Ketamine therapy has emerged as a transformative treatment for mental health conditions like depression, anxiety, and PTSD, as well as chronic pain. Two primary methods—intravenous (IV) and intramuscular (IM) injections—offer distinct experiences, benefits, and considerations. In the following article we explore the differences between IV and IM ketamine therapy, drawing on scientific literature and insights, as both have their particularities but studies show similar levels of safety and effectiveness.
Mechanisms and Administration
Intravenous (IV) Ketamine: IV ketamine is administered directly into the bloodstream via a catheter over 40–60 minutes, ensuring 100% bioavailability, meaning the entire dose reaches the brain. This method is considered to allow more control on dosage over time. IV infusions are easily and often used in non-psychedelic doses, as these are sometimes seen as “secondary effects”. Through our clinical practice we have seen that the psychedelic effects, along with the integration, are essential and transformative parts of the process.
Intramuscular (IM) Ketamine: IM ketamine involves a single injection into a muscle, typically the shoulder or thigh, with effects onsetting within 1–2 minutes and lasting 30–60 minutes. Bioavailability is slightly lower (approximately 93%) due to variations in muscle absorption, but it remains highly effective. IM administration is simpler, requiring no sustained IV access hence a more comfortable and less clinically arranged environment. It is often used in settings where rapid onset is desired.
Both methods target NMDA receptors to enhance glutamate activity, promoting neuroplasticity and alleviating symptoms of depression and pain. However, IV’s gradual delivery contrasts with IM’s rapid, immersive peak, affecting the therapeutic experience.
Efficacy and Therapeutic Outcomes
Studies, such as the randomized trial of Chilukuri et al. from 2014, demonstrate that both IV and IM ketamine produce rapid antidepressant effects. In the study, IV ketamine (0.5 mg/kg over 40 minutes) and IM ketamine (0.5 mg/kg or 0.25 mg/kg) reduced Hamilton Depression Rating Scale (HAM-D) scores by 58–60% within two hours, with effects sustained for three days. No significant differences in efficacy were found between the two routes, suggesting IM can be as effective as IV, even at lower doses. When paired with psychotherapy, IV and IM both enhance outcomes by facilitating emotional processing and integration.
For mental health emergencies, IV ketamine’s faster onset (within seconds) and ability to titrate make it preferred for acute suicidal ideation. Although evidence is still scarce, IV might also be superior to IM in chronic pain cases in which longer and more sustained infusions might be beneficial. IM ketamine, however, offers comparable symptom relief for depression, anxiety, PTSD and other diagnoses, with some patients reporting a more profound, immersive experience due to its rapid peak.
Safety and Side Effects
Both IV and IM ketamine are safe when administered in controlled clinical settings. In very few cases mild, transient side effects such as nausea and dizziness may occur. IV ketamine may cause transient increases in blood pressure, while IM ketamine has a minimal incidence of vomiting during recovery, particularly in pediatric studies. IV administration carries a small risk of vein irritation or extravasation, which is minimized with IM injections. Neither method significantly affects respiratory function, making ketamine safer than other anesthetics. Both IV and IM require professional oversight to ensure safety, particularly for patients with cardiovascular or psychiatric histories.
Patient Experience and Practical Considerations
IV infusions are considered to provide a gradual, controlled experience, often described as smoother, with a longer therapeutic window for psychotherapy integration. However, the need for a catheter throughout the session can feel restrictive, and some patients find the abrupt comedown disorienting. IV therapy requires a clinical setting with trained staff, increasing costs. Furthermore, sometimes patients are required to arrange transportation post-treatment due to lingering effects.
IM injections offer a faster, more intense experience, with effects peaking quickly and dissipating within an hour. Based on reports of patients, the simplicity of a single injection and the ability to move freely during the session is more convenient for the therapeutic session. IM is also sustainable for group therapy settings, where patients receive injections and participate in integration sessions, enhancing accessibility.
Accessibility and Clinical Preferences
Although IV is the most researched route, several associations such as KATA’s (Ketamine Assisted Therapy Association) and The Ketamine Research Foundation advocate for IM in situations in which constant medical supervision is not necessary. The IM model promotes in-depth psychotherapy and is simpler to deliver.
At Clinica Synaptica we work with IM because it offers several compelling advantages. It allows more distancing from the purely medicalized use of psychedelics and permits experiences that can be powerful and transformative, with adequate integration. IM requires a single injection, avoiding the need for sustained IV access, which can be uncomfortable or anxiety-inducing for some patients. IM’s effects begin within 1–2 minutes, providing a quick, immersive experience that some patients find more profound and conducive to emotional breakthroughs.
Both IV and IM ketamine therapies offer effective, rapid relief for mental health conditions and chronic pain, with distinct advantages depending on the individual preference of the patient. IV ketamine provides precise dosing and a gradual experience, making it ideal for those requiring close monitoring. IM ketamine, however, stands out for its simplicity, and rapid onset, offering an effectually more challenging and enriched experience, hence facilitating a compelling alternative.
References
Boroumand Rezazadeh, B. , Zamani Moghadam, H. and Gharavifard, M. (2015). Comparison between intravenous and intramuscular administration of ketamine in children sedation referred to emergency department. Reviews in Clinical Medicine, 2(1), 1-4. doi: 10.17463/RCM.2015.01.001
Chilukuri, H., Reddy, N. P., Pathapati, R. M., Manu, A. N., Jollu, S., & Shaik, A. B. (2014). Acute antidepressant effects of intramuscular versus intravenous ketamine. Indian Journal of Psychological Medicine, 36(1), 71–76. https://doi.org/10.4103/0253-7176.127258
Comparing IV and IM ketamine for the treatment of mental health and pain. (2025, May 8). Innerbloom Ketamine Therapy. https://innerbloomketamine.com/blog/comparing-iv-and-im-ketamine-for-the-treatment-of-mental-health-and-pain/
Rosenbaum, S. B., Gupta, V., Patel, P., & Palacios, J. L. (2024, January 30). Ketamine. StatPearls – NCBI Bookshelf. Retrieved August 20, 2025, from https://www.ncbi.nlm.nih.gov/books/NBK470357/
Saeedi, M., Momeni, M., Esfandbod, M., Farnia, M., Basirani, R., & Zebardast, J. (2014). Comparison of the effect of intravenous ketamine and intramuscular ketamine for orthopedic procedures in children′s sedation. International Journal of Critical Illness and Injury Science, 4(3), 191. https://doi.org/10.4103/2229-5151.141352
Wolfson, P., & Braunstein, M. (n.d.). GUIDELINES FOR THE SAFE PERSONAL USE AND THE EFFECTIVE CLINICAL USE OF KETAMINE. https://ketamineresearchfoundation.org/wp-content/uploads/2025/03/KRF-Ketamine-Guidelines.pdf
