Researched wellness areas for phytocannabinoids like CBD

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One of the speediest-growing subcategories of consumer natural health products is, without a doubt, the CBD sector. In a report, Grand View Research estimated the 2020 global consumer health CBD market to be worth $9.42 billion, with an anticipated compound annual growth rate (CAGR) of 24.6% from 2020 to 2027.

Research linking CBD to health and wellness is also a spirited activity worldwide, the results of which will continue to inform product development opportunities. According to Grand View Research’s report, CBD products are proliferating as oils; tinctures; concentrates; capsules; topical solutions such as lotions, salves and lip balms; as well as edibles encompassing coffees, gum/candies, chocolate and bakery products. The firm noted, “Various industries such as pharmaceuticals, personal care and cosmetics, nutraceuticals, and food and beverages are developing CBD-derived products for health and wellness purposes.”

Researchers have identified more than 110 cannabinoids and 120 terpenes, but authors of one paper asserted that the enzymatic reaction between a resorcinol and an isoprenoid group in the plant can result in nearly 150 phytocannabinoids.1

Carl Germano, CDN, a board-certified clinical nutritionist and vice president for Verdant Oasis, said the emerging science illuminating the importance of the endocannabinoid system (ECS) and the role of hemp phytocannabinoids (including CBD) in supporting the ECS “will certainly dominate nutrition and medicine for decades to come.” However, he stated, focusing only on cannabidiol as one of more than 100 phytocannabinoids “negates the synergism of all family members that contribute to meaningful clinical benefit.”

Work, most of it in vitro and animal, continues to investigate how CBD and its phytocannabinoid siblings affect specific areas of human (and pet) health.

Bone health

CBD is generally thought to be associated with aiding relaxation, calming tension, hastening sleep onset, and easing aches and physical discomfort.

According to Germano, evidence is accumulating on the positive impact of phytocannabinoids, including CBD, on the musculoskeletal system. In the ECS, cannabinoid receptors CB1 and CB2 are somewhat commonly present in bone and have been found to help to regulate bone maintenance.2 One group of researchers explained, “The CB1 receptor is present mainly in skeletal sympathetic nerve terminals, thus regulating the adrenergic tonic restrain of bone formation. CB2 is expressed in osteoblasts and osteoclasts, stimulates bone formation, and inhibits bone resorption.”

CB1 activity serves a protective role in regulating bone mass and may have positive impact on osteoporosis treatment.3 CB2 activity plays a vital role in bone mass maintenance by stimulating the cells that build up bone (osteoblasts) while inhibiting the cells that break down bone (osteoclasts). In animal studies, CBD has been shown to enhance healing of bone tissue and protect against bone loss.4 Preclinical trials demonstrated certain phytocannabinoids increase bone maintenance and healing.5 For example, one study showed a significant increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD may lead to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes.

Therefore, Germano emphasized—in addition to calcium, magnesium, vitamin D and boron—phytocannabinoids should be “at the core of any nutritional protocol addressing healthy bones and bone mass loss.”

Sports/fitness nutrition

In 2018, the World Anti-Doping Agency (WADA) removed CBD from its list of prohibited substances by use in athletes both in and out of competition; the U.S. Anti-Doping Agency (USADA) followed. In 2020, WADA updated its list with the following language: “All natural and synthetic cannabinoids are prohibited, e.g.: In cannabis (hashish, marijuana) and cannabis products. Natural and synthetic tetrahydrocannabinols (THCs). Synthetic cannabinoids that mimic the effects of THC. Except: Cannabidiol.”

A 2020 review concluded this “leaves the door open for CBD use by athletes.”6 The abstract pointed to preclinical studies indicating CBD may be useful to athletes because of “its anti-inflammatory, analgesic, anxiolytic, neuroprotective properties and its influence on the sleep-wake cycle. Unfortunately, almost no clinical data are available on CBD in the context of exercise, which makes its use in this context still premature.”

While protein and caffeine have dominated the exercise category, the role of the ECS in sports performance and recovery is beginning to become “one of the most important stories in sports nutrition,” Germano asserted.

One recent review explored various physiological and psychological effects of CBD that may be relevant to competitive sports and exercise, despite a lack of direct human studies.7 The authors analyzed preclinical animal studies indicating powerful anti-inflammatory, neuroprotective and analgesic CBD effects. The authors concluded the cumulative research merited moving forward with human studies. They wrote, “CBD may exert a number of physiological, biochemical and psychological effects with the potential to benefit athletes. However, well-controlled studies in athlete populations are required before definitive conclusions can be reached regarding the utility of CBD in supporting athletic performance.”

Respiratory/immune health

CBD’s role in upper respiratory health is currently being investigated, and several in vitro studies have uncovered strong evidence to develop human clinical trials. A new study sought to quantify antiviral activity of 32 cannabinoids against Covid. The authors found two of the molecules—delta-9 THC and CBD—were more potent antivirals against the coronavirus than the reference drugs used in the study.8

In a murine model study that mimicked symptoms of acute respiratory distress syndrome, CBD treatment was shown to reverse symptoms through up-regulation of apelin, a peptide that plays a strong role in the central and peripheral regulation of immunity.9 The authors noted that CBD administration significantly increased the apelin expression, “suggesting a potential crosstalk between the apelinergic system and CBD.”

In another study, the authors suggested that cannabidiol launches numerous immunomodulatory and anti-inflammatory effects and also can mitigate uncontrolled cytokine production responsible for damage to lung tissue.10 CBD, as a peroxisome proliferation-activated receptor (PPAR) gamma agonist, regulates “fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function.”

Inflammation levels are implicated in compromised immune function; one in vitro study suggested CBD acted as an anti-inflammatory agent in pro-inflammatory conditions.11 In the experiment, epithelial cells, macrophages and lung fibroblast cells were treated with CBD, and it exerted differential effects on pro-inflammatory molecules interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1, and reactive oxygen species (ROS) levels.

Anxiety

Anxiety and overall nervousness have catapulted to the top of many people’s wellness challenges list, and the ECS—as a recognized stress/mood and anxiety modulator—is a definitive target for CBD product development. Germano explained, “Both cannabinoid and other receptors including TRPV1, 5-HT1a, and GABA [gamma-aminobutyric acid] found in various regions of the brain are all targets for the ECS’s anti-anxiety effects.”

A review analyzing case reports, case series and randomized controlled trials (RCTs) utilizing CBD capsules or sublingual sprays either alone or in conjunction with other therapies in…

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