Synthetic Cannabinoid-Induced Psychosis: Two Adolescent Cases

To the Editor:

W hen used appropriately, marijuana and its structurally analogous derivatives have medicinal properties that humans have exploited for centuries. Unfortunately, Δ9-THC-based drugs beget both therapeutic and undesirable psychotropic actions by activating CB1 cannabinoid receptors (CB1Rs) in the central nervous system (CNS), which can potentially lead to psychotic symptoms. K2, also called Spice, is an emerging drug of abuse that is advertised as “legal marijuana.” Although it is structurally distinct from Δ9-THC, the synthetic cannabinoid compounds in K2 products are derivatives of the well-characterized aminoalkylindole (AAI) class of ligands that also bind and activate CB1Rs (Huffman and Duncan 1997; Huffman et al. 2003, 2005; Seely et al. 2011). Synthetic cannabinoid compounds were initially developed by some pharmaceutical industries and academic laboratories >40 years ago, as possible pharmaceutical agents for the treatment of debilitating pain. It was difficult, however, to separate the therapeutic properties from the unwanted psychoactive effects. In recent years, synthetic cannabinoids compounds are sprayed on “herbal incense” for the purpose of achieving intoxication from smoking; this is similar to, and in most cases more potent than, cannabis (EMCDDA 2009; Nutt 2009). Reported here are two adolescent cases of synthetic cannabinoid-induced psychosis.

Case Presentations

Discussion

Products containing synthetic cannabinoids are marketed as “exotic herbal incense’’ that exudes a rich aroma. Some of the product labels indicate, “not for human consumption,” but when smoked, these products have been reported by some users to have psychological effects similar to those of cannabis. There are numbers of these products marketed under different street names; commonly called K2 or Spice (EMCDDA 2009; Castellanos et al. 2011). The list of “exotic herbal incense” containing synthetic cannabinoids is long but not exhaustive. The “herbal products” by names include, but are not limited to: Spice Smoke Blend, Spice Silver, Spice Gold, Spice Diamond, Spice Arctic Synergy, Spice Tropical Synergy, and Spice Egypt. There are many other herbal preparations containing synthetic cannabinoids. Examples of these are: Yucatan Fire, Smoke, Sence, ChillX, Highdi's Almdröhner, Earth Impact, Gorillaz, Skunk, Genie, Galaxy Gold, Space Truckin, Solar Flare, Moon Rocks, Blue Lotus, Aroma, Scope, OG Potpourri, and many other street names (EMCDDA 2009).

Exact epidemiological data on synthetic cannabinoid use is difficult to track because of difficulties in detection by routine laboratory test. The American Association of Poison Control Centers (AAPCC) reported that hospital emergency departments are experiencing an increase in admissions as a result of poisonings associated with the use of synthetic cannabinoids (NFLIS 2009–2010; Cary 2010a, 2010b). AAPCC received 13 cases in 2009 and by the first half of 2010, there were 567 cases (in 41 states) of people who had suffered adverse reactions to herbal incense products (increase of >4000% between 2009 and the first half of 2010). The commonly reported physical symptoms included sweating, nausea, vomiting, diarrhea, tremors, seizures, listlessness, increase heart rate, and change in blood pressure (Cary 2010a, 2010b; Castellanos et al. 2011). The poison control centers' synthetic cannabinoids exposure call rate for the 6 months from January to June 2011 increased more than the it had for the whole calendar year of 2010 (3237 vs. 2947). The increase in calls is also related to synthetic cathinones, which are believed to be more potent (NFLIS 2009–2010).

Initially, the United States Drug Enforcement Agency used temporary emergency powers to ban some of the synthetic cannabinoids (United States Drugs Enforcement Administration 2011). Since March 2011, five of the synthetic cannabinoids: JWH-018, JWH-073, CP-47497, JWH-200, and cannabicyclohexanol have been prohibited from use and distribution under the Federal Analog Act of the United States Controlled Substances Act (United States Drugs Enforcement Administration 2011). Although similar in structure to marijuana, these synthetic cannabinoids cannot be detected by conventional urine drug testing methods (routine UDS). There are costly tests available using complex and highly sensitive liquid chromatography mass spectrometry techniques to identify the metabolites in urine, saliva, and blood (NFLIS 2009–2010; Cary 2010 a and b; Coulter et al. 2011; Moore et al. 2011). Because of the rapidly increasing number of homologues and analogues of synthetic cannabinoids in the market today, there is very limited reference material available for most of these compounds. This presents a major challenge for government funding, public health, clinical services, and law enforcement policy (NFLIS 2009–2010; Cary 2010 a and b; Coulter et al. 2011; Moore et al. 2011).

Synthetic cannabinoid agonists bind to the same brain receptor (CB1) and trigger similar responses as THC. This may help to explain the likelihood of this compound inducing psychosis; although there is limited evidence to support this hypothesis (Cary 2010a, 2010b; Benford and Caplan 2011; Every-Palmer 2011). Some case reports and articles reported that JWH-018 and other synthetic cannabinoid agonists may actually have more affinity for the CB1 receptor than does THC (Huffman and Duncan 1997; Huffman et al. 2003, 2005; Cary 2010a, 2010b; Benford and Caplan 2011; Every-Palmer 2011). A recent article suggested that synthetic cannabinoid (JWH-018) may induce psychosis in vulnerable individuals, suggesting that those at risk for developing psychosis be advised against using synthetic cannabinoids (Hurst et al. 2011; Every-Palmer 2011). It is notable that there was a family history of psychosis in both of the cases presented previously. Additional case reports revealed psychoactive properties of synthetic cannabinoids including psychosis, euphoria, relaxation, sedation, agitation, nightmares, anxiety, depression, perceptual alterations, change in mental status, intense sensory experiences, increased reaction times, and cognitive impairment (Castellanos et al. 2011).

Conclusions

These case reports, noting the association of psychosis with synthetic cannabinoid use, highly recommend that clinicians obtain an adequate substance abuse history when interviewing adolescents presenting with psychosis, even in the presence of a negative UDS (Every-Palmer 2011; Hurst et al. 2011). Individual states and the Drug Enforcement Agency have both taken action to ban some synthetic cannabinoids; however these drugs remain a growing problem as there are hundreds of homologues and analogues available and the list is increasing at an alarming rate (Pierre 2011). The enforcement and implementations of policies against synthetic cannabinoid usage and distribution will require significant financial resources. In view of current limited funding, the way forward for the general population, legislators, adolescents, parents, families, schools, media, and law enforcement agencies is to educate vulnerable adolescents about the social, emotional, physical, and psychological implications of using this psychoactive drug, which is falsely distributed under the guise of “herbal product.” Finally, further research is needed to explore the potential physical and psychological hazards of synthetic cannabinoids and the contemporaneous public health implications of these compounds on the adolescent population.