Recently there has been a lot of discussion in various states about regulating or banning hemp-derived cannabinoids and intoxicating hemp products.  This has come up in part because these hemp-derived products are circumventing state-legal programs as well as posing public health risk due to lack of regulation.  Let’s take a look at why this is important and also where current focus misses the boat.

What are intoxicating hemp products?

One of the major problems when it comes to understanding the cannabinoid product space is that there are so many products and sources of cannabinoids.  Cannabinoids can be extracted from plant material, they can be synthesized from scratch, or they can be synthesized from another cannabinoid. 

While plant-derived cannabinoids can pose some risk from contamination with heavy metals, pesticides, and mold, human-made chemicals are only as good as the chemist doing the synthesis and purification.  Cannabinoids that are derived from a starting cannabinoid share all of these risks. 

As you recall, hemp is just cannabis that has been bred to produce less that 0.3% THC by dry weight.  However, Congress decided in the Farm Bill of 2018 to treat hemp as its own thing, removing it from the Controlled Substances Act.  The intention, I assume, was to benefit farmers who could grow hemp for industrial use like rope, paper, textile, concrete, and others.  However, a brief paragraph also legalized use of the cannabinoids it produces and any and all derivatives therefrom (page 419 of the 2018 bill).  This was a huge mistake.

Not only did this legalize CBD and many other naturally occurring cannabinoids without adequate safety data or regulation, but it has allowed chemists to start with CBD and produce many other cannabinoids without safety data or regulation.  Immediately we have seen a flood of intoxicating chemicals like delta-8 THC, delta-10 THC, HHC (hexahydrocannabinol), and others.  There are an infinite number of chemicals that can be manufactured so regulating them individually is not feasible.

Safety of hemp products

It turns out that manufacturing cannabinoids, even from other cannabinoids, is nontrivial.  It requires using strong acids, heat, and other catalysts that are inherently dangerous and not easily purified away. 

Furthermore, these reactions produce all manner of byproducts, isomers, enantiomers, and side pathways.   Many of these chemicals are novel and all of them are untested for safety.  Since many of them have the same molecular weight as the intended product, it can be difficult to purify and requires analytic skills and tools that are not typically available in cannabis testing facilities. 

In other words, many hemp-derived products can have, and have been found to have, impurities that the manufacturer is unaware of. 

I had the fortune to work with two colleagues to do a highly technical review of these reactions and contaminants that was published in Cannabis and Cannabinoid Research here. 

Safety of synthetic cannabinoids

Contaminants are not the only problem.  The actual intended product is also a huge issue.  The assumption that cannabinoids are safe is clearly incorrect. 

Look at the lack of safety of synthetic cannabinoids of the K2/Spice variety that cause psychosis and severe self-injurious behavior.  Admittedly those cannabinoids have different structure than those being derived from hemp, but the point that cannabinoids can be dangerous stands.  As such, the novel cannabinoids that are being sold from hemp pose risk as they’ve largely not been studied. 

For example, hemp CBD is being converted to delta-8 THC.  Delta-8 THC (d8) is naturally occurring in cannabis, but at such low levels compared to delta-9 THC (d9) that d8 has never been studied on its own.  Given the vastly larger doses of d8 that people are taking when using a hemp-derived product (compared to what they would be ingesting from cannabis), it is not accurate to ascribe the safety of d9 to d8. 

Other cannabinoids being manufactured from hemp are fully new and not naturally occurring, like delta-10 THC or HHC which have no human safety data.  THC-O acetate, yet another molecule invented from hemp-CBD for intoxicating purposes, has been shown recently to convert to Ketene when vaped.  Ketene is a poisonous gas and has been associated with lung injury. 

Intoxication is not the right test

Right now regulators and politicians are getting around to addressing this unexpected, unregulated market.  However, they are focusing on the wrong aspect of the products – the intoxicating effects.  The intoxication caused by some of these cannabinoids is not the cause of the risk they pose.  The risk comes from the contamination that we discussed above and from the lack of safety data for the product itself.  I’m not worried about d10 because it causes people to get high, I’m worried about it because it could be toxic in some way that we haven’t investigated.   

However, this concern applies to many cannabinoids regardless of their origin.  For example, CBD.  Regardless of whether it is derived from cannabis, hemp, or synthesis, CBD has yet to be proven safe and useful in adult humans.  The GW data (for use of CBD in children with Dravet’s and Lennox-Gastuat Syndromes) are unassailable, but claims that CBD is good for pain, sleep, or anxiety have not been shown in people. 

Further, we do know that high doses of CBD (as have been necessary in the few studies that exist) can have drug interactions and direct liver toxicity.  CBD may well turn out to have good medical uses, though it may require medical monitoring like periodic liver function tests, but it has yet to be proven.  Until then, risk without benefit means it should not be used.

Other cannabinoids, intoxicating or non-intoxicating, like CBG, CBC, THC-V, and many others have even less data available than CBD.  Hence, we should not be regulating based on intoxication, but rather on safety. 

Safety First

Cannabinoids are just chemicals like any other.  They can be good for humans or bad.  Not all cannabinoids are the same as others.  Each must be evaluated for itself.  

Rather than ban all hemp-derived cannabinoids, a move that will typically lead to more misbehavior by industry and consumers, we should be shunting these chemicals into the same regulatory pathway that exists for cannabis products.  This will undermine the cost advantage that unregulated products have today and will either get them out of the market or conform them to the basic safety standards applicable to cannabis. 

Further, however, we should require better human safety data and efficacy data on all cannabinoids so that we can be sure that they are inherently safe and actually provide some benefit.