What is Ketamine? Medical Origins, Safety, and Its Use in Mental Health
Ketamine is a dissociative anesthetic that has evolved from battlefield medicine to a promising new therapy in mental health care. Originally developed in the 1960s and approved by the FDA in 1970 for anesthesia, ketamine is now used to treat depression, PTSD, anxiety, and more.
Ketamine produces a dreamlike, dissociative state that helps many patients break free from entrenched mental patterns. In 2019, the FDA approved a ketamine-derived nasal spray (Spravato) for treatment-resistant depression, marking the first legal psychedelic treatment in the U.S.
This article is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before beginning any treatment. Effects and legality vary by region, diagnosis, and individual needs.
Ketamine History
Ketamine was synthesized in 1962 and approved by the FDA in 1970 as a fast-acting anesthetic. It became a frontline sedative during the Vietnam War due to its effectiveness and safety profile, particularly its ability to provide anesthesia without depressing cardiovascular or respiratory function. In clinical settings, it has been widely used for surgery, pain relief, and emergency medicine.
Its psychedelic and dissociative effects became evident when patients reported vivid hallucinations and altered perception. These properties led to recreational use, particularly in party scenes, but also caught the attention of mental health researchers. Ketamine is chemically different from psilocybin or LSD but is often included in psychedelic therapy discussions due to its mind-altering effects.
Today, ketamine is the only legal psychedelic therapy in the U.S., offered through both clinical infusions and at-home telehealth models. Its rapid antidepressant effects have made it a beacon of hope for individuals with treatment-resistant conditions.
Is Ketamine Legal?
Ketamine occupies a unique legal position compared to other psychedelics, with government approval for off-label use. Legal status of substances can change, be sure to verify the legality of your jurisdiction.
USA
Ketamine is classified as a Schedule III controlled substance, meaning it can be legally prescribed by licensed professionals. It is FDA-approved as an anesthetic and, under the brand name Spravato (esketamine), for treatment-resistant depression. Off-label prescribing is also legal, allowing clinics and telehealth providers to administer ketamine for mental health conditions like anxiety and PTSD.
Europe
Ketamine is a controlled substance in most European countries but can be prescribed for anesthesia. In places like the UK and Germany, ketamine therapy is available through private clinics. Regulation varies by country.
Asia
Most Asian nations classify ketamine as a controlled substance with strict penalties for unauthorized use.
Ketamine Effects
Ketamine’s effects are dose-dependent and can vary significantly between individuals.
Effects on the Brain
Ketamine primarily acts by antagonizing NMDA receptors in the brain, modulating glutamate neurotransmission. This action disrupts normal excitatory signaling and leads to altered neural connectivity and plasticity, which underlie its anesthetic and antidepressant effects.
Effects on the Body
Common physical effects include sedation, dissociation, mild nausea, dizziness, and increased blood pressure. At sub-anesthetic doses, users may remain conscious but detached from their body or environment.
Effects on the Mind
Subjective mental effects include altered sense of self, depersonalization, emotional detachment, and in therapeutic settings, enhanced introspection and mood elevation. Sensory perception may be distorted, leading to unusual visual or auditory experiences.
Therapeutic Benefits of Ketamine
Ketamine therapy has shown beneficial effects on a range of mental health conditions:
Ketamine for depression: This review and meta-analysis of 28 studies documents the benefits of using ketamine for depression. The study found that intravenous ketamine infusions produced rapid and significant improvements in patients with treatment-resistant depression (TRD). In 2019, the FDA approved Spravato (esketamine), a nasal spray derived from the S-enantiomer of ketamine, for the treatment of depression.
Ketamine for post-traumatic stress disorder (PTSD): Ketamine is also being explored as a treatment for PTSD. A randomized and controlled clinical trial demonstrated that individuals with chronic PTSD experienced substantial symptom reduction after just one ketamine infusion. The ketamine group showed a significantly greater improvement in symptoms versus the placebo group, with positive results starting less than 24 hrs after dosing.
Ketamine for obsessive-compulsive disorder (OCD): A clinical study found that a single dose of ketamine led to a rapid reduction in obsessive thoughts and compulsive behaviors. The decrease in OCD symptoms occurred within one to two hours after the ketamine therapy and persisted for at least 24 hours.
Ketamine for anxiety: Generalized anxiety disorder (GAD) is another area being studied for ketamine therapy. This review of 18 studies showed that single-dose infusions of ketamine showed significant positive results for patients with anxiety disorders, with reduced symptoms like irritability and panic. Higher doses showed greater effects on anxiety reduction. The effects showed to be temporary, with anxiety symptoms returning after 2 weeks.
Is Ketamine Safe?
Ketamine is considered safe in medical and therapeutic settings and does not depress respiration like many anesthetics. Clinical trials have shown it to be well-tolerated at low doses, with minimal risk of serious side effects when administered responsibly. However, psychological discomfort and disorientation can occur, particularly at higher doses or in unsupported settings.
Ketamine Side Effects
Common: Nausea, dizziness, increased heart rate, blurred vision, confusion
Less Common: Anxiety, elevated blood pressure, hallucinations
Rare: Bladder issues with long-term high-dose use
Addiction Potential
Ketamine has a low-to-moderate potential for misuse and dependence; chronic frequent use may lead to tolerance and psychological addiction. Clinical settings minimize this risk through controlled dosing.
Frequency of Safe Use
Protocols often space treatments days or weeks apart. Regular use should be monitored by a licensed provider.
Contraindications
Ketamine may exacerbate underlying psychiatric conditions such as schizophrenia or psychosis and can worsen cardiovascular problems due to its stimulant effects.
- History of psychosis or schizophrenia
- Uncontrolled high blood pressure
- Pregnancy or breastfeeding
- Severe liver or bladder conditions
How Long Does Ketamine Last?
- Onset: Usually within 5 to 15 minutes when taken intravenously or intramuscularly; 15 to 30 minutes if snorted.
- Duration: Effects typically last 30 to 60 minutes after IV/IM administration; 1 to 2 hours with snorting.
- Peak: Peak effects occur about 10 to 20 minutes after injection, or 30 to 45 minutes after nasal use.
- Aftermath: Users may feel drowsy or disoriented for 1 to 3 hours post-use.
- Afterglow: Mood enhancement or clarity lasting several hours to days, especially when used in therapeutic contexts.
How Long Does Ketamine Stay in Your System?
Ketamine is metabolized quickly by the liver and typically cleared from the bloodstream within 2–4 hours. However, traces may be detectable in urine for 1–3 days and in hair for up to 90 days. Standard drug tests typically do not screen for ketamine unless specifically requested.
Ketamine Microdosing
Ketamine microdosing involves taking very low doses, keeping the experience below the threshold of dissociative effects. Anecdotally, users report improvements in mood, focus, and anxiety reduction. Clinical data exists on the efficacy of low-dose ketamine for depression and other serious conditions. However care should be taken to ensure safe use, even at low doses.
Always consult a licensed medical provider before beginning any psychedelic-assisted therapy.
