Fall 2010 Newsletter

 

Up in Smoke: Synthetic Cannabinoids

Recently synthetic cannabinoids such as K-2 or “Spice” have become illegal in many states. With law enforcement ready to crack down, Chemir has seen many samples come through to determine if these products will be able to stay on the market.

Background
In 2010, a number of states have decided to make synthetic cannabinoids illegal in their state due to public health concerns. Currently JWH-018 is illegal in Alabama, Arkansas, Georgia, Kansas, Kentucky, Louisiana, North Dakota, and Tennessee. JWH-073 is illegal in Alabama, Arkansas, Kansas, Kentucky, Louisiana, North Dakota, and Tennessee. CP 47,497 and its homologues are illegal in Louisiana and North Dakota. CP 47,497 is illegal in Kansas. HU-211 is illegal in North Dakota and Tennessee. HU-210 is illegal under state statutes in Alabama, Georgia, Kansas, Kentucky, Louisiana, North Dakota, and Tennessee.

Missouri has become the latest state to ban products containing synthetic cannabinoids. A bill was signed making synthetic cannabinoids and products containing them controlled substances. The law went into effect August 28, 2010. Similar legislation has been proposed in several other states, including Florida, Illinois, and New York.

Since these laws have passed Chemir has received multiple samples from companies across the country distributing synthetic cannabinoids. Many of the clients are testing their products to check for the soon-to-be illegal compounds. The charge for possession of an illegal substance is a misdemeanor in most states.

History
Synthetic cannabinoids are functionally similar to Δ9-tetrahydrocannabinol (THC), the active ingredient of marijuana (cannabis). Like THC, they bind to the same cannabinoid receptors in the brain and other organs as the endogenous ligand anandamide. Synthetic cannabinoids were initially created by John W. Huffman, an organic chemist studying in South Carolina. They were designed as cannabinoid receptor agonists for the treatment of pain. However, it proved difficult to separate the desired properties from unwanted psychoactive effects.

Products under the names such as “K2” and “Spice” have been shown to contain the synthetic cannabinoid JWH-018. JWH-018 is a synthetic cannabinoid agonist without the classical cannabinoid chemical structure. It has been used in scientific research as a tool to study the cannabinoid system.

“K2”, “Spice”, and similar products began appearing in Europe in 2006 and started showing up in the United States approximately two years ago. These are now banned in most European countries, but not exclusively in the United States, although the DEA has labeled CP 47,497 and homologues, HU-211, JWH-018, and JWH-073 all as “drugs of concern.” HU-210 is a schedule I controlled substance by federal statutes.

Although often referred to as synthetic cannabinoids, many of the substances are not structurally related to the so-called “classical” cannabinoids, specifically, Δ9-THC. The cannabinoid receptor agonists form a diverse group, but most are lipid-soluble and non-polar, and consist of 22 to 26 carbon atoms. A common structural feature is a side chain, where optimal activity requires more than four and up to nine saturated carbon atoms. The table below lists some of the more common synthetic cannabinoids but is not a complete listing. Synthetic cannabinoids fall into seven major structural groups:

1. Naphthoylindoles

Compound

R1

R2

R3

R4

JWH-018

C5H11

H

H

H

JWH-019

C6H13

H

H

H

JWH-073

C4H9

H

H

H

JWH-081

C5H11

H

-OCH3

H

2. Naphthylmethylindoles

Compound

R1

R2

R3

Unknown

N/A

N/A

N/A

3. Naphthoylpyrroles

Compound

R1

R2

Unknown

N/A

N/A

4. Naphthylmethylindenes

Compound

R1

R2

Unknown

N/A

N/A

5. Phenylacetylindoles

Compound

R1

R2

R3

JWH-250

C5H11

H

-OCH3

6. Cyclohexylphenols

Compound

R1

R2

CP 47,497

C­9H19

H

CP 47,497 (dimethyloctyl homologue)

C­10H21

H

 

7. Classical Cannabinoids

Δ9-THC

HU-210

HU-211


Other cannabinoid receptor agonists include substances such as oleamide and methanandamide, both of which are structurally related to anandamide.

In the pure state these substances are either solids or oils. Smoking mixtures are usually sold in metal-foil sachets, typically containing a small amount of dried plant material to which one or more of the cannabinoids have been added. Presumably, a solution of the cannabinoids has been sprayed onto the herbal mixture.

Case Study
Chemir recently received four samples containing what was purported as incense/herbal blends. Each of these samples contained a small amount of aromatic plant material. These samples were submitted to Chemir for quantitative analysis of any synthetic cannabinoids detected. The cannabinoids are readily resolved using gas chromatography, but their identification and quantitative analysis is limited by the availability of pure reference samples.

Analysis of extracts by Gas Chromatography/Mass Spectrometry (GC/MS) indicated the presence of JWH-018 and JWH-081 in the Sample A. JWH-019 and JWH-250 were detected in the Sample B. JWH-018 was also detected in both Sample C and Sample D.

In this case our client received the results and now has to formulate new products that meet the legislative standards or move their business to a different state.

References
1. "Chemical Class - Cannabinoids". Cayman Chemical. 4 August 2010 http://www.caymanchem.com/app/template/productQualifiers%2CProductQualifier.vm/productqualifier/cannabinoids/a/z

2. "Drugs and Chemicals of Concern". U.S. Department of Justice Drug Enforcement Administration. 5 August 2010 http://www.deadiversion.usdoj.gov/drugs_concern/spice

3. "Drug profile: Synthetic cannabinoids and 'Spice'". European Monitoring Center for Drugs and Drug Addiction. 2 August 2010 http://www.emcdda.europa.eu/publications/drug-profiles/synthetic-cannabinoids

4. Smith, Phillip. "Synthetic Cannabinoids". Stop the Drug War.org. 2 August 2010 http://stopthedrugwar.org/topics/drug_war_issues/specific_drugs/synthetic_cannabinoids

 

 

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