Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity | Huberman Lab Podcast

Added: Aug 7, 2023

Dr. Huberman explains that ketamine and PCP have similar modes of action in the brain, as they are both dissociative anesthetics. He discusses the history of depression treatment and the monoamine hypothesis, which suggests that deficiencies in monoamines like serotonin, dopamine, and norepinephrine contribute to depression. However, he notes that drugs designed to increase these monoamines only work for about 40% of depressed individuals and often have side effects. The podcast then delves into the research on ketamine's clinical benefits. Dr. Huberman highlights a landmark study that showed ketamine's rapid antidepressant effects in patients with major depression. The study found that ketamine induced a euphoric, dissociative state within minutes of administration and provided relief from depression that lasted for several days. He explains that ketamine has also been shown to be effective in treating bipolar depression, PTSD, OCD, anxiety, and substance addiction. Dr. Huberman discusses the dosing regimens used in ketamine treatment and the durability of its effects. He explains that while the immediate effects of ketamine are short-lived, repeated treatments can provide ongoing relief from depression. He emphasizes that ketamine likely acts through multiple mechanisms, including the induction of immediate relief, the provision of relief in the days and weeks following treatment, and the induction of long-lasting changes in neural circuitry. The podcast then explores the mechanism of action of ketamine. Dr. Huberman explains that ketamine blocks the NMDA receptor, which is critical for neuroplasticity. He describes the NMDA receptor as an "end gate" that requires the presence of glutamate and high levels of electrical activity to activate. Ketamine's ability to block the NMDA receptor and induce changes in neural circuitry contributes to its antidepressant effects. Dr. Huberman acknowledges the potential risks of ketamine, including its potential for abuse and addiction. He discusses the importance of using ketamine in the appropriate clinical context and under the supervision of a healthcare professional. He also mentions the need for further research to better understand the long-term effects and optimal dosing regimens of ketamine. He also highlights the role of the opioid receptor system, which is involved in pain relief and mood regulation. Both the NMDA receptor and the opioid receptor system contribute to the neuroplastic changes that occur in the brain when ketamine is administered. The discussion then focuses on the neural circuits affected by ketamine and their role in relieving depression. Dr. Huberman explains that ketamine reduces the inhibitory input from the habenula, a brain structure involved in generating feelings of disappointment, to the reward circuitry of the brain. By doing so, ketamine allows the reward pathway to be more engaged in daily life activities, leading to improved mood and motivation. However, Dr. Huberman emphasizes that the changes in neural circuits brought about by ketamine are not sufficient on their own. They need to be reinforced by adaptive behaviors. Engaging in anti-depressive behaviors, such as seeking out stimulating work, social engagement, and taking care of mental and physical health, is crucial for the long-term effectiveness of ketamine treatment. The podcast also addresses the different forms and routes of ketamine administration. Dr. Huberman explains that the dosage and mode of delivery can greatly impact the effects of ketamine. He warns against taking high doses of ketamine, as it can lead to deep planes of unconsciousness and even death. Additionally, ketamine can induce seizures in individuals who are prone to seizures. Dr. Huberman discusses the different forms of ketamine, including the R, S, and RS forms. He explains that the S form of ketamine is more potent and effective in treating depression than the R form. However, the combined SR form seems to be the most potent for relieving depressive symptoms. He notes that there is currently no published clinical evidence supporting the effectiveness of microdosing ketamine for depression. In conclusion, Dr. Huberman emphasizes that ketamine can provide relief from depression, but it needs to be combined with anti-depressive behaviors to be effective in the long term. He also highlights the importance of careful dosage and administration to avoid potential risks and side effects. Overall, ketamine shows promise as a treatment for depression and PTSD, but further research is needed to fully understand its mechanisms and optimize its use.