Why Every Ketamine Infusion Can Feel Different: Understanding the Variables Behind Each Session

1. The Basics: What Is Ketamine and How Does It Work? Why Every Ketamine Infusion Can Feel Different

Ketamine was originally developed in the 1960s as an anesthetic. In medical settings, it is still used for sedation and pain control, especially in situations that require quick-acting or short-lived anesthesia. Over the past two decades, ketamine’s role has expanded into mental health, where clinicians discovered that at lower, carefully controlled doses, ketamine has a profound effect on mood disorders. In particular, it can effect treatment-resistant depression, anxiety, and post-traumatic stress disorder (PTSD). It is important to keep in mind that every Ketamine Infusion can feel different.

Biologically, ketamine’s primary mechanism of action involves the NMDA (N-methyl-D-aspartate) receptor. This is a key factor in the regulation of glutamate levels in the brain. Glutamate is an excitatory neurotransmitter involved in neuroplasticity, learning, and memory formation. When ketamine blocks NMDA receptors, it leads to a cascade of events that can restore synaptic connections. This fosters a healthier environment for brain cells to communicate. This is one reason why many patients experience rapid relief from their depressive symptoms after a ketamine infusion.

However, ketamine’s effects aren’t limited to biochemistry alone. The subjective experience can vary widely between individuals, and even for the same individual, two sessions can feel very different.

2. The Role of Mindset (“Set”) and Environment (“Setting”)

A critical factor in any psychoactive substance experience—therapeutic or otherwise—is the concept of set and setting. Popularized in psychedelic research, “set” refers to one’s mindset heading into the experience, and “setting” refers to the environment or context in which it takes place.

• Mindset (“Set”): This includes your mood, expectations, past experiences, and current emotional well-being. If you come into an infusion feeling anxious, distressed, or uncertain, the pharmacological effects of ketamine might amplify those feelings. This results in a more turbulent session. Conversely, if you arrive calm, open, and prepared, you may experience a more soothing or insightful journey.
• Environment (“Setting”): The clinical setting, the presence (or absence) of supportive staff, the lighting, sound, and even subtle cues in the infusion room can all shape the subjective nature of a ketamine session. A quiet, softly lit room with comforting music can promote relaxation, whereas a busy environment with unfamiliar sounds may trigger tension and detract from the therapeutic effects.

Because mindset and environment can shift between sessions, it’s not uncommon for one infusion to feel deeply peaceful and enlightening, while the next might be challenging or even unsettling.

3. Biological Variability from One Session to the Next

While mindset and environment play a significant role, biological variability is another major influence. The human body is not a static system. It changes day to day based on numerous internal and external factors, such as:

1. Hormonal fluctuations: Hormones like cortisol, estrogen, and testosterone can influence mood, anxiety levels, and pain thresholds. These hormones vary throughout the day and month, affecting how ketamine interacts with your neurobiology.
2. Sleep: Getting sufficient sleep is critical in all areas of life including your overall sense of well-being and mental health. When you are sleep-deprived your experience during a ketamine session will likely be quite different than when you are well rested.
3. Nutritional status: Your diet and hydration level can impact how your body metabolizes ketamine. If you’re dehydrated or have a recent history of poor nutrition, your infusion experience might differ from a time when you are well-fed and adequately hydrated.
4. Medications and supplements: Other prescription medications, over-the-counter drugs, or supplements you’re taking may modify ketamine’s effects. For instance, certain antidepressants or anxiolytics can either potentiate or diminish ketamine’s impact.
5. Underlying health conditions: Chronic illnesses or acute infections can throw your system off balance, thus changing how your body responds to ketamine on any given day.
6. Progressive tolerance and neurochemical shifts: With repeated treatments, you might develop a slight tolerance to certain psychoactive effects of ketamine. This means you may not feel the same intensity you once did. On the other hand, ongoing neurochemical shifts spurred by ketamine’s antidepressant properties could also transform your subjective experience over time.

These variables, both predictable (e.g., your monthly cycle if you menstruate) and unpredictable (e.g., an unexpected migraine), make each ketamine session unique, even if the dose and setting remain the same.

4. Dose Adjustments and Infusion Protocols

Ketamine infusion therapy is relatively customizable. Clinicians typically begin with an established protocol—often a dose calculated based on your weight or on widely accepted medical guidelines—and then adjust it as needed. This means that one session might be administered at a slightly higher or lower dose than a previous one. This will help to optimize therapeutic effects while minimizing uncomfortable side effects.

• Rate of infusion: Some clinics deliver the ketamine infusion over 40 minutes, while others may extend it to 60 minutes or longer. Even small variations in the rate of infusion can lead to differences in how the ketamine is perceived. This can produce a gentler onset or a more abrupt shift in consciousness.
• Adjunct medications: In some cases, clinicians might add adjunct medications such as benzodiazepines to help manage anxiety or nausea. The presence of these medications can alter the nature of the ketamine experience, making it feel less intense or more sedating.
• Booster sessions: Some treatment plans involve “booster” infusions weeks or months apart. These might be administered at a different dose or infusion rate than the initial protocol, creating a different subjective experience.

Because ketamine therapy is an evolving field, there isn’t a one-size-fits-all approach. Clinicians adjust treatment regimens to strike the right balance between effectiveness and safety, making it more likely that you’ll notice variances from one infusion to the next.

5. Psychological and Emotional Processing

Ketamine can stimulate intense introspective states, where memories, emotions, and thought patterns surface in unusual ways. During an infusion, some people experience vivid imagery, recall past traumas, or gain sudden insights into their personal lives. These psychological and emotional processes can differ drastically from one session to the next, sometimes even from moment to moment within the same session.

• Emotional readiness: If you’ve been working with a therapist or counselor to address core issues in your life, you may be more psychologically prepared for certain emotional revelations than at other times. The additional readiness can lead to deeper insight during one session. Whereas a previous infusion might have felt more disjointed or confusing.
• Shifts in personal life stressors: If you recently resolved a conflict with a loved one or achieved a major life milestone, your emotional landscape might be more stable, potentially facilitating a gentler ketamine experience. Conversely, unresolved stressors or traumatic events might surface more prominently during a subsequent infusion, leading to a more intense or challenging journey.
• Integration between sessions: The period between ketamine infusions is crucial for integration—reflecting on the experience, journaling, or talking with a mental health professional about what arose during treatment. This integration process can fundamentally change how you approach the next session. This can influence your mindset (and thus your experience) when you go back for another infusion.

6. Making the Most of Every Ketamine Infusion

Given how many different variables can shape your ketamine experience, it’s natural to feel a little uncertain about how each session will unfold. However, there are proactive steps you can take to make each session as beneficial as possible:

1. Communicate with your care team: Keep an open dialogue about how you felt during previous infusions. Your doctor or nurse can make informed decisions about adjusting the dose or adding supportive measures if needed.
2. Prioritize self-care before and after: On the day of your infusion, try to get adequate sleep, eat balanced meals, and stay hydrated. After the session, take time to rest, reflect, and avoid overwhelming social or professional obligations until you feel more grounded. Avoid or minimize social media, watching the news, horror movies and anything else that brings up stressful or disturbing emotions.
3. Practice relaxation techniques: Techniques like mindfulness, deep breathing, or gentle stretches can help you settle into a calm and receptive state before the infusion begins.
4. Create a supportive environment: If possible, bring comforting items—a blanket, a small pillow, or a meaningful object—that can provide a sense of security. Music, if approved by your clinic, can also help set a reassuring mood.
5. Integrate, integrate, integrate: Perhaps the most critical step is integrating the insights from your ketamine sessions into everyday life. Keep a journal, talk to a therapist, or join a support group to help ground and make sense of your experiences.
6. Embrace the experience: Allow each session to unfold as it naturally does and try not to force it to be something else. Some infusions may be more challenging than others. It tends to be counterproductive to avoid or fight against the experience.

7. Conclusion: Embrace the Variability

No two ketamine infusions are exactly the same. This variability can be both challenging and rewarding. Factors such as set and setting, biological fluctuations, dosage adjustments, and ongoing emotional work all combine to make each session its own unique journey. Rather than viewing this variability as a sign that something is “wrong” or that ketamine isn’t working, consider it part of the process of exploration and healing.

By approaching each session with openness, communicating honestly with your care team, and dedicating time to integration, you can create a supportive framework that allows you to benefit from ketamine’s full therapeutic potential—even when the experience feels different each time. As with any form of mental health treatment, remember to be patient with yourself, celebrate the small victories, and seek professional guidance along the way. The pathway to deeper healing is often non-linear, and each session might bring new insights, changes, or challenges. It can ultimately lead to profound, life-affirming growth.

NW Ketamine Infusion

January 31, 2025

Disclaimer: This blog does not constitute medical advice but rather a synthesis of published reports and accumulation of personal experience in treating patients using ketamine. The information in this post should not be used to guide medical decisions.