Cannabis Terpenes Provide Pain Relief and Contribute to ‘Entourage Effect’

Summary: Cannabis terpenes, the part of the plant which provides aroma and flavor, may provide therapeutic benefits in controlling pain, a new study reports.

Source: University of Arizona

When it comes to the medicinal and therapeutic properties of Cannabis sativa, an unsolved mystery is whether there exists an ‘entourage effect’, whereby the pain-relieving effects of the plant as a whole are greater than any of its individual parts.

New research from the University of Arizona Health Sciences has found evidence that favors the entourage effect theory and positions cannabis terpenes, the part of the plant that provides flavor and aroma, as a promising new target for pain therapies that would require lower doses and produce fewer side effects.

“A lot of people are taking cannabis and cannabinoids for pain,” said lead researcher John Streicher, Ph.D., a member of the UArizona Health Sciences Comprehensive Pain and Addiction Center and associate professor of pharmacology at the College of Medicine—Tucson.

“We’re interested in the concept of the entourage effect, with the idea being that maybe we can boost the modest pain-relieving efficacy of THC and not boost the psychoactive side effects, so you could have a better therapeutic.”

Terpenes are aromatic compounds found in many plants and are the basic component in essential oils. The terpene linalool, for example, gives lavender its distinctive floral scent. In addition to terpenes, Cannabis sativa contains naturally occurring compounds known as cannabinoids, the most well-known of which are cannabidiol, or CBD, and tetrahydrocannabinol, or THC, the psychoactive component of cannabis.

Researchers found that cannabis terpenes, when used by themselves, mimic the effects of cannabinoids, including a reduction in pain sensation. When combined with cannabinoids, the pain-relieving effects were amplified without an increase in negative side effects.

The paper, “Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity,” was published in Scientific Reports.

“It was unexpected, in a way,” said Dr. Streicher. “It was our initial hypothesis, but we didn’t necessarily expect terpenes, these simple compounds that are found in multiple plants, to produce cannabinoid-like effects.”

Dr. Streicher and the research team, including former graduate student and first author Justin LaVigne, Ph.D., former undergraduate researcher Ryan Hecksel and former postdoctoral fellow Attila Kerestztes, Ph.D., focused on four cannabis terpenes: alpha-humulene, geraniol, linalool and beta-pinene. They evaluated each terpene alone and in combination with WIN55,212-2, a synthetic cannabinoid agonist that stimulates the body’s natural cannabinoid receptors.

When a cannabinoid such as THC enters the body, it binds to one of two cannabinoid receptors—CB1R, which is the most abundant, or CB2R. The receptor then activates neurons that affect physiological processes and behavior. In laboratory experiments, researchers found that all four terpenes activated the CB1R, just like THC.

This shows a cannabis flower
Terpenes are aromatic compounds found in many plants and are the basic component in essential oils. Image is in the public domain

Behavioral studies in mouse models revealed that when administered individually, all four terpenes lowered pain sensitivity, and at least three of the four classic cannabinoid side effects: reduced pain sensation, lowered body temperature, reduced movement and catalepsy, a freezing behavior related to the psychoactive effects of cannabinoids.

When terpenes were combined with WIN55,212-2, researchers saw a greater reduction in pain sensation compared with either the terpene or WIN55,212-2 alone, demonstrating a terpene/cannabinoid interaction in controlling pain.

Dr. Streicher’s ongoing research is focusing on the use of terpenes in combination with opioids and for specific types of cancer-related pain. His long-term goal is to develop a dose-reduction strategy that uses terpenes—generally recognized as safe by the U.S. Food and Drug Administration—in combination with cannabinoids or opioids to achieve the same levels of pain relief with lower doses of drugs and fewer side effects.

About this pain research news

Source: University of Arizona
Contact: Press Office – University of Arizona
Image: The image is in the public domain

Original Research: Open access.
Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity” by Justin E. LaVigne et al,. Scientific Reports


Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity

Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an “entourage effect” whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence.

We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches.

We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action.

These behavioral effects were selectively additive with WIN55,212, suggesting terpenes can boost cannabinoid activity. In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets.

Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.

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  1. We must more and more investigate the topic of helping the sick with cannabis and cbd, this is very important, people are suffering, which should not be allowed in the modern world! The main thing is to understand that you do not need to rely exclusively on cbd, since this is not a medicine, it is a good addition to the list of drugs you are already taking, since cbd does not have poor compatibility with other drugs and has no side effects. As a result, I want to say that this is something that costs more and more
    publicize this topic and help those in need!

  2. I’m very interested in this study, I have had 4 lower lumbar operations and still suffering with chronic pain, so yes I’m very interested in this as long as it will be legal…

    Thank you in advance
    Deborah Bailey

  3. It’s funny as I’ve been saying how this needs to be studied for the past four years. I, myself, got over the waiting game around two months ago and decided to do a little, equipment free experiment by testing two different Myrcene dominant cannabis strains, one of which is considered a sativa strain, whereas the other is an indica strain that supposedly puts you right to sleep. The terpene profiles are very similar, but Myrcene is dominant in both.

    Without the proper equipment, I’m just going to compare the tangible effects of both strains to see how different the effects would be, as if they’re very different, this would confirm that it’s a mix of all of the terpenes that provide specific effects. But if they’re very similar, the primary reasoning would be due to how each individual feels each terpene’s effects.

    Very simple, basic experiment (now that growing is legal where I am). Hopefully this terpene study can go further, as I really do want to research this! If only I could make it into a career, lol.

  4. Late 80’s friend w cancer given morphine. Pain did not subside till a couple puffs of cannabis in addition to morphine.Just saying

  5. It never ends well when people try to fix things that already work just fine. Just let nature do its thing. If everyone trys to approve something that has worked for hundreds to thousands of years then thats when negative things start to happen. I can just see years from now after the government entity’s like the FDA or others get there hands in the cannabis industry it will start causing cancer instead of helping people with cancer. Can’t we just leave well enough alone.

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