Ketamine has been used as an anesthetic in medical settings since the 1970s. It is known as a dissociative anesthetic, creating a trance-like state that provides pain relief and memory loss. More recently, “low dose ketamine” refers to its application at sub-anesthetic doses. This distinct application has emerged as a potential treatment for various conditions beyond its traditional anesthetic role.
What Low Dose Ketamine Treats
Low dose ketamine is explored for challenging medical conditions, particularly those that have not responded well to traditional treatments. It is a focus for treatment-resistant depression, where patients have not found relief with at least two conventional antidepressant medications. Ketamine can provide rapid antidepressant effects, sometimes within hours, a benefit over standard antidepressants that may take weeks to show improvement.
Beyond depression, low dose ketamine is also applied to severe anxiety disorders and post-traumatic stress disorder (PTSD), helping to reduce negative thought patterns and improve emotional regulation. It is also used in managing chronic pain conditions, especially those with a neuropathic component. It offers relief for conditions where other pain medications may be insufficient.
How Low Dose Ketamine Works
The therapeutic effects of low dose ketamine are attributed to its interaction with N-methyl-D-aspartate (NMDA) receptors in the brain. Unlike some other drugs that stimulate these receptors, ketamine acts as an antagonist, blocking them. This blockade leads to a temporary increase in glutamate, a key excitatory neurotransmitter.
This glutamate surge activates other pathways, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor pathway and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. These activations promote synaptogenesis, which is the formation of new neural connections, and increase brain-derived neurotrophic factor (BDNF). The growth of new synapses and enhanced neuroplasticity contribute to ketamine’s rapid antidepressant and analgesic properties, helping to repair weakened neural circuits associated with mood disorders and chronic stress.
Administering Low Dose Ketamine
Low dose ketamine can be administered through several routes, often under medical supervision in a clinical setting. Intravenous (IV) infusion is a common method, delivered directly into the bloodstream, allowing precise control over dosing and high absorption, approaching 99% bioavailability. The effects can be felt quickly with this method.
Another method is intranasal spray, such as esketamine, which is a specific form of ketamine. This route has a lower bioavailability, around 20-30%, and may require more frequent treatments. Oral forms and intramuscular (IM) injections are also used, with IM injections offering about 93% bioavailability. Treatment sessions last from a few minutes for injections to 40 minutes for infusions, and patients are monitored after administration.
Safety Considerations and Side Effects
While low dose ketamine offers therapeutic benefits, it has potential side effects and requires careful safety considerations. Common, short-term side effects include feelings of unreality, dizziness, nausea, and sensory changes. These effects peak within an hour and resolve within a few hours.
Blood pressure and heart rate may temporarily increase during administration, though these changes are often comparable to those experienced during routine daily activities. Less common but more serious risks are associated with long-term, high-dose recreational misuse, not controlled clinical use. These include bladder issues, known as ketamine-associated cystitis, and cognitive impairment.
Patient screening identifies contraindications, such as uncontrolled hypertension, severe cardiovascular disease, or active psychosis. Medical supervision during and after treatment manages immediate side effects and monitors patient well-being.