What is the recommended starting dose for microdosing ketamine (Ketamine) for therapeutic use?

From the Guidelines

There is no standardized recommended starting dose for microdosing ketamine for therapeutic use, as this practice lacks FDA approval and sufficient clinical research to establish safe guidelines. Ketamine is primarily approved as an anesthetic and for treatment-resistant depression when administered in clinical settings under medical supervision. Microdosing ketamine (taking sub-perceptual doses) is experimental and carries significant risks including addiction, bladder damage, cognitive impairment, and cardiovascular complications. Self-administration of ketamine without medical supervision is dangerous and potentially illegal. If seeking ketamine therapy for mental health conditions, patients should consult with healthcare providers who can provide proper clinical administration through approved methods such as intravenous infusions, intranasal sprays (like Spravato), or monitored oral formulations at appropriate therapeutic doses. These established protocols typically involve full therapeutic doses rather than microdoses, with treatment plans tailored to individual patient needs based on medical history, weight, and response to treatment 1.

Some studies have reported the use of ketamine in various settings, including pediatric sedation and analgesia, with dosages ranging from 0.5 to 2.0 mg/kg per dose 1. However, these studies do not provide guidance on microdosing for therapeutic use. The most recent and highest quality study on postoperative pain management in children recommends a dosage of 0.5 mg/kg for ketamine as an adjunct to intraoperative opioids, with a maximum dose of 0.4 mg/kg/h for continuous infusion 1.

It is essential to note that the use of ketamine for microdosing is not supported by strong evidence, and the risks associated with its use, particularly without medical supervision, outweigh any potential benefits. Therefore, patients should not attempt to microdose ketamine without consulting a healthcare provider. Instead, they should explore established treatment options for mental health conditions, such as therapy and FDA-approved medications, under the guidance of a qualified healthcare professional.

In summary, due to the lack of FDA approval and sufficient clinical research, there is no recommended starting dose for microdosing ketamine for therapeutic use, and patients should exercise caution and consult with healthcare providers before attempting any form of ketamine therapy.

From the Research

Microdosing Ketamine for Therapeutic Use

• The recommended starting dose for microdosing ketamine is not explicitly stated in the provided studies, but doses of oral ketamine have ranged from 0.25 to 7 mg/kg and from 50 mg per occasion to 300 mg per occasion in multiple daily dosing, daily dosing, and intermittent dosing schedules 2, 3.
• A study suggests that oral doses of about 2.0-2.5 mg/kg may need to be administered to achieve equivalence to intravenously administered ketamine, due to the poor oral bioavailability of ketamine 3.
• Another study recommends a starting dosage of 0.5 mg/kg racemic ketamine or 0.25 mg/kg S-ketamine as a single oral dose for chronic pain management, with the dosage increased by the same amount if required 4.
• Ketamine has been administered through various routes, including oral, sublingual, transmucosal, intravenous, intramuscular, subcutaneous, intranasal, and rectal routes, with the oral route being the most practical and least expensive 2, 5.

Dosing Strategies

• The dosing strategy for oral ketamine has been one-size-fits-all or individualized through a dose discovery process, with administered doses ranging from 0.25 to 7.0 mg/kg in weight-based dosing sessions and from 25 mg to 300 mg in fixed dosing sessions 3.
• The frequency of dosing sessions and the duration of treatment have varied, with some patients receiving a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases 5.
• The ideal frequency of dosing is perhaps best individualized, wherein ketamine is dosed a little before the effect of the previous session is expected to wear off 5.

Safety and Efficacy

• Oral ketamine has been shown to be effective in treating severe depression, depression with suicidal ideation, and treatment-resistant depression, with a relatively good safety profile 2, 3.
• However, the literature on oral ketamine is thin, and there are many areas that need more investigation, especially matters related to pharmacokinetics, physiologic effects, abuse potential, and strategies to mitigate illicit use, and adverse effects and efficacy relative to other routes of administration 3, 4.