Emergence of Synthetic Drugs Novel classes of synthetic drugs, including synthetic cathinones or “bath salts,” have recently emerged as popular drugs of abuse. Recreational users have turned to synthetic drugs for a number of reasons. The easy availability of the product has certainly contributed. That the legality of synthetic substances had not, until recently, been established made consumers think that they could get “legal highs” without the risk of prosecution. Furthermore, commonly used blood and urine drug screens are not yet routinely available for synthetic drugs, making them more difficult to detect in an intoxicated individual or someone who must undergo drug testing.

Another reason for the popularity of synthetic drugs has been the relative affordability of these substances, particularly when compared to their illegal counterparts. Marketing the products as “bath salts” or “plant food” may provide users with false reassurance about the safety of these products. Finally, the purity of synthetic cathinones and cannabinoids has been shown to be preferred to their natural alternatives, such as cocaine, ecstasy, and marijuana, which have become increasingly impure in recent years.

Synthetic Cathinones

In 2009 and 2010 the abuse of synthetic cathinones became a concern in western Europe, and these substances first appeared in the United States in 2010. Poison control centers in the U.S. began to receive calls regarding bath salts in December of 2010. There was a drastic increase in bath salt usage in 2011 due to the widespread availability and media sensation surrounding these substances. Fortunately, this specific trend seems to have peaked in 2011.

Cathinones are compounds naturally present in the leaves and stems of the khat plant, which is a slow-growing shrub native to Ethiopia and cultivated in East Africa and the Southwest Arabian Peninsula. The practice of chewing the leaves of this plant for its psychostimulant and euphoric effects has been known in these parts of the world for hundreds of years. Today, chewing the leaves for stimulant purposes is popular in certain Middle Eastern countries, particularly Yemen. In 2006, there were an estimated 10 million daily khat users worldwide.

Like amphetamines, cathinone is a central nervous system stimulant, but its potency is less. Clinical data have shown that it can cause an increase in heart rate and blood pressure, euphoria, alertness, and psychomotor hyperactivity. Several studies have illustrated the negative effects of khat chewing, however, which include hypertension, myocardial infarction, gastritis, liver toxicity, insomnia, depression, anorexia, psychosis, impaired memory, and a withdrawal syndrome. In an effort to mimic the positive properties of cathinone while diminishing the adverse side effects, chemists have made minor alterations to the chemical make-up of khat to produce synthetic cathinones.

Synthetic cathinones have been sold over the Internet and at gas stations, convenience stores, and smoke shops. To circumvent drug abuse legislation they have been labeled as “not for human consumption” and sold as bath salts, plant food, and various other pseudonyms. Most commonly called bath salts, these substances have a variety of other street names, including: Bloom, Blue Silk, Charge+, Hurricane Charlie, Ivory Snow, Ivory Wave, Lunar Wave, Ocean Burst, Ocean Snow, Pure Ivory, Purple Wave, Red Dove, Scarface, Sextacy, Snow Leopard, Stardust, Vanilla Sky, White Dove, White Knight, White Lightning, White Rush, and Zoom.

It is noteworthy that although the peak incidence of synthetic cathinone use has been seen in 20-29 year olds, American poison control centers have received reports of exposure in children as young as 6 years old. Synthetic cathinones are most commonly nasally insufflated (snorted) or ingested. Less common methods of use include rectal or gingival administration, inhalation, and intramuscular or intravenous injection. Often several routes of administration are used concomitantly in a single session.

Although investigation of most deaths associated with synthetic cathinones has revealed multiple drugs of abuse, intoxication with these substances alone can cause significant problems. The most common clinical manifestations resulting from synthetic cathinone abuse include agitation, confusion, psychosis, tachycardia, and hypertension. Other commonly reported symptoms are chest pain, palpitations, fever, hyperthermia, nausea, vomiting, diaphoresis, abdominal pain, dyspnea, headache, and seizures.

The legal status of synthetic drugs is variable by country and has been undergoing rapid change. On September 21, 2011, the Drug Enforcement Administration (DEA) used its emergency scheduling authority to enact temporary control over synthetic cathinones in the U.S. The three most prevalent synthetic cathinones-mephedrone, MDPV, and methylone-were placed under Schedule I of the Controlled Substances Act, meaning that they were determined to have no accepted medical use in the U.S. and a high potential for abuse. Possession of these substances thus became illegal.

Due to chemists’ ability to rapidly alter the molecular components of synthetic cathinones, thereby creating new and different drugs, control of these substances remained difficult. On July 9, 2012, President Obama signed into law the Synthetic Drug Abuse Prevention Act of 2012 as part of Senate Bill 3187, the Food and Drug Administration Safety and Innovation Act. This act “amends the Controlled Substances Act to add as a Schedule I controlled substance: (1) any material, compound, mixture, or preparation which contains specified cannabimimetic agents (or the salts, isomers, or salts of isomers thereof); and (2) specified additional hallucinogenic substances.” This verbiage was selected in an attempt to broaden the spectrum of substances classified under Schedule I, and to prevent minor alterations in molecular makeup from allowing the drugs to maintain legality. This Bill has likely played a major role in the decrease in synthetic cathinone abuse since 2011.

Synthetic Cannabinoids

Although they have garnered the most media attention, synthetic cathinones are not the only manufactured substances that have seen a recent increase in use. Synthetic cannabinoids, or herbal marijuana alternatives, most commonly labeled as “Spice” or “K2,” began emerging as drugs of abuse in the U.S. in 2008. Commonly marketed as incense or potpourri, they were similarly labeled “not for human consumption” to bypass legislation. Many of these herbal mixtures do not have ingredients listed on the packaging. Constituents that are often listed are plant/herbal ingredients such as Baybean, Blue Lotus, Dwarf Scullcap, Honey, Indian Warrior, Lion’s Tail, Lousewart, Maconha Brava, Marshmallow, Pink Lotus, Red Clover, Rose, Siberian Motherwort, and Vanilla.

When smoked, these products produce effects similar to those of cannabis found in marijuana, but when analyzed they have not been found to contain tobacco or cannabis. In December of 2008 it was determined that these effects were not entirely the result of herbal components, but that synthetic cannabinoid derivatives comprised part of these mixtures and likely accounted for much of their psychoactive effects.

Some common street names for these synthetic cannabinoid-containing herbal marijuana alternatives other than Spice and K2 include: Albino Rhino Buds, Aroma, Barely Legal, Black Mamba, Bliss, Damiana, Drolle, Exclusive Cherry, Exclusive Mint, Galaxy, Genie, Gorilla, Halo, K2 Summit, Krypto Buds, Red Magic, Sence, Skunk, Solar Flare, Space, Spice Diamond, Spice Gold, Spice Silver, Star Fire, Tai Fun, Yucatan Fire, Zohai, and many more.

As was seen with the synthetic cathinone epidemic, synthetic cannabinoids were easily accessed and sold via the Internet, as well as at gas stations, convenience stores, liquor stores, and head shops. In 2009 the cost was significantly cheaper than marijuana, at approximately $40 per three-gram packet. Users of synthetic cannabinoids generally seek “legal highs” and effects similar to those experienced by smoking marijuana, such as euphoria and relaxation.

The primary active ingredient in marijuana is tetrahydrocannabinol (THC), which binds to cannabinoid receptors in the body. Importantly, synthetic cannabinoids have demonstrated a higher binding affinity for cannabinoid receptors than THC. As a result, they are more potent than THC and psychoactive doses may be very low. Furthermore, while natural THC will exhibit a plateau in terms of dose versus clinical response, synthetic cannabinoids have no ceiling on the dose-response relationship and therefore a greater potential for overdose and toxic effects. Thus, users of synthetic cannabinoids frequently require medical attention.

The most commonly reported side effects are tachycardia, agitation, irritability, anxiety, hallucinations, nausea, vomiting, hypertension, confusion, conjunctival injection (red eyes), and xerostomia (dry mouth). More severe complications that have been reported include seizures, psychosis, and cardiac arrhythmias. As there is no known pharmacologically specific antidote, the management of synthetic cathinone toxicity is supportive care and symptom control. Synthetic cannabinoids are not detected on common toxicological screens that identify THC metabolites. As a result, these tests are of minimal help to the clinician managing a patient with synthetic cannabinoid intoxication or overdose.

Similar to synthetic cathinones, data shows that the peak incidence of synthetic cannabinoid use may have passed. Again, 2011 marked the highest usage according to calls made to American poison control centers. Studies have shown that adolescents comprise a large part of the synthetic cannabinoid-using population. A report of telephone calls made to Texas poison control centers concerning synthetic cannabinoids in 2010 showed that 40.2% of users were less than twenty years old. Furthermore, data submitted to the DEA from a major toxicology laboratory indicated that 30-35% of the samples from juvenile probation centers from July to November of 2010 tested positive for synthetic cannabinoids.

As discussed above, currently all synthetic cannabinoid derivatives fall under the same illegal category as synthetic cathinones, as specified in the Food and Drug Administration Safety and Innovation Act passed by the U.S. Senate and House of Representatives. This, in addition to more widespread knowledge about the risks and adverse side effects of these substances, may help slow the epidemic of synthetic drug abuse.

Conclusions

Although there is evidence to suggest that the peak incidence of synthetic cathinones and cannabinoids has already passed, recent epidemics show us that new emerging toxins will likely pose a public health risk in the future. Relative affordability, easy access, unclear legal status, difficult detectability, and lack of evidence about the dangers of these substances make them attractive for experimentation by adolescents. In addition, diagnostic laboratory studies tend to lag behind these epidemics. It is vital for the clinician to maintain both a basic fund of knowledge and a high index of suspicion when facing clinical toxidromes in order to manage and monitor patients suspected of intoxication with synthetic cathinones, synthetic cannabinoids, and future emerging toxins.

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From issue: 29/09-10