The UA research effort focused on the medicinal and therapeutic properties of the Cannabis Sativa plant species and the so-called ‘entourage effect’ that may occur when plant compounds interact synergistically with one another.

According to the study’s findings, the soothing effect(s) of cannabis terpenes are amplified when combined with cannabinoids. After studying mice to find out if terpenes can also treat pain, members of the university’s pharmacology department learned that terpenes could ease the pain with a cannabinoid-like effect once injected into the mice. “Many people take cannabis and cannabinoids for pain,” said a senior researcher at the University of Arizona Health Sciences Comprehensive Pain and Addiction Center, Dr. John Streicher.“We are interested in the concept of side effects, with the idea that it may be possible to increase the moderate pain-relieving effect of tetrahydrocannabinol (THC), rather than increasing the side effects of psychotropic drugs.

You can have a good cure,” added Dr. Streicher, who also assumes the role of associate professor of pharmacology at Tucson School of Medicine.The results of this UA study suggest that, in the future, patients who suffer from pain could experience improved symptomatic relief from lower doses of cannabinoids and terpenes, thanks to the entourage effect.“In a way, it was unexpected,” said Dr. Strycher. “It was our first hypothesis, but we didn’t necessarily expect terpenes, these simple compounds found in multiple plants, to produce cannabinoid-like effects.”

About the Entourage Effect

The entourage effect2 is a process by which cannabinoids (not to mention the many other compounds in cannabis, including the all-important terpenes, resins, and flavonoids) function synergistically with one another.

During the late 1990s, the term ‘entourage effect’ was first popularized by none other than the “father of cannabis research,” Raphael Mechoulam. Famed for discovering THC more than 50 years ago, the Israeli scientist coined the term alongside Professor Shimon Ben-Shabat and their team of researchers at the Hebrew University of Jerusalem.

Since scientists first confirmed that cannabinoids could amplify one another’s effects, the field of extraction has gone from strength to strength. Although the term ‘entourage effect’ is generally used in the cannabis industry, this extraordinary occurrence is also believed to happen in a vast array of botanical medicines.

Four Cannabis Terpenes Were Focused on for UA StudyTerpenes are aromatic compounds that can be found in a broad spectrum of plants. All types of essential oil contain terpenes as a primary ingredient. Not only is Cannabis Sativa enriched with terpenes, but it is also laden with cannabinoids.The research team responsible for carrying out this study – including Dr. Stricher, former undergraduate researcher Ryan Hexel, lead author and graduate student Dr. Justin Laving, and former postdoctoral fellow Dr. Atila Kereststes – focused on four specific cannabis terpenes.

They were as follows:

Geraniol -  This monoterpenoid and alcohol are colorless yet full of flavor. The terpene naturally occurs in geranium flowers, roses, lemongrass, citrus peels, carrots, and blueberries, to name a few plants. Geraniol is the main component of palmarosa oil, rose oil, and citronella oil. It has been recognized as an anti-inflammatory, antifungal agent, and antibacterial.

Linalool - Linalool, an immune system booster, is as therapeutically potent as it is fragrant. Renowned for acting on the serotonin receptor,4 linalool may help to relieve certain mental health conditions, including anxiety and depression. Aside from cannabis, linalool can also be found in birch bark and lavender.

A-humulene - Ever wondered how hoppy beer gets its unmistakable smell and flavor? The answer is A-humulene, which is favored for its subtle spicy, earthy, and woody notes. For centuries, this terpene has been relied on in holistic Eastern medicinal practices. Research indicates that it may work as a natural appetite suppressant, anti-inflammatory, and antibacterial.

β-pinene - Consuming cannabis that contains β-pinene is a sure-fire way to relieve inflammation, pain, and anxiety. What’s more, this terpene is also a natural Bronchodilator, which helps open airways. Studies show6 that β-pinene may help prevent short-term memory impairment associated with the psychotropic compound THC. Recognizable from its resinous and piney scent, β-pinene is contained.

In basil, rosemary, orange peels, parsley, and pine trees. To accurately ascertain the presence of the entourage effect, researchers assessed WIN55,212-2 – a synthetic cannabinoid receptor agonist with results comparable to THC – on the four principal behaviors noticed in mice. Additionally, the researchers assessed differences in the effects of all four terpenes once they had been applied simultaneously with WIN55,212. They discovered that terpenes successfully managed to ease pain sensitivity in mouse models.

At least three behavioral outcomes were observed: lower pain sensation, decreased body temperature, restricted movement, and catalepsy. When cannabinoids like THC enter the human body, they indirectly trigger cannabinoid receptors, the most common CB1R of CB2R.

Soon after, the receptors spark action among neurons that influence physiological processes, such as mood, behavior, pain-sensation, and memory. Based on the results of their laboratory experiments, researchers found that (similarly to THC) the four terpenes mentioned above reacted through the arousal of the CB1 cannabinoid receptor.

In a rodent model behavioral study, the individual application of all four terpenes successfully reduced pain sensitivity, loss of voluntary motion (catalepsy), and reduced body temperature. When terpenes were mixed with WIN55,212-2, researchers concluded that pain sensation was significantly reduced compared to the sole administration of terpenes or WIN55,212-2.

Conclusion

Although the study’s authors did express recognition of terpenoid activity and synergistic terpene-cannabinoid effects at the CB1 receptor, previously conducted studies have failed to find notable interaction at this receptor. On the other hand, if the entourage effect can be further tested and validated, new therapeutic options will soon begin to transpire for medical cannabis patients.

In the future, Dr. Stricher’s research efforts target the combined use of terpenes and opioids to treat various kinds of cancer-related pain. His vision is to establish sufficient evidence into the way(s) that terpenes can be merged with cannabinoids or opioids as a means of reducing dosage and accomplishing the same level of pain relief with fewer side effects.

The paper, titled “Cannabis Sativa Terpenes are Cannabidioletic and Selectively Enhance Cannabinoid Activity”7, was published in “Activities” in the journal Scientific Reports.