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Science Based 13

By

Winston Peki

CBD for Migraines: Scientific Evidence and Mechanism of Action

CBD and Migraines

Anecdotal evidence shows that CBD can be helpful for migraine.

But is there any scientific evidence backing up the anecdotal?

Today, we’re going to look at whether there’s any evidence that supports the use of CBD for migraines.

We’re also going to use scientific evidence and anecdotal reports to look at how to use CBD for migraines.

For example:

Did you know CBD seems to be much more effective for migraines when combined with THC?

Let’s get started.

Why CBD Could Be Helpful for Migraines

Migraine is a type of headache. Its specific features are a throbbing or pulsing pain. It usually occurs on one side of the head.

Now:

There’s no evidence that CBD can prevent, treat, or cure migraines themselves.

But there’s some evidence that shows CBD could relieve symptoms of migraines.

Migraine attacks usually are accompanied by:

  • headaches,
  • nausea, and,
  • vomiting.

Interestingly, several studies show CBD can reduce symptoms all three of these symptoms.

The biggest benefit of CBD compared to other symptom relievers is that CBD is:

  • considered generally safe in doses up to 1500mg/day,
  • non-addictive, and,
  • doesn’t have psychoactive effects.

Let’s take a look at the research.

Research on CBD and Migraine

To date, there are no studies that looked at the effects of pure CBD on migraines.

All studies looked at a combination of cannabinoids, with CBD being only one part of the total.

There’s currently a clinical trial underway that will look at the effects of the following combination of cannabinoids on chronic migraines:

  • CBD/CBG/THC combination in the following dose: 133/66/4mg daily (1).

Again, while CBD is a large part of the total formulation, it’s not pure CBD.

A 2017 study published by the European Academy of Neurology looked at the effects of CBD + THC on migraines (2).

The treatment was performed in 2 phases.

In phase 1, a group of 49 chronic migraine patients received an oral formulation containing THC and CBD in a 2:1 ratio. They received two different doses: 100mg and 200mg. This was the total dose, mind you. So the 100mg dose contained approximately 33mg CBD. And the 200mg dose had approximately 66mg CBD.

The results of phase 1:

The 100mg dose had no effects whatsoever. But the 200mg dose, reduced migraine pain by 55%.

In the first phase it showed that less than 100mg of the dose (CBD+THC) did not have any effect on the patients; however, when the dose was increased to 200 mg, migraine pain was reduced by 55%.

In phase 2 of the study, 79 chronic migraineurs received a daily dose of 200 mg of the THC-CBD combination for three months. The THC-CBD combination improved migraine symptoms by 40.4%.

As explained the main migraine symptoms are headache and nausea.

And while these study results can’t be attributed to CBD alone…

CBD has anti-nausea and pain-reducing effects (3, 4).

How Does CBD Work for Relieving Migraine Symptoms?

CBD works by interacting with the body at various levels.

CBD interacts with the endocannabinoid system (ECS).

The ECS is a term that specifies the biological system that consists of:

  • ‘Cannabinoid’ receptors,
  • Their ligands called ‘endocannabinoids’, and;
  • Enzymes.

The endocannabinoid system is associated with vital biochemical functions like:

  • The functioning of the central nervous system (5);
  • The functioning of neuronal activity (6);
  • The functioning of the cardiovascular system (7).

The ECS has two central receptors called CB1 and CB2 receptors. And one of the most well-researched endocannabinoids is anandamide.

CBD does not directly interact with the CB1 and CB2 receptors. But it interacts with ECS in different ways.

For example:

CBD slows down the breakdown of anandamide, increasing its concentration (8). Anandamide may suppress pain initiation (9).

CBD is also a ‘negative allosteric modulator’ of the CB1 receptor (10). This means it reduces the ability of CB1 activators to do their work. For example, THC activates the CB1 receptor. CBD reduces many side effects associated with THC. Whether this mechanism is relevant for relieving migraine symptoms is currently unknown.

CBD also interacts with other receptor systems that aren’t part of the ECS, but are involved in pain.

For example:

CBD activates serotonin receptors. It has an especially strong affinity for the 5-HT1a receptor. Recent studies found that activation of 5-HT(1A) receptors (a specific type of serotonin receptor) can decrease chronic pain (11).

Other Cannabis Research

Cannabis contains at least 70 different cannabinoids, 120 different terpenoids, 23 different flavonoids.

CBD is just one compound out of hundreds.

Research indicates that cannabis compounds have synergistic effects.

Research also has looked at the effects of cannabis on migraines.

In 2016, a study was conducted on 48 migraine patients who were given medical marijuana. 39% reported having reduced migraine attacks. However, some patients complained about side effects like drowsiness. While others could not figure out the correct dose (12).

In 2018, another 2032 patients were given medical marijuana for migraine, headaches, and arthritis. Medical marijuana was so effective that most patients were able to switch from opioids to medical marijuana (13).

Now:

The main active compound in medical marijuana is THC. Therefore these results don’t really support the use of pure CBD for migraines. But medical marijuana also always has small concentrations of CBD. It could be that these small concentrations increase the effectiveness of THC, for example.

What Types of CBD Are Good for Migraines?

No research has shown that CBD alone is effective in reducing migraine symptoms. The only study that found positive effects of CBD on migraines, was in the context of a THC+CBD combination.

Based on this study, you would do best to get a THC-dominant product. Only if you don’t have access to a THC-dominant product, should you look for other options. For example, if these products are illegal in your jurisdiction.

The next best option are full-spectrum CBD products. While these products are CBD-dominant, at least they have some THC. Full-spectrum CBD products also have many other cannabinoids and terpenes. So they make a good case for getting the synergistic benefits of combining CBD with other cannabinoids and terpenes.

Now:

If you can’t take any THC, full-spectrum CBD products are out.

CBD isolate is the purest form of CBD. Generally, it’s the least effective form of CBD. But it’s THC-free.

Broad-spectrum CBD contains CBD, plus other cannabinoids like CBN, CBC, and CBG. But it’s always free from THC. That said, you can only know for sure if you have a certificate of analysis.

Based on current evidence, best is a combination of THC and CBD for relieving symptoms of migraine. So when it comes to CBD-dominant products, full-spectrum CBD is the most effective type of product.

How to Use CBD Oil for Migraine?

There is no universal dosage of CBD that works for all patients suffering from migraine pain or any other health issue.

Generally, it’s suggested to start dosing CBD low and slowly up-titrate until desired effects are achieved. This holds true if you’re using CBD to relieve symptoms of any kind. For medical use, always follow the instructions of your physician.

An example of dosing for migraine symptom relief:

Start with 10mg. Up-titrate in steps of 10mg until you get desired symptom relief. The maximum safe dose for CBD is 1500mg/day. That said, most users get good relief for most symptoms with doses ranging from 20mg to 100mg. The higher the dose, the higher the chance of side effects.

CBD can be consumed in various different ways, and each consumption method has its own advantages and disadvantages.

Each consumption method has a different onset, bioavailability, and duration.

The following are the most common consumption methods:

  • Capsules and edibles may take a few hours to show effect but are long-lasting.
  • The thin blood vessels under our tongue and along the cheeks allow quick absorption of CBD. You can put a few drops of your desired dose under the tongue or along the cheeks and wait for at least one minute before swallowing it. The effect of sublingual CBD is produced within 10 to 30 minutes and lasts for at least 1-2 hours. CBD tinctures are perfect for sublingual absorption.
  • Some CBD users opt to smoke or vape their CBD by using vape liquids or CBD-rich flower. Vaping is the fastest delivery system to get CBD into the bloodstream. Smoking allows CBD to penetrate into the bloodstream by passing through the alveoli of the lungs. Even though this delivery system is quick, the effects are also short-lived compared to oral methods of consumption.
  • Topical CBD products such as rubs, lotions, creams, balms, and salves can be used topically. They get absorbed into the skin and joints but don’t enter the bloodstream. So they’re not effective for migraine. Transdermal CBD products do enter the bloodstream, but these products are rare.

Legality

CBD derived from industrial hemp was legalized under the agricultural act 2018, famously known as Farm Bill 2018.

CBD and its related products are considered legal in the EU if they contain less than 0.2 % THC and are derived from industrial hemp.

The FDA has strict policies against CBD companies that sell CBD products as a medicine for treat various health issues. FDA has legalized the first CBD-based medicine called Epidiolex, which is used to treat rare forms of epilepsy and is only available if prescribed by a licensed physician.

Potential Side Effects and Risks

Research has shown that the human body can easily tolerate quantities of CBD up to 1500mg/day. But the higher the dose, the higher the chance of side effects.

In some users, CBD can cause:

  • gastrointestinal issues,
  • appetite problems,
  • drowsiness.

CBD can also interact with different over-the-counter and prescription medicines. Any medication that gets metabolized by a group of enzymes called cytochrome p450 enzymes, can interact with CBD.

60% of the clinically prescribed medications are metabolized by CYP3A4, a type of cytochrome p450 enzyme. CBD can inhibit CYP3A4. By taking CBD with one of these medications, you could increase drug blood levels. This could even result in overdose.

If you are taking any prescription drug, make sure to consult your doctor before taking CBD with it.

Will CBD Get You High?

THC is the main active component that is responsible for the psychoactive effects of marijuana. CBD is non-impairing and non-psychoactive. It can’t produce a mind-altering effect. It will not get you high even if it is consumed in much larger quantities.

That said, if you take a full-spectrum CBD product, you may feel a little bit high. Full-spectrum CBD products have small THC concentrations. But for some, these small concentrations are high enough to get them a bit high.

You can also fail a drug test when taking CBD products.

If you want to avoid this, only use CBD isolate products.

What’s Next

Go  to our CBD Hub to learn more about CBD-related topics.

Scientific References

  1. A.O. Kaup, Cannabidiol 133mg + Cannabigerol 66mg + tetrahydrocannabinol 4mg vs placebo as adjuvant treatment in chronic migraine , Cannabidiol 133mg + Cannabigerol 66mg + Tetrahydrocannabinol 4mg vs Placebo as Adjuvant Treatment in Chronic Migraine – – Full Text View – ClinicalTrials.gov. (n.d.). https://www.clinicaltrials.gov/ct2/show/NCT04989413 (accessed April 22, 2022).
  2. Review of the 3rd European Academy of Neurology Congress 2017. (2017, 10 augustus). European Medical Journal. Retrieved on 22 april 2022, from https://www.emjreviews.com/neurology/congress-review/review-of-the-3rd-european-academy-of-neurology-congress-2017/
  3. Parker, L. A., Rock, E. M., & Limebeer, C. L. (2011). Regulation of nausea and vomiting by cannabinoids. British Journal of Pharmacology, 163(7), 1411–1422. https://doi.org/10.1111/j.1476-5381.2010.01176.x
  4. Cuñetti, L., Manzo, L., Peyraube, R., Arnaiz, J., Curi, L., & Orihuela, S. (2018). Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. Transplantation Proceedings, 50(2), 461–464. https://doi.org/10.1016/j.transproceed.2017.12.042
  5. Zou, S., & Kumar, U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Molecular Sciences, 19(3), 833. https://doi.org/10.3390/ijms19030833
  6. Marsicano, G., & Lutz, B. (2006). Neuromodulatory functions of the endocannabinoid system. Journal of endocrinological investigation, 29(3 Suppl), 27–46. https://pubmed.ncbi.nlm.nih.gov/16751707/
  7. Montecucco, F., & di Marzo, V. (2012). At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction. Trends in Pharmacological Sciences, 33(6), 331–340. https://doi.org/10.1016/j.tips.2012.03.002
  8. Pacher, P., Bátkai, S., & Kunos, G. (2006). The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacological Reviews, 58(3), 389–462. https://doi.org/10.1124/pr.58.3.2
  9. Clapper, J. R., Moreno-Sanz, G., Russo, R., Guijarro, A., Vacondio, F., Duranti, A., Tontini, A., Sanchini, S., Sciolino, N. R., Spradley, J. M., Hohmann, A. G., Calignano, A., Mor, M., Tarzia, G., & Piomelli, D. (2010). Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nature Neuroscience, 13(10), 1265–1270. https://doi.org/10.1038/nn.2632
  10. Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan-Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 4790–4805. https://doi.org/10.1111/bph.13250
  11. Bardin, L. (2011). The complex role of serotonin and 5-HT receptors in chronic pain. Behavioural Pharmacology, 22(5 and 6), 390–404. https://doi.org/10.1097/fbp.0b013e328349aae4
  12. Rhyne, D. N., Anderson, S. L., Gedde, M., & Borgelt, L. M. (2016). Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 36(5), 505–510. https://doi.org/10.1002/phar.1673
  13. Baron, E. P., Lucas, P., Eades, J., & Hogue, O. (2018). Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort. The Journal of Headache and Pain, 19(1). https://doi.org/10.1186/s10194-018-0862-2

Post last updated on: April 22, 2022

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Winston Peki

Reviewing vaporizers, growing supplies, CBD products and scientific articles about cannabis, cannabinoids, and vaping since 2012. Read more about Winston here. LinkedIn

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© Copyright www.herbonaut.com · All Rights Reserved. The content on this website is for informational purposes only and is not intended as medical advice. Medical advice should always be obtained from a qualified medical professional for any health conditions or symptoms associated with them. Every possible effort has been made in preparing and researching this material. We make no warranties with respect to the accuracy, applicability of its contents or any omissions.

Science Based

This article is based on scientific studies, written by Winston Peki and fact-checked by experts.

Inside this article, you can find references to peer-reviewed scientific studies. The numbers in the parentheses (1, 2, …) are clickable links to these peer-reviewed scientific studies. In some cases, the link will give you direct access to the study, while in other cases if you want to read the full study, you either have to pay the publisher a fee or find a free version of the study elsewhere.

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Scientific References

A.O. Kaup, Cannabidiol 133mg + Cannabigerol 66mg + tetrahydrocannabinol 4mg vs placebo as adjuvant treatment in chronic migraine , Cannabidiol 133mg + Cannabigerol 66mg + Tetrahydrocannabinol 4mg vs Placebo as Adjuvant Treatment in Chronic Migraine - - Full Text View - ClinicalTrials.gov. (n.d.). https://www.clinicaltrials.gov/ct2/show/NCT04989413 (accessed April 22, 2022).

Review of the 3rd European Academy of Neurology Congress 2017. (2017, 10 augustus). European Medical Journal. Retrieved on 22 april 2022, from https://www.emjreviews.com/neurology/congress-review/review-of-the-3rd-european-academy-of-neurology-congress-2017/

Parker, L. A., Rock, E. M., & Limebeer, C. L. (2011). Regulation of nausea and vomiting by cannabinoids. British Journal of Pharmacology, 163(7), 1411–1422. https://doi.org/10.1111/j.1476-5381.2010.01176.x

Cuñetti, L., Manzo, L., Peyraube, R., Arnaiz, J., Curi, L., & Orihuela, S. (2018). Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. Transplantation Proceedings, 50(2), 461–464. https://doi.org/10.1016/j.transproceed.2017.12.042

Zou, S., & Kumar, U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Molecular Sciences, 19(3), 833. https://doi.org/10.3390/ijms19030833

Marsicano, G., & Lutz, B. (2006). Neuromodulatory functions of the endocannabinoid system. Journal of endocrinological investigation, 29(3 Suppl), 27–46. https://pubmed.ncbi.nlm.nih.gov/16751707/

Montecucco, F., & di Marzo, V. (2012). At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction. Trends in Pharmacological Sciences, 33(6), 331–340. https://doi.org/10.1016/j.tips.2012.03.002

Pacher, P., Bátkai, S., & Kunos, G. (2006). The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacological Reviews, 58(3), 389–462. https://doi.org/10.1124/pr.58.3.2

Clapper, J. R., Moreno-Sanz, G., Russo, R., Guijarro, A., Vacondio, F., Duranti, A., Tontini, A., Sanchini, S., Sciolino, N. R., Spradley, J. M., Hohmann, A. G., Calignano, A., Mor, M., Tarzia, G., & Piomelli, D. (2010). Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nature Neuroscience, 13(10), 1265–1270. https://doi.org/10.1038/nn.2632

Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan-Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 4790–4805. https://doi.org/10.1111/bph.13250

Bardin, L. (2011). The complex role of serotonin and 5-HT receptors in chronic pain. Behavioural Pharmacology, 22(5 and 6), 390–404. https://doi.org/10.1097/fbp.0b013e328349aae4

Rhyne, D. N., Anderson, S. L., Gedde, M., & Borgelt, L. M. (2016). Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 36(5), 505–510. https://doi.org/10.1002/phar.1673

Baron, E. P., Lucas, P., Eades, J., & Hogue, O. (2018). Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort. The Journal of Headache and Pain, 19(1). https://doi.org/10.1186/s10194-018-0862-2