Durham Police said the crash involved 32 vehicles and closed traffic between Exits 274 and 276. That's near the Fayetteville Road and Streets at Southpoint exits.
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Many motorists were stuck in the aftermath for three hours.
Pat Shine said his Tesla was one of the first vehicles involved in the crash. He was trying to get home from Garner to Chapel Hill.
"It did feel a little tornado-ey because there was a lot of lightning and some dust from the construction getting blown around," Shine said. "By the time everything happened, it had almost completely cleared."
He said he slowed down when he saw a truck in front of him slow down, and then he got hit from behind
"There were some cars that were completely underneath tractor trailers ... surprised people weren't more injured," Shine said.
All drivers were urged to avoid the area. Police diverted traffic off the interstate.
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All lanes reopened just before 8:30 p.m., nearly four hours after the crashes happened.
Though no official word has yet been released, there did not appear to be indications that anyone was seriously injured.
32-car crash closes I-40 westbound in Durham
ABC11 is working to learn more about the specific cause of the crash. It happened while severe weather was moving through the area, causing damage across the region.