The Potential Risks of Synthetic Cannabinoids

A new study looks at the effects of the synthetic cannabinoid JWH-018, found in Spice. The researchers reveal what makes this compound and other synthetic cannabinoids a risky alternative to natural cannabis.

Cannabinoids: A Quick Primer

Cannabinoids are compounds that interact with your body’s endocannabinoid system. Naturally occurring cannabinoids (known as endocannabinoids) and cannabinoid receptors make up this biological system. These two classes of molecules fit together like a key into a lock and control a surprising amount of biological functions, including your appetite, mood, memory, and even your immune system.

There are three main classes of cannabinoids that interact with the endocannabinoid system.

1. Endocannabinoids

Our bodies make our own cannabinoids called endocannabinoids, like anandamide.

2. Phytocannabinoids

There are also the cannabinoids that come from the cannabis plant. These are technically called phytocannabinoids, but most people just refer to them as cannabinoids. THC and CBD are the most well known. They hijack our innate endocannabinoid system and make us feel intoxicated.

3. Synthetic Cannabinoids

Lastly, there are synthetic cannabinoids. Scientists created these compounds in the lab to mimic the effects of phytocannabinoids. Their original purpose was to help scientists study the effects of cannabinoids without needing THC, a heavily restricted substance in most countries.

The Rise of Synthetic Cannabinoids

In the last decade, governments around the world have loosened restrictions and regulations on cannabis. Prior to this shift, synthetic cannabinoids became popular as a legal alternative to cannabis.

Companies co-opted synthetic cannabinoid compounds from the lab and turned them into recreational substances. They began marketing herbal mixtures such as Spice and K2 that were sprayed with synthetic cannabinoids, claiming they mimicked the effects of cannabis.

What are the risks?

According to both the UN and the CDC, synthetic cannabinoids are far from harmless.

People have been using cannabis for centuries and it’s still one of the most popular recreational drugs. Researchers have also thoroughly studied the effects of THC and CBD and know their risk profiles very well.

However, similar studies don’t exist for synthetic cannabinoids. On top of this, their very design makes them more likely to cause harm.

Like THC, synthetic cannabinoids bind to cannabinoid receptors. But because they were designed in the lab to have a tight molecular fit, synthetic cannabinoids bind to the receptors much more strongly than THC. As a result, the effects can be stronger and the risk of overdose is greater.

There are many cases of patients being admitted to the emergency room complaining of tachycardia, hallucinations, seizures, anxiety, panic attacks, and acute psychosis after consuming synthetic cannabinoids.

Studying the Effects of Synthetic Cannabinoids

JWH-018 is the synthetic ingredient in Spice. Researchers from Maastricht University in the Netherlands have been working to study and document its effects on humans.

The team published the results of a small pilot study and recently published the results from a slightly larger clinical trial in the British Journal of Pharmacology.

The researchers recruited 17 healthy adults who used cannabis. The participants inhaled either a non-psychoactive hemp placebo or a dose of JWH-018 (between 2-6 mg) from a glass pipe. The researchers then monitored the participants for 12 hours and tested them for their vital signs, cognitive performance, and subjective experience.

The Results

To the researchers’ surprise, there was a striking variability in the participants’ response to JWH-018. Some reported feeling very intoxicated while others felt nothing after taking the same dose.

The cause was most likely due to differences in drug delivery rather than participant sensitivity. The researchers found that the pipes of the “responder” participants had less residual JWH-018 than the “non-responder” participants.

The responders also had higher blood levels of JWH-018 than non-responders. Blood levels of JWH-018 peaked within 5 minutes after ingestion, but subjective intoxication peaked much later. This is very similar to the effects of THC.

The responder participants reported feeling intoxicated. The cognitive tests revealed that JWH-018 has many similar effects as THC, such as impaired reaction time, memory, and eye tracking performance. But with such small doses, the effects of JWH-018 were not very severe.

The responders also reported feelings of confusion and amnesia as well as changes in perception resulting in depersonalization and derealization. These are symptoms often reported in cases of synthetic cannabinoid overdose and are collectively called the zombie effect.

Takeaway Lessons

The biggest takeaway from this new study is that synthetic cannabinoids can be hard to dose. And this is exactly what makes them so risky.

The researchers in the study carefully controlled the amount of JWH-018 they administered to the participants. They also gave the participants a strict protocol and observed them while they ingested the drug. Despite these controls, some participants ended up with twice as much JWH-018 in their blood than others that received the same initial dose.

If researchers in a lab couldn’t control the dosing of JWH-018, imagine how difficult it would be to control in a real-life setting.

As this study demonstrated, even low doses can result in moderate effects. Herbal blends of synthetic cannabinoids like Spice are often not homogenous. It would be easy for someone feeling little effect to continue smoking, leading to sudden impairment and possible overdose.

Closing Thoughts

This is the first controlled clinical study of this size to look at the effects of the synthetic cannabinoid JWH-018. The researchers found that many of the compound’s effects are similar to THC.

However, synthetic cannabinoids bind much more strongly to cannabinoid receptors. Combined with tricky dosing, users can more easily overdose on synthetic cannabinoid herbal blends than natural cannabis.

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