Preliminary blood tests have shown "signs of narcotics" in Anne Heche's system as her family said she is "not expected to survive" the fiery car crash which left her in a coma.
The Los Angeles Police Department (LAPD) has said additional testing is required to rule out any substances that were administered in hospital.
It comes as LAPD spokesman Matthew Cruz has confirmed the crash is being investigated as a felony driving-under-the-influence (DUI) traffic collision.
He added that preliminary blood tests "did show signs of narcotics".
Law enforcement sources told celebrity news site TMZ that Heche was found to be under the influence of cocaine at the time of the crash.
Fentanyl was also found in the 53-year-old's blood but further testing needs to take place to determine if it was in her system before the collision, the sources added.
The strong opioid is sometimes used as a painkiller in hospital and so may have been administered as part of her treatment.
Heche suffered significant burns and lung damage after crashing into a two-storey house in the Mar Vista area of Los Angeles on the morning of Friday 5 August.
She remains in a coma in a critical condition in hospital a week later.
Heche's family issued a statement on Thursday saying the actress was being temporarily kept on life support.
"Unfortunately, due to her accident, Anne Heche suffered a severe anoxic brain injury and remains in a coma, in critical condition. She is not expected to survive," the statement read.
"It has long been her choice to donate her organs and she is being kept on life support to determine if any are viable."
The statement added: "Anne had a huge heart and touched everyone she met with her generous spirit.
"More than her extraordinary talent, she saw spreading kindness and joy as her life's work - especially moving the needle for acceptance of who you love.
"She will be remembered for her courageous honesty and dearly missed for her light."
Pictures and video footage obtained by TMZ following the incident showed Heche driving a blue Mini Cooper, which was later pictured severely damaged at the scene.
The Los Angeles Fire Department (LAFD) said the vehicle "erupted in heavy fire" after it crashed into the property.
59 firefighters took 65 minutes to access, confine and fully extinguish the flames within the heavily damaged structure, according to an LAFD report.
Heche is the former partner of US talk show host Ellen DeGeneres - the pair began dating in 1997 before separating in 2000 - and is known for films including Donnie Brasco, Cedar Rapids and the 1998 Psycho remake.
In an updated press release on Thursday, the LAPD confirmed an investigation was underway into the incident.
"On August 5 2022 at around 10.55am a vehicle driven by Anne Heche collided with a residence in the 1700 block of Walgrove Avenue," the report stated.
"Heche sustained significant injuries, was rendered medical attention by the Los Angeles Fire Department and subsequently transported to a local hospital where she is still receiving medical attention.
"As part of an investigative process, West Traffic Detectives composed a search warrant for a blood sample from Heche, which is common practice for a case of this manner."
The release added: "This case is still an active and ongoing investigation and is currently in the process of gathering additional evidence; to include final toxicology results, and medical records from both parties involved.
"It is the intent of the investigating Detectives to present this case to the appropriate prosecuting office: the Los Angeles County District Attorney or the Los Angeles City Attorney's office once all pertinent evidence has been gathered."