Mr Santos added his voice to a growing list of influential figures in Latin America demanding a rethink of the policies that have been used for decades to fight the drugs trade.
He said legalising softer drugs such as marijuana worldwide could help improve international efforts to deal with harder drugs such as cocaine and heroin.
"The world needs to discuss new approaches ... we are basically still thinking within the same framework as we have done for the last 40 years," he said.
Asked if making marijuana legal could offer a way forward, Mr Santos said it could and that he would support it "provided everyone does it at the same time". But he emphasised that other countries needed to take the lead, saying the issue was "a matter of national security" for Colombia, whereas "in other countries this is mainly a health and crime issue".
"Drug trafficking is what finances the violence and the irregular groups in our country. I would be crucified if I took the first step," he said in an interview with Metro, the global free daily newspaper chain.
His comments are the latest sign that Latin American nations scarred by violence associated with the trafficking of drugs to the US and Europe want to pressure global leaders to tackle the issue afresh.
Last month Felipe Calderón, the Mexican president, used a speech in New York to warn the US that as the world's "largest consumer of drugs" it may have to consider legalisation "to reduce the astronomical earnings of criminal organisations".
In June a report by politicians and former world leaders said that the global war on drugs has fuelled organised crime and recommended an end to the criminalisation of drug users and the legalisation of some banned substances.
Ernesto Zedillo, Fernando Henrique Cardoso and Cesar Gaviria, former presidents of Mexico, Brazil and Colombia respectively, were among the 19-member commission that drew up the report.
The Telegraph 26th October 2011
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Colombian president calls for legalisation of marijuana