List of Ketamine Side Effects
Companies selling ketamine therapy rarely address ketamine’s side effects — but they are a genuine cause for concern. Here’s everything you need to know before you try ketamine — regardless of whether it’s clinical or recreational.
Research surrounding ketamine’s potential to help with certain conditions is promising — to say the least — but the risks aren’t anything to gloss over.
The vast majority of people tolerate occasional doses of ketamine well and only deal with minor side effects. But this isn’t universal — there are plenty of cases where people undergoing casual ketamine treatments suffer serious side effects.
Every drug has its risks, but ketamine presents some unique considerations pharmacologically compared to other psychedelics like magic mushrooms or LSD (lysergic acid diethylamide).
Even in therapeutic settings, many of the concerns we’ll go over below have cropped up within small samples of short-term clinical studies.
Let’s dive into the side effects of ketamine use and how they impact users:
Ketamine Risks: At A Glance
Ketamine regularly affects users in a few negative ways — generally broken into two categories: side effects and adverse reactions.
Side effects generally refer to lighter negative experiences as the result of the intoxication of ketamine.
The main side effects concern ketamine’s action on:
- The Heart and Cardiovascular Systems
- Cognitive Capabilities and Neurological System
- Psychological and Psychiatric Well-Being
Adverse reactions are more serious — and more likely when using ketamine in large doses for long periods.
Some of the ways ketamine can result in serious, sometimes lasting, damage include impacts on:
- Activity/Behavior — Ketamine has a high potential for abuse and addictive/chaotic behavior
- Cognitive Capabilities — Heavy ketamine use can leave a lasting impact on short- and long-term memory
- The Urinary Tract — Urinary problems are one of the most common concerns for frequent ketamine users, and ignoring them can be deadly
- The Liver — Closely related to the urinary tract, the impact on the liver can be equally as detrimental
Additionally, it’s important to approach with caution or steer clear of ketamine while on other medications impacting the central nervous system, including:
- Opiates, benzodiazepines, alcohol, and other depressants
- Stimulants, decongestants, and allergy medication
- Anything other medication impacting the urinary tract, liver, and cardiovascular system
1. High Blood Pressure
During and immediately after a ketamine session, it is common to experience an elevated heart rate and blood pressure. Occasionally, this can lead to irregular heartbeat patterns and pain or tightness in the chest.
One study found both systolic and diastolic blood pressure readings rose shortly after dosing, peaking between 30–50 minutes with a 10–50% increase in values.
Most people work through this uncomfortableness quickly, and some even experience a decrease in both blood pressure and heart rate [2]. For most, this didn’t present any major noticeable symptoms, and their blood pressure returned to normal within 2–4 hours.
Blood pressure elevation isn’t an inherent problem, but it does make ketamine use riskier for people with a history of hypertension or heart problems. Patients with healthy hearts will tolerate the temporary increase in activity well, but the risk gets higher as the heart’s health deteriorates.
2. Rapid Heart Rate
One of the most common side effects of ketamine is rapid heart rate (called tachycardia). It’s caused by ketamine’s action on the sympathetic nervous system — which is the part that controls the “fight or flight” stress-response. Ketamine stimulates the release of catecholamines (such as adrenaline) which causes heart rate to increase.
This side effect is one of the main reasons why people with heart problems or who are taking medications to control heart rate should avoid using ketamine.
Related: Who is not suitable for ketamine therapy?
3. Intoxication
Many would argue that intoxication is not a side effect, but a primary action of the drug. Whether this is a side effect or not depends on the reason for taking ketamine. Many of it’s antidepressive and antianxiety benefits rely on it’s unique psychoactive effect profile.
However, when treating pain, the intoxicating effects of ketamine are often considered a side effect.
The intoxicating profile of ketamine is often left out of research papers too — instead referring to this interaction as simply “cognitive effects” [1].
Related: Does Ketamine Therapy Get You High? | What Does Ketamine Feel Like?
4. Disorientation
Ketamine is a dissociative, which is a type of drug that gives you the feeling that your mind isn’t connected to your body. This can make it difficult to coordinate, move, or even feel the various parts of your body.
It’s common to feel lightheaded and dizzy, and you may even feel nauseous or vomit from the disorientation of the new perceptual state. You may also feel a heavy sedation or fatigue settle in.
5. Poor Memory & Concentration
Ketamine use also impairs memory and concentration, and you may find it difficult to hold on to a topic or thought long enough to express or understand it. This can fuel frustration and confusion if you don’t know what to expect before going into the experience.
One rodent study found that ketamine altered several proteins and messengers responsible for memory, potentially accelerated by an elevated body temperature [3]. Ketamine primarily works by antagonizing N-methyl-d-aspartate receptors (NMDAR), elevating glutamate transmission to the brain.
This neurotransmitter is the receptor responsible for exciting neurons to perform their specific action. In the case of NMDAR, the beneficial site of action is the prefrontal cortex and amygdala, which help with processing emotions and stabilizing mood.
However, in the hippocampus (responsible for memory formation and retrieval), it may be a problem. Excess glutamate can overstimulate neurons, causing them to atrophy and become less effective [4].
6. Severe Dissociation (K-Holing)
Ketamine is a dissociative anesthetic, which means you can expect to feel disconnected from your body and sense of self. In high doses, ketamine enthusiasts refer to the full disconnect of brain and body as feeling like an infinite fall from a great height — known as the “k-hole.”
While clinics will give slightly lower doses, dissociation and losing coordination with your sense of body and self can bring on anxiety, fear, and irritability. Psychomimetic — symptoms mimicking psychosis — are common as well and can feel alarming if you’re not expecting them.
As with the above, these typically resolve by the time ketamine has worn off, but that doesn’t necessarily mean they’re over.
7. Anxiety
It’s possible to have an experience that sticks with you, bringing on anxiety and fear for quite some time after your session has ended. A bad trip can have a lasting psychological impact on users, even if it’s the only negative experience of a psychedelic.
Extreme cases could even present as post-traumatic stress disorder (PTSD) with constant reminders of terrifying experiences. More common is a sense of fear, depression, or dread following a few days after the trip.
This is why education is so important for any drug you intend to use. Know how to increase your chances of having an enjoyable time (like preparation and integration). Education and preparation are the best tools for ensuring you have a good and safe experience with any drug.
8. Bladder Pain
As ketamine is metabolized, it’s converted into norketamine which then travels through your kidneys and into your bladder fully intact. This compound, and others like it, have been shown to damage the mucosa protecting the inside of the bladder from your acidic urine [12]. If this goes on for long enough, it can result in pain and (eventually) blood in the urine.
Adverse Reactions of Ketamine
There is very little emphasis on adverse events in ketamine research, which should be alarming, considering the major concerns surrounding ketamine use. Ketamine therapy requires frequent (sometimes 2/week) infusions of high doses, making these treatments susceptible to some of these concerns.
For the most part, these risks are low when ketamine use is infrequent or over a short period. While there’s a lot we still don’t know about the potential for adverse reactions to ketamine — largely due to the underreporting in research — frequency of use correlates with the risk of complications.
The more ketamine you use, the more likely you are to experience serious health problems as a result. While many of the concerns go away when people stop using ketamine, they are also more likely to return if the person takes ketamine again.
Here are some of the main problems you might experience:
1. Addiction & Abuse
Ketamine has an addictive potential that providers often overlook. Any substance capable of disconnecting you from your current problems — especially one that reliably brings on a happier disposition and lasts under 30 minutes — is prone to chaotic use.
Classical psychedelics often build a rapid tolerance, making abuse more difficult (though not impossible), but ketamine doesn’t have this effect. Though a tolerance does build through repeated ketamine doses, it’s not nearly to the level of other psychedelics.
Addictive behavior with ketamine is especially dangerous and capable of creating complex medical problems. Many of the other concerns related to ketamine below are avoidable or reversible through breaks or stopping ketamine use altogether.
However, as addictive behaviors form, this becomes less possible.
2. Cognitive Concerns
One of the major problems with long-term ketamine abuse is associated with repeatedly activating the hippocampal region [5]. This might permanently impair a person’s memory of surroundings and locations (spatial memory) along with “schizotypal and dissociative symptoms.”
In addition to aiding in navigation, spatial memory plays a key role in your short-term memory. Chronic over-stimulation of this region will cause it to shut down and, in extreme cases, may even leave a lasting effect for years.
Temporary loss of short-term memory is common while under the effects of ketamine, but it seems that repeated use can have a long-term impact. As mentioned above, cognitive side effects are rarely discussed, and we don’t know if they’re short-term and build up over time or if they’re harmless with limited use.
3. Urinary Tract Problems
Urinary tract problems are extremely common in people who frequently use ketamine — as high as 30% of users, according to one study out of Hong Kong [6]. Generally, the frequency and duration of use relate to the likelihood of developing symptoms. However, one study excluded participants with prior drug use and had one participant drop out. The person had to see a urologist after the fourth dose [7].
One thing is clear — the longer a person continues to use ketamine after symptoms appear, the more likely it is they’ll do permanent damage [8]. In extreme cases, lower urinary tract symptoms (LUTS), like frequent, difficult, or poor urination, can move upward in the system.
The treatment is usually as simple as ceasing ketamine use, but it can lead to urinary system dysfunction if patients continue using ketamine after symptoms appear. From here, the kidney can swell along with the bladder, and eventually, the system can shut down altogether.
In this case, the cure is surgery — “augmentation enterocytoplasty,” specifically — to remove a section of the intestine, open the bladder, and suture it to the removed intestine to enlarge it.
It should go without saying: this is a painful procedure with lasting complications.
4. Liver Problems
The urinary tract also has a delicate relationship with your liver, which filters toxins out of the body through your urinary (or excretory) and digestive systems. Each time a person takes ketamine, their liver has to kick into high gear to process the drug and its metabolites (some of which could be toxic to the liver and body itself).
A study of 297 ketamine users with urinary tract dysfunction found that 9.8% of them also had injuries to their bile ducts in the liver (sclerosing cholangitis) [9]. More alarmingly, one case study found patients who received prolonged ketamine infusions due to complications with a COVID-19 infection were more likely to contract this rare liver condition [10].
This presents a new potential risk for people who chronically or chaotically use ketamine — they may be more susceptible to liver problems if they continue to use ketamine after testing positive for COVID-19. It’s still far too early for us to know this for sure, however.
Ketamine Drug Interactions
Ketamine affects several systems within the body, so many prescription or over-the-counter medicines have interactions with ketamine.
Some of the primary drugs to avoid mixing with ketamine include:
- Allergy and decongestant medications
- Muscle relaxers and bronchodilators
- Sympathomimetics (stimulators of the adrenal system)
- Antidiuretics
- Benzodiazepines, opioids, and other respiratory or cardiac depressants
- It’s likely best to avoid anything affecting the main areas ketamine impacts — the opioid receptors, central nervous system, NMDARs, and more. Avoiding all medications would be the best bet, though some antidepressant medications seem to be fine to take alongside ketamine.FAQ: Ketamine Side Effects
Here are some of the common questions people ask regarding ketamine side effects.
1. Is Ketamine Therapy Safer Than Recreational Use?
Possibly, but only in the sense of having a safe supply of ketamine and (hopefully) medical oversight. Side effects and adverse reactions have happened in many clinical trials and are possible in any setting.
Just because you take a drug at a clinic doesn’t mean it’s a completely different drug. The doses in ketamine therapy are similar to the ones someone might use for heavy recreational use, and some regimens call for up to 2 infusions per week to start.
2. What’s the Safest Form of Ketamine?
All forms of ketamine are likely to have the same problems associated with them as they all produce a similar level of metabolites [11]. Infusions and injections can feel more overwhelming since they have a more rapid onset, potentially resulting in more immediate side effects, but this is the only difference in safety.
There is a misconception that ketamine doesn’t require metabolism when users don’t take it orally. While more bioavailable through injections and sublingual application, it still goes through the same breakdown process — the only difference is the location, timeframe, and absorbability.
3. How Do You Treat Ketamine-Induced Problems?
The easiest way to treat adverse reactions to ketamine is to immediately stop using it and seek medical care as soon as symptoms arise. While the vast majority of problems go away after ketamine use stops, a medical professional is the best person to tell you if this is your case or not.
Always take your concerns seriously and seek help from a qualified professional on the best course of action.
4. How Long Do Side Effects of Ketamine Therapy Last?
Most side effects go away immediately after the ketamine wears off, but this isn’t always the case. Some side effects linger for a time or, in the event of long-term, chronic use, can leave a lasting effect.
Most drugs have side effects, and they’re often something people come to expect out of the treatment — always know the difference between what’s typical and what’s a serious medical concern beforehand. Always research substances first and understand what you’re getting into.
5. Can I Take SSRIs/Antidepressant Medication With Ketamine?
This is the expectation in the case of Spravato, but this won’t always be the case. Due to the lack of research, off-label clinics and telehealth providers might determine it isn’t a risk they’re willing to take.
Introductory research indicates it isn’t a concern, but the decision is up to you and your mental health provider.
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References
- Short, B., Fong, J., Galvez, V., Shelker, W., & Loo, C. K. (2018). Side-effects associated with ketamine use in depression: A systematic review. The Lancet. Psychiatry, 5(1), 65–78. https://doi.org/10.1016/S2215-0366(17)30272-9
- Szarmach, J., Cubała, W. J., Włodarczyk, A., & Wiglusz, M. S. (2019). Short-term ketamine administration in treatment-resistant depression: Focus on cardiovascular safety. Psychiatria Danubina, 31(Suppl 3), 585–590. https://pubmed.ncbi.nlm.nih.gov/31488795/
- Shi, M., Ding, J., Li, L., Bai, H., Li, X., Lan, L., Fan, H., & Gao, L. (2020). Effects of Ketamine on Learning and Memory in the Hippocampus of Rats through ERK, CREB, and Arc. Brain Sciences, 11(1), 27. https://doi.org/10.3390/brainsci11010027
- Pal, M. M. (2021). Glutamate: The Master Neurotransmitter and Its Implications in Chronic Stress and Mood Disorders. Frontiers in Human Neuroscience, 15, 722323. https://doi.org/10.3389/fnhum.2021.722323
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