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by Roseann Vorce, Ph.D., 
Department of Pharmacology and Toxicology
Michigan State University 

In Florida, a naked man under the influence of “bath salts” is discovered eating the face of a homeless person, in a public place and in broad daylight.  A policeman’s bullet barely slowed him down, and he stopped only when killed by another bullet.  In Michigan, a young adult with an appetite for smoking “K2-Spice” recruited a friend to help him kill his family.  They bludgeoned the father to death and severely injured the mother and brother with baseball bats.  What the heck is going on?

The short answer is that a new category of psychoactive agents has appeared on the drug scene.  Dubbed “SLIDs” (Synthetic Legal Intoxicating Drugs) by a group at the Cleveland Clinic, these recreational pharmaceutical compounds generally are legal, easy to obtain, and relatively cheap, but they exert powerful effects on the central nervous system.  Use of SLIDs has been linked to many reports of behavior that can only be described as bizarre.  People under the influence of SLIDs experience a wide spectrum of effects, including hallucinations, delusions, seizures, hyperthermia, and cardiovascular crises.  Legislators are scrambling to make SLIDs illegal, and new legislation is being enacted around the country.

The subset of SLIDs known as bath salts were discussed in this forum earlier.  Today’s blog will introduce the synthetic cannabinoids, more commonly known as K2-Spice.

 Synthetic Cannabinoids

The synthetic cannabinoids comprise a group of related compounds that exert psychoactive effects similar to those produced by marijuana.  Known as K2, Spice, and many other names, these compounds often are sold as herbal incense in specialty shops and on the internet.  However, the synthetic cannabinoids are not found in nature, but are created in the laboratory and sprayed on various dried herbs.  The synthetic compounds are related to the primary psychoactive ingredient of marijuana, delta-9-tetrahydrocannabinol (THC).  THC is produced naturally by the hemp plant, Cannabis sativa, also known as marijuana.  When the leaves and buds of the hemp plant are smoked or ingested, THC is absorbed and produces the characteristic effects of the natural plant, including a sense of well-being and altered sensory perception.

The pharmacological effects of THC are mediated by cannabinoid receptors.  Because THC is only a partial agonist at the cannabinoid receptors, the effects of the natural compound are limited.  Regardless of the amount of THC absorbed, the receptors can never be fully activated by marijuana.  In contrast, the synthetic cannabinoids are full agonists, capable of producing effects that are much more intense than those of natural THC.  Unfortunately, the greater efficacy of the synthetic cannabinoids also causes more severe adverse effects.  Synthetic cannabinoids have been reported to cause dysphoria, agitation, anxiety, and paranoia, as well as adverse effects on the cardiovascular and nervous systems (elevated blood pressure, increased heart rate, psychosis, and seizures).  The severity of adverse effects caused by the synthetic cannabinoids is reflected in the increased incidence of emergency room visits and queries to poison control centers following use of these drugs.

Barriers to Legislative Action

The social and medical costs of SLIDs are substantial.  Legal loopholes have made it difficult to control the manufacture and distribution of these designer drugs.  Although SLIDs are very powerful drugs, they are not marketed as drugs and typically are labeled, “Not for human consumption.”  This deceptive practice has allowed the manufacturers and dealers of SLIDs to avoid regulation of their products.  Legislators have made some of these compounds illegal, but a simple re-design of the drug structure or preparation of a different salt allows manufacturers to skirt the law.  In addition, detection and quantification of SLIDs remains a challenge due to their structural diversity.  This situation has left analytic chemists scrambling to develop validated methods to analyze multiple chemical species simultaneously.

Recently, legislation was proposed in Michigan (Senate Bill 1082)  [signed into law 6/19/2012 by Gov. Rick Snyder] that will outlaw all derivates of synthetic cannabinoids, as well as variations of many other illicit drugs.  The bill was written to capture the predictable chemical changes that manufacturers are likely to make so that they can comply with current laws while continuing to supply SLIDs to consumers.  By using wording that covers a broad range of chemical entities, legislators hope to prevent manufacturers from continuously creating and selling new versions of illegal drugs.

In addition to Michigan, many other states have adopted or are considering legislation to outlaw derivatives of SLIDs.  Although legislation at the state level will not stop internet sales of SLIDs, it will keep K2-Spice, bath salts, and their pharmacological relatives out of local convenience and specialty stores.

References:
Jerry J, Collins G, and Streem D.  Synthetic legal intoxicating drugs:  the emerging “incense” and “bath salt” phenomenon (2012) Cleve Clin J Med. 79:258-64. http://www.ccjm.org/content/79/4/258.long

Cox AO, Daw RC, Mason MD, Grabenauer M, Pande PG, Davis KH, Wiley JL, Stout PR, Thomas BF, Huffman JW (2012) Use of SPME-HS-GC-MS for the Analysis of Herbal Products Containing Synthetic Cannabinoids. J Anal Toxicol 36:293-302.

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