Synthetic Vs. Natural Cannabinoids: What’S The Difference?

Synthetic Vs. Natural Cannabinoids

Synthetic cannabinoids are compounds created to provoke an extreme reaction from our endocannabinoid system (ECS). Keep reading to find out the differences and similarities between the natural cannabinoids found in cannabis, and the synthetic analogues produced to mimic them.

It is highly likely you have heard of the synthetic herbal mix “spice”, also known as K2, which is designed to mimic the effects of cannabis. However, when it interacts with the body, it is nothing like natural cannabinoids, instead leaving the user with extremely severe side effects.

The bottom line is, most synthetic cannabinoids are bad news. We say “most” because, while all synthetic cannabinoids are designed to “overload” our endocannabinoid system, they don’t all have harmful repercussions. Before we look at the approved synthetic cannabinoids that are available, it is worth understanding the relationship between natural cannabinoids and our endocannabinoid system.

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Cannabis is predominantly made up of a sophisticated blend of cannabinoids, terpenes, and flavonoids. When we smoke or otherwise ingest weed, these compounds interact with our endocannabinoid system, initiating a windfall of effects.

Smoke a high-THC strain, and effects range from fits of giggles and the munches to full-blown couch-lock. Because the body is biologically designed to process cannabinoids, these effects pass over time, without (in most cases) residual effects. Sometimes, if we blazed hard the night before, we may feel groggy the next day—but for the most part, life goes on as usual.

The Endocannabinoid System Relies On Balance


This concept of harmony and balance is what makes cannabis incredibly versatile for both recreational and medicinal users. The plant is enjoyed in numerous ways, with no severe or lasting side effects. However, as our understanding of cannabinoids grows, so too does the potential for manipulation. Synthetic cannabinoids, despite being similar at a molecular level, go against the principles of balance and harmony exhibited by natural cannabinoids.

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When consumed under normal circumstances, cannabinoids interact with the endocannabinoid system mainly via two types of receptor (CB1 and CB2). The nature and location of a receptor influence the subsequent effect. For example, THC binds to CB1 receptors primarily found in the brain, while other cannabinoids have a stronger affinity for CB2 receptors located throughout major organs.

Receptors are activated by cannabinoids using a “lock and key” principle. If the chemical structure of the cannabinoid matches the lock on a receptor, the two interact. This mechanism is what stops the body from processing excessive amounts of cannabinoids.

It is a biological action that has evolved over millions of years, and is the reason why no one has ever lethally overdosed on cannabis—the endocannabinoid system's job is to promote a dynamic equilibrium called homeostasis, and thus keep cannabinoids at tolerable levels.

Synthetic Cannabinoids Disrupt Homeostasis


Synthetic cannabinoids are compounds created artificially in a lab, rather than extracted directly from a cannabis plant. Their base chemical structure is similar to that of their natural counterparts, but it is the remainder of the compound that differs. If we refer back to the lock and key principle, natural cannabinoids are either an exact fit for specific locks (receptors), or not. Synthetic cannabinoids, on the other hand, have a general shape that allows them to activate a receptor through force.

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The endocannabinoid system is pushed into overdrive as it struggles to cope with the surge of cannabinoids it doesn't fully recognise. Rather than keeping all our biological systems in a state of homeostasis, it is forced to compensate and disrupt specific physiological processes in favour of others.

With synthetic substances like spice, the potential outcomes are seizures, psychotic episodes, suicidal tendencies, and severe cravings—not even remotely similar to the effects of consuming natural cannabinoids!

Synthetic Cannabinoids Do Have Positive Applications


Overloading the endocannabinoid system is not without some positive applications—under very specific circumstances. GW Pharmaceuticals, a British pharmaceutical company, is at the forefront of synthetic cannabinoid development.

The difference is that both Sativex and Epidiolex are used to treat debilitating medical conditions, rather than induce them. Sativex is a mouth spray used to treat muscle spasms[1] associated with multiple sclerosis (MS), while Epidiolex supports children with two types of severe epilepsy[2].

At their core, both of these synthetic cannabinoids work in the same way as spice. They act as a highly concentrated dose of cannabinoids that triggers an extreme reaction from the endocannabinoid system, and can still inflict significant side effects as a result. The difference is that both analogues were created with a beneficial outcome in mind—this is not the case with spice.

Synthetic Cannabinoids Are Beneficial Under Specific Circumstances


Although the very nature of synthetic cannabinoids goes against the core principles of cannabis and its cannabinoids, pharmaceutical companies have been able to tailor their effects to be somewhat beneficial—or to be more precise, beneficial enough to offset adverse side effects. The challenge for future research is to understand how these synthetic compounds can retain their efficacy while moving to be more in line with the endocannabinoid system’s ethos of balance.

No matter the outcome, a great deal more study and analysis are needed. In 99% of scenarios, synthetic cannabinoids will not be suitable nor safe to use for mainstream consumers. Even the compounds that have been developed to be medically beneficial are approved on a case by case basis, with limited approval on the global stage.

For the majority of us, the potential healing power of natural cannabinoids presents the best option for cannabinoid therapies.

We are not making medical claims. This article has been written for informational purposes only, and is based on research published by other externals sources.

External Resources:
  1. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receivi... - PubMed - NCBI -
  2. GW Pharmaceuticals Announces New Physician Reports of Epidiolex(R) Treatment Effect in Children and Young Adults With Treatment-Resistant Epilepsy -