Posts Tagged "headache treatment"


Last updated on April 10th, 2021 at 05:34 am

MIGRAINE HEADACHES EXPLAINED.

@Neuralgroover

Migraines are a very intense type of headache that are often accompanied by other symptoms, including nausea, vomiting, sensitivity to light and sound, as well as neurological symptoms such as visual disturbances, numbness or tingling, speech disturbances (slurred speech, difficulty getting words out), weakness, vertigo, cognitive dysfunction or “cognitive fog”, among other things. Migraines tend to be more prevalent in women than in men, with a 3:1 ratio. A common risk factor for migraines often involves family history, but not for everyone.  People who suffer from migraines report intense feelings of pain, including a pulsating/throbbing sensation. This often occurs on 1 side of the head, but can also involve both sides. Exercise and activity during a migraine will often make it worse. Migraine is usually associated with nausea, and/or sensitivity to light (photophobia) and sound (phonophobia)  Migraines often come in different phases, which are called prodrome, aura, the headache phase, and postodome, but not everyone gets all 4 phases:

  • The prodromal phase of a migraine often marks the beginning of a migraine attack and can happen over a period of a few hours ranging to a few days. Some of the symptoms include irritability and depression; food cravings; yawning and tiredness; and fatigue or muscle stiffness. Some patients report their prodrome as just a difficult to describe feeling that they recognize as an early warning sign of an impending migraine. Not every migraine attack includes the prodromal phase.
  • The aura phase of a migraine doesn’t necessarily always happen in every migraine attack, and only about 25% of patients with migraine get aura. Historically, those that get aura are called “classical migraine”, whereas “common migraine” refers to the more common variety of migraine which isn’t associated with aura. A large number of people who have migraines report that during the aura phase, they experience loss of sight, numbness, and other symptoms. Visual aura (loss of vision, jagged lines, flashing, colors, shapes, wavy lines, kaleidoscope, shimmering, expanding blind spot, etc.) are the most common aura. This is followed by numbness and tingling on 1 side (especially face and arm), and then dysphasia (trouble speaking; slurred speech, getting words out). There are also less common types of aura such as hemiplegic migraine aura (1-sided weakness), and brainstem aura (previously called “basilar migraine”; slurred speech, vertigo, tinnitus, double vision, hearing impairment, decreased level of consciousness, ataxia/imbalance). The aura phase should last between 5-60 minutes per ICHD3 criteria. Hemiplegic migraine can be associated with 1-sided weakness which can last up to 3 days. If the other types of aura last longer than 60 minutes, it is called prolonged or atypical aura, and usually warrants a brain CT or MRI, although it is not too uncommon to see. .
  • The headache phase of a migraine is often the longest and most intense period of a migraine. Symptoms include intensive throbbing, nausea, giddiness, irritability, stiffness, and soreness. According to ICHD3 criteria, an untreated or unsuccessfully treated migraine attack should last 4-72 hours. A headache lasting longer than 72 hours (3 days) is called status migrainosus. It is not uncommon for a refractory migraine to last days and sometimes weeks for some patients.
  • The postdrome phase is the drawing down of a migraine attack. It can last for up to 48 hours and some of the lingering symptoms remain from the other phases of a migraine attack. Patients often report feeling wiped out, fatigued, and sore as if they were “hit by a bus”.

 

According to the American Migraine Foundation, more than 36 million people suffer from migraines (although now estimated to be closer to 39 million), but only one out of three people actually talk to their doctors about their pain.

Statistics About Migraines and Their Prevalence

According to several different sources, migraines are one of the most common types of illness in the world. More specifically, it is ranked as the 3rd most prevalent illness in the world. It is estimated that migraine affects about 39 million Americans, and 1 billion worldwide. For example, 1 in 4 households in the United States have an individual that suffers from migraine attacks. Migraines impact 18-20% of women (1 in 5) and 6% of men (1 in 16) in the United States and they are also fairly common in children.

Migraines are also a common cause for an emergency room visit. In fact, there are more than 1.2 million emergency room visits each year in the United States for someone who is suffering from an acute migraine attack. Patients with migraine have a greater than 1.5 fold increase in office visits, and a greater than 2 fold increase in ER visits and hospital admissions. Migraines can also diminish the quality of life for the people who suffer from them. More than 4 million adults suffer from chronic migraine pain, which is an individual who is experiencing more than 15 days of migraine pain each month. Approximately 3% of patients will transform from episodic migraine to chronic migraine each year. Overall, it is estimated that 3-5% of patients in the United States have chronic migraine. Also, 20% of people who suffer from chronic migraines are disabled. Disability due to migraine peaks between the ages of 15-49 years old, which are peak employment years. Thus, migraine now accounts for the 2nd leading cause of years lived with disability following low back pain! Migraine also accounts for 50% of all neurologic disability. All of this puts a very high price tag on migraine, with an estimated 36 billion dollars spent in migraine costs in the United States each year.

 

Migraines in Children

Migraines are commonly undiagnosed in children. They are more commonplace in adolescent children, but 10% of school-age children suffer from migraines. Half of all migraine sufferers have their first migraine attack before they turn twelve and if a child has one parent who suffers from migraines, they have a 50% chance of developing migraines during their lifetime. Also, boys under the age of twelve tend to have migraines more often than girls, but that trend reverses in adolescence, typically with onset of menarche (which also highlights the hormonal influence on migraine).

 

What Causes Migraines?

There are a number of reasons that people suffer from migraines, but the true cause of them is not fully understood. Genetics and environmental factors play a role. In fact, around ⅔ of migraine cases run in families. Migraines also tend to happen in people who are prone to stress, bipolar disorder, and depression. There are also some common triggers for migraines, including:

  • Drinks, such as alcohol and caffeinated beverages.
  • Work stress or stress at home.
  • Bright lights or strong smells.
  • Drastic changes in one’s sleep cycle.
  • Bouts of overexertion.
  • Changes in the weather or other barometric pressure changes
  • Certain foods and food additives such as MSG, nitrates, aspartame, and other substances such as artificial sweeteners.

 

Migraine Theories:

1) Vascular theory; “vascular headache” (outdated):

a) Lack of blood flow (ischemia) caused by vasoconstriction (narrowing) of the intracranial arteries (arteries inside the brain) caused migraine aura.

b) The vasoconstriction was then followed by rebound vasodilation (dilation) of the arteries. This dilation activated pain receptors on the arteries, and this was the cause of the pulsating headache.

c) This theory has since been disproven and outdated. Studies have also shown that the physical pulsations of the arteries did not correlate to the pulsating sensations of the headache pain.

2) Neurovascular theory (current):

a) Migraine is a neurogenic process with secondary changes in cerebral perfusion (related to neuronal dysfunction and hypometabolism during an attack). In other words, migraine is an electrical neurological event in the brain, not an event triggered by blood flow changes. This electrical event influences changes in brain metabolism such as hypometabolism and hypermetabolism. When the neurons are in a hypometabolism state, they have less oxygen and glucose requirement since they are not as active, and thus there is a lack of blood flow (not due to vasoconstriction of the brain arteries). This can be followed by hypermetabolism in which there is an increase in oxygen and glucose requirements and thus, increase in blood flow (so not necessarily simply rebound vasodilation).

 

b) Migraine aura is a good illustration of this phenomenon. Migraine aura is caused by an electrical wave spreading across the cortex of the brain moving at about 3 mm per minute (not by vasoconstriction as per the older vascular theory). At the front of this spreading electrical wave it causes hypermetabolism and an increase in blood flow. This hypermetabolism causes the “positive” migraine aura features (colors, flashing lights, kaleidoscope, shapes, zig-zags, tingling sensory changes, etc.). Following this electrical wave there is “neuronal depression” and hypometabolism, associated with a decrease in blood flow. This hypometabolism causes the “negative” migraine aura features (loss of vision, black spots, numbness, etc.). Depending on where this wave spreads, you may get different aura symptoms; visual aura as it spreads across the occipital (visual) cortex, sensory/numbness/tingling as it spreads across the parietal (sensory) cortex, dysphasia (trouble speaking, slurred speech) as it spreads across the frontotemporal (speech) cortex, one sided weakness in hemiplegic migraine as it spreads across the frontal (motor) cortex, brainstem symptoms such as vertigo, tinnitus, double vision, hearing loss, imbalance, decreased level of consciousness, slurred speech (previously called basilar migraine, now called migraine with brainstem aura) as it spreads across the brainstem.

 

c) The electrical event of migraine not only causes the changes in metabolism as described above, but the trigeminal nerves are also activated. Think of migraine as an electrical switch that gets turned on in the brainstem. It then turns on and activates the trigeminal nerves. The trigeminal nerves innervate all of the arteries in the brain and through the meninges surrounding the brain. When activated, the trigeminal nerves release a variety of inflammatory proteins (such as CGRP) and neuropeptides. The result of this is 3-fold:

1st, these inflammatory peptides cause neurogenic inflammation around the brain. Think of it like a sterile (non-infectious) meningitis. So, when you’re having a migraine, exercise and activity, moving around, bouncing in a car, etc. often worsen the pain.

2nd, it causes cerebral vasodilation in the brain and meninges. The dilation itself does not cause the pain, but rather it triggers the trigeminal nerves which innervate the arteries, and this sends signals back to the brain that something is going on, which in turn causes more release of inflammatory proteins and causes the migraine to worsen. This is the basis of why it is called the neurovascular theory of migraine.

3rd, it enhances and exaggerates the transmission of pain from the trigeminal nerves, into the brainstem, and into the cortex of the brain where the pain is recognized.

 

At baseline, a patient with migraine who is not having a headache always has a state of neuronal hyperexcitability in the cerebral cortex, especially in the occipital cortex (which is why the majority of aura symptoms tend to be visual aura). So, they have a much lower threshold to a migraine being activated and triggered as compared to someone without migraine. In other words, the neurological system in a patient with migraine can be thought of as always being in a hyperactive, hypersensitive, overdrive state with the “volume turned way up” compared to a person without migraine. Thus, I tell my patients the goal of preventive treatment is to “turn the volume down” and increase the threshold of migraine being triggered so easily.

 

What Are Some Common Treatments for Migraines?

There are two categories of treatment for any type of headache, including migraines. Migraines can be treated through abortive or preventive means. Abortive treatment for any type of headache includes medications such as aspirin, which treats the headache while it’s happening. Preventative treatments are intended to keep a headache or migraine from happening so frequently. Here are some of the different types of treatments for migraines.

 

Abortive Treatment for Migraines

The goal of migraine abortive treatments is to stop individual migraine attacks at onset so the migraine does not reach full severity, ends quickly, and your function is restored and maintained rather than having to go lay down and miss the whole day in bed.  Over-the-counter pain relievers for migraines, such as aspirin or ibuprofen, are fairly commonplace. Some more aggressive abortive treatments include prescription medications like triptans (such as Maxalt) that block pain pathways within the brain. Some people may also receive anti-nausea drugs and opioid prescriptions to deal with more intense migraine symptoms. The migraine specific abortive/acute (as needed) treatments include triptansgepants (Ubrelvy, Nurtec), ditans (Reyvow) or neuromodulatory devices.

Preventative Treatments for Migraines

Medications that lower blood pressure, antidepressants, anti-seizure drugs, CGRP monoclonal antibodies, and even botox are some of the common preventative treatments for migraines. The classification of the preventive medicine typically has nothing to do with its purpose when it is used for migraine. For example, there are specific anti-blood pressure medicines that are good for migraine prevention. However, they do not work for migraine because of blood pressure changes, but rather they affect the electrical pathways of migraine. The same scenario goes for the antidepressant/anti-anxiety and anti-seizure categories. The medicines selected within each of these preventive categories are very specific and based on clinical trials and evidence. In other words, not all medicines within a specific medication class (such as all antidepressants) have evidence for migraine prevention, but rather very specific ones within that class. Medications that are designed to lower blood pressure can sometimes prevent migraines with aura and without aura. Certain types of antidepressants can help prevent migraines, but have some undesirable side effects in some individuals. Anti-seizure drugs, such as Topamax, can reduce the frequency of migraines in some individuals. The preventive migraine treatments should be used until the migraine and headache frequency is significantly improved consistently for several months. As mentioned above, this can be done with a variety of medications which may also include the CGRP monoclonal antibody (mAb) treatments (Aimovig, Ajovy, Emgality, Vyepti), Botox, natural supplements, herbals and vitamins, or neuromodulatory devices.

Alternative Treatments for Migraines

Some other types of treatment for migraines include acupuncture, cognitive behavioral therapy, supplements, essential oils, yoga, meditation, and other techniques designed to enhance relaxation. For some individuals, exercise can decrease the frequency of migraines. In fact, some studies have shown that a routine exercise program can be just as effective as some of the prescription preventive medications used for migraine. Neuromodulatory devices that are FDA cleared for migraine prevention are also available and include sTMS (SAVI, SpringTMS, sTMS mini),  eTNS (CEFALY), and nVNS (GAMMACORE), all of which are discussed in much greater detail here. There are also nutraceuticals and supplements which have good evidence for migraine prevention.

 

Finding Help For Migraines

Migraines remain a poorly understood medical condition, but there are treatments available. Only 4% of people suffering from migraines work with a headache specialist or a pain specialist. It is estimated that preventative treatment could benefit around 25% of people who suffer from severe migraines.

If you suspect that your headaches are migraines, you should see your doctor. Furthermore, any type of headache warrants at least one visit with your doctor to make sure there are no concerns by medical history or examination for any other worrisome causes of your headaches. They may refer you to a neurologist or other type of headache specialist. Oftentimes, a wide variety of tests may be given, including CT scans and MRIs, to see what is contributing to the cause of the migraine. The good news is that migraines can be successfully managed for the majority of patients, and that many people live with them thanks to the treatments that they receive.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

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Last updated on April 10th, 2021 at 05:00 am

WHEN TO SEE A HEADACHE SPECIALIST AND HOW TO PREPARE TO GET THE MOST FROM THE APPOINTMENT.

@Neuralgroover

 

Background

I see patients in our headache center from all over the United States and from many other countries. Many patients travel hundreds of miles by car or airplane for these visits, due to the shortage of available headache specialists (about 570 in the US). Many patients are lucky enough to be relatively close to a headache specialist. Whichever scenario you fall into, you want to get the most out of your appointment with a headache specialist in order to get on a better path to less headache or facial pain burden.

 

When to see a headache specialist

So first of all, when should you see a headache specialist? First off, any type of headache, head pain, or facial pain, is reason enough to see a headache specialist. Basically, headache specialists specialize in any type of pain or discomfort involving anywhere in the head or face. They also commonly see patients that may have other neurological symptoms which may not necessarily be associated with headaches, but their doctor wants to rule out a migraine “equivalent” disorder. Some patients can have neurologic symptoms without headache (visual, sensory, speech, vertigo, weakness, nausea/vomiting, abdominal pain), which may actually reflect a painless migraine disorder, such as migraine aura without headache. I have compiled a list below of a few of my thoughts of when your headache or facial pain treatment journey signals that it is time to see a headache specialist.

 

Reasons to see a headache specialist:

-You have a headache, head pain, or facial pain.

-Your doctor tells you, “your headache is all in your head”.

-Your doctor tells you, “there’s nothing else I can do for you”.

-Your doctor says, “I don’t treat much headache, but…”.

-You continue to have frequent headaches despite trying several preventive medications.

-You just don’t feel like you are making any progress despite a couple office visits with your doctor or their NP or PA (or you never even get to see the doctor).

-You don’t feel like your doctor is listening to you or taking your symptoms seriously.

-The doctor spends only a few minutes in the visit, so you feel rushed and unable to discuss all of your concerns.

-Your doctor is googling your symptoms in the office.

-Your doctor recommends that you take opiates/opioids for migraine treatment.

-Your doctor says it is ok to use NSAIDs, OTCs or triptans more than 10 days per month or butalbital/fioricet/fiorinal more than 5 days per month on average for migraine treatment.

-Your doctor says your headache is “because you are depressed”.

-Your doctor does not give you a more specific classification or name for your diagnosis.

 

What information should you gather before the visit?

Unfortunately, we all know how strapped for time most physicians are during office visits due to a variety of factors such as low insurance reimbursement and the need to increase patient volume to compensate for this and break even. So to get the most out of your office visit, making it efficient and helpful, it is important to compile certain information in preparation. Typing out this information and bringing it to your office visit is a great idea. It is also a great idea to keep this as a running file that you can continue adding to in your personal files. This helps to eliminate time wasted in the office that could easily be organized and thought through prior to the visit, allowing more time for the important parts of the office visit; optimizing the diagnosis and treatment plans. Some of this information you may not have available, and that is certainly ok. You may be able to retrieve some of it from records, memory, and your local pharmacist.

Never assume that your local doctor’s office has faxed all of your records ahead of the visit. If that happens, great. However, many times patients are told that the records will be sent, but when we see the patient, we have no records that were sent. So, it is always best to bring all of your records yourself. Furthermore, it is good to have copies of all of your medical records, testing, etc. for your personal files anyway.

 

The following list are items that I have found to be the most useful for patients to have gathered and thought of prior to the visit, allowing the most efficient and useful office visit:

A) Acute/abortive headache or pain treatments (used “as needed”). This information is also needed in order to pursue insurance approvals for various types of treatments such as the newer gepants (Ubrelvy, Nurtec) or ditans (Reyvow).

-All that have been tried (which triptans, NSAIDs, neuromodulation devices, etc.)

-Doses used

-Responses (effectiveness, side effects) of each treatment

 

B) Preventive headache or pain treatments (used daily to lessen headache frequency/severity). This information is also needed in order to pursue insurance approvals for various treatments such as Botox or the CGRP mAb antagonists (Aimovig, Ajovy, Emgality, Vyepti).

-All that have been tried

-Maximum doses used

-Duration that each treatment was used

-Responses (effectiveness, side effects) of each treatment

 

C) Testing

-All CD and radiology reports for all brain MRIs, CTs, and other relevant testing for your headache or pain. Most CDs do not include the radiology report, and you need to request that separately. It is a good idea to have copies of all of these things for your personal files regardless. Bring them all to the office visit for the doctor to review.

-All bloodwork done in the past 5 years. Labs particularly important for headache evaluations include TSH, CBC, CMP, Vitamin D, Vitamin B12, ESR, CRP, ANA, to name a few, but this may vary and include more or less, depending on the specific clinical scenario.

 

D) Think about the clinical features of your headache or facial pain as listed below. These will be important questions that your headache specialist will ask. So, it is good to answer these questions in your head prior to the visit, so you can provide more accurate and thought out answers. This helps to prevent being put on the spot by questions you never really thought about which may result in forgetting some important details. For a free headache and facial pain self-diagnosis tool which incorporates all of these important questions that a headache specialist asks, look here.

-Location of the headache or facial pain

-Frequency of the headache or facial pain attacks

-Duration of the headache or facial pain attacks

-Description and characterization of the headache or facial pain attacks

-Neurological symptoms associated with the headache or facial pain (visual disturbances, numbness, tingling, weakness, speech disturbances, vertigo, etc.)

-Other associated symptoms with the headache or facial pain (nausea, sensitivity to light or sound, one sided autonomic features (runny eye, red eye, runny or congested nose, droopy or puffiness around eye))

 

Conclusions:

If you are able to gather all or much of the above listed information prior to your headache specialist appointment, you’ll be well on your way to a much more efficient and beneficial office visit. As a result, you and your doctor will be able spend more time in the office discussing the most important things rather than spending it trying to look up records or digging through your memory for various details. As a result, your doctor will have more time to better formulate a list of the most likely diagnoses, and best treatment approaches for minimizing the disruption of your headache or facial pain on your life. Good luck!!

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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Last updated on April 10th, 2021 at 05:10 am

VISUAL SNOW, PERSISTENT MIGRAINE AURA, MIGRAINOUS STROKE, AND WHAT YOU SHOULD KNOW.

@Neuralgroover

INTRODUCTION

The International Classification of Headache Disorders-3 (ICHD-3) classifies persistent aura without infarction (stroke) and migrainous infarction as two of the four reported complications of migraine, both of which are very rare. The other two reported complications of migraine include status migrainosus and migraine aura-triggered seizure, but these will not be discussed here1. 

 

MIGRAINE PATHOPHYSIOLOGY

In order to discuss persistent migraine aura without infarction or migrainous infarction, it is crucial to understand migraine pathophysiology, which involves a multitude of complex processes throughout the cortex, brainstem, and cerebral vasculature. The pathophysiology of migraine has evolved from the vascular theory to the neurovascular theory of migraine. The older vascular theory proposed by Wolff viewed migraine as beginning with cerebral vasospasm causing focal ischemic (lack of blood flow) symptoms (aura) followed by extra and/or intracranial hyperperfusion (excess blood flow) from vasodilatation leading to the migraine pain. 2 This theory made good sense for how stroke or persistent neurological symptoms could develop, from the period of cerebral vasospasm and constriction. However, in later studies of migraine with aura, regional hypoperfusion developed before and outlasted focal neurologic symptoms, and this dissociation of time, perfusion changes and symptoms indicated that these neurologic symptoms were not caused by truly ischemic blood flow, but rather the apparent hypoperfusion is secondary to a disturbance in brain metabolism. 3-6

Lashley first described his own visual aura and hypothesized that the aura was due to a spreading abnormality migrating over the visual cortex at a rate of 3-5 mm per minute in 1941. 7 In 1944, Leão described spreading depression as a wave beginning with a brief neuronal burst associated with transient increased blood flow followed by a longer lasting neuronal electrical suppression with decreased blood flow in an animal model. 8-10 Subsequent studies confirmed this initial focal hyperemia followed by posteriorly to anteriorly spreading oligaemia (reduced blood flow) and regional cerebral blood flow reduction, which does not reach critical ischemic values, in a wave-like manner at approximately 2-5 mm per minute. This spreading regional cerebral blood flow reduction is independent of arterial territories, and does not cross cytoarchitectural borders or neuronal discontinuity such as the central sulcus or lateral sulcus, confirming impaired neuronal metabolism with subsequent regional cerebral blood flow reduction, rather than true ischemia. 3-6 This remains the basis for the now current neurovascular theory of migraine.

Most studies have been unable to show significant ischemic cerebral blood flow changes during migraine attacks. Results have shown alterations in cerebral blood volume, relative cerebral blood flow, and tissue mean transit time (MTT) in the grey matter of the occipital cortex contralateral (opposite) to the side of aura during an attack, while others have shown global cerebral blood flow increase, and others have shown hypoperfusion of the whole hemisphere, but never true ischemic hypoperfusion. 11-14 Notably, cerebral blood flow changes correlate poorly with migraine pain, and neurogenic inflammation in the trigemino-vascular system is suspected to be the primary cause of migraine pain, rather than arterial vasodilatation. 11,15

 

PERSISTENT AURA WITHOUT INFARCTION

The ICHD-3 defines persistent aura without infarction as aura symptoms persisting for 1 week or more without evidence of infarction on neuroimaging. It should occur in a patient with a history of migraine with aura and typical of previous auras except that one or more aura symptoms persist for 1 week or more. Neuroimaging must show no evidence of infarction, and symptoms are not better accounted for by another ICHD-3 diagnosis. The aura symptoms are often bilateral and may last for months or years. It is important to differentiate persistent aura without infarction from symptomatic aura as a result of cerebral migrainous infarction. Aura symptoms lasting more than 1 hour and less than 1 week are classified as probable migraine with aura.

There are two primary types of persistent migraine aura that are described. One is persistent primary visual disturbance in which the patients describe “visual snow” or “television static” in both visual fields in both eyes, and some report additional intermittent scotoma or oscillating lights. 16 The other is persistent migraine aura with typical aura, in which patients describe scotoma, fortification, or oscillation in one hemifield (one side of vision), and does not go away (sometimes also called status aura). 16

The specific pathophysiology of persistent migraine aura without infarction remains unknown, although several theories exist. Some of these theories include low cerebral magnesium levels, abnormal cerebral energy metabolism, greater cerebral reactivity of NMDA receptors to glutamate, lower threshold for triggering cortical spreading depression, low cortical preactivation due to thalamocortical hypoactivity, sustained hyperexcitability of the visual cortex without significant dynamic modulation, sustained cortical neuronal dysfunction, intracortical disinhibition, loss of inhibitory GABA-ergic interneurons resulting in a network imbalance leading to a reverberating cycle of cortical spreading depression (small cortical infarctions below MRI sensitivity in the occipital cortex has been one proposed mechanism), or a combination of any of these possibilities. 16-21

The evaluation for persistent migraine aura without infarction should focus on excluding intracranial pathology, primarily stroke, although other intracranial etiologies need to be excluded. Brain MRI scan is preferable with MRA of the brain and neck (to also assess the arteries), but if medically contraindicated, brain CT scan with CTA of the brain and neck (to assess the arteries) can be pursued. Contrast administration for either type of scan is suggested, although not mandatory. A detailed neuro-ophthalmologic examination is also required. Studies investigating other imaging modalities for persistent migraine aura without infarction, including FDG-PET, MR-PWI, and Tc99m-HMPAO-SPECT, have shown conflicting and inconsistent results.

Treatment for persistent aura without infarction is undefined, and generally based on medication trial and error. The literature reveals an extensive list of medications tried and failed, with most attempting to target neuronal hyperexcitability. Treatments and medications which have been assessed have included anticonvulsants (lamotrigine, topiramate, valproic acid, gabapentin, phenobarbital, phenytoin, carbamazepine), benzodiazepines (clonazepam, diazepam), antidepressants (amitriptyline, cymbalta, buspirone, fluoxetine, nortriptyline, sertraline, dothiepin), anti-hypertensive (atenolol, acetazolamide, flunarazine, metoprolol, propranolol, verapamil, nifedipine, nimodipine, furosemide), NSAIDs (acetylsalicylic acid, ibuprofen, flurbiprofen, diclofenac, indomethacin, naproxen) analgesics (acetaminophen, butalbital, codeine), and a variety of other medications (baclofen, citicholine, ergotamine, ketamine, cyproheptadine, methylphenidate, methylprednisolone, pizotifen, prochlorperazine, promethazine, sumatriptan, memantine). The vast majority of these medications have shown no evidence of benefit. 16 Of them, lamotrigine has shown the most evidence of benefit, while divalproex sodium, baclofen, sertraline, nifedipine, nimodipine, acetylsalicylic acid, and furosemide have reported varying degrees of benefit from complete to partial resolution of symptoms. 16   

Abortive migraine options can include the gepants (Ubrelvy, Nurtec ODT), ditans (Reyvow), NSAIDs and other conventional abortives, although triptans and ergots should be avoided.

MIGRAINOUS INFARCTION

The ICHD-3 defines migrainous infarction as one or more migraine aura symptoms associated with an ischemic brain lesion in a correlating anatomical clinical territory demonstrated by neuroimaging. It should occur in a patient with a history of migraine with aura and typical of previous attacks except that one or more aura symptoms persists for more than 60 minutes, and it should not be better accounted for by another diagnosis. Clearly associating an ischemic stroke and a migraine attack in a migraine sufferer can be difficult. Cerebral infarction of other etiologies can coexist with migraine, can present with symptoms resembling migraine with aura, or cerebral infarction can occur during an attack of migraine with aura, and this is the only scenario that would be consistent with migrainous infarction.

Migrainous infarction occurs predominantly in the posterior circulation and in younger women. In the Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis (CAMERA) study, these infarct-like white matter lesions found in migraineurs (primarily in migraine with aura) were predominantly located in the posterior circulation, especially in the cerebellum. 22,23 However, these infarctions are not necessarily considered migrainous infarctions and the mechanisms are unclear.

Multiple studies have confirmed the association with increased stroke risk in women with migraine with aura. Women younger than age 45 who have migraine with aura, have a 2 fold increased risk of stroke. Notably, migraine without aura does not appear to have the same increased risk. This risk increases to 6 fold in the setting of oral contraceptive use containing estrogen, and more than 9 fold with combined smoking and oral contraceptive use. 24 Menstrual migraine and the use of hormonal therapy and birth control is discussed in more detail here. Women who are smokers and have migraine with aura should consider estrogen containing oral contraception a contraindication. Oral contraceptive use in non-smoking women with migraine with aura is more controversial. The World Health Organization (WHO) and American College of Obstetrics and Gynecology (ACOG) suggest that in non-smoking women under age 35 with migraine with aura, there is an acceptable lower risk of oral contraceptive use. However, if they are over age 35, the risk is unacceptably higher and oral contraceptive use is contraindicated. According to the International Headache Society (IHS), in non-smoking women with migraine with aura who are either younger or older than age 35, taking into account other risk factors should individualize the decision for oral contraceptives. 24 These would include ischemic heart disease, family history of early heart disease at a young age of less than 45 years old, heart disease with concern for emboli such as atrial fibrillation, uncontrolled hypertension, hyperlipidemia, diabetes, obesity, systemic disease associated with increased stroke (connective tissue disease, sickle cell, hypercoagulability), etc. In women with an increased risk of stroke, and especially with multiple vascular risk factors, non-estrogen methods of birth control such as progesterone-only forms of contraception should be recommended.

Research has also reported that after high blood pressure, migraine with aura was the second strongest single predictor of heart attack and strokes, ahead of diabetes, smoking, obesity, and family history of early heart disease. 25 This increased risk was not seen in migraine without aura. It is not necessarily thought that migraine with aura causes the stroke, but rather it is a marker for young women at a greater risk for cardiovascular disease. However, the reasons for these associations are unclear, likely multifactorial, and clearly need to be further defined. Traditional vascular risk factors such as hypertension, smoking, diabetes and hyperlipidemia still show the strongest contribution to cardiovascular disease, so these should be optimized, especially in those with migraine with aura to reduce risk of both heart disease and stroke. 25

Some theorized mechanisms of migrainous infarction include vasospasm, endothelial dysfunction, vascular endothelium-related hypercoagulability during cortical spreading depression and the aura phase, or genetic alterations of the wall of the small cerebral arterial vessel walls. 26-31

The evaluation for migrainous infarction is similar to that of persistent migraine aura without infarction. By definition, an ischemic infarct in a correlating anatomic area to symptoms should be seen on MRI or CT of the brain. This warrants a further standard stroke evaluation, including imaging of the intra and extracranial vasculature (including carotid arteries), as well as cardiac evaluations beginning with transthoracic echocardiography. Electrocardiogram and telemetry should also be pursued to evaluate for paroxysmal arrhythmias such as atrial fibrillation.

Treatment of migrainous infarction is the same as with any ischemic stroke. The initial goal is to evaluate for potentially treatable etiologies (such as cardioembolic source) and treat accordingly. Otherwise, secondary stroke risk factor modifications are the goal and include antiplatelet therapy in combination with optimal control of blood pressure, hypertension, hyperlipidemia, diabetes, tobacco cessation, and healthy lifestyle changes.

Abortive migraine options can include the gepants (Ubrelvy, Nurtec ODT), ditans (Reyvow), NSAIDs and other conventional abortives, although triptans and ergots should be avoided.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

REFERENCES

  1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2013;33:629-808.
  2. Wolff HG. Headache and Other Head Pain. New York: Oxford University Press, 1963.
  3. Olesen J, Larsen B, Lauritzen M. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 1981;9:344-52.
  4. Lauritzen M. Pathophysiology of the migraine aura. The spreading depression theory. Brain 1994;117 ( Pt 1):199-210.
  5. Lauritzen M, Skyhoj Olsen T, Lassen NA, Paulson OB. Changes in regional cerebral blood flow during the course of classic migraine attacks. Ann Neurol 1983;13:633-41.
  6. Lauritzen M,  Olesen J. Regional cerebral blood flow during migraine attacks by Xenon-133 inhalation and emission tomography. Brain 1984;107 ( Pt 2):447-61.
  7. Lashley KS. Patterns of cerebral integration indicated by the scotomas of migraine. Arch Neurol Psych. 1941;46:331-339.
  8. Leao AAP. Spreading depression of activity in cerebral cortex. Journal of Neurophysiology 1944;7:359-390.
  9. Leao AAP,  Morrison RS. Propagation of spreading cortical depression. Journal of Neurophysiology 1945;8:33-45.
  10. Leao AAP. Pial circulation and spreading depression of activity in the cerebral cortex. Journal of Neurophysiology 1944;7:391-396.
  11. Thomsen LL, Iversen HK, Olesen J. Cerebral blood flow velocities are reduced during attacks of unilateral migraine without aura. Cephalalgia 1995;15:109-16.
  12. Kobari M, Meyer JS, Ichijo M, Kawamura J. Cortical and subcortical hyperperfusion during migraine and cluster headache measured by Xe CT-CBF. Neuroradiology 1990;32:4-11.
  13. Sakai F,  Meyer JS. Regional cerebral hemodynamics during migraine and cluster headaches measured by the 133Xe inhalation method. Headache 1978;18:122-32.
  14. Tfelt-Hansen PC,  Koehler PJ. One hundred years of migraine research: major clinical and scientific observations from 1910 to 2010. Headache 2011;51:752-78.
  15. Moskowitz MA. Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 1993;43:S16-20.
  16. Thissen S, Vos IG, Schreuder TH, Schreurs WM, Postma LA, Koehler PJ. Persistent migraine aura: new cases, a literature review, and ideas about pathophysiology. Headache 2014;54:1290-309.
  17. Relja G, Granato A, Ukmar M, Ferretti G, Antonello RM, Zorzon M. Persistent aura without infarction: decription of the first case studied with both brain SPECT and perfusion MRI. Cephalalgia 2005;25:56-9.
  18. Chen WT, Lin YY, Fuh JL, Hamalainen MS, Ko YC, Wang SJ. Sustained visual cortex hyperexcitability in migraine with persistent visual aura. Brain 2011;134:2387-95.
  19. Wang YF, Fuh JL, Chen WT, Wang SJ. The visual aura rating scale as an outcome predictor for persistent visual aura without infarction. Cephalalgia 2008;28:1298-304.
  20. Chronicle E,  Mulleners W. Might migraine damage the brain? Cephalalgia 1994;14:415-8.
  21. Coppola G, Parisi V, Di Lorenzo C, et al. Lateral inhibition in visual cortex of migraine patients between attacks. J Headache Pain 2013;14:20,2377-14-20.
  22. Kruit MC, van Buchem MA, Launer LJ, Terwindt GM, Ferrari MD. Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: the population-based MRI CAMERA study. Cephalalgia 2010;30:129-36.
  23. Kruit MC, Launer LJ, Ferrari MD, van Buchem MA. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain 2005;128:2068-77.
  24. Tepper SJ, Tepper DE. The Cleveland Clinic Manual of Headache Therapy, 2nd ed. . Switzerland: Springer International Publishing, 2014.
  25. Kurth T, Bubes V, Buring J. Relative Contribution of Migraine with Aura to Cardiovascular Disease Occurrence in Women. Neurology 2013;80.
  26. Pezzini A, Del Zotto E, Giossi A, et al. The migraine-ischemic stroke relation in young adults. Stroke Res Treat 2010;2011:304921.
  27. Pezzini A, Del Zotto E, Giossi A, Volonghi I, Grassi M, Padovani A. The migraine-ischemic stroke connection: potential pathogenic mechanisms. Curr Mol Med 2009;9:215-26.
  28. Kurth T, Chabriat H, Bousser MG. Migraine and stroke: a complex association with clinical implications. Lancet Neurol 2012;11:92-100.
  29. Kurth T. Migraine and ischaemic vascular events. Cephalalgia 2007;27:965-75.
  30. Tietjen EG. Migraine and ischaemic heart disease and stroke: potential mechanisms and treatment implications. Cephalalgia 2007;27:981-7.
  31. Bousser MG,  Welch KM. Relation between migraine and stroke. Lancet Neurol 2005;4:533-42.

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Last updated on April 8th, 2021 at 11:51 pm

MEDICAL MARIJUANA (CANNABIS) FOR MIGRAINE, HEADACHE AND PAIN. A CRASH COURSE OF EVERYTHING YOU NEED TO KNOW.

@Neuralgroover

BACKGROUND

Medical marijuana (medical cannabis) for treatment of migraine, headache, pain, and chronic pain has become an increasingly hot topic of interest. As states continue to legalize the use of medical marijuana, there are increasing discussions and questions about its medical uses. What are the best medical marijuana strains for migraine, headache, and pain? Is medical marijuana helpful for migraine, chronic migraine, headache, pain, and chronic pain? How is medical marijuana used and dosed? Is medical marijuana legal to use? What are the side effects of medical marijuana? How do you get medical marijuana? How does marijuana differ from CBD (cannabidiol)? What is the best CBD dose for pain? What is the best CBD dose for migraine? What is the best THC dose. How do you increase CBD dosing, THC dosing, or cannabis dosing?

 

Patients ask about these treatments all the time, so this blog is to provide a comprehensive overview to answer all of these questions and much more. Reading the whole blog will give you a comprehensive, yet condensed detailed education of its history and everything you need to know about cannabis, CBD, and THC for medical use, with an additional focus in the treatment of migraine and pain. Alternatively, you can skip down to find the specific topic that you are looking for information on. For example, specific suggestions for how to begin CBD or THC dosing, and a schedule of how to titrate upwards can be found below. If you would like to skip to a specific topic, here is the sequence of the topics discussed:

 

-HISTORY CRASH COURSE OF MARIJUANA (CANNABIS) IN THE TREATMENT OF MIGRAINE, PAIN, PROHIBITION, AND RETURN TO LEGAL STATUS.

-STATES WHERE MEDICAL AND RECREATIONAL (ADULT-USE) MARIJUANA (CANNABIS) ARE LEGAL.

-MEDICAL MARIJUANA (CANNABIS) USE FOR PAIN AND MIGRAINE.

-WHAT TYPES OF MARIJUANA (CANNABIS) ARE THERE AND HOW DO YOU KNOW WHICH ONE TO USE?

-WHAT IS THE EVIDENCE FOR MARIJUANA (CANNABIS) USE FOR MIGRAINE?

-GENERAL SUGGESTIONS OF HOW TO USE MEDICAL MARIJUANA (CANNABIS).

-HOW DO YOU ESTIMATE THC CONTENT, WHAT IS THE BEST THC DOSE, AND HOW DO YOU USE THC?

-WHAT IS THE BEST CBD DOSE AND HOW DO YOU USE CBD?

-SIDE EFFECTS AND ADVERSE REACTIONS OF MEDICAL MARIJUANA (CANNABIS).

-WHAT IS CANNABIS HYPEREMESIS SYNDROME AND HOW DO YOU TREAT IT?

-CANNABIS (MARIJUANA) ADDICTION AND ABUSE

 

When many people hear the term “medical marijuana”, they think of a street drug with no true medicinal qualities, used only for recreation and abuse. Their mind immediately activates the visual hippie imagery of the 1967 Summer of Love and 1969 Woodstock festival. However, this is an outdated view in the scientific research community. The term “marijuana” (sometimes spelled marihuana) is a loaded term with many negative connotations including old political and racial associations, and is associated with the plant being used recreationally as a drug of abuse. Cannabis is the scientific name of the plant and is the preferred terminology.

 

It is best to think of cannabis, as a broad class of medication. Within this medication class there are many types of cultivars (strains, breeds), or more accurately, chemovars (chemotypes). “Cultivar” is short for “cultivated variety”, while “chemovar” refers to “chemical variety”. The older cultivar classification system (Sativa, Indica, Ruderalis) has evolved to the more current, scientific, and simplified chemovar classification system. These systems are discussed in more detail further down under the treatment section.

 

Each chemovar has standardized reproducible compositions of cannabinoids and terpenes, which are the phytochemicals in cannabis that make up most of the medicinal qualities. The CBD and THC (tetrahydrocannabinol) cannabinoids and terpenes are discussed further down, and are also discussed in great detail here. Similar to a medication, there will be some variation in benefits, responses, effectiveness, and side effects between patients for each chemovar. Also similar to a medication, there are common characteristics attributed to each chemovar that the majority of users will experience.

 

For comparison of this concept, antidepressants are a broad class of medication. Within this medication class there are many types of drugs. Each drug has standardized reproducible compositions of neurotransmitter targets. Similarly, there will be some variation in benefits, responses, effectiveness, and side effects between patients for each drug, and a set of common characteristics attributed to each drug that the majority of users will experience.

 

HISTORY CRASH COURSE OF MARIJUANA (CANNABIS) IN THE TREATMENT OF MIGRAINE, PROHIBITION, AND RETURN TO LEGAL STATUS.

To understand the current legal status of cannabis, it is important to know the history of cannabis, detailed here. The use of cannabis for medicinal purposes dates back to ancient times, with a Western/Central Asian botanical origin. Medicinal uses have been documented to 4000 BC or more. Chinese physicians were using it for joint pains and analgesia in childbirth 5000 years ago. Fast forward to 1839 when Dr. William Brooke O’Shaughnessy introduced the Western world to the medicinal uses of Cannabis indica, or “Indian hemp”, after he spent a professorship in Calcutta, India and learned of its uses while there. He advocated for its use in analgesia and muscle relaxation.

 

Throughout the 1800s into the 1900s, it was being recommended by many prominent physicians of those times for numerous diseases, particularly pain, headache, chronic daily headache, migraine, and chronic migraine, and was being used both acutely and preventatively.

 

In 1890, Sir John Reynolds, President of the British Medical Association, and Physician to the Royal household, wrote a paper in Lancet on his 30 years of experience prescribing cannabis for variety of ailments, particularly migraine and neuralgia.

 

In 1915, the “Father of modern medicine”, Sir William Osler, was recommending cannabis for migraine treatment in his historic medical textbook of those times, The Principles and Practice of Medicine. He went on to suggest that when treating migraine, “Cannabis indica is probably the most satisfactory remedy. Seguin recommends a prolonged course.” Dr. E.C. Seguin whom he referenced was a well-known neurologist and was the President of the NY Neurological Society. He was a vocal proponent of cannabis for migraine.

 

Cannabis-based preparations had been listed in the US Dispensatory in 1845. In North America, some pharmaceutical companies including Bristol-Meyers Squib, Parke-Davis, and Eli Lilly were producing cannabis-based preparations, as was Burroughs-Wellcome & Co. in England.

 

In the 1930s, Harry Anslinger was leading the Federal Bureau of Narcotics, which was essentially the early DEA. He began a campaign against cannabis, attempting to associate psychosis, mental deterioration, addiction, and violent crimes to cannabis use. He claimed cannabis was a drug of abuse used by minority and low-income communities. Instead of using the term cannabis when he was pushing his prohibition bill in front of congress in 1937, he purposely would use the term “marijuana,” subtly trying to convey a racial connection since it was commonly associated with recreational use among poor Mexican immigrants who would bring it from Mexico to the USA at that time. He reportedly chose his terminology wisely to fit this agenda and distance the plant from the more scientific term cannabis along with its growing uses for medicinal and industrial purposes. Furthermore, marijuana has a general connotation of being used as an intoxicant and recreationally, whereas cannabis has more of a scientific association. For all of these reasons, cannabis should really be the preferred terminology over marijuana.

 

The Marihuana Tax Act of 1937 was passed, attributing large fines and prison time to anyone involved with cannabis. Some historians also discuss influence on this law from prominent businessmen such as Andrew Mellon and the DuPont family since the hemp industry was gaining traction in industrial uses, posing a threat to synthetic and other more common competitor products, but that is a whole different discussion. The AMA (American Medical Association) strongly opposed this law.

 

In 1938, Dr. Robert Walton argued against the new Marihuana Tax Act and published a comprehensive review of cannabis, referencing 12 experts on its effectiveness for migraine.

 

In 1941 cannabis preparations were taken off the US Pharmacopoeia and National Formulary.

 

In 1942, Dr. Fishbein, the Editor of JAMA (Journal of the American Medical Association), published his recommendations for oral preparations of cannabis over ergotamine for menstrual migraine. Other physicians also published supporting evidence for cannabis in migraine treatment.

 

Then the 1960s hit, where there was a resurgence of recreational marijuana use. This left a lasting and ongoing negative stigma of cannabis. Again, cue the visual hippie imagery of the 1967 Summer of Love and 1969 Woodstock festival. Unfortunately, many people who are not aware of cannabis history have been stuck in this mindset since…

 

The final nail in the coffin for legal cannabis use came with the Controlled Substances Act of 1970. This is what changed cannabis to its schedule 1 drug illegal status, of which it has remained since that time. The Assistant Secretary of Health, Dr. Roger O. Egeberg, stated his reason as follows, “Since there is still a considerable void in our knowledge of the plant and effects of the active drug contained in it, our recommendation is that marijuana be retained within schedule 1 at least until the completion of certain studies now underway to resolve the issue.”

 

Well, we are well past those studies Dr. Egeberg mentioned, and extensively more have been completed since then, yet cannabis remains federally illegal, despite all the evidence and vast amount of knowledge that we have gained from research. Thus, it is only a matter of time until the tide finally turns completely, and cannabis is rescheduled from Schedule 1 in my opinion.

 

So, cannabis has been a schedule 1 drug since 1970. Schedule 1 drugs also include heroin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (Ecstasy). According to the United States Drug Enforcement Agency (DEA), Schedule I drugs have a high potential for abuse, and have no accepted medical treatment use. If you are saying to yourself, that cannabis doesn’t seem like it fits into this category, you are certainly part of the majority opinion, which has shifted over the years. The DEA has continued to claim that cannabis has “no accepted medicinal use”, a statement which has no evidence to support it, but rather more evidence exists that disprove that claim.

 

Interestingly, despite this claim of no medicinal benefit, the US Government’s Department of Health and Human Services was awarded a patent (US Patent #6,630,507) for “cannabinoids as antioxidants and neuroprotectants” in 2003. Furthermore, the FDA has approved 3 synthetic versions of cannabinoids for medicinal purposes. Two are synthetic forms of THC (Dronabinol (Marinol), Nabilone (Cesamet)), and one is a purified form of CBD (Epidiolex). So, these statements and facts are clear contradictions to one another…

 

The schedule 1 classification has been a huge barrier preventing US federal funding for research and the legal ability to even proceed with research, although this has loosened up in recent years. This has historically been the primary hurdle in conducting medical research needed to obtain the evidence-based medicine in support of cannabis in the US. Meanwhile, many other countries such as Israel and Canada have been researching for years and have federal cannabis programs. For example, the Canadian equivalent to the US FDA is Health Canada. They have maintained a successful federal cannabis program for years. Despite this schedule 1 hurdle in the US, there has been accumulating evidence for various therapeutic benefits of cannabis, especially in the treatment of pain disorders.

 

In 1976, the FDA began an Investigational New Drug Program, after a glaucoma patient sued the government on grounds that cannabis was helping him, and won. This program closed in 1992, and 13 patients in the program at the time of closure were allowed to continue. Most recently, there were still 2 remaining who still receive monthly government supplied cannabis; one for multiple hereditary exostoses (painful bone tumor disorder), and the other for glaucoma. Access to this government supplied cannabis has since been controlled by the National Institute on Drug Abuse (NIDA), and the only federally approved cannabis source for decades has been from a farm at the University of Mississippi, who has had an ongoing contract with the federal government since 1968.

 

Through the 1990s-2000s, there was growing commentary from leading physicians and journals supporting cannabis for medicinal purposes. This has been accompanied by a growing push by medical organizations to reschedule cannabis to allow research and for patients who need it when they have failed all conventional treatments. Some of these organizations include American Academy of Neurology (AAN), American Medical Association (AMA), Epilepsy Foundation, American Journal of Public Health, and American Academy of Pediatrics (AAP).

 

In 2013, Dr. Sanjay Gupta MD, CNN Chief Medical Correspondent, issued a public apology article retracting his previous anti-marijuana stance which can be read here. He noted that “of more than 20,000 papers published in recent times, only 6% of the studies look at potential benefits of cannabis, while all the rest investigate potential harm, leading to an inherent bias and a profoundly distorted view.” He went on to further say:

“Well, I am here to apologize. I apologize because I didn’t look hard enough, until now. I didn’t look far enough. I didn’t review papers from smaller labs in other countries doing some remarkable research, and I was too dismissive of the loud chorus of legitimate patients whose symptoms improved on cannabis. Instead, I lumped them with the high-visibility malingerers, just looking to get high. I mistakenly believed the DEA listed marijuana as a Schedule 1 substance because of sound scientific proof. Surely, they must have quality reasoning as to why marijuana is in the category of the most dangerous drugs that have “no accepted medicinal use and a high potential for abuse.” They didn’t have the science to support that claim, and I now know that when it comes to marijuana neither of those things are true. It doesn’t have a high potential for abuse, and there are very legitimate medical applications. In fact, sometimes marijuana is the only thing that works. We have been terribly and systematically misled for nearly 70 years in the United States, and I apologize for my own role in that.”

 

Dr, Gupta has done a series of documentaries on CNN about the medicinal benefits of cannabis and are very enlightening to watch. This change in Dr. Gupta’s public opinion was also occurring along with spreading anecdotal cases of children with refractory pediatric epilepsy who were improving dramatically with CBD extracts from cannabis. One of these children, Charlotte Figi, became the poster child for this movement. In fact, the cannabis strain bred and extracted for high CBD for these purposes (Charlotte’s Web), was named after her. Unfortunately, she died 4/7/20 at the age of 13, and was remembered here.

 

STATES WHERE MEDICAL AND RECREATIONAL (ADULT-USE) MARIJUANA (CANNABIS) ARE LEGAL.

The legal use of medicinal cannabis continues to increase globally, including the United States. In 1996, CA became the 1st state to pass the Compassionate Use Act, allowing the legal use of cannabis for medicinal purposes. Since that time, legalized cannabis has continued to grow. As of 11/4/20, medical use of cannabis is legal in 35 states (AK, AR, AZ, CA, CO, CT, DE, FL, HI, IL, LA, ME, MD, MA, MI, MN, MO, MS, MT, ND, NH, NJ, NM, NY, NV, OH, OK, OR, PA, RI, SD, UT, VT, WA, WV) + Washington DC. Recreational marijuana use (“adult use”) is approved in 15 states (AK, AZ, CA, CO, IL, MA, ME, MI, MT, NJ, NV, OR, SD, VT, WA) + Washington DC. Despite a number of states legalizing cannabis use at the local level, it is still illegal federally in all states.

 

States which have medical cannabis programs have a list of qualifying conditions, which vary by state. The State Medical Board certifies doctors to “recommend” medical cannabis (Certificate to Recommend; CTR). The physician then confirms the qualifying condition and signs a “recommendation” form for potential benefit from medical cannabis. The patient then takes the recommendation to the local dispensary (which are also highly regulated by the state) and the patient discusses the best options there. However, it is important to remember that under the CSA (Controlled Substances Act), cannabis remains a schedule I drug, so doctors can’t “prescribe” cannabis. They can only “recommend” it. Also, interstate travel with any amount of cannabis or plant extract (including CBD products with THC content >0.3%) violates federal law and could potentially result in federal drug trafficking charges with stiff penalties of prison time and fines.

 

In 2009, the Justice Department sent a memorandum to federal prosecutors stating that patients and their providers should not face federal prosecution if they are following state law. In 2013 the Cole Memorandum was sent to US Attorney Generals, reinforcing that the Justice Department would not enforce federal prosecution in legal states who are following their state laws. In 2018, the Cole Memorandum was rescinded by Attorney General Jeff Sessions, which sent shockwaves through the industry. However, President Trump has continued to reinforce his support in protecting states that have legalized cannabis from federal prosecution. There have been discussions of re-evaluating the rescheduling of cannabis to remove the federal schedule 1 illegality, and it is suspected to be only a matter of time until this eventually happens.

 

MEDICAL MARIJUANA (CANNABIS) USE FOR PAIN AND MIGRAINE.

In medical cannabis registries, the most commonly reported reason for cannabis use is chronic pain of various types. Because of the increasing evidence of cannabis in the treatment of pain, the Canadian Pain Society revised their consensus statement in 2014 to recommend cannabinoids as a third-level therapy for chronic neuropathic (nerve) pain based on the abundance of supporting evidence and a NNT (number needed to treat) estimated at approximately 3 (the number of patients needed to treat for 1 of them to receive benefit). In 2017, The U.S. National Academies of Sciences, Engineering, and Medicine published a statement that the use of cannabis for the treatment of pain is supported by well-controlled clinical trials and that there is substantial evidence that cannabis is an effective treatment for chronic pain in adults. In February 2019, the World Health Organization (WHO) recommended that cannabis be rescheduled and removed from the most restrictive scheduling category.

 

Cannabis works through our endocannabinoid system. The endocannabinoid system is a normal and important biological system within everyone which helps to maintain homeostasis. It plays a role in many regulatory physiological processes across all organ systems, and is widely distributed throughout the central nervous system (brain and spinal cord) and peripheral nervous system (nerves outside of the spinal canal). This system is involved in the “runner’s high” as well. Notably, it plays a very strong role in pain pathways. This system works by the interaction of our own natural endocannabinoids turning on or turning off various endocannabinoid receptors throughout our body.

 

Over 540 phytochemicals have been described in cannabis, 18 different chemical classes, and more than 100 different phytocannabinoids. THC and CBD have been the most researched and are considered the major cannabinoids. There are many additional cannabinoids referred to as minor cannabinoids. The quantities of major and minor cannabinoids are widely variable between different types of cannabis chemovars. There is evidence for analgesic and anti-inflammatory effects in many of the cannabinoids. Cannabinoids are unique to the cannabis plant, and can be thought of as the “plant equivalents” of our own endocannabinoids. So, they interact with the same endocannabinoid receptors in our body as our own endocannabinoids do. The existing literature and research on the treatment of pain have primarily studied cannabis itself with its variable and often undefined combinations of THC, CBD, other cannabinoids, terpenes, and other constituents. These compounds, especially cannabinoids and terpenes, play significant roles in influencing one another and working together. The synergy and interactions between these compounds are referred to as the “cannabis entourage effects”. Thus, the medicinal benefits of cannabis are suspected to be from the “entourage effects”, more so than any of the individual components alone.

 

THC is a major cannabinoid and the most researched in cannabis. THC causes the psychoactive qualities (“high”) of cannabis. THC has been shown to be 20 times more anti-inflammatory than aspirin and 2 times as anti-inflammatory as hydrocortisone. It is also a potent anti-emetic (anti-nausea), which is why there are two FDA-approved synthetic THC medications for chemotherapy related nausea and vomiting (Dronabinol, Nabilone). THC is the cannabinoid which is tested for in drug tests. It is important to know that most CBD products contain trace amounts of THC, although there are some varieties that do not. It is typically a negligible amount unlikely to show up on a drug test, but it is not completely risk free. You can read about the different types of CBD products here. THC can be detected by a variety of ways, although most commonly it is tested in the urine. Here are the general timeframes that it will show positive:

  • Blood:
    • Few hours to 1-2 days after a single use
    • In heavy users (multiple times a day), possibly up to a week
  • Saliva:
    • Appears in saliva an hour after use, detectable for up to 1-2 days
  • Urine:
    • 5-12 days after one-time use
    • 11-18 days when used 2-4 days/week
    • 33-48 days when used 5-6 days/week
    • Around 50-65 days if used daily (stored in adipose tissue)
  • Hair:
    • Generally 90 days, but some hair follicle tests can go back years

CBD is the other major cannabinoid and has gained a lot of attention as a therapeutic agent over the past several years given a wide range of reported anecdotal benefits. It is discussed in much greater detail here. In contrast to THC, CBD is non-intoxicating (no “high”). Furthermore, it helps to neutralize some of the negative THC side effects. CBD has been shown to be several hundred more times anti-inflammatory than aspirin. Greater than 65 molecular receptor targets and greater than 80 mechanisms of action have been identified. There have been scientific, animal models, and very limited human clinical trials documenting its anti-inflammatory and analgesic (pain-relieving) properties. However, there are no high-quality research studies to date evaluating isolated pure CBD in any pain, migraine, or other headache disorders. So, it is unclear how much benefit CBD in isolation provides outside of the presumed entourage effects that it contributes to.

 

In November 2017, The World Health Organization (WHO) concluded that CBD exhibits no evidence for abuse or dependence potential, and that there is no evidence of public health related problems associated with its use. In January 2018, the World Anti-Doping Agency (WADA) removed CBD from their prohibited list, no longer banning use by athletes. In December 2018, the Agriculture Improvement Act (Farm Bill) was signed into law. This legalized the agricultural growth and use of hemp (cannabis strains containing 0.3% THC or less) and hemp derivatives such as CBD. The Farm Bill also removed hemp from the Controlled Substances Act, making it no longer an illegal substance under federal law. Up until the Farm Bill was passed, any form of cannabis or cannabis derivatives (including CBD) have been federally illegal since the Controlled Substance Act of 1970. Therefore, it is important to remember that cannabis chemovars and CBD oils with greater than 0.3% THC are still illegal federally, require a medical cannabis card for use, and are illegal to cross state lines with. In May 2019, TSA began to allow travel with CBD products containing 0.3% or less of THC.

 

The terpenes account for many of the pharmacological properties of cannabis, as well as many medicinal herbs, plants and essential oils. They are the source of flavors, aromas, and other characteristics that help differentiate cannabis cultivars. Terpenes are often used in many household products such as limonene (citrus), pinene (pine, conifer), and linalool (lavender) to name just a few. Similar to the cannabinoids, many have anti-inflammatory and analgesic properties.

 

WHAT TYPES OF MARIJUANA (CANNABIS) ARE THERE AND HOW DO YOU KNOW WHICH ONE TO USE?

As discussed at the beginning of the blog above, there are many types of cannabis chemovars that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and chemovar characteristics. Different chemovars have different ratios of these compounds, and thus have different characteristics.

 

The older cultivar (strain, breed) classification system was based on strain appearance, smell, and clinical effects. Cannabis Sativa strains were generally described by patients as uplifting, energetic, creative, euphoria, spacey, cerebrally-focused effects, and better for day use, while cannabis Indica strains were typically described as calming, relaxing, sedative, full body effects such as “body buzz”, and better for night use. Cannabis ruderalis (hemp) strains were considered predominantly or purely high CBD without any real clinical use effects.

 

However, biochemical studies of specific strain names often do not accurately distinguish CBD and THC content, which was the predominant basis for strain classification. Strain characteristics and clinical effects are dependent on varying ratios of major and minor cannabinoids and terpenes, not only from CBD:THC ratios, as there are no significant differences in CBD:THC ratios between many Sativa and Indica strains when studied chemically. Most strains used today are hybrid strains genetically cross-bred for standardized CBD, THC, terpenes, and minor cannabinoid content.

 

The older cultivar classification system has evolved to the newer and more scientific chemovar (chemotype) classification system, and is divided into type I-III chemovars. This system allows medical users to find a chemical profile better matching their pharmacological needs.

 

Type I chemovars are THC predominant. They are high THC (>0.3%, but generally >10-20%), and low CBD (<0.5%, but generally <2%). They are very intoxicating, and associated with recreational more than medical use. They are moderately-heavily psychedelic with changes in perception and sensory awareness and have the potential for significant physiological changes in heart rate and blood pressure. They can intensify relief from symptoms like nausea or pain, so terminal cancer patients may be one of the few true medical uses for these chemovars.

 

Type II chemovars are more balanced THC and CBD. They are high THC (>0.3%, but generally 3%-10%), and high CBD (>0.5%, but generally 1%- 14%). They are intoxicating to a lesser degree than Type I chemovars. They can be mildly-moderately psychedelic with milder cerebral and cognitive changes in perception and sensory awareness possible. In general, they can be more effective at treating symptoms with less negative side effects.

 

Type III chemovars are CBD predominant. They are low THC (<0.3%, but generally 0%-1%), and high CBD (>0.5%, but generally 5%-20% or more). They have low to no intoxication side effects. There is little to no cognitive impairment for most, but there can be possible mild effects in sensitive users, depending on the THC content.

 

WHAT IS THE EVIDENCE FOR MARIJUANA (CANNABIS) USE FOR MIGRAINE?

The benefits of cannabis/cannabinoids in various chronic pain disorders has been well established. These benefits are suspected to likely extrapolate to headache disorders including migraine given overlapping neurobiological pathways of pain. There are some notable interactions and synergies between the cannabinoid receptors and pathways of migraine involving the trigeminovascular system (including the same receptors that the triptans work on) and serotonergic system. A more detailed discussion of this physiology can be read here and here. The medical literature regarding treatment of headache, migraine, and facial pain disorders shows limited supporting evidence for cannabis/cannabinoids in the treatment of chronic headaches, migraine including chronic migraine, medication overuse headache, cluster headache, idiopathic intracranial hypertension, and multiple sclerosis (MS) associated trigeminal neuralgia. However, the majority of this limited supporting evidence consists primarily of case series, case studies, case reports, surveys, clinical/anecdotal reports, and one retrospective analysis. There have been no placebo-controlled studies of cannabis for headache disorders or migraine thus far. There are only two prospective trials containing a control group evaluating the use of cannabinoids in the treatment of headache disorders, both of which showed benefit. The details and references of these studies and all of the smaller case studies mentioned can be read here and here.

 

Part of the difficulty in these types of trials, besides the federal illegality and the schedule 1 status of cannabis, is that there are so many variations of chemovars. It is unknown what chemovars and varieties of cannabis might be most helpful for migraine treatment. Most likely, it is not a one size fits all. Similar to how patients have a wide variety of therapeutic responses to abortive and preventive migraine treatments (what works for one person often does not work for another, etc.), responses to chemovars is probably similar. One person may respond very well to a specific chemovar, while another may respond better to a different one. Everyone is different, so like the trial and error process of trying different medications to see which may work best, cannabis chemovars most likely have a similar process.

 

With that said, there have been a couple studies evaluating a large medical cannabis registry, in an attempt to determine what chemovars patients with migraine and headache prefer to use. In one study, which can be read here, chemovars with high THC and low CBD were most preferred. “OG Shark” was the most preferred chemovar and consisted of high THC/THCA (tetrahydrocannabinolic acid) and low CBD/CBDA (cannabidiolic acid), with predominant terpenes β-caryophyllene and β-myrcene. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Notably in that study, many headache patients replaced pharmaceuticals with cannabis, most commonly opiates/opioids (43.4% in headache patients, and up to 73% in chronic pain patients), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anticonvulsants (7.7%), muscle relaxers (7%), and ergots (0.4%).

 

In a follow up study (publication pending) 6 of the top 8 preferred chemovars were again high THC/low CBD, with “Headband” (22-24% THC, <1% CBD), “Warlock CBD” (8-11% THC, 8-11% CBD), and “Master Kush” (24-26% THC, <1% CBD) all tied for the top preferred cannabis chemovar. All three of these chemovars again had β-caryophyllene as one of their top 3 predominant terpenes, along with a mix of linalool, limonene, β-myrcene, bisabolol, and humulene as one of the top 3 predominant terpenes between them. There were 2 preferred chemovars which had high CBD and lower THC. They were “Warlock CBD” (8-11% THC, 8-11% CBD) which was in a 3-way tie for top preferred chemovar as mentioned above, and “Cannatonic” (3-7% THC, 6-10% CBD).

 

GENERAL SUGGESTIONS OF HOW TO USE MEDICAL MARIJUANA (CANNABIS).

Cannabis can be used by smoked, vaporized, oral, oral-mucosal, topical, or rectal routes of administration. Oral routes cause a slower onset of action and a prolonged duration of action. Smoking and vaporizing cause the fastest onset of action and the shortest duration of action. Smoking is not recommended due to the production of unhealthy respiratory irritants and toxins. Vaporizing is a newer technique with a goal of suppressing irritating respiratory toxins by heating cannabis to a temperature where active cannabinoid vapors form, but below the point of combustion where smoke and associated respiratory toxins are produced.

 

Start low on the dose, go slow, and stay on as low of a dose as possible. This promotes tolerance to the THC psychoactive effects. Use the lowest dose THC possible, and use CBD and THC together because CBD helps to neutralize some of the negative THC side effects. Approximately 15-20% CBD with less than 1% THC is a good starting point to consider. CBD predominant preparations are better for working and daytime use, while THC predominant preparations are better for after work and at bedtime. Long acting oral formulations are better for chronic conditions and symptoms. Vaporization can be an as needed (prn) for episodic symptom exacerbations. Driving should be avoided for at least 4 hours after inhaled cannabis, 6 hours after ingested cannabis, and 8 hours if euphoria is experienced.

 

Common dosing quantities and terminology include one cannabis cigarette (“joint”) = 0.3-0.5 grams, one eighth = 3.5 grams, one quarter = 7 grams, and one ounce = 28 grams. Based on peer-reviewed literature, the majority of patients using smoked or orally ingested cannabis for medical purposes have been observed to use between approximately 10-20 grams of cannabis per week, 1-3 grams per day, and a frequency of 3-4 times daily. With that said, specific dosing recommendations are not available, and this is one area of much needed research in order to determine the best dosing for various disorders.

 

The matching of the proper chemovar to the proper patient will be widely variable based on the targeted symptoms and the patient’s experience with cannabis. The anti-pain effects of THC may need a Type I or Type II chemovar, although the side effect profile will be higher (highest with Type I). The anti-anxiety or anti-inflammatory effects of CBD may require a Type II or Type III chemovar. Type III chemovars will have the least risk of side effects. Patients new to cannabis should be started with a Type II or Type III chemovar and it can be adjusted as needed and as tolerated.

 

HOW DO YOU ESTIMATE THC CONTENT, WHAT IS THE BEST THC DOSE, AND HOW DO YOU USE THC?

For THC dosing, 1-2.5 mg is a good starting dose. For example, starting at bedtime and increase 1-2.5 mg every few days at bedtime or daytime (depending on treatment goals) until benefits or side effects are reached. At 5 mg THC, many will experience benefit without excess side-effects. At 10 mg, most will have side effects. At 15 mg or more it may cause psychiatric side effects. The total daily THC dose should be less than 20-30 mg to limit adverse effects and tolerance. In addition, THC should preferably be used with CBD as mentioned above because it helps to neutralized out some of the negative THC side effects. Use of high dose THC chemovars more than 5 grams per day of flower suggests possible tolerance or misuse, and is usually unjustified medically unless perhaps an end stage cancer patient.

The best way to estimate the mg of THC in flower to get the goal THC dose is as follows. Say that you have 1 gram (1000 mg) of flower (typical cannabis cigarette quantity) from a chemovar with 10% THC. That means 1 gram flower contains 100 mg THC (1000 mg x 10%)!! With that formula in mind, you can easily figure out the THC content by switching out those numbers of weight and THC percentage in the flower or product being used. Taking this example a step further, 30 mg would be just more than 1/3rd (30 mg THC goal / 100 mg THC), 20 mg THC would be 1/5th of the 1 gram flower quantity (20 mg THC goal / 100 mg THC), 10 mg THC would be 1/10th of the 1 gram flower quantity (10 mg THC goal / 100 mg THC), 5 mg THC would be 1/20th of the 1 gram flower quantity (5 mg THC goal / 100 mg THC), and so on. So the easiest way to fine tune your THC dose from your flower would be to divide 1 gram of flower into a specific fraction as outlined (depending on dosing goals), so you can know exactly how much to use and exactly how much THC you are ingesting.

 

WHAT IS THE BEST CBD DOSE AND HOW DO YOU USE CBD?

For CBD dosing, a good general guideline of how to begin CBD dosing with a gentle titration is as follows:

-Week 1: 5-10 mg at bedtime

-Week 2: 5-10 mg twice daily

-Weeks 3-4: 5-10 mg three times daily

-Weeks 5 onwards: 20 mg three times daily

It is suspected that high doses are likely needed for pain and inflammation disorders, but this needs to be clarified with research. There are no established dosing guidelines or max doses established. For reference, doses of 400-600 mg/day showed benefit in anxiety, doses of 600-800 mg/day showed benefit in psychosis, and doses up to 2500 mg/day (25-50 mg/kg) have been used in epilepsy studies.

 

SIDE EFFECTS AND ADVERSE REACTIONS OF MEDICAL MARIJUANA (CANNABIS).

Side effects are influenced by dose, method of administration, patient tolerance, chemovar of cannabis, ratios of THC to CBD, cannabinoids, terpenes, production quality control (toxins, fungus, bacteria, heavy metals, etc.) to name a few. Many studies have been inconclusive or contradictory in terms of association with stroke, heart attack. This publication provides the most comprehensive review of cannabis and its recognized side effects. The most common side effects (which vary depending on the chemovar) include dizziness, dry mouth, increased appetite, disturbances in concentration, and sedation/drowsiness. Less common side effects can include incoordination, euphoria, anxiety, and paranoid thinking. In the majority of trials, side effects have been well tolerated, mild to moderate, transient, and not bothersome enough that many patients withdrew from studies. Overdose can occur and is typically from high THC content and oral dosing. Signs may include tachycardia, arrhythmia, confusion, panic attack, extreme paranoia, and hallucinations.

 

From existing research, there is concern for possible long-term cognitive side effects of cannabis use during adolescent years when the brain is still rewiring, pruning, and organizing itself. Studies suggest a decline in IQ/neurocognitive function when used frequently under age 18. In adults, a larger study suggested problems in verbal memory recall after chronic cumulative use (after 5 years of cumulative frequent/chronic use, 1 in 2 people may recall 1 word less from a list of 15 words). Current users had both decreased verbal memory and processing speed.

 

According to “The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research”, published by the National Academies of Sciences, Engineering, and Medicine in January 2017, the following are conclusions regarding cannabis side effects based on existing literature reviews.

 

For cardiovascular risk, there is limited evidence of cannabis triggering an acute MI (heart attack), ischemic stroke, or subarachnoid hemorrhage. There is no evidence to support or refute chronic cannabis use and increased risk of acute heart attack.

 

For cancer risk, there is moderate evidence of no association between the incidence of lung cancer (cannabis smoking), or the incidence of head and neck cancers. There is no or insufficient evidence to support associations with other cancers.

 

For respiratory disease risk, there is substantial evidence for worse respiratory symptoms and more frequent chronic bronchitis episodes (long-term cannabis smoking).

 

For neurocognitive risk, there is moderate evidence of impairment in the cognitive domains of learning, memory, and attention with acute cannabis use, but limited evidence for persistent impairments in cognitive domains of learning, memory, and attention after sustained cannabis abstinence.

 

For mental health risk, there is substantial evidence for development of schizophrenia or other psychoses in those at risk genetically, with the highest risk among the most frequent users. There is moderate evidence for increased symptoms of mania and hypomania in bipolar disorder. There is a small increased risk of depressive disorders and an increased incidence of social anxiety disorder. There is an increased incidence of suicidal ideation and suicide attempts with higher incidence in heavier users, and an increased incidence of suicide completion.

 

For prenatal, perinatal, and neonatal exposure, there is substantial evidence between maternal cannabis smoking and lower birth weight. During lactation, the amount reaching the infant is very low, although the effects of this are unknown. Therefore, it is recommended to not use cannabis in either pregnancy or breastfeeding.

 

There is substantial evidence for an increased risk of motor vehicle crashes. There is moderate evidence for increased risk of overdose, especially among pediatric populations. There is no or insufficient evidence for all-cause mortality, and there has been no documented death exclusively attributed to cannabis overdose or use. Cannabis has been shown in toxicology studies to be 114 times less lethal than alcohol. In fact, the deadliest substances in one toxicology study in order were alcohol, heroin, cocaine, tobacco, ecstasy, methamphetamine, and lastly, cannabis.

 

WHAT IS CANNABIS HYPEREMESIS SYNDROME AND HOW DO YOU TREAT IT?

Cannabis hyperemesis syndrome (CHS) has become increasingly seen as states legalize cannabis. It presents with clinical symptoms of cyclical nausea/vomiting, diffuse abdominal pain, and the need to take frequent hot showers (this is a pathognomonic sign).

 

Episodes of these symptoms last 24-48 hours, may last 7-10 days, and often recur with re-exposure of cannabis. CHS tends to be associated with high-dose, high-THC regular cannabis use. It can be confused with CVS (cyclical vomiting syndrome), and is differentiated by a history of chronic cannabis use and frequent hot bathing which produces temporary relief. The etiology (cause) of CHS is not fully understood. It has been theorized that there is a dysregulation of the endogenous cannabinoid system by downregulation of CB1 (cannabinoid 1) receptors, and in the GI (gastrointestinal) tract this may slow gastric motility, causing hyperemesis. Genetic differences in the cytochrome P450 system (enzymes in the liver which metabolize drugs) has also been proposed. The TRPV1 receptor in our bodies interacts with the endocannabinoid system. More specifically, anandamide (our main natural endocannabinoid) works at this receptor (one of many). Interestingly, this receptor is also the capsaicin receptor, and is activated by heat such as in hot peppers (which contain capsaicin). Therefore, it has also been proposed that perhaps the fact that these patients take frequent hot showers/baths for relief is because they are indirectly activating their endocannabinoid system.

 

Treatment of CHS revolves around cannabis cessation. There is no way around it. Supportive therapy can assist with fluid resuscitation. Capsaicin 0.075% topically to areas of the abdomen, back of arms, and areas that hot water gives symptom relief have shown some benefit (not using on private areas or mucosal surfaces). Antipsychotics such as Haloperidol and Olanzapine showed some temporary benefit. Conventional antiemetics, antihistamines, serotonin antagonists, benzodiazepines have shown limited evidence for effectiveness, and opiates should be avoided.

 

CANNABIS (MARIJUANA) ADDICTION AND ABUSE

Comparative addiction rates between substances have included tobacco 32%, heroin 23%, cocaine 17%, alcohol 15%, and lastly cannabis 9% (but 17% when used in adolescence, and 25-50% in adolescents who are using daily). Tolerance develops much faster with high potency high THC chemovars.

The DSM-5 recognizes 5 cannabis-associated disorders:

-Cannabis Use Disorder

-Cannabis Intoxication

-Cannabis Withdrawal

-Other Cannabis-Induced Disorders (Cannabis Intoxication Delirium, Cannabis Induced Psychotic Disorder, Cannabis Induced Anxiety Disorder, Cannabis Induced Sleep Disorder

-Unspecified Cannabis-Related Disorder

 

An estimated 3-4% of users meet criteria for Cannabis Use Disorder. The prevalence decreases with age, with the highest ages 18-29 years old (4.4%), and lowest ages 65 and older (0.01%). Cannabis Use Disorder is divided into mild (2-3 criteria), moderate (4-6 criteria), and severe (7 or more criteria). These criteria include any of the following:

  • Cravings and urges to use cannabis
  • Failure to fulfill major role obligations (work, school or home)
  • Unsuccessful attempts to quit/cut down
  • Spends excessive time in acquisition, using or recovering from use
  • Using Cannabis in larger amounts or for longer than you meant to (tolerance)
  • Continued use despite consistent social or interpersonal problems
  • Recurrent use in hazardous situations
  • Important social, occupational, or recreational activities are given up or reduced because of cannabis use
  • Needing more cannabis to get the effect you want (Tolerance)
  • Uses despite negative effects (physical or psychological)
  • Development of withdrawal symptoms, which can be relieved by taking more of the substance

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

References

 

 

 

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Last updated on April 6th, 2021 at 07:23 am

NATURAL MIGRAINE TREATMENT FOR PREVENTION WITH VITAMINS AND SUPPLEMENTS. WHICH ARE BEST?

@Neuralgroover

Worldwide, migraine affects more than 10-12% of the population, with approximately 1 billion migraineurs estimated worldwide.1 It is estimated that there are 39 million migraineurs in the US, accounting for 12% of the US population. Migraine affects 18% of women and 6% of men2,3. Nearly 25% of U.S. households include someone with migraine.

 

In 2016, migraine was determined to be the 2nd leading cause of all global disability, and the 2nd leading cause of all neurological disease burden4. Migraine accounts for 50% of all neurologic disability. Furthermore, chronic pain in general is the largest contributor to years lived with disability globally5, and is associated with tremendous negative impacts on social, economic, and personal function.

 

In addition to the attack-related disability, many sufferers live in fear because their migraines disrupt their ability to work, go to school, partake in social activities, or care for their families, and this significantly limits their overall quality of life. More than 90% of migraine sufferers are unable to work or function normally during their attacks. American employers lose more than $20 billion each year as a result of 113 million lost workdays due to migraine.6

 

Migraine treatment is divided into acute (as needed) and preventive (prophylactic) therapy. Most existing preventive therapies are adopted from anti-epileptic, antidepressant, and antihypertensive medications. However, many of these medications are not well tolerated, resulting in poor compliance. Adherence to oral migraine preventative medication is around 26% at 6 months and declines to 17% at one year.7 This is often due to intolerable side effects. Many patients, due to lack of efficacy of preventative treatments, often resort to overuse of acute medications. This results in additional decline in quality of life and economic burden.8 Onabotulinumtoxin-A (Botox) is currently the only FDA-approved treatment available for chronic migraine. However, most patients must fail at least three preventative treatments prior to receiving Onabotulinumtoxin-A. As such, Onabotulinumtoxin-A is typically a fourth line option for the prevention of chronic migraine. In addition, it is not approved for patients who have episodic migraine. There are 4 calcitonin gene related peptide (CGRP) monoclonal antibody antagonists that have been approved for the prevention of migraine.  There also exists a limited number of neuromodulatory devices. Lack of insurance coverage of these devices precludes their routine use in clinical practice.  This confers a large unmet need for additional preventive migraine treatments and additional therapeutic targets.

 

Migraine prevention is a key aspect to maintaining a good quality of life.  Abnormal neuronal membrane ion channels, low ionized magnesium levels, increased excitatory glutamatergic activity, and mitochondrial dysfunction with abnormal energy metabolism are associated with migraine. The goal of nutraceuticals is to target these factors in order to improve energy metabolism and reduce neuronal hyperexcitability in the brain. Patients often seek natural migraine treatment with complementary and alternative medicine (CAM) after finding standard prescription treatments intolerable due to side effects, or just ineffective. Many patients feel that “natural” substances are less toxic than prescription medications. Thus, the nutraceutical and herbal supplement industry is a multibillion-dollar industry. CAMs include, but are not limited to, nutraceuticals (vitamins and supplements such as magnesium, coenzyme Q10 (CoQ10), vitamin B2 (riboflavin), alpha lipoic acid, vitamin D, 5-HTP, fish oil, melatonin), and herbal preparations (butterbur, feverfew, ginger, and cannabidiol). Other natural treatments such as yoga and meditation for migraine treatment can also be very helpful.

 

The use of CAMs has been significantly rising in the US and Europe9–12, and is becoming more evident especially in patients with migraine and other headache disorders. In a recent questionnaire-based survey in Germany and Austria, 81.7% of patients seen in tertiary outpatient headache clinics reported use of CAM13.  There are a multitude of different migraine related supplements on the market with variable combinations or sold separately as the individual components. Below, we discuss the most commonly used and studied supplements for migraine prevention.

 

VITAMINS and SUPPLEMENTS FOR MIGRAINE PREVENTION:

  1. Magnesium

Magnesium has a Level B (2nd highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society.14 It is also rated highly and recommended by the Canadian Headache Society.15 This is a higher evidence recommendation than many of the prescription medications we use for migraine prevention. More than 325 enzymes are magnesium dependent, many of which are brain enzymes. Magnesium is involved in all reactions that involve the formation and utilization of adenosine-5′-triphosphate (ATP) in energy metabolism16–19. Proper magnesium levels are known to help normalize blood pressure, have anticoagulant, anti-platelet aggregating effects, regulate cell proliferation, protein synthesis, cellular energy and cell membrane stability, as well as blood sugar levels19–21. Studies have shown low levels of brain magnesium22,23 may be a contributor to migraine pathophysiology. Magnesium influences multiple steps in the current understanding of migraine pathophysiology including cortical spreading depression, serotonin receptor activity, neurotransmitter release, interference with inflammatory mediators, nitric oxide production, platelet aggregation, vascular tone, NMDA receptor interaction, CGRP release, production and release of substance P which activates pain fibers24–31. Magnesium is a mineral that functions as a coenzyme for various neurologic functions and other physiologic mechanisms.    According to two double-blind studies, high-dose oral magnesium supplementation appears to be effective in migraine prophylaxis. Trials have shown that magnesium supplementation is very effective in migraine treatment, with migraine attack reductions of up to 42%.32–37 Other studies have also shown benefit in migraine prevention when combined with coenzyme Q10 and feverfew as well.38 Magnesium (250 mg twice a day or 500 mg at bed) has a relaxant effect on smooth muscles such as blood vessels. We often give intravenous magnesium to patients who come into the emergency department for migraine because it helps to break the migraine. Three trials found 40-90% average headache reduction when used as a preventative. Magnesium also demonstrated the benefit in menstrually related migraine. Magnesium is part of the messenger system in the serotonin cascade and it is a good muscle relaxant. Some forms can be useful for constipation which can be a side effect of other medications used to treat migraine. Good sources include nuts, whole grains, and tomatoes.

 

There are different forms of magnesium, and we’ll discuss the most common types. Magnesium types can be tailored to patient characteristics as follows.39 Magnesium glycinate is a good choice for those with a sensitive stomach who have gastrointestinal side effects such as diarrhea with other forms of magnesium. It is anecdotally also helpful with anxiety and sleep. Magnesium threonate also has low risk of gastrointestinal side effects and anecdotally helpful with cognitive function and brain fog symptoms. Magnesium malate has low gastrointestinal side effects and is reportedly more energizing and anecdotally often helpful in fibromyalgia and chronic fatigue syndrome. Magnesium citrate is one of the most studied, popular, and well-absorbed forms of magnesium. It can also be mixed easily with liquids if you can’t take pills. However, it comes with a higher risk of diarrhea and gastrointestinal side effects, although this could be helpful for those with constipation. Magnesium oxide is also well studied, cheap, and often used for heartburn and indigestion. However, it is not well absorbed and can have some laxative side effects as well, so can also be helpful for constipation.

 

Dosing should generally be somewhere between 400-800 mg daily. It should preferably contain 24 mmol (600 mg) of elemental magnesium daily as magnesium citrate​ based on trials that showed benefit with this specific one more than others, and this is the recommendation of the Canadian Headache Society.15 If this type is not tolerated, other forms of magnesium as discussed above are certainly acceptable.

 

  1. Vitamin D3 (Cholecalciferol)

Vitamin D deficiency is a worldwide problem. Vitamin D is not actually a vitamin, but a hormone that the body makes from a type of cholesterol in the skin when it is exposed to UVB radiation from the sun. Small amounts also come from diet. It has anti-inflammatory activities, analgesic effects, may reduce nitric oxide and assists in magnesium and calcium absorption. Deficiency is suspected to play a role in mechanisms responsible for migraine and other pain syndromes, and vitamin D levels have been shown to be low in chronic migraineurs40. The best form is vitamin D3 (cholecalciferol) anywhere from 1,000 to 4,000 IU daily.

 

  1. 5-HTP (5-Hydroxytryptophan)

This is an amino acid that is made by the body from tryptophan (amino acid you get from your diet), and is involved in mood, sleep, and pain regulation. 5-HTP is typically produced from the seeds of the Griffonia simplicifolia plant. 5-HTP is converted into serotonin (5-hydroxytryptamine), an important brain neurotransmitter involved in migraine pathways and other neurologic pathways. 5-HTP is also converted into melatonin which aids in sleep, as well as dopamine, another important neurotransmitter. The effects of 5-HTP are felt to be similar to the antidepressants that are thought to increase the amount of serotonin available to the brain, and thus a mood enhancing chemical. Some studies have suggested that 5-HTP was as effective as some prescription migraine medications such as propranolol and methysergide (75% improvement in methysergide vs. 71% improvement in 5-HTP) in reducing the frequency and severity of migraines41–45. Side effects can include nausea, diarrhea, and stomach pain, and it should be used cautiously with medications which increase serotonin levels (such as most antidepressants) due to potential risk of serotonin syndrome. Typical doses are around 100–200 mg, 2–3 times per day with meals.

 

  1. Fish oil (Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA))

Fish oils are found in the tissues of fish. They contain a certain type of fat called omega-3. Potential mechanisms for anti-inflammatory effects of fish oil include inhibition of inflammatory mediators (eicosanoids and cytokines), and synthesis of lipid suppressors of inflammation (resolvins)46. Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) give rise to these resolvins which are anti-inflammatory and inflammation resolving47. These compounds may relieve joint pain and stiffness in a similar way as non-steroidal anti-inflammatory drugs (NSAIDs)46,48. One study reported dramatic decreases in headache frequency (15 per month down to 2 per month) and decreases in headache severity (reduction from 5 to 3 on a 7-point scale)49. Fish oils have also been studied and found to be useful in other inflammatory conditions such as rheumatoid arthritis46,48,50–53. Large trials have showed a significant beneficial effect on pain, morning stiffness, number of painful and/or tender joints and NSAID consumption50. Recommended dosing consists of 30% EPA and DHA with a ratio of EPA to DHA of 1.5. Research suggests the minimum dose needed to reduce the joint inflammation associated with arthritis is 2.7 grams of omega-3 (EPA + DHA) daily, which could also be divided such as 900 mg EPA and 450 mg DHA twice daily.

 

  1. Melatonin:

Increasing evidence shows correlation between melatonin secretion and headache conditions. Melatonin supplementation has shown decreased headache intensity and duration. It is widely used as a sleep aid. Sleep is nature’s way of dealing with migraine. A dose of 3 mg is recommended to start for headaches including cluster headache. Higher doses up to 15 mg has been reviewed for use in cluster headache and have been used, if not making too groggy in the morning. The rationale behind using melatonin for cluster is that many theories regarding the cause of cluster headache center around the disruption of the normal circadian rhythm in the brain. This helps restore the normal circadian rhythm. It should be taken at least 2 hours before bedtime.

 

MITOCHONDRIAL SUPPLEMENTS FOR MIGRAINE PREVENTION:

Mitochondria are the powerhouses within all cells of the body. These crucial metabolic organelles use oxygen to produce ATP, which is the primary energy source for the cell, and thus, for your body. Mitochondrial dysfunction leads to impaired oxygen metabolism and is suspected to play a role in migraine pathophysiology. Some migraineurs have been shown to have reduced mitochondrial activity which may lead to altered neuronal processing, and therefore a lower threshold for migraine attacks54–58. Riboflavin (vitamin B2), CoQ10 (ubiquinone; CoQ10), and alpha lipoic acid (thioctic acid) all play key roles in mitochondrial activity, and therefore have been implicated in migraine treatment by optimizing mitochondrial functioning.

 

  1. Riboflavin (Vitamin B2)

Riboflavin assists nerve cells in the production of ATP, a principal energy storing molecule. Riboflavin is an essential precursor to coenzymes involved in electron transport in oxidation reduction reactions within the Krebs cycle. This metabolic cycle is critical in production of ATP and generation of energy in the mitochondria, oxidative metabolism, maintaining membrane stability, and for all energy-related cellular functions59,60. It is necessary for many chemical reactions in the body. Brain riboflavin metabolism is suspected to affect migraine pathophysiology via several mechanisms, providing migraine preventive benefit.36,37

 

Riboflavin has a Level B (2nd highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society.14 This is a higher evidence recommendation than many of the prescription medications we use for migraine prevention. The Canadian Headache Society Guidelines strongly recommend B2 for migraine prevention as well.15 There have been at least 3 clinical trials of riboflavin using 400 mg per day all of which suggested that migraine frequency can be decreased. All 3 trials showed significant improvement in over half of migraine sufferers. Trials of riboflavin have suggested significant improvements in migraine by up to 59%61. Riboflavin (Vitamin B2): 200 mg twice a day (or 400 mg daily). The supplement is found in bread, cereal, milk, meat, and poultry. Most Americans get more riboflavin than the recommended daily allowance, however riboflavin deficiency is not necessary for the supplements to help prevent headache. One side effect to be aware of is that it can turn your urine bright neon yellow, although this is not harmful. Recommended dosing is 200 mg twice daily (or 400 mg once daily).

 

  1. Coenzyme Q10 (Ubiquinone; Ubiquinol; CoQ10)

CoQ10 is present in every membrane of all cells in the body62. Similar to riboflavin, CoQ10 plays a crucial role in electron transport and energy metabolism given its heavy involvement in mitochondrial function. CoQ10 is incorporated into the mitochondria, where it facilitates the transformation of fats and sugars into energy, thus it is often marketed to be an “energy enhancer”. Studies have shown that a nutritional supplement of CoQ10 can reduce the frequency of migraine attacks by improving the energy production of cells as with riboflavin. It also functions as an antioxidant by protecting against toxic oxidative reactions in the body, and CoQ10 tissue levels are known to decrease with age19,63. In one study, CoQ10 was found to be low in about 1/3rd of patients studied, and when replaced, headache frequency improved64. Migraine frequency was shown to improve significantly in more than 61% of patients in one study65, and 50% of patients in another study,66 supporting use for migraine prevention.36 Other studies have also shown benefit in migraine prevention when combined with magnesium and feverfew as well.38 The Canadian Headache Society guidelines strongly recommend use of CoQ10.15 Suggested dosing is around 150 mg-200 mg twice a day.

 

  1. Alpha Lipoic Acid (Thioctic Acid)

Alpha lipoic acid enhances the metabolism of oxygen and energy production by mitochondria67, and has shown reduction of migraine frequency68 when studied. Doses are typically around 300 mg twice daily.

 

HERBAL SUPPLEMENTS FOR MIGRAINE PREVENTION:

  1. Feverfew (Tanacetum parthenium)

Feverfew is a common garden herb native to Europe and popular in Great Britain as a treatment for disorders typically controlled by aspirin. The mechanism of action is unknown but is believed to be related to a chemical called parthenolide which helps the body use serotonin more effectively. Serotonin helps prevent migraine and assists with resolution when it occurs. Parthenolide also inhibits the release of histamine which is linked to pain and inflammation. Consistency of active ingredients in different products can be a problem. Some formulations don’t have the active ingredient (parthenolide) that prevents migraine. A parthenolide content of 0.2% is generally recommended.

 

Feverfew has a Level B (2nd highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society.14 This is a higher evidence recommendation than many of the prescription medications we use for migraine prevention. The anti-migraine action36–38,69–75 of Feverfew is felt to be related to the parthenolides within the leaves. Studies have shown that the parthenolides provide anti-inflammatory and analgesic effects through several mechanisms involved in the migraine process that normally lead to pain. These include inhibition of phospholipase A, prostaglandin biosynthesis and platelet aggregation, and actions on serotonin including release of serotonin from platelets and white blood cells, as well as interaction at various serotonin receptor subtypes19,76–89. Study results have been variable based on wide variations in the strength of the parthenolides and differences in the stability of feverfew preparations used. However, a new, more stable feverfew extract (MIG-99) was created and showed a significant improvement in patients with high-frequency migraine90,91. The recommended dosing is generally around 50 mg twice daily (standardized to a high parthenolide content of 0.7% and stability measures of parthenolide), or, preferably MIG-99 6.25 mg three times daily if it can be found.

 

  1. Butterbur Extract (Petasites hybridus)

Butterbur is an extract derived from the petisides hybridus root, which has been used for medicinal purposes since ancient times. Butterbur is a well-researched and proven herbal supplements for migraine prevention36,69,70,92. For many years, it was the only supplement with a Level A (highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society,14 with a higher evidence recommendation than many of the prescription medications we use for migraine prevention. However, this recommendation was withdrawn a few years ago given a small handful of cases of liver failure reported in Germany. Although it is classified as an herbal supplement in the US, it is a licensed pharmaceutical medicine in Germany (Petadolex). Its two active compounds, petasin and isopetasin, help reduce cerebral blood vessel spasm and stop the inflammatory cascade which occurs in migraine93–95. Butterbur is thought to act through anti-inflammatory inhibition of leukotriene biosynthesis for its analgesic effects but also has calcium channel regulatory properties, both of which play a role in migraine19.

 

Studies have also shown anti-inflammatory effects mediated through inhibiting the additional inflammatory enzymes cyclooxygenase and prostaglandin production96. Notably, this is also what gives aspirin its anti-inflammatory effect. Trials have shown very positive results with significant decreases in migraine frequency of up to 58-77%, with 91% reporting overall improvement97–100. Side effects can include burping/belching. Raw butterbur root contains toxic chemicals that must be filtered out during the manufacturing process. To be sure you are choosing a safe product, look for a formulation that does not contain pyrrolizidine alkaloids since these are toxic to the liver. Recommended dosing is typically around 75 mg twice daily (free of Pyrrolizidine Alkaloids (PAs), standardized to contain a minimum of 7.5 mg of petasin and isopetasin).

 

  1. Ginger (Zingiber Officinale)

Ginger has anti-histamine and anti-inflammatory properties such as blocking pain-producing prostaglandins101,102, and helps with circulation and potentially headache. It is also widely used to treat nausea and vomiting, which accompany migraine103, and this is what it is primarily useful for. Recommended dosing ranges from 100-200 mg three times per day to 150 mg twice daily (standardized to contain 20% of gingerol and shogaol (dosage).

 

  1. CBD (Cannabidiol)

There have been a multitude of studies documenting the analgesic and anti-inflammatory benefits of medicinal cannabis (marijuana) across many chronic pain syndromes104–106, and it has been a historical treatment for headache and migraine for centuries.105–109 A detailed overview of medical cannabis for the treatment of migraine and chronic pain is discussed here. The vast majority of supporting evidence of cannabis and cannabinoids involves various chronic pain syndromes. These benefits are hypothesized to extend to headache disorders such as migraine given overlapping neurobiological pathways of pain. Some data suggests that cannabinoids appear to work uniquely within the inherent anatomical pathways of migraine (including serotonergic triptan pathways) and pain.104,105,107–139 Unfortunately, the majority of data supporting the use of cannabis and cannabinoids in migraine and headache disorders is based on case series, case reports, surveys and anecdotal evidence.105,107,145–154,108,155–161,134,135,140–144 There has been one retrospective study of cannabis use in the treatment of migraine which reported strong statistically significant findings of benefit.162 There have been only two limited prospective trials of cannabinoids containing a control group in headache disorders. One reported significant benefit in chronic daily headache associated with medication overuse headache,163 and the other reported significant benefit in both the acute and preventive treatment of chronic migraine.164

 

Given the growing evidence of cannabis and cannabinoids in the treatment of chronic pain and other medical conditions, in February 2019 The World Health Organization (WHO) recommended that cannabis be rescheduled and removed from the most restrictive scheduling category. In January 2017, the National Academies of Sciences, Engineering, and Medicine concluded that the use of cannabis for the treatment of pain is supported by well-controlled clinical trials and that there is substantial evidence that cannabis is an effective treatment for chronic pain in adults.165 In 2014, the Canadian Pain Society revised their consensus statement to recommend cannabinoids as a third-level therapy for chronic neuropathic pain based on the abundance of supporting evidence and a NNT (number needed to treat) estimated at approximately 3.166

 

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two predominant cannabinoids found in cannabis and are discussed in more detail here. CBD is several hundred more times anti-inflammatory than aspirin.104 There have been scientific, animal models, and limited human clinical trials documenting its anti-inflammatory and analgesic properties.167–176 In contrast to THC, CBD is non-intoxicating (no “high”).167 In November 2017, The World Health Organization (WHO) concluded that CBD exhibits no evidence for abuse or dependence potential, and that there is no evidence of public health related concerns associated with its use.177 In January 2018, the World Anti-Doping Agency (WADA) removed CBD from their prohibited list, no longer banning use by athletes.178

 

In December 2018, the Agriculture Improvement Act (Farm Bill) was signed into law in the United States. This legalized the agricultural growth and use of hemp (cannabis strains containing 0.3% THC or less) and hemp derivatives such as CBD, as well as removed hemp and its extracts (including CBD) from the Controlled Substances Act, making it no longer an illegal substance under federal law.

 

Thus, the use of CBD products has been exploding and is a new industry projected to exponentially increase into a multi-billion dollar industry179,180. Many patients are using these products for a variety of reasons181,182, most commonly in pain, including migraine prevention, given their easy access and availability. However, there are no studies evaluating CBD alone in treatment of migraine or any other headache disorders, so this is purely anecdotal. CBD products can readily be purchased online from a multitude of companies, in local health food and drug stores, and common retail pharmacies.183 CBD and suggested dosing (which are not currently clearly known) are discussed in much greater detail here. Medical marijuana (cannabis) for the treatment of migraine is also discussed in much greater

 

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