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A 2021 study entitled "Biological Basis of Cannabinoid Medicines" that was published in the journal Science explored the biochemical underpinnings that sometimes result in positive health outcomes for cannabis and hemp consumers, particularly those involving cannabidiol (CBD) and tetrahydrocannabinol (THC).
"Since its first mention ∼4000 BC, Cannabis sativa has evolved through selective cultivation from being a source of durable fiber (hemp) to a plant enriched in bioactive ingredients [such as CBD and THC]," reported the study. It noted that more than 100 "potentially bioactive phytocannabinoids" have been cataloged, "yet their precise structure-function relationships are mostly unclear."
The Study
The scientists reported that the most studied cannabinoids are CBD and THC and that "high-grade cannabis subspecies can produce over 20 percent yield of either compound." The study noted that these cannabinoids "have potential application in many illnesses."
The study noted that the choice of which cannabinoid(s) to study on the part of researchers "remains a formidable challenge" due to "many phytocannabinoids producing similar pharmacological effects through different mechanisms."
The study noted that the choice of which cannabinoid(s) to study on the part of researchers "remains a formidable challenge" due to "many phytocannabinoids producing similar pharmacological effects through different mechanisms."
THC & CB1 Receptors
The investigation reported that "THC action in humans is dependent on the CB1 cannabinoid receptor, which is the most abundant G protein–coupled receptor in the brain" and one of the two major endocannabinoid system receptors types. This is in addition to the CB2 receptor, which is found in greatest density in the peripheral nervous system, including the tissues, glands, and organs of the immune system.
The study's authors noted that most research studies on the topic "focus on THC because of its psychostimulant effects," whereas CBD is an abundant cannabinoid that constitutes "up to 50% of total phytocannabinoid content" but is a "nonpsychotropic component."
The study noted the "anti-inflammatory and tissue-protective effects" of CBD and explained that this efficacy may result from the fact that this cannabinoid interacts with multiple types of bodily receptors beyond CB2, including TRPV1 and GPR55.
"Additionally, CBD enhances antioxidant cellular defenses."
"Additionally, CBD enhances antioxidant cellular defenses by scavenging hydroxyl radicals and can counteract THC action intracellularly" via the CB1 receptor, wrote the scientists.
Lending more insight to the underlying biochemical mechanisms involved in the interaction of the two major cannabinoids, CBD and THC, the study reported that "these potential cellular and molecular sites of action are not limited to the brain, but apply to pancreas, muscle, liver, and gut—suggesting that cannabinoids may have applications in diverse settings."
More Than CBD & THC
"It is important to recognize that cannabis is more than just THC and CBD," wrote the study's authors, noting that cannabinoids that typically appear in the plant in considerably lower volumes—such as cannabigerol (CBG)—"could individually be biologically powerful and even supersede or modify THC and/or CBD action."
CBD molecular structure
The study recommended the "continued structure-function study of phytocannabinoids" and noted that "combinations of phytocannabinoids might deliver relief to disorders with complex etiology [cause or origin]."
The research noted that, within the human endocannabinoid system, molecules other than CBD and THC are produced internally that are called endocannabinoids. The two major endocannabinoids are 2-AG and anandamide. These cannabinoids "form the molecular backbone of the endocannabinoid system," wrote the study.
The insightful scientific investigation stated that 2-AG and anandamide are "functionally redundant" and that both endocannabinoids can adopt to particular types of cells in the brain and peripheral tissues.
The insightful scientific investigation stated that 2-AG and anandamide are "functionally redundant" and that both endocannabinoids can adopt to particular types of cells in the brain and peripheral tissues.
"An expanding catalog of endocannabinoid-like molecules are being recognized for their modulation" of a range of ECS receptors, reported the study. It also noted that the endocannabinoids 2-AG and anandamide feature "activity-dependent production" (are made on-demand) and that they degrade relatively quickly, resulting in "short-lived action."
Epilepsy & Alzheimer's
"A prominent clinical niche being explored for cannabinoid medicines is treatment-resistant epilepsy," reported the study, noting benefits shown in prior studies involving both rodents and also trials with humans.
"Rescuing neurons from oxidative damage and...dysfunction [with]...CBD could partly underpin the substantial reduction in seizure frequency seen in clinical trials," wrote the scientists. They noted that phytocannabinoids such as CBD and THC "may also have applications in diseases associated with aging."
"This is largely because aging tissues contain increased amounts of immune cells, which remove cellular debris," explained the study's authors. They said that the activation of CB2 receptors in the ECS by THC "may offer relief in neurological disorders [such as] Alzheimer's, Parkinson's, and Huntington's diseases" and that this may involve the molecules limiting
inflammation. They also observed that THC binding with CB1 receptors in the ECS "might improve cognition."
Activation of CB2 receptors in the ECS by THC "may offer relief in neurological disorders [such as] Alzheimer's, Parkinson's, and Huntington's diseases."
The current study noted how a previous study of rodents in an Alzheimer's disease model "rescued memory deficits." It reported that cannabinoid behavior typically involves both "correcting synaptic neurotransmission and protecting neurons from degeneration" and that cannabinoids exert these effects "at more than one cellular target."
Biphasic Response Curves
The scientists also noted that most cannabinoids display something called a biphasic response curve that "manifests as beneficial effects at low concentrations and [potentially] harmful effects at high concentrations."
The study identified an "obstacle to the therapeutic use of THC" in the fact that this cannabinoid sometimes "exacerbates inflammation."
The study also noted that cannabinoid therapy "is also potentially applicable [to] the management of neuropathic pain" that may be "induced by a lesion or disease of the...nervous system" and that pain reductions have been noted in rodent studies.
