Notes from the Field: Ketamine Detection and Involvement in Drug Overdose Deaths United States, July 2019 June 2023 MMWR

In particular, only for CRPS, there is evidence of medium to longer-term pain relief. For chronic pain, ketamine is used as an intravenous analgesic, mainly if the pain is neuropathic. Ketamine is especially useful in the pre-hospital setting due to its effectiveness and low risk of respiratory depression.Ketamine has similar efficacy to opioids in a hospital emergency department setting for the management of acute pain and the control of procedural pain.

Mechanism of action

It is likely on the basis of this evidence, that the urinary tract pathology seen is related directly to ketamine and/or its metabolites. In addition, there are four reported cases from the palliative care setting in patients using pharmaceutical-grade analgesic ketamine who developed LUTS (91, 92). However, in the animal study discussed above, mice were only exposed to intraperitoneal ketamine and still developed mononuclear infiltration occurring throughout the urological tract, in the glomeruli, ureters, and bladders (90).

The researchers wanted to call the state of ketamine anesthesia “dreaming”, but Parke-Davis did not approve of the name. As a result, norketamine plasma levels are several-fold higher than ketamine following oral administration, and norketamine may play a role in anesthetic and analgesic action of oral ketamine. In a single-case study, the concentration of ketamine in cerebrospinal fluid, a proxy for the brain concentration, during anesthesia varied between 2.8 and 6.5 μM and was approximately 40% lower than in plasma. When the anesthesia was maintained using nitrous oxide together with continuous injection of ketamine, the ketamine concentration stabilized at approximately 9.3 μM. In 1–5 minutes after inducing anesthesia by rapid intravenous injection of ketamine, its plasma concentration reaches as high as 60–110 μM. The typical intravenous antidepressant dosage of ketamine used to treat depression is low and results in maximal plasma concentrations of 70 to 200 ng/mL (0.29–0.84 μM).

Brain damage

However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. Harm reduction approaches for substance use are strategies that limit fatal overdoses. It can be unpredictable and difficult to gauge ketamine quantity, and in some cases, overdose may occur, leading to life-threatening situations and, sometimes, death (Addiction Center, 2025; San Francisco AIDS Foundation, n.d.).

At sub-anesthetic doses, ketamine produces a dissociative state, characterised by a sense of detachment from one’s physical body and the external world that is known as depersonalization and derealization. Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. To date, there have Tramadol interactions been three retrospective case series (n≥10) published, covering 93 patients reporting chronic urological effects in long-term recreational ketamine users (see Table 4) (86, 93, 94). Recently lower urinary tract symptoms (LUTS) of dysuria, increased frequency of small volume micturition, suprapubic pain and, if severe, painful haematuria have been reported amongst long-term ketamine users. The same group were then followed up for a year, and the frequent ketamine users with increasing ketamine doses were more likely to have cognitive deficits, especially with spatial working memory and pattern recognition memory tasks, and both short- and long-term memory was affected (66). Recently, the long-term effects of recreational, non-medical ketamine use have come under scrutiny.

The risk of ketamine-related overdose deaths comes when ketamine is co-abused with other drugs or alcohol. The combination of ketamine with other drugs, particularly drugs that have a depressing effect on the central nervous system (CNS), substantially increases the likelihood that someone will experience a ketamine-related overdose. It is important to note that this lethal dose estimate is for ketamine in the absence of other drugs — alcohol and other drugs of abuse substantially increase the likelihood of a ketamine-related overdose. A ketamine overdose is a true medical emergency and without medical intervention can be fatal. Among the most dangerous signs of a ketamine overdose is respiratory depression, which is a state where inhibition of normal brain activity in the area that controls breathing causes dangerously slow and irregular breathing.

This effect has however led to recreational, non-medical misuse and there has been evidence of this since 1967 (5). Signs might include severe confusion, drowsiness or unconsciousness, high blood pressure, irregular heartbeat or chest pain, vomiting, and convulsions or hallucinations (Figure 2). Users attempting to reach the “k-hole” may accidentally overdose—especially if other substances and alcohol are also ingested (Addiction Center, 2025). K-hole can be described as taking too much ketamine, resulting in users feeling completely numb or disconnected from the body (San Francisco Aids Foundation, n.d.). Figure 1 shows the short- and long-term effects of ketamine use, such as dizziness, headaches, memory problems and impaired cognitive and urinary function. At smaller doses, this can leave a person feeling happy or like they are dreaming/floating, but at larger doses, it can lead to confusion or inability to move or speak (NIDA, 2024).

Provide Information to Medical Personnel

• While ketamine is marketed legally in many countries worldwide, it is also a controlled substance in many countries.
• A ketamine overdose is a true medical emergency and without medical intervention can be fatal.
• In 2020, 1.3% of 12th graders were found to have misused the drug for recreational purposes—this number was at 0.7% only a year prior.
• A majority of deaths with ketamine detected involved illegally manufactured fentanyls (IMFs) (58.7%), followed by methamphetamine (28.8%) and cocaine (27.2%).
• There are different ways to identify a person the signs of a potential ketamine addiction.
• During July 2019–June 2023, ketamine was detected in What are the implications for public health practice?

Other k-hole symptoms include marked confusion, unexplainable experiences, floating sensations, and mind/body dissociation. Learn what a k-hole is and the symptoms people experience in this state. When someone has “fallen into a k-hole” (the slang term for this ketamine effect), they are temporarily unable to interact with others or the world around them. A “k-hole” is how it feels when you take a high enough dose of ketamine that both your environmental awareness and bodily control become very impaired. Ketamine disrupts communication between specific brain regions, inducing a trance-like/dissociative state while providing pain relief, sedation, and amnesia. Ketamine is a dissociative anesthetic widely utilized in medicine since its development in the 1960s.

In cases of severe symptoms, particularly agitation/aggression, benzodiazepines may be required (51). Of the 23 deaths in which ketamine was identified in post-mortem samples in the United Kingdom between 1993 and 2006, only 4 were attributed to lone ketamine poisoning (60). When ketamine is reported in post-mortem samples, it is often either alongside another intoxicant or in the setting of trauma. Indeed, death and non-fatal emergencies attributed to ketamine use are considered to be very rare (37).

Possible biochemical mechanisms of ketamine’s antidepressant action include direct action on the NMDA receptor and downstream effects on regulators such as BDNF and mTOR. Pore blocking of the NMDA receptor is responsible for the anesthetic, analgesic, and psychotomimetic effects of ketamine. Naltrexone potentiates psychotomimetic effects of a low dose of ketamine, while lamotrigine and nimodipine decrease them.

Ketamine is an anesthetic, and its overdose can impact many people’s physical and mental functioning. Professional treatment can start anyone battling addiction on the path to a healthier and happier life. However, it’s easy to get ketamine abuse wrong because of its potency; it’s more powerful than speed or coke weight for weight, so it’s easy to accidentally overdose. “It’s easy to get ketamine abuse wrong because of its potency; it’s more powerful than speed or coke weight for weight, so it’s easy to accidentally overdose.” Chronic 2cb effects effects of ketamine toxicity are typically reversible, with management focusing on abstinence. Chronic effects of ketamine toxicity can result in cholangiopathy and cystitis, which can be confirmed by endoscopic retrograde cholangiopancreatography and cystoscopy, respectively.

Habits for Proper Mental Health

This minimizes the need for close medical supervision throughout the period of withdrawal—allowing those in recovery to move forward and focus on the second stage of their treatment. However, for many ketamine abusers, withdrawal isn’t a major issue, as ketamine doesn’t produce a clinically significant withdrawal syndrome. Ketamine withdrawal treatment aims to help you get off the drug and stay off it. However it manifests itself, if you have an addiction to ketamine, you need to seek help. You may also have experienced severe side effects but still be taking the drug.

Users may be become agitated, aggressive, paranoid, and display dissociative-type symptoms. Recreational use of ketamine can cause a number of troublesome neuro-behavioural/neuropsychiatric effects. Any description of acute ketamine toxicity is complicated by the fact ketamine is commonly part of a poly-substance use scenario. It is often stated that the bulk of illicitly available ketamine is derived by diversion of legitimate veterinary and medical supplies; however, illicit manufacturing laboratories have now also been reported, particularly in China and South-East Asia (41).

However, it is important to note that ketamine is a controlled substance categorized as a Schedule III drug. Because of this, ketamine has attracted attention as a possible treatment for the condition. While researchers are still learning more about how ketamine works, some of its effects are believed to stem from blocking glutamate receptors in the brain. Some people continue to feel disconnected from the world around them (and from their life), and may even develop ongoing symptoms of psychosis.

After 12 step programs for addiction recovery promising preclinical research in animals, ketamine was tested in human prisoners in 1964. The presence of norketamine, a pharmacologically active metabolite, is useful for confirmation of ketamine ingestion. Urine is often the preferred specimen for routine drug use monitoring purposes.

There is evidence from beyond the recreational use setting linking ketamine with urological pathology. Ketamine pretreatment doubles its hepatic microsomal metabolism in rats, and both the catalytic activity and protein expression of the rat microsomal cytochrome P-450 system is enhanced by repeated daily ketamine administration (83, 84). Anecdotally, ketamine use in humans is characterised by binging, the drug being repeatedly used until a user’s supply has been exhausted (78, 79). It is not certain how ketamine causes these effects, but antagonism of the NMDA-R is thought to be important, as is dopaminergic depletion in the prefrontal cortex (3, 26, 69). Superstitious conditioning, a form of associative learning, is also more common amongst frequent ketamine users and this process may precede outright delusional thinking (67). A dose-dependent relationship was reported on 1-year follow-up, with frequent users being more delusional than infrequent, abstinent, and non-users, respectively (66).

• From the forensic literature regarding death following recreational ketamine use, blood ketamine concentrations within the range of 0.1 to 7.0 mg/l have been reported alongside the presence of another co-ingestant such as ethanol, opiates, amphetamine, or cocaine (56–59).
• However, there is still a possibility, and overdose is more prevalent when ketamine is mixed with other drugs.
• Upon the arrival of medical emergency services, provide detailed information about the situation.
• Ketamine is a dissociative drug, which means that it can make users feel detached from reality and themselves.
• This article will delve into these signs, shedding light on the indicators that someone may be experiencing an overdose situation.
• This is because of a tolerance build-up, where larger amounts of ketamine are required to produce the desired high.

Excessive ketamine use can lead to intoxication, causing symptoms such as confusion, hallucinations, and impaired motor function. Keep in mind that individual reactions may vary, and the severity of symptoms can depend on factors such as the person’s tolerance, weight, and overall health. Therefore, it’s essential to remember that ketamine should only be used under the supervision of a qualified medical professional and as prescribed for legitimate medical purposes.

Ketamine has also been used for treatment of refractory status epilepticus. Ketamine is also used for anesthesia in a range of veterinary procedures, such as for dogs, cats, and other animals. One of the advantages of ketamine in the surgical setting is that ketamine does not have a substantial effect on breathing or heart function. Most surgeries also require anesthetics that reduce muscle tone and movement.

Ketamine: Uses, Effects, Interactions & Addiction

Ketamine, in the form of esketamine, is approved in the United States for treating treatment-resistant depression. At sufficiently high doses, users may experience what is called the “K-hole”, a state of dissociation with visual and auditory hallucination. The discovery of antidepressive action of ketamine in 2000 has been described as the single most important advance in the treatment of depression in more than 50 years. These investigations demonstrated ketamine’s short duration of action and reduced behavioral toxicity made it a favorable choice over phencyclidine (PCP) as an anesthetic. Blood or plasma ketamine concentrations are usually in a range of 0.5–5.0 mg/L in persons receiving the drug therapeutically (during general anesthesia), 1–2 mg/L in those arrested for impaired driving, and 3–20 mg/L in victims of acute fatal overdosage.

The intensity of side effects depends on the dose of ketamine. Ketamine overdose may be fatal in some people, including those who smoke, intake of caffeine, and drink alcohol. Ketamine overdose can cause various health complications.