Ketamine
Learn more about ketamine, a tranquilizer and frequent party drug.
This content is made in collaboration with Blossom.
Overview
Common Nicknames
Ket, K, special k
Drug Class
Dissociative anaesthetic
Drug Form
Crystalline powder, injectable liquid, nasal spray
Route of Administration
Insufflation, injected, or given intranasally
What is the science of Ketamine?
Ketamine is used by doctors worldwide as an anaesthetic, sedative and, more recently, as a treatment for depression. It's a small molecule that binds to many receptor types on the surface of human neurons, the most important of which is the NMDA receptor, normally activated by glutamate, the brain's most commonly-used neurotransmitter. Ketamine stops the NMDA receptor from opening in response to glutamate, slowing the activity of the neurons it sits on. Because so many neurons rely on glutamate and NMDA receptors, this has wide-ranging effects, including prompting neurons to release more GABA, the ‘anti-anxiety’ neurotransmitter targeted by drugs like Xanax and Valium. Combined with effects on dopamine, opioid and serotonin receptors, this gives ketamine pain-relieving, anaesthetic, psychedelic and antidepressant properties that vary with dose. Physical effects can include a rise in blood pressure and heart rate, and an opening of the airways.
More precisely, at the lower doses used for depression treatment, ketamine appears to preferentially block NMDA receptors sitting on a particular type of inhibitory brain cell. This has the effect of temporarily disinhibiting other neurons, triggering a burst of glutamate release that sets off a cascade, including activation of a different receptor type (AMPA), release of a brain growth factor called BDNF, and activity in a cellular pathway called mTOR, all of which are thought to drive a rapid increase in connections between brain cells in the prefrontal cortex. This is the leading explanation for how a single dose of ketamine can improve mood so quickly, days or weeks faster than a typical antidepressant.
Ketamine used clinically comes in two mirror-image forms, R- and S-ketamine (street ketamine is typically an unseparated mixture of both). The S-form binds the NMDA receptor three to four times more strongly and produces stronger anaesthetic and dissociative effects, while early research suggests the R-form may offer meaningful antidepressant effects with fewer side effects, which is why both forms are being developed separately as potential treatments.
What are the risks?
Fatalities or hospitalisation from ketamine almost always occur from the combination with other drugs, particularly alcohol. Taking ketamine with stimulants (such as cocaine and ecstasy) may overload your heart. Depressants such as alcohol, GHB or heroin make the effects of ketamine stronger. This could make you fall unexpectedly unconscious, and you may be at risk of stopping breathing or suffocating on your own vomit.
In controlled clinical settings, where doses are much lower and carefully measured, the acute picture looks different: dissociation, altered perception, transient rises in blood pressure and heart rate, dizziness, headache and nausea are common but typically resolve within one to two hours, which is why supervised administration involves at least two hours of monitoring afterwards. Even in this controlled context, people with uncontrolled high blood pressure, unstable cardiovascular disease, or an active psychotic disorder are usually excluded from treatment.
Habitual ketamine use is well-known to be damaging to the bladder. Ketamine-induced urinary cystitis results in pain when urinating and a feeling that your bladder has got smaller or that you need to pee all the time. There have been reports of long-term ketamine users requiring bladder transplants. Regular heavy use has also been linked to liver problems and to cognitive impairment, particularly affecting memory and the brain's planning and decision-making functions.
Ketamine can make you vulnerable to accidental injury and death; even smaller amounts might reduce your ability to make sensible decisions or recognise hazards, like roads, cold temperatures, or bodies of water. Being on ketamine could also make you vulnerable to crimes like robbery or sexual assault.
Like any drug bought from a drug dealer or online, it’s not possible to guarantee the contents of a bag of ketamine just from looking at it or trying it. Other drugs or compounds may be mixed in, and these could have dangerous, unaccountable effects, which may occur at lower doses than those of ketamine.
How might the drug make you feel?
Ketamine affects your conscious experience. A snorted dose typically takes effect within 5 to 10 minutes, peaks after 15 to 30 minutes, and lasts around an hour; in clinical settings using intravenous or nasal spray dosing, the timing and intensity are somewhat different and more tightly controlled.
Ketamine affects your conscious experience. A dose of ketamine insufflated (snorted) will typically take effect in 5-10 minutes, reach its peak in 15-30 minutes, and last for around an hour. At lower doses, the effect may feel similar to alcohol, reducing inhibitions and anxiety. As dosage increases, the psychedelic properties cause confusion, hallucinations, a sense of dissociation from time and space, and potentially feelings of anxiety and unease. It can reduce the ability to control your movements, including to speak, and the anaesthetic and analgesic (pain-killing) effects cause a numbness that could have dangerous consequences. At higher doses still, you may enter a state of profoundly altered consciousness known as a ‘k-hole’, in which your experience of reality is almost completely detached from what is actually going on around you. Depending on your surroundings and your mental state before taking the drug, this may be a stressful experience, and being physically incapacitated could put you at risk if you are in an unsafe environment. At the highest doses, a complete loss of consciousness can be achieved, which is what allows ketamine to be used as a surgical anaesthetic.
Is Ketamine addictive, and what are the long-term effects?
It is possible to become addicted to ketamine. Some people use it outside a party setting specifically for its dissociative and mood-altering effects. Tolerance can build with repeated use, meaning a higher dose is needed to get the same effect, which is itself a warning sign. Clinically, ketamine is understood to carry a genuine risk of dependence: it produces rewarding effects, tolerance develops with repeated use, and a withdrawal syndrome involving craving, anxiety and physical symptoms has been documented. This is a meaningful way ketamine differs from classic psychedelics like psilocybin or LSD, which don't carry this kind of dependence risk. Some users end up attending detox clinics, and even after developing bladder problems from ketamine use, some continue using it because it temporarily eases that same pain, deepening the cycle of harm.
Long-term, higher-dose use can have lasting effects on the body, including bladder disease, kidney problems, stomach pain, depression and a decline in memory. The psychological effects of chronic use can also seriously affect work, relationships and education.
Harm Reduction and Drug-Drug Interactions
There are always risks to using ketamine. However, if you do take drugs, you can make simple choices to improve the chances of a good experience. Here are some things to consider: drug testing kits can be ordered online, and testing services are present at many festivals. It is advisable to test your ketamine before taking it, as some batches can be especially strong or cut with other substances, which can lead to death. First-time users should start with a lower dose, and all users should remember to take less than they think they need and wait for the previous dose to fully take effect before taking more. Consider your state of mind before taking ketamine to avoid an anxious, exaggerated response to the drug.
Ketamine has interactions with more than 400 other drugs. It shouldn’t be used in conjunction with stimulants or depressants, as both will have negative effects on your body and could be fatal. The most common drug interaction that causes users harm is with alcohol, which can slow your breathing and lead to unconsciousness. Depressant drugs have a major interaction with ketamine, such as benzodiazepines and opioid analgesics, which can cause respiratory depression. Other interactions worth noting include antidepressants and sympathomimetics such as vasopressin. Another common medication with an interaction is theophylline; taken together, the threshold for seizures could be lowered, which can be dangerous if you take theophylline to control your seizures. Ketamine also has interactions with some foods, including grapefruit and grapefruit juice, leading to high levels of toxins in your body.
Medical Uses
A landmark study in 2000 first showed that a single low-dose intravenous ketamine infusion produced rapid antidepressant effects in major depression, and a 2006 study replicated and extended this specifically in treatment-resistant depression, establishing the dosing protocol still used as a reference point today. This led to the development of esketamine (marketed as Spravato), the S-form of ketamine delivered as a nasal spray, which was approved in 2019 for use alongside a newly started oral antidepressant in treatment-resistant depression, based on a mixed but ultimately supportive set of Phase III trials, including one that showed continued treatment reduced the risk of relapse. A 2020 approval extended esketamine's use to major depression with acute suicidal thoughts or behaviour, based on trials showing rapid symptom reduction within 24 hours in that specific, high-risk group. Most recently, a large 2025 trial supported esketamine's approval as a standalone treatment, without requiring a newly started oral antidepressant alongside it, the first time this has been approved as monotherapy for treatment-resistant depression.
Beyond depression, intravenous ketamine has also been studied for bipolar depression, with rapid effects comparable to what's seen in unipolar treatment-resistant depression, and for PTSD, where multiple smaller trials have shown mixed but generally encouraging results. Early, exploratory work is also looking at ketamine for OCD, chronic pain and some substance use disorders, though evidence in these areas is far less developed than for depression. An R-form version of ketamine (arketamine) is also in early human trials, with the hope that it may offer meaningful antidepressant benefit with less dissociation and fewer side effects than the currently used forms.
Outside psychiatry, ketamine continues to play an established role in treating chronic and hard-to-manage pain, including complex regional pain syndrome and nerve pain, and in reducing reliance on opioids during and after surgery.
Many questions remain unresolved: how long people should stay on ketamine treatment once they respond, how often maintenance doses should be given, and what the long-term effects of repeated dosing look like in people who may need treatment for years.
Myths and Misconceptions
Ketamine is horse tranquiliser
Ketamine is used to sedate or anaesthetise a wide range of animals, including horses, but also humans. In fact, it’s one of the most widely used drugs by medics worldwide, particularly in lower-income, disaster or emergency settings, because of its low cost and safety, and because it’s injectable, rather than a gas.
Ketamine is not addictive
Although ketamine doesn’t have withdrawal symptoms like cocaine or opioids, it can still affect the reward pathways in the brain that cause addiction. Many people who become addicted to ketamine find that they are using the drug to self-medicate. If you use ketamine, be mindful of your motivations for doing so, and remember that there are drug and mental health services available if you need support.
Ketamine is not a psychedelic
‘Classical psychedelics’ are those which target the 5-HT (serotonin) receptors. However, this classification leaves out many drugs which we know also produce a psychedelic experience and have similar effects. There has been a shift, therefore, to classify psychedelics under a new term – psychoplastogens, drugs that open a critical window of neuroplasticity. This state of plasticity may be what gives the drugs their clinical benefits.
I will experience a k-hole if I have ketamine therapy
Whilst a k-hole is entirely possible, it is not always going to happen every time you take ketamine. A k-hole more often happens at high doses of ketamine. Clinically administered ketamine will be highly controlled doses so that this is avoided. It is important to understand that medical-grade ketamine will differ from ketamine that you could buy on the street, and the dose in a medical setting will be tightly controlled so that your experience is more likely to be positive.
Ketamine therapy is too experimental and untested
The pharmacology of ketamine is well understood, and it has decades of research supporting its use. Ketamine is a Schedule 2 drug, whilst most other psychedelics are Schedule 1. This makes research into the drug less restricted, and so the psychiatric applications of ketamine are more developed.
History and Where the Research Stands
Ketamine was first synthesised in 1962 as a safer alternative to PCP for use as an anaesthetic. Human trials began in 1964, and by 1970 it had been approved as a dissociative anaesthetic, going on to become widely used in emergency medicine, battlefield surgery and paediatric anaesthesia, largely because it maintains normal breathing reflexes and stable blood pressure during sedation, unlike many other anaesthetics.
For decades afterwards, ketamine's main role in psychiatric research was as a way to study psychosis experimentally, since low doses could reliably produce dissociative, perceptual disturbances that researchers used to study schizophrenia. It wasn't until 2000 that researchers at Yale showed a single low-dose ketamine infusion could rapidly relieve depression, a finding replicated and extended in treatment-resistant depression in 2006. Over the following decade, both clinical research and off-label ketamine infusion clinics expanded rapidly across the US and internationally, often operating outside standard psychiatric regulatory oversight, which raised real concerns about inconsistent standards of care, patient screening and commercial motivations, concerns worth bearing in mind for anyone considering treatment at a private ketamine clinic today. In parallel, formal drug development focused on the S-form of ketamine, leading to the 2019 approval of esketamine nasal spray, a milestone that established a model of closely supervised, in-clinic administration that has since influenced how regulators are approaching other psychedelic-assisted therapies.
Ketamine's current legal status differs by product and context. Recreationally, ketamine is a controlled drug, and unauthorised possession or supply is illegal. Medically, it is available only via prescription and supervised administration, a picture that itself is split in two: esketamine nasal spray has a clear regulatory approval pathway for treatment-resistant depression, while the more commonly used racemic (mixed R- and S-) ketamine is generally administered off-label, outside a specific approved depression indication, through infusion clinics and compounded preparations. This distinction matters in practice, since the evidence base, monitoring standards and oversight differ meaningfully between the two.
