Ketamine vs Medical Ketamine – Understanding the Difference

The story of ketamine is one of contrasts — a drug that can both harm and potentially heal.

Ketamine has a range of uses and medical applications. Its presence on the World Health Organisation’s List of Essential Medicines is a testament to its medical benefits.

Ketamine was first synthesised as an anaesthetic in the early 1960s and is still used for this purpose today. Recently, ketamine has been the study of intense research for its potential applications for treatment-resistant depression. However, its popularity as a recreational drug conflicts with this. How can a substance that many people struggle with that can cause multiple serious harms, including liver and bladder toxicity, be touted as a wonder drug?

We’re going to dive into the history of ketamine, both recreationally and medically, and what the latest research says about ketamine as both an antidepressant and the implications of ketamine addiction, withdrawal symptoms and detox.

 

A brief history of ketamine

Soon after its development, ketamine became popular in medicine as an anaesthetic and was widely used in the Vietnam War. Researchers were looking for a chemical capable of sedation without suppressing breathing or the cardiovascular system. With its short duration and relative lack of toxicity when taken in the short term, ketamine is still used as an anaesthetic.

Ketamine is used on animals as well as humans, which has contributed to its somewhat misleading label as a ‘horse tranquiliser’. In fact, ketamine is used as an anaesthetic in veterinary medicine on a wide range of animals, not just horses, due to its quick onset and ability to allow the patient to continue to breathe spontaneously.

Ketamine as a recreational drug

Initial reports of the recreational use of ketamine started almost as soon as it was discovered – in the mid-1960s – but it did not become widely used until the mid-1990s. Despite ketamine’s powerful dissociative properties, it has become a popular party drug. This is principally due to its ability to induce euphoria, disconnection and trance-like states.

Using ketamine recreationally increases the risk of ketamine addiction. One of the most serious side effects, ketamine bladder syndrome, can cause many painful symptoms that impair quality of life. If allowed to continue, it can result in renal failure, which is life-threatening.

Street ketamine, like any unregulated drug, runs the risk of being contaminated. This year, UK public health authorities released a warning about contaminated ketamine on the Isle of Man that was causing users to stop breathing and go into cardiac arrest. This means the batch was very likely contaminated with something else.

If ketamine is dangerous recreationally, how can it be safely used to treat depression?

Medical ketamine treatment differs from recreational uses in several key ways.

Doses are lower than what is typically used recreationally and are administered for a much shorter period of time. Medical ketamine is also guaranteed to be ‘clean’, e.g. free from contaminants found in street ketamine, and is administered differently – either intravenously or as a nasal spray, in very precise doses. As the doses are lower and more controlled, the risk of withdrawal symptoms is minimised.

Ketamine therapy is medically supervised. The patient is not at risk of harming themself when disassociated and cannot compulsively re-dose. It is this compulsive redosing and sustained use that leads to more severe medical complications, like bladder damage.

These controls make medical ketamine used in treatment much safer. This is why it’s important that people do not try to use ketamine to self-medicate for depression. Because of its short duration, this can encourage people to take more and more over a shorter period of time, increasing the risk of drug addiction. This is not safe and can lead to complications. If you’re using ketamine to self-medicate for depression, support is available.

How ketamine is used in treatment-resistant depression

Ketamine is made of two compounds called arketamine and esketamine – and it is esketamine that is currently being used and studied to treat depression. There is no evidence to suggest that esketamine is a ‘safer’ compound than ketamine itself, and studies have suggested that ketamine and esketamine efficacy are about the same. But esketamine has acquired approval from the US Federal Drug Administration for treating depression, while ketamine has not. The reasons for this may be slightly cynical.

Ketamine does have FDA approval – as an anaesthetic and has done so for a long time. To ensure commercial viability, drug companies need to bring a novel compound with a new patent to the market. This is easily done by seeking a patent for esketamine instead of using and studying ketamine off-label.

Nevertheless, there may be slight benefits to esketamine. Compared to arketamine, esketamine binds more readily to the brain’s NMDA receptors – and these are the receptors that researchers are targeting. NMDA receptors are found in the brain and in nerve cells and are associated with the brain’s ability to rewire itself (neuroplasticity), memory, learning and brain development.

It’s theorised that esketamine’s success as an antidepressant arises from its ability to block the activity of these receptors. This means other neurotransmitters and pathways are boosted, which may be why it seems to have rapid antidepressant effects.

There is also some evidence that it helps the brain to rewire and form new connections. This is promising, but as the research is still in its infancy, we don’t yet know if this is the case.

A 2023 trial found that 55% of patients with treatment-resistant major depression responded to ketamine treatment. This is why studies continue – we don’t know why it works yet, but there’s promising evidence suggesting that it does. However, this treatment needs to be medically supervised.

 

Ketamine in drug addiction and ketamine as a therapeutic drug – the difference

Ketamine is a powerful drug with a high addiction potential, which is why medical use needs to be strictly controlled.

People struggling with ketamine addiction are taking the drug at far higher doses. Unlike some other forms of drug addiction, ketamine is more associated with psychological than physical dependence. However, people struggling with ketamine addiction will still experience withdrawal symptoms when attempting to discontinue the drug, making supported detox programmes crucial for beating their dependence.

If you’re using ketamine to self-medicate for depression or have found your use of it feels beyond your control, we can help.

UKAT offers comprehensive advice, treatment, detox and rehab services tailored to you and what you need.

Contact our dedicated team today to find out more.