Natural, Semisynthetic and Synthetic Cannabinoids

Urgent first

Synthetic cannabinoid products sold as "K2" or "Spice" are linked to severe and sometimes life-threatening illness. [1] If someone has a serious reaction, FDA advises calling 9-1-1 or going to the nearest emergency room. [2] In the US you can also call Poison Help at 1-800-222-1222. See Poison Help by country.

Three categories

This page explains the categories. It does not describe how any compound is made.

Natural cannabinoids

The plant contains at least 125 cannabinoids according to NIDA, [3] but most occur only in small amounts. Natural does not mean safe or well studied. See Cannabinoids Explained for the plant family.

Semisynthetic cannabinoids

A review of hexahydrocannabinol (HHC) says that semisynthetic cannabinoids made from hemp extracts appeared as recreational drugs after US hemp legislation changes, with hemp-derived CBD becoming a starting material for compounds such as HHC, which appeared on the drug market in 2021. [4] FDA says delta-8 THC is not found in significant amounts in the plant, so concentrated amounts are typically manufactured from hemp-derived CBD. [2] FDA notes that this process can leave harmful by-products and that products may contain other cannabinoids and variable concentrations. [2]

What is known and unknown:

• Known. The European Union Drugs Agency authors report that semisynthetic cannabinoids mimic the effects of delta-9 THC, and that over 30 compounds are now monitored in Europe. [5] Reported products are often mislabeled and can contain undeclared substances or contaminants. [5]
• Unknown. Little is known about the pharmacology, toxicology, metabolism and long-term effects of most of them. [5] For HHC, preclinical studies indicate THC-like properties and human pharmacology is yet to be investigated. [4]
• Reported harm. A hospital case report describes severe sedation, low blood pressure and abnormal heart rate after a man ingested HHC and HHC-P mixed in food; the authors say amounts in illegal products can be high. [7] A single case cannot show how often this happens.

NIDA says there is limited research on delta-8 THC, delta-10 THC, THC-O-acetate, THCP, HHC and HHC-O-acetate. [3] Each has its own page: Delta-8 THC, Delta-10 THC, HHC, THCP and Cannabinoid Acetates. We do not treat marketed amounts as safe or as established human safety data.

Fully synthetic cannabinoids

NIDA describes synthetic cannabinoids as lab-made substances chemically similar to compounds in the cannabis plant, though they often produce very different effects. [1] Illicitly made versions are typically added to vaping cartridges or sprayed onto dried plant material, and are sometimes called K2 or Spice. [1] NIDA says people have used them partly because they are mostly undetected by routine urine drug screens. [1]

A 2023 systematic review of 64 reports found synthetic cannabinoids may be more toxic than THC and longer-lasting. It identified tachycardia and seizures as the most common toxicity symptoms, and 14 studies reported deaths. [8] The reviewers specifically flag higher risk for people with epilepsy or schizophrenia. [8] Evidence label: evidence of harm for illicit Spice/K2 products.

Not every synthetic cannabinoid is a street drug. FDA has approved dronabinol (a synthetic form of delta-9 THC) and nabilone (structurally similar to THC) as prescription medicines. [6] NIDA also notes some synthetic cannabinoids have current or potential medical uses. [1] Prescription results do not carry over to consumer products. See Cannabis Medicines vs Consumer Products.

Why the categories matter for consumers

• A "hemp-derived" label does not tell you whether a compound is natural. FDA notes some delta-8 products are labeled simply as "hemp products," which may mislead consumers. [2]
• Laws treat these compounds differently and change quickly. See Intoxicating Hemp-Derived Products in Law. This is not legal advice.
• A product's contents may not match its label. See Adulterated and Mislabeled Cannabinoid Products.