Ketamine is an unusual drug that has been gaining a lot of attention in recent years. Though initially approved by the FDA as an anesthetic, clinicians, doctors, and researchers are now testing it as an atypical treatment for some psychiatric disorders. This tranquilizer has been studied to help with depression, suicidal ideation, and PTSD – and now, there’s a ketamine treatment for anxiety, too.
But how does it work? And more importantly, is using a tranquilizer like ketamine as a treatment for anxiety safe and effective in the long-term?
These are the questions we aim to explore in this article.
Traditional Treatments for Anxiety
Before we discuss ketamine, it’s important to understand traditional anxiety treatments.
Patients with anxiety symptoms often take advantage of multiple treatment pathways at one time to get the best results. These may include: 1 2 3
- Home remedies such as supplements and meditation
- Controlled diet and exercise
- Cognitive exercises (usually under the direction of a psychiatrist)
However, for individuals who don’t benefit from these therapies, medication treatments are often the next resort. Doctors often prescribe antidepressants, such as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (selective norepinephrine reuptake inhibitors), as the first course of action. Some medical professionals may also look to beta-blockers or buspirone. In some cases, benzodiazepines are prescribed instead of or in addition to these other treatments. 1 2 3
However, each of these drugs can carry significant downsides. As for antidepressants, patients may experience weight gain, new or worsening depression, decreased sex drive, and other unwanted side effects. When it comes to benzodiazepines, these tranquilizers can be habit-forming, which means they’re often a short-term solution rather than a long-term strategy. This can leave patients high and dry when it comes time to wean off the drugs, especially if their symptoms haven’t improved. 1 2 3
More critically, according to Psychiatry Advisor, an educational resource for working psychiatry professionals, an estimated 30-40% of anxiety patients may never see an improvement due to these drugs. It is this group of patients who have the most to gain from ketamine treatments. 1
Ketamine Treatment for Anxiety
There are two basic types of treatments available in ketamine clinics, as administration sites are often called. While we know that they act differently in the brain, more research is needed to determine the cause of the differences.
Racemic ketamine, also known as IV (intravenous) ketamine, is a mixture of two distinct ketamine molecules. This blend, given via IV or subcutaneous (below the skin) injection, was first approved as an anesthetic in the 1960s, and since then has become a popular off-label treatment for depression and anxiety. 4
Esketamine, on the other hand, was only approved by the FDA in 2019. This nasal spray uses only one ketamine molecule and appears to have many of the same benefits (and risk factors) as IV ketamine. 4
How Does Ketamine Work in the Brain?
As we mentioned above, using ketamine treatment for anxiety is often reserved for those who don’t respond to typical treatments. Due to smaller trial pools, we’re just beginning to learn how ketamine acts in the brain.
Preliminary studies show that ketamine works by antagonizing a brain receptor called NMDA. This receptor is responsible for releasing a neurotransmitter known as glutamate. As an NMDA antagonist, ketamine blocks the receptor from taking in glutamate after it’s released, which artificially increases the amount of glutamate in the brain. In turn, glutamate activates another receptor called the AMPA receptor. 1 4 5
This combined process appears to kickstart synaptogenesis, which is forming new pathways in the brain. By blocking NMDA receptors and activating AMPA receptors, other molecules are released in the brain, too. These help neurons build, connect, and communicate via new pathways in the brain. In turn, this affects a person’s mood, thought patterns, and cognition in ways that decrease depression and anxiety symptoms. 1 4 5
Ketamine may affect the brain in other ways, too – likely at the same time. While the research is still in its infancy, some clinicians have suggested that ketamine may affect how the brain reacts to inflammation, affecting mood disorders. Furthermore, ketamine – by way of synaptogenesis – appears to increase communication in certain parts of the brain more than others. 4 5
Studies on the Effectiveness of Ketamine Treatments for Anxiety
Now that we have a baseline understanding of ketamine treatments let’s examine what the leading scientific studies have to say about their safety and effectiveness.
Study 1: Ketamine & Anxiety Disorder
This double-blind, randomized, placebo-controlled crossover trial examined 18 adults with a diagnosed social anxiety disorder. Researchers in the study compared the effect of IV ketamine on social anxiety symptoms (compared to a saline placebo). Each infusion was given in random order with 28 days between additional infusions per patient. Anxiety symptoms were assessed three hours after infusion and again daily for 14 days. At the end of the study, researchers found that ketamine resulted in a “significantly greater” reduction in anxiety symptoms than the saline placebo infusion.
Study 2: Ketamine Injection Trial
This university clinic study was an uncontrolled, open-label study that examined the effects of weekly subcutaneous ketamine injection on 20 patients. Ten men and ten women took part in this study; 15 were diagnosed with generalized anxiety disorder, while 18 suffered from a social anxiety disorder. Patients were given 1-2 weekly ketamine doses for three months and monitored for negative side effects in addition to anxiety symptoms. Data were collected across 18 months between December of 2015 and June of 2017. At this end of this time, researchers concluded that:
- Weekly subcutaneous ketamine doses were safe and well-tolerated
- Post-dose dissociation reduced with additional doses
- Anxiety ratings declined by half or more within an hour after dosing
- 18 out of 20 patients reported improved social and/or work functioning after treatment
Study 3: Ketamine For Non-Comorbid Patients
This study evaluated the efficacy of ketamine treatment for anxiety in 12 patients with generalized or social anxiety disorders who did not have comorbid depressive symptoms. The purpose of this study was to examine the effects of ketamine on anxiety without the compounding factors of an additional mental disorder that could cloud the results. Patients were given increasing doses of ketamine by subcutaneous injection once per week for three weeks: 0.25mg/kg the first week, 0.5mg/kg the second week, and 1.0mg/kg the third week. Upon conclusion, this study found that:
- Ketamine reduced anxiety within 1 hour of dosing
- Symptom relief lasted a minimum of 7 days
- Negative side effects decreased each week
Risks of Ketamine Treatments
Although ketamine is classified as a nonnarcotic, nonaddictive substance with many proven benefits, that doesn’t mean that it’s without its risks. While most side effects are mild, both infusion and nasal spray administrations may cause: 1 4 5
- High blood pressure
- Increased pulse
- Nausea or vomiting
- Dissociation, or “out-of-body” experiences
Furthermore, because ketamine can cause psychedelic effects such as hallucinations, it has the potential to be abused by some users. Those who take ketamine at higher doses or across more extended periods may experience more problematic side effects, including psychosis and neuropsychiatric symptoms, cystitis, and lower urinary tract infections. 1 4 5
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