Ketamine is a dissociative anesthetic with a potential for recreational misuse.1 Ketamine overdose has numerous troubling symptoms that can impact mental and physical functioning.2 Recent studies have cited a worldwide increase in ketamine misuse, so it’s becoming more critical to understand the potential adverse effects of using this drug.3,4 Then, in the 2000s, researchers found that doses of ketamine that didn’t put people to sleep could rapidly reduce symptoms of depression, because, the thinking went, the drug altered the physical circuitry of the brain. Ketamine is a powerful dissociative anesthetic that can make people feel detached from things such as pain sensations and other environmental elements.5 Though pharmaceutical use in both human and veterinary medicine exists, there are many potential adverse effects of ketamine misuse, including the potential for dose-dependent toxicity, or ketamine overdose.2 At high doses, ketamine can Benzodiazepine withdrawal induce general anesthesia — unconsciousness — but at low doses, it causes these antidepressant and dissociative effects.
In an experiment with purely ketamine anesthesia, people began to awaken once the plasma level of ketamine decreased to about 2,600 ng/mL (11 μM) and became oriented in place and time when the level was down to 1,000 ng/mL (4 μM). The typical intravenous antidepressant dosage of ketamine used to treat depression is low and results in maximal plasma concentrations of 70 to 200 ng/mL (0.29–0.84 μM). Dissociation and psychotomimetic effects are reported in people treated with ketamine at plasma concentrations of approximately 100 to 250 ng/mL (0.42–1.1 μM). Blocking of the NMDA receptor results in analgesia by preventing central sensitization in dorsal horn neurons; in other words, ketamine’s actions interfere with pain transmission in the spinal cord.
This discovery sparked additional psychiatric research on ketamine. In 1999, the Drug Enforcement Administration (DEA) classified ketamine as a Schedule III controlled substance. Known as “Special K,” ketamine was abused for psychedelic out-of-body experiences. In early rat testing, ketamine did not appear addicting. Ketamine was synthesized in 1962 (a mixture of two mirror-image molecules, R- and S-ketamine) and developed as an alternative to phencyclidine (PCP).
What should I tell my care team before I take this medication?
- These reactions are less frequent in children and more common in women, with increasing doses and rapid bolus administration.31,177
- In 2024, Shafique and colleagues94 published a comprehensive review of the literature comparing S-ketamine and R-ketamine in depression.
- This includes areas relevant to anaesthesia and perioperative medicine, such as acute and chronic pain management, ICU sedation, and even tumour suppression in those undergoing surgical resection of malignancies.
- Although there are promising animal and preclinical studies, the authors caution that overall data on R-ketamine in humans are limited.
- “Doctors shouldn’t prescribe it by itself – only with antidepressants, if other treatments aren’t effective.”
- When friends and family who are depressed ask me if they should seek out ketamine as a potential option, I tell them that it doesn’t make sense unless they have tried oral antidepressants.
- Some people have an almost complete sensory detachment that they compare to a near-death experience.
Due to the bronchodilating properties of ketamine, it can be used for anesthesia in people with asthma, chronic obstructive bipolar disorder and alcohol airway disease, and with severe reactive airway disease, including active bronchospasm. Ketamine’s clinical and antidepressant effects can be influenced by co-administration of other drugs, though these interactions are variable and not yet fully understood. Liver and urinary toxicity have been reported among regular users of high doses of ketamine for recreational purposes. Ketamine is legally used in medicine but is also tightly controlled, as it is used as a recreational drug for its hallucinogenic and dissociative effects. Nonetheless, this treatment can often help patients to reclaim the energy and motivation they need to better address their own personal problems themselves, which in turn can lead to better mental health.
- Also, why use an intravenous or injected ketamine instead of intranasal Spravato, with its precautions?
- Subjects completed three test days involving the 40-minute intravenous administration of placebo, ketamine hydrochloride (0.1 mg/kg), or ketamine hydrochloride (0.5 mg/kg).
- At lower doses, it has psychoactive properties and has gained popularity as a recreational drug.
- According to the Drug Enforcement Administration (DEA), recreational forms of ketamine are commonly known as Special K, KitKat, Vitamin K, and other slang terms.
- Researchers believe this activity helps with ketamine’s uses in anesthesia, pain management, and depression treatment.
- If you or someone you care about need help with ketamine or other substance use, reach out to American Addiction Centers (AAC) to connect with an admissions navigator, who can answer your questions and explain your options.
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.
General anesthesia denotes a sleep-like state, while dissociative refers to the effect of feeling disconnected. Doctors use it to induce general anesthesia for medical procedures that do not require muscle relaxation. Under the Controlled Substances Act, health experts consider ketamine a schedule III non-narcotic substance. We want to know what happens at the molecular level and at the neural circuit level that could cause these different effects. The primary tool we use to measure brain states is the EEG.
Ketamine safety, side-effects, and toxicity
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).
After an intravenous injection of tritium-labelled ketamine, 91% of the radioactivity is recovered from urine and 3% from feces. This also explains why oral ketamine levels are independent of CYP2B6 activity, unlike subcutaneous ketamine levels. Low oral bioavailability of ketamine is due to the first-pass effect and, possibly, ketamine intestinal metabolism by CYP3A4. It is biotransformed by CYP3A4 and CYP2B6 isoenzymes into norketamine, which, in turn, is converted by CYP2A6 and CYP2B6 into hydroxynorketamine and dehydronorketamine.
Its ability to provide pain relief and sedation without suppressing breathing as much as other anesthetics makes it useful in emergency medicine. This intense experience can be frightening and disorienting, representing the peak of the drug’s dissociative capabilities. The dissociative state induced by ketamine makes a person feel profoundly separated from their own body and external reality. Ketamine is a medication classified as a dissociative anesthetic, meaning it produces a sense of detachment from one’s environment and self. Call your doctor for medical bromide detox advice about side effects. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use.
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.
Understanding Ketamine – Effects, Risks, and Staying Informed
Pore blocking of the NMDA receptor is responsible for the anesthetic, analgesic, and psychotomimetic effects of ketamine. At anesthetic doses, 10–20% of adults and 1–2% of children experience adverse psychiatric reactions that occur during emergence from anesthesia, ranging from dreams and dysphoria to hallucinations and emergence delirium. Potentially, ten more people with bipolar depression per 1000 may experience brief improvement, but not the cessation of symptoms, one day following treatment.
“Large amounts of data suggest that your ability to make rational, correct decisions is completely disrupted when you take ketamine, as long as it’s in your system,” Sanacora says.. “People can hear things, see things, feel things differently. Some providers assess patients via telepsychiatry for the first visit and then mail or give patients ketamine to take home and self-administer. The number of patients with a ketamine prescription rose more than fivefold between 2017 and 2022. Consequently, patients may be prescribed ketamine off-label, by injection, at home.
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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.
Another form of ketamine called R-ketamine is currently being studied for treatment-resistant depression. A form of ketamine known as esketamine nasal spray was approved by the FDA in 2019 under the name Spravato for use in treatment-resistant depression. The DEA says higher doses of recreational ketamine can cause serious reactions.
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The typical symptoms of ketamine-induced cystitis are frequent urination, dysuria, and urinary urgency sometimes accompanied by pain during urination and blood in urine. In February 2022, the US Food and Drug Administration (FDA) issued an alert to healthcare professionals concerning compounded nasal spray products containing ketamine intended to treat depression. Among people receiving esketamine, 12.1% (2.5 to 24.4%) encountered some relief at 24 hours, and 10.3% (4.5 to 18.2%) had few or no symptoms. There were 18.7% (4.1 to 40.4%) more people reporting some benefit and 9.6% (0.2 to 39.4%) more who achieved remission within 24 hours of ketamine treatment.
The second-line treatments are epithelium-protective agents such as oral pentosan polysulfate or intravesical instillation of hyaluronic acid. Management of ketamine-induced cystitis involves ketamine cessation as the first step. All these adverse effects are most pronounced by the end of the injection, dramatically reduced 40 minutes afterward, and completely disappear within 4 hours after the injection. The most common psychiatric side effects are dissociation, visual distortions, and numbness.
Since then, several meta-analyses have shown that ketamine provides rapid antidepressant effects in MDD and treatment-resistant MDD, with improvements lasting from days to weeks.81, 82, 83, 84 In 2024, Wang and colleagues85 found ketamine also significantly reduced depression in the postnatal period. In 2000, Berman and colleagues80 published the first placebo-controlled trial of the antidepressant properties of ketamine in MDD, highlighting NMDA receptor modulation as a potential treatment mechanism. Ketamine has been used in the treatment of both acute and chronic pain at doses that either use light sedative effects or at entirely subanaesthetic doses. Many people want to know about ketamine, a drug used for treatment-resistant depression. We found that different anesthetic drugs, like propofol, ketamine, sevoflurane, and dexmedetomidine, cause very distinct brain oscillatory patterns. The dissociative effects are pretty prevalent in patients taking ketamine.
While patients being treated with the opioid antagonist Suboxone (buprenorphine and naloxone) cheered the new telemedicine rules, extended through 2024, the rules also currently enable an at-home ketamine phenomenon. Patients are observed at least two hours after receiving the agent and typically receive psychotherapy and other treatments for depression. The FDA approved Spravato contingent on patients enrolling in a risk evaluation and mitigation strategies (REMS) program before receiving the drug at a center approved to administer it. This meant it was similar to codeine and buprenorphine—having accepted medical benefits but abuse potential. Still, nonhuman primate testing has shown it is addicting, depending on dose, route of administration, frequency, and current and past drug use.
Others are looking at combining ketamine with other therapies to enhance its effectiveness and reduce the need for repeated doses. Some scientists are investigating compounds that mimic ketamine’s antidepressant effects without the psychoactive properties. Despite these concerns, the potential therapeutic applications of ketamine continue to excite the medical community. It’s as if the drug slowly rewires your brain’s circuitry, potentially altering the very essence of who you are.
Ketamine, however, also acts on a wide range of other cellular targets, resulting in interesting and diverse effects on both physiological and pathological processes. Intravenous ketamine is prescribed off-label, so there are no hard-and-fast rules. It should only be used when other medications to treat depression have failed. Ketamine helps the brain form new neural pathways, according to research. Ketamine increases levels of the neurotransmitter glutamate in the brain, according to research. Antidepressants may slowly build up levels of the neurotransmitter serotonin in the brain.