Due to its euphoric, dissociative, and hallucinogenic properties, ketamine has been abused as a recreational drug, which has led to rigid regulation of medication. The COVID-19 pandemic has been an unprecedented challenge for the American population which was reflected in increased reports of problems regarding their mental health. Approximately one in ten people stated that they had started or increased substance use because of the COVID-19 pandemic. Furthermore, rates of suicidal ideation have significantly increased when compared to pre-pandemic levels, with more than twice the number of adults surveyed in 2018 indicating suicidal thoughts “within the last 30 days” at the time they were surveyed.

Conditions Treated

Ketamine has anti-inflammatory effects, stimulates the cardiovascular system and decreases inotropic effects, which makes it convenient for use in septic patients 46. Therefore, the combination of ketamine with benzodiazepine could be used for traumatic brain injury, such as intracranial hypertension in emergencies 81. Ketamine primarily exerts its analgesic, anesthetic, and psychomimetic effects via antagonism of NMDA receptors in the central nervous system (CNS). In the spinal cord’s dorsal horns, the antagonistic effect on NMDA receptors results in interference with pain transmission, leading to profound analgesia and prevention of central sensitization 16,17. These effects cumulatively lead to amnestic, analgesic, and dose-dependent anesthetic actions, as well as cataleptic and unique-to-ketamine dissociative states 18. The primary factor behind the antidepressant effects is the inhibition of NMDA receptors, leading to the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.

Ketamine and the Brain: Understanding Neuroplasticity

It is effective in disorders such as depression, bipolar affective disorder, chronic pain, asthma, and even in the treatment of alcohol and heroin addiction (Table 1). Furthermore, ketamine triggers the mammalian target of rapamycin (mTOR) pathway, resulting in the deactivation of glycogen synthase kinase 3 (GSK-3) and the inhibition of eukaryotic elongation factor 2 (eEF2) kinase phosphorylation 19,20,21,22. The active metabolite of ketamine, hydroxynorketamine, does not demonstrate notable interactions with the NMDA receptor. However, it indirectly stimulates AMPA receptors, potentially playing a role in the swift onset of ketamine’s antidepressant effects 23.

It is important to note that ketamine is no longer safe when individuals take it inappropriately. The danger increases with regular use since it can harm health and other aspects of life. The authors of a 2023 review of studies suggested that the type of ketamine and the right dose are key factors influencing how well it works as a treatment for depression. They also noted that higher doses of ketamine appear to help reduce depression symptoms at all stages of treatment.

• Due to this effect and its ability to sedate and incapacitate people, rapists may use it as a date-rape drug.
• One of the pearls of the field of pharmacoepidemiology is that it’s not just about safety or effectiveness, it’s about safety and effectiveness and the balance of these.
• Ketamine’s effects are primarily due to its action as an NMDA receptor antagonist.
• Systematic reviews and meta-analyses provide support for robust, rapid and transient antidepressant and anti-suicidal effects of ketamine.
• It leads to changes in sensory experiences, dream-like states, and also a distortion of sights, colors, sounds, self, and one’s environment.

AMPA receptor activation induces downstream effects, leading to the upregulation of brain-derived neurotrophic factor (BDNF) and the activation of the signaling receptor tropomyosin receptor kinase B (TrkB) 10. If you or a loved one is considering going to one of these clinics, make sure to ask questions about their experience and training related to ketamine and mental health care. Ask for information about the function of the clinic, including whether they simply provide ketamine or integrate the drug into multi-faceted care for depression. Although these severe reactions are uncommon, trained health care providers are aware of them and carefully monitor patients to react quickly if problems arise. The dangers of ketamine use are higher when the drug is given by inexperienced providers or used recreationally and without medical oversight.

Ketamine Abuse

However, choice of adjunctive therapy should also be informed by the symptoms of the patient population. Explore the diverse applications of ketamine therapy including its uses in anesthesia, pain management, and mental health treatment for depression, anxiety, PTSD, and suicidal ideation. The impact of ketamine on opiate tolerance and hyperalgesia, along with its direct analgesic effects, has promoted a growing trend in its utilization for chronic pain conditions.

What other drugs will affect ketamine?

The study concluded that a single ketamine infusion improved the outcome of cocaine-dependent adults engaged in mindfulness-based behavioral modification, by promoting abstinence, diminishing craving, and reducing the risk of relapse 42. However, the sample in the study was relatively homogeneous, with a majority of subjects being African American and male, with minimal psychiatric comorbidity 42. Thus, the effects of early-life ketamine administration maybe age and sex-specific, and it is possible that adolescent administration of ketamine for the treatment of depression may lead to an increased risk of addiction later on in life 42. Further research must be conducted on human subjects in order to determine the significance of these results in a clinical setting. Ketamine is an N-methyl-d-Aspartate receptor agonist with well-established safety and efficacy as an analgesic and anaesthetic.

Mental Health Treatments with Ketamine for Treatment Resistant Depression

Other areas of concern included retrospective classification of outcomes, selection bias, deviations from intended interventions and ketamine: what is it, uses, treatments, effects, and more effects missing outcome data. According to the AMSTAR Checklist, the majority of the systematic reviews were of critically low quality. Frequent critical issues were lack of reference to a registered review protocol, and lack of risk-of-bias analysis and consideration of risk of bias in the interpretation of findings.

• Knowing how ketamine can be used medically and therapeutically shows its important role in mental health care, making it a valuable tool in fighting both depression and anxiety disorders.
• It is a substance with sedative and dissociative properties, affecting a person’s sensations and their perceptions of reality and their environment.
• Ketamine is a dissociative anesthetic developed in the 1960s, primarily used for anesthesia during surgeries.
• In some places, you can get this drug compounded by a pharmacy for in-home use, which is really asking for trouble.
• It was also shown that ketamine is safer and more effective in regional than in general anesthesia.

Using Vraylar Off-Label for Treating Adult ADHD: An Evidence-Based Overview

“During esketamine treatment, there’s just a brief increase in blood pressure. You have to be very careful, maybe not even get the treatment, but I do have people that have had that, I just have neurosurgery consult to make sure that it’s safe,” explained Salzbrenner. Dr. Salzbrenner said people who may not be good candidates for esketamine include those with a significant history of substance use disorder, vascular disease, traumatic brain injuries, and difficulty with emotional control or tolerance of stress. Brady said some side effects of ketamine can be controlled with IV medicines when they arise during treatment.

The use of ketamine for general anesthesia or chronic pain in young children and pregnant women should be carefully considered as prolonged exposure can negatively affect fetal or young children’s brain development 138. Ketamine (2-chlorohenyl-2-methylamino-cyclohexanone), initially known as “CI-581” in chemical structure, is a phencyclidine (PCP) derivative. Calvin Stevens invented the substance called ketamine in 1962 at the Parke-Davis Pharmaceutical Company 1,2. Ketamine primarily functions as a noncompetitive antagonist targeting the N-methyl-D-aspartate (NMDA) receptor (NMDAR), but its mechanism of action is complex.

In addition to using ketamine as an anesthetic, doctors may also prescribe it for “off-label” use. Off-label use allows licensed medical professionals to provide patients with an FDA-approved substance, but for uses that have yet to be officially approved by the agency. There are many medications that have well-known and well-documented off-label uses, including ketamine. Some people may not keep up with their treatments, especially if they can’t afford it or if their insurance doesn’t cover it.

Recent trends indicate a shift in ketamine use from clubs to home settings, increasing the risk of dependency and highlighting the need for harm reduction strategies. “When ketamine is in your system, you’ll likely have the dissociative effects, but that’s not the treatment,” Krystal says. The ketamine treatment is the reaction of your brain to ketamine, how your brain responds to exposure to ketamine.” The antidepressant effects of ketamine happen in the days and weeks after the drug (at the appropriate dose) is in your system, Krystal says. The best clinical evidence shows that patients should start treatment twice per week for 4 weeks. If a patient experiences substantial improvement (generally around 50% improvement in symptoms), the treatment pattern would shift to once per week for another four weeks.