The 2018 Farm Bill Created an Unregulated Market for Potent Synthetic Cannabinoids Made From CBD | Research

The takeaway

The US 2018 Farm Bill inadvertently enabled a growing market for CBD-derived synthetic cannabinoids, including potent compounds with unknown safety profiles and acetate esters linked to vaping lung injuries.

Drug policy makers and regulators; public health officials; consumers of CBD-derived products.

Novel CBD-derived cannabinoids reportedly have greater CB1 agonist activity than delta-9-THC

What the researchers found

The CBD-derived cannabinoid market has expanded from delta-8-THC to include potent synthetic cannabinoids with greater agonist activity at CB1 receptors than delta-9-THC. The acetate ester motif (linked to EVALI vaping lung injuries) has been incorporated into multiple THC analogues. Products contain under-researched reaction side products from manufacturing. Regulatory oversight is virtually nonexistent.

Why it matters

Millions of Americans are consuming CBD-derived cannabinoids that may be more potent than THC, contain unknown reaction byproducts, and include chemical structures linked to serious lung injuries. This represents a regulatory blind spot created by the Farm Bill's hemp legalization that could become a public health crisis.

The numbers in context

Delta-8-THC was the first widely marketed product. Novel cannabinoids now include sidechain variants with purportedly greater CB1 agonist activity than delta-9-THC. The acetate ester motif (implicated in EVALI) is being incorporated into multiple THC analogues. Production uses fully synthetic routes rather than simple isomerization.

How the study worked

Narrative review summarizing current scientific knowledge on psychoactive cannabinoids synthesized from CBD, including delta-8-THC, O-acetyl-THC, and novel sidechain variants. Reviews manufacturing processes, regulatory gaps, epidemiological findings, and pharmacological concerns.

What this study cannot tell us

The review relies on limited available research, as most CBD-derived cannabinoids have never been formally studied. Market composition changes rapidly, potentially outpacing the review. The actual prevalence of adverse events may be substantially underreported.

How to read the evidence

Moderate: timely review synthesizing available evidence on an emerging public health concern, but limited by the scarcity of formal pharmacological studies on these novel compounds.

When this study was published

2024 review.

The bigger picture

The trajectory mirrors previous substance crises. Like bath salts and synthetic cannabinoids (K2/Spice) before them, CBD-derived products exploit regulatory gaps to sell psychoactive substances as "legal" alternatives. The key difference is scale: CBD-derived cannabinoids are sold in mainstream retail settings to consumers who may not realize they are using untested synthetic drugs.

Questions still open

How many consumers realize they are using synthetic cannabinoids rather than natural cannabis derivatives? Would DEA scheduling of specific CBD-derived compounds address the market, or would manufacturers simply shift to new analogues?

Common questions

What are CBD-derived cannabinoids?

They are psychoactive compounds chemically synthesized from CBD (cannabidiol) extracted from legal hemp. Delta-8-THC was the first, but the market now includes many novel synthetic cannabinoids created through chemical modification of CBD, some potentially more potent than natural THC.

Why is the acetate ester a concern?

Vitamin E acetate, a similar acetate compound, was identified as the primary cause of the 2019 EVALI vaping lung injury outbreak. The incorporation of acetate ester structures into THC analogues raises concerns about similar pulmonary toxicity when these products are vaped.

Read the original research

Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill.

Medical cannabis and cannabinoids, 7(1), 10-18

View on PubMed ↗Publisher’s paper ↗

Citation

Zawatsky, Charles N; Mills-Huffnagle, Sara; Augusto, Corinne M; Vrana, Kent E; Nyland, Jennifer E. (2024). Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill.. Medical cannabis and cannabinoids, 7(1), 10-18. https://doi.org/10.1159/000536339