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The entourage effect: How cannabis compounds may be working together

January 8, 2020
entourage effect in cannabis, smoking marijuana with different strains
(Michal Strychowski/Stock)

This article was originally written October 28, 2015 and has since been updated.


Take a close look at your cannabis buds. They’re covered in sticky, shining dots of resin, and in this resin are hundreds of therapeutic compounds that contribute to the effects and benefits of cannabis.

This theory that various cannabis compounds work together to create unique effects and benefits has been coined “the entourage effect.”

You’re likely already acquainted with the plant’s two most famous compounds, THC and CBD, but there are many other compounds the plant produces in lesser abundance that seem to play a supporting role in the overall effects of a particular strain.

This theory that various cannabis compounds work together to create unique effects and benefits has been coined “the entourage effect.”

What is the entourage effect?

When we smoke or vaporize cannabis, our bodies take in hundreds of botanical compounds. Each one arrives with unique effects and benefits, and their behavior may change in the presence of other compounds. This is the entourage effect.

It’s kind of like how your mood might change depending on your social environment. How do you behave when you’re alone, at a party with strangers, or hanging out with your best friend? Your mood and the personality you project shift depending on who’s in the room.

To illustrate the entourage effect in cannabis, let’s work with the two compounds you’re likely familiar with: THC and CBD. In a 2010 study, patients with cancer pain were given either a pure THC extract or an extract containing near-equal levels of both THC and CBD—patients given the THC/CBD combo reported having less pain.

Related

How cannabis relieves different types of pain

But cannabis is far more than just THC and CBD. It also produces other cannabinoids like CBN, CBC, CBG, and dozens more—as well as terpenes, which are aromatic compounds also readily found in the essential oils of lavender, orange, black pepper, eucalyptus, and much more. With such a diversity of useful compounds in cannabis, the possible synergies could make your head spin with excitement.

Unfortunately, there are very few studies that explore these synergies in humans—it’s still only a theory supported by a small body of research, and, of course, loads of anecdotal evidence from curious cannabis enthusiasts around the world experimenting with new varieties of the plant.

Cannabinoids and terpenes potentially work together

This theory of the entourage effect is thoroughly described in a review called Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects,” authored by Dr. Ethan Russo—a neurologist and pharmacologist who has long studied cannabis compounds and how they affect the body.

In this review, Dr. Russo details the studied benefits of common cannabis compounds, and based on their pharmacology, describes their potential synergistic effects. For example, the cannabinoids CBD and CBG have been found to inhibit the bacterial staph infection MRSA—how might they be even more effective when combined with the MRSA-fighting terpene pinene or when prepared with terpenes that increase skin permeability?

Let’s look at a specific strain example.

granddaddy purple cannabis strain

Strain: Granddaddy Purple

Cannabinoids and terpenes: THC (diamonds), myrcene (blue), caryophyllene (fuchsia), pinene (green)

Potential synergies: Understanding the potential benefits of THC, myrcene, and caryophyllene, one might recommend this strain to someone looking to achieve sleep (thanks, myrcene), while simultaneously addressing pain and inflammation (thanks, THC and caryophyllene).

The diversity of cannabinoids and terpenes native to cannabis flower is often why some consumers prefer bud over extracts; there are so many compounds with their own respective potential benefits in the flower to enjoy.

Related

What are cannabis terpenes and what do they do?

A few more potential synergies detailed in “Taming THC” include:

  • The pine-scented terpene pinene may help counteract compromised memory caused by THC.
  • A combination of CBD and the peppery terpene caryophyllene may be beneficial in the treatment of addiction.
  • CBD and the citrus-scented terpene limonene might work together to alleviate anxiety.
  • THC plus the cannabinoid CBN can potentially yield enhanced sedating effects.

To reiterate, the entourage effect remains an unproven theory. But as terpenes and novel cannabinoids become objects of consumer intrigue, we’re likely to find more research on the horizon.

Related

How might terpenes contribute to the ‘entourage effect’ of cannabis?

THC- and CBD-only medicines

So which cannabis products are more likely to promote this so-called entourage effect?

Cannabis flower certainly contains a wide variety of cannabinoids and terpenes by virtue of being a raw herbal product. But some cannabis extracts also offer a rich diversity of cannabinoids and terpenes. We call these full-spectrum cannabis extracts.

Related

What is CBD oil? A beginner’s guide to cannabidiol extracts

Oils, ingestible capsules, dabs, vape cartridges… full-spectrum extracts can come in many forms. What characterizes them as “full-spectrum” is the long list of chemical compounds they retain. That means the extract could deliver THC, CBD, CBG, CBN, myrcene, caryophyllene, limonene, and much more—all in one convenient package.

Not all cannabis extracts capture the wide array of compounds produced by the cannabis plant. Some are refined as a means to remove THC—called broad-spectrum cannabis extracts—or formulated to contain one single compound, usually CBD or THC—called isolates.

cbd oil, full spectrum, broad spectrum, isolate, marijuana

CBD oil can be formulated in one of three ways: full spectrum, broad spectrum, and isolate. Full-spectrum CBD oils deliver the widest variety of therapeutic compounds, followed by broad-spectrum CBD oil which has all trace of THC removed. CBD isolate contains nothing but CBD. (Leafly)

While many people prefer cannabis products that provide lots of cannabinoids and terpenes, there are reasons to enjoy isolates; you know precisely which cannabinoid you’re ingesting, and you don’t have to worry about absorbing any cannabinoids you may not be interested in.

Related

Does CBD show up on a drug test?

Among THC-only medicines are synthetic renderings of THC, the two most common being Marinol (dronabinol) and Cesamet (nabilone). These are FDA-approved pharmaceuticals often prescribed to treat cancer-related nausea or pain. But as we saw in the 2010 study mentioned earlier, these isolate medicines may not be as effective as combination medicines that include both THC and CBD.

And considering CBD helps curb the adverse side effects of THC, notably anxiety, it’s not hard to imagine why some prefer a combination over pure THC. A 2011 survey on forms of consumption found only 1.8% of 953 patients preferred synthetic THC isolates over inhaled or infused methods.

A ‘treasure trove’ of medicinal possibilities

Raphael Mechoulam, one of the most esteemed cannabis researchers in history, calls cannabis a “neglected pharmacological treasure trove” in a 2005 paper. Neglected by researchers? Absolutely. But to some extent, by consumers like us, too.

For decades, cannabis has been regarded primarily as a vessel for the almighty high-bringer that is THC. Even in legal markets with a wide variety of options, many people still reach for the strain with the highest THC content.

Related

Beyond THC: It’s time to assert the primacy of terpenes

In response to this decades-long demand for higher highs, the plant has been bred to contain virtually nothing but THC. Practically every other cannabinoid is a whispered afterthought, with some high-CBD cultivars posing exceptions. Getting the plant to produce a diverse “treasure trove” of therapeutic compounds will require a lot of time—and consumer demand.

Interest in terpenes and rare cannabinoids is beginning to flow in, if only at a slow trickle. We’re starting to see, for example, cannabis breeders focus on CBG production and extract producers capture novel cannabinoids like CBN, CBC, and delta-8-THC. And research on terpene entourage effects is also increasing in interest.

With the continued spread of legalization and information, it’s nice to think we’re not too far off from unlocking the treasure trove cannabis has to offer.


Sources:

http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01238.x/pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751232/pdf/146-0706415a.pdf

http://files.iowamedicalmarijuana.org/petition/2012/Johnson_2010.pdf

http://www.ncbi.nlm.nih.gov/pubmed/24175484

https://www.ncbi.nlm.nih.gov/pubmed/9721036

  • Sarah Elaine Weeks

    Love the info graphics! So so so very helpful!

  • Chili Bu Tube

    first off, stop using the term ‘marijuana’
    if your going to attempt to educate people on Cannabis at least use the proper terminology,
    secondly it is ensemble effect NOT entourage effect…
    simply look at what the two words mean..

    en·tou·rage
    ˌänto͝oˈräZH/
    noun
    a group of people attending or surrounding an important person.
    “an entourage of bodyguards”
    synonyms: retinue, escort, cortège, train, suite;

    ********************************************************************

    en·sem·ble
    änˈsämbəl/Submit
    noun
    1.
    a group of musicians, actors, or dancers who perform together.
    “a Bulgarian folk ensemble”
    synonyms: group, band; More
    2.
    a group of items viewed as a whole rather than individually.
    “the buildings in the square present a charming provincial ensemble”
    synonyms: whole, entity, unit, body, set, combination, composite, package

    so now you know 😉

    #0peration0vergrow

    • jorel22

      good point.

    • Michael

      Down voted for the attitude. The mean-spiritedness wasn’t necessary as your point could have been conveyed in a more constructive, less condescending manner. Otherwise, yes, ensemble is a more accurate term, but we all understood what the author meant and he/she was most likely referencing Dr. Russo’s study.

      • Jonathan Messer

        He didn’t have attitude. I found his information on point and informative, even though it’s something I already know.

        • Juergen Meixner

          Chili Bu Tube, you too, has it all. 🙂

          “And this hypocrisy I found among them the worst: that even those who command may pretend the virtues of those who serve.”

          Friedrich Wilhelm Nietzsche
          (1844-1900), German philosopher, essayist, lyricist and writer

          Source: Nietzsche, So spoke Zarathustra. A book for everyone and no one. 1883-1885 (1st complete edition 1892), first printing 1883. Third part, 1884. From the diminishing virtue

          Discovery of the ENDOCANNABINOID SYSTEM!

          VIVEKA

          https://www.facebook.com/photo.php?fbid=10204480226990566&set=a.1200745463650.2028330.1378976258&type=3

    • Sandee Glavas Waldo

      Chili Bu Tube.. If you understood a cancer cell….and how cannibinoids surround it….the word “entourage” IS quite appropriate 🙂

    • Ian

      Hi, Cannabis journalist here – entourage effect is indeed the correct term. It was first reported in 1998 by the famous Dr. Mechoulam and S. Ben-Shabat and further backed up in 2011 in an article in the British Journal of Pharmacology by Russo [https://www.ncbi.nlm.nih.gov/pubmed/21749363]. Whether or not it makes sense to you, it is the correct term and is in-keeping with progressive cannabis science. If you want to educate, first do your own research 😉

      • Avery

        Thank you!

    • Joe Adair

      You’re right about ‘marijuana’; it’s a racist term and needs to go.

      With regard to entourage v ensemble, it’s definitely ENTOURAGE; the important person the other elements surround, is THC.

      • Hahaha, saying marijuana is racist ? What a joke

    • Stéphane Blouin

      Relativise bro,

      Truly the latin name is Cannabis, and that slang term marijuanna is for a wild mexican tobbacco, and I think you are correct, a proper wording would be Synergy or Synergical effect,
      Synergy
      1. the interaction of elements that when combined produce a total effect that is greater than the sum of the individual elements, contributions, etc.; synergism.

      However that term Entourage has been used in the field for a very long time and it is almost universalized at this point. Sometime words are derived from their original meaning and distorted with common usage. This is referred to as connotation vs denotation.

      At the same time don’t be too harsh on people who are on our side. You know… it’s not like the author is a complete ignoramus just because of a couple words. This is very important information that can save millions of human lives, and how much suffering? Let’s calm down and relax.

    • Travis Cesarone

      You missed something. “Entourage 2: surroundings.”
      Entourage effects suggest modulating properties or surrounding effects on the pyschoactive structure. Not the effects of the entire chemotype including THC, as “Ensemble Effect” would suggest.
      Cheers Chili
      #freeandfair

  • Gina Bilotta Salminen

    I get Whole Plant Medical Cannabis products from Leafline Labs in Minnesota. They are fantastic!! I have adult onset Facio Scapulo Humeral Musculat Dystrophy. Despite progression, he Whole Plant Medical Cannabis oil based products of oral suspension mixed with coconut oil for long lasting benefits 8-12 hours. If flavoring is desired they use organic vanilla sugar, and pure orange oil. And I use vape oils, which I am allowed to have 6 puffs every 4-6 hours. But I usually save vaping for night time, unless it is a bad day with breakthrough symptoms. I have been through the Opiates, the awful epidurals, and things for pain for over 15 years. None of that gave me back the function and motivation, like the whole plant medical cannabis products. In Minnesota Leaf Product is not allowed. So the Whole Plant Medical Cannabis products come in Suspensions, vape oils, tinctures usually used sublingual, capsules, topicals, transdermal patches, other edibles besides measured suspension, and probably every other delivery method I am not able to think of right now, or don’t know of. I never knew I would get to relive and rediscover some parts of my life, because of Whole Plant Medical Cannabis. I am beyond thankful. I think I would die without it.

    • Suzy Qusy

      You aren’t getting true whole plant healing when using chemical solvents to create a product. True whole plant is literally the whole plant and not an extract of what was once flowers, leaves and seeds – that is assuming the product initially used the whole plant. Pushing chemical solvents through the plant material and then discarding the true plant material kills off 99% of the terpenes and 80% of the valuable broad spectrum cannabinoids. I know you are trying to sell product here, but it isn’t true Whole Plant Medicine. It’s an extract. Vaping is dangerous. It uses more dangerous chemicals than extracts. People need to look into Bubble Lungs. Anytime you take a whole plant product and turn it into something that is anything but the whole plant you can no longer call it whole plant.

      • Anytime you take a whole plant product and turn it into something that is anything but the whole plant you can no longer call it whole plant.

        Fair enough. Language is important. Consuming every herb, root, and plant in its 100% whole form, though, is not a requirement for longevity, and extracting compounds or parts of the plant for nutrition doesn’t lead to bad health.

        Product formulator and manufacturer here ($2M+ annual sales in Whole Food stores, etc). I’ve watched top Tibetan doctors create their herbal formulas in blackened backrooms outside of Jomsom, Nepal. People traveled for many miles to get their herbal concoctions, and in every case, these top-of-their-field docs used extractions of the plants they were using. Those final black balls were the result of soaking, steam, cooking, pressing, and alcohol extraction, just as they’d done it for hundreds of years.

        Definitely, the newly minted “entourage effect” is validation to the power of including a variety of compounds in plant formulas, something herbalists have known for a long time. But there’s no need for us to chew on Willow bark for its aspirin effect in order to stick with a whole plant belief.

        • Kyle

          wow very well put!

  • Donna Gordon Pike

    So sad to see some alleged experts whacking the shit out of people about who knows more about a medicinal plant. This is a healing plant people, it actually kills pain and helps with a myriad of health issues so why don’t you alleged experts stop knocking other people’s knowledge and help them by either offering up sound advice, or assistance with delivering a good product to them to HELP them with sickness? Holy shit, would you argue about which pharmaceutical company makes the best amoxicillin?

    Help one another. If you want to be a hater, look in the mirror and do it there and if you don’t like it, don’t share it.

    • thank you

    • JuiB1966

      Beautiful message beautifully written. Let’s hope it’s heeded. Cheers!

    • BREEDER

      When you get scientific with it to at least some degree,,it is much more effective and credible.That’s the audience you have out there.
      p.s. the behavior of someone loaded on THC isn’t always the one who should present the argument. Nice page,,thank you http://www.leafly.com

  • Ryan Miller

    I find it so funny that people are saying hemp oil has no value. Depending on the strain of hemp, hemp can contain many cannabinoids, and terpenes that have huge medical benefits. Yes full plant extract with THC will work the best but you can not say that high CBD hemp oils have no value. I have seen people take some of Hempmeds RSHO gold label in the middle of a seizure and the seizure stopped immediately tell me how this is no medical value. This oil has low THC but is high in CBD and is a full spectrum oil with over 84 trace cannabinoids and natural terpenes. I have seen children having 100’s of seizures a day go down to 0 a day from these oil. So you so called experts can say what ever you want to but the truth is in the pudding. Also the companies oils are already used medically in Brazil for many illnesses and these products are from hemp oil containing only small amounts of THC: http://www.medicalmarijuanainc.com/health-authorities-brazil-approve-importation-rsho-first-time-multiple-sclerosis-patient/ .. Why are people fighting over this, both hemp and the cannabis plant have huge medical benefits.

    • Bill Landreth

      So true

    • Bee Mayes

      the answer is ‘reefer madness’. people are still blinded by the lies.

  • Robert Root

    I use medical marijuana to manage symptoms of Multiple Sclerosis which has been severely impacting my life in many ways. When I started using medical marijuana in March of 2017 I thought that just including CBD (Cannabidiol) would be enough to benefit me. What I discovered that the entourage effect is very real, some amount of THC needed to be taken to see the full effects. I’ve only been using approach for 6 months so I am still searching the exact mix that works for me, my Doctors (my PCP and prescribing Physician) couldn’t understand my resistance using THC but when I gave in and introduced THC to my daily regimen I started noticing many benefits that I did not expect, the best unexpected benefit is that I am able to urinate and fully empty my bladder. This is a huge problem of people with MS and is the cause of countless bladder infections which is extremely dangerous for people with compromised immune systems.
    I believe that there are many benefits to using whole plant medication as there are many terpenes and other compounds other beneficial compounds that cannot be obtained reliably by chemical and CO2 extraction. Also I believe that some edibles should be introduced as the benefits are more fully seen and longer lasting when consumed.

    • Thanks for your testimony – I too noticed a better urination pressure if you will. It makes everything work better, since we are cannabinoid deficient from 80 years of prohibition.

  • Steve Bogna

    I make my own coconut oil as a topical or an oral medicine–I usually get 13-14% THC and 2 to 3% CBD and CBN. I won’t buy someone else’s products. I broke 60 bones and had 100 surgeries from one motorcycle accident, so I don’t need additional side effects. All pain pills are poison. As an amputee, nothing works 100% but I won’t pay good money for serious negative side effects.

  • Rafael Ladeira

    The whole Plant = TRUE MEDICINAL

    Isolated compounds = Can help one or another individual, but its a GAME FROM PHARMACEUTICAL INDUSTRY! They can get PATENT isolating compounds. But cant patent a plant.

    Babylon

  • Lloyd W

    It is worth noting that the entourage effect is a proposed mechanism of modulation of the psychoactive effects of cannabis. It hasn’t been really been proven scientifically, reports of the entourage effect are mainly anecdotal. There needs to be more research before you make health claims like these.

    Source: https://www.scientificamerican.com/article/some-of-the-parts-is-marijuana-rsquo-s-ldquo-entourage-effect-rdquo-scientifically-valid/

  • Whole plant FTW!

  • yiehom

    I am lost. Do I follow THC? CBD? a mix of both? The whole plant? Please answer the question.

    • Anon Amos

      What is your goal? For most medical users it would be a mix, coming from the whole plant.

  • Duane Sugarbaker

    Sounds like the only way to get whole plant is to yip it out of the ground and start eating. Is there anybody that extracts the oils from the whole plant including the roots. And why isn’t that a good idea?

    • Heather Kaye Rath

      I dont use the roots at all (but you can) however I so juice my plant! I pluck leaves directly off my growing plant and pop them in my juicer in the mornings. It gives me the pain relief without the high. Doing this is consuming thca

  • 360dunk

    I’ve been using RSO oil for over a year now, as a preventative measure, with amazing results. I don’t have cancer and I’m hoping the oil will help keep things that way. I always get the 1:1 ratio of RSO (equal parts THC and CBD) and have noticed I now sleep like a log and the arthritis pain is far more manageable.

  • jimbro44

    Arizona Organix in Phoenix had a high CBG strain like 4 years ago but then the mother died and it disappeared.
    I just now finally found a CBG tincture but I think it may be an isolate (So i would combine w flower), but it’s expensive and I wish I could get high CBG strain again.

  • Freddie Cadmus

    Is there a way to make nasal mist out of cannabis liquid?