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Top 10 Facts on Synthetic Cannabinoids: Not So Nice Spice

Spice

Spice looks innocent enough, but it’s dangerous!

Recent outbreaks of synthetic cannabinoid-related emergency department visits across the country have been in the news lately. Between April 1 and May 31, 2015, Mississippi reported 1243 emergency department visits due to adverse events from synthetic cannabinoids,1 with 10% requiring intensive care unit (ICU) admission, 11% non-ICU admission, and 17 potentially related deaths.1 The US experienced a 229% increase in poisonings attributable to synthetic cannabinoids from January to May 2015 when compared with the same time period in 20142; Mississippi accounted for a remarkable 35% of all reports.1 The large number of cases reported in Mississippi is attributable in part to an enhanced surveillance process instituted by the Mississippi State Department of Health and the Mississippi Poison Control Center. Because of the growing prevalence of this problem, providers nationwide should be aware of the facts.

1- Synthetic Cannabinoids Are Not Marijuana/Cannabis
Although these illegal substances are commonly referred to as synthetic cannabinoids, cannabinoid receptor agonists, cannabimimetic agents, Spice, synthetic marijuana, or even legal marijuana, they should not be confused with marijuana/cannabis or the legal synthetic cannabinoids/cannabinoid receptor agonists such as Cesamet (nabilone; Meda Pharmaceuticals Inc, Somerset, NJ) or Marinol (dronabinol; Δ9-tetrahydrocannabinol; AbbVie Inc, North Chicago, IL).1, 3, 4, 5 Illegal synthetic cannabinoids/Spice are not marijuana/cannabis, but rather a collection of numerous laboratory chemicals that interact with the cannabinoid receptor in the brain to mimic marijuana to induce a marijuana-like high.5 The synthetic chemicals designed to mimic marijuana bind to the same cannabinoid receptors in the brain as delta 9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive component of marijuana.3

2- Synthetic Cannabinoids Are Often More Potent Than Marijuana/Cannabis4
One reason Spice may be more potent than marijuana is because the chemical components bind more strongly to the cannabinoid receptor in the brain; they also may interact with other receptors in the brain that marijuana does not.3 Symptoms may resolve spontaneously without intervention and vary, including mild to moderate intoxication-like symptoms, nausea, emesis, weakness, tachycardia, hypertension, and agitation.1, 4 Several news reports have described users in states of “excited delirium,” significantly agitated, tearing off their clothes, and sweating profusely. Severe symptoms include significant cardiac arrhythmias, myocardial infarction, psychosis, respiratory depression, flaccid paralysis, hyperthermia, rhabdomyolysis, seizures, coma, and even death.1, 4, 6 Intoxication management usually centers on airway, breathing, circulation, and life-threatening issues first, followed by supportive care.4, 6 Fluid resuscitation may be needed, as well as electrolyte correction.3 Benzodiazepines are usually first-line treatment for anxiety/agitation; physical restraint may be necessary.4, 6, 7 Significant psychosis with behavioral disturbances can occur, which may not be calmed with typical methods; in these instances, antipsychotics may be helpful.6, 7 Anecdotally, in our state, some of the patients presented with significant psychotic behaviors; the atypical antipsychotics seemed to assist more than the benzodiazepines in those cases. However, caution should be used with antipsychotics and other medications that can decrease seizure threshold as there have been reports of synthetic cannabinoids causing seizures.4, 6 Because Spice intoxication presentations are varied, the treatment is individualized by scenario; the specific treatments used, observation time, and whether or not to admit (non-ICU or ICU) should be decided on a case-by-case basis and depend on the severity of the symptoms and comorbid conditions. Consulting a toxicologist may be helpful; Poison Control (800-222-1222) can also assist with management questions.

3- Synthetic Cannabinoids Are Ever-changing
The 2012 Synthetic Drug Abuse Prevention Act made 15 synthetic cannabinoids Schedule I8; the Drug Enforcement Administration continues to designate active Spice chemicals and their analogs Schedule I, making these products illegal to sell, buy, or possess.8 In January 2015, 3 more were made Schedule I, including AB-CHMINACA8 (Figure 1). However, the clandestine manufacturers change the chemical formulations frequently to evade law enforcement.3 MAB-CHMINACA is an example of the tweaked difference from AB-CHMINACA (Figure 1). Like all of these emerging synthetic cannabinoids, the full extent of their physiological and toxicological effects is unknown at this time. Some states have enacted broad/generic language describing synthetic cannabinoids and analogs; for example, per Mississippi Code 41-29-113, all synthetic cannabinoids are currently illegal. However, because synthetic cannabinoids are not marijuana, they will not show up as marijuana on a typical urine drug screen.3 Confirmation testing such as gas chromatography/mass spectrometry will detect some specific synthetic cannabinoid compounds; but with rapidly changing components, even confirmation detection is unlikely because “their identification and quantitative analysis is limited by the availability of pure reference samples.”5

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– Ann M. Kemp, RPh, MD, Molly S. Clark, PhD, ABPP, Thomas Dobbs, MD, MPH, Robert Galli, MD, Justin Sherman, Pharm D, Robert Cox, MD, PhD

This is an article in press and will appear in an upcoming issue of The American Journal of Medicine.

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