Over the past year, it has been hard to avoid news reports involving people getting high on “bath salts” and “incense” (also known as “Spice” or “K2”). Addiction treatment professionals have been overwhelmed by questions regarding why one would want to “snort bath salts” or “smoke incense.”
These substances are not what they appear to be. They are sold as bath salts and incense and are labeled “not for human consumption” simply to avoid regulation by the US Food and Drug Administration (FDA). In reality, they are powerful psychoactive drugs, with effects that mimic those of more commonly abused drugs such as amphetamines and marijuana. Until recently, they were legally available over the counter at quick-marts, head shops, and on the Internet. Because they are relatively new, they may not be detectable on routine urine drug screens, and users may be unaware of the specific chemicals contained in them.
These drugs, which we have collectively termed synthetic legal intoxicating drugs (SLIDs), are increasing dramatically in use.1–3 A survey of youths at a rave party indicated that 21% had used one of them on at least one occasion.4 The general impression held by the drug-using public is that SLIDs are relatively cheap, are not detected on standard urine drug screens, can produce a powerful high, and, until recently, were readily available through legitimate sources.
Physicians need to be aware of SLIDs in order to recognize and manage the intoxication syndromes associated with these substances when encountered in clinical practice, and in order to educate patients about their potential dangers.
SYNTHETIC CANNABINOIDS MARKETED AS INCENSE
Herbal incense products that could be smoked as an alternative to marijuana started appearing on the Internet in Europe in 2004. By 2008, when such products first appeared in the United States, their use in Europe was already widespread.
Initially, consumers were led to believe that such herbal smoking blends were safe, legal alternatives to marijuana, and that it was the proprietary blend of herbs that was responsible for the “natural” high. Spice, a specific brand name, was originally trademarked in England as incense and also as an herbal smoking product.5
Legal authorities, however, suspected that these herbal blends were adulterated with synthetic substances. In December 2008, the first such substance was found when Austrian authorities isolated a synthetic cannabinoid, JWH-018, from an herbal incense product.6 By the end of 2009, five other synthetic cannabinoids—CP-47,497, HU-210, JWH-073, JWH-250, and JWH-398—had been isolated from various herbal incense samples around the world.7
The synthetic cannabinoids in herbal incense products are not derived from the hemp plant (Cannabis sativa), but are synthesized in laboratories and are formulated to interact with the endogenous cannabinoid receptors in the brain to produce psychoactive effects.
Synthetic cannabinoids are full agonists; natural THC is only a partial agonist
Two types of cannabinoid receptors have been discovered in humans: CB1 and CB2. Both types are found in the central nervous system, and CB2 is also found extensively in the periphery. CB1 is the receptor responsible for the psychoactive effects of cannabinoids, including altered consciousness, euphoria, relaxation, perceptual disturbances, intensified sensory experiences, cognitive impairment, and increased reaction time.6 The physiologic role of CB2 remains uncertain.
The major psychoactive cannabinoid in naturally occurring marijuana is delta-9-tetrahydrocannabinol (THC). The so-called classic cannabinoids, such as HU-210, are analogues of THC and are based on its chemical structure. The rest of the synthetic cannabinoids commonly found in incense products differ in chemical structure from naturally occurring cannabinoids such as THC, but have activity at the CB1 receptor and are thus psychoactive.
Of clinical relevance is that THC is only a partial agonist at the CB1 receptor, while all synthetic cannabinoids commonly found in incense products are full agonists at CB1.7 This difference is important because partial agonists bind to receptors but stimulate them only partially and therefore exhibit a plateau effect in terms of dose vs clinical response. In contrast, full agonists have no ceiling on the dose-response relationship and therefore have a greater potential for overdose and severe toxic effects.
Despite uncertainties, use is widespread
Most of the synthetic cannabinoids in herbal incense products were developed for research purposes, and there are almost no reliable scientific data on their effects in humans. Of additional concern is that no research has been conducted on their pyrolytic effects, ie, how these chemicals are transformed when they are burned, such as when consumers smoke them. Furthermore, herbal incense products often vary in their active substances and concentrations, so consumers really do not know what they are getting.
Despite the many uncertainties, the use of these products is widespread. Data submitted to the US Drug Enforcement Administration (DEA) from a major toxicology laboratory indicated that from July through November of 2010, 3,700 samples tested positive for either JWH-018 or JWH-073. This report also indicated that 30% to 35% of specimens submitted by juvenile probation departments were positive for synthetic cannabinoids.8