The Controlled Substance Act classifies ketamine as a Schedule III non-narcotic drug. One of the dangers of ketamine overdose involves a higher risk of accidents and injuries due to impaired alertness. Both alcohol and ketamine are central nervous system depressants, so the combined effects are dangerous. Due to this effect and its ability alcohols effects on lung health and immunity pmc to sedate and incapacitate people, rapists may use it as a date-rape drug. Ketamine makes people feel detached from their environment, eases pain, and produces hallucinations, which has led to its inappropriate use.
Off-label unsupervised use of ketamine is a risk to many besides Matthew Perry.
In moments of crisis, when time is of the essence, ketamine’s swift action could literally be a lifesaver. Ketamine doesn’t just target run-of-the-mill depression. This serendipitous discovery set the stage for a new chapter in ketamine’s story.
They are also counseled on the risks of engaging too soon in activities requiring full alertness; for example, they are advised to avoid driving until the day after treatment. Patients are monitored for sedation, blood pressure, and possible dissociation during treatment and observation. In 2023, the National Academy of Medicine awarded Dennis Charney, John Krystal, and Husseini Manji the Sarnat International Prize in Mental Health for their discovery leading to esketamine. The late George Aghajanian, M.D., collaborated with neuroscientist Ronald Duman on a Yale study showing how ketamine worked—by inducing synaptic neuroplasticity.
In this article, we’ll discuss ketamine’s medical uses, side effects, and more. But there is still much more to learn about how ketamine works, how it could be dosed, and what long-term effects it may have on the body. The drug is also popular for recreational use because of its dissociative effects.
Ketamine has been suggested as a possible therapy for children with severe acute asthma who do not respond to standard treatment. A possible option may be maintenance therapy with ketamine, which usually runs twice a week to once every two weeks. In particular, only for CRPS, there is evidence of medium to longer-term pain relief. It has the added benefit of counteracting spinal sensitization or wind-up phenomena experienced with chronic pain. Ketamine is an option in children as the sole anesthetic for minor procedures or as an induction agent followed by neuromuscular blocker and tracheal intubation.
Both reported ketamine as safe and effective in a resource-constrained environment, with a low incidence of reported major adverse events. In 2002, Bonanno50 reported that ketamine with a benzodiazepine provided safe and effective general anaesthesia during the civil war in Somalia. Ketamine in this application has the additional benefits of few to no life-threatening adverse effects of accidental intravenous or intrathecal administration. A recent meta-analysis conducted by Xiang and colleagues45 drinking out of boredom in 2024 found that ketamine combined with local anaesthetic provided prolonged duration of analgesia, particularly when used for peripheral nerve blocks, compared with use of local anaesthetics alone.45
Is ketamine therapy covered by insurance or Medicare?
Some studies suggest the drug may have other medical uses, but more research is necessary to prove its safety and effectiveness in these areas. High doses can also cause death that stems from their physical effects. No person with alcohol use disorder or alcohol intoxication should take ketamine, even in doctor-prescribed doses, as it can cause death. However, the authors did highlight that the anxiety-relieving effects of ketamine are temporary, with symptoms often returning around 2 weeks after taking it.
The dissociative effect of ketamine that is produced by high doses is often described by recreational users as the “K hole”—a separation of the mind and body, or a hallucinatory “out of body” experience. Minor side effects of the drug include tearing (lacrimation) when emerging from the dissociative anesthetic state. Veterinarians often use ketamine with sedative drugs to produce balanced anesthesia and analgesia, and as a constant-rate infusion to help prevent pain wind-up. In veterinary anesthesia, ketamine is often used for its anesthetic and analgesic effects on cats, dogs, rabbits, rats, and other small animals.
Refractory status epilepticus (RSE) is a form of status epilepticus that does not respond to standard antiseizure drugs. Off-label means using the drugs to treat conditions the FDA has not approved. However, doctors sometimes prescribe it for “off-label” uses, such as depression. Ketamine is a Schedule III non-narcotic that the Food and Drug Administration (FDA) has approved for use only as a general anesthetic.
We are interested in identifying biomarkers that allow us to measure brain states clinically, and particularly in finding biomarkers for unconsciousness. It’s more severe in some patients but less in others. ” The answers varied among patients, but most answered “yes” to a large proportion of these questions. We used a questionnaire called the Clinician-Administered Dissociative States Scale, or CADSS, to evaluate the dissociative state.
General Health
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. After absorption ketamine is rapidly distributed into the brain and other tissues. 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. However, changes in 11C raclopride binding may be due to changes in dopamine concentrations induced by ketamine rather than binding of ketamine to the D2 receptor.
Imaging studies have shown mixed results on inhibition of striatal 11C raclopride binding by ketamine in humans, with some studies finding a significant decrease and others finding no such effect. Early research by the Philip Seeman group found ketamine to be a D2 partial agonist with a potency similar to that of its NMDA receptor antagonism. Ketamine has been found to increase dopaminergic neurotransmission in the brain, but instead of being due to dopamine reuptake inhibition, this may be via indirect/downstream mechanisms, namely through antagonism of the NMDA receptor. Collectively, these findings shed doubt on the involvement of monoamine reuptake inhibition in the effects of ketamine in humans. With a couple of exceptions, ketamine actions at other receptors are far weaker than ketamine’s antagonism of the NMDA receptor (see the activity table to the right).
Risks of ketamine
- This medication was approved as a therapy for treatment-resistant depression.
- Outside the clinic, the drug is reportedly popular among Silicon Valley’s tech elite, and a feature at some wellness retreats, including those for leadership development, corporate team building, or couples counseling.
- By blocking this receptor, ketamine disrupts the normal signaling of glutamate, the most abundant excitatory neurotransmitter in the brain, which leads to the dissociative and anesthetic effects.
- These searches produced 5,268 non-duplicate citations; 185 articles (case reports, case series, pharmacokinetic studies, animal studies pertinent to pharmacology, and reviews) were considered relevant.
- NMDA receptors play a key role in many central nervous system processes, including synaptic function, neuroplasticity, learning, and memory, with interesting implications for a variety of neurological diseases.102
- A single dose of intravenous ketamine has been shown to result in a response rate greater than 60% as early as 4.5 hours after the dose (with a sustained effect after 24 hours) and greater than 40% after 7 days.
In the end, the tale of ketamine serves as a powerful reminder of the complexities inherent in treating the human mind. As we move forward with ketamine, we must apply these lessons wisely, always striving to balance innovation with caution, hope with realism. And as it does, it continues to challenge our understanding of consciousness, mental health, and the intricate workings of the human mind. Its full potential, along with its risks and limitations, is still unfolding.
- The drug was approved by the FDA as Spravato in 2019, first for treatment-resistant depression and, later, for major depressive disorder with acute suicidal ideation.
- One thing’s for sure – the ketamine revolution has forced us to rethink our approach to mental health treatment.
- If you or a loved one is living with an addiction to ketamine, there’s nothing to be ashamed of.
- First up, there’s the potential for addiction and dependence.
- Ketamine can cause dissociation and nausea, and other adverse effects, and is contraindicated in severe heart or liver disease, and uncontrolled psychosis.
- Psychotomimetic effects decrease when adding lamotrigine and nimodipine and can be counteracted by pretreatment with a benzodiazepine or propofol.
- This also explains why oral ketamine levels are independent of CYP2B6 activity, unlike subcutaneous ketamine levels.
Current theories include nitric oxide-induced inflammation, IgE-mediated hypersensitivity, microvascular changes, and direct ketamine toxicity.185, 186, 187 In 2015, Mazzeffi and colleagues179 conducted a review of ketamine use in cardiac surgery and cardiac surgical ICU. Ketamine is often the recommended induction agent in these patients because of its haemodynamic properties.175,176 It should be noted that the avoidance of hypotension is crucial in managing traumatic brain injury to prevent secondary brain injury, morbidity, and mortality.176 After brain injury, cerebral autoregulation is disrupted, and blood flow is dependent on systemic blood pressure and ICP.
Ketamine also has low protein binding (up to 50%164,165) compared with propofol (98%166) Drug tapering and is highly lipid soluble, crossing the blood–brain barrier and reaching therapeutic levels rapidly without significant dose adjustment, even in relatively low circulating protein states or acidosis.165 Despite this, the exact effect of ketamine on malignancies remains unclear, and some animal studies have demonstrated that induced ketamine addiction in mice can increase breast tumour invasion and size, without affecting proliferation.161 The potential for ketamine to become a useful adjunct in the management of a wide range of malignancies, particularly in the perioperative period, has led to growing interest in this field of research. In 2019, Duan and colleagues159 described ketamine as attenuating the malignant potential of cancer cells and preventing cell migration through NMDA antagonism. For example, Saito and colleagues157 demonstrated that lung carcinoma cell lines have greater sensitivity to ketamine than neuroglioma cells; however, both cell types exhibited dose-dependent reductions in cell proliferation and migration and an increase in apoptosis. The 2023 review by Johnston and colleagues147 highlights the proposed links between depression and chronic inflammation, preliminary evidence for the use of ketamine in this area, and the need for ongoing research.147
Buckle up, folks, because ketamine can take you on quite the emotional journey. It’s not uncommon for ketamine users to report feeling as if they’ve traveled to different dimensions or communed with entities beyond our realm of understanding. It’s like your brain decides to take a little vacation from the mundane task of remembering everyday details.
Is Ketamine Safe?
An update on ketamine and its two enantiomers as rapid-acting antidepressants. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. The future of mental health treatment may well depend on it.
A 2019 large-scale study found that written reports of ketamine experiences had a high degree of similarity to written reports of NDEs in comparison to other written reports of drug experiences. In a group of chronic high-dose ketamine users, the frequency of liver injury was reported to be about 10%. Studies indicate that ketamine-induced cystitis is caused by ketamine and its metabolites directly interacting with urothelium, resulting in damage of the epithelial cells of the bladder lining and increased permeability of the urothelial barrier which results in clinical symptoms. Urinary toxicity occurs primarily in people who use large amounts of ketamine routinely, with 20–30% of frequent users having bladder complaints.
The promise of revolutionary treatments must always be balanced against the imperative to do no harm. The path forward for ketamine will require careful navigation of scientific, ethical, and regulatory landscapes. It’s shown us that rapid relief from debilitating conditions like severe depression is possible, challenging the status quo of traditional psychiatric medications. The challenge lies in harnessing its therapeutic potential while mitigating the risks.