Ketamine & Alcohol: A Combination Best Avoided

Alcohol is among the most popular, widely available drugs, and its toxic and addictive potential is well-known. The same can be said for ketamine. While (mostly) safe on their own, combining these drugs together substantially increases your risk of adverse effects — which can be fatal in severe cases.

Here’s what you need to know to mitigate risk.

Can You Mix Ketamine & Alcohol?

While we typically consider alcohol and ketamine to be relatively safe drugs on their own, combining them can significantly enhance the potential dangers of both substances.

Alcohol (ethanol) and ketamine both produce toxic metabolites — compounds left over after metabolism.

One study suggests the synergistic effects of the two can bolster the toxicity of both ketamine and ethanol [1]. This study observed drug screenings from various parts of the world involving ketamine admissions in hospitals, noting:

• Ethanol was present in 27% of Australian ketamine overdoses between 2000–2019
• Between the years 1993-2006 in the UK, 50% of postmortem ketamine deaths showed the presence of alcohol
• 25% of patients in Bologna, Italy, who sought emergency care for ketamine had alcohol present in their systems
• Studies in party/rave contexts showed at least 65% of ketamine users were also consuming alcohol
• Alcohol is likely present in the lives of up to 98% of people who frequently use ketamine

The correlation isn’t positive, but plenty of other studies have shown the long-term effects of combining alcohol and ketamine can be dangerous, too.

The Effects of Mixing Ketamine & Alcohol

The effects of mixing ketamine and alcohol can be enjoyable or alarming, depending on how prepared and willing you are for the experience. 

Both drugs interact with some of the same receptors and, as a result, alcohol can bolster some effects of ketamine — specifically, sedation, cognitive decline, loss of balance, inability to move, and others. It’s also common to experience high levels of nausea, “the spins” associated with alcohol, and headaches the following day.

Combining the two is especially dangerous for individuals without a tolerance to one or both drugs. Since they work synergistically, even a small amount of alcohol and ketamine together in a naive user can be fatal.

People enjoy mixing the two for the elevated effect, but it’s worth noting that many who try the combination avidly warn others to avoid it. Whether someone finds it enjoyable depends on expectations, dosage, surroundings, company, and personal preference.

Ketamine & Alcohol Risks

Mixing ketamine and alcohol is rarely fatal, though it can be dangerous. There are several areas of concern when it comes to the combination, with the main ones being:

1. Cognitive Concerns — Alcohol and ketamine greatly impact cognition, memory, and other core behavioral factors. This amnesia has led to ketamine’s use as a tool for sexual assault and “date rape.”
2. Mood and Behavioral Risks — In the short term, combining ketamine and alcohol can lead to long-term effects on mood and cognition in frequent users. It can also cause higher levels of anxiety and depression and occasionally cause schizophrenic symptoms.
3. Cardiovascular Problems — Ketamine and alcohol both affect the cardiovascular system. Combined, they could result in a higher likelihood of chest pain, heart palpitations, irregular/fast heartbeat, and more.
4. Respiratory Depression — Both drugs can cause breathing to slow, and the synergistic effect could be dangerous.
5. Urinary Tract Issues — Ketamine’s effect on the urinary tract and liver, paired with ethanol’s toxicity in the kidneys, could make for an exceptionally harmful combination.
6. Addictive Potential — One study found a significantly higher level of dopaminergic reward following the use of ketamine and ethanol in combination than individually [2]. This may mean the combination has a higher likelihood of dependence and chaotic use patterns.

Binging on Ketamine & Alcohol Increases Risk

A recent rodent study reported the combination of ketamine and alcohol “consistently exhibited an increase in the conditioned rewarding effects by 2.34 fold [3].” While research concerning its effects on humans is scarce, this points to a potentially massive area of concern.

The elevated dopaminergic reward of drug use is a major reason people continue using them even after health complications arise. Reports detail this phenomenon with ketamine’s impact on the urinary tract [4], and it’s common with alcohol dependence as well.

Problems often extend into mental health concerns as well. In one study, rodents were placed on a 3-day regimen of daily ethanol and ketamine infusions and presented elevated levels of anxiety and depression [5].

Alcohol has depressant effects on its own, and while ketamine is a popular antidepressant treatment, the pairing seems to have the opposite effect. These effects may occur in the short term but often develop into long-term problems with heavy use.

Harm Reduction Tips for Mixing Ketamine & Alcohol

It’s best to avoid mixing ketamine and alcohol, but the reality is that it’s a widespread practice. Should you decide to partake, simple measures can help lower the risk.

1. Start Low, Go Slow — Start with less alcohol and ketamine than you usually would since they’ll be stronger together. Get a feel for the combination before slowly, incrementally taking more. Remember, alcohol can take up to an hour to take effect. 
2. Know What You’re Doing — At a minimum, understand the appropriate dosage, the types of effects you should expect, and when you should start to be concerned.
3. Test Your Ketamine — If you’re combining ketamine and alcohol, you’re likely getting your ketamine from a clandestine source devoid of regulation. While it’s certainly possible to have a source for pure, safe ketamine, you should always test every batch before taking it. 
4. Have a Healthy Mindset and a Safe Setting — Surround yourself with people you trust in an environment you feel comfortable in, with a relaxed mindset. Do not attempt to self-treat depression with ketamine and expect a minor depressive potential from combining it with alcohol.
5. Don’t Use Alone — Always have someone you trust nearby (preferably sober or at least more sober than you) in case something goes wrong.
6. Know the Red Flags — Be prepared for potentially difficult experiences and have a friend ready to jump in if you’re overdosing or experiencing a serious medical concern.
7. Take Long Breaks — The stress alcohol and ketamine place on the system isn’t something you should subject your body to often. Give yourself time to rest between taking ketamine and alcohol together, and avoid both for a minimum of a couple of weeks.

Pharmacological Effects of Mixing Ketamine and Alcohol

Here’s a breakdown of the main effects ketamine and alcohol have on the system [1]:

Affected Area	Activity	Effect
Glutamate	Both activate the release of glutamate and reduce its rate of absorption, resulting in high concentrations.	Glutamate is an excitatory neurotransmitter, and large doses can overwhelm the brain with excitement and activity — contributing in large part to the effects of ketamine.
Gamma-aminobutyric acid (GABA)	Alcohol mimics GABA, inhibiting the same receptor and impacting the natural production of this neurotransmitter.	GABA is the inhibitory chemical messenger, bringing rest, relaxation, and calmness to the brain Impacts on the natural production of GABA can cause a variety of mental health concerns.
Dopamine	Ketamine and alcohol both activate dopamine release, and ketamine prevents the absorption of dopamine back into the system by directly activating the D2 dopamine receptor.	The release of dopamine and resistance to absorbing it results in high levels of the “reward” neurotransmitter and is likely the biggest cause of euphoric and schizophrenic-like symptoms of ketamine.
cAMP-Responsive Element Binding (CREB) Protein	Ketamine and alcohol both inhibit crucial components of CREB formation and release.	CREB is responsible for our long-term memory, meaning this is likely a key factor in the amnesiac potential of ketamine and alcohol.
5-hydroxytryptamine-2A (5HT2A) Receptors	Ketamine activates these receptors directly along with the above mechanisms; alcohol restricts serotonin release, with some opposing effects to ketamine.	The combination of ketamine and alcohol likely results in less serotonin — the regulator of happiness, memory, and many other functions — production and release than ketamine on its own.
Acetylcholine (Ach) / The Chologinergic System	Ketamine inhibits Ach, the primary messenger of this system.	In combination with some of the other effects, it may help with an elongated boost of adrenaline response in the system and help to release serotonin.

Co-Toxicities of Ketamine & Alcohol

The side effects of ketamine or alcohol use alone are both likely harsher than consumers often realize. Together, they can bolster the harm and create severe and lasting damage. 

Some of the concerns surrounding ketamine and alcohol toxicities include:

• Neuro-inflammation — Inflammation of neurons and overstimulation of the brain is a key factor in the depressing quality of combining ketamine and alcohol. Over prolonged periods, this inflammation can result in lasting damage to mental health.
• Liver Toxicity — Ketamine and alcohol are both toxic to the liver, though we don’t know the mechanisms for ketamine. Whether it’s the same pathway as ethanol or a different one, either option is dangerous.
• Urinary Tract Toxicity — Ketamine’s toxicity on the urinary tract is one of its major concerns. Ethanol also has damaging qualities on this system through different mechanisms, compounding the harm to the system.
• Cardiovascular Stress— Ketamine and alcohol both put stress on the heart and cardiovascular system and can result in lasting damage from recurrent use. The impact can be dire or even deadly for anyone with problems in this area already.
• Respiratory Cellular Damage — The cellular stress and damage ketamine and alcohol both put on the respiratory system can make frequent consumers more vulnerable to developing breathing concerns or conditions.

This is likely not an exhaustive list since very little research surrounds this combination. 

Ketamine for the Treatment of Alcohol Use Disorder (AUD)

On the other end of the spectrum, some research suggests ketamine could help with alcohol use disorder (AUD). This is likely a result of ketamine’s potential to treat anxiety and depression — two major factors of AUD [6].

Heightened levels of depression and anxiety can often drive a person back to old habits and problematic drug use. Ketamine can assist by providing rapid relief from these symptoms for many.

The downside of ketamine therapy is that it rarely has a long-lasting effect on patients; most effects wear off within a week or so. For people dealing with anxiety or depression who want to return to alcohol, however, instantaneous relief may be more important than a long-acting one.

Depending on the severity of your use before seeking treatment, clinicians may prescribe a schedule of infusions over several months or advise patients to come as needed. Since ketamine therapy sessions can fit within a window of an hour or two, this could become a significant line of defense for people wanting to leave their dependence behind.

However, given the current scarcity of research on the topic, it’s still too early to know for sure.

Pharmacological Mechanisms: Ketamine Therapy for Alcohol Use Disorder

Alcohol has many similar mechanisms to ketamine, with chronic use leading to changes in functionality. The main receptor they interact with is the N-methyl-D-aspartate receptor (NMDAR), which regulates several bodily functions. 

Chronic antagonism through alcohol can cause some of the functionality to atrophy — or degenerate due to chronic inhibition.

Some of the different ways frequent, chaotic alcohol consumption can affect people include:

• Glutamate Inefficiency — Chronic alcohol use dulls the functionality of the excitatory neuron glutamate, leading to depression, stress, and a negative outlook.
• Gamma-aminobutyric Acid (GABA) Production Problems — The flipside of glutamate, GABA is an inhibitory neurotransmitter that alcohol mimics. Though it results in depression and sedation, GABA also has a rewarding component that gives it an addictive quality as well.
• Neurogenesis/Neuroplasticity Regulation Concerns — NMDARs are partially responsible for the growth of new neurons and nerve tissue (neurogenesis) and the development of new neuronal connections (neuroplasticity). Chronic activation through alcohol can harm the production and regulation of this function, contributing to mood and cognition concerns.

Ketamine may help reverse some of these effects and stave off cravings and the anxiety/depression associated with withdrawal. While there’s still a lot to learn about the effects of ketamine on individuals with AUD, it could help restore the functionality of all these components temporarily.

Until we know for sure, however, we cannot say for sure that ketamine could be helpful.

Frequently Asked Questions: Ketamine & Alcohol

Here are some of the most common questions people ask about ketamine and alcohol:

1. Is It Safe To Mix Alcohol and Ketamine?

No, mixing ketamine and alcohol can be incredibly dangerous. While it’s a common combination in club and concert settings, there are serious risks to consider before partaking.

Users can mitigate many of the risks through education, consuming reasonable quantities, and other harm-reduction practices, but there will always be risks.

2. How Long Should I Wait Between Taking Ketamine and Alcohol?

You should wait until the effects fully wear off before drinking alcohol after taking ketamine (and vice versa). There’s very little risk of an adverse experience from either drug in reasonable amounts as long as the other has entirely worn off.

3. Is Ketamine Combined With Alcohol Addictive?

Yes — both ketamine and alcohol are addictive, and research suggests the combination may be even more so. If you do decide to combine alcohol and ketamine, do so sparingly and with long breaks before doing so again to prevent building tolerance or dependence.

4. What Should I Do if I’m Having a  Reaction to Ketamine and Alcohol?

Seek immediate medical attention if you or someone else is having a bad reaction to alcohol and ketamine. Potentially deadly side effects can arise, and a medical professional can screen for and treat them properly.

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