How Ketamine is Transforming Mental Health Treatment
On my podcast, MindBody Matters I interviewed Dr. Les Cole, author of the best selling book, The Ketamine Effect.
Ketamine therapy has moved from battlefield anesthetic to one of the most promising innovations in modern mental health care. In a recent interview, Psychotherapist and author Dr. Les Cole, whose 2023 book The Ketamine Effect: A Practical Guide to Understanding Ketamine Treatment and Your Inner Healing Journey shared his insights into the science, psychology, and spiritual dimensions of ketamine-assisted psychotherapy.
Drawing on decades of clinical experience, personal history, and emerging neuroscience, Dr. Cole offered a rare, integrated look at how ketamine supports deep healing. Below is a comprehensive overview of the ideas explored in the interview — from ketamine’s origins to its role in neuroplasticity, trauma therapy, ego dynamics, and long-term transformation.
Battlefield Origins
In the late 1960s and early 1970s, ketamine was introduced as an anesthetic during the Vietnam War. Unlike other anesthetics of the time, ketamine didn’t suppress breathing, allowing medics to treat wounded soldiers quickly and safely without intubation. This unique safety profile saved lives and solidified ketamine’s role in emergency medicine.
Unexpected Mood Benefits
By the 1970s, clinicians began using ketamine as an alternative anesthetic for older adults. Many patients woke from surgery with surprising and consistent effects:
reduced anxiety
lighter mood
decreased depressive symptoms
These observations planted the seeds for decades of psychiatric research.
Decline and Resurgence
Recreational misuse in the 70s–90s led to tightened regulations and a slowdown of clinical research. But early 2000s studies reignited scientific and medical interest. Ketamine’s rapid antidepressant effects — especially for treatment-resistant depression — drew significant attention.
By 2018, Dr. Cole began exploring ketamine-assisted psychotherapy himself, finding it uniquely suited to trauma work and deep psychological healing.
Neuroplasticity, BDNF, and the 72-Hour Therapeutic Window
Dr. Cole emphasizes that ketamine is not merely a mood-lift or psychedelic “experience.” It’s a neurobiological catalyst.
Ketamine works by:
Blocking NMDA receptors, which temporarily interrupts habitual patterns of brain activity.
Triggering a glutamate release.
Activating AMPA receptors, which stimulate key growth pathways.
Increasing BDNF and mTOR — both essential for synaptogenesis, or the formation of new neural connections.
This cascade dramatically boosts neuroplasticity, creating an opportunity for new emotional, cognitive, and behavioral patterns to emerge.
The Critical Window
The first 72 hours after a ketamine session represent a period of heightened brain adaptability. This window is ideal for:
psychotherapy
cognitive reframing
somatic work
healing trauma
shifting long-standing patterns
This synergy between ketamine and psychotherapy is what makes ketamine-assisted therapy so powerful.
The Common Ketamine Progressive Narrative (CKPN) Framework
To bring structure to ketamine therapy, Dr. Cole and colleagues developed the CKPN model, outlining five therapeutic stages:
Preparation – education, intention-setting, safety planning
Induction – IV, IM, or oral administration
Activation – the psychological and physiological experience
Integration – exploring metaphors, reframing trauma, grounding somatic insights
Follow-Up – ongoing support and behavioral reinforcement
This framework ensures that ketamine treatment remains safe, intentional, and therapeutically meaningful.
Different Ketamine Modalities: IV vs. Oral
Dr. Cole highlights important differences between administration methods:
IV Ketamine
100% bioavailability
Onset within minutes
45–50 minute session
Most predictable and often used for medical treatment-resistant depression
Oral Ketamine
30–35% bioavailability
Slower onset
Longer, gentler experience
Mild post-session fuzziness is common
Both approaches can be clinically effective when properly administered and integrated.
What Patients Commonly Experience
According to Dr. Cole, ketamine sessions often evoke:
A deep sense of relaxation or “kinesthetic peace”
A loosening of the emotional rigidity associated with depression, anxiety, or PTSD
The ability to observe traumatic memories without being overwhelmed
A temporary softening of the rigid ego — the defensive, controlling self shaped by trauma
When this ego softens, patients gain access to a more fluid, compassionate, authentic sense of self. This internal shift is often the cornerstone of long-term healing.
Key Safety Facts
It has been used medically for over 50 years.
Therapeutic doses (100–300 mg) are far below anesthetic or recreational levels.
Clinical treatment involves careful medical screening and supervision.
Ketamine is safer than many classic psychedelics due to its medical history and predictable effects.
High-profile overdose cases, such as actor Matthew Perry’s, involved extremely high, non-clinical doses combined with other substances — situations entirely unrelated to therapeutic practice.
The Psychology: Rigid Ego vs. Fluid Ego
This is one of Dr. Cole’s most interesting contributions.
Rigid Ego
Rooted in early life defense mechanisms
Reactive, narrow, self-protective
Reinforces repetitive negative patterns
Dominant in chronic depression and anxiety
Fluid Ego
Flexible and spacious
Capable of observing without reacting
Able to express authenticity and compassion
Open to new experiences and narratives
Ketamine temporarily “lifts” the rigid ego, allowing individuals to experience themselves with greater openness — a powerful catalyst for inner healing.
Neuroscience Spotlight: The Default Mode Network (DMN)
The DMN is the brain network responsible for:
rumination
self-criticism
worry
persistent depressive loops
Ketamine reduces DMN activity, creating silence in the inner chatter and giving people space to encounter themselves beyond their symptoms.
It’s a biological reset that blends seamlessly with psychological insight.
Inner Healing: Beyond Symptom Relief
Dr. Cole views ketamine therapy not just as a psychiatric intervention but as a deep inner healing journey.
This process often involves:
reconnecting with wounded or dissociated parts of the self
gaining new perspectives on childhood experiences
developing mindfulness and self-observation
expanding beyond limiting identity narratives
integrating difficult emotions with compassion
He likens psychotherapy to “care of the soul” — an ongoing path rather than a quick fix.
Ketamine, Spirituality, and the Authentic Self
Many patients report experiences resembling meditation or spiritual practice. Ketamine can help individuals access what Dr. Cole calls the authentic self — a state of fluid awareness, presence, and interconnectedness.
This dimension doesn’t require religious interpretation. It simply reflects the expansive quality of consciousness that emerges when defensiveness softens and neuroplasticity increases.
Why Ketamine Therapy Matters
Medically safe and highly effective for treatment-resistant depression, anxiety, and PTSD
Promotes rapid neuroplasticity, enabling meaningful therapeutic change
Facilitates access to a more compassionate, flexible sense of self
Reduces rumination by quieting the Default Mode Network
Most effective within a structured framework (CKPN)
Supports lifelong inner growth, not just symptom relief
As Dr. Cole puts it, healing is a journey — not a single session, not a chemical trick, but an unfolding process of deepening presence and awareness.
Historical Timeline of Ketamine
1960s–1970s - Developed for battlefield anesthesia in Vietnam; early mood benefits observe
1970s–1990s - Recreational misuse leads to legal restrictions
Early 2000s - Renewed interest in ketamine for severe depression
Ketamine Therapy: Key Concepts at a Glance
Aspect Description Mechanism NMDA blockade → glutamate surge → AMPA → BDNF/mTOR → neuroplasticity
Therapeutic window. First 72 hours are critical for integration.
The Ketamine Effect book by Dr. Les Cole paints a vivid picture of why ketamine-assisted psychotherapy is reshaping mental health treatment. It bridges neuroscience, trauma therapy, and spiritual philosophy to show that ketamine isn’t just about symptom relief — it’s about reconnecting with the deeper, more expansive parts of ourselves.
As ketamine research accelerates and more clinicians adopt structured therapeutic models, its role in mental health care will only continue to grow.
