Synthetic Vs Natural Cannabis: What’S The Difference?

Marguerite Arnold

Cannabis Entrepreneur And Journalist

Marguerite Arnold

Last updated: December 28, 2022

There is still a great deal of misunderstanding about the differences between natural, plant-derived cannabinoids—or phytocannabinoids—and synthetic cannabinoids. There is further confusion surrounding synthetic cannabinoids produced for specific medical purposes vs those created for illegal commercial sale.

On the legit side, there are forms of synthetic CBD and THC that are legally produced and sold as pharmaceuticals or health products. Dronabinol, which harnesses THC as an active ingredient, is frequently produced using chemicals from outside of the plant.

On the other side of the ledger are illicit synthetics. The drug K2, also known as Spice, is one example of an illegally produced cannabinoid. It is also a highly dangerous one that has been known to cause a range of serious health effects, and even death.

For the average cannabis consumer, here is a simple rule of thumb: most synthetically produced cannabinoids are bad news. Avoid them. With that in mind, let’s take a look at the differences between natural cannabis and synthetic cannabis, and see what this means for consumers.

Not All Cannabis Is Created Equal

There are several ways to synthesise cannabinoids—chemical structures that bind to or impact cannabinoid receptors found in the human body.

Well over 100 naturally occurring phytocannabinoids can be derived from the cannabis plant, including CBD and THC. As legalization continues to progress globally, more and more studies are being conducted on such cannabinoids, both individually and in combination.

Another way to create cannabinoids is in a lab. There are over 300 synthetic cannabinoids in existence. While some are under the impression that these sometimes-legal substances are “safer” than natural cannabinoids, nothing could be further from the truth.

Finally, it’s worth noting that cannabinoids are also synthesised by the human body! Endocannabinoids such as anandamide and 2-arachidonoylglycerol are produced to modulate a wide range of physiological processes via the endocannabinoid system (ECS) and its receptors.

What Is Natural Cannabis?

So considering the above, the two forms of “natural cannabis”, or, more accurately, “natural cannabinoids” are phytocannabinoids and endocannabinoids. Both endo and phytocannabinoids are capable of binding to or otherwise impacting cannabinoid receptors and enzymes, causing a variety of effects.

Yet, unlike synthetic cannabinoids, natural cannabinoids will not overstimulate cannabinoid receptors to the point of being dangerous.

Examples Of Natural Cannabis

Any cannabinoid extracted from the cannabis plant can be considered a natural phytocannabinoid. Some examples include:

• THC
• CBD
• CBG
• CBC
• THCA
• CBDA
• THCV

The two main examples of natural endocannabinoids in humans are anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

What Is Synthetic Cannabis?

Though they are undoubtedly different, both synthetic and natural cannabinoids work by stimulating receptors of the endocannabinoid system, most notably CB1. Indeed, synthetic cannabinoids are more accurately described as cannabinoid receptor agonists.

Rather than being created from cannabis-derived compounds, synthetic weed is made using a variety of other chemicals and processes. Again, some of these are more scientifically sound than others. In the case of government-approved pharmaceuticals, the idea is to mimic the action of cannabinoids in the safest way possible. With street synthetic marijuana, the likelihood of experiencing adverse effects is much greater.

However, even pharmaceutical companies have found that altering cannabinoids to achieve certain effects can be dangerous. Rimbonant was a cannabinoid medicine produced to limit appetite that caused suicidal thoughts in patients, and was thus removed from the market.

Synthetics produced in a non-pharmaceutical environment, without even basic controls, can be even more dangerous than this, if not lethal outright.

Synthetic cannabinoids generally fall into the following categories (Presley et al., 2013):

• Cyclohexylphenols
• Naphthoylindoles
• Naphthylmethylindoles
• Naphthylmethylindenes
• Naphthoylpyrroles
• Phenylacetylindoles
• Adamantoylindoles
• Tetramethylcyclopropylindoles

Other kinds of synthetically produced cannabis receptor agonists include oleamide, which is commonly used in plastics manufacturing ("Synthetic cannabinoids and 'Spice' drug profile”).

Oleamide and methanandamide, and other synthetic cannabinoids, are structurally related to our own anandamide endocannabinoid, the so-called “bliss” chemical.

Synthetic cannabinoids are also almost always “isolates”, meaning there is only one chemical intended to stimulate the internal cannabinoid receptors of the body. Sometimes, such compounds are synthesised from part of a THC molecule and modified in a lab. However, many forms of synthetic cannabis never come into contact with natural cannabinoids.

As a synthetic substance, there is really no way to know what other chemicals were used to create synthetic marijuana bought on the street. Many are laced with opioids; some contain poison. These substances are then often mixed with or sprayed onto natural plants and herbs to hide their chemical makeup.

Examples Of Synthetic Cannabis

Many synthetic marijuana products are deliberately designed to avoid legal restrictions on cannabis, and are sometimes marketed as “not for human consumption”. The synthetic cannabinoids found in such products often have a greater, but not positive, effect on the cannabinoid receptors of the body.

Since the beginning of this century, more than 142 synthetic cannabinoids have been found by authorities in Europe. They can appear even in products such as gummy bears and vape products purporting to be natural CBD or THC.

Here are a few brand names and titles associated with illicit, and often dangerous, synthetic cannabinoids:

• Spice
• K2
• Yucatan Fire
• Sence
• Chill X
• Smoke
• Genie
• Algerian Blend

The Endocannabinoid System Relies On Balance

While phytocannabinoids are capable of stimulating or influencing ECS receptors and enzymes to a greater degree than our own endocannabinoids, the nature of natural cannabis means it never goes overboard.

The two main cannabinoid receptors in the body, CB1 and CB2, are crucial to helping the human body maintain dynamic balance, aka homeostasis. Located throughout the brain and body, these receptors work via a lock and key principle. If the chemical structure of the cannabinoid matches the “lock” on the receptor, it acts like a key to make the receptor respond.

It is this mechanism that stops the body from processing excessive amounts of cannabinoids; it is also this feature that prevents lethal overdoses. With synthetic cannabis, however, these cannabinoids are given a general shape that allows them to “burst open” the lock and stimulate receptors to a degree that is unfavourable or dangerous.

Synthetic Vs Natural Cannabis

Now that we’ve reviewed the general principles of natural and synthetic cannabis, it’s time to get into a little more detail.

Chemical Structure

Synthetic cannabinoids are cannabinoid receptor agonists. However, they are not chemically identical to naturally occurring cannabinoids. Most are soluble in fats and consist of between 22 to 26 carbon atoms. Most also have what is called a “side-chain”, featuring four to nine saturated carbon atoms. The optimal binding affinity for CB1 is believed to be between 5 and 8 carbon atoms, with any more actually decreasing activity ("Why does alkyl chain length matter," 2020). Little else is known about the detailed pharmacology (and toxicity) of synthetic cannabinoids, as very few formal studies have been conducted.

Natural cannabinoids, however, tend to feature 21 carbon atoms, although this is not always the case. Side chain length can also vary significantly. However, this variation in structure lies within a certain window that prevents any seriously adverse effects from occurring.

Application

Natural cannabinoids have long been used for holistic or religious purposes beyond “just” relaxation. That said, cannabinoids like THC are also used recreationally.

Synthetic cannabinoids were originally used for several reasons. The first was to mimic natural cannabinoids for medical purposes, particularly in the past when marijuana reform had yet to become a legitimate discussion. Others were used in manufacturing and for non-human consumption.

Tragically, the current market of synthetics was created largely by illicit producers hoping to legally market their products, even in places where cannabis is now legitimate, but with no concern for human safety or health. Most synthetic cannabinoids are made to be smoked—although it is possible to find them in edible products, such as candies. Gummy bears are a popular edible to infuse synthetics with—often with tragic results. People have died from eating such products. Many have ended up in the hospital.

Pharmacological Effects

Some synthetic compounds have been produced in labs to mimic natural cannabinoids for therapeutic purposes. In the US, the FDA has approved the following synthetic cannabis substances, which are available only with a prescription: Marinol (dronabinol), Syndros (dronabinol), and Cesamet (nabilone) ("FDA and cannabis: Research and drug approval process," 2020). These drugs are used in specific circumstances and are not widely prescribed.

Apart from the potentially higher potency of these products, these substances also have a potentially much longer half-life, leading to longer-lasting effects.

The pharmacological effects of natural CBD, natural THC, and other phytocannabinoids are still under review. While comprehensive clinical trials are emerging, with many others underway, we have yet to understand the full scope of characteristics of individual cannabinoids. However, current research points to some highly encouraging potential.

Side Effects Of Synthetic Cannabinoids

While this is not an exhaustive list, here are some of the side effects reportedly caused by synthetic cannabinoids:

• Dizziness
• Nausea and vomiting
• Paranoia
• Poor coordination
• Shortness of breath
• Seizures
• Palpitations
• Passing out
• Death

Safety

Unless the synthetic cannabinoid ingested is properly manufactured in a pharmaceutical lab that is also certified for medical use, all synthetic cannabinoids should be considered highly dangerous. Beyond this, many are mixed with other dangerous chemicals and drugs. In the United States, the Food and Drug Administration has even found these products to contain a rat poison called brodifacoum, which is added to supposedly “extend” the effects. As such, these products can cause severe illnesses and even death.

The best and safest policy is to avoid them completely. They are not regulated, and usually produced solely for illicit purposes by companies that have no concern for you as a person.

Natural cannabis, however, presents a much less worrying safety profile, although the intoxicating nature of marijuana can still increase the risk of motor vehicle accidents and cause acute and long-term effects on one’s health ("Cannabis," n.d.).

Is Synthetic Cannabis Really That Dangerous?

The short answer is yes. Synthetics produced outside the legal system are almost always hazardous. One of the largest problems is that manufacturers deliberately market their products to look legit.

Counterfeit cannabinoids have shown up in edibles, like candy, in counterfeit hash, and, of course, in pre-manufactured vapes. There have been numerous reports of consumers falling ill or even dying after consuming them.

Luckily, there are ways, such as the EZ Test THC, to determine if a sample actually contains THC. In a matter of seconds, you can save yourself the headache of consuming something synthetic.

EZ Test THC

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Can Synthetic Cannabis Be Beneficial?

Some synthetic cannabinoids can be used in an attempt to improve human health. These include legal cannabinoid drugs such as Sativex, which can be produced from either natural cannabinoids or synthetics, Epidiolex, which is made solely from CBD or synthetic equivalents, or Cesamet, also known as nabilone, which is approved to treat movement disorders like Parkinson’s.

Many patients, however, prefer to be medicated not only with naturally derived cannabinoids, but formulas harnessing multiple natural cannabinoids and cannabis plant constituents, rather than just isolates.

The Best Approach Is To Grow Your Own Cannabis

The best way to ensure that your cannabis is natural and without chemical additives is to grow it yourself. However, this can also be hazardous if you live in a part of the world where this practice is still illegal. Still, growing a small plant or two is arguably safer than risking your health with synthetic cannabis bought from untrustworthy subjects. Be safe out there.