“K2” and “Spice” drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as “legal highs”. These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate “not for human consumption”, the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications.

Objective To report a case of seizures and supraventricular tachycardia (SVT) following confirmed synthetic cannabinoid ingestion. Background Despite widespread use of legal synthetic cannabinoids, reports of serious toxicity following confirmed use of synthetic cannabinoids are rare. We report severe toxicity including seizures following intentional ingestion of the synthetic cannabinoid JWH-018 and detail confirmation by laboratory analysis. Case Report A healthy 48 year old man had a generalized seizure within thirty minutes of ingesting an ethanol mixture containing a white powder he purchased from the Internet in an attempt to get high. Seizures recurred and abated with lorazepam. Initial vital signs were: pulse, 106/min; BP, 140/88 mmHg; respirations, 22/min; temperature, 37.7 °C. A noncontrast computed tomography of the brain and EEG were negative, and serum chemistry values were normal. The blood ethanol concentration was 3.8 mg/dL and the CPK 2,649 U/L. Urine drug screening by EMIT was negative for common drugs of abuse, including tetrahydrocannabinol. On hospital day 1, he developed medically refractory SVT. The patient had no further complications and was discharged in his normal state of health 10 days after admission. The original powder was confirmed by gas chromatography mass spectrometry to be JWH-018, and a primary JWH-018 metabolite was detected in the patient’s urine (200 nM) using liquid chromatography tandem mass spectrometry. Discussion Synthetic cannabinoids are legal in many parts of the world and easily obtained over the Internet. Data on human toxicity are limited and real-time confirmatory testing is unavailable to clinicians. The potential for toxicity exists for users mistakenly associating the dose and side effect profiles of synthetic cannabinoids to those of marijuana. Conclusion Ingestion of JWH-018 can produce seizures and tachyarrhythmias. Clinicians, lawmakers, and the general public need to be aware of the potential for toxicity associated with synthetic cannabinoid use.

The aminoalkylindole agonists JWH-018 and JWH-073 are contained in “K2/SPICE” products sold as “legal marijuana”. Previous human metabolic studies have identified (ω)-hydroxyl and (ω)-carboxyl metabolites as biomarkers indicative of product use. However, other primary metabolites exhibiting similar chromatographic properties and mass spectra are also excreted in human urine. Analytical standards were used in this study to identify new primary metabolites as (ω-1)-hydroxyl derivatives of JWH-018 and JWH-073. The liquid chromatography tandem mass spectrometry (LC-MS/MS) procedure coupled with an automated solid-phase extraction procedure incorporating deuterium labeled internal standards provides rapid resolution of the (ω)- and (ω-1) metabolites with adequate sensitivity, precision, and accuracy for trace analysis in human urine. Results from four urine specimens collected after individuals reportedly self-administered either JWH-018 or a mixture of JWH-018 and JWH-073 showed the following: 1) all tested metabolites were excreted in high concentrations, 2) (ω)- and (ω-1)-hydroxyl metabolites were exclusively excreted as glucuronic acid conjugates, and 3) approximately 5–80% of the (ω)-carboxyl metabolites were excreted as glucuronic acid conjugates. This is the first report to identify and quantify (ω-1)-hydroxyl metabolites of JWH-018 and JWH-073 and the first to incorporate automated extraction procedures using deuterium labeled internal standards. Full clinical validation awaits further testing.

IntroductionCannabinoid hyperemesis syndrome (CHS) is an entity associated with cannabinoid overuse. CHS typically presents with cyclical vomiting, diffuse abdominal pain, and relief with hot showers. Patients often present to the emergency department (ED) repeatedly and undergo extensive evaluations including laboratory examination, advanced imaging, and in some cases unnecessary procedures. They are exposed to an array of pharmacologic interventions including opioids that not only lack evidence, but may also be harmful. This paper presents a novel treatment guideline that highlights the identification and diagnosis of CHS and summarizes treatment strategies aimed at resolution of symptoms, avoidance of unnecessary opioids, and ensuring patient safety.MethodsThe San Diego Emergency Medicine Oversight Commission in collaboration with the County of San Diego Health and Human Services Agency and San Diego Kaiser Permanente Division of Medical Toxicology created an expert consensus panel to establish a guideline to unite the ED community in the treatment of CHS.ResultsPer the consensus guideline, treatment should focus on symptom relief and education on the need for cannabis cessation. Capsaicin is a readily available topical preparation that is reasonable to use as first-line treatment. Antipsychotics including haloperidol and olanzapine have been reported to provide complete symptom relief in limited case studies. Conventional antiemetics including antihistamines, serotonin antagonists, dopamine antagonists and benzodiazepines may have limited effectiveness. Emergency physicians should avoid opioids if the diagnosis of CHS is certain and educate patients that cannabis cessation is the only intervention that will provide complete symptom relief.ConclusionAn expert consensus treatment guideline is provided to assist with diagnosis and appropriate treatment of CHS. Clinicians and public health officials should identity and treat CHS patients with strategies that decrease exposure to opioids, minimize use of healthcare resources, and maximize patient safety.