Ketamine Assisted Psychotherapy: Effectiveness and Research

Ketamine is a synthetic, psychedelic compound that was used for decades as a general anesthetic, either on its own or in combination with more common anesthetics like Nitrous Oxide. It was approved for human use by the US Food and Drug Administration (FDA) in 1970. Its quick effectiveness and pain-relieving properties made it a successful battlefield anesthetic in the Vietnam War. However, the later discovery of some of ketamine’s side effects led it to be sparingly used as a general anesthetic in operating rooms. Even so, it continues to be administered in trauma care and certain emergency room and surgical procedures, especially those involving children. It is also widely popular as an animal tranquilizer and veterinary anesthetic. 

Ketamine is a dissociative drug, which means it can cause temporary detachment from reality, feelings of separation between the body and mind, and visual and auditory distortions. Its ability to cause hallucinations within minutes of administering has led to its abuse as a street drug comparable to LSD and PCP, or angel dust. Used under controlled conditions, though, ketamine has therapeutic applications that range from dealing with chronic pain, epileptic seizures, various types of depression, obsessive-compulsive disorder (OCD), suicidal thoughts, and post-traumatic stress disorder (PTSD), among others.   

Ketamine comes in two distinct types. The first is Racemic ketamine – made up of two mirror-image molecules called R-ketamine and S-ketamine. It is used as an intravenous (IV) infusion and has been very effective in the treatment of war veterans suffering from PTSD, depression, and other medical issues. The second type of ketamine is called Esketamine, an FDA-approved compound administered as a nasal spray and effective in the treatment of Major Depressive Disorder (MDD) and treatment-resistant depression (TRD). 

Multiple studies and clinical trials investigating the therapeutic effects of ketamine remain ongoing, with early reports indicating promising results.

What to expect from ketamine therapy

Ketamine is being used successfully as an alternative therapy to treat a variety of physiological and psychiatric problems. It is typically not used as a first-line defense remedy and is instead reserved for cases in which traditional treatment methods have failed. Related psychedelic drugs like psilocybin, LSD, MDMA, and others cannot be legally administered outside clinical trials. However, ketamine and Esketamine can be prescribed for off-label treatments (use of a legal drug to treat conditions it is not approved for), including those for chronic pain, severe depression, anxiety, suicidality, PTSD, and other mental health conditions.  

Ketamine is distinct in function from other psychedelics. It works to alter neural activity in the brain by affecting a neurotransmitter called glutamate. This means that when taken in low doses, ketamine effectively rewires the brain’s internal networks, building new connections between neurons and detaching certain existing ones. This property is key to ketamine being effective in treating mental health conditions that other drugs are incapable of impacting. 

In a therapy setting, ketamine is usually administered through a drip – either as an intravenous or an intramuscular infusion. Therapy sessions in such cases can last for 45 minutes to an hour. The dissociative experience starts almost immediately and wears off 15-20 minutes after the drip stops. The effects are similar for patients who are administered Esketamine nasally, although they may then be required to spend up to two hours in a relaxing environment. For most patients, ketamine therapy is a deeply relaxing experience, the positive effects of which can last for months. Here’s what you can expect during a ketamine therapy session: 

• Enhanced sensitivity to light and sounds
• Out-of-body experiences; the feeling of floating in the air
• Temporary changes in perception of time 
• Sensory distortions, especially with light and colors
• Mild drowsiness and occasional dizziness
• Moderate, temporary increase in blood pressure and heart rate

The effects of ketamine in low doses are usually short-lived but intense. Any residual side effects such as nausea typically dissipate rapidly, and you’re likely to feel normal in half an hour or less. 

Remember that you are required to undergo a thorough clinical evaluation to determine if you are eligible for ketamine therapy. Please consult a doctor or registered medical practitioner if you’d like to know more about this line of treatment. 

Neuroplasticity

Neuroplasticity is the brain’s ability to change, reorganize, and adapt itself in the face of changing conditions. It can happen in response to learning, new experiences, or as a result of trauma or injury. Neuroplasticity involves brain cells called neurons forming new connections and pathways (called synapses) while deviating from or discarding older ones. Some neural networks controlling autonomous functions like breathing and heartbeat are ‘hard-wired’, meaning they continue without any voluntary intervention on our part. However, certain other networks are malleable and can continue their normal functions while simultaneously rearranging themselves to accomplish newer functions. This neuroplasticity is part of the normal development in a young brain reacting to new information, learning, and growing physical abilities in a young child, for instance. However, the same ability also comes into effect in crisis situations, like the loss of a limb or sense organ, or a major medical incident like a stroke. 

What is remarkable about ketamine is that it has been shown to consistently increase neuroplasticity in mice, that too within 24 hours of being administered.

Although evidence is scant, some researchers believe ketamine can replicate these effects in the human brain. Promising results came from a 2018 study on patients with MDD and TRD, who were administered a single, low dose of ketamine intravenously for up to 60 minutes. Participants reported reduced depression within hours, with positive effects lasting days and as long as two weeks in some cases. Although further confirmation is awaited, researchers surmise that these effects can only be a result of ketamine’s neuroplastic abilities.

A separate study with similar findings involved 30 participants with MDD on whom at least two traditional treatments for depression had failed. This was a double-blind, placebo-controlled study, meaning that neither the clinical staff nor the participants involved knew what treatment was being administered to a particular subject. At the end of the trial, 70% of participants reported a 50% or greater decrease in symptoms of depression one day after being given ketamine.  

Studies such as these on ketamine-induced neuroplasticity are a reason for genuine optimism in patients and doctors grappling with acute mental health conditions, especially ones that defy conventional cures. A second source of hope is the effect of ketamine on the brain’s default mode network (DMN) – a state of brain activity that kicks in when people are focused on their internal mental state rather than on external tasks.  

DMN activates when an individual is engaged in contemplative introspection, memory and recollection, or thoughts of the future. While that is generally a passive, neutral activity in a healthy person, it can be agonizingly painful for someone battling depression, substance abuse, or suicidal thoughts. The activation of DMN in such persons can open them up to a sea of negative thoughts and emotions. What’s interesting about ketamine is that studies have shown it can reduce the functional intensity of DMN. In other words, ketamine can lead to a quieter mind, especially one that is free of the disturbing internal chatter that plagues people with certain mental conditions. Its effects are akin to turning the volume down on your mental activity. 

Benefits & side effects

Ketamine stands out from the traditional treatments for several debilitating and chronic conditions for three reasons:

1. It blocks a category of cells in the brain called NMDA receptors, the malfunctioning of which leads to conditions like depression and anxiety. By blocking NMDA receptor signals, ketamine alleviates these symptoms and allows the brain time to rewire itself.
2. Ketamine reduces dependence on highly addictive narcotic and opioid-based analgesics in people suffering from chronic pain. This eliminates complications arising from long-term painkiller use and makes it a great alternative to traditional pain-management treatments.
3. Ketamine works very quickly, showing effects within minutes and continuing to show positive results for weeks and months after being administered, in some cases. Conversely, a traditional antidepressant can take several weeks to build up in the body before taking effect.

These benefits make ketamine an invaluable drug and treatment of last resort for a wide array of medical conditions, including several different types of severe depression, PTSD, suicidality, severe anxiety, bipolar disorder, substance abuse, and chronic pain. There is also good clinical data to suggest ketamine therapy helps people with OCD, eating disorders like anorexia and bulimia, and social anxiety disorder. 

On the flip side, ketamine can induce side effects like dizziness, drowsiness, nausea, and confusion. In most cases, these effects are mild and do not last beyond the therapy session. Further, patients with certain conditions linked to cardiac health, schizophrenia, psychosis, high blood pressure, and alcohol or drug-induced intoxication are not considered suitable for ketamine therapy. 

What do we know so far?

Scientific evidence supporting the therapeutic benefits of ketamine has been steadily building up over the past few years. There is now a substantial body of research and clinical data to back up claims of ketamine’s efficiency in treating three mental health conditions: 

• Severe depression
• Suicidal ideation
• Severe PTSD

In 2006, researchers at the National Institutes of Health published the results of clinical tests on 18 patients diagnosed with treatment-resistant depression, all of whom had been through an average of six different antidepressants without much effect. 71% of the patients reported reduced depressive feelings within hours of receiving a single dose of ketamine. Another study conducted in India in 2019 involving 25 patients reported significant improvement within the first hour of a ketamine dose, with positive benefits retained till the end of one month. 

Other studies have corroborated these findings, helping establish ketamine’s unbelievably rapid effects not just in the treatment of depression, but PTSD and suicidality as well.

A case in point here is a 2022 double-blind, placebo-controlled trial conducted in France on 156 patients with suicidal thoughts. The group was split into two, one given two intravenous doses of ketamine and the control group receiving a saline solution as a placebo. 63% of subjects who had received ketamine were in full remission of suicidal thoughts by the third day, with positive effects lasting for up to six weeks after ketamine was administered. Side effects were limited and no psychotic symptoms were reported. The researchers concluded that ketamine showed rapid and persistent benefits in patients with suicidal thoughts, attributing the high rate of success to ketamine’s “analgesic effect on mental pain”.  

Patients with PTSD, likewise, have been shown to be positively impacted by ketamine therapy. A 2021 study found that ketamine was far more effective in reducing PTSD symptoms than an anti-anxiety control drug. 67% of participants who received ketamine reported improvement in their conditions, with positive effects lasting beyond 27 days. 

Besides depression, suicidality, and PTSD, there are strong indications suggesting ketamine is an effective therapy for a host of other physical and mental health problems mentioned above. Multiple research studies and clinical trials investigating ketamine therapy efficiency in treating these medical conditions remain ongoing.   

FAQs

How long does ketamine stay in your system? 

It depends on several factors like a person’s age, body mass index (BMI), genetics, liver functionality, and overall health. Ketamine shows up in blood tests only up to 24 hours after a dose. It can show up in urine tests for 30 days after being administered, and after many months in hair tests.

Ketamine for depression cost?

A single ketamine infusion can cost up to $500 on average. A course of six infusions with pretreatment consultation can cost you up to $4,500.    

What is ketamine infusion?

Ketamine infusion is the process of administering ketamine either into the veins (intravenous) or muscles (intramuscular) to treat a range of physical and mental health conditions. It is a procedure that must only be undertaken in controlled clinical conditions after due consultations with a doctor or registered medical practitioner. 

Is ketamine safe?

Ketamine is considered safe when taken in low doses under prescribed clinical conditions. Consult a doctor to check if any condition you are suffering from makes you eligible for ketamine therapy.