Synthetic Cannabinoids Offers Real Highs and Real Risks

While much of the discussion about marijuana in recent years has focused on its legalization in multiple states, disturbing developments with its chemical cousin — synthetic cannabinoids — have kept emergency room physicians busy.

In July 2015, 600 people presented in New York City emergency rooms for toxic reactions to synthetic cannabinoids, according to U.S. News and World Report.1 Adverse reactions have risen dramatically in the past year.

The novel compounds found in synthetic marijuana have unknown receptor-binding affinity, which may produce severe toxicity. The unsupervised and clandestine nature of their production increases the risk of contaminants. One outbreak of severe illness associated with a specific synthetic cannabis affected 12 states from mid-March through May 2015. At the same time, Mississippi reported 1,200 emergency visits and 17 deaths likely related to the use of synthetics and Alabama had 1,000 emergency visits and five deaths, according to The New England Journal of Medicine.2

What is in these synthetics? A mixture of innocuous plant material, such as basil or oregano, sprayed with a not-so-innocuous mixture of manufactured cannabinoids. These chemicals mimic cannabis by affecting the same neuroreceptors and producing a quick, intense and unpredictable high when smoked or brewed as tea. Liquid versions are also produced that can be vaped like e-cigarette fluids. All of them are readily available at gas stations and convenience stores around the country.3

The synthetics — known as Spice, K2, Black Mamba and a host of other names — are easy to obtain. While technically illegal, as analogs of illegal substances, they are marketed as legal. It is difficult for regulators to identify, track and specifically ban these substances because they are lab produced. When law enforcement determines exactly what is in a brand or type of synthetic and lists it as an illegal drug, the chemists then modify the ingredients.

There is a China connection that makes synthetic cannabis production fundamentally different from other illegal drugs. These chemicals are not produced in a hidden laboratory or in someone’s basement. They are manufactured by sophisticated laboratories, some of which produce high-grade products for pharmaceutical and agricultural companies.4

Legal or illegal, synthetic cannabis is now the third most commonly abused drug in American high schools, behind only natural marijuana and the attention deficit hyperactivity drug Adderall, according to the 2014 University of Michigan Monitoring the Future drug-use report.

Where the active ingredient in cannabis is tetrahydrocannabinol (THC), the synthetics may have THC or several other related compounds that have 10 times the potency of natural THC. 5 With no regulation and no organic limitations on the concentration of the cannabinoids, the synthetics vary significantly from batch to batch — as can the response to their use.

For adolescents and young adults attracted to their easy availability, purported legal status and expected marijuana-like effects, the actual experience of the synthetics can be a very nasty surprise.

Users report that they experience the same elevated mood, relaxation and altered perception common with marijuana — along with symptoms of psychosis, often quite severe, including extreme anxiety, paranoia and hallucinations. The drugs can also cause elevated heart rate, heart attack, kidney damage, seizures, stroke, vomiting, violent behavior, suicidal thoughts, coma and death.

The incidence of acute psychosis has become so notable that it’s been called “spiceophrenia.”6 Characteristics include combativeness, paranoid delusions, disorganized thoughts and severe agitation. Adverse effects do not seem to be dose dependent and may be seen in both first time and chronic users. Combining the synthetic cannabis with organic cannabis or cocaine appears to increase the risk of psychosis.

Drug screens cannot detect the synthetics, so proper diagnosis depends on patient or other reporting.

While there is no recommended protocol for treating acute psychosis or toxicity associated with synthetic cannabis, antipsychotics and benzodiazepines may be used to treat symptoms, according to a presentation made at the American Academy of Addiction Psychiatry’s 2013 Meeting and Symposium by Andrea Bulbena-Cabre, MD. Psychiatric admission may also be required. In some cases patients have required admission to intensive care units.

Most users report smoking or vaping the synthetics only occasionally. Regular users who stop may experience withdrawal symptoms that include craving, anxiety, insomnia, anorexia caused by vomiting and nausea, headaches, sweating and elevated heart rate.

Regardless of what’s in the new synthetics, two things are certain: It’s an entirely different and far more dangerous substance than your father’s weed.

1. Sederer L. The Not-So-Nice Spice. U.S. News and World Report. Aug. 5, 2015.
2. Trecki J, Gerona RR, Schwartz MD. Synthetic Cannabinoid-Related Illnesses and Deaths. New England Journal of Medicine. 2015;373:103-107.
3. DrugFacts: Synthetic Cannabinoids. National Institute on Drug Abuse. Revised November 2015.
4. Halford B. A Glimpse Inside the Sophisticated World of Synthetic Cannabinoids. Chemical and Engineering News. April 10, 2015.
5. Melville NA. Synthetic Cannabis Triggers ‘Spiceophrenia.’ Medscape. December 12, 2013.
6. Papanti D, et al. Human Psychopharmacology. 2013;28:379-389