Spice’s Most Dangerous Substances: What Are 5F-x Synthetic Cannabinoids?

The primary compounds behind the fatal drug Spice, it’s understandable that synthetic cannabinoids in the 5F-x family have garnered quite a bit of negative attention over the last few years. Medical researchers from Hungary to the United States have scrambled to determine what, exactly, is behind all the deaths attributed to Spice since circa 2014.

Based on all the available medical research, it certainly appears that 5F-x synthetic cannabinoids are the culprits we’re looking for. Learn what these dangerous synthetic compounds are, why they’re used in Spice, and what the research says about how they can harm the human body.

What are synthetic cannabinoids?

In general, the term “synthetic cannabinoid” refers to any compound bearing a structural resemblance to a cannabinoid that was, nonetheless, made artificially and not derived from cannabis. In some cases, synthetic cannabinoids can be harmless and just as useful as their natural counterparts.

All too often, however, the process of synthesizing cannabinoids takes a wrong turn, and the resulting compound is not something fresh, natural and new but is — on the contrary — an abominable Frankenstein’s monster ready to harm countless unsuspecting victims. Originally created by the United States Army in the 1970s as part of an effort to “weaponize marijuana,” synthetic cannabinoids in the 5F-x category continue to haunt the Western world to this day.

How are 5F-x synthetic cannabinoids different?

While the biochemistry can get somewhat complicated, synthetic cannabinoids in the 5F-x family are essentially designed to stimulate your CB1 receptors as much as possible with absolutely no buffers or limits. One way in which these synthetic cannabinoids are “unlimited” is in how they recirculate themselves, not their metabolites, over and over across your cannabinoid receptors.

Natural cannabinoids, even the ultra-potent THCP, transform into other substances as they’re digested or otherwise processed in the body. That’s part of why natural cannabinoids cannot cause overdose. You can easily overdose on 5F-x synthetic cannabinoids, though, because they do not break down into metabolites and instead remain in your system, accumulating as you use more.

What are some examples of 5F-x synthetic cannabinoids?

There is no officially established terminology for synthetic cannabinoid nomenclature, and different research groups may use their own designations. The following all appear to be distinct synthetic cannabinoids in the 5F-x group according to the available scientific literature:

- 5F-MDMB-P7AICA
- 5F-MDMB-PICA
- 5F-ADB
- 5F-MDMB-PINACA
- 5F-ADF-PINACA
- 5F-PB-22

To learn more about how synthetic cannabinoids in the 5F-x family affect your body, we’ll take a look at the following studies:

(2022) In vitro and in vivo pharmacology of nine novel synthetic cannabinoid receptor agonists

Examining synthetic cannabinoids in the 5F-x and other families, this study found that these cannabinoids all “bound to and activated CB1 and CB2 receptors with high affinity” but that they also (oddly) caused hypothermia.

(2022) Structure-activity relationships for 5F-MDMB-PICA and its 5F-pentylindole analogs to induce cannabinoid-like effects in mice

Interestingly, this study found that not all 5F-x cannabinoids stimulate your CB1 receptors. It confirmed that 5F-x synthetic cannabinoids cause hypothermia, and it also found that they cause catalepsy (paralysis).

(2021) Pharmacokinetics and Pharmacodynamics of the Synthetic Cannabinoid, 5F-MDMB-PICA, in Male Rats

This study confirms that concentrations of 5F-x cannabinoid metabolites “were much lower than the parent drug,” emphasizing the potential for overdose inherent to these compounds. The authors identified 5F-MDMB-PICA in particular as “a potent CB1 agonist.”

5F-x synthetic cannabinoid case reports

Research studies are only one half of the equation. We also have to look at case reports related to 5F-x cannabinoid fatalities and injuries:

(2023) ‘Flying high?’—Jump from a height in a ‘Spice’ high?: A case report on the synthetic cannabinoid 5F-MDMB-P7AICA

A post-mortem was performed on a 31-year-old man who jumped to his death. It was found that he had high concentrations of 5F-MDMB-P7AICA in his system, potentially contributing to a delusional state leading to his jump.

(2022) Fatal intoxication with new synthetic cannabinoids 5F-MDMB-PICA and 4F-MDMB-BINACA—parent compounds and metabolite identification in blood, urine and cerebrospinal fluid

A 33-year-old man lost consciousness and later died after smoking an unknown substance in a pipe. Multiple synthetic cannabinoids, including 5F-MDMB-PICA, were detected post-mortem.

(2021) Near-Fatal Spice Intoxication of a Toddler

In this case, it appears a three-year-old got a hold of a Spice vape pen or gummy. The poor child nearly died, and “5-fluoro-MDMB-PICA metabolites” were detected in blood work.

(2014) Four Postmortem Case Reports with Quantitative Detection of the Synthetic Cannabinoid, 5F-PB-22

In one of the first series of case reports ever published on the subject, researchers found traces of 5F-x cannabinoids in every one out of four drug overdose cases they examined, providing initial evidence that these substances might be highly toxic.

Conclusion: Is there any merit to 5F-x synthetic cannabinoids?

To be blunt, no, there is no medical or scientific merit to synthetic cannabinoids in the 5F-x family. The US Army should never have made them, and they certainly shouldn’t have tested these abominable drugs on their servicemen.

These days, all 5F-x synthetic cannabinoids do is tear families apart and consign countless promising youths to the depths of drug addiction. Spice and other drugs containing 5F-x cannabinoids are billed as being “better than weed” while, in reality, they’re awful approximations of real cannabinoids and have incredible potential to harm.

If you’re concerned that you or a loved one has ingested a dangerous concentration of synthetic cannabinoids, call 911, or call the Poison Control Hotline at 800-222-1222. 5F-x synthetic cannabinoids have no place on the shelves of our gas stations and convenience stores — do your part to spread awareness of these serious threats to public health.

Sources

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