The term Designer Drug was first used by law enforcement during the 1980s to denote synthetic opioids (e.g. fentanyl and meperidine derivatives sold as China White heroin) and synthetic psychostimulants (e.g. methylenedioxymethamphetamine or Ecstasy and bromodimethoxyphenylethylamine or Nexus) that began to flood into the illicit drug market.1-3 When these Designer Drugs first appeared on the streets many were quasi-legal because no laws banned their specific chemical structures. The definition of a Designer Drug thus came to be:
A psychoactive drug deliberately synthesized or marketed to avoid anti-drug laws or mimic the effects of a banned substance usually by modifying the molecular structures of existing drugs to varying degrees or by creating entirely different chemical structures to produce effects similar to banned psychoactive substances.4
In 2007, the term Designer Marijuana loosely extended the definition of a Designer Drug to include varieties of the marijuana plant that were usually grown indoors often using hydroponics from specially bred strains. These plants were also carefully handled during their growth and manipulated to produce maximum quality and THC concentrations.5 So as not to confuse designer plants with designer drugs, I will use the term Designer Cannabinoids to describe the recent growth of synthetic cannabinoid-like chemicals being sold as incense or herbal smoking blends on the internet and at head shops under a variety of trade names like Spice Gold®, Spice Silver®, Spice Diamond®, Buddha Melt or Blend®, Yucatan Fire®, Genie®, Smoke®, and Skunk®.6 These products were first sold in Europe and Canada around 2002. Those who smoked the various Spice® incense products claimed that they produced marijuana-like effects and seemed about four times stronger than marijuana. Prior to 2008, laboratory analysis of the substances contained in the Spice® product packets could detect no abused drug or chemical responsible for their alleged effects. This led one expert to suggest that users were simply experiencing a placebo effect from the incense. However, these analyses also failed to detect any of the alleged herbs listed on the packet labels raising suspicion that these products may actually contain unknown chemicals that produced effects similar to those produced by cannabinoids found in marijuana. In December 2008, THC Pharm, a German pharmaceutical firm developing synthetic THC compounds for medicinal uses, announced that they had discovered a synthetic cannabinoid, JWH-018 in three versions of Spice® herbal smoking blends.6,7 The University of Freiburg in Germany discovered a second synthetic cannabinoid, CP 47,497 along with three of its homolog chemicals in a variety of Spice® incense products about a month later. Varying concentrations and ratios of these two synthetic cannabinoids are responsible for the psychoactive effects of the many different Spice® products that are commercially available.8
To check the validity of these reports, I accessed the U.S. Drug Enforcement Administrations (DEA) Drugs and Chemicals of Concern website. I was surprised to find that the DEA actually listed 3 additional synthetic cannabinoids that have been found in various Spice® products recently seized by customs officials. These are the Designer Cannabinoids: HU-210, HU-211, and JWH-073.7,9 The naming of these synthetic chemicals appear to follow the convention of using the discoverers initial and the number of the particular synthesis that created it. For instance JWH-018 comes from John W. Huffman who first created the molecule. On January 22, 2009 CP 47,497 and its homologues along with JWH-018 and its homologues were added to the schedule of controlled drugs in Germany. Several other countries have now made these molecules as well as other Designer Cannabinoids illegal. The U.S. has not yet added these chemicals to its list of controlled substances because they are not considered to be structural or positional isomers of any controlled substance.8,10 However, since Designer Cannabinoids produce effects similar to those of the marijuana plant cannabinoids which are illegal, they may fall under the Federal Analog Act of 1986. This section of the U.S. Controlled Substances Act makes any chemical that produces substantially similar effects as a Schedule I or II drug to also be treated as a Schedule I or II drug if the chemical is intended for human consumption.11 The Designer Cannabinoids sold as herbal smoking blend products seem to meet the controlled substance designation of the Analog Act since they are intended for human consumption. But, those products sold as incense often come with specific labels warning the purchaser not to consume or smoke it so the incense products may not come under the Analogue Act. The government will have to prove that Spice® intended to sell their incense products for consumption rather than aroma in order to designate those materials as illegal substances.
The ability of pharmaceutical chemists to produce synthetic molecules that mimic the effects of more complex compounds found in plants and animals plays a major role in the development of medicines. This relies on the traditional practice of making slight modifications to a parent molecule and probing the biological effects that result from the modification. Results are used to formulate a Structure-Activity Relationship (SAR) of parent molecule to determine the essential atoms and the spatial relationships needed to produce a desired effect.12 The opioid pain medications methadone and Darvon® were created by studying the SAR of the morphine molecule. The chemical structures of these synthetic opioids are radically different from that of morphine and other opiates found in the opium poppy. However, they still retain the same effects of opiates because their SAR retains the essential parts of the morphine molecule needed to produce the desired analgesic effect. It appears that this SAR technology was used to create a number of new Designer Cannabinoids that can produce the same or even more powerful effects as those produced by the cannabinoid molecules found in a marijuana plant. Since these Designer Cannabinoids have molecular structures that are very different from the 66 cannabinoids isolated from the marijuana plant, it seems unlikely that they would test positive for THC or the THC metabolites usually identified by traditional drug testing methods. Various forum entries on this issue posted on internet sites seem to confirm that those who smoke Spice® and the other incenses or herbal smoking blends containing designer cannabinoids are not testing positive for marijuana use. Still, much research is needed to confirm that the Designer Cannabinoids will not test positive for marijuana abuse.
More importantly, even more research is needed to determine if any potential health or addiction risks occur from the use of these synthetic chemicals. Pharmaceutical chemists have documented a phenomenon known as a SAR Paradox whereby a small change in a molecule results in unexpected changes in the pharmacologic actions produced by that molecule. This can consist of greatly increasing or decreasing the potency of a substance or can result in a molecule with totally different pharmaceutical effects altogether.12 This raises other concerns about the recent growth of Designer Cannabinoid abuse because it is unlikely that any of the products, including those in current use, will ever be clinically tested for safety or efficacy, a government requirement of any substance before it can be made available for human consumption.
P.S. On July 10, 2009 the first medical case report on Spice Gold® dependence documenting a definitive withdrawal phenomena was published by physicians working at the Dresden Technical University in Germany.13 A 20 year old male reported steadily increasing his smoking of Spice Gold® to 3g per day over a period of 8 month. After 2 days of hospitalization this young man began to experience inner unrest, drug craving, nocturnal nightmares, profuse sweating, nausea, tremor, headache, increased blood pressure, insomnia, and increased heart rate. The patient stated that he had experienced symptoms upon abrupt cessation of smoking Spice® a few weeks prior to being admitted to the hospital which was quickly abated by resuming intake of the substance. This was clear evidence to him and his physicians that he was experiencing a withdrawal syndrome from smoking this substance. The patient was treated over 18 days in the hospital with several symptomatic medications. During his hospitalization, the patients withdrawal symptoms peaked in severity on days 4 to 7 of abstinence and fully resolved with treatment after 18 days of hospital care.
Darryl S. Inaba, PharmD., CADC III
July 2009
References
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9. Drug Enforcement Administration Office of Diversion Control (2009), Drug and Chemicals of Concern: Spice Cannabinoid, http://www.deadiversion.usdoj.gov/drugs_concern/index.html accessed 7/2/09 accessed 6/12/09
10. Drug Forum (2009), Spice Cannabinoid, http://www.deadiversion.usdoj.gov/drugs_concern/spice/index.html accessed 6/12/09 accessed 7/11/09
11. Public Law 99-570 Subtitle E Controlled Substance Analogue Enforcement Act of 1986, http://www.brockport.edu/~govdoc/SocPol/pl99570.pdf accessed 7/11/09
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