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The Biological Effects of Ketamine Abuse

Written By Stuart Croft
Reviewed By Tiffany Green
Medically Reviewed By Dr David Barker
Updated March 1, 2024

Ketamine, originally developed as a post-operative analgesic to replace PCP in the 1960s, soon found its way into the recreational use space. ‘K’, ‘Special K’, or ‘Vitamin K’, as it’s known on the streets, has powerful hallucinogenic and dissociative effects, altering and distorting how the user perceives sight and sounds and making it a popular party drug during the 70s and 80s. By the time the 90s rolled around, it had lost some of its popularity due to the emergence of more affordable drugs with the same physical and psychological effects, such as LSD, PCP, and mescaline.

Fast forward to today, and ketamine is back. In recent years, ketamine has seen a resurgence in popularity in the UK and abroad, with, worryingly, much of its new user base belonging to Gen Z. With more and more teenagers and young adults abusing ketamine— Devon County saw a 53% increase in ketamine abuse since 2022, and other counties have issued warnings to parents—it is only prudent for us to understand the effect that this powerful narcotic can have on our brains and bodies. 

For more information about ketamine abuse among young people, withdrawal, and treatment options, feel free to read our article on ketamine and increased prevalence within substance misuse.

Ketamine abuse in context

Ketamine is open to abuse via several delivery methods: it may be snorted as a powder, mixed into alcoholic drinks, injected, or smoked, often mixed in with other drugs such as cannabis, amphetamines, or cocaine. Mixing ketamine with other drugs, a phenomenon known as polydrug use, can amplify its psychoactive effects and bring additional effects depending on what it is mixed with. A study published in PubMed found that cannabis, PCP, and speed were among the most commonly used drugs alongside ketamine, with the drugs either being mixed into a drug cocktail or taken sequentially (Lankenau and Clatts).

Polydrug use among ketamine users is very common, with up to 71% of users in a study in Sydney, Australia, reporting using ecstasy alongside ketamine (Monaghan and Curran). With such high rates of multi-drug abuse, many of those addicted to ketamine will bear the physical and psychological brunt of several harmful substances at once.

Biological effects of ketamine abuse

Immediate biological effects of ketamine

On the brain

Ketamine’s psychoactive effects kick in within minutes of ingestion, with snorting, injecting, and smoking having a more immediate effect than mixing it into a drink. Its effects are fairly short-lasting, approximately 30 to 60 minutes, often resulting in users taking multiple doses in succession to maintain their high (Drug Enforcement Administration (DEA)). 

While the neurochemical workings of all drugs are complex and require years of study to fully understand and appreciate, in short, ketamine works by blocking a specific neuroreceptor (NMDA receptors) and increasing extracellular glutamate (a neurotransmitter that affects both mood and perception) in some areas of the brain, while reducing it in others (Lazarevic et al.). 

This altered neurochemistry leads to sensations of dissociation or detachment, feeling like your mind is disconnected from the body; hallucinations accompanied by a distorted sense of time and space; and feelings of euphoria. These combined effects make it popular with those seeking to escape their lives for about an hour.

In higher doses, ketamine may lead to a loss of consciousness or a state of agitation that includes feelings of paranoia, anxiety, dizziness, and ataxia, the loss of coordination. Signs of overdose may include seizures, stupor, or coma (Orhurhu et al.).

On the body

Ketamine also has an immediate effect on the body. Our acute physical response to ketamine includes an increased heart rate and blood pressure as a response to ketamine’s stimulant properties (despite being classified as an anaesthetic, ketamine has certain stimulative effects). Other immediate physical effects of ketamine on the body include excessive salivation; nystagmus, a condition in which the eyes make repetitive, uncontrolled movements; and mydriasis, or dilation of the pupil.

While small doses of ketamine have a stimulative effect on the cardiovascular and respiratory systems, higher doses can have the opposite effect. Ketamine overdoses can lead to respiratory depression or even apnea; hypotension or low blood pressure; and bradycardia, or a slower than normal heart rate (Orhurhu et al.)

While pure ketamine overdose fatalities are rare, the risk of overdosing increases significantly when combined into drug cocktails. If the user loses consciousness after taking ketamine, seek immediate medical assistance, as it may reduce breathing rate enough to cause brain damage or death.  

Short-term biological effects of ketamine misuse (1 to 7 days)

Ketamine and metabolites can typically be detected in the blood for 24 to 72 hours after ingestion. While its acute effects will have worn out during this period, it can still have noticeable effects on one’s neurochemistry and body. The intensity of its effects is affected by how much was taken, the time since the previous ketamine dose, and personal physiological factors.

On the brain

Various studies have proven ketamine to be an effective and rapid antidepressant, especially in cases where depression has not responded to other treatments (Oxford Health, NHS Foundation Trust). While the context of this article is ketamine as a party drug instead of a treatment, its antidepressant properties remain. When ketamine is not mixed with other substances, which will inevitably have their own effects in the short term, up to 70% of users may experience improved mood for at least 24 hours, with up to 50% of users experiencing the effect for around 72 hours. 

The amount of ketamine one takes is a major determining factor in how it might affect the brain in the short term. There is evidence to support the claim that it may benefit cognitive ability, and evidence to the contrary. Acute administration of low doses of ketamine has been shown to improve visual memory, simple working memory, and complex working memory in individuals with treatment-resistant depression (Zhang and Ho); however, heavier users in other studies showed signs of memory impairment, although many of the participants in the study showed improvement after quitting the drug (University College London)

On the body

First time ketamine users are unlikely to experience many side effects that affect normal physiological functions. While some users might experience nausea and abdominal pain as well as the effects of other substances taken, the negative effects of ketamine really only start to accumulate with prolonged abuse.

Long-term biological effects of ketamine abuse (extended/repeated periods of misuse)

Ketamine, like other substances and drugs, can have disastrous consequences for both the brain and body when taken repeatedly over an extended period of time. Although ketamine presents a lower risk of developing a physical dependency when compared to other drugs, such as opioids, many users habitually turn to ketamine due to its euphoric and dissociative properties. This is compounded by the fact that ketamine is regularly available on black markets at a competitive price. Many of the symptoms of long-term ketamine abuse are classified as severe and are likely to cause a dramatic drop in quality of life and life expectancy.

On the brain

Prolonged or intense periods of ketamine abuse has the potential to alter the brain’s physical structure, particularly in the areas responsible for memory and executive function. Frontiers in Neuroanatomy published a study of 440 chronic recreational ketamine users (2–9.7 years of abuse with a mean use of 2.4g per day) in 2022, and found that recreational ketamine use was associated with reduced grey matter volume, decreased white matter integrity, and lower levels of functional thalamocortical and corticocortical connectivity, the latter leading to reduced communication between the thalamus (the brain’s relay station for sensory and motor signals) and the cerebral cortex (responsible for complex functions like thought, perception, and decision-making) (Strous et al.). All of these changes are associated with neurocognitive decline.

Along with structural changes in the brain, long-term recreational ketamine abuse is also associated with the development of mental health disorders such as depression and anxiety disorder. It’s important to note that this is still an active area of study, with individuals receiving measured doses of ketamine as treatment for depression showing very low risk of developing mental health disorders, even in the long run; however, a 2014 study found that 35% of recreational users suffered from mood, anxiety, or other psychiatric disorders (Fan et al.)

On the body

Long-term ketamine abuse is strongly associated with bladder, liver, kidney, and gallbladder dysfunction, although it may also cause harm to the cardiovascular and gastrointestinal systems.

The most commonly reported toxic effect of ketamine is urinary tract abnormalities. Chronic use may cause ulcers or open sores; cystitis, or inflammation of the bladder; and fibrosis, the thickening or scarring of tissue in the bladder. This has led to the development of the term ‘ketamine bladder syndrome’, which, in its early stages, leads to incontinence and hematuria, or blood in the urine. Allowed to advance through continued ketamine abuse, it may lead to hydroureter and hydronephrosis, conditions characterised by the enlargement of the urethra and streching of the kidneys due to a buildup of urine, respectively (Pappachan et al.). When caught early enough and ketamine use ceases, some of the damage can be reversed through treatment; however, beyond a certain point, the damage becomes irreversible. In these cases, the patient might have to resort to living with a stoma—a surgically made hole in the abdomen with a bag for collecting urine.

The responsibility for removing ketamine from the system falls squarely on the liver. Ketamine is metabolised (broken down at the molecular level) in the liver, with the metabolites excreted into the urine and bile. These metabolites are toxic and can cause concentrations of bilirubin, alkaline phosphates, and alanine aminotransferase at more than twice the upper normal limit in the liver (Wong et al.). This buildup of toxins may lead to liver fibrosis, an increased risk of liver cancer; and varices, enlarged veins in the oesophagus in people with cirrhosis. 

Summary

Although ketamine has been around since the 1960s, it remains a heavily studied drug. Although originally developed as a post-operative anaesthetic, these days it’s gaining popularity as an effective treatment for depression when other measures have failed. In a medical setting and administered by trained medical personnel, it seems to present a minimal risk for complications or unintended side effects. 

At the same time, ketamine is also seeing a surge in popularity as a party drug. Partygoers looking for a temporary high rarely do so under medical supervision, and often resort to mixing ketamine with other substances to enhance its effects. When this behaviour is repeated again and again, ketamine starts posing serious physical and psychological health risks and is associated with a myriad of morbidity factors. 

If you or a loved one is struggling with ketamine abuse, seeking professional medical assistance to help you beat ketamine addiction sooner rather than later can be the difference between a happy and productive life and having your brain and organs potentially irreversibly damaged by a potent narcotic. 

Feel free to contact Gladstones Clinic at 0808 258 2350 or through our online portal. Our trained and experienced addiction specialists will gladly talk you through our treatment options or answer any further questions you have concerning ketamine abuse.

For more information on ketamine’s resurgence into popularity, especially among teenagers and young adults, feel free to read our article on ketamine and increased prevalence within substance misuse.

Get professional help in dealing with addiction

If you would like more information on our addiction rehab programme, feel free to contact Gladstones Clinic at 0808 258 2350 for an obligation-free discussion or advice.

Works Cited

Drug Enforcement Administration (DEA). “Drug Fact Sheet: Ketamine.DEA.gov, Drug Enforcement Administration (DEA), 2020, https://www.dea.gov/sites/default/files/2020-06/Ketamine-2020.pdf. Accessed 27 February 2024.

Fan, N., et al. “Profiling the psychotic, depressive and anxiety symptoms in chronic ketamine users.Psychiatry research, vol. 237, 2016, pp. 311-315. National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906312/. Accessed 27 02 2027.

Lankenau, S. E., and M. C. Clatts. “Patterns of Polydrug Use Among Ketamine Injectors in New York City.NCBI, Substance Use Misuse, 2005, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1899171/. Accessed 27 February 2024.

Lazarevic, V., et al. “Ketamine decreases neuronally released glutamate via retrograde stimulation of presynaptic adenosine A1 receptors.Molecular Psychiatry, vol. 26, no. 12, 2021, pp. 7425-7435. National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872981/. Accessed 27 02 2024.

Monaghan, L., and H. V. Curran. “In and out of the K-hole: a comparison of the acute and residual effects of ketamine in frequent and infrequent ketamine users.PubMed, Addiction (Abingdon, England), 2001, https://pubmed.ncbi.nlm.nih.gov/11331033/. Accessed 27 February 2024.

Orhurhu, V. J., et al. “Ketamine Toxicity.StatPearls, 2023. National Library of Medicine, https://www.ncbi.nlm.nih.gov/books/NBK541087/. Accessed 27 02 2024.

Oxford Health, NHS Foundation Trust. “Risks and benefits.Oxford Health NHS Foundation Trust, Oxford Health NHS Foundation Trust, 2022, https://www.oxfordhealth.nhs.uk/ketamine/risks-benefits/. Accessed 27 February 2024.

Pappachan, J., et al. “Multiorgan dysfunction related to chronic ketamine abuse.Proceedings (Baylor University. Medical Center), vol. 27, no. 3, 2014, pp. 223-225. National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059572/. Accessed 27 02 2024.

Strous, J., et al. “Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review.” Frontiers in Neuroanatomy, vol. 16, 2022. National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8972190/. Accessed 27 02 2024.

University College London. “Heavy ketamine use affects short-term memory | UCL News – UCL – University College London.University College London, 17 November 2009, https://www.ucl.ac.uk/news/2009/nov/heavy-ketamine-use-affects-short-term-memory. Accessed 27 February 2024.

Wong, G., et al. “Liver injury is common among chronic abusers of ketamine.” Clinical gastroenterology and hepatology, vol. 12, no. 10, 2014, pp. 1759-1762. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/24534547/. Accessed 27 02 2024.

Zhang, M. W.B, and R. C.M Ho. “Controversies of the Effect of Ketamine on Cognition.Frontiers in Psychiatry, vol. 7, no. 47, 2016. National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809869/. Accessed 27 02 2024.

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