The Friends star’s autopsy report revealed on Friday that he had died as the result of an accident caused by “acute effects” of the drug. 

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It said he had undergone ketamine infusion therapy for depression and anxiety a week and a half before his death aged 54 on October 28.

But the ketamine in his system when he was found unresponsive in his Jacuzzi could not have been from that therapy session, according to the report.

Matthew’s ex Kayti Edwards says it’s unlikely he would have bought the drugs on the street and suspects they came from a doctor or nurse.

Mom-of-four Kayti, who runs a horse rescue in California, told The U.S. Sun: “I’m pretty sure that in Matthew’s brain ketamine infusions at a doctor’s would count as still being sober.

“In his brain it’s not the same as going on the street to buy crack or heroin.

“That probably was the stepping stone for him to go back to doing drugs.

“I think the doctors who had been working with Matthew should be investigated.

“I’m pretty sure he would have had an in with a doctor. 

“It’s very hard to get ketamine on the street but it is very easy for a doctor or a nurse to get.”

Kayti, 47, dated Matthew in 2006, worked as his assistant in 2011 at the height of his drug addiction and remained friends with him.

She had previously told The U.S. Sun she suspected he had relapsed after spotting several tell-tale signs prior to his death at his home in the upscale Pacific Palisades neighborhood of Los Angeles.

Kayti, who is the step-granddaughter of Mary Poppins legend Julie Andrews, said that she noticed several red flags after his death.

They included posting more than usual on social media, which she said was out of character.

She revealed that the use of his Batman-based alter ego “Mattman” was also something he did while high. 

And she recalled that Matthew – who shot to fame in the 1990s as beloved Friends character Chandler Bing – liked to get in water and be alone while taking drugs. 

His haunting final post on Instagram, five days before his death, showed him in his Jacuzzi and was signed “Mattman.”

Kayti, who last spoke with the star last year after he published his memoir Friends, Lovers And The Big Terrible Thing, said: “I wasn’t surprised when the medical examiner’s report dropped. 

“I already knew what it was so it wasn’t shocking to me. 

“I wasn’t there so I don’t know exactly what happened but I do know Matthew as a person and a friend and I know the patterns that led up to this. 

“I could see it from a mile away, he didn’t seem right during the last couple weeks of his life. 

“The sober people who knew him have never hung out with him when he was getting high so they wouldn’t know the signs.”

‘LOVED TO EXPERIMENT WITH DRUGS’

Matthew’s autopsy detailed how his current assistant found him floating face down in the water upon returning to his home after running errands.

The assistant plunged into the hot tub and dragged Matthew’s body to the steps then called 911.

First responders pulled Matthew from the water and onto the nearby grass, where he was pronounced dead.

Contributing to his death factors included drowning, coronary artery disease, and the effects of buprenorphine – a drug used to treat opioid addiction as well as acute and chronic pain.

Senior deputy medical examiner Raffi Djabourian found that there were “high levels of ketamine found in his post-mortem blood specimens.”

“The main lethal effects would be from both cardiovascular overstimulation and respiratory depression,” the report stated.

Ketamine infusions are used by medical professionals to treat depression but the dissociative anesthetic can also be taken recreationally.

There was no evidence of alcohol or other drugs like cocaine, methamphetamine, heroin, PCP, or fentanyl in the actor’s system.

Matthew had been very open about his battle with alcohol and opioid addiction, which he detailed in his memoir last year.

Kayti has previously said that when she worked as his assistant, Matthew would send her to pick up drugs including heroin and crack for him, even while she was pregnant.

The former model said: “Matthew loved to experiment with different drugs. 

“He would want to try different things to see what worked best for him.

“I remember he got heroin at one point and one of his friends showed him how to smoke it.

“He was always down for trying different stuff but I’m pretty sure the ketamine was a new thing because I never saw him doing it.”

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If you or someone you know is affected by any of the issues raised in this story, call SAMHSA (Substance Abuse and Mental Health Services Administration) at 1-800-662-HELP (4357).