The Truly Essential Thing That is Missing from the Extraction of CBD Oil

After ten weeks of devotion to CBD oil, I must admit, I was getting a little cross-eyed and experiencing some other negative side effects from the withdrawal of writing about essential oils! Thankfully, my symptoms have subsided by refocusing on my positive obsession in a recent online publication.

This article was the follow up in my series on Natural Path which explained the differences between CBD oil, cannabis essential oil, and the whole “entourage” of the cannabis plant. In Part II, I reviewed the benefits of the variety of terpenes found within cannabis essential oil. I also reported on a clinical study of its positive impacts on subjects’ brains and nervous systems.

In the past, my accolades for terpenes were also expressed within another of my mega-article series on the variations among the different frankincense species. I am not alone in my fancying of these fabulous compounds. As an example, this article supplies nitty-gritty details on each of the ones found in cannabis essential oil. (Note that some of the references are in vitro and in vivo studies.)

As mentioned in the above article, these terpenes are not just found in the essential oil of cannabis. For instance, limonene is present in citrus oils and B-carophyllene is a constituent of both copaiba and black pepper essential oils. The latter has specifically been found to interact with the non-psychoactive cannabinoid receptor, CB2. This results in influencing the endocannabinoid system and creates many restorative effects. I discussed them in relation to copaiba here.

In a review on the endocannabinoid system, cannabinoids, and pain, the authors provide an explanation of the interactions of the phytocannabinoids and terpenes regarding synergy with pain and inflammation treatment. Below is a highlight on B-carophyllene:

Terpenes are quite potent and affect animal and even human behavior when inhaled in very low concentrations. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of Cannabis-based medicinal extracts. Of particular interest are the phytocannabinoid–terpene interactions that could produce synergy with respect to treatment of pain and inflammation. Phytocannabinoid–terpene synergy increases the likelihood that an extensive pipeline of new therapeutic products is possible from this age-old plant.

The synergistic contributions of cannabidiol to Cannabis pharmacology—and specifically analgesia—have been scientifically demonstrated. Preclinical and clinical data indicate that cannabinoids administered together are more effective at ameliorating neuropathic pain than the use of a single agent.104,106

The terpene B-caryophyllene is found in a number of commonly available plants, including black pepper, cinnamon, clove, and other spices. It selectively binds to the CB₂ receptor at nanomolar concentrations and acts as a full agonist. B-Caryophyllene and cannabidiol occur abundantly in Cannabis sativa. So this plant species produces at least two entirely different chemical substances able to target CB₂ receptors differentially. While studies on the pharmacokinetics of ?-caryophyllene are still on-going, it is already clear that this terpene is readily bioavailable. Unlike many polyphenolic natural products, it is not metabolized immediately but shows a Tmax >1 h after one single oral administration. Orally administered B-caryophyllene (<5 mg·kg^?1) produces strong anti-inflammatory and analgesic effects in wild-type mice but not in CB₂ receptor knock-out mice, which is a clear indication that it may be a functional CB₂ ligand.107

On-going studies show that B-caryophyllene is effective at reducing neuropathic pain in a CB₂ receptor-dependent manner.108 Like other CB₂ ligands B-caryophyllene inhibits the pathways triggered by activation of the toll-like receptor complex CD14/TLR4/MD2, which typically leads to the expression of pro-inflammatory cytokines (e.g. IL-1 beta, IL-6, IL-8, and TNF alpha) and promotes a Th1 immune response that plays a critical role in neuroinflammation, sensitization, and pain.109 Therefore, the FDA-approved food additive B-caryophyllene seems an attractive candidate for clinical trials targeting the CB₂ receptor. Indeed, in cases of intractable or difficult-to-control pain, combination therapy with small doses of opioid and non-psychoactive cannabinoid receptor agonists may be an alternative way to circumvent the undesirable side effects of opioids yet obtain far greater analgesic efficacy than achieved with cannabinoids alone.56,110

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