Ketamine

Description

Ketamine is a dissociative and strong numbing drug (anaesthetic) with unusual effects on the body. It speeds up rather than slows down breathing. Ketamine is used medically as a general anaesthetic for both humans and animals, as an antidepressant (esketamine) for treatment-resistant depression, and as a recreational drug acquired through the unregulated (‘illicit’) market.

Ketamine is a dissociative anaesthetic which creates an apparent detachment of the mind from the body. Chemically related to phencyclidine (PCP, ‘Angel dust’) it is widely used as a veterinary and a human anaesthetic.

Medically it is regarded as a very safe anaesthetic as it does not depress respiration. Ketamine is also used for recreational purposes and has become increasingly popular over the last 10 years. In recent years, esketamine (a single form of ketamine) has been approved for treatment-resistant depression therapy in several countries.

In its pharmaceutical form, ketamine is supplied as a nasal spray, or clear liquid for injection. However, on the streets ketamine is usually sold as a fine white crystalline powder, although tablets and liquid may sometimes be found. Ketamine may sometimes be passed off as another drug.

For more information, including harm reduction, visit our 'safer injecting' section here.

At lower doses, the effects include a sense of euphoria and may involve mild hallucinations. Physically, there may be a sense of numbness and general lack of co-ordination leading to difficulty walking, standing and talking. Nausea or vomiting is not uncommon. People who use ketamine also occasionally report “flashbacks” after use.

At higher doses a full psychedelic effect may be experienced – the “K Hole”. This is often experienced as a complete out of body sensation in which some may believe that they have entered another world or crossed over into another realm of consciousness. The phrase ‘near-death experience’ is sometimes used, of course few of us have had a genuine near death experience, so the reference criteria for this description is highly subjective.

A feeling of paralysis has been reported in which the person is fully conscious and can see but cannot move or speak. These feelings may have a spiritual or supernatural quality.

The physical effects at higher doses can include temporary blackouts and paralysis, which may occur along with loss of control over bowel and bladder movements.

Pharmacology

Ketamine interacts with a vast number of receptors, channels and enzymes in the central and peripheral nervous systems (CNS and PNS) which produce the varying and dose-dependent effects associated with ketamine use. Ketamine functions in pain perception, the cardiovascular, gastrointestinal and respiratory systems by interacting with the related signalling molecules in the nervous system.

Ketamine is primarily known for interacting with NMDA (N-methyl-D-aspartate) receptors, where it acts as a non-competitive antagonist. This means it binds to and then blocks the NMDA receptors from functioning. The predominant sought-after effect of ketamine is the ‘dissociative’ effect, similar to other NMDA receptor antagonists such as dextromethorphan (DXM) and memantine.

Interactions of ketamine within the CNS results in this state of ‘dissociative anaesthesia’ – sensory loss and analgesia but without actual loss of consciousness. While some of these interactions are explored below, note that the research is constantly evolving and non-NMDA receptor effects of ketamine are disputed.

In the CNS, ketamine may interact with

• Nitric oxide synthase (NOS): ketamine inhibits NOS, and therefore the production of nitric oxide or NO (not to be confused with nitrous oxide or N2O, aka laughing gas) which plays a role in pain perception.
• Sigma receptors: ketamine has a low affinity for the sigma receptors 1 and 2 and it is thought that the analgesic effects of the sigma receptor are not activated by ketamine.
• Opioid receptors: ketamine has a preference for the mu and kappa receptors, but its affinity for these receptors is 10 times less than that for NMDA. Reports show that naloxone (the opioid antagonist which counteracts the effects of opioids) does not work in countering the effects of ketamine, suggesting that ketamine’s interaction with opioid receptors does not have a significant impact on its effects. (See the Morphine section for a fuller explanation of opioid receptors).
• Calcium channels: ketamine blocks calcium channels, which again contributes to the analgesic effects.
• Sodium channels: ketamine has shown to have local anaesthetic properties possibly due to its interaction with sodium channels found in nerve endings of pain perceiving fibres.
• Cholinergic, noradrenergic and serotonergic neurotransmission: in the spinal cord, ketamine acts to inhibit uptake of neurotransmitters involved in the pain perception. Simply put, it increases certain transmitters that work to inhibit pain.

In the peripheral nervous system, it increases catecholamines (which include adrenaline) in the cardiovascular system to increase heart rate and blood pressure (this is dose-related) and in the respiratory system which causes bronchodilation (relaxation of certain airway walls, causing them to open).

Intravenously, the onset of action is a few seconds, intramuscularly (injected into muscle/fat) it is 4 minutes, and intranasally (snorted) it is 1–3 minutes. When taken intranasally, ketamine’s effects last for around 1–2 hours.

Harm Reduction

General advice

• Start low, go slow: Take a small amount and wait until you can feel the effects before taking more/anything else.
• Try not to use alone: If something goes wrong, someone is there to get help.
• Sesh-proof your space: Avoid open water and make sure you have somewhere to sit or lie down if your legs go jelly.
• Be careful mixing: Mixing ketamine with other depressants increases the risk of losing consciousness – avoid if you can, otherwise take less of each, as they can increase the effects and risks.
• Carry naloxone: Some counterfeit drugs in the UK have been found to contain strong opioids.
• Test your stuff: You can’t see whether your baggy contains ketamine or another drug by eye. Find out how to send a sample to WEDINOS for testing here: https://www.wedinos.wales or pick up some test strips at our Harm Reduction Hub
• K-cramps?: If you’re experiencing stomach cramps or changes in frequency or ease of urinating, seek medical help.
• If you’ve been prescribed ketamine and you notice a tolerance starting to develop (you need to keep taking more to get the same effect) speak to your doctor – don’t just start increasing your dose yourself.
• If you have become physically dependent on ketamine, the symptoms of abruptly stopping are likely to be even worse. It’s important to get proper medical advice on how to reduce your intake slowly.
• It’s also possible to become psychologically dependent on the drug (feeling like you need it all the time). If you think this is happening, see your doctor as soon as possible, but don’t suddenly stop taking it.

Ketamine harm reduction

Ketamine can sometimes produce effects that can lead to health and/or social harms, including:

• hallucinations
• blurred vision
• irrational behaviour
• seizures
• breathing difficulties
• anxiety and racing heart

Ketamine slows reflexes and impairs coordination, so minor accidents like bumping into objects are common. Thanks to its anaesthetic effects, any sense of pain is significantly reduced, leading some to only become aware of these knocks when bruises develop later.

Ketamine severely impairs coordination so no attempt should be made to drive or operate machinery while under its effects.

Taking ketamine can also induce distortions in perception of time and space and even relatively simple tasks such as judging distances and speed (for example crossing a busy road) can be compromised. Several deaths have occurred when people have attempted to swim on ketamine, so care should be taken to avoid bodies of water, even the bath.

Individuals consuming ketamine may also experience nausea and/or vomiting. Oral use is most commonly associated with unpleasant sensations and severe side effects. Regular use, especially in conjunction with alcohol consumption, can cause bladder infections (see 'ketamine bladder' below).

Ketamine is a drug where ‘setting’ needs to be carefully considered, it is prudent to be with friends who are not drug naïve or in an environment that you have no control over.

Ketamine is found as an ‘impurity’ in some ‘ecstasy’ tablets. Due to similarities in appearance, ketamine may also be confused with other drugs such as amphetamine and cocaine, despite the fact that the action of ketamine is very different from psychostimulants. This has resulted in some individuals having bad experiences as they are not prepared for the effects and there is no dose tolerance between the drug types.

Ketamine has the potential to be both physically and psychologically dependence-forming. Regular use can lead to the development of tolerance, where larger doses are needed to achieve the same effect. Ketamine is more psychologically dependence-forming than classical psychedelics. Repeated long term use can occasionally result in more severe problems like psychosis, or bladder, liver and kidney damage. Individuals who use it regularly may find it difficult to stop. It is not wise to discontinue from large doses abruptly and some degree of tailing off towards termination is suggested. When a person attempts to reduce the daily volume of a drug to which they have become dependent, it is clear that there is potential for postponing cessation repeatedly, so setting firm targets and sticking to them is crucial.

Ketamine bladder

Long-term ketamine use has been shown to damage the bladder and urinary tract, causing ‘ketamine cystitis’ or ‘ketamine bladder syndrome’. This manifests itself in symptoms such as urinary frequency, urgency, pressure, pain, incontinence and/or bleeding from the bladder. The aetiology (reasons for damage) are not fully understood, but chronic use can cause ulcers/wounds and stiffening of the bladder walls, which shrink the size of the bladder.

Mixing

As an increasingly popular club drug, ketamine is often associated with polydrug use (the use of several drugs simultaneously or consecutively). It is most commonly mixed with other popular club drugs, such as ecstasy and cocaine (Calvin Klein or CK is a slang term for this combination). Combining ketamine with alcohol or other depressant drugs is particularly dangerous because it increases the risk of losing consciousness.

What are the risks of injecting Ketamine & how can you inject more safely?

When ketamine is injected and any injecting equipment is shared (needles, syringes, spoons, filters or other paraphernalia), there is a risk of contracting Hepatitis B and C, HIV (which can lead to AIDS) and other blood-borne diseases. These viruses can be extremely resilient, and normal cleaning will not eliminate them, particularly in the case of Hepatitis, which can live outside the body (in certain circumstances) for up to three months. People who are infected with these viruses usually appear healthy, and may not develop the disease for years. From the moment someone is infected however, they carry the virus in their blood, and can infect others through sexual intercourse (particularly with HIV) and sharing any injecting equipment, even spoons and filters.

Those who inject can protect themselves from HIV/AIDS and Hepatitis by always using clean equipment, obtainable from needle exchanges and some chemists, and not sharing with anyone else. For more information, including harm reduction, see our 'safer injecting' section here.

History

Ketamine, developed in 1962, as CI-581, was first synthesized by Parke-Davis scientist Calvin Stevens. Pharmacological investigations in human subjects began in 1964 and it was initially promoted as a fast acting general anaesthetic. A few years later, in 1970, it was used as a battlefield anaesthetic, as it has less effect on depressing the respiratory system than opioids.

The first evidence of illicit use of the drug was on the West Coast of America. Later, during the late 1970s and early 1980s abuse began to increase across the country, especially among certain sub-cultures (e.g. ‘psychonauts’ and ‘New Age’ spiritualists). It was used in psychiatric and other academic research through the 1970s, culminating in 1978 with the publishing of the neuroscientist and psychoanalyst John Lilly's ‘The Scientist’ and Marcia Moore, who died of hypothermia in the woods behind her house after a large dose of IV ketamine. Around the same time, ketamine became widely available in a range of formulations including capsules, powder, crystals, tablets, ampoules and solutions.

Starting in the mid-1980s ketamine was beginning to be linked to ‘rave’ culture, partially as an experience in itself and also as a come-down, ‘chill-out’ antidote to the psycho-stimulants and hallucinogens popular in the culture.

Today, there are still valid medicinal uses of ketamine for anaesthetic reasons, though its use is tightly restricted. Additionally, ketamine is sometimes prescribed privately for people with treatment-resistant depression, either as an infusion or nasal spray (Spravato). The most common access to non-prescribed ketamine has been to obtain it through diversion from pharmaceutical suppliers of legal chemicals or theft from veterinary clinics or purchased from the East, often India, where less stringent controls have been in place in the pharmaceutical industry until recently.

Ketamine has, over the past few years, been thought of as a ‘club drug’ (this term is used for a number of illicit drugs, primarily synthetics, that are most commonly encountered at parties, clubs and ‘raves’). In the ‘MixMag’ surveys of recent years ketamine has held a place high on the list of clubbers’ most frequently used drugs. This is not to say ketamine is not still popular with ‘psychonauts’ (‘a person who explores, experiences, and studies their subconscious and subjective reality through the use of a range of drugs’), as it certainly is. Since the COVID-19 pandemic, ketamine prices have dropped and ketamine use has increased across the UK, particularly among young people.

Law

• Class B (as of 10th June 2014)
• Schedule 2

Possible offences

• Possession
  • Maximum sentence – 5 years/fine/both
• Possession With Intent To Supply
  • Maximum sentence – 14 years/fine/both
• Supply (including being concerned in supply, conspiracy to supply, aggravated supply and offer to supply)
  • Maximum sentence – 14 years/fine/both
• Production
  • Maximum sentence – 14 years/fine/both

In practice maximum sentences are rarely used, for more detailed and accurate information go to our sentencing page.