Deputy Prime Minister Nick Clegg is calling for a royal commission on drugs, just five days after the prime minister and the home secretary rejected the idea.
On Monday an all-party committee of MPs recommended there should be a fundamental review of Britain's drugs laws, but David Cameron said that was unnecessary.
Now Mr Clegg has said the worst thing people can do is close their mind to drug reforms.
Mr Clegg told the BBC he wanted to break what he called the "conspiracy of silence", where politicians while in government refuse to consider alternatives to the so-called war on drugs because it is "all too controversial".
By calling for a royal commission to be set up, the deputy prime minister is at complete odds with David Cameron who emphatically rejected the idea.
A royal commission is a public inquiry, established by the head of state, into a defined subject and overseen by a commissioner who has quasi-judicial powers.
"I don't see this as a thing between myself and the prime minister," Mr Clegg said. "It's what do we as a country believe is the right thing to do."
Asked if he was at risk of being soft on drugs, Mr Clegg said: "There's nothing hard about turning your back against the evidence."
He said he wanted the government to look at the system in Portugal where all drugs have been depenalised and also at the experience in the US states of Washington and Colorado where marijuana was recently legalised.
"If you are anti-drugs, you should be pro-reform. That is my view," he said.
At their party conference last year, the Liberal Democrats voted to establish a panel to consider decriminalising the use of all drugs. Reform of drug laws is an issue that has long been pursued by some in the party.
However, Mr Clegg has now set himself at odds with his Conservative coalition partners. He told the prime minister of his intention to support a royal commission, in defiance of Mr Cameron's publicly stated position, at a meeting in Downing Street.
"Both the prime minister and I are relaxed about the idea that this isn't an identikit government," Mr Clegg said.
"The home secretary and indeed the prime minister are perfectly entitled to say that they want the government's present approach to be given a chance to work and don't want the distraction of a royal commission.
"My view is that we've been waging the war on drugs for almost 40 years, and I don't think by any stretch of the imagination it has worked."
The Home Office and Downing Street both say there is no need to review Britain's drug laws, pointing out that drug use is falling while numbers in treatment are rising.
However, Mr Clegg has said the drugs minister at the Home Office, Liberal Democrat Jeremy Browne, will be sent on a fact-finding mission to look at the experience in countries experimenting with decriminalisation and legalisation.