What Is Ketamine Used for Medically? Alcoholism Could Be Next for Drug After Promising Study

A study has found that ketamine infusions combined with psychological therapy can help severe alcoholics abstain for longer periods of time.

The results of the phase II trial, which have been published in The American Journal of Psychiatry, demonstrated that treatment with three infusions of ketamine in low doses was well tolerated by patients with alcohol use disorder (AUD) and associated with more days of abstinence from alcohol over a six-month follow-up period.

The Ketamine for reduction of Alcohol Relapse (KARE) trial, led by the University of Exeter in the United Kingdom, involved 96 people with alcohol abuse issues who were abstinent at the start of the trial.

Researchers found that participants who received ketamine infusions combined with therapy stayed completely sober for 162 of 180 days, representing 87 percent abstinence. This was more than 2.5 times higher than the group that only received a placebo and therapy.

The study is a phase II trial, meaning that it was conducted primarily to test the feasibility and safety of the treatment.

But the results provide an early indication that ketamine infusions alongside psychological therapy may be beneficial in the treatment of severe alcoholism. Further trials involving larger numbers of patients will be required to confirm the effects.

The trial was the first of its kind to examine whether a low dose of ketamine could help prevent people from quickly returning to heavy drinking after stopping, when combined with therapy.

Alcohol abuse accounts for more than 5 percent of the world's disease burden, but many people with AUD do not respond to currently available drug and behavioral treatments.

Evidence from previous research suggests that ketamine may be an effective treatment to help people abstain from alcohol.

In part, this is due to the fact that ketamine appears to have antidepressant properties. Recently, the U.S. Food and Drug Administration and European Medicines Agency approved esketamine—a drug derived from ketamine—as a therapeutic for treatment-resistant depression.

Depressive symptoms are common in people with AUD and the likelihood of alcohol relapse is elevated in people with such symptoms. Ketamine may help people to abstain by temporarily alleviating depressive symptoms.

Ketamine may also provide a window during which psychological therapies can be more effective. Early evidence shows that the drug increase neurogenesis, the process by which new neurons, or nerve cells, are formed in the brain. This process is known to be disrupted in people with addictions.

Boosting neurogenesis may allow the patient to integrate lessons learned from psychological therapies and other addiction management strategies more easily. In addition, the subjective experience of someone receiving ketamine infusions may help patients gain a new perspective that could aid the process of psychological therapy.

Ketamine induces a sense of disassociation and disembodiment that some have described as producing a kind of "observer state" similar to that reported in people who practice mindfulness, allowing patients to consider thoughts and emotions from a more removed perspective.

Ketamine is a versatile medicine and perhaps the most widely used anesthetic in the world. The World Health Organization (WHO) lists ketamine—also used for analgesia, or pain relief—as an essential medicine.

Ketamine is safer to administer than other anesthetics and pain relief drugs because it does not depress breathing or lower blood pressure. It also does not require expensive patient-monitoring equipment.

According to the WHO, the drug's high level of safety make it "indispensable" for surgery in low- and middle-income countries, disaster zones and conflict areas where anesthesiologists may not be available, and where running water, electricity and oxygen supplies are not easily accessible.

In recent years, there has been significant research into the drug's potential for the treatment of depressive disorders and epileptic seizures, and, to a lesser extent, anxiety conditions.

John Krystal, a professor of psychiatry at Yale University, who was not involved in the KARE trial, told Newsweek that the study was "exciting," highlighting a novel potential therapeutic use of ketamine for the treatment of addiction.

In the study, the group of participants that received psychotherapy during the ketamine administration increased their abstinent days by nearly 16 percent.

"These data are somewhat remarkable in that a very short-acting drug, ketamine, appears to produce persisting reductions in alcohol consumption," Krystal said.

"However, we will need to see this work replicated and extended to fully understand the clinical impact of this intervention. After all, a 16 percent increase in the number of abstinent days is desirable, but ultimately we are seeking treatments that drastically reduce or essentially eliminate heavy drinking days.

"The authors remind us that this was a modest proof-of-concept study and we should not expect it to answer questions related to clinical significance. I hope that this exciting work is followed by studies that help to more definitively shed light on the clinical impact of ketamine used within this treatment framework," he said.

Krystal said that the results of the study were "somewhat paradoxical" given that ketamine is also a commonly abused recreational drug.

"Ketamine is a drug with significant abuse liability. In some parts of the world, it is among the most commonly abused substances. Therefore there has been significant hesitancy in prescribing ketamine as a treatment for patients with substance use disorders," he said. "For example, patients with active substance use disorders other than tobacco were excluded from most of the Esketamine studies involved in the approval process."

According to Krystal, the therapeutic effect of ketamine on drinking in patients who have both depression and AUD could be seen as a consequence of the reduction in depressive symptoms—which may worsen the urge to drink.

But the increase in neuroplasticity, beginning several hours after ketamine infusion and lasting for several days, may also enhance the impact of psychotherapies that aim to extinguish the craving for alcohol, or improve control over impulses to drink.

Update 01/21/22, 6:06 a.m. ET: This article was updated to include comments from John Krystal.