How does ketamine work as a drug in the body and brain?
Ketamine is a dissociative anaesthetic. When used medically, it is given in high doses that blocks pain signals and makes people unconscious. The lower doses used recreationally produce very different effects, sometimes including hallucinations, which are not well understood. There are similarities between the strange states of mind caused temporarily by ketamine and the experiences of people suffering from schizophrenia.
Does ketamine have any medical uses?
Ketamine is an essential medical and veterinary drug used for anaesthesia and pain relief under a wide range of circumstances. Ketamine is much less likely than other anaesthetics to depress the heart and respiration, so it is the anaesthetic agent of choice in low income countries and in environmental/conflict disasters where there are few trained medical personnel, anaesthetic machines or consistent sources of electricity. In the western world ketamine is the most commonly used veterinary anaesthetic, particularly in horses and the more unusual species. In developed countries ketamine is less commonly used for routine anaesthesia in people as it may cause hallucinations during recovery; more conventional anaesthetics are preferred where trained anaesthetists and appropriate equipment are readily available to monitor the patient and support respiration.
Ketamine is a potent pain killer and is particularly useful for children undergoing agonizing procedures such as treatment of burns. It is now also an important treatment for chronic pain.
New therapeutic uses for ketamine have more recently been identified, including treatment of depression and refractory status epilepticus. A single low dose of ketamine can rapidly lift depression, although the effect does not last long-term. It is thought to work by causing new connections (synapses) to be made in the brain. This is a promising lead for the development of new treatments because conventional antidepressants take some time to work. Self-treating using ketamine puts the user at risk of the harmful effects of ketamine, and it has not yet been established through large-scale trials that the benefits outweigh the risks.
What are the effects of ketamine?
Ketamine produces very different effects depending on whether someone takes a little or a lot. It is a strong drug and it is easy to take more than intended. It is therefore better for inexperienced users to start with a small dose first before they consider trying to get the effects of a larger dose.
Low to moderate doses
Ketamine can give sensations of lightness (like walking on the moon), dizziness, and euphoria. It makes people’s thoughts flow randomly; ideas can seem special and important, or pleasantly or unpleasantly muddled. Things may begin to look and sound different or somehow unreal. There is always a higher risk of accidents whilst using ketamine. Taking any depressant drug, such as alcohol, can very easily and quickly make the effects much stronger and riskier.
Higher doses
The more ketamine that is taken, the harder it is to stand up and move about. Quite large quantities lead to exceptionally odd feelings such as separation between the mind and the physical body, which some find pleasurable and others find distressing. Unpleasant side-effects like nausea and vomiting can occur. Ketamine can produce delusional thoughts much like those associated with schizophrenia. Very large quantities lead to users losing touch with their identity and surroundings altogether, which is called k-holing. People k-holing may be unresponsive, although inside their mind they may be experiencing vivid hallucinations. Users can have notions and hallucinations which can feel very real, and can be anything from wonderful conversations with angels, to being convinced they are dying. The risks of accidents, overdoses and anxiety described below are increasingly significant at higher doses.
Ketamine, 2-(2-chlorophenyl)-2-(methylamino)-cyclohexan-1-one, is a dissociative sedative with analgesic and anaesthetic properties, now being investigated as an antidepressant, alone and as part of ketamine-assisted therapy.
Discovered in 1962 by Calvin L. Stevens, and first tested on humans in 1964, ketamine was approved for medical use by the USA in 1970 and remains widely used to this day. Ketamine quickly became popular as a recreational drug in clubbing and rave culture, being appreciated for its euphoriant properties and mild stimulant effects when taken in small amounts. At higher doses, ketamine can also create hallucinogenic and dissociative effects, such as the distortion of sights, colours, sounds, sense of self and the environment.
Despite over 50 years of medical use, modern research is exploring new applications of ketamine in the treatment of mental health conditions, particularly for the treatment of depression. Ketamine is being studied as a standalone antidepressant, and in the form of ketamine-assisted therapy, with promising preliminary evidence leading to ketamine being granted ‘breakthrough status’ by the FDA.
These educational resources provide everything you need to understand the role of ketamine in medicine and the potential of ketamine as an antidepressant, and of ketamine-assisted therapy in the treatment of depression.