There is "no obvious" link between tough laws and levels of illegal drug use, a government report has found.
Liberal Democrat Home Office minister Norman Baker said the report, comparing the UK with other countries, should end "mindless rhetoric" on drugs policy.
He accused the Conservatives of "suppressing" the report for months.
Tory MP Michael Ellis said the Lib Dems had "hijacked" the report for political gain. The government says it has "no intention" of decriminalising drugs.
The row comes ahead of a debate on government policy on drugs in the House of Commons later.
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Norman Baker MP: "We shouldn't assume locking people up is the answer"
The Home Office report compared the UK's approach to drug misuse with that of 13 other countries.
After examining a range of approaches, from zero-tolerance to decriminalisation, it concluded drug use was influenced by factors "more complex and nuanced than legislation and enforcement alone".
But it found there had been a "considerable" improvement in the health of drug users in Portugal since the country made drug possession a health issue rather than a criminal one in 2001.
The Home Office said these outcomes could not be attributed to decriminalisation alone.
Mr Baker believes treating drug use as a health matter would be much more effective in minimising harm.
AnalysisDanny Shaw, BBC home affairs correspondent
The divisions within the coalition could not be more sharply exposed.
The official Home Office position is that its drug strategy is working.
Norman Baker, the Liberal Democrat minister with responsibility for drugs, says "radical" change is needed.
Mr Baker's claims have been fuelled by his department's own report, which finds no link between how tough a country is on drugs and how many people use them.
It's an important finding, but the study also makes clear that drug policy is highly complex - approaches which may work abroad can't necessarily be implanted into the UK.
The Home Office barely mentioned the report in its press release, focusing instead on plans to change the law on legal highs.
Mr Baker's intervention has ensured the report takes centre stage.
"Let's look at what works rather than presuming locking people up is the answer," Mr Baker said.
"People are treated as a number, they're given a fine, they're given a caution, they're put in prison and none of that changes their drug habit.
"If we're interested in changing people's behaviour then we need to look at it from a health point of view."
DecriminalisationEarlier this year Deputy Prime Minister Nick Clegg pledged to abolish prison sentences for the possession of drugs for personal use.
Mr Clegg challenged David Cameron to look at issues such as decriminalisation, despite the prime minister previously rejecting calls for a Royal Commission to consider the issue.
Danny Kushlick, the founder of the group Transform, which has been campaigning for the legal regulation of drugs in the UK for almost 20 years, said the report was an important step.
"For the first time in over 40 years the Home Office has admitted that enforcing tough drug laws doesn't necessarily reduce levels of drug use," he said.
"Decriminalising the possession of drugs doesn't increase levels of use."
Legal highsA separate Home Office report calls for a blanket ban on all brain-altering drugs in a bid to tackle legal highs.
Currently, when a legal high is made illegal, manufacturers are avoiding the law by tweaking the chemical compound and creating a new substance.
The government will consider legislation introduced in Ireland four years ago that bans the sale of all "psychoactive" substances but exempts some, such as alcohol and tobacco.
Drug laws in some parts of the world have been relaxed in recent years.
Last year, Uruguay became the first country in the world to make it legal to grow, sell and consume marijuana.
From the start of this year, Colorado became the first US state to allow stores to sell cannabis for recreational purposes.
Have you had a serious drug habit? How was your addiction treated? You can email your experiences to haveyoursay@bbc.co.uk.
If you are willing to be contacted by BBC journalists please include a telephone number.
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