality, and is located behind the eye (per orbital) or in the temple, sometimes radiating to the neck or shoulder.  Analogies frequently used to describe the pain are a red-hot poker inserted into the eye, or a spike penetrating from the top of the head, behind one eye, radiating down to the neck, or sometimes having a leg amputated without any anesthetic.  The condition was originally named Horton’s Cephalalgia after Dr. B.T Horton, who postulated the first theory as to their pathogenesis.  His original paper describes the severity of the headaches as being able to take normal men and force them to attempt or complete suicide.  From Horton’s 1939 paper on cluster headache:
“Our patients were disabled by the disorder and suffered from bouts of pain from two to twenty times a week.  They had found no relief from the usual methods of treatment.  Their pain was so severe that several of them had to be constantly watched for fear of suicide.  Most of them were willing to submit to any operation which might bring relief.”
Thus, cluster headaches are also known by the nickname “suicide headaches.”
The cardinal symptoms of the cluster headache attack are the severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15–180 minutes, if untreated, and the attack frequency of one to 16 attacks in 48 hours.  The headache is accompanied by at least one of the following autonomic symptoms:  ptosis (drooping eyelid), miosis (pupil constriction) conjunctival injection (redness of the conjunctiva), lacrimation (tearing), rhinorrhea (runny nose), and, less commonly, facial blushing, swelling, or sweating, all appearing on the same side of the head as the pain.   The attack is also associated with restlessness, the sufferer often pacing the room or rocking back and forth.  Less frequently, he or she will have an aversion to bright lights and loud noise during the attack.  Nausea rarely accompanies a cluster headache, though it has been reported.  The neck is often stiff or tender in the aftermath of a headache, with jaw or tooth pain sometimes present.  Some sufferers report feeling as though their nose is stopped up and that they are unable to breathe out of one of their nostrils.
Secondary effects are inability to organize thoughts and plans, exhaustion (in response to such extreme stress, body shuts down and only wants to sleep/repair), and depression.  Patients tend to dread facing another headache, may adjust their physical activities or ask help to accomplish normal tasks, and may hesitate to schedule plans in reaction to the clock-like regularity of the pain schedule leading to social isolation.
Cluster headaches are occasionally referred to as “alarm clock headaches” because of their ability to wake a person from sleep and because of the regularity of their timing:  both the individual attacks and the clusters themselves can have a metronomic regularity; attacks striking at a precise time of day each morning or night is typical, even precisely at the same time a week later.  The clusters tend to follow daylight saving time changes and happen more often in spring and fall equinox.  This has prompted researchers to speculate an involvement of the brain’s “biological clock” or circadian rhythm.
In episodic cluster headaches, these attacks occur once or more daily, often at the same times each day, for a period of several weeks, followed by a headache-free period lasting weeks, months, or years.  Approximately ten to fifteen percent of cluster headache sufferers are chronic; they can experience multiple headaches every day for years.
Cluster headaches occurring in two or more cluster periods lasting from 7 to 365 days with a pain-free remission of one month or longer between the clusters are considered episodic.  If the attacks occur for more than a year without a pain-free remission of at least one month, the condition is considered chronic.  Chronic clusters run continuously without any “remission” periods between cycles.  The condition may change from chronic to episodic and from episodic to chronic.  Remission periods lasting for decades before the resumption of clusters have been known to occur.
Cluster headaches have been classified as vascular headaches.  The intense pain is caused by the dilation of blood vessels that creates pressure on the trigeminal nerve.  While this process is the immediate cause of the pain, the etiology (underlying cause or causes) is not fully understood.
Recently, researchers have linked low testosterone as a possible cause of cluster headaches.
Among the most widely accepted theories is that cluster headaches are due to an abnormality in the hypothalamus;  Dr Goadsby, an Australian specialist in the disease has developed this theory.  This can explain why cluster headaches frequently strike around the same time each day, and during a particular season, since one of the functions the hypothalamus performs is regulation of the biological clock.  Metabolic abnormalities have also been reported in patients.
The hypothalamus is responsive to light—day length and photoperiod;  olfactory stimuli, including sex steroids and corticosteroids;  neurally transmitted information arising in particular from the heart, the stomach, and the reproductive system;  autonomic inputs;  blood-borne stimuli, including leptin, ghrelin, angiotensin, insulin, pituitary hormones, cytokines, blood plasma concentrations of glucose and osmolarity, etc.;  and stress.  These particular sensitivities may underlay the causes, triggers, and methods of treatment of cluster headache.
There is a genetic component to cluster headaches, although no single gene has been identified as the cause.  First-degree relatives of sufferers are more likely to have the condition than the population at large.
Tobacco consumption may trigger cluster headaches, and the affliction is often found in people with a heavy addiction to cigarette smoking.  In some cases, second hand smoke may trigger cluster headaches.  However, it is not clear if there is a causal relationship between smoking and cluster headaches.  Some researchers think that people who suffer from cluster headaches may be predisposed to certain traits, including smoking or other lifestyle habits
Cluster headaches often go undiagnosed for many years, being confused with migraine or other causes of headache.
Many times a headache diary is useful- tracking when and where the pain occurs, how severe it is, how long the pain lasts, and coping strategies used will help a physician distinguish between the types of headaches.
Cluster headaches are benign, but because of the extreme and debilitating pain associated with them, and potential risk of suicide, a severe attack is nevertheless treated as a medical emergency.  Because of the relative rareness of the condition and ambiguity of the symptoms, some sufferers may not receive treatment in the emergency room and people may even be mistaken as exhibiting drug-seeking behavior.
Other types of headache are sometimes mistaken for cluster headaches.
Chronic Paroxysmal Hemicranias (CPH) is a condition similar to cluster headache, but CPH responds well to treatment with the anti-inflammatory drug  indomethacin and the attacks are much shorter, often lasting only seconds.
Some people with extreme headaches of this nature (especially if they are not unilateral) may actually have an ictal headache.  Anti-convulsant medications can significantly improve this condition so sufferers should consult a physician about this possibility.

Treatment/Prevention

A wide variety of prophylactic medicines are in use and patient response to these is highly variable.  Current European guidelines suggest the use of the calcium channel blocker verapamil at a dose of at least 240 mg daily.  Steroids, such as prednisolone/prednisone, are also effective, with a high dose given for the first five days or longer (in some cases up to 6 months) before tapering down.  Methysergide, lithium and the anticonvulsant topiramate are recommended as alternative treatments.  In Australia, Neurologist John Watson has also reported success with Epilim and Tegretol in some chronic, treatment-refractory cases.

Intravenous magnesium sulfate relieves cluster headaches in about 40% of patients with low serum ionized magnesium levels.  Melatonin has also been demonstrated to bring significant improvement in approximately half of episodic patients.
Over-the-counter pain medications (such as aspirin, paracetamol, and ibuprofen) typically have no effect on the pain from a cluster headache.  Unlike other headaches such as migraines and tension headaches, cluster headaches do not respond to biofeedback.
Medications to treat cluster headaches are classified as either abortives or prophylactics (preventatives).  In addition, short-term transitional medications (such as steroids) may be used while prophylactic treatment is instituted and adjusted.  With abortive treatments often only decreasing the duration of the headache and preventing it from reaching its peak rather than eliminating it.  Preventative treatment is always indicated for cluster headaches, to be started at the first sign of a new cluster cycle.
During the onset of a cluster headache, many people respond to inhalation of  100 % oxygen (12-15 liters per minute in a non-re-breathing mask).  Some people have found better results with 25 liters per minute.  There is also a study (commenced 2011) using an “on-demand” valve that can deliver up to 160 liters per minute.  When oxygen is used at the onset this can abort the attack in as little as one minute or as long as 10 minutes.  Once an attack is at its peak, oxygen therapy appears to have little effect so many people keep an oxygen tank nearby to use at the very first sign of an attack.  An alternative first-line treatment is subcutaneous or intranasal administration of sumatriptan.  Hyperbaric oxygen therapy has been used successfully in treating cluster headaches though it was not shown to be more successful than surface oxygen.

Triptans

Sumatriptan and zolmitriptan have both been shown to improve symptoms during an attack.

Other

Some non-narcotic treatments that have shown mixed levels of success:  are Botox injections along the occipital nerve, as well as sarapin (pitcher plant extract) injections.
Lidocaine and other topical anesthetics sprayed into the nasal cavity may relieve or stop the pain, normally in a few minutes, but long-term use is not suggested due to the side effects and possible damage to the nasal cavities.
Previously, vaso-constrictors such as ergot compounds were also used, and sufferers report a similar relief by taking strong cups of coffee immediately at the onset of an attack.  Cafergot, a cheap off-the-shelf vaso-constrictor, has been shown to stop cluster headaches within 40 minutes of ingestion.  BOL (2-bromo lysergic acid diethylamide), a non-psychedelic form of the ergot-derived psychedelic LSD, has shown promise in the treatment of cluster headaches.
Kudzu, a common vine from the Pea subfamily Faboideae, may prove to have a role in the management of cluster headache.
Other abortive remedies that work for some include   ice, hot showers, cool or lukewarm water sprayed on the face around the sinus, temple, and ear areas, breathing cold air, application of White Flower analgesic balm beneath the nostrils, caffeine, and drinking large amounts of water in the early stages of an attack.  Vigorous exercise has been shown in some cases to be very effective in relieving and aborting an acute attack by increasing the levels of oxygen within the body.  This could also be due to an increase in adrenaline and changes in blood pressure.  Some people report that sexual intercourse and specifically orgasm may terminate an attack possibly by acutely modulating hypothalamic function.  Concentrating one’s thoughts to a remote part of one’s anatomy, such as the opposite little toe, reduced the length of attacks.  Headaches are self-perpetuating by concentrating the mind on the symptoms.

Epidemiology

While migraines are diagnosed more often in women, cluster headaches are more prevalent in men.  The male-to-female ratio in cluster headache ranges from (4:1 to 71).  It primarily occurs between the ages of (20 to 50) years.  This gap between the sexes has narrowed over the past few decades, and it is not clear whether cluster headaches are becoming more frequent in women, or whether they are merely being better diagnosed.  Limited epidemiological studies have suggested prevalence rates of between (56 and 326) people per 100,000.

History

The first complete description of cluster headache was given by the London neurologist Wilfred Harris  in 1926.  He named the disease Migrainous neuralgia.
Cluster headaches have been called by several other names in the past including:   Erythroprosopalgia of Bing, Ciliary neuralgia, Erythromelagia of the head, Horton’s headache (named after Bayard T. Horton, an American neurologist), Histaminic cephalalgia, Petrosal neuralgia, sphenopalatine neuralgia, Vidian neuralgia, Sluder’s neuralgia, and Hemicrania angioparalyticia.

Cannabinoids and Cluster Headaches

Research and Testimonials:

In summary, a small number of case reports and survey studies suggest a possible benefit of cannabis for the treatment of acute headache.  Such benefit is plausible in view of the pharmacological effects of THC and synthetic cannabinoids.  Methodologically rigorous studies to support this view, however, are lacking. Further research in this area seems warranted; especially as more, US states legalize the use of marijuana for medical purposes.  Novel compounds with cannabinoid-like mechanisms of action may hold promise for patients with headaches that are refractory to currently available treatment options.  It will be important to carefully quantify the harm to benefit balance of such treatments.  Many potential users are young people, including women of childbearing potential, and the primary headache disorders are conditions of long duration.  Such treatments must be held to the same standards of proof applied to other pharmacological interventions for headache.
It has been suggested that one explanation for migraine and other headache disorders, at least in some patients, may be an underlying endocannabinoid deficiency.

There are a number of reasons why naturally occurring cannabis or cannabinoid drugs might have a pharmacologic effect on headache.  Cannabinoids are active in areas of the brain known to be involved in migraine pathophysiology, including areas suspected of being involved in the generation of migraine. The endogenous compound anandamide appears to modulate pain signalling in the central nervous system.  It also potentiates 5-HT1A and inhibits 5-HT2A receptors, so effects on serotonergic pain transmission also may be involved in any therapeutic effects on headache.
The data suggest that CB receptors may have therapeutic potential in migraine, cluster headache or other primary headaches.
Cluster Attacks Responsive to Recreational Cannabis and Dronabinol
Pharmacological preparations of cannabinoid compounds have a variety of therapeutic uses in medicine, including different pain syndromes, but have not been previously reported as beneficial for cluster headache.  We present a patient with cluster headache who was refractory to multiple acute and preventive medications but successfully aborted his attacks with recreational marijuana use; subsequent use of dronabinol provided equally effective pain relief.

Given the lack of responsiveness to multiple agents, dronabinol [Marinol pill] 5 mg was substituted for marijuana for acute treatment of his cluster headaches; dronabinol consistently provided dramatic relief within 5 to 15 min of ingestion.
Cannabis should be considering a prophylactic when it comes to cluster headaches.  I have been using it for over forty years.  I have had cluster headaches my whole life.  It was not properly diagnosed until I was 30 years old.  I discovered on my own that if I smoke good quality cannabis (typically home grown or medical grade) it helps prevent them from occurring as often and reduces the severity.  After onset, it has limited effect for me.  It does reduce the pain but does not eliminate it.  I would love to see very clinical trials of this done so that we could further refine the exact cannibiniods that affect this problem.  It may lead to a better understanding of the cause and effect.
Smoking marijuana and taking its legal medicinal derivative, dronabinol helped one patient with cluster headaches, according to a report from the Montefiore Headache Clinic.  Dronabinol is approved for the treatment of nausea and loss of appetite.  Many patients have reported the effectiveness of smoking marijuana or taking dronabinol for the relief of pain.  .  In view of this report, it seems reasonable to try dronabinol in patients who failed Imitrex injections, oxygen and preventive drugs, such as high dose of verapamil, lithium, and topiramate.

Inhaled Cannabis Aborts Cluster Headaches, Journal Reports
“Marijuana use at the onset of his headaches consistently brought complete relief within five minutes of inhalation for each attack”
Neurologists from the Albert Einstein College of Medicine in New York reported that a 19-year-old patient with a cyclical pattern of cluster headaches responded favorably to smoked cannabis.  The patient lacked responsiveness to numerous traditional treatments – including prednisone, sumatriptan (trade name: Imitrex), and oxycodone – but did report, “Marijuana use at the onset of his headaches consistently brought complete relief within five minutes of inhalation for each attack”.
Investigators reported that the patient also received relief from the administration of five-milligram doses of synthetic oral THC (dronanabinol).  They wrote, “[D]ronabinol was substituted for marijuana for acute treatment of his cluster headaches; dronabinol consistently provided dramatic relief within five to fifteen minutes of ingestion”.
Researchers concluded, “We present a patient with cluster headache who was refractory to multiple acute and preventive medications, but successfully aborted his attacks with recreational marijuana use.  The beneficial effect may be related to the high concentration of cannabinoid receptors in the hypothalamus, which has been implicated as a site of dysfunction in neuroimaging studies of patients with cluster headache.”
Bronx, NY:  Inhaling cannabis completely relieved the pain associated with cluster headaches, according to a case study published in the journal Headache.

Recommendation:  Whole plant extract, Sativa x Indica hybrid, vaporizer, under the tongue, spray.

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