Application Note 559. Synthetic cannabinoids are compounds made to mimic the effects of natural cannabinoids found in the cannabis plant (marijuana). They were first synthesized by pharmaceutical companies seeking to mimic the beneficial analgesic and anti-nausea effects of cannabis while trying to eliminate the psychoactive euphoric effects for which the plant is so abused. In the mid 1980’s, these compounds began appearing in herbal incense, marketed as “legal highs” under the names “Spice” and “K2.” Effects are similar to those of cannabis, but with reports of increased anxiety and paranoia. In early 2011, the US DEA regulated five of these compounds as Schedule I drugs.Simple, robust and precise analytical methods are needed to quantitate these now illegal compounds in biological matrices for forensic purposes. Here we will focus on JWH-018 and JWH-073. The reported metabolites seen in urine are the alkyl-hydroxyl and alkyl-carboxy metabolites of each compound.