Synthetic Cannabinoids: The Next Frontier or Just a False Start?

Cannabidiol, or CBD as it’s commonly known, has been exploding onto the market at a surprising clip over the past few years. As marijuana itself becomes increasingly legal, with full nationwide legalization very much within the realm of possibility, perhaps the rise of CBD is less shocking than it might seem to old folks like me. After all, it wasn’t that long ago that D.A.R.E. was coming into our elementary school classrooms, telling us that marijuana was a gateway drug and that one puff of this green leaf would almost guarantee a life riddled by heroin addiction and crack smoke.


Today, CBD is all over the place. If you live in California, you can’t so much as experience mild back pain or a headache without someone popping into frame and extolling the benefits of CBD. It’s natural, they say, and so much healthier for you than all that Big Pharma stuff. It can cure everything from joint pain to anxiety to the agony of cancer. As a writer, it’s not my place to judge whether or not CBD is the panacea its proponents claim, but it is worth considering, especially as dozens of vape shops throughout the country are being targeted in the latest round of the Vape Epidemic Witch Hunt. As major cities across the country consider sweeping legislation either banning or cracking down on e-cigarettes, many of these stores have positioned themselves to transition to the CBD market should the vape economy collapse.


Is this a wise decision or will the CBD market prove to be as shaky and assailable as the vape market has shown itself to be? It’s hard to say at this point, but some recent breakthroughs in CBD technology have certainly made the entire industry seem even more appealing than before. At the same time, there are forces working against CBD manufacturers and studies which may or may not hold up under scrutiny which call into question some of CBD’s potential merits. 


What We Actually Know About CBD

In the past month, Zynerba Pharmaceuticals announced another advancement in the clinical trials of their synthetic CBD drug Zygel. This medicine is indicated for the treatment of Deletion Syndrome and is derived from a particular synthetic version of CBD. Since this drug was fast-tracked by the FDA, it is likely to become the first synthetic CBD drug approved by the federal body. But let’s back up for just one second before we rush headlong into the recent development of synthetic CBD.


After all, what exactly is cannabidiol?


The basic definition of CBD is that it’s a naturally occurring substance found in the cannabis plant. Tetrahydrocannabinol (THC) is the other main chemical found in the cannabis plant, and this is the psychoactive element – i.e. the part that gets you high. As such, CBD does not provide the effects commonly associated with smoking marijuana. The euphoria, the sedation, and the appetite-altering effects are not present in CBD by itself. That having been said, the murky legal status of both CBD and THC at the moment means that a person should always be sure to use trusted brands with third-party testing.


Instead of the psychoactive properties for which THC is famous, CBD instead is well-known, at least anecdotally, for a wide variety of health benefits, very few of which have been approved or formally recognized by any medical bodies. People have claimed relief from ailments as diverse as seizures, anxiety, insomnia, and various pains. Likewise, CBD’s partner drug THC has been credited with treating anorexia, nausea, and glaucoma. At present, Epidiolex is the only FDA-approved, CBD-based medication currently on the market. This drug is indicated for certain types of epilepsy. 


While the science isn’t exactly clear-cut, let’s take a look at what researchers have concluded in regard to CBD. Keep in mind, of course, that this research has only become possible over recent years. As such, there’s only a handful of valid studies and they’re mostly using small samples. The Department of Veteran Affairs found that CBD can work with neuropathic (inflammation of the nerves) pain, but not other types of pain. The National Academies of Sciences, Engineering and Medicine found “conclusive or substantial evidence” that it’s effective in treating chronic pain, nausea, and vomiting. Lastly, Cochrane found “a lack of good evidence that any cannabis-derived product works for any chronic neuropathic pain”. So… conflicting results.


The industry does, however, have a much longer history of animal testing. In these studies, scientists have found – pretty overwhelmingly – that CBD has anti-inflammatory and analgesic properties. This would seem to support some of the later research conducted on humans, while conflicting with other reports – notably, the outlier at Cochrane. Interestingly, these studies also seem to show a connection between CBD and THC, in that they seem to complement each other when used in tandem. For instance, a 1:1 ratio will allow a person to tolerate more THC for pain relief without succumbing to the side effects of lethargy and impairment. Likewise, the THC increases the analgesic and pain relief effects of the CBD.


Of course, these studies were largely conducted on rats and it’s going to be difficult to find any type of consensus until further research is conducted. With the increasingly legal status of cannabis, in general, and the upcoming advances in lab-grown CBD and THC, the conclusive research industry watchers are looking for may be just around the corner.


However, just because there may be a lack of hard, clinical evidence for the various alleged health benefits of CBD doesn’t mean people aren’t buying it at an incredibly pace in a variety of formats. From oils to pills to vape juice, CBD is just about everywhere – and with the rise of synthetic CBD, it looks like they may become more omnipresent than ever in the near future.


The Rise of The Synths

Which brings us back to the present day, where companies are pushing the envelope and advancing CBD oils beyond the limits we currently know.


While Zygel is a drug specifically for the treatment of Deletion Syndrome, it is based on a synthetic CBD called H2CBD. While this sounds the name of a robot from the Star Wars universe, it is actually an advanced synthetic derivative from the cannabis plant which has been proven effective in treating certain seizure conditions in rats. As Zygel rushes to market, researchers at UC Davis are conducting studies on H2CBD with an eye towards creating a drug which can compete with Epidiolex. 


With all eyes in the scientific community trained on the progress of synthetic CBD, there is already a synthetic THC on the market called dronabinol, marketed as Marinol, and used in the treatment of cancer therapy. Given the success of a synthetic THC, it seems quite likely that synthetic CBD is here to stay.


The obvious advantage of synthetic CBD over harvesting it from cannabis plants is two-fold. Firstly, it eliminates our reliance upon harvesting plants. Cannabis plants are challenging to grow, requiring a great deal of resources and manpower. Once methods of synthesizing CBD are well-established, people will be able to create it in a fraction of the time and effort currently required. This advantage will however be a double-edged sword, given the climate surrounding pharmaceuticals in this country. While the ease of manufacturing synthetic CBD should drive down prices on potentially life-saving medicines, it’s equally likely that this gap will be gobbled up by greedy CEOs. In theory, however, this synthesis will be a good thing.


The other benefit has to do with the questionable legal status of cannabis plants. Although nationwide laws are trending towards federal legalization, there is no guarantee that this will happen. If cannabis plants remain illegal in certain parts of the country, having a means to access just CBD without growing the entire cannabis plant will be vital. Similarly, there are people who aren’t big fans of marijuana for personal or religious reasons who may be turned off from CBD by its connection to THC. Synthetic CBD may be appealing to people in this camp, since it won’t even be derived from the same plant.


Finally, synthetic drugs are the norm for just about every type of medicine. Even aspirin was initially discovered in the bark of trees. Imagine if we had never learned to synthesize this crucial drug; we would have groves of willow trees covering the entire planet to keep up with our needs. As such, it’s hard to view the synthesis of cannabinoids as anything but inevitable.


The Argument For Synthetic Cannabinoids


As we’ve already touched on, there are some very good reasons people are getting excited about synthetic CBD. Synthesizing CBD will eventually become less expensive than harvesting it naturally. It would be difficult to justify placing legal restrictions on synthetic CBD and it may be more appealing to certain kinds of people.


Additionally, THC and CBD are fairly easy to extract from cannabis plants, as they occur in high volumes. Other cannabinoids, however, are much harder to extract. CBG and THCV, for instance, are only found in trace amounts in the cannabis plant. If we could synthesize these cannabinoids, we may be able to find clinical benefits from them, specifically, and manufacture them at higher volumes than would be possible at present. While it’s still presently more expensive to synthesize CBD, it would be much more cost-effective to manufacture these lesser cannabinoids in a lab than to harvest them.


When you consider all the various cannabinoids in the cannabis plant, the research possibilities really begin to open up. At the moment, scientists really only have experience with THC and CBD, as these are the easiest to extract and study given our current harvesting techniques. Once synthesis becomes commonplace, however, we’ll be able to truly understand each of the various chemicals occurring in the plant, potentially unlocking entirely new avenues of scientific and medical discovery and research.


A big concern, however, as CBD enters this new territory, is the way in which pharmaceutical companies will likely strive to profit from it. While cannabinoids are naturally occurring and cannot be patented, Big Pharma will always find a way to make their money. In this case, experts are predicting that pharmaceutical companies will simply combine cannabinoids with proprietary medicines in order to patent them and maximize their profit. As always, technological advances should theoretically benefit us all, but capitalism will no doubt take the lion’s share of the spoils.


The Case Against Synthetic Cannabinoids


While cannabis, CBD, and synthetic advances in medical research can be very exciting, there are just as many health professionals expressing concern over the rising popularity of CBD – specifically synthetic CBD. While these health risks may not apply to the types of high-quality medicinal CBD that pharmaceutical companies aim to produce, the negative impact of any synthetic CBD will likely be used to target and ban all synthetic CBD products – so it’s worth knowing!


Arguably the biggest and most recent point of contention regarding synthetic CBD is a study showing that users of synthetic cannabinoids are more likely to have seizures and risk coma than those using natural cannabis. In this study, of course, synthetic CBD was lumped together with K2 and Spice, which is a bit inflammatory, one suspects, by design.


The research behind this study was led by Dr. Sarah Ann Anderson-Burnett, an adolescent medicine fellow in pediatrics and Columbia University. According to her, “synthetic cannabinoids… are associated with severe neuropsychiatric effects on adolescents and require higher acuity care than adults”. Basically, the premise of the study was that synthetic CBD can mess up younger people even while it has valid medicinal use for adults.


Anderson-Burnett’s study analyzed 348 subjects, all between the age of 13 and 19, and all of whom were treated in the ER for cannabinoid-related toxicity. In those who suffered coma or central nervous system depression, her results showed that synthetic CBD accounted for far more of the ER visits than cannabis. Nearly 28% of synthetic cannabinoid users experienced these traumatic events, while only 10% of cannabis users suffered similarly.


The study goes on to show that 19% of synthetic CBD cases included seizure, as compared with 6% in cannabis users. Naturally, this was a relatively small study with limited scope. After all, they were not able to differentiate which synthetic CBD was used in each case. Most of the teenagers in the study were also admitted with multiple substances in their system, which could easily cloud the results further.


Nevertheless, the study offers some big and frightening numbers, which will surely frighten parents. As we’ve seen with vaping in general, it doesn’t take an overwhelming amount of evidence to turn large chunks of the population against something they have no experience with personally and don’t fully understand. If synthetic CBD products turn out to be even a fraction as helpful as their proponents claim, it would be an absolute travesty to see research and production halted over potentially unfounded hysteria.


The Real Dangers of “Designer” Synthetic Cannabinoids


To fully understand the evolving debate surrounding synthetic cannabinoids, it’s important to understand their historical context. As researchers and scientists begin to make advances in these drugs, one must grasp how synthetic cannabinoids have been used prior to these recent medical breakthroughs.

That brings us to the dangers of unregulated synthetic cannabinoids. You may have heard of “spice” or “K2” in the past. Most people know that these are drugs which are similar to, but much more dangerous than, marijuana. The actual chemical explanation behind this is the difference between partial- and full-agonists. THC is a partial-agonist to the endocannabinoid CB1 receptor. This means that it binds partially to the receptor in your brain, providing the euphoria and other effects for which marijuana is known. Many of the unregulated and illegal synthetic cannabinoids out there operate as full-agonists. This means that the body cannot effectively remove the cannabinoid, destroying the receptor entirely in the process.


Obviously, this sounds dangerous – and it is – but it’s a result of the inherently unregulated nature of black market drugs. Synthetic cannabinoids have a long history of being created by street chemists. These individuals use no quality control nor are they subject to any type of oversight. Their only goal is to create a drug which is highly effective, addictive, and potent in small doses. This means that they’re also unstable, unpredictable, and can vary from batch to batch. Teenagers who wound up hospitalized and participating in the Anderson-Burnett study, for example, were very likely victims of a “bad batch” of these designer drugs.


Just like illicit vape counterfeiters, street dealers who crank out deadly and overly potent synthetic CBD are selfish operatives doing damage to the entire industry and feeding ammunition to the cranks who will likely take aim at the emerging synthetic CBD market. Companies who try to market clinically proven medications with proper oversights and quality control will have to contend with the unfair stigma surrounding these drugs.


That having been said, there’s no doubt that illicit CBD products can be extremely dangerous. As the market continues to expand, it’s important to research, understand, and advocate for the reputable brands on the market. A little bit of knowledge can be extremely powerful, and the more you do to help others around you understand this complex issue, the better off everyone will be.


Don’t let people say that “all synthetic CBD is dangerous”. This has been true, in the past. However, altruistically-minded people are working hard to shift the paradigm so that one day CBD can be used in healthcare throughout the world instead of potentially worse pharmaceutical options which currently exist.


The Synthetic Haze


There’s a ton of moving parts and ongoing developments in the world of CBD. First, synthetic CBD products are the bane of people’s existence, next thing we’re seeing doctors and researchers telling us they can create them safely. It’s important not to let yourself get overwhelmed by the sheer volume of information coming out on the subject. Proponents of the drug have a tendency to oversell CBD, while its opponents tend to operate out of malice or ignorance.


There is a middle ground, however. And the important points to take away are as follows:


  • CBD is not a psychoactive drug. THC is the psychoactive part of the cannabis plant and can be entirely separated from CBD. Those who do not partake in mind-altering substances can still safely partake in CBD if it is properly manufactured.
  • Synthetic CBD drugs are not yet on the market, but they will be soon. People should understand the vital difference between new, quality controlled CBD drugs and the old “designer street drugs” commonly referred to as synthetic CBD.
  • There is a real and meaningful danger to unregulated synthetic CBD compounds which should not be ignored. Just because critics of medicinal CBD may try to extend these dangers to include all synthetic cannabis products does not mean they’re entirely wrong. Never buy synthetic CBD (or any other drugs, for that matter) from an unknown or less-than-reputable manufacturer or vendor.


At the end of the day, CBD isn’t for everyone. Perhaps you’ve tried it in the past and had little or no meaningful experience. Others absolutely swear by it. The point, however, is that it’s exciting to see science branch off in this direction. As doctors and researchers get better at creating CBD in a lab, the possibilities they may unlock become seemingly endless. Will synthetic CBD save the world? It’s unlikely, but you really never know. If we somehow manage to avoid cooking the entire planet in the next century, who knows what kinds of medical advances lay down the road upon which science is currently embarking. Frightening times we live in, but exciting as well.