another 41; in 2011, another 49; and in 2012, there were 73 more. In 2013, a further 81 were identified: a total of 268 new drugs in just four years. These have not been limited to cathinones, with 35% being cannabinoids and the rest being composed of stimulants, benzodiazepines, psychedelics, dissociatives and to a lesser extent, every other class of drugs, even ibogoids and nootropics. The largest group of drugs being monitored by the EMCDDA is synthetic cannabinoids, with 209 different synthetic cannabinoids reported between 2008 and 2021 - including 11 new cannabinoids identified for the first time in 2020. Safety The safety of research chemicals is untested and little if any research has been done on the toxicology or pharmacology of most of these drugs. Few, if any, human or animal studies have been done. Many research compounds have produced unexpected side-effects and adverse incidents due to the lack of screening for off-target effects prior to marketing; both bromo-dragonfly and mephedrone seem to be capable of producing pronounced vasoconstriction under some circumstances, which has resulted in several deaths, although the mechanism remains unclear. Substituted phenethylamines such as the 2C family and substituted amphetamines such as the DOx family have also caused a limited number of deaths. Law Due to the recent development of many designer drugs, laws banning or regulating their use have not been developed yet, and in recent cases novel drugs have appeared directly in response to legislative action, to replace a similar compound that had recently been banned. Many of the chemicals fall under the various drug analogue legislations in certain countries, but most countries have no general analogue act or equivalent legislation and so novel compounds may fall outside of the law after only minor structural modifications. In the United States, the Controlled Substances Act was amended by the Controlled Substance Analogue Enforcement of 1986, which attempted to ban designer drugs pre-emptively by making it illegal to manufacture, sell, or possess chemicals that were substantially similar in chemistry and pharmacology to Schedule I or Schedule II drugs. Other countries have dealt with the issue differently. In some, the new drugs are banned as they become a concern, as in Germany, Canada, the United Kingdom, and Sweden. In Sweden, the police and customs may also seize drugs that are not on the list of drugs covered by the anti-drug laws if the police suspect that the