Gordon Brown is facing a series of protest resignations by some of his top advisers, resigned drugs tsar Professor David Nutt warned today.
The former chairman of the Advisory Council on the Misuse of Drugs claimed that further members of the Government panel were ready to follow him out of the door.
Prof Nutt was forced to quit yesterday amid intense controversy about his views on the harmfulness of drugs and his criticism of Government policies.
He had been especially scathing about the decision of the Prime Minister and then home secretary Jacqui Smith to upgrade cannabis to class B - in defiance of his advice.
Speaking to BBC Radio 4's Today programme this morning, Prof Nutt said: "He is the first Prime Minister, this is the first Government, that has ever in the history of the Misuse of Drugs Act gone against the advice of its scientific panel.
"And then it did it again with ecstasy and I have to say it's not about (me) over-stepping the line, it's about the Government over-stepping the line.
"They are making scientific decisions before they've even consulted with their experts."
Prof Nutt went on to say that many of the other 30 members of the drugs advisory council were highly disgruntled by the Government's position and could also be set to resign.
"I know that my committee was very very upset by the attitude the Prime Minister took over cannabis. We actually formally wrote to him to complain about it," he said.
"I wouldn't be surprised if some of them stepped down. Maybe all of them will."
Home Secretary Alan Johnson asked Prof Nutt to resign because he had "lost confidence" in his ability to give impartial advice.
Mr Johnson accused the professor of going beyond his remit as an evidence-based scientist and accused him of "lobbying for a change in government policy".
"It is important that the Government's messages on drugs are clear and as an adviser you do nothing to undermine the public understanding of them," Mr Johnson wrote to Prof Nutt.
"As my lead adviser on drugs harms I am afraid the manner in which you have acted runs contrary to your responsibilities.
"I cannot have public confusion between scientific advice and policy and have therefore lost confidence in your ability to advise me as chair of the ACMD."
Drugs charity DrugScope said the development was "extremely serious and concerning", while an academic accused Mr Johnson of undermining scientific research.
The row erupted earlier this week when, in a paper for the Centre for Crime and Justice Studies at King's College, London, Prof Nutt attacked what he called the "artificial" separation of alcohol and tobacco from other, illegal, drugs.
He accused Ms Smith of "distorting and devaluing" scientific research.
When she reclassified cannabis, which he said created only a "relatively small risk" of psychotic illness, she fell victim to a "skunk scare" he said.
And he claimed advocates of moving ecstasy into class B from class A had "won the intellectual argument".
All drugs, including alcohol and tobacco, should be ranked by a "harm" index, he said, with alcohol coming fifth behind cocaine, heroin, barbiturates and methadone.
Tobacco should rank ninth, ahead of cannabis, LSD and ecstasy, he said.
He also repeated his claim that the risks of taking ecstasy are no worse than riding a horse.
DrugScope director of communications, Harry Shapiro, said: "The Home Secretary's decision to force the resignation of the chair of an independent advisory body is an extremely serious and concerning development and raises serious questions about the means by which drug policy is informed and kept under review."
Richard Garside, director of the centre at King's, accused Mr Johnson of undermining scientific research.
He said: "I'm shocked and dismayed that the Home Secretary appears to believe that political calculation trumps honest and informed scientific opinion.
"The message is that when it comes to the Home Office's relationship with the research community, honest researchers should be seen but not heard."
Former government chief scientific adviser Sir David King said today that Prof Nutt had gone too far in criticising ministers' decision-making.
But, speaking also on Today, he said the Government had "lacked courage" when faced with the science.
"The reason (the Home Secretary) is giving is effectively 'he should not put this advice into the public domain'.
"Absolutely wrong. But I do feel that if David was critical of Jacqui Smith and her individual decision-making that's stepping over the line."
He added: "I think the Government has lacked courage in backing David's committee's advice.
"I think it's a lack of courage in the Government that is a big issue here."