How Does Ketamine Work?

If patients take ketamine several times a week at high doses for an extended period, this can result in irreversible problems with memory and thinking, and increase their risk of delusions. Perry’s case is a tragic example of why it’s not a good idea for doctors to prescribe, or patients to take, ketamine at home—a practice that my colleagues and I have warned against. Especially since the news media reported that ketamine played a significant role in the death of actor Matthew Perry, a lot of patients wonder if ketamine/esketamine is actually safe. Ketamine and esketamine were approved for forms of depression that haven’t responded to traditional oral antidepresants (such as fluoxetine/Prozac, sertraline/Zoloft, etc.). Beginning in the mid-2010s (see figure 1 in this paper), more doctors started offering ketamine as a treatment for depression. This includes benefits for mental health conditions such as treatment-resistant depression, PTSD, and suicidal ideation.

Medical use dosage forms

The short answer is yes, when it’s done with the proper safeguards. 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. As a general rule, at least 4 weeks of treatment are required before it can be known if an antidepressant is helpful. (The exception would be when a patient is imminently suicidal, in which case the treatment would often be started while the patient is hospitalized.) What counts as “trying” an oral antidepressant?

Glutamate is an important neurotransmitter, a kind of brain chemical that plays a role in typical brain function. The team at Delamere are here to answer any questions you may have about starting a ketamine detox or rehab; contact us by phone or online to get started. Urinary system damage – Persistent use of ketamine more than a couple of times a week can lead to kidney and bladder damage. Users may complain from a racing heart rate and palpitations, which can lead to ongoing trauma ever after the physical effects subside.

Whereas, low ketamine enhanced novelty detection compared to controls, higher doses impaired novelty detection (Schumacher et al., 2016). In rats, different 5–7-days dosing regimens of ketamine yielded opposite effects on cognitive tasks in which the rats had to detect novel objects, or novel placement of objects. It needs to be considered however, that there may be a U-shaped dose-effect relation between ketamine and cognitive changes. In rats, ketamine was found to acutely elevate presynaptic glutamate in the prefrontal cortex at AMPA/kainite receptors (Moghaddam et al., 1997), and prolonged ketamine exposure may provoke cell death by regional glutamate-induced excitotoxicity. Mice treated with 3 or 6 months daily subanesthetic doses (30 or 60 mg/kg) of intraperitoneal ketamine showed hyperphosphorylation of tau-protein hampering trafficking of AMPA-receptors, which in turn worsened signal transduction (Li et al., 2019). Together, these findings suggest that long-term intensive ketamine use may affect the structure and function of cortical gray and white matter, especially in frontoparietal regions.

• Although only a subset of recreational ketamine users are reported to develop dependence (Muetzelfeldt et al., 2008) and tolerance (Bonnet, 2015), the current review suggests several potential mechanisms for addiction that should be further explored to gain an understand of ketamine abuse.
• Gail Serruya, M.D., is a psychiatrist with years of training in psychotherapy, who recently founded Voyage Healing PC, a ketamine-assisted psychotherapy clinic in Philadelphia.
• Ketamine helps the brain form new neural pathways, according to research.
• Like the drug itself, Stewart got his start in combat medicine during the Vietnam War.
• The team at Delamere are here to answer any questions you may have about starting a ketamine detox or rehab; contact us by phone or online to get started.
• This is usually when other treatments haven’t worked (therapy resistant depression).

In addition, ketamine has some anti-inflammatory properties. Ketamine also has smaller effects on other receptor subtypes, such as the dopaminergic and opioid receptors. The NMDA receptor plays a role in how glutamate transmits messages between brain cells.

We have a circuit in our brain, called the default mode network, whose activity is linked to the endless ruminating chatter in our mind about the past and the future. I believe there will be much research in the future as to how patients may leverage this neuroplastic window. If a patient hasn’t responded to traditional antidepressants, this doesn’t mean they won’t respond to ketamine.

How long the effects last

• Studies suggest low doses of ketamine can stimulate glutamate production and help repair connections in the brain, especially between the prefrontal cortex and the hippocampus.
• Although the identified lower gray and white matter volumes or integrity could suggest direct neurotoxic effects of ketamine, the observed higher structural and functional connectivity and dopamine binding may suggest indirect compensatory effects.
• Ketamine also encourages your brain to release a special protein called Brain-Derived Neurotrophic Factor (BDNF).
• As rates of depression and anxiety have increased dramatically, people have sought therapies outside the standard regimen of oral antidepressants and talk therapy.
• Since 2019, medical specialists in the Netherlands are allowed to prescribe ketamine against depression.
• From mood swings and anxiety to teary comedowns, ketamine can cause immediate changes to our mental health.
• As psychiatrists, we probably don’t pay enough attention to patients’ social and economic circumstances as well as their lifestyle choices, which can all have huge effects on mental health.

While promising studies show that ketamine may be effective for some behavioral health conditions, substance use disorders, and chronic pain conditions, it is not risk-free. Typically, the only ketamine-derived treatment for depression that insurance will cover is the FDA-approved nasal spray esketamine (Spravato). Other drugs that cause glutamate release – such as benzodiazepines – can dampen ketamine’s effects.

Medical Uses and Emerging Research

The most important one is that ketamine/esketamine should be administered while the patient is in a clinic (as opposed to at home). The reasons for this are that ketamine/esketamine are riskier than standard antidepressants, require substantial commitments of time, and are more expensive. As rates of depression and anxiety have increased dramatically, people have sought therapies outside the standard regimen of oral antidepressants and talk therapy. Keep in mind that ketamine has serious side effects which can be dangerous. Your doctor can tell you about the latest research and medical uses for ketamine, including the pros and cons of the drug.

Despite the absence of prospective studies, some first insights might be gained from retrospective cohort studies in recreational ketamine users (UNODC, 2016). Small case series of ketamine administration in various doses for up to one year in patients with MDD or chronic pain suggest that some of these neural side effects may remain with prolonged ketamine use (Cvrcek, 2008; Szymkowicz et al., 2013). Powdered ketamine is often cut with other drugs, so it’s very hard to tell what the long-term effects will be—interactions can be very unpredictable. Illegal ketamine, often used recreationally, is unregulated, may be contaminated and carries higher risks of overdose, addiction and health complications due to unknown purity and unsafe use. To better understand people’s experience of ketamine and how it might be best used in medical treatment, we surveyed hundreds of people who self-identify as struggling with ketamine addiction.

Results

In addition, street ketamine might not be pure ketamine but could be contaminated with other drugs, which would strengthen this confounding. Nonetheless, evidence exists for opposite clinical effects of low dose vs. high dose ketamine. The observed upregulation of dorsolateral prefrontal D1 receptors in ketamine users might be a compensatory mechanism for deficient prefrontal dopamine function underlying impaired working memory function (Narendran et al., 2005). Also, white matter changes in one of these studies preceded more widespread cortical atrophy with longer ketamine use, supporting that axonal cells are most vulnerable for glutamate-induced excitotoxicity by ketamine. Excitation of AMPA receptors specifically induces axonal damage (Fowler et al., 2003), which could provide a potential mechanism for the prominent white matter changes observed after sustained ketamine exposure in three of the reviewed studies.

Ketamine therapy helped her depression and PTSD, but not her anxiety. Though some, he says, may talk or make a comment about the music playing on their headphones or some part of their experience, or perhaps ask where they are. The dissociative experience starts quickly and takes about 15 to 20 minutes to wear off after the drip ends. Most research stops the initial treatment at 6 weeks.

More recently, researchers have explored its potential as a treatment for severe depression and mood disorders. Perry suffered from opioid use disorder and turned to ketamine as an alternative treatment. These distortions, linked to the drug’s psychoactive properties, interfere with normal visual processing pathways in the brain. Ketamine’s effects on visual perception manifest as visual distortions, altering an individual’s experience of their surroundings.

Despite the promising short-term effects, ketamine recently has been emerging as a drug of abuse. We performed a systematic review of studies reporting functional and structural brain changes after repeated ketamine abuse. In addition, ketamine can be helpful for pain, which many people experience during the late stages of terminal illness. At certain doses, ketamine can result in a mystical or spiritual experience. We know that in rodent studies, ketamine can cause the brain to grow new nerve cells and can make existing nerve cells sprout new connections between each other.

Do you use ketamine often or in large amounts? When using ketamine as an anti-depressant, it’s important this is done under supervision of a doctor. When we look at people who go out between the ages of 16-35, the percentage is a lot higher at 25%. This research gives us a good overview of drug usage in alcohol as a seizure trigger the Netherlands. Like people who go out a lot, students, or citizens of a specific city.

The drug hit headlines recently when linked to the death of The Vivienne, real name James Lee Williams. “Doctors shouldn’t prescribe it by itself – only with antidepressants, if other treatments aren’t effective.” Intravenous ketamine is prescribed off-label, so there are no hard-and-fast rules.

For example, using ketamine with alcohol or other central nervous system (CNS) depressants can result in profound respiratory depression and death.3 The range of effects felt can be somewhat unpredictable and may vary in severity based on the amount of the drug consumed. In relatively recent years, ketamine has gained popularity as a “club drug” used by teenagers and young adults at raves or parties.3 A national survey of American youth in 2023, estimated that nearly 1% of all high school seniors had used ketamine in the past year.4 Ketamine/esketamine is not a cure-all or “magic bullet” that will somehow alleviate all of a suffering patient’s problems. The best clinical evidence shows that patients should start treatment twice per week for 4 weeks. The clinical evidence shows that there’s no added benefit to receiving ketamine/esketamine more than twice per week.

Also, they found a correlation between higher sgACC connectivity with the dmPFC and higher depression scores in women, but not in men. However, since subjects had to be abstinent from ketamine for only 48 hours, and since the direct effect of ketamine can last for more than 48 hours, the altered frontal network organization might also be a direct result of ketamine instead of a long-term side effect (Zarate et al., 2012). This may suggest that ReHo is initially increased more by ketamine use but famous people who died from alcoholism that this increase eventually decreases with more prolonged and intensive use, which may alter functional organization in frontal networks. The higher ReHo in the left precentral frontal gyrus was negatively correlated with estimated total lifetime ketamine consumption and ketamine craving (Liao et al., 2012). Lower functional connectivity was found between the thalamus and the motor-, posterior parietal- and prefrontal cortex.

If you snort it, the effects begin after 3 to 10 minutes. Some people find this G6PD medications interesting or even insightful, but others find it frightening. It can feel like you can’t move or speak. A k-hole is a very intense experience.

Adolescent-onset users showed a significantly smaller left precuneus volume than the adult-onset group and the healthy control group. Gray matter volumes in rOFC, rMPFC and rNAC were negatively correlated with ketamine dependence severity and gray matter volumes of the rOFC, rmPF, lCN, lGP, lH, and rNAC negatively correlated with cognitive performance (Liu et al., 2016; Tang et al., 2016). However, cortical atrophy occurred earlier than 3 years in a patient who had been using a high dose of 3 grams ketamine per day (Wang et al., 2013). Changes were observed in both white and gray matter across the internal capsule, basal forebrain, cerebellum and diencephalon.