Herbal Marijuana Alternatives
Herbal Marijuana Alternatives (HMAs) such as K2 or Spice are sold as alternatives to marijuana that provide similar clinical effects but are not detectable by the traditional marijuana screening methods. They are basically blends of herbs adulterated with synthetic cannabinoid compounds. These synthetic compounds were initially designed by pharmaceutical companies when searching for cannabinoid receptor agonists with the same analgesic and anti-inflammatory effects of tetrahydrocannabinol (THC), without the psychotropic effects. HMAs are typically sold on the internet or in head shops as incense products, bath products, air fresheners or meditation potpourri and are sold under such names as Spice, Spice Gold, Spice Diamond, K2, Silver, Aroma, Arctic Spice, Genie, Scene and Dream. They are most commonly smoked, but they can also be infused or inhaled. Although these products first emerged on the internet and in specialty shops beginning as early as 2004, it was only in 2008 that synthetic cannabinoids were officially identified as the active ingredients in “Spice,” a compound which had been marketed as an herbal blend. In early 2009, several European countries announced that any compounds containing these substances would fall under the Narcotics Law, making it illegal for them to be sold online and in head shops. That same year, the United Kingdom (UK) amended the Drugs Act of 1971 to list synthetic cannabinoids as controlled substances. However, rather than deterring sale and use of these substances, the ban only spurred development of new synthetic cannabinoid products, such as JWH-073, JWH-019, and JWH-250, among others. In March 2011, the United States Drug Enforcement Administration (DEA) ordered a temporary ban on five synthetic cannabinoids, including JWH-018, JWH-073, JWH-200, CP-47,497 and CP 47,497-C8.
The pharmacological effects of HMAs are likely from both the herbal ingredients and the added synthetic cannabinoids, although there is not much evidence or literature regarding the psychotropic effects of these herbs. Commonly used herbs in the HMAs include baybean, beach bean, blue lotus, dog rose/rosehip, lion’s ear/tail, wild dagger, etc. Other substances such as synthetic opioids, monoamine oxidase inhibitors, and oleamide, a fatty acid derivative with cannabinoid-like activity, have also been isolated in many Spice products. The synthetic psychoactive compounds found in many HMA products were initially foreign to most forensic laboratories and presented a challenge to identification and referencing of these materials. Detection of these drugs is further hindered by the variable, unpredictable makeup of each product, particularly as the products are modified in response to ever-changing legal restrictions.
The synthetic cannabinoids are not structurally similar to THC but they are agonists of the cannabinoid receptors (CB1 and CB2) and may even have some effect on other receptors as well including NMDA . It is thought that the euphoric effects of the drug are due to its agonist properties at the CB1 receptor. Though in vitro studies indicate that JWH-018 acts as a full agonist at the receptor, THC is a partial agonist. Furthermore, when compared to THC, JWH-018 has a more than fourfold higher affinity for the CB1 receptor and a 10-fold higher affinity to the CB2 receptor.
Due to the lack of medical literature and research regarding the HMAs, the clinical effects are primarily known from case reports and case series. In addition to the extensive assortment of ingredients found in synthetic cannabinoid products such as Spice, there is also a wide variation in the quantity of substances present, leading to a significant incidence of accidental overdoses requiring hospitalization. Psychiatric effects that have been reported include anxiety, paranoia, avoiding eye contact, agitation, delusions, and psychosis. Common side effects of HMA include tachycardia, diaphoresis, conjunctival injection, and dry mouth. Nonetheless, the desired effects of Spice blends are frequently described as euphoric. Anxiety is one of the main unwanted side effects of acute intoxication, while severe anxiety and depression have been reported during withdrawal. Interestingly, Spice and similar products do not contain cannabidiol, a component of cannabis which antagonizes CB1 and CB2 receptors and is thought to produce anxiolysis. Although there are limited data, several deaths that occurred after taking synthetic cannabinoid products, particularly K2, have been attributed to suicide and coronary ischemic events.
The synthetic cannabinoids are not detectable by current immunoassay lab tests for THC but are detectable by gas chromatography-mass spectrophotometry (GC-MS) lab testing. When product samples are obtained, the parent synthetic cannabinoid may be detected using GC-MS lab testing. However, the metabolites of the synthetic cannabinoids may be the only detectable compounds present in human blood or urine. These are detected with metabolite-based liquid chromatography-mass spectrometry (LC -MS) lab testing. Currently, commercial testing for synthetic cannabinoids in human samples of blood and urine, as well as HMA samples, is available from some commercial labs.
Any patient with unfavorable symptoms after an HMA exposure should be directed to an emergency room via ambulance as it is difficult to ascertain the exact drugs involved in an HMA exposure. A Regional Poison Control Center should be consulted. Acute management consists of supportive care with the use of benzodiazepines, if needed, for the control of agitation and anxiety. In general, all patients should be observed until the resolution of abnormal vital signs, vomiting, and psychiatric symptoms. It is important to note that the common symptoms described with HMAs such as agitation and tachycardia are not typical of those seen with marijuana exposure, making the diagnosis more difficult. Although there is no antidote for HMA exposure, there are agents being studied. CB1 antagonists, such as SR141716, have been found that may reverse the psychotropic effects of marijuana. Animal models have also shown that naltrexone may attenuate THC’s effects. These agents may become more relevant if the use of HMAs and synthetic cannabinoids continue to rise.