Among the details that emerged Thursday about actor Matthew Perry’s death was that the Friends star had been undergoing intravenous ketamine therapy.
The coroner concluded that the treatment, which is available in both the US and Britain, did not cause Perry’s death, and prosecutors allege the drug was supplied illegally.
Five people, including two doctors, Perry’s assistant and an alleged drug dealer, were indicted for supplying drugs to Perry outside of his treatment plan.
Perry, 54, has openly admitted to a history of drug abuse, and prosecutors allege the defendants exploited his addiction to profit from it.
What is Ketamine?
Ketamine is an anesthetic drug that can be used in medical settings to treat depression, anxiety, and pain.
However, it also has dissociative effects – distorting vision, hearing and perception of time – and has a calming and relaxing effect, which is why it is sometimes used illicitly.
According to addiction advice service Talk to Frank, ketamine increases heart rate and blood pressure and can make users confused and agitated, which could lead to them harming themselves without realising.
Chronic ketamine use has been associated with liver damage and can also cause bladder problems, including incontinence.
What is Ketamine Infusion Therapy?
Ketamine is used to treat depression when traditional antidepressants have not worked.
“On a biological level, the areas of the brain involved in disappointment are probably switched off,” says Professor Rupert McShane, a psychiatrist at the University of Oxford who runs an NHS ketamine treatment clinic. “Those areas are probably involved in depression.”
Dr Rajalingam Yadu, a consultant at London’s Royal Free Hospital, who also runs the ketamine therapy clinic Save Minds, told the BBC that the patients he treats suffer from long-term depression and have usually tried at least seven different medications without any improvement.
“These are people who have tried everything in life, have extreme suicidal thoughts and will commit suicide if given the opportunity.”
The treatment has also been used by celebrities, including Perry and billionaire entrepreneur Elon Musk, who has said he has used ketamine to treat depression.
In an interview with CNN in March, the X and Tesla owner said the drug “helps me get out of negative feelings.”
How does ketamine infusion therapy work?
Ketamine therapy works by giving a smaller amount of the drug intravenously than is used for anesthesia.
“For depression, we use doses that are lower than what we use for chronic pain, really lower than what patients would receive as an anaesthetic,” says Dr Mario Juruena, a psychiatrist at King’s College London who specializes in treatment-resistant mental illness.
Ketamine works faster than traditional antidepressants, but its effects also wear off more quickly.
“The drug has a short half-life, so at any one point in time patients only have a very short time to feel the effects,” Dr Juruena told the BBC, stressing the importance of monitoring patients’ mental health to prevent depression relapsing.
Dr Yadu said that unlike other mainstream antidepressants, ketamine has been shown to act on nerves that interact with the chemical glutamate, the most abundant neurotransmitter in the nervous system.
Some studies suggest that ketamine may also help reverse synaptic pruning (the elimination of neurons), which occurs naturally but may also be associated with chronic stress and depression.
“When you become depressed, neurotransmitters in the brain seem to shrink,” Prof McShane told the BBC. “So some of the neurons in a depressed state become more like winter trees. And when you give them ketamine, they become more like spring trees.”
He added that the drug could reduce the “cycle of rumination” that exacerbates suicidal thoughts and depression.
Experts are studying why it works for some patients and not for others.
Dr Juruena told the BBC that more than 60% of patients responded well to ketamine treatment, which was usually given alongside other antidepressants or psychological therapy.
Clinicians warn that taking ketamine, even under the supervision of a medical professional, can have side effects, though Dr. Juruena says these are not common because of the low doses.
Dr Yadu said while many of his patients’ experiences have been positive, some have been unpleasant and can bring back bad memories.
“Ketamine can be very effective for people where other drugs have not worked, but one of the problems is that you have to keep taking it, and we’re not used to that being a good thing,” Prof McShane said.
Yadu said he wouldn’t use ketamine to treat patients with addiction tendencies, but some doctors are considering it as a treatment for drug and alcohol addiction.
However, administering ketamine “intravenously,” or through an infusion, is not the only way to treat patients with ketamine.
Dr. Juruena said it can also be given as an injection, nasal spray or capsule.
Why was ketamine infusion therapy not considered a factor in Perry’s death?
Experts say that to be effective as an antidepressant, ketamine must be administered in precise, small doses through an intravenous infusion.
However, an autopsy found that Perry had high levels of ketamine in his blood and that he died from “acute adverse effects” of the drug.
The coroner also found that he had last received intravenous ketamine treatment more than a week before his death, by which time the drug’s effects had worn off.
Doctors also said Perry had much higher levels of ketamine in his system when he died.
Prosecutors allege that Perry’s assistant administered at least 27 ketamine injections to Perry in the four days before his death.