Is the cannabis entourage effect real?

Is the cannabis entourage effect real?

Emma StoneAugust 13, 2020   Share   Print

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Whether you’re a seasoned cannasseur or a newbie to the herb, you’ve probably heard about the entourage effect. This phenomenon refers to the synergy that takes place when THC, CBD, minor cannabinoids, and terpenes work together to provide health benefits.

This is also frequently referred to as “whole-plant medicine” or “whole-plant synergy,” and it rests on the premise that cannabis products with many diverse compounds can deliver health benefits that isolated cannabinoids and compounds on their own cannot.

Professors Raphael Mechoulam and Shimon Ben-Shabat first made a case for whole-plant synergy in 1998. Their research argued that the body’s endocannabinoid system responds more favorably to whole-plant cannabis extracts by increasing the activity of the two primary endocannabinoids. This potent synergy also hints at why botanical whole-plant drugs are often more effective than drugs containing an isolated plant molecule.RelatedThe entourage effect: How cannabis compounds may be working together

These days, the entourage effect has become absorbed into the cannabis lexicon and is regularly splashed across products with abandon. But what does the entourage effect really entail, and how should we understand it now, in light of emerging research? 

A flurry of studies published within the last year have started digging deeper into the understanding of the phenomenon. Researchers are investigating the distinctive compounds believed to provoke the entourage effect, with one study even questioning whether the entourage effect has been over-pitched.

According to some study findings, the mechanisms that drive the entourage effect are not as clear-cut as cannabis marketing would have us believe. 

So what do we really know about the entourage effect?

For starters, there is evidence that some cannabinoids boost the effects of other cannabinoids. For example, THC can enhance the therapeutic performance of CBD, and minor cannabinoids may contribute benefits too.

In a study on breast cancer tissuein vitro and on test animals, the presence of minor cannabinoids improved the outcome. “Cannabis extract was much more effective than THC isolate in tumor kill and growth reduction,” said Dr. Ethan Russo, MD, pioneering researcher on the entourage effect and founder/CEO of CReDO Science. “The synergy of the cannabis extract could be accounted for by the presence of significant quantities of cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA) in the extract, compared to the THC alone.”

Additionally, this study of CBD by itself vs. an extract with the whole plant and CBD, showed that the whole-plant extract was just as effective at treating severe epilepsy, but with a 20% smaller dose, said Russo.RelatedWhy CBD works better with a little THC (even if you don’t want to get high)

But for Dr. Jordan Tishler, MD, expert cannabis physician, and Instructor of Medicine at Harvard Medical School, elements of the entourage effect have been proven but overgeneralized. “There is irrefutable evidence, for example, that CBD … modulates the effects of THC at the main receptor site. Therefore the entourage effect is real,” he said. 

“The entourage effect also explains why pure THC is not particularly effective, and whole-plant cannabis is better,” he said. However, he argues that the effects of the entourage effect have been extrapolated beyond the current evidence. “Ideas that other chemicals are important for CBD to work are unsupported at present.” 

Tishler also articulates that the role of minor cannabinoids like CBG or CBN is not yet fully understood in relation to THC or other cannabinoids. “In other words, many molecules may play a role supporting the action of THC, but this does not mean that they have a role supporting other cannabinoids,” he said.

As scientists take these nuances into account, new forms of understanding the entourage effect have been proposed. The entourage effect might more helpfully be understood as two distinct phenomena

  • the intra-entourage effect, referring to interactions between cannabinoids and terpenes
  • the inter-entourage effect, which denotes cannabinoid-to-cannabinoid interactions and terpene-to-terpene interactions

While there’s evidence to support an inter-entourage effect, there’s less research to support an intra-entourage effect.RelatedWhat is the endocannabinoid system and what is its role?

What about terpenes?

The general consensus is that terpenes are a critical player in the entourage effect. Research into cannabinoid-terpene synergy, however, has been relatively scant until recently. A bundle of findings released within the past year suggests that terpenes may not contribute to the entourage effect in the way we’ve been led to believe. 

According to a study published in March 2020, terpenes present in cannabis may not facilitate the entourage effect at all. The researchers found no evidence that five of the most common terpenes—myrcene, α- and β-pinene, β-caryophyllene, and limonene—facilitated an entourage effect by binding to the body’s cannabinoid receptors.

According to other research released this year, nor is there evidence that terpenes facilitate an intra-entourage effect—when cannabinoids and terpenes work together—by interacting with different cannabinoid pathways in the body. 

As is often the case with cannabis research, however, these results aren’t conclusive. In an April 2020 study on mice, researchers showed that three common cannabis terpenes—humulene, pinene, and geraniol—activated the CB1 receptor. The CB1 receptor is responsible for inducing physiological responses, such as reduced pain perception. These terpenes kicked off CB1-specific physiological responses among the mice, suggesting that terpenes can offer therapeutic benefits.

According to Tishler, there’s insufficient evidence that terpenes contribute to the synergy of whole-plant cannabis. That’s not to dismiss these aromatic compounds as ineffective, though. “There are two exceptions,” said Tishler. “Myrcene, which causes drowsiness but does so independently, not as part of the entourage effect; and β-caryophyllene which may be important in pain control.”RelatedWhat are cannabis terpenes and what do they do?

So is the entourage effect real?

Tishler states the entourage effect is a real phenomenon that is misunderstood. “At present, our understanding of the interactions of the entourage effect is pretty limited,” he said. There isn’t enough data to make specific products or recommendations based on other cannabinoids or terpenes. That doesn’t mean there isn’t whole-plant alchemy occurring, but we haven’t yet consolidated our understanding of the mechanisms at work. 

“On a clinical level, products that are pure THC and CBD seem less effective than whole cannabis, suggesting that there is/are, indeed, other chemicals involved—it just remains unclear which, and how they work,” said Tishler.

Despite the conflicting findings emerging in some of the literature, Ethan Russo remains a firm proponent of the entourage effect. “Despite the occasional failures to demonstrate entourage benefits that could be attributed to preparations that are not therapeutically optimized, the concept of the entourage effect is well-established contemporaneously,” he asserted. 

Russo does point to inconsistent standards in the quality of cannabis as potentially being responsible for mixed findings. 

“It remains extremely challenging for consumers or their caregivers to access the most effective and highest quality cannabis-based medicines,” explained Russo. “This can only be achieved by mandating that full analytical and safety information, including complete cannabinoid and terpenoid profiles via certificates of analysis on current batches, be available at point of sale. This will need to be coupled with better education on the pharmacological contributions of the various cannabinoid and terpenoid components.”

This new compound in CBD products can help with sleep, anxiety, and focus

This new compound in CBD products can help with sleep, anxiety, and focus

Elizabeth Enochs – August 27, 2020

CBD producers are starting to add L-theanine, a compound commonly found in green and black teas, to their products. Learn about its wellness benefits and how it works well with CBD.

Approximately 40 million American adults suffer from anxiety. CBD can help tremendously, as well as with sleep issues and burnout, but did you know that some CBD products also contain an amino acid called L-theanine, which is primarily found in green and black teas? 

We talked to some experts to shed light on how L-theanine can reduce anxiety, improve sleep, and boost mental clarity.

How CBD and L-theanine can reduce anxiety

The pharmacological effects of L-theanine on mood may be related to the endocannabinoid system via the GABA system, which works to regulate the body’s responses to stress and stressful situations, according to a statement from Dr. Junella Chin, head of the medical advisory board at cannabisMD, God’s Greenery, and Miraculo, and Michael Klein, CEO of Miraculo, cannabisMD, and God’s Greenery. 

GABA is a neurotransmitter that sends messages to and from the brain and the nervous system, with the ultimate goal of managing fear and anxiety. GABA receptors live on nerve cells, receiving messages from GABA neurotransmitters which help control nerve impulses.

Both CBD and L-theanine reduce anxiety and promote relaxation. L-theanine increases relaxed brain waves (alpha EEG waves) and increases GABA levels as well. GABA also directs the body to power down and to tell our bodies we are safe. It helps reduce anxiety, calms the nervous system, fosters sleep, and relaxes the muscles. Cannabis creates a surplus of GABA in the brain, creating a quieting and calming effect, said Chin and Klein.

Indeed, research shows that CBD and high-CBD cannabis strains can help ease anxiety for most people, so taking CBD and L-theanine together is essentially a double shot of calm. RelatedHow to use cannabis for anxiety

How CBD and L-theanine can improve sleep 

A wealth of research suggests CBD may help people fall asleep and stay asleep longer, primarily by reducing anxiety symptoms that typically keep people awake. While L-theanine doesn’t actually induce drowsiness, Dr. Chin said since anxiety is a common factor in sleeplessness, L-theanine and CBD can be helpful in treating insomnia because both compounds reduce anxiety and promote relaxation.

2008 study monitored electrical activity in the brains of healthy, young participants who received 50mg of L-theanine while resting with their eyes closed. Later, the test was performed again while participants were engaged in a passive activity. 

In both cases, it was found that L-theanine increased alpha brain waves, which promote “Deep relaxation and clear the mind of unwanted thoughts or distractions. This helps decrease sleep latency, the amount of time it takes you to go from being fully awake to sleeping,” said Chin.

The increased GABA levels from L-theanine can also cut down on the time it takes to fall asleep.RelatedThe best cannabis strains for sleep and insomnia

How CBD and L-theanine can boost mental clarity and focus

While most studies on L-theanine and increased mental clarity and focus center around the powers of caffeine and L-theanine, L-theanine by itself reportedly blocks glutamate receptors, which are responsible for feelings of restlessness, stress, and anxiety. 

With or without caffeine, this 2016 study shows that L-theanine reduces stress and anxiety without causing drowsiness, making it easier to focus on difficult tasks. 

It’s also true that some CBD products and CBD-dominant strains can help boost focus as well, making CBD and L-theanine a great combo for studying and work.  

L-theanine’s impact on sleep quality plays a role too, according to Chin. Quality REM (rapid eye movement) and NREM (non-rapid eye movement) sleep are crucial for mental clarity and focus. Nightly REM-rich sleep benefits cognitive functions like decision-making, and REM-sleep dreaming fuels creativity, said Chin. RelatedThe best cannabis strains for sparking creativity

By improving sleep, both L-theanine and CBD may help improve mental clarity and focus during waking hours. “REM-rich sleep allows us to make more intelligent decisions and actions. Emotional IQ depends on getting sufficient REM sleep night after night,” said Chin. 

NREM sleep helps transfer and make safe newly learned information into long-term storage sites of the brain, said Chin, referencing one study in which a GABA/L-theanine mixture was found to significantly increase NREM sleep in mice. 

“During the deep stages of NREM sleep, the body repairs and regrows tissues, builds bone and muscle, and strengthens the immune system. As a result of all this, CBD and L-theanine may help restore clarity and sharpen memory and improve focus during the day,” she said.RelatedThe best cannabis strains for focus and ADD/ADHD

A note on ideal dosages and potential risks 

When it comes to CBD, full-spectrum CBD is widely considered more therapeutic, and it’s safest to buy CBD products from companies who participate in third-party lab testing. Though it’s important to note that supplements aren’t regulated by the U.S. Food & Drug Administration (FDA) in the same way other foods and drugs are, L-theanine has received a GRAS—generally recognized as safe—notice from the FDA.

Many L-theanine-infused CBD products currently available contain anywhere from 50-100mg of L-theanine, but Amanda A. Kostro Miller, RD, LDN, who serves on the advisory board for Fitter Living, recommends even higher doses.

“Benefits of L-theanine were seen with supplementation of 200mg a day for four weeks,” she said, referring to a 2019 double blind trial. She also points out a systematic review from 2019 which states that effective supplementation of L-theanine is 200-400mg a day, but longer and larger studies are needed. “It’s important to note that some studies on L-theanine may also have used green tea or products of green tea [i.e., with caffeine], which could confound the results.”

Dr. Chin said L-theanine is best taken as a standardized extract in capsules, and she suggests taking 400-600mg a half-hour before bedtime.

It’s always a good idea to talk to your primary care physician before introducing any new supplement into your daily routine, but not unlike CBD, your safest bet with L-theanine is probably to start low and go slow. Also, keep in mind that both L-theanine can lower blood pressure.