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Minor Cannabinoid Therapeutic Uses

Welcome to Cannabis Conclusions, a unique educational series from Higher Learning LV that is targeted at hemp and cannabis industry professionals. This series provides readers with the conclusion section from important modern peer-reviewed research studies.


A November 2021 study entitled "Minor Cannabinoids: Biosynthesis, Molecular Pharmacology, and Potential Therapeutic Uses" that was published in the journal Frontiers in Pharmacology focused on "the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds."


Study Conclusions

"Preclinical data and early clinical studies support the continued investigation of phytocannabinoids for the treatment of pain, inflammation, neurodegeneration, cancer, and other disorders. Natural products have historically been valuable sources of novel compounds developed into pharmaceuticals. Such was the case with the isolation of salicin from the bark of the Willow tree and the subsequent synthesis of aspirin.


"Δ9-THC (Dronabinol) is currently approved by the U.S. FDA for the treatment of nausea associated with cancer chemotherapy and as an appetite stimulant for patients with AIDS. Nabiximols (Sativex®) containing a mixture of Δ9-THC and CBD from the cannabis plant is approved in Canada and Europe for the treatment of MS spasticity.


"Use of Δ9-THC is associated with acute psychotropic effects including euphoria, sedation, anxiety, cognitive impairment, and in some patients, paranoia and hallucinations."

"It is also indicated for the treatment of neuropathic pain in MS and for pain relief in patients with advanced cancer. However, use of Δ9-THC is associated with acute psychotropic effects including euphoria, sedation, anxiety, cognitive impairment, and in some patients, paranoia and hallucinations.


"Minor cannabinoids and their chemical homologs offer the potential medicinal benefits of Δ9-THC without adverse effects. Recently, Δ9-tetrahydrocannabiphorol (Δ9-THCP) and cannabidihexol (CBDH), homologs of Δ9-THC and CBD, were synthesized and shown to produce anti-nociceptive effects in mice at doses comparable to Δ9-THC. Future studies will need to evaluate the risk versus benefit of these and other minor cannabinoids when compared to Δ9-THC and traditional analgesic drugs.


"In addition to the CB1/CB2 receptors and 'off target' binding sites described in this review, minor cannabinoids may bring about their pharmacological effects by interacting with other receptors and ion channels. Along with GPR55 and GPR18, de-orphanized receptors including GPR3, GPR6 and GPR12 are emerging as possible targets for minor cannabinoids.


"These receptors are highly expressed in neuronal tissues and are postulated to participate in neuroprotection, anti-nociception and brain development. Although the affinity of these receptors for minor cannabinoids has not yet been examined, CBD is known to function as an inverse agonist at all three receptors.


"Advances in the bioengineering of cannabinoid synthesis enzymes...should expand the production of both natural and novel minor cannabinoids."

"However, it is unclear whether CBD binds to an orthostatic site on the receptor or if it modifies receptor activity via an allosteric site. While TRP channel agonism/antagonism provides a major mechanism of action for many of the minor cannabinoids, voltage-gated ion channels, such Na+ and Ca2+ channels are also regulated by cannabinoids.

"When tested in parathyroid cells, the synthetic cannabinoid WIN 55,212-2 and the endocannabinoid 2-AG reduce the peak Na+ current and shift the voltage-dependence of Na+ channel inactivation to more negative membrane potentials. In addition, when applied at low micromolar concentrations, CBD inhibits the Na+ current in heterologous cells expressing various Na+ channel subunits (NaV1.1, NaV1.3 NaV1.6, etc.).


"Combining cannabinoids with terpenes, flavonoids, and polyphenols could create countless possibilities in the era of personalized healthcare."

"CBD also inhibits T-type Ca2+ channels (CaV3.x) in mouse sensory neurons. Whether CBD acts directly to regulate the conduction of the Na+ and Ca2+ channels, or acts indirectly to alter the properties of the cell lipid membrane will require further investigation.


"Advances in the bioengineering of cannabinoid synthesis enzymes in yeast and other microbial systems should expand the production of both natural and novel minor cannabinoids. The ability to combine these cannabinoids with terpenes, flavonoids, polyphenols and other cannabis-based chemicals could create countless possibilities in the era of personalized healthcare.

"It is predicted that new cannabinoid products might be formulated to meet the therapeutic needs of different demographic groups and could be available in numerous delivery systems, including topical creams, tablets, transdermal patches, vaporizers, and more. Women represent one demographic group where cannabinoids could offer a variety of health care benefits. Cannabinoid receptors are ubiquitously distributed in reproductive tissues and AEA and the FAAH enzyme are found in the ovaries, oviducts and endometrium.


"New cannabinoid products might be formulated to meet the therapeutic needs of different demographic groups and could be available as topical creams, tablets, transdermal patches, vaporizers, and more."

"Cannabinoid-based suppositories containing Δ9-THC and CBD are already available for relieving menstrual cramps, and as drug discovery progresses, natural and unnatural cannabinoids may prove effective for reproductive system issues, from endometriosis and fibroids to perimenopause symptoms.


"Of course, the effectiveness of these cannabis products must first be confirmed through large, randomized and controlled clinical trials. Much of our current knowledge of the medicinal benefits of minor cannabinoids has come from subjective and anecdotal patient reporting, rather than through rigorous clinical trials. In order to move forward, researchers, clinicians and regulatory officials will need to work together to ensure that phytocannabinoid products meet the necessary therapeutic and safety standards."


View the original study.



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