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 … Similar to cannabis, or not? If you’re a bit hazy on the facts on synthetic cannabinoids, find out everything you need to know from FRANK. 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
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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How you might feel Happy, relaxed, talkative and/or anxious, paranoid, sedated. Read more about how it feels Effects on your body Effects are similar to cannabis but stronger. Side effects can include nausea and mood swings. Also, sweating and tingly feelings in fingers and toes. Loss of muscle coordination. Read more about how it feels How long it takes to work Usually smoked so pretty immediate. Slower if swallowed. (Read more) Read more about how long it takes to work How long the effects last Varies from about 1 to 6 hours depending on the specific chemical. Read more about how long the effects last Common risks Easy to want more and take larger doses. Mental health can get worse. Psychotic episodes can be triggered, usually in those already susceptible, and last for weeks. Read more about the risks Mixing Drugs Mixing drugs is always risky but some mixtures are more dangerous than others. Read more about mixing with other drugs
How it looks, tastes and smells
What does it look like?
In their pure form, synthetic cannabinoids are either solids or oils. They are then added to dried herbs, vegetable matter or plant cuttings to make a smoking mixture (so that it looks more like real herbal cannabis).
The most commonly known synthetic cannabinoid is Spice.
The smoking mixtures are packaged in small, often colourful sachets with labels describing the contents as incense or herbal smoking mixture, and usually stating ‘not for human consumption’.
There are many different names given to herbal smoking mixtures, some of the most common are listed in the ‘Also called’ section at the top of the page.
There are many different brand names for smoking mixtures, but it is not uncommon for different brands to contain the same synthetic cannabinoids.
How do people take it?
Synthetic cannabinoids are normally used in a similar way to cannabis:
They can be mixed with tobacco, rolled up into a spliff or joint, and then smoked.
They can be smoked without tobacco using a pipe or bong.
As e-cigarettes have become more available, there are reports of some people using e-cig technology for synthetic cannabinoids, and that e-liquids containing synthetic cannabinoids have been produced that can be used with normal e-cigs.
They can also be swallowed, eaten with food or made into a drink.
There are increasing reports of synthetic cannabis edibles, looking like sweets such as gummies, lollipops, and other sweets.
How it feels
How does it make you feel?
Since synthetic cannabinoids act like cannabis, the effects – good and bad – are similar. Some users will feel happy and relaxed, may get the giggles, feel hunger pangs and become very talkative. Others mainly feel ill or paranoid.
Because synthetic cannabinoids react more strongly with the brain’s cannabis receptors they’re more potent than natural cannabis. This means it’s easier to use too much and experience unpleasant and harmful effects.
Synthetic cannabinoids act like THC, the active substance in natural cannabis, but are often more potent, so it’s easier to use too much and experience unpleasant and harmful effects.
Typical effects include:
Feelings of being happy, euphoric and relaxed, with some people gettings the giggles, feeling hunger pangs and becoming very talkative, while others get more drowsy.
Mood and perception can change, and concentration and coordination may become difficult. Synthetic cannabinoids, possibly because of their potency, are more likely to be associated with hallucinations than natural cannabis.
Some will have quite bad reactions, such as paranoia, panic attacks and forgetfulness.
How long the effects last and the drug stays in your system depends on how much you’ve taken, your size and what other drugs you may have also taken.
Physical health risks
The risks of synthetic cannabinoids are similar to natural cannabis, but because synthetic cannabinoids are more potent, it is easy to use too much and experience the unpleasant and harmful effects. This higher potency also means that the effects may last for longer.
Also, because many synthetic cannabinoids are new, they may have unknown effects too.
We know that there have been a number of deaths that have been associated with the use of synthetic cannabinoids, either on their own or with other substances. There may also be risks from smoking the plant material itself – as occurs with tobacco and cannabis smoking.
Reported side-effects from using synthetic cannabinoids include:
- feelings of lightheadedness, dizziness, confusion and tiredness
- feeling excited, agitated and aggressive
- mood swings
- anxiety and paranoia
- suicidal thoughts
- memory problems and amnesia
- nausea and vomiting
- hot flushes
- increased heart rate and blood pressure, which may cause chest pains and damage your heart and even cause a heart attack
- excessive sweating
- fingers, toes or muscles feel numb and tingly
- tremors, seizures and fits
Other risks for synthetic cannabinoids:
Research suggests that they may be an association between using synthetic cannabinoids and acute kidney injury.
Many synthetic cannabinoids have a chemical structure that is similar to serotonin, a natural chemical found in the body. It’s been suggested that there’s a risk that synthetic cannabinoids could overstimulate the serotonin system (called serotonin syndrome), which can result in high fever, rapid pulse, sweating, agitation, confusion, convulsions, organ failure, coma and even death.
Because of the way that smoking mixtures are made, there can be differences in the concentration of synthetic cannabinoids in individual packets and between different batches. You can never be 100% sure of how powerful a dose you are going to take.
Mental health risks
Synthetic cannabinoids are more likely to be associated with hallucinations than natural cannabis, possibly because of their potency.
Use of synthetic cannabinoids can cause psychotic episodes, which in extreme cases could last for weeks.
Regular use could cause a relapse of mental health illness or increase the risk of developing a mental illness, especially if you have a family history of mental illness.
What is synthetic cannabinoids cut with?
Synthetic cannabinoids are usually sold in ‘herbal’ smoking mixtures. Sometimes these smoking mixtures have been found not to contain any synthetic cannabinoids at all!
Any dried herbs, vegetable matter or plant cuttings can be mixed or sprayed with synthetic cannabinoids to make smoking mixtures. A number of different plants are often listed on the packaging of smoking mixtures, but these might not actually be present in the mixture.
It’s also possible that the dried herbs, vegetable matter or plant cuttings themselves may produce an unwanted effect or be covered in a toxic substance, such as a pesticide, or there may be residues of the solvents, such as acetone and methanol, used in the mixing/spraying process, remaining on the smoking mixture.
There have been a few studies carried out on the level of synthetic cannabinoids present in smoking mixtures which suggest that there can be differences in the concentration of synthetic cannabinoids in between different batches and packets. This could be because the mixing or spraying missed some of the smoking mixture or over-sprayed some of it.
The chemical composition of synthetic cannabinoids and the ingredients of smoking mixtures are changing all the time, so you can never be sure of what you’re getting, how powerful it is, and how it could affect you.
Is it dangerous to mix with other drugs?
Mixing synthetic cannabinoids with alcohol or other drugs can be especially dangerous. It can increase the risks of both drugs and can lead to a greater risk of accidents or death.
Also, because synthetic cannabinoids can overstimulate the serotonin system, it is important to avoid mixing them with antidepressants, such as Prozac, as they both stimulate serotonin activity in the brain, which can lead to serotonin syndrome, causing high fever, rapid pulse, sweating, agitation, confusion, convulsions, organ failure, coma and even death.
Can you get addicted?
Research suggests that you can become dependent on synthetic cannabinoids, especially if you use them regularly. Whether or not you’re dependent will be influenced by a number of factors, including how long you’ve been using it, how much you use and whether you are just more prone to becoming dependent.
If you have used synthetic cannabinoids regularly you could find it difficult to stop using and you might experience psychological and physical withdrawals when you do stop. The withdrawals can include cravings for synthetic cannabinoids, irritability, mood changes, loss of appetite, weight loss, difficulty sleeping and even sweating, shaking and diarrhoea.
Class: Psychoactive Substances
Some volatile substances are covered by the 2016 Psychoactive Substances Act, which means it’s illegal to give away or sell.
There’s no penalty for possession, unless you’re in prison.
Supply and production can get you up to 7 years in prison, an unlimited fine or both.
Like drink-driving, driving when high is dangerous and illegal. If you’re caught driving under the influence, you may receive a heavy fine, driving ban, or prison sentence.
If the police catch people supplying illegal drugs in a home, club, bar or hostel, they can potentially prosecute the landlord, club owner or any other person concerned in the management of the premises.
Additional law details
Synthetic cannabinoids and the law
- Although some synthetic cannabinoids have been legal in the past, many have been illegal for some time. A large number of synthetic cannabinoids and any mixtures that contain illegal drugs, including brands like Black Mamba and Annihilation, are Class B drugs and are illegal to have, give away or sell.
It’s important to realise that since 26 May 2016, when the Psychoactive Substances Act came into effect, none of these drugs are legal to produce, supply or import (even for personal use, e.g. over the internet) for human consumption.
The synthetic cannabinoids that were made illegal under the Misuse of Drugs Act, are still covered by that legislation. All other psychoactive substances not currently covered by the Misuse of Drugs Act now fall under the Psychoactive Substances Act.
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.
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.
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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