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Is cbd oil good for cluster headaches

Cannabis and CBD Oil for Headache Relief [How Do They Work?]

According to the National Institute of Neurological Disorders and Stroke, headaches are the most common cause of pain. They account for many days off from work and school annually and pose a significant economic and personal burden.

Most people suffer from headaches occasionally, but for some, they are a regular occurrence. They can also range from mild to completely debilitating.

Furthermore, chronic headaches can be challenging to treat. In fact, some medications can lead to more headaches when patients use them frequently.

Therefore, many people are seeking more natural ways to ease the pain. In this article, we look at cannabis and CBD oil for headaches. Here’s all you need to know.

Types of Headache

There are over 150 types of headache disorders. Some of these are primary, meaning that they occur independently of any other medical condition. Others are secondary, meaning that they result from another disease, including:

  • Stress
  • Infections
  • Sinus problems
  • Tumors
  • Strokes
  • Nerve disorders

To simplify matters, we will focus on four of the most common types of headache: tension-type headaches, migraines, cluster headaches, and medication overuse headaches.

Tension-Type Headache

Tension-type headaches (TTH) are extremely common. They occur due to tension in the muscles of the shoulders, neck, scalp, and jaw.

They are often stress-related and tend to affect the forehead, temples, or base of the skull. Patients who suffer from TTH describe the pain as tight or band-like.

Migraine

Migraines are another common type of headache. They are usually one-sided, and the pain is throbbing in nature. Migraines may be accompanied by other symptoms such as aversion to bright lights and nausea.

Some migraine patients also experience an ‘aura’ before the onset of an attack, including flashing lights, zig-zags, or other sensory changes. A migraine can last 4–72 hours from beginning to end.

Cluster Headache

Cluster headaches (CH) are a severe kind of headache that usually occurs around one eye. Patients describe the pain as piercing, sharp, or burning.

Cluster headaches can happen every day for weeks or months at a time. Each headache can last between 15 minutes and three hours.

Medication Overuse Headache

Some prescription and over-the-counter headache medications can worsen symptoms if a patient takes them too frequently. This phenomenon is known as medication overuse headache (MOH) or ‘rebound headache.’

What Causes Headaches?

In many cases, it is unclear exactly what causes headaches. However, scientists believe that the widening and narrowing of blood vessels play a role in certain kinds of headaches, especially in migraines and cluster headaches. Certain areas of the brain, including the hypothalamus, may also be involved in certain types of headaches.

Foods, smells, or other environmental changes can trigger headaches. For women, monthly hormonal changes may also be a factor.

Some people find that certain foods, smells, or other environmental changes can trigger headaches. For women, monthly hormonal changes may also be a factor.

Conventional Headache Treatments (Not Cannabis-Based)

There are many different headache treatments, and the most appropriate one depends on the type and severity of the symptoms as well as the suspected cause.

For mild, everyday headaches, over-the-counter remedies could be enough to offer some relief. However, for more severe or recurring headaches, preventative treatment may be necessary. This could include medication like beta-blockers, some antidepressants, or anti-seizure medications.

However, many of these medications can cause side effects, especially with regular use. Therefore, many people are turning to natural remedies such as cannabis.

Cannabis for Headaches

Humans have used cannabis to relieve headaches for thousands of years. Ancient Assyrian manuscripts state that it can “bind the temples.” Meanwhile, ancient Ayurvedic texts recommend it for “diseases of the head.”

Reports of using cannabis for headaches have continued throughout history, including Greek, Persian, and Arabic documents. Western doctors also promoted its use, including Dr. John Russel Reynolds, Queen Victoria’s physician.

Generally speaking, doctors recommended low doses for both the prevention and treatment of headaches. The aim was to achieve symptom relief with minimal intoxication. Throughout the 19th and early 20th centuries, there were multiple reports of successfully treating headaches with cannabis.

A state by state guide. …

However, after the herb became illegal, things changed dramatically. People began to see cannabis as a dangerous drug, and research into its benefits all but ground to a halt.

Therefore, there are very few clinical trials regarding the use of cannabis for headaches. That said, there are many anecdotal reports of it having beneficial effects. For example, this 2017 review for Cannabis and Cannabinoid Research lists several case studies and surveys with positive results.

Fortunately, in the past few years, experts have begun to recognize the healing potential of cannabis once more. This has led to increased research on various topics, including cannabis for headaches and migraines.

Studies on Cannabis for Headaches

Several modern studies have investigated the effect of cannabis on various types of headaches. Here is what they have discovered so far.

Research on Cannabis for Headaches and Migraines

In 2019, The Journal of Pain published an article on the short-term and long-term effects of cannabis on headaches. It reviewed data from a medical marijuana application called Strainprint.

The results showed that there were 12,293 sessions of cannabis use for headaches and 7441 sessions for migraine relief. Just under 90% of the participants reported symptomatic relief from headaches, and 88% reported relief from migraines. The average reductions in severity were 47% and 50%, respectively.

A 2016 study for Pharmacotherapy supports the benefits of cannabis for migraines, specifically. It assessed 121 patients who received medical marijuana on a physician’s recommendation. The average number of migraines per month reduced from 10.4 to 4.6. However, some of the patients experienced adverse effects, including drowsiness and difficulty controlling their dose.

Studies on Cannabis for Cluster Headaches

Another study, this time for Cephalalgia in 2013, looked at cannabis for cluster headaches. It included 139 patients, 27 of which had tried marijuana for CH. The results showed that just under 26% found some relief, but 22% experienced negative effects.

One possible explanation is that cannabis can increase heart rate and blood pressure while widening the blood vessels. All of these factors could potentially contribute to cannabis triggering a headache.

Research on Cannabinoids for Medication Overuse Headache

A 2012 study for the Journal of Headache and Pain investigated the synthetic cannabinoid nabilone for MOH.

It was a randomized, controlled, crossover trial in which patients took either ibuprofen or nabilone for headaches. The participants did not know which medication they were receiving. After eight weeks, the participants had a medication-free week and then switched to the other drug.

The results showed that nabilone was more effective than ibuprofen in the treatment of MOH. It also helped to reduce dependence on other drugs and improved overall quality of life.

How Does Cannabis Work for Headaches?

Some types of headaches appear to involve a system called the trigeminovascular pathway. It is a collection of nerve cells that supply the blood vessels in the head. The process relies on a variety of neurochemicals. They include calcitonin gene-related peptide (CGRP) and nitric oxide (NO).

When this system becomes overactive, the blood vessels widen and narrow abnormally, potentially leading to headaches and migraines. Other factors, such as serotonin release and inflammation, may also play a role.

All of the above may have an intricate relationship with the body’s endocannabinoid system (ECS). The ECS is responsible for keeping our bodies in balance using chemicals called endocannabinoids. Scientists have hypothesized that a deficiency of these endocannabinoids could be an underlying cause of migraines.

Scientists have hypothesized that a deficiency of endocannabinoids could be an underlying cause of migraines.

For example, migraine sufferers appear to have reduced levels of endocannabinoids in their cerebrospinal fluid. They also may have higher than average levels of CGRP and NO.

Cannabis has a significant impact on the ECS as it contains molecules that mimic the action of endocannabinoids. Therefore, it may be able to impact some of the different elements that contribute to headaches and migraines.

Other potential mechanisms for how cannabis works for headaches include impacting serotonin release and reducing inflammation. However, we are only beginning to uncover this complicated relationship. Much more research is necessary before we can fully understand the link between headaches and the ECS.

CBD Oil for Headaches

If you do not have access to medical marijuana for headaches, another option is CBD oil. It is possible to extract CBD from cannabis or hemp, and the latter is widely available throughout the country.

CBD is just one of the medicinal compounds that cannabis produces, and it has many of the benefits of the whole plant. The main difference is that it does not cause users to feel high. CBD is known for a wealth of benefits, including antioxidant, anti-inflammatory, and neuroprotective properties.

In terms of using CBD for headaches, it appears to enhance the activity of the ECS by slowing the breakdown of endocannabinoids. It also interacts with serotonin receptors in the brain. Although there is no research specifically on CBD oil for headaches, it may still be worth a try.

Updated 2022 guide to CBD oil…

Most experts consider it to be safe with minimal risk of side effects. Therefore, it is legal in the majority of places. However, there is a risk of CBD interacting with other medications, so some caution is necessary.

It is also important to note that the CBD market is not well-regulated at present. Therefore, many brands are selling substandard products with little to no cannabinoid content. It is advisable to conduct thorough research before buying CBD oil for headache relief to ensure that you choose a reputable brand.

Cannabis and CBD Oil for Headache Relief: Final Thoughts

Although the research into cannabis and CBD oil for headaches is lacking, there is plenty of anecdotal evidence to support their use. In fact, doctors across the world have been recommending marijuana for headaches for centuries.

Before diving in, be sure to ask a medical professional for guidance. There are some reports that suggest cannabis could make headaches worse, especially cluster headaches. Therefore, careful dosing is essential. It is also important to get an accurate diagnosis to ensure your headaches are not a sign of a serious underlying issue.

Finally, remember to use cannabis responsibly and always check your state’s laws before taking either marijuana or CBD oil for headache relief.

Is CBD Good For Cluster Headaches & Migraines?

Most people will be familiar with the occasional mild headache. But for sufferers of more severe migraines or cluster headaches they can be severe and life altering. And with a wide range of possible treatments, but no guaranteed cures, it’s not surprising more and more people are looking at CBD for migraines and cluster headaches.

Migraines are common, affecting roughly 1 in 5 women and 1 in 15 men in the UK. Cluster headaches are thankfully rarer, and tend to occur more for men, in their 30s and 40s.

What causes migraines and cluster headaches?

The exact causes of both migraines and cluster headaches are currently unknown. Migraines are suspected to be the result of changes in the chemicals, nerves and blood vessels in the brain. Cluster headaches are linked to increased activity in the hypothalamus part of the brain.

Migraine and cluster headache sufferers often have a close relative who also has the condition, suggesting that there may be a genetic link in making people more susceptible. And smokers also tend to run a higher risk.

Specific periods of attacks tend to be associated with migraine triggers. These can include stress, tiredness, particular food or drink, strong smells, or for women, starting your period (also known as hormone headaches or menstrual migraines).

Cluster headaches also tend to occur at the same time each day, often at similar times of the year.

There are different types of migraine, but they are generally categorised as a moderate or severe headache felt as a throbbing pain on one side of the head, often accompanied by feeling sick, vomiting or increased sensitivity to light or sound. A cluster headache is a sharp, excruciating pain often felt around the eye, temple and sometimes face on one side of the head.

Common migraine symptoms

The most common types of headaches are associated with tension, and most people will be familiar with a constant aching on both sides of the head, tighter neck muscles and a feeling of pressure between the eyes. These can also be brought on due to the cold or flu, dehydration, not eating regular meals or overindulging in alcohol, and tend to be mild enough that they don’t stop you doing everyday activities.

Migraines are more severe, and can mean some people are confined to their bed for days at a time. There are various types including:

  • migraine with aura – where there are specific warning signs just before the migraine begins, such as seeing flashing lights
  • migraine without aura – the most common type, where the migraine happens without the specific warning signs
  • migraine aura without headache, also known as silent migraine – where an aura or other migraine symptoms are experienced, but a headache does not develop

If you suffer from frequent or severe migraine symptoms, you should see a GP.

  • a red and watering eye
  • drooping and swelling of 1 eyelid
  • a smaller pupil in 1 eye
  • a sweaty face
  • a blocked or runny nostril

Is CBD good for migraines and cluster headaches?

There are currently no absolute medical cures for migraines and cluster headaches, but treatments to prevent attacks and relieve symptoms range from over-the-counter painkillers for migraines, to injections and electrical nerve stimulation for cluster headaches.

Prevention methods include a generally healthy lifestyle, reducing stress and tiredness, quitting smoking, and medication in the case of cluster headaches.

Currently there are relatively few studies looking at the role of CBD for migraines and cluster headaches. One study looked at cannabinoids as “Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population” ( link )

The studies that do exist suggest that CBD may help to relieve the pain of migraines and cluster headaches. For example, “Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science” ( link ), “The Use of Cannabis for Headache Disorders” ( link ), and “Emerging Role of (Endo) Cannabinoids in Migraine” ( link ).

Many migraine and cluster headache treatments focus on prevention, rather than pain relief. And this is where CBD could be beneficial as part of general well being to reduce causes of headaches including stress, anxiety and tiredness.

How to take CBD for migraines and cluster headaches

There are a variety of ways to integrate CBD into your general daily routine, and the most common are either as a CBD Oil , or CBD Capsules . Both are quick and simple ways to see if CBD is the right choice for you, although we’d always recommend checking with your doctor before taking any supplement, especially if you’re already on any medication.

Anyone starting out with CBD should begin with a low dose to allow your Endocannabinoid system to be introduced to your new routine. So you might begin with the 4% Full Spectrum CBD Oil for a time before moving to our 8% or 15% options if required.

CBD Oil is taken orally, with 1 to 3 drops twice a day dropped under your tongue and held there for a minute before swallowing.

If you prefer, CBD Capsules are also available, and our 1.5% capsules are vegan friendly, and infused with Turmeric and Black Pepper.

Useful migraines/cluster headaches links

Ultimately CBD is not a cure for migraines and cluster headaches. But the potential benefits of CBD taken for general well being might contribute to less frequent attacks and lower pain during bouts of headaches.

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KYND products are intended for use by those of the appropriate legal age according to local law.

The Use of Cannabis for Headache Disorders

Department of Psychiatry, Center for Medicinal Cannabis Research, University of California, San Diego, La Jolla, California.

* Address correspondence to: Igor Grant, MD, Department of Psychiatry, Center for Medicinal Cannabis Research, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, E-mail: [email protected]

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

Abstract

Headache disorders are common, debilitating, and, in many cases, inadequately managed by existing treatments. Although clinical trials of cannabis for neuropathic pain have shown promising results, there has been limited research on its use, specifically for headache disorders. This review considers historical prescription practices, summarizes the existing reports on the use of cannabis for headache, and examines the preclinical literature exploring the role of exogenous and endogenous cannabinoids to alter headache pathophysiology. Currently, there is not enough evidence from well-designed clinical trials to support the use of cannabis for headache, but there are sufficient anecdotal and preliminary results, as well as plausible neurobiological mechanisms, to warrant properly designed clinical trials. Such trials are needed to determine short- and long-term efficacy for specific headache types, compatibility with existing treatments, optimal administration practices, as well as potential risks.

Introduction

Headache is a major public health concern, with enormous individual and societal costs (estimated at $14.4 billion annually) due to decreased quality of life and disability. 1 Each year, ∼47% of the population experience headache, including migraine (10%), tension-type headache (38%), and chronic daily headache (3%). 2 A sexual dimorphism exists for headache disorders, with women 2–3 times more likely to experience migraine 3 and 1.25 times more likely to experience tension-type headache than men. 4

The present review will focus largely on migraine, tension-type headache, trigeminal autonomic cephalalgias (specifically cluster headache), and medication-overuse headache (MOH). Migraine is classified as a 4–72 h headache that is typically unilateral, pulsating, of moderate-to-severe intensity, and associated with photophobia and phonophobia. 5,6 Tension-type headache is classified as frequent, infrequent, or chronic, typically presenting with bilateral tightening pain of mild-to-moderate intensity and lasting minutes to days. 6,7 Cluster headache is defined as severe unilateral pain in orbital, temporal, and/or supraorbital locations, lasting 15–180 min and typically occurring frequently and at regular intervals. 6,8 MOH is a chronic condition (occurs more than 15 days per month) that develops from frequent use of anti-headache medications. 6,9

The pathophysiology of headache disorders is still under investigation. However, it is believed that migraine and cluster headaches are initiated in the brain in areas such as the hypothalamus, brainstem, or possibly cortex. 6 Tension-type headaches can not only originate in the central nervous system but may also be triggered by myofascial tissue, often developing in response to stress. 10 Regardless of origin, headaches usually involve overactivation of the trigeminovascular pathway, resulting in the release of vasoactive peptides, such as calcitonin gene-related peptide (CGRP) and substance P, as well as vasoactive mediators such as nitrous oxide (NO), which can lead to further sensitization of nociceptive receptors in the head and neck. 11 Serotoninergic signaling, parasympathetic efferents, inflammation, and increased intracranial pressure also play important roles in headache disorders. 12,13

Treatment depends on the underlying headache condition; however, some popular options include NSAIDs for mild headaches and triptans, anti-depressants, verapamil, or ergotamine for more severe or chronic headaches. 14 These may be complemented by nonpharmacological interventions such as cognitive-behavioral therapy or relaxation training. 15 Despite many treatment options, less than half of headache sufferers experience remission, and many continue to develop more severe or chronic headaches throughout their lifetime. 16 Moreover, headache disorders are often underrecognized and undertreated. 17 This current situation warrants an exploration of additional treatment options for headache disorders, with favorable side-effect profiles and efficacy in refractory patients.

One such option, cannabis, has been ignored in the United States for the past several decades but has an established history in the treatment of headaches. Assyrian manuscripts from the second millennium BCE recommended cannabis to “bind the temples,” 18 and Ayurvedic preparations in the third and fourth centuries BCE were indicated for “diseases of the head” such as migraines. 19 The prescription of cannabis was even recommended in ancient Greece, with Pedanius Dioscorides describing its use in his De Maternia Medica as a treatment for “pain of the ears.” 20 Other citations documenting the use of cannabis for headache disorders arise from the ninth century in the Al-Aq-rabadhin Al-Saghir, the earliest known document of Arabic pharmacology. 19 Further recommendations are found in Persian texts from the 10th 21 and 17th centuries. 22 Prominent physicians of the Middle Ages, including John Parkinson 23 and Nicholas Culpeper, 24 also recommended the use of cannabis for headache.

The reintroduction of cannabis to the West in 1839 25 began a century of its use as an effective treatment for headache disorders 26 until its illegalization in 1937. 27 Notable physicians who espoused the benefits of cannabis for headache disorders included John Russell Reynolds, the personal physician of Queen Victoria, 28 American neurologist Silas Weir Mitchell, 29 the president of the New York Neurological Society Edouard C. Seguin, 19 William Gowers, a founding father of modern neurology, 30 and Sir William Osler, often considered the father of modern medicine. 31

When cannabis was deemed illegal by the U.S. government, its therapeutic use and research into its medical potential was largely discontinued. To this day, there are few clinical investigations of the use of cannabis for headache; however, the studies that have emerged demonstrate potential efficacy. In addition, numerous pre-clinical investigations 18 have validated the role of endocannabinoids in preventing headache pathophysiology, which suggests a mechanistic role of cannabis in the treatment of these disorders. Although the cannabis plant comprises more than 100 cannabinoids, there has been little study of the individual effects of these cannabinoids on headache disorders; therefore, the present review will focus largely on the clinical potential of the cannabis plant as a whole.

The present review has four unique aims: (1) Highlight common historical trends in the use of cannabis in the treatment of headache to inform future clinical guidelines. (2) Briefly present the current clinical literature on this topic, with a focus on more recent publications that have not been discussed in past reviews. (3) Compile various preclinical studies into a prospective integrated model outlining the role of cannabinoids in the modulation of headache pathogenesis. (4) Outline several 19,32–35 future directions that warrant exploration based on the limited, but promising findings on this topic.

Materials and Methods

The material presented was drawn from standard searches of the PubMed/National Library of Medicine database, influential sources of current medical literature, and past review articles. Search keywords included cannabis; cannabinoids; headache; migraine; cluster headache; medication-overuse headache; tetrahydrocannabinol; cannabidiol; clinical trial; placebo; and double blind. CliniacalTrials.gov was also queried for studies that have not yet been published. Individual articles were selected based on historical, clinical, or preclinical relevance to cannabinoids or cannabis as a treatment for headaches.

Historical Use of Cannabis for Headache

Historical reports, though not ideal forms of evidence, are important resources for understanding the potential use of cannabis in the treatment of headache disorders. Clinical publications between 1839 and 1937 provide valuable insights into the most effective practices, challenges, and benefits during an era when cannabis was commonly used to treat headache. A summary of historical treatment practices using cannabis for migraines can be seen in Table 1 . Historical sources indicate that cannabis was used as an effective prophylactic and abortive treatment for headache disorders. Although dosing varied among physicians, most prescribed alcohol extractions of the drug in the range of ¼ to ½ grain (16–32 mg). 28,32,36–40 This dose was likely chosen to minimize the effects of intoxication while also providing effective therapeutic relief. Other providers suggested that doses should be progressively increased until modest effects of intoxication were felt. 19 For prophylactic treatment, these doses were usually administered two to three times daily for weeks or even months. 28,32,36–38 Acute treatment often involved higher doses taken as needed and, in some cases, smoked cannabis was recommended. 19,41–42

Table 1.

Historical Reports of the Use of Cannabis as a Treatment for Headache (19th and Early 20th Century)

Usage Administration Sample Result Source
Migraine A: 0.03 fluid ounce of alcohol extract 1 h before pain onset 4 Case studies Distinct termination of migraine. All patients experienced improvement, some were cured. Donovan 41
Migraine A: 21.6 mg 2 Case studies Immediate relief and elimination of headache for 14 months after treatment. No lasting harm. Reynolds 27
P: 21.6 mg—three times daily
Migraine/headache P: 21.6 mg, 1–2 times per day (can increase to 43.2 mg) 9 Case studies and clinical experience Responses in majority of cases. Usually lasting relief, sometimes curative. Palliative during headache. Greene 35 ; Russo 18
Clavus hystericus and migraine P: 21.6 mg to 43.2 mg every night Textbook Palliation even in severe cases. Waring 36
Migraine or sick headache P: Taken before each meal (Women: 21.6 mg increased to 32.4 after 2–3 weeks; Men: 32.4 increased to 48.6) Clinical experience Majority of patients reported migraine relief for months. Seguin (1878) cited in Russo 18
Migraine or sick headache A: 21.6–32.4 mg at beginning of attack. Clinical experience Found to be the most effective drug for migraine. Can abort attacks in some cases. Ringer 37
P: 21.6–32.4 mg, 2–3 times daily, for weeks or months continuously.
Migraine P: 8.1–16.2 mg of solid extract twice a day. Clinical experience Helpful prophylactically and abortively, even in cases of migraine refractory to other treatments. Hare 40
A: Take as needed
Chronic daily headache P: 21.6–32.4 mg (increasing if necessary), 2–3 times per day for weeks to months. 4 Case studies Cured complaints in a majority of cases. Mackenzie 38
Migraine P: 16.2 mg twice a day continuously Short report Given immediately will stop attack, given periodically will reduce severity and frequency. Suckling 39
A: Take 16.2 mg during onset of attack

A, abortive; P, prophylactic.

Early reports of cannabis for the treatment of headache appear to be largely positive, with many patients experiencing a decrease in the frequency and intensity of their headache episodes. In some cases, headache was cured entirely even after cannabis discontinuation. 28,32,36–42 Furthermore, these early clinical reports praise the apparent safety of long-term cannabis use, as well as its added benefits of mollifying the nausea and anxiety that often accompany headaches. A common emphasis was placed on the importance of specific purity, preservation, and administration of the cannabis as well as patient adherence in the efficacy of treatment.

Clinical Studies on Cannabis Use for Headache

The schedule 1 classification of marijuana in 1970 has made rigorous clinical studies on the treatment efficacy of this substance difficult. Currently, there are no placebo-controlled clinical studies examining the use of cannabis for headache; nevertheless, there have been a number of other studies published that give insight into its therapeutic efficacy ( Table 2 ). 19,43–58 However, care should be taken when interpreting the findings from these studies. With one exception, 53 these studies did not include a control group, and given that the placebo effect can be altered by the context of treatment, 59 it is reasonable to expect a significant placebo response given the pre-existing public popularity and notoriety of cannabis. Moreover, self-reports and case studies may have a bias toward immediate improvement without awareness of possible dependence, rebound, or withdrawal responses, which are important concerns in headache treatment. 60 In fact, studies show that headache can be induced in 23.2% patients undergoing cannabis withdrawal. 61

Table 2.

Clinical Reports of the Use of Cannabis or Exogenous Cannabinoids as a Treatment for Headache

Subject population Type of study Significant findings Source
3 Chronic smokers Case series Migraines after cannabis cessation. Remission of headache with return to use in one patient. El-Mallakh 42
Patient with migraine Case report Women found superior relief of migraine with cannabis compared with beta-blockers, opiates, and ergots. Petro (1997) cited in Russo 18
Patient with migraine Case report 18 years of treatment failure with standard pharmaceuticals, found success with smoked cannabis. Grinspoon and Bakalar 45
Patient with migraine Case report Successful treatment with cannabis that did not produce inebriation. Terwur (1997) cited in Russo 18
121 Patients prescribed cannabis for migraine Retrospective study Migraine occurrences decreased from 10.4 to 4.6 per month; 39.7% had a positive effect, 19.8% had decreased frequency, and 11.6% had aborted pain. Rhyne et al. 46
5 Cases of chronic migraine headache Case series All cases successfully treated with dronabinol or cannabis. In one case, cannabis improved response more than dronabinol. In three cases, cannabis was used to abort headache in the prodromal phase. Mikuriya 48
1655 Patients seeking physician recommendation for medical cannabis Survey 40.8% of applicants reported improvement of headache symptoms with cannabis. Nunberg et al. 49
3 Subjects with chronic headaches Case series Smoking cannabis caused relief similar or greater than ergotamine and aspirin. Noyes Jr. and Baram 50
30 Outpatients with medication-overuse headache Clinical Trial (RDAC—Crossover) Nabilone was superior to ibuprofen in reducing pain intensity, analgesic intake, and medication dependence while improving quality of life. Pini et al. 52
Patient with refractory cluster headache Case report Smoked cannabis or dronabinol at the beginning of cluster headache provided complete immediate headache relief. Robbins et al. 53
113 Patients with chronic cluster headache Survey 26% regularly used cannabis. Use as treatment unknown. Donnet et al. 54
139 Patients with chronic cluster headache Survey Overall, 45.3% had used cannabis, and 19.4% had used it to treat cluster headache; 25.9% found efficacy, and the remainder found variable or negative effects. Leroux et al. 55
Patient with pseudotumor cerebri Case report Complete resolution of headache with smoking cannabis in

Evans and Ramadan 56
112 Patients with MS-associated trigeminal neuralgia Survey Overall, 70% found relief from trigeminal neuralgia, and 90% found chronic pain relief. Consroe et al. 57

MS, multiple sclerosis.

Nabilone, a synthetic cannabinoid mimicking tetrahydrocannabinol (THC), has been shown to decrease analgesic intake while reducing MOH pain in a double-blind, placebo-controlled trial. 53 In this study, 26 patients with treatment refractory MOH completed a course of either nabilone (0.5 mg) or ibuprofen (400 mg) for 8 weeks, then after a week-long washout period, completed a second 8-week course of the previously excluded medication. Oral cannabinoid administration was chosen over an oromusocal THC spray, both because oral administration avoids the concentration peaks that can lead to euphoric effects and because chronic administration better overcomes individual differences in bioavailability. Although both substances showed improvement from baseline, nabilone was significantly more effective than ibuprofen in reducing pain intensity, analgesic intake, and medication dependence, as well as in improving quality of life. This study also examined the safety of nabilone as a treatment for headache and found that patients only experienced mild adverse effects that disappeared after discontinuation of the medication. The results of this study are significant, especially given that MOH is exacerbated by many pharmacological treatments. This study also highlights the potential value of cannabis in combination therapies, as a supplement to traditional treatments, or as a secondary treatment in refractory cases. Currently, a multicenter, double-blind, placebo-controlled study is being performed to examine the safety and efficacy of a dronabinol, or synthetic THC, metered dose inhaler for the treatment of migraine (clincaltrials.gov, NCT Identifier: > NCT00123201). When published, this study could give valuable insights into the efficacy and risks of cannabinoids for the treatment of migraines.

Cannabis and cannabinoids have been studied clinically for other conditions, showing efficacy in the treatment of neuropathic/chronic pain, spasticity, and nausea. 62–66 These three conditions are associated mechanistically and qualitatively with the experience of headache and, although the clinical literature for each of these conditions exceeds the scope of this review, it is plausible that their efficacy will carry over in the treatment of headache disorders as well. For example, the analgesic properties of cannabis seen in the treatment of neuropathic pain will likely apply to chronic headache, the antispasmodic properties seen in the treatment of multiple sclerosis could apply to muscle strain known to induce tension headaches, and the antiemetic properties seen in the treatment of chemotherapy-associated nausea might also palliate migraine-induced nausea.

Many individuals are currently using cannabis for the treatment of migraine and headache with positive results. In a survey of nine California clinics (N=1746), physicians recorded headaches and migraines as a reason for approving a medical marijuana ID card in 2.7% of cases, and 40.7% patients self-reported that cannabis had therapeutic benefits for headaches and migraines. In another California survey of 7525 patients, 8.43% of patients reported that they were using medical cannabis to treat migraines. Another survey of 1430 patients found that 9% of patients were using medical cannabis to treat migraines (subdivided into 7.5% for classical migraines, 1% for cluster headaches, and 0.5% for others). Other studies have reported the use of cannabis for migraine or headache relief, with specific estimates including 5% (N=24,800) and 6.6% (N=128) for migraines and 3.6% (N=128) and 7.4% (N=217) for headache.

Other studies have looked specifically at the change in the occurrence of headache disorders with use of cannabis. 52 One retrospective study described 121 patients who received cannabis for migraine treatment, among whom 85.1% of these patients reported a reduction in migraine frequency. 47 The mean number of migraines at the initial visit was 10.4, falling to 4.6 at follow-up visits after cannabis treatment. Moreover, 11.6% of the patients found that, when smoked, cannabis could effectively arrest the generation of a migraine. These results indicate that cannabis may be an effective treatment option for certain migraine sufferers.

Reports from 139 cluster headache patients 56 indicate that cannabis could have value in treating a portion (25.9%) of these patients as well. However, cannabis was reported to provoke cluster headache attacks in some patients (22.4%) as well. One possible explanation for this provoking effect is that cannabis is known to increase heart rate, increase blood pressure, and cause systemic vasodilation. 67 Cluster headache sufferers seem to be highly sensitive to vasodilation of the carotid tree and increased oxygen demands, findings that are supported by evidence that alcohol is a reliable trigger and supplemental oxygen is an effective abortive therapy. 68 The increased oxygen demand and/or the vasodilation effects of cannabis could theoretically be responsible for this exacerbation in some cluster headache sufferers. Interestingly, cluster headaches appear to show improvement with treatment using hallucinogens such as d-lysergic acid amide (ergine or LSA), psilocybin, and lysergic acid diethylamide (LSD). 33 As such, it is possible that the psychoactive properties of THC could play a role in the treatment of cluster headaches.

Case reports also give insights into the mechanisms behind the anti-headache action of cannabis. Smoking cannabis has been reported to relieve pain associated with pseudotumor cerebri, 57 a condition that is characterized by an increase in the intracranial pressure of an uncertain etiology. This suggests that the therapeutic effect of cannabis in some headache conditions could be a result of reducing intracranial pressure. In fact, dexanabinol, a synthetic cannabinoid, has been found to relieve intracranial pressure and improve outcomes after traumatic brain injury. 69

Cannabinoids and Headache Pathophysiology

The pathophysiological mechanisms of many headache disorders are not entirely understood. Nevertheless, preclinical data examining the effects of endocannabinoids on the neurological and vascular systems demonstrate the influence of endocannabinoids in modulating several major components of migraine pathogenesis ( Table 3 and Fig. 1 ). 35,70–85