Introduction

Nearly 15 million Americans struggle with alcohol use disorder (commonly known as alcoholism, addiction, and abuse), while 107 million are estimated to have the condition worldwide. Of those, some 140,000 will die due to excess alcohol consumption in the United States alone – making this a critical disorder to address. Unfortunately, it’s also one of the most challenging conditions to successfully treat, with a relapse rate of up to 60%. However, there may be a new tool emerging to help combat this potentially deadly disease. Research into the use of the psychedelic and dissociative anesthetic ketamine has yielded favorable results.^{(1, 2, 3, 4)}

Recent results from Phase II clinical trials show promise for reducing alcohol relapse by utilizing psychological therapy combined with ketamine to treat alcoholism. This study, featured in The American Journal of Psychiatry, was conducted by British researchers affiliated with several medical centers.⁽⁵⁾

What Is Alcohol Use Disorder?

Alcohol abuse contributes to roughly three million deaths each year worldwide. It can have serious side effects for those it doesn’t kill, including significant cognitive disabilities and poor health, according to the World Health Organization (WHO). The Centers for Disease Control also estimates that excessive alcohol use costs the American taxpayer $249 billion annually, of which $27 billion is attributed to healthcare alone. Overall, the harmful use of alcohol is responsible for 5.1% of the global disease burden, and is a leading risk factor for premature death and disability. Additionally, alcohol use disorder is a leading worldwide cause of death for people aged 15 to 49 years old.⁽⁶⁾

Some may have an image of people suffering from addiction as uncaring, unwilling to change, or too stubborn to attempt recovery. Dismissing people with a substance use disorder as having “brought it on themselves” is entirely false. Alcoholism is a brain disorder, which can make a person more vulnerable to relapse, often despite their best efforts.⁽⁷⁾

According to criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), alcohol use disorder (AUD) is described as a “maladaptive pattern of substance use leading to clinically significant impairment or distress.” In other words, an individual suffering from alcoholism has a reduced ability to stop or control drinking alcohol despite experiencing negative health, social life, or work consequences. This disorder can be classified as mild, moderate, or severe. At least two or more of the following criteria must occur at any time in the same 12-month period to receive a diagnosis of alcohol use disorder:

The DSM-5 defines tolerance as either:

Withdrawal occurs by either:⁽⁸⁾

How Ketamine May Help Treat Alcohol Use Disorder

There are multiple changes in the brain associated with alcohol use disorder. Critical neurotransmitters, such as dopamine, glutamate, and serotonin, are affected. This is where ketamine for alcoholism may help.⁽⁹⁾

Depression and stress are often associated with alcohol abuse and contribute to relapses. This association has led researchers to hypothesize that similar treatments may help all of these conditions. 

Alcohol use disorder is currently treated with the drugs disulfiram, naltrexone, and acamprosate and with psychological counseling. However, these treatments have limitations, so researchers are looking for more effective ways to manage the condition.

Among many drugs evaluated in research studies, ketamine shows some of the greatest potential in treating alcoholism and other substance use disorders. Ketamine, and its derivative esketamine, may also have significant promise as a novel medication for other conditions, such as depression. The Food and Drug Administration (FDA) has approved ketamine for use as a treatment for depression in the form of esketamine (marketed as Spravato). Other studies found that ketamine may have the potential to manage anxiety and obsessive-compulsive disorder (OCD).⁽¹⁰⁾

Ketamine treatments may help manage alcohol use disorder through different mechanisms. The drug is best known for its ability to modulate the neurotransmitter glutamate (a major excitatory neurotransmitter). However, it also influences dopamine, serotonin, and norepinephrine. Additionally, ketamine appears to help positively rewire the brain and support new connections between neurons in a process known as neurogenesis (the growth and development of new neural connections).^{(11, 12, 13, 14)}

Some studies found that ketamine treatment may be an effective therapy to sustain abstinence from alcohol. 

The Phase II clinical trial discussed here assessed the safety and efficacy of ketamine compared with a placebo in increasing abstinence in individuals with alcohol use disorder. Additionally, researchers evaluated the benefits of ketamine combined with mindfulness-based relapse prevention therapy versus ketamine and alcohol education.⁽⁵⁾

Ketamine to Treat Alcohol Abuse Study Methodology

The study was designed as a double-blind, placebo-controlled Phase II clinical trial. Double-blind means that neither the participants nor the researchers know which treatment participants receive until the study is completed. 

Placebo control means that one group received the treatment of ketamine while the other group received a dummy pill. In this study, the researchers offered four treatments: two of them using ketamine infusions, and the other two placebos in the form of saline infusions. Ketamine or saline infusions were combined with either psychological therapy or alcohol education. 

A Phase II clinical trial is a study that tests whether a new treatment works for a certain condition. It may also provide information about the treatment’s safety and effects. 

This trial studied 96 patients (35 women and 61 men) diagnosed with severe alcohol use disorder as per DSM-5 criteria. The mean age of the participants was 44.07 years old. The subjects were randomly assigned to one of the following four treatments:

The participants were asked to report the percentage of days they abstained from alcohol, with a six-month follow-up.

Ketamine for Alcohol Abuse Study Results

According to the researchers, the treatment with three weekly ketamine infusions was well-tolerated by participants, with no serious adverse reactions reported. Ketamine therapy was associated with more days of abstinence at the six-month follow-up. Those who received the ketamine treatment abstained from alcohol longer than those who received a placebo. 

The study also found that using psychological therapy combined with ketamine led to a greater reduction in drinking than ketamine plus alcohol education. 

Researchers found no significant difference in relapse rate when comparing the groups who received ketamine versus the placebo groups. 

Potential Impact of the Study

A potential new treatment, such as ketamine-assisted therapy, may pave the way for a significant reduction in alcohol relapse. This, in turn, has the potential to drastically change alcohol abuse disorder’s impact on people across the globe. A significant reduction in this deadly disease may help keep families together, prevent the loss of loved ones, and support the most heavily impacted communities in recovery.  

Overall, this Phase II clinical trial highlights the promising potential of ketamine and the benefits of using ketamine combined with psychological therapy to manage alcohol abuse. The study also showed that using ketamine as a medicine is largely well-tolerated. This is important because ketamine is known to have psychedelic effects and can cause addiction when taken in higher doses, misused, or taken without medical supervision. However, more research is needed before ketamine becomes an approved treatment for alcohol addiction.

Raising awareness about critical research into ketamine therapy is an important part of ensuring that much-needed, larger trials continue. With the relatively recent approval of esketamine as an add-on therapy for treatment-resistant depression, there is hope that ketamine may become a treatment for addiction and other conditions affecting mental health. 

Sources

Sources

1. U.S. Department of Health and Human Services. (n.d.). Alcohol Facts and Statistics. National Institute on Alcohol Abuse and Alcoholism. Retrieved January 24, 2023, from https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics

2. Ritchie, H., & Roser, M. (2018, April 16). Alcohol consumption. Our World in Data. Retrieved January 24, 2023, from https://ourworldindata.org/alcohol-consumption

3. Centers for Disease Control and Prevention. (2022, July 6). Deaths from excessive alcohol use in the United States. Centers for Disease Control and Prevention. Retrieved January 24, 2023, from https://www.cdc.gov/alcohol/features/excessive-alcohol-deaths.html#:~:text=More%20than%20140%2C000%20people%20die,how%20you%20can%20take%20action.

4. Moos RH, Moos BS. Rates and predictors of relapse after natural and treated remission from alcohol use disorders. Addiction. 2006 Feb;101(2):212-22. doi: 10.1111/j.1360-0443.2006.01310.x. PMID: 16445550; PMCID: PMC1976118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976118/

5. Grabski, M., McAndrew, A. Lawn, W., Marsh, B., Raymen, L.… & Celia J.A. Morgan, C.J.A. (2022). Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder. The American Journal Of Psychiatry. https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2021.21030277

6. World Health Organization (WHO) Alcohol, An Overview https://www.who.int/health-topics/alcohol#tab=tab_1

7. National Institutes on Alcohol Abuse and Alcoholism: Understanding Alcohol Use Disorder https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/understanding-alcohol-use-disorder

8. Medscape: What are the DSM-5 criteria for Alcohol Use Disorder? Updated March 2020 https://www.medscape.com/answers/285913-41535/what-are-the-dsm-5-criteria-for-%20alcohol-use-disorder

9. Lovinger, D.M.(2008) Communication Networks in the Brain. Alcohol Research and Health https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860493/

10. Worrell, S.D., Gould T.J. (2021). Therapeutic potential of ketamine for alcohol use disorder. Neuroscience and Behavior Review https://pubmed.ncbi.nlm.nih.gov/33989669/

11. Mion, G., Villevieille T. (2013) Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings). CNS Neuroscience and Therapeutics https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493357/.

12. Lily R Aleksandrova, Phillips A.G.(2021).Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends in Pharmacological Sciences https://pubmed.ncbi.nlm.nih.gov/34565579/

13. Yamamoto S, Ohba H, Nishiyama S, Harada N, Kakiuchi T, Tsukada H, Domino EF. Subanesthetic doses of ketamine transiently decrease serotonin transporter activity: a PET study in conscious monkeys. Neuropsychopharmacology. 2013 Dec;38(13):2666-74. doi: 10.1038/npp.2013.176. Epub 2013 Jul 24. PMID: 23880871; PMCID: PMC3828538.

14. Zorumski CF, Izumi Y, Mennerick S. Ketamine: NMDA Receptors and Beyond. J Neurosci. 2016 Nov 2;36(44):11158-11164. doi: 10.1523/JNEUROSCI.1547-16.2016. PMID: 27807158; PMCID: PMC5148235.