There is "no obvious relationship" between tough laws and levels of drug use, a government report has suggested.
The research compared the UK with countries like Portugal, where possession of small amounts of drugs no longer carries criminal sanctions.
Liberal Democrat Home Office minister Norman Baker said the findings should prompt the end of "mindless rhetoric" on drugs with a new focus on treatment.
The government said it had "no intention" of decriminalising drugs.
End Quote Norman Baker Home Office ministerLet's look at what works rather than presuming locking people up is the answer"
The report comes as the Home Office launches a clampdown on "legal highs".
'Historic'The report explored different ways in which 13 countries approach drug misuse and compared them with the UK.
After examining a range of approaches, from zero-tolerance to decriminalisation, it concluded that drug use is influenced by factors "more complex and nuanced than legislation and enforcement alone".
However, the report 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 cannot be attributed to decriminalisation alone and the UK government had "absolutely no intention of decriminalising drugs."
Mr Baker said treating drug use as a health matter would be much more effective in minimising harm.
His party leader, Nick Clegg, wants responsibility for drug addiction to be moved from the Home Office to the Department of Health - a move supported by some Labour MPs.
In the House of Commons later, MPs will debate a motion put forward by Green MP Caroline Lucas calling on the government to conduct a "cost-benefit analysis" of the Misuse of Drugs Act.
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.
He added: "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.
"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 is going to consider legislation introduced in Ireland four years ago that bans the sale of all "psychoactive" substances but exempts some, such as alcohol and tobacco.
Mr Baker said: "From today we will start looking into the feasibility of a blanket ban on new psychoactive substances across the whole of the UK, clamping down on the suppliers and head shops rather than the users.
"This approach had a dramatic impact on the availability of legal highs when introduced in Ireland, but we must ensure it would work here too."
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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