title: Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications.
abstract: BACKGROUND
  Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abusable designer drugs. In the early 2000s, SC became popular as "legal highs" under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests.
  
  
  METHODS
  We present here a comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, United States; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, United States.
authors.forename: Marisol S
authors.initials: MS
authors.lastname: Castaneto
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Gorelick
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, United States; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, United States.
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Desrosiers
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, United States; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, United States.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hartman
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, United States.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pirard
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, United States. Electronic address: mhuestis@intra.nida.nih.gov.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D015198:Designer Drugs / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D013759:Dronabinol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D015198:Designer Drugs; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013759:Dronabinol
keywords: CB(1)/CB(2) agonists; Designer drug; Epidemiology; Pharmacodynamics; Spice; Synthetic cannabinoids