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The non-psychoactive component of Cannabis Sativa, cannabidiol (CBD), has centered the attention of a large body of research in the last years. Recent clinical trials have led to the FDA approval of CBD for the treatment of children with drug-resistant epilepsy. Even though it is not yet in clinical … As the industry matures and as increasingly savvy consumers begin to demand higher quality at a lower cost, the future of cannabinoid manufacture lies not in natural plants but in chemical synthesis CBD can be either natural or synthetic. Here's the difference between the two types and why it matters.

Synthetic and Natural Derivatives of Cannabidiol

The non-psychoactive component of Cannabis Sativa, cannabidiol (CBD), has centered the attention of a large body of research in the last years. Recent clinical trials have led to the FDA approval of CBD for the treatment of children with drug-resistant epilepsy. Even though it is not yet in clinical phases, its use in sleep-wake pathological alterations has been widely demonstrated.Despite the outstanding current knowledge on CBD therapeutic effects in numerous in vitro and in vivo disease models, diverse questions still arise from its molecular pharmacology. CBD has been shown to modulate a wide variety of targets including the cannabinoid receptors, orphan GPCRs such as GPR55 and GPR18, serotonin, adenosine, and opioid receptors as well as ligand-gated ion channels among others. Its pharmacology is rather puzzling and needs to be further explored in the disease context.Also, the metabolism and interactions of this phytocannabinoid with other commercialized drugs need to be further considered to elucidate its clinical potential for the treatment of specific pathologies.Besides CBD, natural and synthetic derivatives of this chemotype have also been reported exhibiting diverse functional profiles and providing a deeper understanding of the potential of this scaffold.In this chapter, we analyze the knowledge gained so far on CBD and its analogs specially focusing on its molecular targets and metabolic implications. Phytogenic and synthetic CBD derivatives may provide novel approaches to improve the therapeutic prospects offered by this promising chemotype.

Keywords: Cannabidiol; Cannabidiol analog; Cannabidiol derivative; Cannabinoid; Sleep; Synthetic cannabidiol.

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What’s the Deal with Synthetic CBD?

As scientists, you’ll likely be aware that your morning vitamin C tablet does not originate from a lemon grove on some sunny Sicilian hillside. But what about consumers? Do they know that their “natural” supplements come from a chemical plant and not an actual plant? And, if it’s efficacious, safe, and cheap, do they care? The industrialized reality is that many naturally-occurring chemical compounds, including ascorbic acid, can be produced far more efficiently (and at potentially lower cost) than their natural equivalents.

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And few (naturally-occurring) compounds have generated as much interest – or shown as much therapeutic promise – as the cannabinoid CBD. So it should come as no surprise that CBD is the next “supplement” set to be overtaken by a synthetic revolution.

Some surveys estimate that one in three people in the US have tried CBD and up to six million people in the UK are self-medicating with CBD products to help with diverse problems, including anxiety, insomnia. and chronic pain. And yet the quality and content of cannabis-based products are often unknown – and some products are even illegal or potentially dangerous. Why? Because plant-derived products are impure by their very nature, containing contaminants, such as pesticides, and other (unwanted) cannabinoids, such as THC, and even unnatural cannabinoid degradents, depending on the extraction process.

Growing Cannabis at scale is more an agricultural than a scientific endeavor; small environmental variations can lead to large differences in plant quality, purity, and cannabinoid yield – this is not news to the industry. Cannabis is also particularly effective at absorbing lead, cadmium, and nickel from the soil, which is great for environmental remediation, but certainly not when it comes to selling food and cosmetic products.

Synthesis is currently the only way to meet strict (albeit unenforced) European requirements on cosmetics ingredients (which do not permit origin material that is illegal in any member state) or to meet specific institutional requirements, such as those from the World Anti-Doping Agency (which prohibits all cannabinoids except CBD, in any amount).

Referred as bio-identical or nature identical, depending on the market, synthetic CBD is now the dominant base material against which naturally occurring CBD purity is tested.

Following these trends, and as quality and safety regulations for the CBD industry are further developed and implemented for the consumer market, synthetic CBD is becoming an increasingly appealing alternative. I’d like to reiterate an important point: high-quality synthetic CBD is chemically identical to naturally-occurring CBD. Referred as bio-identical or nature identical, depending on the market, synthetic CBD is now the dominant base material against which naturally occurring CBD purity is tested.

Why the need for reiteration? Unfortunately, synthetic cannabinoids have garnered a great deal of bad press thanks to synthetic analogues (think: “spice”!) that act upon the same receptor but do not occur in nature. Thankfully, (known) cannabinoid analogues are illegal, but their existence has given the synthetic CBD sector somewhat of a marketing headache.

But where does synthetic CBD come from? Well, in the case of biotechnology company PureForm Global, the starting base material is actually a citrus terpene, while high-flying Cellular Goods are touting future commercialization of CBD via a biosynthetic route (a form of fermentation).

Though pathways in CBD synthesis vary and other cannabinoids (including THC) can be accidentally produced, a number of manufacturers are now producing CBD without any detectable unwanted cannabinoids. Such purity is better for consumers (especially those subject to professional testing) and for formulators, who can put greater amounts of CBD in products without risk of exceeding the assumed limit of 1 mg per container.

For many people, words like “plant/herbal extract” and “natural origin” sound better or safer – for humans and the environment – than “chemical synthesis.” But the synthetic route – at least for CBD – actually uses fewer chemicals than solvent and gas extraction, making it more eco friendly. There is also no need for fertilizers or pesticides – and thus no risk of residues. And there is no risk of dangerous, potentially cancer causing mycotoxins, which is an ongoing challenge for cannabis growers everywhere. All good for humans. In addition to being purer, each batch is consistent, free from pesticides, and traceable.

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Right now, despite the advantages of synthetic CBD, the vast majority of products contain plant-derived CBD – and, especially for those stated to be “broad spectrum,” these are highly likely to contain THC in trace or greater amounts (not to mention the other known and unknown impurities). In my view, if we’re thinking about CBD as a health and wellness product, this needs to change.

My view is clearly shared by the EU, who have already rejected multiple Novel Food applications from hemp growers (the application deadline for CBD brands looking to gain Novel Food certification was March 31, 2021). And though products with an application submitted were allowed to remain on sale from April 1, who knows how many of these products will meet the Food Standard Authority’s (FSA) strict requirements? It is Biosportart’s view that synthetic producers of CBD that follow clear manufacturing and testing protocols, such as PureForm Global, have a serious upper hand when it comes to achieving full Novel Food status from the FSA.

As we begin to understand the benefits and side effects of individual cannabinoids, the industry must evolve and mature.

Don’t get me wrong, Cannabis sativa is an amazing plant. It has co-evolved with mammals for millions of years and contains a whole suite of interesting, interacting chemicals – the full potential of which we are just beginning to understand. Indeed, we are only now emerging from what could be described as the “dark ages” of Cannabis; for so many years, social stigma and a strict legal environment have prevented the plant’s incredible benefits from being extracted, researched, and applied.

But as we begin to understand the benefits and side effects of individual cannabinoids, the industry must evolve and mature. In my view, CBD synthesis solves many challenges and provides the means to achieve purity, consistency, and yields at a scale that allows adoption of CBD for a wider variety of consumer and medical applications, unlocking just one beneficial aspect of this incredible plant.

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Natural vs. Synthetic CBD: What’s the Difference?

The rise in the popularity of CBD brings an increase in various CBD products that individuals can take.

It can be confusing to distinguish the difference between natural and synthetic CBD. Read on to find out more about the difference between the two and the benefits of each type.

What Is CBD?

Cannabidiol (CBD) is a naturally occurring compound found in cannabis. While cannabis contains around over 100 different cannabinoids, like tetrahydrocannabinol (THC), and minor cannabinoids, like CBN and CBG, CBD is probably the most well known.

Each cannabinoid has its own features, therapeutic properties, chemical structure, and benefits. CBD is well-known for its versatility and well-tolerated nature, and because of this, it is often isolated and made into CBD-based oils, tinctures, topical creams, and edibles.

All cannabinoids interact with the endocannabinoid system (ECS) to produce therapeutic effects. CBD is no different. The ECS is a complex cell signalling system found within all mammals that consist of endocannabinoids and receptors. These receptors are on the brain, on body tissues, and within the nervous system. The ECS is responsible for regulating many body processes, so when CBD interacts with these receptors, effects are experienced.

What Is Natural CBD?

Before being included in a product, different forms of CBD must go through a specific process of manufacturing and refinement. Natural CBD comes from the cannabis plant (either hemp or marijuana) and is extracted in one of a number of different ways, including ethanol, oil, or CO2 extraction. After the CBD has been successfully extracted, additional processing can be done.

With most extraction methods other cannabinoids are present in the initial extract – these may be retained (full spectrum), selectively removed (broad spectrum) or totally removed (isolate) to produce different forms of CBD suitable for different uses.

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The Benefits

Natural forms of CBD can provide wide-ranging benefits that span our mental and physical health.

Pain

Chronic pain is one of the most popular reasons for CBD use. CBD not only changes how the brain perceives pain throughout the body but can also decrease inflammation levels. During high inflammation levels, swelling can push against nerve endings, which send pain signals to the brain. CBD has long been associated with its anti-inflammatory properties .

CBD can also interact with receptors in your brain and nervous system to decrease pain perception . Because of this, CBD has emerged as an effective natural alternative to traditional painkillers without any of the nasty side effects.

Sleep

CBD has emerged as a possible treatment to decrease symptoms of insomnia and sleeplessness. As mentioned earlier, CBD can interact with the ECS and receptors in the brain to promote calm feelings, slow a racing heartbeat, and even slightly decrease blood pressure. All of this can reduce stress and therefore encourage sleep .

Anxiety

CBD can interact with the ECS receptors in the brain and nervous system to promote relaxation . This also comes without adverse side effects often seen in traditional medication.

Anxiety and depression often walk hand in hand. While CBD itself doesn’t directly increase serotonin levels in the body, it can also interact with serotonin receptors to improve serotonin uptake and expression. This means more of the happy hormone, resulting in elevated mood levels, which can improve focus and concentration.

What Is Synthetic CBD?

While natural CBD is produced from hemp or cannabis plants, synthetic varieties of CBD are produced either by chemical synthesis using ingredients like limonene, or by biological synthesis using modified yeast or other bacteria.

High-quality synthetic CBD and natural CBD are considered to be chemically identical to each other, with studies confirming that both types of CBD have identical chemical structures. Synthetic CBD is an appealing alternative for industries requiring strict legal regulations and requirements, like the cosmetic industry. While natural CBD is popular amongst users for its wide-ranging effects, the production of synthetic CBD is a valuable asset for a wide range of consumer applications requiring high yield and consistency.

Natural vs. Synthetic CBD

Natural and synthetic cannabinoids, including CBD, are not very different from each other. However, there are some key differences .

Generally, synthetic CBD is produced to contain more specific yielding pure CBD molecules, while natural CBD extracts often come with other naturally occurring compounds, like cannabinoids, terpenes, and flavonoids.

Because of their composition, which includes other compounds, cannabinoids and terpenes can also bind to one or more cannabinoid receptors. This can therefore alter the therapeutic effect of natural CBD.

Regarding their affinity, synthetic CBD is often designed to have a high affinity for receptors, resulting in lasting effects. In comparison, natural CBD is considered to be more gentle, with a moderate affinity for receptors. This affinity can also be short-lasting and overpowered by other compounds or modulators.

Finally, natural CBD is a popular option as the other naturally occurring compounds can work together to create the entourage effect . This phenomenon amplifies the effects of the individual compounds to create a potent experience for the user.

The Bottom Line

Both natural and synthetic CBD provide therapeutic effects for the user and can be purchased for use in many countries.

Choosing high-quality CBD products from a reputable company is essential, and checking in with your health professional before starting use is recommended.

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