Ketamine & Neuroplasticity: Long-Term Brain Effects

The United States is experiencing an ever-increasing mental health crisis, which has only been exacerbated by the socially-isolating COVID-19 pandemic. In 2023, 45% of adults ages 35 to 44 reported a mental illness, compared to 31% in 2019 (source: apa.org). People living with mental illnesses, such as chronic anxiety and depression, tend to have less flexible neurons with fewer connections, amongst other structural issues.

Ketamine can provide safe and rapid antidepressant relief, revitalizing the brain’s ability to form new connections and enhancing overall receptiveness to psychotherapy. Ketamine’s therapeutic effects stem from a variety of mechanisms in the brain:

• Increased BDNF: Ketamine increases Brain-Derived Neurotrophic Factor (BDNF), which has complex downstream effects. This effect is dose-dependent and time-limited (around one week, with peak at 2-3 days).
• Lowering the Default Mode Network: Ketamine has been shown to reduce the functional activity of the Default Mode Network (DMN), which can give the patient a chance to take a break from habitual thoughts and gain perspective.
• Enhanced Neuroplasticity: Ketamine enhances neuroplasticity by upregulating BDNF. This effect opens a window of opportunity for psychotherapeutic intervention.
• Intrinsic Anti-Depressant Effects: Ketamine has rapidly-acting antidepressant and mood-enhancing effects, with a response rate of approximately 50-80% and duration ranging from 2-3 days up to 2 weeks or more. Evidence also supports a unique anti-suicidal effect, independent of antidepressant response.
• Dissociation: Ketamine's dissociative effect may provide patients the opportunity to gain a new perspective on a traumatic or unpleasant situation.
• Responsiveness to therapy: Following a Ketamine dosing session there is a critical period which allows for higher responsiveness to therapy, caused by the aforementioned effects.

The mechanisms underlying ketamine’s effects on the brain.

While in the short term, ketamine can provide rapid relief in symptoms through increased neuroplasticity, psychotherapy supports the process of meaning-making and the cultivation of anchors through new practices and ways of being that both primes the brain for these new insights and then supports their ongoing integration. Leveraging ketamine as an adjunct to psychotherapy, also known as Ketamine-Assisted Psychotherapy (KAP), has been shown to be effective for significantly improving clinical outcomes. Read more about KAP and the clinical evidence via our blog.