The victims were found Thursday afternoon at a homeless camp in Glen Burnie.
Police said they used a beer can to smoke the product, which goes by the name "Scooby Snax." A short time later, all of the victims became unconscious. An empty package was recovered from the scene.
Police said they seized additional synthetic marijuana, known as spice, from the business where the victims bought it.
The victims are a 57-year-old man, a 52-year-old man, a 38-year-old man, and a 45-year-old woman. Two of them were listed in critical condition, police said.
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This incident comes as hospitalizations due to synthetic marijuana have spiked recently nationwide.
Poison control centers nationwide reported 359 cases in January of illnesses from synthetic cannabinoids, which mimic the effects of the main psychoactive ingredient in marijuana but can be far more potent. There were 273 in February and 269 in March. But the number skyrocketed to just over 1,500 in April, according to the American Association of Poison Control Centers.
All 50 states have banned cannabinoids by outlawing specific compounds since 2011, and a federal law in 2012 added certain cannabinoids to the U.S. controlled substances list, according to the National Conference of State Legislatures.
The Drug Enforcement Administration says a major problem has been chemical makers, including many in Asia, slightly changing chemical compounds so they're no longer banned controlled substances.
Synthetic marijuana usually is non-marijuana plant material sprayed with cannabinoids and marketed under brand names like Spice, K2 and Scooby Snax. It emerged in the U.S. around 2008 and became readily available in small retail outlets like convenience stores and head shops, as well as on the Internet, according to the Office of National Drug Control Policy.
It generally costs about $30 per 3-gram package, similar to marijuana. Many brands list "not for consumption" on the small packages in an apparent attempt to avoid regulation, authorities say.
It became popular because it was easy to buy, people wrongly thought was harmless and its chemicals aren't detected on standard drug tests, the National Institute on Drug Abuse says. But it can be more potent than regular marijuana and can cause vomiting, seizures, hallucinations, elevated blood pressure, loss of consciousness and death, health officials say.
The Associated Press contributed to this report.