Drug overdose and intoxication are significant causes of accidental death, and can also be used as a form of suicide. Death can occur from overdosing on a single or multiple drugs, or from combined drug intoxication due to poly drug use. Poly drug use often carries more risk than use of a single drug, due to an increase in side effects, and drug synergy. Drug use and overdoses increased significantly in the 1800s due to the commercialization and availability of certain drugs. For example, while opium and coca had been used for centuries, their active ingredients, morphine and the cocaine alkaloid, were not isolated until 1803 and 1855 respectively. Cocaine and various opiates were subsequently mass-produced and sold openly and legally in the Western world, resulting in widespread misuse and addiction. Efforts to prohibit various drugs began to be enacted in the early 20th century, though the effectiveness of such policies is debated. Deaths from drug overdoses are increasing. Between 2000 and 2014, fatal overdoses rose 137% in the United States, causing nearly half a million deaths in that period, and have also been continually increasing in Australia, Scotland, England, and Wales. (Full list...)