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Stephen Greene was the deputy administrator of the Drug Enforcement Administration (DEA) from 1991, replacing John Lawn's deputy Terrence Burke, until his retirement from the DEA in 1996. He also served as acting administrator temporarily for part of 1993 and 1994, after Robert C. Bonner's resignation and before President Clinton appointed Thomas Constantine as his successor.

Greene was one of the first generation of DEA agents when the agency formed in 1973, serving in overseas offices in Saigon, Hong Kong, and Bangkok, and domestic offices in Los Angeles and Baltimore. He supervised many of the DEA's operations against the Medellín and Cali cocaine cartels in Colombia, and before ascending to the number two spot as deputy administrator, had been the DEA's director of operations.

During Greene's time as acting administrator, the Medellín cartel he had fought for years finally declined in power. Its head, Pablo Escobar, had been shot and killed by the Colombian National Police after a 17-month manhunt following his escape from prison. Escobar's top lieutenants had turned themselves in late in 1990, and his most trusted assassins had been killed shortly thereafter. The cartel was without the strong leadership that had guided it, and quickly became a shadow of what it had been. Its chief Colombian competitor, the Cali mafia, rushed to fill the power vacuum. Each cartel had distinguished itself with a different approach in the previous decades. The Medellín cartel was violent, flashy, and brutal, while the Cali mafia were less interested in making a name for themselves so long as they could make a profit. They posed as legitimate Colombian businessmen, laundering their money through active business fronts, taking many cues from the American mafia families that posed as sanitation company and nightclub owners.

They were also happy to spend their money locally, and their prosperity benefited the Cali region, giving them significant economic control over their surroundings. By the time the Medellín cartel was no longer there to take the spotlight off them, they had 20 years to consolidate power and build connections.

With the fall of the Soviet Union in 1990, the Cali mafia and other cocaine cartels took the opportunity to move into Eastern Europe, where political, economic, and cultural chaos created a ripe market for hard drugs and few borders were guarded with anything approaching efficacy.

Greene's tenure both as deputy administrator and acting administrator also took place during a surge of heroin consumption in the United States, as American drug users gained access to significant amounts of the cheapest, purest heroin ever available in the country. The heroin was supplied both by the traditional southeast Asian opium cultivators (particularly Laos and Myanmar) and by Colombian cocaine cartels that sought to diversify their portfolio as the crack epidemic reached a plateau. Meanwhile, the prominence of so many hard drugs had again turned public opinion with regard to marijuana, which was now seen as considerably less dangerous than it had been at the start of the 1980s. Greene found himself addressing repeated requests to reclassify marijuana as a Schedule II drug (effectively legalizing medical marijuana), which he took a firm stance against.

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