Ketamine has been around for decades, but its use to treat certain health conditions remains controversial because of the risk for serious side effects and its potentially addictive qualities.
Ketamine has been approved by the U.S. Food and Drug Administration to be used as an anesthetic during diagnostic and surgical procedures. But because of its mind-altering effects, it also has gained popularity as a party drug under name likes "special K" and "super acid."
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Some doctors also use it off label to treat depression and other mental health conditions, as well as chronic pain.
These off-label uses have gained momentum since the beginning of the COVID-19 pandemic, when telemedicine regulations were loosened, including the ability to remotely prescribe controlled substances without a doctor's visit. It now can be prescribed to patients to take at home with very little supervision. This has some scientists concerned because there is very little data on the drug's safety and efficacy, especially long-term, and there are no definitive protocols for doctors and patients to follow.
Before the pandemic, ketamine had to be administered under careful medical supervision, either at in-patient or out-patient settings, because it can trigger hallucinations and a temporary spike in blood pressure.
Critics of the relaxed regulations point out that at-home treatment gives patients opportunities to take more ketamine than prescribed and give their drugs to someone else.
"One of the big concerns about ketamine is about its abuse liability," John Krystal, a Yale researcher who helped define the drug's therapeutic potential, told Bloomberg News. "If people are getting many doses at home, then the potential for abuse goes up significantly."
When the federal COVID-19 health emergency ends in May, it may become more difficult for doctors to prescribe ketamine for at-home treatment of mental health issues. If the Biden administration reinstates the Ryan Haight Act, a 2008 law that bars the prescription of controlled substances through telemedicine, ketamine users may be required to attend some in-person visits.
But The Washington Post reported in December that the Drug Enforcement Administration is working to make permanent the temporary waiver that allows ketamine and other medications to be prescribed remotely.
At least eight companies have provided ketamine via telemedicine since the pandemic began, the newspaper reported. Three of them, including the two best known companies – Nue Life and Mindbloom – have combined to treat more than 10,000 patients at home.
The New York Times recently interviewed more than 40 patients who have been using telemedicine to gain easier and less expensive access to ketamine to treat their mental health conditions. Though many called ketamine life-changing, some said they experienced serious bladder damage and struggled with the misuse of the drug and addiction. Many of them don't report these side effects out of fear that they no longer will be able to get the one drug that has been successful at treating their symptoms.
Dr. Michael D. Banov, a psychiatrist in Atlanta, and Dr. Rachel E. Landrum, of Louisiana State University, have warned that at-home ketamine treatments also pose the risk of dangerous interactions with other drugs that patients may be taking.
"With the self-administration and availability of multiple dosing with at-home ketamine, there is an opportunity for intentional or unintentional overadherence and overdosing," they wrote in a piece for Psychiatric Times. "There is a risk with combining at-home ketamine with alcohol or drugs of abuse including opiates, amphetamines, or benzodiazepines, or with legitimately prescribed medications that could have serious and life-threatening interactions."
Another source of concern is that many patients are getting their ketamine prescriptions filled by compounding pharmacies, which make different variations of the drug, including tablet and lozenge forms. But these pharmacies do not undergo the same scrutiny as drug manufacturers.
Some doctors argue that even in-person ketamine clinics can be risky. At some of these clinics, patients must undergo screening to qualify, and they must meet with a therapist before and after receiving their treatments. Yet, there are few industry standards and, because these clinics aren't federally regulated, there are no clear guidelines to follow.
Dr. Smith Das, an associate professor at Stanford University and chairwoman of the American Psychiatric Association's Council on Addiction Psychiatry told NBC News that "people are getting treatments that haven't been well-proven, well-studied or following any guidelines."
What the research shows
Many experts say more research is needed on the safety and efficacy of ketamine, especially its long-term use. But past research has suggested it may be an effective treatment for several conditions.
Ketamine, a sedative, has been shown to be effective at reducing suicidal thoughts and treatment-resistant depression. Researchers aren't sure why, but one theory suggests that the drug boosts the ability of brain cells to communicate with each other. Some studies have shown that ketamine stimulates the regrowth of the synapses that connect the cells in the brain. People with treatment-resistant depression often have fewer of these synapses.
A study published in the British Medical Journal demonstrated ketamine's ability to reduce suicidal thoughts. Among 156 hospitalized adults, many of those given two doses 24 hours apart, in addition to standard care, found that their suicidal thoughts dissipated. By day three, 63% were in full remission, compared to about 32% of the patients who only received standard care.
But though ketamine offered faster relief, the effects of the drug were similar to standard care by the six-week mark. The researchers also found that ketamine helped patients with bipolar disorder the most – and not those with major depression. Other studies have shown similar results.
In 2019, the FDA approved a version of ketamine, called esketamine, for treatment-resistant depression. It has since been approved for people with depression and acute suicidal ideation. It is given as nasal spray, but must still be administered under medical supervision because it can have same mind-altering effects as ketamine.
Penn Medicine scientists have been trying to determine which parts of the brain circuit are affected by ketamine. So far, they have discovered that the drug impacts excitatory and inhibitory neurons, but it is still not clear if these neurons are responsible for ketamine's antidepressant effect.
Other studies have suggested ketamine can be an effective treatment for anxiety and anorexia, as well as substance use disorders, such as alcohol, cocaine, or opioid use disorder.
Research on its use in chronic pain also has been promising. Studies have shown ketamine can reduce neuropathic pain caused by chemotherapy and nerve injuries. It also has been used as an experimental treatment for Complex Regional Pain Syndrome, a chronic condition characterized by burning pain that starts in a limb after an injury and spreads to the whole body.
Research on ketamine's effects on chronic pain shows the drug can block the calcium that sets off the pain transmission neurons in the central nervous system. This reverses the sensitization process, giving the nerve cells time to heal.
Weighing the risks
When administered in carefully controlled doses under medical supervision, ketamine is considered safe by many scientists. But it does not come without risks. Common side effects include disorientation, aches and pains, impaired judgement, anxiety and clumsiness.
In some people, ketamine can cause a temporary spike in blood pressure and heart rate, breathing difficulties and an increase in intracranial pressure. Liver injury and cognitive deficits after treatment are possible, too.
The side effects vary depending on how ketamine is used and the dosage given, as well as the overall health of the person. They also can include nausea or vomiting, urinary problems, seizures, heart arrhythmia, cardiac arrest, hallucinations and addiction. Some data suggests that long-term use may lead to difficulties with memory, executive functioning, attention and self-control.
Ketamine is not recommended for anyone who has a medical condition in which high blood pressure could lead to an aneurysm, heart attack or aortic tear. It also is not recommended for people with schizophrenia or those who are pregnant or breastfeeding.