From: hubermanlab
Ketamine is a compound garnering significant attention for its clinical applications in treating depression, PTSD, and other conditions, as well as for its potential for recreational use. A crucial aspect of understanding ketamine’s effects relates to its dosing and the method of delivery, which significantly influence its efficacy and potential risks.
Injectable Routes and Dosages
In clinical contexts, ketamine is often administered via injection. The typical dosing used in studies for treating depression involves intramuscular (IM) or intravenous (IV) injections. The dosage for these clinical applications is often set at 0.5 mg per kilogram of body weight. This dosing is intended to achieve a subanesthetic state, which yields desired therapeutic effects without inducing full anesthesia. The effects are seen within minutes and can persist for several days.
Clinical Dosing
In clinical settings, the standard dosing for ketamine administered via injection is 0.5 mg/kg body weight. This dosage allows for rapid and controlled onset of effects and is accompanied by medical supervision.
Oral and Sublingual Administration
Apart from injections, ketamine can also be administered orally or sublingually. These methods represent wider availability for both clinical and recreational use. However, they present some pharmacokinetic challenges:
- Oral Administration: Typically, only about 25% of orally ingested ketamine is bioavailable, meaning only a quarter of the substance makes its way into the bloodstream in an active form.
- Sublingual Administration: This method fares slightly better, with about 35% bioavailability. The sublingual route involves placing a dissolvable form, often a troche, under the tongue for absorption.
Bioavailability Variations
Oral and sublingual ketamine doses need to be higher to achieve similar blood plasma levels as injection due to reduced bioavailability: approximately 25% for oral and 35% for sublingual routes.
Equivalent Dosing
To achieve therapeutic effects similar to those from injections, higher doses are required for oral or sublingual administration due to lower bioavailability. For example, a person weighing 100 kg (approximately 220 pounds) might receive 50 mg of ketamine through injection, whereas the equivalent oral dose would need to be around 150 mg to ensure adequate plasma levels.
Dosing Equivalents
For a 100 kg individual:
- Injection: 50 mg
- Oral: 150 mg
- Sublingual: Proportionate adjustments are required similar to oral dosing.
Risks and Considerations
Careful consideration of dosing is crucial as ketamine’s effects vary with concentration and delivery method. Different individuals metabolize it differently, which can affect the onset and intensity of effects. Overdosing, especially combining with other sedatives or alcohol, can lead to deep anesthesia or fatal consequences.
Clinical vs. Recreational Use
In clinical settings, ketamine administration comes with supervision to manage doses and monitor patient responses, reducing risks. Recreational use, however, lacks such safeguards and can involve unsafe dosing practices, leading to potentially dangerous states like the infamous “k-hole,” a severe dissociative state near unconsciousness. For those exploring recreational use, it’s critical to understand the risks and safety measures to mitigate harm.
Conclusion
Understanding the dosing and delivery methods is essential for leveraging ketamine’s therapeutic potential while minimizing risks. Clinical environments provide controlled settings that adjust dosing to individual needs and response, ensuring safety and efficacy. Meanwhile, recreational use raises substantial risk when dosing variations and metabolic differences are not accounted for, emphasizing the need for caution and responsibility.
For a more detailed discussion on ketamine’s mechanisms and broader effects, please refer to the full discussion on the Huberman Lab Podcast: [00:07:00].