We are experiencing a mental health crisis, and rates of depression and suicide continue to rise. According to the Surgeon General, Dr. Vivek Murthy, “Mental health has become the defining public health and societal challenge of our time ” (CDC, 2023). Over 30% of the population is suffering from mental health disorders and addiction (SAMHSA, 2021), and seventy percent of those suffering do not receive any mental health treatment. (Chatterjee, 2023). In the face of this, it is imperative that the field of mental health broaden its horizons in search of potential treatments. One such option is the medication, ketamine, which has demonstrated considerable utility in addressing major depressive order and suicidality. (Yavi et al., 2022; Dadiomov & Lee, 2019). Ketamine is a dissociative anesthetic. An improved analog of PCP, it was discovered in 1912 and developed for pain relief and anesthesia. It was widely used during the Vietnam war for battlefield surgery in the 1970s. It is a particularly safe anesthetic, as it does not impact respiration. Consequently, it has been widely used for decades in pediatric and veterinary settings.
Then in 2019, ketamine, which is a generic drug, was rescheduled as a medication for treatment resistant depression. Ketamine traveled a bumpy road on its path to approval for psychological well-being. This was largely due to its association with underground drug culture, which has seen ketamine as a recreational drug of abuse. You may have heard the term k-hole associated with rave dance parties. The term ‘k hole’ was originally coined during the Vietnam War, when ketamine was used with injured soldiers in need of medical treatment on the battlefield. Medics injected ketamine into these injured soldiers and placed them in a ditch to wait for evacuation to a field hospital.
However, in the 1990’s, researchers began studying its potential for addressing psychological well being. It was found to be helpful in addressing treatment resistant depression (Berman et al., 2000 ) as well as clients struggling with alcohol use disorder (Kolp, Friedman, Young, & Krupitsky, 2006). In those research protocols, both conditions were treated with ketamine plus supportive psychotherapy, presaging the growing interest in ketamine assisted psychotherapy. Traditional anti-depressants that target the neurotransmittter, serotonin, are only helpful for about a third of the population (Informed Health, 2020). Psychiatry spent many years focused on serotonin, believing it to be the most important neurotransmitter involved in mood regulation. In fact glutamate is the most ubiquitous neurotransmitter in the brain; therefore changes to it lead to a diverse cascade of effects. Ketamine is a glutamate modulator that acts at the NMDA receptor leading to more diffuse neural connectivity. Ketamine also affects protein synthesis and expression leading to the development of new neurons and healthier dendrites.
Dendrites are extensions that grow out from the neuronal body, and their function is to facilitate communication between neural cells. Research has shown that after a single ketamine administration, dendritic growth is more robust for one month (Phoumthipphavong, Barthas, Hassett, & Kwan, 2016). The most significant mental health benefits of ketamine administration are antidepressant effects, neurogenesis, and synaptogenesis. The latter refers to the growth of new neuronal connections, which is particularly helpful in developing new patterns of behavior and enhancing cognitive and emotional flexibility. Imagine skiing down a well grooved vs a fresh slope – ketamine is like a fresh blanket of snow that allows for the possibility of new paths and new behaviors.
Currently, ketamine is utilized as part of two different approaches to treatment – the traditional biologic / psychiatric model and the psychotherapeutic model. Both approaches are helpful for neuro-adaptive changes, such as addressing depression and addiction. Ketamine is also currently being researched with affirming results for the treatment of PTSD, alcoholism, OCD, and personality disorders (Martinotti, et al., 2021; Feder, Rutter, Schiller, & Charney, 2020; Fineberg et al. 2023). Historically, psychiatric medicine has adhered to a biologic model which seeks to modulate brain chemistry in order to dampen symptoms and avoid pain without necessarily addressing root causes. In this model ketamine is usually delivered intravenously under the supervision of an anesthesiologist to reduce symptoms. Ongoing treatment is generally necessary for continued symptom reduction. Conversely, the psychotherapy model seeks to effect change by not only leveraging the psychopharmacologic effects of the molecule but also focuses on the setting and psychotherapeutic framework, while seeking meaning in the experience and content of the altered state (Drozdz et al., 2022).
The biochemical administration of ketamine is of great value, but ketamine delivered in a medicalized environment can feel scary for some. The ketamine experience, or trip, can be profoundly disorienting. Having such an experience while accompanied by an IV in the arm and a blood pressure machine beeping by one’s side may limit potential for healing and growth.
The psychotherapeutic model is generally delivered in a less medicalized and more soothing office environment by a psychologist or psychiatrist. This is representative of how ketamine assisted psychotherapy (KAP) attends to the role of setting and relationship (Dore et al., 2019). The psychotherapeutic (KAP) model also utilizes widely variable dosing ranges, which can be differentiated as psychedelic or psycholytic. The psychedelic dose range yields an altered or expanded sense of reality outside of psychic norms. These appointments are generally three hours long. Prior to administration, the initial portion is spent attending to relationship, safety, and familiarity. With psychedelic dosing, clients are lying down, wearing eye shades, listening to a curated soundtrack and encouraged to direct their attention internally towards visions, feelings, and insight.
Ketamine can allow clients to re-experience their personal narratives from a different perspective. The disassociative aspect allows for a separation between autobiographical experience and its emotional charge, which allows for a sense of space between the experience the world and the response to it. The duration of the altered state is dose dependent but generally lasts for about one hour. As the effects taper off and patients resume speaking, the psychologist/psychiatrist supports clients in exploring their experience and processing what can sometimes feel like fleeting insights and recollections. Alternately, psycholytic dosing is high enough to soften defenses yet is still low enough to keep clients present in the room and able to engage in a psychotherapeutic relationship. Psycholytic dosing sessions are generally a two hour experience. Clients maintain a relational connection throughout the session. The softening of the defenses allows for deeper access to conscious and unconscious intrapsychic obstacles as well as a more spacious field for exploring affective, relational, or somatic themes. This can be very helpful for addressing rigidity as well as creative and emotional blocks.
Whether for psycholytic or psychedelic effects, KAP can be delivered in a variety of routes of administration. Oral administration is with rapidly dissolving tablets or troches. Intranasal employs aerosolized ketamine or Spravato (a non-generic, prescription formulation). Intramuscular injection utilizes small and relatively painless syringes. Within ketamine assisted psychotherapy (KAP), the cadence at which ketamine is recommended is individualized and dependent upon the presenting symptoms and situation. Early research indicated six sessions within three weeks reduced depressive symptomotology with subsequent quarterly maintenance to maintain the anti-depressant effect (Andrade, 2017). In practice, a more efficient use of this model often sees weekly sessions at a slightly higher dose. As the neuronal/dendritic changes that enhance connectivity last one month – many clients benefit from monthly ketamine administration followed by weekly therapeutic integration aka psychotherapy. Those sessions focus on the importance of what patients do in the days and weeks after ketamine administration in order to initiate and maintain new systems of thought, affect, and behavior.
To summarize – ketamine assisted psychotherapy is the art and science of leveraging the biologic benefits of the medicine within the relational therapeutic container. It does not simply count on change to arise from a molecule being added to the brain. Rather, healing and change are modulated by how behavior and belief systems are consciously activated while the medication is acting on the neural framework (Joneborg et al., 2022). It also emphasizes the role of intentionality and goals subsequent to dosing days. As a psychiatrist, I have spent over a decade prescribing medications which often reduce clients’ capacity to feel. It is exciting to evolve towards a modality of healing that encourages clients to encounter their internal world and feel their feelings within a safe container, so that we can explore the root causes of their illness and effect lasting positive change.