Use of the drug in the city centre has left scores of users rendered like “zombies” and passing out.
Greater Manchester Police (GMP) said they dealt with 58 Spice-related incidents between Friday and Sunday.
Chief Superintendent Wasim Chaudhry, from GMP’s city centre team, said officers were doing all they could to tackle the issue but it was “a problem that we cannot afford to get any worse”.
He said: “Those who take Spice are often left incapacitated or seriously ill and need the help of our partners in the NHS and ambulance service.
“They can also become aggressive and become a danger to themselves and others.
“The truth is, tackling the issues caused by Spice is putting pressure on public services and is taking up a lot of our resources. Particularly in Manchester city centre.
“A multi-agency approach is the only way we can fight this battle.
“As a result we have been working with Manchester City Council’s adults and children’s services, rough sleeper team, outreach teams and local charities as well as North West Ambulance Service and the NHS.”
He said the force had increased the number of specially-trained officers to try and combat the issue and help those using the drug to access support.
Effects of the drug can be extreme, causing hallucinations, psychosis, muscle weakness and paranoia.
Videos of users of the drug have gone viral, some left catatonic and twitching while standing up or slumped against walls or over bins or benches.
In December last year, third-generation synthetic cannabinoids, found in Spice, were classified as a Class B drug under the Misuse of Drugs Act - making possession of the drug illegal.