What’s different about ketamine?
Ketamine is an alternative medicine for depression and anxiety. It doesn’t carry the same side effect profile as more traditional antidepressants - serotonin selective reuptake inhibitors, or SSRIs - which often includes sexual side effects, weight gain, and emotional numbness. For people who’ve had difficulties with SSRIs, ketamine may be a better option. It works faster than traditional antidepressants, and the neuroplasticity effects are strong, meaning the results are deeper than surface-level symptom relief. It is well known to produce new connections in the brain. That is, ketamine can help to get at the root cause of the psychological pain rather than just at the symptoms that arise as a result.
Why low dose (psycholytic) ketamine?
You may have heard of ketamine in the context of psychedelics, and indeed, at higher doses, it works as a psychedelic. However, our dosing is different from psychedelic dosing and carries substantial and different benefits. The doses we prescribe are psycholytic. This means that it produces an immediate state of calm and ease, and a sense of mental spaciousness. Ketamine is in the “dissociative” class of medication, which this means that people can experience their difficult emotions with a sense of psychological space and without a sense of being overwhelmed. There are a few key benefits: First, unlike psychedelic experiences, psycholytic ones are less likely to be intense. Second, because they’re much less emotionally draining, people can take these doses regularly, and maintain a consistent level of medicine in their brain over time, leading to more stable results. Third, with psychedelic dosing, you may not be clearheaded enough to engage in therapy, meditation, or other practices, whereas with psycholytic therapy, you’re able to more effectively due to the sense of openness and calm. In combination with ketamine’s known neuroplasticity, this may mean an opportunity for greater impact of therapeutic or meditative approaches.
How does ketamine work in the brain?
Ketamine’s effects in the brain are very complex, and are still being actively studied by many researchers around the world. There are multiple ways in which ketamine works in the brain, and these ways probably all interact with one another. Some of the most well known mechanisms involve the neurotransmitters Glutamate and GABA. There are many different kinds of neurotransmitters (chemical messengers) in the human brain, but Glutamate and GABA are the most common ones because they are the the top excitatory (promoting neurons firing) and inhibitory (blocking neurons firing) neurotransmitters, respectively. Ketamine is an antagonist (meaning, it blocks) a neurotransmitter receptor called NMDA, which is found on both GABA and Glutamate neurons. It’s thought to block the GABA receptors more effectively, meaning that GABA doesn’t inhibit neurons firing as often if ketamine is taken - this leads to an overall increase in neural activity in the prefrontal cortex. Ketamine is also known to interact with a another neurotransmitter receptor - AMPA, which may be responsible for a sequence of molecular events that include proteins that promote neuroplasticity through new connections (proteins like Brain-Derived Neurotropic Factor, or BDNF as well as others like mTor, eEF2, and GSK-3). In all, we are still learning about the complex behavior of ketamine in the brain, but we do know that it promotes new neural connections, which are probably at the root of its antidepressant and anti-anxiety effects.
The history of ketamine
Ketamine was first discovered in 1960s as an anesthetic, and it’s still being used in emergency rooms and surgeries all over the world. Its safety profile is excellent (meaning that even as an anesthetic, it doesn’t impair the respiratory system so it’s regularly used even in surgeries with children). The World Health Organization has repeatedly recommended that ketamine be considered an “essential” medicine and not monitored as a dangerous substance. Around the turn of the century, the medical community began discovering the antidepressant potential of ketamine, when people who received the medicine medically began reporting reductions in depressive and even suicidal symptoms. Over the last two decades, there’s been more and more research that revealed the profound potential of this medicine to impact mental health, leading many prominent professors of psychiatry to call it the biggest psychiatric breakthrough of the century.