Disclaimer: None of the information in this article constitutes medical advice, and is just the opinion of the writer(s). Ketamine is illegal in many jurisdictions, and the information in this article is for patients considering assisted psychotherapy with a licensed medical professional in jurisdictions where medical applications of ketamine are legal. We do not recommend or condone recreational ketamine use.
Ketamine is an anesthetic (pain reliever) with hallucinogenic effects. It was approved by the Food and Drug Administration (FDA) in the U.S. in 1970 as an anesthetic, but most of the medical research on ketamine is as a potential therapeutic agent for treating depression.
In this article we’ll review some of the medical research on ketamine and conclude whether we believe it’s effective for depression based on the data. We’ll also review some of the side effects and risks associated with its use.
A recent clinical trial tested ketamine therapy’s effects on depression, and compared the results with patients taking a popular pharmaceutical antidepressant. The researchers found that one single ketamine infusion was more effective than the pharma drug, and sustained infusions (3x weekly over the course of 2 weeks) provided additional benefit.
59% of depressed patients achieved a significant (greater than 50%) reduction in their symptoms after the ketamine infusions. This study was sponsored by a Canadian university so there are no funding bias concerns.
Medical trials as far back as the year 2000 show ketamine to be effective for depression, with the linked study finding a ketamine IV to be significantly more effective in treating depression than a placebo.
A 2020 review published in the Current Topics in Medicinal Chemistry journal assessed many individual trials on ketamine and depression, and found that it was effective on average. The reviewers noted that ketamine therapy was especially effective in patients who didn’t respond to standard pharmaceutical antidepressants.
Researchers in the ketamine review also found that ketamine was more effective in depression with overlapping bipolar disorder compared to major depression alone.
We can conclude from the medical data that ketamine therapy is effective for treating depression on average, when applied in a clinical and controlled setting.
How Does It Work?
Ketamine is an antagonist of n-methyl-d-aspartate (NMDA) receptors in the brain, and this is thought to be the main biological process by which it’s effective for depression, as previous research has shown NMDA dysfunction to be associated with depression.
By inhibiting NMDA receptors expressed in GABA neurons, ketamine can block excitatory glutamate signaling in the brain based on medical research.
More recent research has also highlighted several biochemical pathways that may be positively influenced by ketamine. Specifically, ketamine inhibits hyperpolarization-activated cyclic nucleotide gated cationic (HCN1) channels, which may have sedative effects.
The linked review also reports that ketamine metabolites can activate mTOR which has effects on prefrontal cortex functioning, but the research is early-stage and the researchers aren’t exactly sure how ketamine influences these channels.
At a high level, what all of this means is that early research suggests that ketamine may have normalizing effects on brain function in some patients. Depression caused by specific types of chemical dysfunctions in the brain (such as NMDA receptor activity) seem to be aided by ketamine therapy.
Ketamine Side Effects
Ketamine is a psychoactive drug, which is why it’s so important that it’s used in a clinical setting, as accurate dosage plays an important role in patient safety.
The most common side effects of ketamine are psychiatric (mental) rather than physical, since it’s a hallucinogenic drug. 38% of studies analyzed in a thorough ketamine medical review reported mental side effects, and 72% of studies reported dissociation in some patients.
Cardiovascular side effects are relatively common in acute ketamine use, with blood pressure tending to increase on average. Headache and dizziness are also common.
Researchers have noted that ketamine has been studied in regards to safety and toxicity for short-term use, but long-term safety data is lacking. We simply don’t have enough medical data to determine the long-term risks of ketamine therapy for depression.
Ketamine For Pain
Since ketamine was initially approved for pain management, it’s not surprising that there is significant medical data showing its beneficial effects on pain.
A medical review published in the Anesthesia & Analgesia journal assessed previous clinical trials of ketamine use for pain, and found that it can provide significant short-term benefit when applied in an IV.
Similar to the research on ketamine for depression, the reviewers noted that while the short-term data was strong, there was lacking long-term data on ketamine for chronic pain. So the current state of the research seems to indicate that ketamine may be effective for acute pain, but there’s not enough data to conclude it’s effective for long-term pain management for conditions like arthritis.
Ketamine For Anxiety
Ketamine may be an effective anxiolytic. A clinical trial from 2020 tested ketamine therapy on patients with treatment-resistant anxiety disorders. The study was double-blinded, meaning neither researchers nor patients knew which group was receiving ketamine and which was receiving placebo treatment. This is the medical gold standard as it eliminates bias.
The study found that ketamine was more effective than placebo for anxiety, and that the anxiety improvements after ketamine therapy persisted for up to one week after a single treatment.
Another medical study on ketamine for anxiety found similar results. Patients with treatment resistant anxiety or social anxiety disorder (SAD) were administered weekly injections of ketamine for 3 months. 18 of the 20 patients studied reported significant reductions in anxiety, and “marked improvements in functionality and in their personal lives.”
This study wasn’t placebo-controlled, so the results are weaker than the first one.
Research on ketamine for anxiety is more early-stage than ketamine for depression, but the compound does seem to be effective at least short-term for anxiety. We look forward to longer-term trials.