Study Summary: Progress Beyond CBD & THC

A 2021 study entitled "Cannabis Sativa: Interdisciplinary Strategies & Avenues for Medical & Commercial Progression Outside of CBD & THC" that was published in the journal Biomedicines investigated a number of minor cannabinoids that may deliver positive efficacy that rivals their major counterparts cannabidiol (CBD) and tetrahydrocannabinol (THC).

"Cannabis sativa (cannabis) is arguably one of the world's most versatile crops. While the genetic origin and evolution of cannabis is a long-standing and heavily debated topic, in broad terms, today, cannabis can be separated into two distinct categories, specifically 'hemp' and 'marijuana'," reported the study.

The Study

The researchers noted that two new cannabinoids were recently discovered that are "nearly identical in structure to THC and CBD." "Notably, Δ9-THCP was demonstrated to possess higher cannabimimetic [its ability to mimic the endocannabinoids 2-AG and anandamide] activity than THC and its recent discovery is therefore postulated as a potential candidate cannabinoid responsible for variation in pharmacological properties," noted the study's authors, who said the discovery of CBDP and THCP increases "the likelihood of secondary metabolites present in cannabis resin that remain to be discovered."

The study explained how "a range of phenotypic and chemotypic traits" from cannabis may be of use to the textile, medicinal, food, and energy industries and that cannabis "is extremely versatile and hardy, hence the application of the colloquial term for this species, 'weed.'"

"Cannabis 'is extremely versatile and hardy, hence the application of the colloquial term for this species, weed.'"

The researchers noted that, while CBD and THC have gained much attention and that a large amount of research has been devoted to these major cannabinoids, "significantly less attention in medical research has been paid to the potential for the minor phytocannabinoids to treat illnesses" and that there is a strong need for "methods to produce these cannabinoids cost-effectively [in] commercial volumes."

Results

The study noted that "THC is associated with multiple side effects" and that "pharmaceutical-standard THC and CBD are expensive to produce." It described how previous research revealed that the CB1 cellular receptors of the human endocannabinoid system (ECS) "were primarily localized to areas responsible for (1) higher cognitive function, (2) movement, and (3) control of sensory and motor functions of the autonomic nervous system."

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The study described how CB1 receptors and the ECS interact with other "systems in the brain...to modulate stress response and associative learning processes." It described how CB1 receptors are more present outside of the brain and central nervous system than previously believed. "Two CB1 receptor isoforms [variants] have...been identified, both of which display distinct expression patterns in pancreatic β-cells and [the] liver," reported the scientists.

The research detailed several ECS cellular receptors beyond CB1 and CB2, including GPR18, GPR55, and a small family of TRPV (transient receptor potential vanilloid) receptors. The TRPV family of four receptors (TRPV1 through TRPV4) are activated by a variety of cannabinoids. In addition, the study noted that CBD and THC activate additional receptor types, including glycine receptors.

The study noted that research into the role of cannabinoids in human disease "is still in its infancy," but that the field "abounds in promising preliminary studies."

The study noted that research into the role of cannabinoids in human disease "is still in its infancy," but that the field "abounds in promising preliminary studies." For example, the study said "cannabinoids, both of the endo- and phytocannabinoid categories, have been demonstrated to provide protection against neurodegeneration," implying a potential role in diseases of aging that involve a decline in cognitive capacity and neurodegeneration, including Alzheimer's disease and Parkinson's disease.

Wrote the scientists: "Eighty-two individual cannabinoids from 10 cannabinoid types...are among the constituents that comprise the chemical cornucopia of glandular trichomes":

(1) CBG

(2) CBC

(3) CBD

(4) Δ9-THC

(5) Δ8-THC

(6) cannabicyclol (CBL)

(7) cannabielsoin (CBE)

(8) cannabinol (CBN)

(9) cannabinodol (CBND)

(10) cannabitriol (CBT)

The study noted that many other types of phytomolecules commingle with these cannabinoids, including terpenes, terpenoids (terpene-like molecules), hydrocarbons, sugars, and fatty acids.

Some THC isomers feature nearly identical molecular structure

Interestingly, the study observed that the application of nitrogen, phosphorus, and potassium to cannabis plants during growth "reduced THC, CBN, and CBD content, but increased CBG content," while the application of humic acid lowered the "THC, CBD, CBG, THCV, CBC, CBL, and CBT content."

Other minor cannabinoids covered by the study included:

• CBGA: The acidic precursor to CBG (cannabigerol) is "the key [cannabinoid] required for the synthesis of the three primary [major] cannabinoids—cannabichromenic acid (CBCA), which produces CBC (cannabichromene); THCA (tetrahydrocannabinolic acid), which produces THC; and CBDA (cannabidiolic acid), which results in CBD."

• Delta-8 THC: The study reported that "Δ8-THC has been shown to possess higher antiemetic [anti-nausea] effects than THC" and has been "successfully trialed for repressing emesis in children," a statement supporting the acceptable safety profile of this newly popular cannabinoid. The study also noted that, similar to thousands of anecdotal testimonies from consumers and similar observations from medical professionals, "Δ8-THC appears required to be administered at higher doses than THC to display a similar degree of psychoactive properties."

• THCA: The study reported that THCA, the acidic precursor to delta-9 THC, "has been shown in rodent culture...to reduce the abundance of inflammatory and oxidant markers."

• THCB: This is a four-carbon side chain variant of THC that has demonstrated "CB1 and CB2 binding affinities similar to those of THC" in rodent studies. Preliminary evidence suggests that THCB may potentially act as an analgesic for pain management and that, like many cannabinoids and terpenes, it possesses anti-inflammatory properties.

• THCP: Sporting a molecular structure that is nearly identical to its chemical cousin delta-9 THC, THCP "was demonstrated to possess higher cannabimimetic activity than THC and its recent discovery is therefore postulated as a potential candidate cannabinoid responsible for variation in pharmacological properties," reported the study.

• THCV: This varin isomer of delta-9 THC was shown to produce "anxiolytic [anxiety lowering], hypothermic, and antinociceptive [antipain]...effects" in mice. THCV has also demonstrated the ability to "reduce inflammation and attenuate hyperalgesia" (abnormally increased sensitivity to pain) in rodent studies. "Similarly, THCV delayed onset of abnormal involuntary movements associated with Parkinson's disease" and also reduced the severity of seizures in a rodent model.

Conclusions

The study noted that new research "has begun to reveal the pharmacology and molecular targets of the minor cannabinoids." The scientists observed that "there is a range of medical ailments that could be addressed through endocannabinoid augmentation using secondary [cannabinoids from] cannabis."

The important role of CBGA

The study's authors determined that there is a need for "significant characterization of minor cannabinoid pharmacology," particularly preclinical and clinical trials involving humans. They also noted that affordable and practical industrial-scale production of CBD, THC, and the minor cannabinoids is considered to be "still in [its] infancy" and that the situation "remains a clear barrier to large-scale commercialization of pharmaceutical cannabinoids."

"In conclusion, there are multiple enticing and potentially profitable opportunities for commercial and academic growth in the cannabis market outside of THC and CBD"

The study summarized that "it is likely that a molecular genetic modification approach will be applied to cannabis to generate new opportunities for the improved yield of specific minor and major cannabinoids."

"In conclusion, there are multiple enticing and potentially profitable opportunities for commercial and academic growth in the cannabis market outside of THC and CBD," reported the study.

View the original study.

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