Officers executed warrants at addresses across both towns today, and made arrests on suspicion of conspiracy to supply class A and class B drugs.
Those arrested are a 52-year-old man from Burnley, and three men from Nelson, aged 33, 38 and 43. They all remain in custody at this time.
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The warrants were carried out as part of a cross-border drug supply investigation, believed to be based in the east of the county.
As part of the investigation, police recovered significant amounts of cocaine, ketamine and cannabis, as well as other drug paraphernalia.
Officers also seized mobile phones, cash and a quantity of drugs.
DI Tom Edmondson, of East CID, said: “These arrests and significant drug seizures are part of our ongoing proactive efforts to ensure East Lancashire is a difficult place for organised criminal gangs to operate. We will continue to target those who seek to profit from the drugs trade and from the misery and suffering of others.
“If you know of or are concerned about potential illegal activity in your area I would encourage you to contact the police on 101 and we will take the appropriate action."