The peer-reviewed research that focuses on ketamine as an intervention for treatment-resistant depression, or as a tool in managing depression, points in a promising direction: ketamine can be an effective and viable treatment option.
But what factors contribute to making ketamine an effective tool in the treatment of depression?
Ketamine’s Dissociative & Psychedelic Properties
Ketamine’s properties make it both a dissociative and psychedelic compound. At certain doses, people can experience both the physical and psychological dissociative effects, as well as the subjective psychedelic effects.
This is a two-part experience quite unique to ketamine, and drives many of the reasons ketamine is effective in managing/treating depression.
There is science demonstrating that the dissociative effect itself, has a direct effect on the antidepressant qualities of ketamine.
“Antidepressant effects can occur in patients who do not experience even transient dissociative effects, and vice-versa.
It is worth considering that dissociation is part of the unique effect of ketamine that is not shared by conventional antidepressants: an altered sense of self that can also lead to a new state of contentment.”
Wolfson M.D., Phil. The Ketamine Papers: Science, Therapy, and Transformation (pp. 393-394). Multidisciplinary Association for Psychedelic Studies. Kindle Edition.
Some subjective markers of dissociation, according to the CADSS scale include:
- A feeling of moving in slow motion
- Experiencing sensations as if in a dream-like state
- A sense of being separated from the direct experiences
- An out-of-body perspective
- Feeling disconnected from the body
- Events happening at a perceived faster pace
- Disconnection from the sense of time
For someone living with depression, the felt experience of dissociation in this context can provide a respite, or the ‘breathing room’ to rest, reflect, and begin taking control again.
As a compliment to the dissociative effects, ketamine at certain doses can produce or give rise to an experience which also contains psychedelic properties.
"If your eyes are closed, then it’s a different visual experience. If you close your eyes even right now and actually look at what you’re seeing, it’s not just darkness or nothing—you see lights, and shapes, and colors. Most of us tend not to sit around on a daily basis with our eyes closed just watching the show, but during a ketamine infusion, you may watch the show, and it will likely be more colorful, brighter, it can have a texture to it, and you can feel like you’re travelling around in it. You’re not hallucinating—it’s really there, and it just takes on a different meaning. But this is why people sometimes describe it as psychedelic or “trippy.”
Wolfson M.D., Phil. The Ketamine Papers: Science, Therapy, and Transformation (p. 499). Multidisciplinary Association for Psychedelic Studies. Kindle Edition.
Some properties of ketamine/psychedelics include:
- Novel or altered ways of thinking or feeling, perhaps accessing alternate or mystical states of consciousness
- Visual imagery: including colors, shapes, visualizing the movement of energy, archetypal images, or watching clips of your life play back on a film real as an observer,
- New sensory patterns: including alterations in touch, smells, and physical sensations
- Increased connections in regards to memories and present circumstances
By providing a potential avenue for new insights, experiences, and connections, the ketamine experience can also provide a therapeutic compliment to the neurochemical benefits.
The dissociative and psychedelic properties of ketamine manifest themselves in the experience primarily in two ways: providing biological and phenomenological benefits, and helping generate experiential and emotional insights.
“When looking at the tools we have out there to treat depression, we have typically had to rely on the medicine to do the work. This aligns with the medical model in understanding that we take something, something happens in our mind or body, and we hopefully feel better. We are a passive participant," Kristin Arden, Lead Clinician at Mindbloom, said. "Ketamine works in that way too, but also affords us a whole other avenue of healing potential. We are able to gain insights, perspectives, and find peace on the medicine. All in a time where our brain is primed to heal and grow thanks to the neurobiological effects of the ketamine. We can, in a way, take back a degree of self-agency in our healing process.”
Neurobiological Benefits & Experiential Insights
There are a number of biological (specifically neurochemical) effects from ketamine that are helpful in treating the underlying neurobiology associated with depressive symptoms.
One of the ways depression and its symptoms manifest is through neural pathways and certain synaptic connections becoming “cemented,” promoting patterns of thinking with strong momentum carrying them. This makes depressive thoughts or feelings both routine and frequently recurring. Over time, this damages the health of the neurons themselves.
Mindbloom’s Science Director, Dr. Casey Paleos, summarizes it as such:
“The end result of all these glutamate-related neuronal changes is a brain much more predisposed to manifesting the constellation of subjective phenomena we call depression and anxiety.”
In order to address this predisposition, ketamine has 3 neurochemical benefits in particular that are beneficial:
- Upregulating Neuronal Production: Ketamine increases the production of new neurons, supplying the brain with healthy and vital neurons, the basis for more effective and harmonious connections in the brain.
- Upregulating Release of BDNF (brain-derived neurotrophic factor): BNDF, colloquially referred to as ‘fertilizer for the brain’ helps promote neuron growth, overall health, and ongoing maintenance. Providing both short and long-term benefits.
- Stimulating mTOR: mTOR regulates many processes involved in cell growth and healing worn out synaptic connections, and also stimulates activity/growth in the prefrontal cortex and hippocampus, essential areas for emotional regulation.
From the biological perspective, ketamine produces a cascade of effects that are beneficial for short and long-term repair and flourishing of the cells, neurons, and synaptic connections that healthy, balanced brains need.
These neurobiological effects create an environment primed for new programed responses to triggers, new understandings of ourselves and the world around us and emotional regulation.
The biological effects of ketamine are generally dose-dependent, and will often occur when ketamine enters the body. Although we have a great amount of science that has helped us understand how ketamine works as an antidepressant, there is still a lot to that is unknown and being actively explored.
Alongside its dissociative properties, at certain doses ketamine can also induce novel subjective experiences or classic psychedelic phenomenology. This sense of experience or journey can provide important insights and felt experiences that can help us manage depression in the short and long-term.
“A ketamine psychedelic experience tends to offer up the possibility for transformation of the self by isolating the mind to some extent from external sensations, altering body consciousness toward an experience of being energy without form, and by amplifying and scrambling the contents of mind in unpredictable ways—all of this generating the potentiality for changes in consciousness that may be beneficial and persistent. Coming back from a ketamine journey as a somewhat different being is quite predictable.”
Wolfson M.D., Phil. The Ketamine Papers: Science, Therapy, and Transformation (p. 646). Multidisciplinary Association for Psychedelic Studies. Kindle Edition.
There are a few ways the ketamine experience can do this:
- Novel Insights: With dissociation comes a sense of being separate from yourself. With this perspective individuals can spot certain behavioral patterns, environmental triggers, or see how they act in a new way. These insights can catalyze short-term respite or long-term positive behavior/mood change.
- Embodied Feelings: The ketamine experience can induce a number of embodied emotions/feelings. For those with depression, having an embodied experience of calm, joy, contentment, or elation can be a powerful reminder or positive reinforcement that these states are possible for them. This can change long term outlooks and actions.
- Cognitive Distancing: Both during and for a brief window after a ketamine session, it’s possible that individuals may notice more ‘space’ between an external stimulus and their internal reaction to it. This space can provide the room to change behavior, remove automatic self-sabotaging habits, all of which are valuable in managing depression.
Acute Responsiveness & Long-Term Durability
Unlike other traditional treatment options for depression (namely psychotherapy, pharmacology, or a combination of the two), ketamine is fast-acting and acutely responsive.
Ketamine is classified as a RAAD (rapid-acting antidepressant) providing felt relief from major symptoms within hours or days, rather than weeks or months that traditional psychotherapeutic or pharmacological methods can take to demonstrate effects.
With this immediate response, it provides a foundation or “breathing room” for the patient and clinician to begin working on longer-term behavior/mood change.
Complimentary to the acute responsiveness of ketamine are the lasting effects after a session. This is known as the “durability” of the effects.
There are a few factors that contribute to the long-term durability of ketamine therapy:
- Insights gained from the psychedelic properties can allow for long-term positive behavior/mood change with effective integration
- Insights are gained during a time the brain is primed to process these new insights thanks to things like neuroplasticity and synaptogenesis. Through integration, we work on reinforcing the new pathways and connections; helping them fire and wire together.
- Through a series of treatments "stacked" or placed close together, we aim to build up a solid foundation of the substance in your system. This also reinforces the phenomenon of incremental and compounding improvements in baseline mood, attitude and perspective over a period of time.
Ketamine is a unique treatment in this regard, as single sessions have the potential to provide both short-term, rapid-acting relief, but also build toward long-term elevations in mood, brain health, and overall symptomatology.
These are some reasons we understand ketamine's unique role to play in the treatment of depression, and why it is showing such promising results already.
Given its ability to address both neurobiological and phenomenological experiences, and providing both short and long-term benefits — ketamine is uniquely positioned, and uniquely effective, to be a valuable treatment for depression.
This article is for informational purposes only and is not intended to be a substitute for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. If you are in a life-threatening situation, call the National Suicide Prevention Line at +1 (800) 273-8255, call 911, or go to the nearest emergency room.
Important FDA Safety Information
Ketamine is not FDA-approved for the treatment of depression or anxiety. Learn more about off-label uses here.
Side effects of ketamine treatment may include: altered sense of time, anxiety, blurred vision, diminished ability to see/hear/feel, dry mouth, elevated blood pressure or heart rate, elevated intraocular or intracranial pressure, excitability, loss of appetite, mental confusion, nausea/vomiting, nystagmus (rapid eye movements), restlessness, slurred speech, synesthesia (a mingling of the senses).
Do not proceed with ketamine treatment if any of the following apply to you:
- Allergic to ketamine
- Symptoms of psychosis or mania
- Uncontrolled high blood pressure
- CHF or other serious heart problem
- Severe breathing problem
- History of elevated intraocular or intracranial pressure
- History of hyperthyroidism
- Other serious medical illness
- Pregnant, nursing, or trying to become pregnant
Ketamine has been reported to produce issues including, but not limited to, those listed below. However, lasting adverse side-effects are rare when medical protocols are carefully followed.
While ketamine has not been shown to be physically addictive, it has been shown to cause moderate psychological dependency in some recreational users.
- In rare cases, frequent, heavy users have reported increased frequency of urination, urinary incontinence, pain urinating, passing blood in the urine, or reduced bladder size
- Ketamine may worsen problems in people with schizophrenia, severe personality disorders, or other serious mental disorders.
- Users with a personal or family history of psychosis should be cautious using any psychoactive substance, including ketamine, and discuss potential risks with your MindBloom clinician before proceeding with treatment.
- The dissociative effects of ketamine may increase patient vulnerability and the risk of accidents.
To promote positive outcomes and ensure safety, follow these ketamine treatment guidelines:
- Do not operate a vehicle (e.g., car, motorcycle, bicycle) or heavy machinery following treatment until you’ve had a full night of sleep
- Refrain from taking benzodiazepines or stimulants for 24 hours prior to treatment
- Continue to take antihypertensive medication as prescribed
- Avoid hangovers or alcohol intake
- Refrain from consuming solid foods within 3 hours prior to treatment and liquids within 1 hour prior to treatment
- Ketamine treatment should never be conducted without a monitor present to ensure your safety