How Does CBD Actually Work?

I’ve spent the better part of the last 2 years researching CBD and working on this article.

To get the facts straight (or straighter), I brought in Martin A. Lee to help me.

He’s an ex-Harvard professor and the founder of ProjectCBD, one of the leading global authorities on CBD research.

Let’s dive right in.

What is CBD?

CBD stands for cannabidiol, which is a naturally occurring, organic compound found in the resin of Cannabis sativa species.

CBD is one of 113 active compounds found in cannabis and is especially abundant in hemp (which is a subspecies of cannabis), however it can also be found in other types of cannabis in significant amounts.

CBD is non-intoxicating and it doesn’t make users high.

What conditions does CBD help with?

Martin A. Lee
Martin: CBD interacts with the endocannabinoid system and the endocannabinoid system is implicated in pretty much all diseases. So theoretically, if one modulates the endocannabinoid system as CBD does, you could be affecting many many different conditions.

I think where CBD has shown great promise thus far is, obviously, certain neurological conditions like epilepsy but, I think, in the future there’s a great deal of promise in the area of metabolic disorders—diabetes, obesity and so forth.

Given the great extent to which these conditions are problematic now and there’s really an epidemic situation with respect to metabolic disorders and diabetes, that would be a great emphasis on CBD in the future.

How does CBD work?

CBD produces effects firstly by inhibiting an enzyme that degrades anandamide (a cannabinoid that our body produces, also known as the “bliss” molecule) and in doing so, it increases its healing effects.

Anandamide naturally has a very short life span.

Now, anandamide is a neurotransmitter that binds to CB1 and CB2 receptors (part of our endocannabinoid system) and boosting its levels produces a bunch of positive effects on the body — regulates pain perception (by desensitizing TRPV1 receptors), increases appetite, kills cancer cells, increases neurogenesis (therefore lowering anxiety and depression) and modulates the immune system response.

Secondary effects of CBD come from its activation of 5-HT1A receptors and several ion channels that stimulate production of serotonin, mediate pain perception, inflammation and body temperature.

Besides being responsible for increasing serotonin levels, 5-HT1A receptors also play a role in the secretion of dopamine which is why CBD may be helpful to people with schizophrenia and Alzheimer’s (8).

CBD also stimulates the production of endorphin (which also makes you feel awesome) and oxytocin, a hormone that produces anti-aggressive and calming effects and is responsible for the feeling of emotional bonding.

CBD blocks GPR55 receptor signaling, with preliminary research showing a possible effect in slowing down the growth of certain cancers.

GPR55 is a receptor that is located in the brain, spleen, adrenals and certain areas of gastrointestinal tract and is involved in creating cancer cells, influencing their migratory behavior, and inducing unwanted inflammation (for example, Crohn’s Disease patients have higher concentrations of this receptor).

Very preliminary in vitro and animal studies have shown that inhibiting GPR55 signaling reduces tumor growth. (9)

Bottom line:

  • CBD helps you keep anandamide in your system longer, making you feel less anxious and depressed, and relieving pain.
  • CBD activates 5-HT1A receptors, which help you secrete more “feel good” hormones, like endorphin, serotonin and oxytocin.
  • CBD blocks GPR55 signaling, which might slow down the growth and migration of certain cancers.

What are the side effects of CBD?

CBD has been extensively researched on all mammals.

Studies done on humans focused on using oral administration or inhalation so they correlate pretty well in their reported results with how the general public would use CBD.

Back in 2011, Bergamaschi created a review of 132 CBD studies, analyzing both effects and side effects of this amazing compound.

Here’s what the review concluded:

“Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans.” (10)

The side-effects of CBD have mostly been found in vitro or in animals studies. Human studies did not show any side effects.

In vitro and animal studies found a few issues with CBD, revolving around alterations of cell viability, reduced fertilization capacity, and inhibition of hepatic drug metabolism and drug transporters.

Other reported side effects of CBD are mild to low and include low blood pressure, dry mouth, light-headedness, sedation and drowsiness.

Studies say that mixing CBD with pharmaceuticals might produce some side effects, as CBD interacts with drug metabolizing enzymes that belong to the cytochrome P450 family.

For folks out there that are not chemistry majors, this means that CBD is metabolized via an enzyme that various drugs inhibit.

Other pharmaceuticals can induce this same enzyme, leaving us with less available CBD.

In the end, most studies recommend consulting your physician before mixing CBD with pharmaceutical drugs.

Does CBD interfere with medication?

Martin A. Lee
Martin: CBD does interact with a lot of different pharmaceuticals and if one is taking particularly high doses of CBD as an isolate (single molecule CBD which is sold on the Internet under the false assumption that CBD alone is better than CBD with the other components of the plant) you run into a problem with drug interactions.

The problem with this is that if you’re using a CBD isolate, you usually need much higher doses for it to be effective.

We don’t see a problem with drug interactions once CBD in low doses is a part of the whole plant remedy.

How much CBD oil should you take?

cbd dosage chart

The trick to getting the CBD dosage right is to start with a low (minimum) dose and gradually increase the dosage until you feel better. Only then should you keep it at that level for up to 90 days or longer.

The best CBD dosage for most people would be a total of 12 mg of CBD a day, applied in 3 equal doses.

For people who suffer from medium to high severity of symptoms, this starting dosage can go up to 22-30 mg of CBD a day.

For epilepsy patients, 3 mg/kg a day for 30 days is a good starting dose and the one used in several CBD positive studies.

However, there is a big obstacle in CBD dosing and that is the fact that patients cannot figure out how to calculate their CBD dosage and how many drops to take.

When you buy a CBD product, for example oil, its producer should provide information on how much CBD is in every milliliter (gram). Then you can calculate how much CBD is in every drop (1 ml=20 drops) and figure out your dosing.

Let me illustrate this with an example:

Let’s say that you just bought a bottle of CBD oil from a licensed producer in Canada.

You paid $100 for a 45 ml bottle and the product label claims that the CBD content inside it is 26 mg/ml.

You’re a first time user who suffers from mild anxiety, so you decide to start your therapy with 12 mg of CBD per day.

But how many drops is that?

Well, since there are 20 drops in 1 ml and each ml contains 26 mg of CBD, then 20 drops of your CBD oil give you 26 mg of CBD.

If you divide the CBD content per milliliter with 20, you can find out how much CBD is in a single drop — in this case we have 26/20=1.3. Our fictional oil provides 1.3 ml of CBD per drop.

Remember, you need 12 mg of CBD per day at first, so 9-10 drops of this particular fictional oil per day will help you meet your daily dose.

In this case, your starting therapy would be 3-4 drops of CBD oil, 3 times a day.

You can do the same with CBD-rich flowers, as 1 gram is equal to 1 milliliter.

As I previously mentioned, it takes up to 2 hours for CBD to kick in, so after each application wait a bit and see how you respond.

How to know you’re buying a quality CBD oil?

Martin A. Lee
Martin: That’s actually very difficult to know for certain. It’s easy to access CBD oils on the Internet, derived from industrial hemp but the quality of these products is questionable sometimes.

There was a recent survey published in the Journal of the American Medical Association (6) which indicated that about 70% of the CBD products tested, and they tested about 85 randomly ordered products, have shown to be mislabeled, that the labels did not correspond with what was actually in the product.

Now, the good news is that 30% were well labeled. But even if it’s well labeled there’s a few things that people should look for:

  1. It’s better to go for a CBD product that’s derived from the United States — Colorado, Kentucky, Oregon — one of these places that they’re growing hemp (they’re actually growing marijuana that they’re harvesting early) or they’re growing a hybrid between hemp and marijuana. But there’s enough CBD in the plant to make it worthwhile to extract from, but still under 0,3% THC, which is the limit above which it’s no longer considered hemp, below which it is.
  2. Avoid product makers claiming that they derived their product from seed, or stem of the plant. You can’t get CBD from the seed or the fiber to any appreciable degree at all.
  3. Avoid products that contain additives. That’s propylene glycol, ethylene glycol — these are potentially very harmful. They shouldn’t be included in any product that’s meant to be healthy, particularly if you smoke it or vaporize it.
  4. Avoid the products being imported from Europe, because the hemp plants they’re growing in Europe are not grown for CBD, they’re grown for fiber and for seed. It’s better probably to get products that originated in Colorado or Kentucky. And I don’t say that incidentally because I’m from the US and I’m trying to boost US companies, it’s just that they’re growing better plants. In Europe they’re growing plants that are not meant for CBD. They grow them for their initial purpose and then the leftovers, the biomass, the parts of the plant they don’t use to get the seed or fiber, then they extract from that. So it’s sort of the leftovers they use and it’s just not a very good source. It’s better to extract CBD from high resin plants, or a plant that has a lot of cannabinoids and a lot of CBD in it, because then you need less plants to extract from.
  5. Try to buy from companies that grow organically or grow in the United States, since the federal government does not apply there.

That being said, it’s possible to get good, clean products. The industry is still somewhat in its infancy and, unless people have access to analytical labs where they can test these products, in a lot of ways it’s still rolling the dice as you don’t quite know.

But look for products coming out of Colorado or Kentucky, with a full spectrum. Avoid isolates, don’t get just CBD alone, it should be part of a spectrum of plant extract.

Sooner or later, these products will be better regulated and that’ll give consumers a lot more confidence.

References

  1. Welty TE, Luebke A, Gidal BE; Cannabidiol: promise and pitfalls; Epilepsy Currents; September 2014; 14(5):250-2.
  2. Mecha M, Feliú A, Iñigo PM, Mestre L, Carrillo-Salinas FJ, Guaza C; Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors; Neurobiology of Disease; November 2013; 59:141-50.
  3. Kaur G, Andriola M, Manganas L; Efficacy of Cannabidiol in Children with Intractable Epilepsy; Neurology; April 2017; 88(16).
  4. Shannon S, Opila-Lehman J; Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report; The Permanent Journal; 2016; 20(4):108-111.
  5. Zuardi AW, Crippa JA, Hallak JE, Bhattacharyya S, Atakan Z, Martin-Santos R, McGuire PK, Guimarães FS; A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation; Current Pharmaceutical Design; 2012; 18(32):5131-40.
  6. Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R; Labeling Accuracy of Cannabidiol Extracts Sold Online; JAMA; November 2017; 318(17):1708-1709.
  7. Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA; Safety and side effects of cannabidiol, a Cannabis sativa constituent; Current Drug Safety; September 2011; 6(4):237-49.
  8. Liu CS, Chau SA, Ruthirakuhan M, Lanctôt KL, Herrmann N; Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer’s Disease; CNS Drugs; August 2015; 29(8):615-23.
  9. Singh NS, Bernier M, Wainer IW; Selective GPR55 antagonism reduces chemoresistance in cancer cells; Pharmacological Research; September 2016; 111:757-766.
  10. Iffland K, Grotenhermen F; An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies; Cannabis and Cannabinoid Research; June 2017; 2(1):139-154.
Categories CBD

35 thoughts on “How Does CBD Actually Work?”

  1. Very informative. I like that there is not “CBD is an answer to every symptom.” When I read the benefits that are touted in some articles it sounds exaggerated and like wishful thinking.
    I love science.

  2. Thank you, Luke, for your incisive and understandable information on CBD. i have done much research on CBD and your analysis was the best I have read. I will pass it along to my friends. Keep up the good work.

    • Thank you Diane, it took a while to understand its mechanism of action, but it’s so good to be able to explain CBD in layman terms as it’s such a wonderful compound.

  3. I’m learning, but I need more.

    I have a friend that had brain surgery. The surgery went very well, but he now experiences seizures and profound exhaustion.

    Can you tell me where to go for more information that may be of help to him?

  4. Awesome review on CBD We would like have link to your data on our websites.

    Our US brands in HEMP ME, PET HELP, and EASY BUTTER MAKER

    Please inform how we would be about to do that.

    • Thanks Larry, you can cite parts of this review on your website and just let your visitors know where it’s from.

    • We have an in-depth guide on how to make Rick Simpson Oil and so the process would be the same for CBD heavy oil, instead you’d just use high CBD strains.

  5. Hi Luke; I’m on immune suppressors (azathioprine) and my platelets took a dive! My GP said he had a pt on coumadin whose INRs went out of whack. Looks like a probable adverse side effect.
    Are you aware of a anticoagulating effect?

    • Yes, this is something that I haven’t mentioned in the article but I think I replied to someone’s comment here. CBD, when combined with pharmaceuticals metabolized by the cytochrome P450 system, may produce adverse side effects. This is because CBD is metabolized by the same enzyme system. For example, one such drug is warfarin and there was a study recently published that noted clinical significance and advised that “INR levels should be monitored in patients when cannabinoids are introduced”. Here’s a link to the study.

  6. Great article. My daughter is considering the use of CBD for anxiety. Is there any long term effect using this product or is it still to early to tell?

    • Controlled CBD administration is generally considered safe in the long term. There is a review of 132 studies dealing with the safety of CBD (study) and all evidence we have points to the fact that CBD is completely safe as a compound. That being said, a lot of manufacturers are still trying to capitalize on the hype so I think choosing a supplier is paramount—if you’re in Canada I would go to a Health Canada licensed producer. I’m not affiliated with any LP but this is my opinion when it comes to buying medical cannabis oil.

  7. Good article. I like the dosage chart. However, I understand that CBD Oil has an absorption rate of about 3 to 6%. One, is that correct? and Two, does your chart take that under consideration. It would seem to me that is a very important component in this entire discussion.
    Thanks!

    • Hey Tom — this chart does not take that into account because this article does not deal with different CBD products (like oil for example), it just explains the compound and its benefits. Bioavailability depends on the consumption method, not so much on the type of product itself. Sublingual administration should be your best bet, as some oromucosal sprays reportedly have as much as 90% absorption rate.

  8. do u know of any companies that is safe to buy from.If products r better from in the states and not out of the country.So many r selling on the internet.

    • If you live in Canada then I suggest going to a licensed producer for your oil. Reputable hemp CBD brands are Elixinol and Green Mountain CBD, even though it’s advisable to get the whole-plant extract.

  9. Is CBD derived from Cannibis better than CBD derived from hemp? Wish that it were easier to determine the amount of CBD per ML.

  10. Thanks for the interesting article about CBD. You mentioned int he article that edibles could take one to two hours to take affect. It seems important to keep this in mind so you can monitor how the edibles are effecting you.

  11. Hi, just wondering if you can tell me what prescription drugs are not recommended with the use of CBD AND THC?
    My husband is currently on a menu of medications.. seroquel, endom???, clamazapam, ketamin and hydro morph and a few others I cant even think of. His pain still never relents, so we have decided to go this route and see what happens.
    We have tried literally everything, from multiple treatments, surgeries, pain stimulation inserted into his spine, connected to 16 peripheral nerves.. the list goes on.
    But we have decided to go down the CBD, THC medications and see if any help is available.
    thanking you.

  12. Just to clear things up, Both psycho active cannabis (above 1% THC) and hemp (below 0.3% THC) are Cannabis sativa. Hemp is known as Cannabis sativa hemp. Also you make it sound like only Europe and USA has CBD products and grows cannabis. Typical for so many Americans to know so little about there northern neighbours Canada. Canada has been producing high volumes of high quality cannabis products both illegally in the past and legally today as we are now the only country on the planet that has full legalization of Cannabis for both medicinal and recreational uses after Uruguay. Have you ever heard the phrase BC bud? Funny I met a man in Texas who thought BC bud was from Columbia and even argued the fact. The BC stands for British Columbia which is the most western province in Canada. A large amount of the weed past and present consumed in the states came from that region formany years. Consider your self schooled.

    • Thank you John! Just wondering where did I say that hemp and high-THC cannabis are not both Cannabis sativa? I completely agree with that nomenclature!
      We are a Canadian website and are well aware of how good the BC bud is, but our American friend Martin’s answer to that specific interview question could not be changed and edited to promote Canada, for the sake of good journalism. You rock though and this was a cool comment to read nevertheless. 😀

  13. 30% are labeled wrong? Holy cow I didn’t realize it was that high. I wonder if its the same in Canada where the government is really controlling all the product?
    Also great article Luka

    • Thank you Kevin! Yeah it apparently is, but that is why legalization is important. The LP’s in Canada must test their product in independent labs so I don’t think there’s any false labeling going on there.

  14. I am learning a lot about CBD these days. At first, I was skeptical about trying it but now I’m recommending this to my family as well 😛 I’ve tried a few online brands but I still need to find a perfect one for my back pain problem. This guide is what I need, so bookmarked this. Also, this dosage chart is what I was looking for.
    Thanks Luka!

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