In the paper “Ketamine Can Reduce Harmful Drinking By Pharmacologically Rewriting Drinking Memories” a group of researchers examined the use of ketamine in treating patients who engage in harmful drinking or have alcohol use disorder (AUD), a.k.a. alcohol abuse.
We can answer the question we pose in the title with one word:
Yes.
However, we’re not quite at the point where we know exactly how to use ketamine to reduce alcohol use, misuse, and abuse. What the science tells us so far is that in some cases, in controlled conditions, ketamine can reduce alcohol consumption and curtail alcohol abuse.
What is ketamine?
Ketamine is an anesthetic medication that – when administered in low doses either intravenously or intranasally (nasal spray) – evidence shows is effective for treating depression and other mental health disorders. Preliminary research suggests ketamine may also be a viable treatment for problem alcohol use, abuse, and/or substance use disorders. The research team working on the study identified several previous publications that indicate the positive impact ketamine can have on people who engage in problem drinking or substance use.
The previous studies showed ketamine can help:
- Prolong abstinence from alcohol use
- Prolong abstinence from heroin use
- Reduce craving for cocaine
- Reduce cocaine use
In this new study, researchers explored a novel approach to the use of medication in treating problem alcohol use. To understand how this approach is different, it’s important to understand what medication-assisted treatment is, and how it works in other contexts.
What is Medication-Assisted Treatment?
The Substance Abuse and Mental Health Services Administration (SAMHSA) defines MAT as follows:
“MAT is the use of medications, in combination with counseling and behavioral therapies, to provide a ‘whole-patient’ approach to the treatment of substance use disorders. Medications used in MAT are approved by the Food and Drug Administration (FDA) and MAT programs are clinically driven and tailored to meet each patient’s needs.”
For example, medication-assisted treatment for opioid use disorder (MAT for OUD) involves medications that either block the action of opioids in the brain, partially block the action of opioids in the brain, or occupy opioid receptors in the brain without causing the euphoria or elation associated with opioids. In addition, MAT can help reduce the severity of opioid withdrawal symptoms and decrease cravings for opioids, both of which significantly reduce the likelihood of relapse.
The medications currently approved for OUD are buprenorphine, methadone, and naltrexone. SAMHSA indicates that MAT for people with OUD with these approved medications has the following benefits, above and beyond mitigating withdrawal symptoms and reducing opioid cravings:
- Decrease overall opioid use
- Decrease risk of fatal overdose
- Reduce criminal activity
- Restore typical function in family, social, and academic situations
- Increase time in treatment
- Restore ability to seek and secure work/employment
Those outcomes are all positive. For some people with OUD, those changes are both life-changing and life-saving. That’s why researchers have a compelling interest in finding an effective medication of alcohol use, misuse, and abuse. Like opioid use disorder, alcohol use disorder (AUD) and/or excess alcohol use can lead to physical problems and emotional problems. It can also disrupt relationships, impair work performance, academic achievement, and degrade overall quality of life and wellbeing.
In other words, AUD and/or excess drinking can cause serious harm to individuals and families. To understand the scope of the alcohol problem in the U.S., let’s take a look at the latest prevalence data on alcohol use, alcohol use disorder, and treatment for problem alcohol use in the U.S. and around the world.
Alcohol Use Disorder: Facts and Figures
Here’s a condensed version of the definition of alcohol use disorder published in the Diagnostic and Statistical Manual of Mental Disorders, Volume 5 (DSM-5):
“Alcohol use disorder (AUD) is a chronic, relapsing condition characterized by an impaired ability to stop or control alcohol use despite clinically significant impairment, distress, or other adverse consequences.”
Using that definition as a foundation, we can understand that alcohol use disorder is a chronic, relapsing medical condition. In that way, it’s similar to other chronic, relapsing medical conditions such as diabetes or hypertension. Those conditions respond well to medication, which means it’s possible that a condition like AUD may respond well to medication as well – and evidence shows that it does.
In the U.S., there are currently five medications approved by the Food and Drug Administration (FDA) for the treatment of alcohol use disorder:
- Disulfiram
- Acamprosate
- Naltrexone
- Nalmefene
- Baclofen
Alcohol Use Disorder in the U.S. and Around the World: Facts and Figures
Here’s the most recent reliable data on the prevalence of AUD in the world, as published by the World Health Organization (WHO):
- AUD diagnosis, total:
- 4 million people
- AUD is involved in 5.9% of deaths worldwide:
- Men: 7.6%
- Women: 4.0%
Now let’s look at the types of problems related to excess alcohol use and/or AUD.
- The WHO indicates excess alcohol use causes:
- Cardiovascular disease
- Cancer
- Liver disease
- Accidents and injuries
- The WHO also indicates excess alcohol use increases worldwide rates of clinical mental health diagnosis, including:
- Depressive disorders
- Anxiety disorders
- Other mental health disorders
The facts tell us that excess alcohol use is a significant problem around the world, and contributes to a wide range of physical and mental health disorders and conditions: that’s why researchers and clinicians engage in an ongoing search for any type of treatment that can reduce the harm caused by excess alcohol use, including any potential medications.
We shared the statistics on what alcohol use looks like around the world. Now we’ll report the rates of problem alcohol use in the U.S., published by the National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) in the 2021 National Survey on Drug Use and Health (2021 NSDUH).
Here’s the data:
Alcohol Use in the U.S: 2020
- Used alcohol in the past month:
- Total: 133.1 million
- Binge drinking:
- Total: 60.0 million
- Binge drinking by age:
- Young adults 18-25: 9.8 million
- Adults 26+: 49.3 million
- Adolescents 12-17: 995,000
- Underage drinking: 3.2 million
- Alcohol use disorder (AUD):
- Total: 29.5 million
- Alcohol use disorder by age:
- Adolescents 12-17: 894,000
- Young adults 18-25: 5.0 million
- Adults 26+: 23.6 million
Treatment for Alcohol Use Disorder: 2021
- Received treatment:
- Total: 1.4 million
- That’s just 4.6%
- Received treatment, by age:
- Adolescents 12-17: 32,000
- That’s just 3.6%
- Young adults 18-25: 136,000
- That’s just 2.7%
- Adults age 26+: 1.2 million
- That’s just 5.0%
- Adolescents 12-17: 32,000
The last set of AUD statistics we’ll look at ties these figures directly to the primary topic of this article: the number of people who received medication-assisted treatment for alcohol use disorder.
Treatment for Alcohol Use Disorder With Medication
- Received any treatment for alcohol use, with or without AUD diagnosis:
- 2.6 million
- That’s around 11%
- Received medication for AUD, among those diagnoses with AUD:
- 381,000
- That’s around 15%
- Received medication for AUD, with AUD diagnosis:
- 265,000
- That’s just 0.9%
We can see that what we call the treatment gap – i.e. the difference between the number of people who receive treatment and the number of people who need treatment – is far too large. That’s one more reason the search for effective AUD treatment with medication continues: millions of people report problem drinking and/or AUD, and only a small percentage get the treatment they need.
If scientists can find a medication that increases likelihood of successful treatment, and reduces likelihood of relapse, then we can use that medication to help people restore balance to their lives and live free from addiction.
MAT for Alcohol Use: Ketamine Technique Different Than MAT for OUD
We described the broad strokes of how MAT for OUD works above. In a nutshell, medications for opioid use disorder work by occupying the same structures in the brain opioids typically occupy, without causing the euphoria or elation – known as reinforcing properties – related to opioid use.
When a substance has properties that lead to pleasure or positive feelings, those properties are reinforcing. That means we form a memory of the way they make us feel – elated, euphoric, good – and when we think about those substances, we remember those feelings. Those good feelings, and the memory of those good feelings, drive our behavior.
When a person ingests a substance like alcohol that makes them feel good, they form a memory of that substance. That positive memory causes them to seek the substance: when they think about the substance, the memory is good, which means they’re likely to ingest the substance again. When this process is repeated over and over, risk of disordered use – a.k.a. abuse or addiction – increase dramatically.
Researchers designed a protocol wherein they interrupt what happens when a person who drinks alcohol thinks about alcohol. They hypothesized that if they administered ketamine at the time the person calls up that memory of alcohol, the ketamine might reduce the power and reduce the reinforcing quality of that memory. This, in turn, they hypothesized, would reduce overall alcohol intake and potentially eliminate problem drinking.
Medication for OUD, on the other hand, eliminates the reinforcing properties of opioids by occupying the opioid receptors in the human brain, rather than interrupting the association of the memory of opioids from the positive feelings associated with them.
Ketamine for Alcohol Abuse: The Experiment
To test their hypothesis, researchers divided 90 beer drinkers into three groups:
- Experimental Group 1: Memory Retrieval + Ketamine Group, called RET+KET
- Control Group: Memory Retrieval + Orange Juice Group, called NoRET+KET
- Experimental Group 2: Memory Retrieval + Placebo, called RET+PBO
Here’s how the experiment worked.
Day One: Measuring Urges and Creating Memories
Researchers gave participants in all three groups a glass of beer and told they could drink it after looking at and rating a series of images. They then rated the power of their urge to drink triggered by either pictures of orange juice or pictures of beer, then rated the urge to drink the beer they received, and how much they thought they’d enjoy drinking that beer.
All three groups followed the same process.
Day Two: Retrieving and Destabilizing Memories
Researchers repeated the process from the first day, with key differences. In the NoRET+KET group, they replaced the beer with orange juice, and showed only images of orange juice instead of images of beer. For all three groups, the researchers withheld the drink – either beer or orange juice – at the time they promised they’d allow participants to drink it.
This caused what’s called a negative prediction error, a phenomenon that’s known to destabilize memories. Instead of reinforcing and consolidating the memory, an interruption caused by withholding the glass of beer or orange juice resulted in neither consolidation nor reinforcement.
During that window of time, researchers administered either ketamine or placebo (saline) for 30 minutes using and intravenous drip.
Day Three: Measuring Urges and The Power of Memories
On the third day, participants followed the same protocol as the first day. The most important part of this day was rating the urge to drink on a five point scale from greatly decreased to greatly increased. Researchers then conducted follow up assessments at one, three, and six months post treatment, and performed a final assessment nine months post treatment.
Now let’s see what they found.
Ketamine for Alcohol Abuse: The Results
Researchers measured reactivity to pictures of alcohol on the third day of the experimental protocol, which took place ten days after treatment with ketamine or placebo. Here are the results:
Reactivity to Alcohol:
- RET+KET group: All members of this group reported significant reductions in the anticipation of how good the beer would taste, the urge to drink the beer, and the urge to drink more beer after finishing the beer.
- NoRET+KET group: No members of this group reported reduction in anticipation, urge to drink, or urge to continue drinking.
- RET+PBO: No members of this group reported reduction in anticipation, urge to drink, or urge to continue drinking.
Drinking Behavior:
-
Experimental Day Three:
- RET+KET group: Significant reduction in drinking days
- NoRET+KET group: Small reduction in drinking days
- RET+PBO: No significant reduction in drinking days
-
One Month:
- RET+KET group: Significant reduction in overall alcohol consumption
- NoRET+KET group: Small but significant reduction in overall alcohol consumption
- RET+PBO: No significant reduction in overall alcohol consumption
-
Two Months:
- RET+KET group: Significant reduction in overall alcohol consumption continued
- NoRET+KET group: Significant reduction in overall alcohol consumption, but not as large as the RET+KET group
- RET+PBO: No significant reduction in overall alcohol consumption
-
Three Months:
- RET+KET group: Significant reduction in overall alcohol consumption stabilized
- NoRET+KET group: Significant reduction in overall alcohol consumption stabilized
- RET+PBO: Significant reduction in overall alcohol consumption appeared
-
Six Months:
- RET+KET group: Reduction in overall alcohol consumption remained stable
- NoRET+KET group: Reduction in overall alcohol consumption stabilized
- RET+PBO: Significant reduction in overall alcohol consumption stabilized
-
Nine months:
- RET+KET group: Another significant reduction in overall alcohol consumption occurred
- NoRET+KET group: Another significant reduction in overall alcohol consumption occurred, but not as large as the RET+KET group
- RET+PBO: Significant reduction in overall alcohol consumption stabilized
What we see here is informative – but it’s not exactly what we expected. The first metric, reactivity to alcohol, conformed to expectations: the ketamine group showed significant reduction in alcohol-related urges, while the other two groups showed no such reduction.
Then the results get interesting.
The experiment confirms that interrupting memory consolidation affects overall alcohol use, with all three groups eventually showing significant reductions in overall alcohol use for up to nine months after treatment. The two groups who took ketamine showed significant reductions earlier in the experimental process, which indicates that in this context, ketamine is effective in augmenting the interruption of memory consolidation, and can result in rapid and long-lasting reductions in both the urge to drink alcohol and overall alcohol consumption.
That’s an important finding, which has the potential to change the way we treat substance use, misuse, disordered use, and addiction in the years to come. To confirm the “yes” answer to the question we pose in the beginning of this article, we now have data on our side.
In the experiment we discuss in this article, ketamine did, in fact, lead to a reduction in alcohol abuse.
How This Research Helps
The study we discuss above is one of the first of its kind. Researchers looked at two methods that are new to addiction treatment: memory reconsolidation interruption and ketamine infusions. They found that the combination of ketamine and interrupting memories reduced reactions to alcohol-related cues – i.e. the pictures – quickly, and the results persisted for nine months.
Here’s how the research team describes these results:
“Comprehensive reductions in cue reactivity and meaningful, lasting reductions in alcohol consumption outside of the lab after a single brief manipulation are unprecedented in alcohol research. This speaks to the potential scope of the reconsolidation-interference approach.”
Whereas psychosocial approaches such as cognitive behavioral therapy (CBT) rely on creating cognitive strategies to suppress alcohol-related cue reaction over a period of weeks or months, this approach overwrites those reactions almost immediately, and result in behavioral change. Researchers believe a comprehensive approach, utilizing ketamine, memory reconsolidation interruption, and traditional therapy may improve outcomes for people who engage in problem drinking and/or people with clinically diagnosed alcohol use disorder (AUD).
Here’s more analysis from the study authors:
“This is the first study to demonstrate interference with the reconsolidation of maladaptive alcohol memories in humans using ketamine. These findings highlight the promise of reconsolidation interference as a therapeutic mechanism in harmful drinking, alcohol and substance use disorders…and may of the next generation of more effective long-term treatments for addictive disorders.”
The method and the use of ketamine have promise: that’s certain. If researchers find a combination of approaches that can become the gold-standard treatment for AUD, in the way that current MAT is considered the gold standard treatment for OUD, then providers everywhere can offer new hope to people with alcohol use disorder, people who engage in problem drinking, or people who simply want to reduce their overall alcohol consumption.
