The European Union is fuelling political disengagement by voters and driving the rise of extremist parties, Boris Johnson has warned.
The London mayor - who announced on Sunday he was backing the "out" campaign - said voters were becoming increasingly disillusioned at the inability of their elected politicians to take decisions in the face of control from Brussels.
In one of his most outspoken attacks on the EU, he said that if the forthcoming in/out referendum delivered a vote to remain in, Britain faced a further erosion of democracy.
At the same time, he appeared to suggest that a vote for Brexit could be a platform for the UK to negotiate a new, improved settlement with Europe.
Mr Johnson's intervention, just a day after David Cameron appealed on the steps of Downing Street for voters to back his re-negotiation deal, galvanised the referendum debate.
His declaration - putting an end to months of speculation - was a huge boost for the Brexit campaign, potentially giving it a popular figurehead able to connect with voters in a way few other Westminster politicians can manage.
It came as a bitter blow for Mr Cameron, however, who had long believed that his old rival from their days at Eton and Oxford would ultimately fall in behind his reform package.
The Prime Minister now faces the opposition of five of his Cabinet ministers and a large swathe of Tory backbenchers as well as his party's most charismatic figure.
The Prime Minister will set out details of the deal agreed during marathon talks in Brussels and the next steps in the referendum - to be held on June 23 - in a Commons statement.
Writing in his weekly column in the Daily Telegraph, Mr Johnson said the referendum offered a "once in a lifetime chance" to deliver "real change" in Britain's relations with her European neighbours.
"There is only one way to get the change we need - and that is to vote to go; because all EU history shows that they only really listen to a population when it says 'no'," he said.
As it was, voters could already see the "impotence" of national elected politicians to deal with issues such as immigration.
"That enrages them; not so much the numbers as the lack of control. That is what we mean by loss of sovereignty - the inability of people to kick out, at elections, the men and women who control their lives," he said.
"We are seeing an alienation of the people from the power they should hold, and I am sure this is contributing to the sense of disengagement, the apathy, the view that politicians are 'all the same' and can change nothing, and to the rise of extremist parties."
He said Mr Cameron's promised bill to assert the sovereignty of the of the UK Parliament might have a "chilling effect" on some of the more federalist ambitions of the European Commission and Court of Justice but would not "stop the machine".
"At best it can put a temporary and occasional spoke in the ratchet," he said.
Mr Johnson's announcement immediately drew claims that he was positioning himself to mount a challenge for the Conservative leadership.
He was also strongly attacked by the former deputy prime minister Lord Heseltine for jeopardising the position of the City of London.
The mayor however insisted that while such claims "cannot be entirely dismissed" they were likely to prove to be exaggerated.
"We have heard this kind of thing before, about the decision to opt out of the euro, and the very opposite turned out to be the case," he said.