The Promise of Ketamine for Depression (and insights from my personal journey through)

I’m lying on a mattress on the floor of my therapist’s office, a blanket pulled up to my neck. Soft music starts to play. She instructs me to swish the dissolving tablet around in my mouth for 15 minutes before I swallow. I feel my eyes start to water a bit at the bitter sting of the orange-flavored ketamine occasionally spilling into the back of my throat. My cheeks start to ache. Can I really do this for 12 more minutes? After 9, I start to feel a sense of relaxation settle into my body and the last 5 drift by almost unnoticed. I swallow and pull the eye mask down over my eyes before my arms and the rest of my body disappear altogether.

It's completely dark behind the eye mask, and I can’t tell if I’m asleep or awake or somewhere in between. I don’t know if the fractals of light before my open eyes are real or just a trick my mind is playing. And suddenly I’m crying. Sobbing. Overwhelmed by a feeling of being held for the first time in my life. The earth beneath my back has somehow dissolved and now I’m being cradled on all sides by a loving god-like energy. I let myself be carried, swept away, until I’m floating down a river that runs through a dark cave. I’m reaching for something – a light trapped inside a rock, levitating above my head, just out of reach. I begin to feel frustrated that I can’t reach the truth inside this light until I’m reminded – “just let go.” I stop reaching and let the river carry me into a forest where Shiva is weaving an elevator out of tree branches. I get in and ride the elevator to the top of the forest canopy. In the sky, there’s a funeral and suddenly my hands and arms and my entire body begin dissolving. It’s my funeral. I become dust, carried in the wind, slowly coalescing and taking new form as a white bird. I know this bird to be my spirit. Gradually the sky darkens and I’m soaring through a constellation of stars, not knowing where I’m going but feeling that I’m being guided by a loving hand that knows the way.

None of it makes sense but somehow it carries more meaning than anything I’ve ever experienced. Ketamine is a dissociative drug approved by the FDA as a general anesthetic. In 2019, its derivative medicine, esketamine, was approved as a nasal spray in sub-anesthetic doses for major depression. Ketamine, though, as used in sublingual and IV doses in ketamine assisted therapy (KAP), is still considered to be used off-label for depression, addiction and PTSD.

Proposed Mechanisms of Ketamine for Mental Health

Results from the clinical trial released in 2022 following 403 patients with treatment-resistant depression show that 55 percent of those receiving ketamine twice per week for three weeks had at least a 50 percent improvement in their depression. The most amazing part? These improvements lasted for the entire six-month monitoring period following treatment. In another study, ketamine produced a 55% rate of improvement in suicidal ideation within just 24 hours, results that lasted for up to 6 weeks.

What is it about ketamine, a drug that was never intended to be used to treat depression, that’s making people turn their focus away from traditional antidepressants? With most antidepressant medications, the effect of the drug only lasts as long as the drug is in your system. When you take ketamine, it triggers a cascade of reactions, resulting in an increase of brain derived neurotrophic factor (BDNF) that enables new neural connections to grow. In other words, it’s the reaction of the body to ketamine, not the presence of ketamine in the body that generates its effects. If this sounds familiar, that’s because it’s not unlike how we know homeopathic medicine to work.

Psychedelic medicines have been used across cultures for centuries, believed to be a vehicle for transcendence that open up the mind to a broader perception of the nature of reality and its intersection with the divine. There are varying schools of thought regarding where ketamine falls among these medicines. Higher doses of ketamine can induce psychedelic states of ego-dissolution in which people lose touch with the physical realm and detach from any prior sense of identity.

At lower doses, ketamine is thought to produce a psycholytic effect. The goal of a psycholytic session is to experience a non-ordinary state of consciousness while still remaining in touch with the present moment. From my experience taking a lower dose, I think there’s a large gray area in between where psychedelic states can be accessed while still “remaining in the room.” I believe this has much to do with both the individuality of the client and the setting created by the therapist.

Regardless of which type of experience a person has, both states are predominantly characterized by a quieting of the area of the brain called the default mode network (DMN). The DMN gets activated when our mind is in a passive, non-task oriented state. It’s the part of our brain responsible for ruminating and searching for what is wrong…and where “I’m not good enough” and “I don’t deserve that” live. Ketamine, along with other psychedelic medicines, are known to reduce functional activity in the DMN, effectively allowing us to view our problems from a wider perspective by using different parts of our brains.

When experienced in conjunction with traditional psychotherapy, such non-ordinary states of consciousness relax the walls that come up when trying to access painful emotions. This allows for therapeutic breakthroughs at an exponentially faster rate. For many, even, these states leave us with an ineffable sense of hope and connectedness that only a brush with the divine could.

The Integration of Naturopathic Medicine with Ketamine

As a naturopathic physician, my role in supporting clients through KAP is in the referral and integration stages. There is a critical period of 48 hours after administration of ketamine where neuroplastic changes are still taking place. Here’s an incomplete list of what can be done during this time to maximize the therapeutic benefits of ketamine:

1. No alcohol: Aside from the fact that alcohol can exacerbate the short-term side effects of ketamine, specifically sedation, disorientation, dizziness, lack of coordination and nausea, alcohol can also dampen ketamine’s therapeutic effects. Alcohol is a depressant that impairs neuroplasticity, the very thing we want to promote with ketamine. It can also interfere psychologically with your ability to reflect on and integrate insights during the post-KAP period.

   
   

2. Avoidance of negative media, news, etc.: Think of the brain after KAP like a sponge. When neuroplasticity is enhanced, information from your environment is being absorbed and integrated into new connections. If we want to form a new worldview that’s more optimistic than before, we must be mindful of what input we’re feeding our brains. Meditation, an early bedtime, warm baths, walks in nature, journaling and painting are all great ways to fill this time instead.

   
   

3. Omega-3 fatty acids: I recommend supplementation with at least 2,000mg/day EPA + DHA, with >60% EPA. These fatty acids, derived from cold-water fatty fish, like salmon, mackerel and sardines, are essential to support neuroplastic changes. A recent review found that doses similar to this were effective for improving depressive symptoms, so it’s often best to remain consistent with this dose before and after KAP if depression is part of your reason for seeking treatment.

   
   

4. Magnesium: Magnesium and ketamine have overlapping, synergistic mechanisms of action in the brain, including modulating glutamate and GABA systems and increasing BDNF. The two appear to have a superadditive antidepressant effect when combined, though further research is needed to confirm. A dose of 144mg of magnesium from 2,000mg magnesium threonate is generally well tolerated and effective.

   
   

5. B Vitamins: B Vitamins, especially B1, B6 and B9, are essential for overall nerve health and communication. Specifically pertaining to ketamine therapy, they play a significant role in neuroplasticity and nerve regeneration. One study even found that individuals with higher serum B12 levels tended to respond better to ketamine treatments than those with lower levels.

It's true that KAP may not be for everyone. We still have a long way to go in understanding whether ketamine is safe for people who experience states of psychosis. The promise it holds, though, for those in the depths of depression wondering if life is still worth another try, is nothing short of a miracle. I’m thinking of a world where we all have access to dormant parts of our subconscious mind that hold truths of our inherent worth, lovability and goodness. This is a world I’d like to be in.

In love & mental health,

Dr. Amin

https://mcimh.com