Ketamine is well-tolerated in therapeutic dosing ranges. 

Unlike all other injectable anesthetics, ketamine does not suppress respiratory drive,  or decrease cardiac output, blood pressure, or heart rate. In fact, ketamine transiently increases cardiovascular function, output, heart rate, and blood pressure by about 10-20 points. When used for psychiatric purposes, these sympathomimetic effects, albeit mild, should nonetheless be accounted for when screening for safety (e.g. if someone couldn’t walk or run relatively briskly without harm, they should not use ketamine).

Adverse effects

Ketamine’s most common adverse effects include drowsiness, dizziness, light-headedness, nausea, poor coordination/unsteadiness, blurry/double vision, feeling strange or ‘unreal’, abnormal sensations (numbness, tingling), slurred speech, headache, dry mouth or hypersalivation, and trouble concentrating. Effects resolve completely in nearly all patients within 2-4 hours for intramuscular or intravenous, and in 6-12 hours for oral or sublingual if swallowed.

Contraindications and concomitant medications

Absolute contraindications for ketamine include uncontrolled hypertension, unstable cardiovascular disease, unstable medical condition, ketamine allergy, active ketamine abuse or dependence, acute mania or mixed state, and history of primary psychotic disorder. 

Relative contraindications that require careful risk analysis include a remote history of ketamine abuse or dependence and/or active substance use disorder, thyroid disease, glaucoma, and extreme personality disorder,

Psychostimulants should be avoided on dosing day due to their potentiation of a synergistic effect between the ketamine and the stimulant from a sympathomimetic, mainly cardiovascular standpoint (and depending on the relative risk level of the population). Benzodiazepines (especially high doses that are chronically administered) should also be avoided due to their potential to blunt ketamine’s effects. Cannabis and alcohol should also be avoided, mainly for the sake of preparation and integration rather than any neurochemical contraindication.

Preparation

You will have at least two, pre-medication, preparation sessions. These will include background gathering, psychoeducation, consent discussions and intention setting. 

Medication

You will be referred for an external consultation from a medication provider. During this appointment the provider will determine if medication is appropriate. If appropriate, the dosage of the medicine will be determined with consideration of your goals for treatment. You may experience a trance-like state or a psychedelic state, depending on the dosage. You, the client, will be in charge of picking up your Ketamine prescription and bringing it to the KAP session. 

Dosing 

KAP sessions are 3 hours. 

At the dosage we will administer for therapy, you will most likely experience mild anesthetic, anti-anxiety, anti-depressant and potentially psychedelic effects. You are likely to experience a relaxation from ordinary concerns while maintaining conscious awareness of the flow of mind. Realistically, not everyone will have an experience that will be life-altering. Setting appropriate expectations is essential. Everyone’s experience is different, we can not predict what you will experience. 

It is incredibly important to get the “set” and “setting” as foundational starting points for medicine exposure. Intention-setting is strongly encouraged prior to any medicine exposure. Following one’s intention is not always possible due to the fleeting nature of thoughts and experiences under the influence of this medicine.

We will start our KAP session with grounding and down-regulation. During medicine exposure you can expect to be under an altered state of consciousness for 30-45min. You will recline comfortably for the duration of your session. Eye masks are provided and background music will be played. As you go deep into your inner world, you may be silent or you may verbalize what you are experiencing. This state has been described as “floating” and “transformational”.  This period is expansive and you will be aware of, and engaged with, your mind flow. 

You may experience important positive changes in personality, mood and cognition during treatment. Some experiences may be temporarily disturbing to you. The ketamine experience is designed to enable your own healing wisdom to be accessed for your benefit. The psychotherapy support you receive will aid you in making your experiences valuable and understandable.

As you come out of this state of consciousness, with new freedom and insights, the session will go into an integration phase. Following the medicine administration, we will have the opportunity to discuss the experience and integrate. Your KAP therapist will help you to integrate and provide valuable context for your experience. You will also have the opportunity to have a PEMF and Red Light Therapy treatment. 

Following a dosing session, you will not be able to drive home. All patients receiving ketamine will need transportation to and from your appointment. No food or drink is permitted before sessions. Please carefully read the pre-post session guidelines. This will be discussed with you during your intake session.

Integration

Integration, psychotherapy sessions will be 24-48 hours following dosing session(s) with the attempt to integrate your experiences into your current life. These sessions are 50 minutes and can be in-person or virtual.

There’s an experience of “unfolding” that happens during and often days, weeks and months following Ketamine exposure.

Ketamine is used as an anesthetic dissociative. The medicine’s dissociative impact allows you to access an unusual state of consciousness and disconnect from your natural  “defense safety mechanisms” which have been developed throughout your life. These safety mechanisms have been important and have served a purpose through your life; they’ve kept you safe. They may have also inadvertently developed patterns of undesired behaviors which might include: anxiety, depression, avoidance and other maladaptive coping mechanisms. 

As you disconnect from your natural defenses, you’re able to tap into your inner healing wisdom. This wisdom is a part of you, this wisdom guides you to heal yourself and recognize what you need to face, address, feel, know, see and process to best help you. Our bodies are designed to self-heal. When we are born, our bodies have a blueprint to heal. For example, when we get a cut, our body heals itself. Our brain is the same, if we are able to surrender the defense safety mechanisms, we can access the internal healing mechanism and internal wisdom: psychologically, emotionally and behaviorally.

There are several forms of administration: Sublingual (SL), Intramuscular (IM), Intravenous (IV) and Intranasal (IN). Bioavailability is determined by administration type. 

How is KAP different from IV Ketamine Infusion? 

Intravenous ketamine generally occurs in a medical setting with no therapeutic support. KAP is possible and available during IV administration, if requested. IV Ketamine is offered from Rooted Health, Kansas City: www.rooted.health 

What are the Ketamine Assisted Psychotherapy Treatment Pre and Post Session Guidelines?

Before your session:

– No alcohol 72-hours before treatment
– Any medication taken 72- hours before treatment MUST be discussed and cleared with the treatment team
– No food 4 hours before treatment
– No drink 1 hour before treatment
– No coffee, tea, or caffeinated beverage 5 hours before treatment

Your medication session will be 3 hours; the impact of the medication is approximately 45min-1 hour.

After your session:

– No alcohol 72-hours after treatment
– Any medication taken 72- hours before treatment MUST be discussed and cleared with the treatment team
– You will need to arrange for a ride home after your treatment as you cannot drive or operate heavy machinery 12 hours after treatment
– To maximize the benefit of the treatment it is recommended to take the rest of the day off

If you are experiencing any medical emergency following your medication session, please call your medical provider and/or 911 or go to the nearest Emergency Room.

Ketamine’s major clinical and psychological effects are interwoven, and collectively include decreases in anhedonia (inability to experience pleasure), pessimistic thinking, social and emotional avoidance and dissociation, and rejection sensitivity. All of these are hallmarks of depression, often expressed in and as the patient’s self-reinforcing belief that they are ‘permanently broken’ and incapable of engaging with others, thus keeping depressed and traumatized people from seeking reward and taking pleasure from and through engagement in the world.

Ketamine is a psychoactive molecule known as arylcyclohexylamine, first synthesized as a drug in 1962. Classified as a dissociative anesthetic, it has FDA indications and approval for procedural sedation and analgesia (pain relief) for decades.

This medicine is now an “off-label” treatment for various mental health conditions and other conditions including chronic pain that have not improved with conventional treatment.

Ketamine is classified as a dissociative anesthetic because dissociation between the peripheral and central nervous system is its primary mechanism of action for anesthesia. Analgesia (making it an effective anesthetic) is central to its psychological effects (creating a subjective experience of dissociation from one’s body and identity). 

Ketamine mechanisms of action: microscopic

At the microscopic level, ketamine acts as an antagonist at the brain’s NMDA receptor – one of the two major receptor types for glutamate (the other being the AMPA receptor), the primary excitatory neurotransmitter for the central nervous system (‘gas pedal’) with widespread and manifold impacts on all aspects of the neuronal life cycle. This is a different pathway than that of other psychiatric drugs such as the SSRIs, SNRIs, lamotrigine, antipsychotics and benzodiazepines.

The brain uses glutamate ubiquitously to signal from transmitting to receiving neurons in order to fire impulses – acting to induce an action potential in contrast to GABA—the primary inhibitory neurotransmitter (‘brakes’). If the receptor is the lock and the neurotransmitter the key, the brain’s NMDA and AMPA receptors represent two different locks to the same key (glutamate), and ketamine, as a non-competitive NMDA receptor antagonist, works to disinhibit the release of glutamate, shunting it to the AMPA receptor (which significantly stays open) and blocking the NMDA receptor and the release of GABA: in effect, ‘putting the breaks on the break.’ 

In disinhibiting the release of glutamate at the synaptic level, a molecule called BDNF (brain-derived neurotrophic growth factor—essentially brain fertilizer) is upregulated, activating a process known as mTORC1, which stimulates the cell to produce more synapses, making it more connected to its environment that translates to ketamine’s positive clinical and psychological effects on mood and behavior.

Ketamine mechanisms of action: macroscopic

On the macroscopic level, ketamine’s global brain effects hinge on its sensory input dissociation between the central nervous system (CNS) and peripheral nervous system (PNS), and between the default mode network (DMN) and the salience network (SAL) and central executive network (CEN). Along similar lines to the default mode network, the salience network and central executive network are hypothesized networks of different brain regions, with the default mode network exhibiting dominance over both of them in highly depressed people. 

The default mode network first emerged in neuroimaging studies of brains performing tasks (‘task positive’) versus at rest, with the latter state of introspection/day-dreaming (where the mind goes when not task positive) subsequently dubbed the ‘default mode.’ Research evidences default mode network hyperactivity in cases of depression, ruminative illnesses, and abhorrent connectivity to the salience and central executive networks, such that the overall constellation of such diagnoses is one of over-rumination and misattribution of the salience or meaningfulness of the emotional tone ruminated on. 

This dysregulation further impairs executive function around the subjects of rumination and belies the structural phenomenon underlying the functional phenomenology of depression and anxiety, whereby the brain continuously slips back into its negativistic grooves as the neuronal networks associated with the activity of rumination are both strengthened and combined with a diminishing capacity to form new pathways.

However, through acute upregulation of BDNF and increased neuroplasticity, ketamine diminishes hyperactivity in the default mode network and enhances activity in the salience and central executive networks, creating a window of time in which the brain’s baseline functioning state (in a depressed person) is snapped out of grid and less weighted toward its negativistic grooves. 

Stress, neuroplasticity, and brain health

The brain is a dynamic, living organism, constantly changing and moving on a microscopic level in quite miraculous ways. One such facet of this change is that which presents on the synaptic level in terms of neuron-to-neuron connections, referred to as ‘neuroplasticity’ – plasticity meaning changeability/malleability, and applying to both brain structure and function. The brain is highly neuroplastic, and there is a positive correlation between its neuroplasticity and its overall ‘health’ such that mental illness actually refers to conditions that decrease neuroplasticity. 

One of the main markers of brain cell health are its ‘dendrites’ or ‘dendritic spines’–sub branches that added together comprise a synapse (the microscopic junction where the presynaptic axon [output] of one neuron meets the dendrite [input] of another). When an action potential (electrical signal) travels between the presynaptic terminal of an axon (which is insulated by the myelin sheath, or a layer of fatty tissue that facilitates the transmission of electric signals) to the postsynaptic terminal of the dendrite, neurotransmitters are released into the synaptic cleft. These diffuse across the synapse in a lock and key fashion, docking with the postsynaptic receptor on the dendritic spine, and causing an electrical signal to propagate into the receiving neuron. This chain reaction occurs from neuron to neuron on a massive scale. Multiplied into the billions range this is how the brain works – with every neuron both transmitting and receiving signals from other cells constantly, and with the brain’s overall neuroplastic condition varying both from person to person; within a person across their lifespan; and as a function of age and stress. 

If applied chronically to an individual over time, emotional or physical stress will have the effect of diminishing neuroplasticity as illustrated in the withering of dendritic spine density. Specifically, this is seen in relation to ‘excitatory postsynaptic potential’ or EPSP – the electric charge that exists as a result of the summation of dendritic inputs. How much of an electrical impulse the postsynaptic cell receives is visibly and structurally observable under the microscope in terms of dendritic spine density and the amplitude of the electrical signal, whereby chronic stress will lead to diminished amplitude of the signal and functional deficits at the neuronal level.. 

Impaired neuroplasticity on the level of structure results in cognitive inflexibility on the level of function, eroding resilience to stressful stimuli (as the brain becomes less able to form new connections); promoting distortions in our mental representations of ourselves and the world; and exacerbating states of chronic stress which further impair neuroplasticity and increase inflexibility in a vicious cycle ending in a DSM diagnosis.

Ketamine and the neuroplastic window

When neuroplasticity results in changing connections between neurons over time, what determines these connections is how often they are fired in sequence. The brain contains chains of signal pathways/networks in which different neurons in different brain regions fire in sequence to effectuate different types of behaviors (for example, learning to play the piano requires the centers controlling motor function). This process can be encapsulated by the saying ‘neurons that fire together wire together.’ 

Ketamine administration effectuates a complete restoration of dendritic spine density and post-synaptic function after a single dose and day. Similar effects will present after ~three months with an SSRI/SNRI or electro-convulsive therapy (mapping onto time course for effectiveness of these treatments).

With ketamine, the effect occurs very rapidly after a single intervention, and while it doesn’t last forever the upregulation of BDNF observed after ketamine treatment opens a neuroplastic window within which neurons are able to create more synaptic connections and facilitate a larger throughput of signal through particular circuits. 

This process applies to any activity one could be engaging in, to either their benefit (learning to play the piano) or detriment (rumination, self-recrimination) and can be extended through repeated infusions or other psychotherapeutic interventions e.g. cognitive behavior therapy, dialectical behavior therapy, EMDR – all of which will be more effective as a result. 

Clinical trials are beginning to substantiate this, and in conjunction with anecdotal evidence, it appears that essentially any activity (e.g. language acquisition) the brain is used for following a ketamine treatment will be enhanced. Although the negativistic grooves present in depressed populations do not disappear altogether, after ketamine there is a greater capacity to form alternative pathways within this window of brain malleability and to shift the trajectory toward greater resilience in the face of stress.

The durability multiplier effect

The effectiveness of a single dose of ketamine lasts anywhere from a few days to weeks depending on the person. In the absence of any concomitant psychotherapy this is very promising, but of central interest is how to prolong the duration of effect. 

Adapting a model similar to electro-convulsive therapy to the context of ketamine demonstrates the most evidentiary support in terms of extended benefit, outlined as 2 sessions per week for 2-3 weeks (4-6 treatments, usually 6) and maintenance infusions varying from once a week to once a month. This protocol, known as the National Institute of Mental Health (NIMH) protocol for treatment resistant depression of a 40-minute drip infusion dosed at .5mg/kg, is not combined with concomitant psychotherapy which often sustains the effect much longer and may decrease the need for repeated infusions. 

This protocol does however present a durability multiplier effect, whereby repeated infusions over a few weeks in close succession can prolong the effect out anywhere from three to six months in some cases (without any other interventions or antidepressant use). 

Ketamine, has a rapid onset effect; a higher response rate and longer duration with just one to a handful of treatments; mild and transient adverse effects; a robust anti-suicide effect; safe co-administration with most other psychiatric medications; and encompasses many new and emerging clinical indications.