How does IV Ketamine work?

IV Ketamine works by blocking NMDA receptors in the brain, which helps to rapidly restore neural pathways and alleviate symptoms of depression.

How long does a session take?

A typical IV Ketamine infusion session lasts about 40 to 60 minutes, followed by a brief recovery period in our clinic.

IV NAD+ Therapy With Ketamine: How It Works

Most people don’t go looking for NAD+.

They arrive there indirectly, after years of trying to fix something that doesn’t quite respond. Medications that flatten more than they restore. Therapy that helps but doesn’t fully shift the baseline. Or more recently, ketamine, which can create something rare in mental health: a rapid, undeniable change.

And then comes the question. What allows that change to hold?

That question is where NAD+ belongs. Because if ketamine operates at the level of signal, how neurons communicate, NAD+ operates at the level beneath it: whether those neurons have the energy, stability, and resilience to sustain anything new.

This isn’t about stacking treatments. It’s about understanding layers of biology that are usually treated in isolation.

Why Combine IV NAD+ With Ketamine Infusions?

Ketamine’s effect is often described as a reset. That’s not wrong, but it’s incomplete.

What it actually does is more precise and more fragile. By blocking NMDA receptors, ketamine triggers a surge in glutamate signaling that rapidly activates pathways tied to neuroplasticity. Within hours, the brain begins increasing BDNF, reorganizing synaptic connections, and loosening patterns that may have been fixed for years.

For a period of time, the brain becomes unusually capable of change. That window is the opportunity. It is also the risk, because plasticity without support doesn’t necessarily lead to stability. It can just as easily collapse back into the same patterns if the underlying cellular environment hasn’t shifted. This is the part most conversations skip.

Neuroplasticity is not just a signaling event. It is metabolically expensive. Building and stabilizing new synaptic connections requires energy, intact mitochondrial function, controlled inflammation, and the ability to repair cellular stress as it happens. That entire system depends on NAD+.

NAD+ is not a mood enhancer. It does not produce a subjective “lift” in the way ketamine can. Its role is quieter and more fundamental. It sits inside every neuron, enabling the processes that keep that neuron functional under stress, producing ATP, repairing DNA damage, and activating sirtuins that regulate inflammation and cellular survival. When NAD+ levels are low (and they often are in the context of chronic stress, depression, or substance use), the brain is operating with reduced capacity at exactly the moment it is being asked to change.

That mismatch matters. Ketamine initiates the shift. NAD+ supports the conditions required to sustain it. They are not overlapping interventions. They are sequential in logic, even when administered in parallel. One creates possibility. The other helps make that possibility durable.

There is, to be clear, no large-scale randomized trial that has tested this combination directly. That absence is real, and it should be acknowledged, but the absence of a combined trial is not the absence of a rationale. We have decades of research describing how ketamine drives synaptic plasticity, and equally deep literature showing how NAD+ regulates mitochondrial function, neuroprotection, and cellular repair. When you place those two bodies of evidence next to each other, the relationship becomes difficult to ignore.

Plasticity demands resources. NAD+ helps supply them. And in clinical practice, that distinction shows up not as theory, but as a difference in how patients stabilize after the initial breakthrough - whether the gains fade quickly or begin to organize into something more consistent.

What Is IV NAD+ Therapy, Really?

There’s a tendency to introduce NAD+ like a definition, a coenzyme involved in cellular metabolism, and move on. While technically correct, it misses the point. What matters is not what NAD+ is, but what stops working when it isn’t there in sufficient amounts.

Every neuron in your brain is metabolically demanding. It is constantly maintaining electrical gradients, recycling neurotransmitters, repairing minor damage, and adapting to new inputs. None of that happens passively. It requires energy, and not in a vague sense—specifically, it requires ATP, produced inside mitochondria.

NAD+ is essential to that process. Without adequate NAD+, the machinery that produces cellular energy slows down. The cell doesn’t die, but it becomes less efficient, less adaptable, and more vulnerable to stress. Over time, that reduced capacity shows up in ways that feel psychological but are deeply biological: slower thinking, reduced emotional range, difficulty recovering from stress, a kind of internal drag that isn’t easily explained.

This is one of the reasons NAD+ has become relevant in conversations about mental health. Not because it targets mood directly, but because it supports the systems that allow mood regulation to happen at all.

It also plays a second role that’s easier to overlook but just as important: repair. Neurons accumulate damage constantly, oxidative stress, DNA breaks, inflammatory signaling. Under normal conditions, that damage is managed and resolved. NAD+ is required for many of those repair pathways, including the activation of sirtuins, proteins that help regulate inflammation and cellular survival.

When NAD+ levels decline, repair doesn’t stop entirely. It becomes less effective. The system drifts. Small inefficiencies compound. And over time, the brain becomes less resilient to the very stressors it’s trying to adapt to. This is not a single-cause explanation for depression or anxiety. It’s something more subtle: a shift in baseline capacity.

IV NAD+ therapy is designed to intervene at that level. By delivering NAD+ directly into the bloodstream, it bypasses the bottlenecks of digestion and conversion that limit oral supplements. The goal is not stimulation. It’s restoration—bringing cellular systems back to a level where they can respond appropriately to other treatments, including ketamine.

Why NAD+ Levels Matter More Than Most People Realize

It’s easy to think about mental health as a problem of signaling: too much of one neurotransmitter, not enough of another. That model has dominated psychiatry for decades. It’s also incomplete.

Neurotransmitters don’t operate in isolation. They depend on the condition of the cells producing and responding to them. And those cells, in turn, depend on energy, repair, and inflammatory balance - all processes that are influenced by NAD+.

When NAD+ levels decline, several things begin to shift at once. Mitochondria become less efficient, which reduces the energy available to neurons. That alone can affect how consistently neural circuits fire and reset. At the same time, the regulation of oxidative stress becomes less precise, leading to low-grade inflammation that can interfere with signaling pathways tied to mood and cognition.

There is also an effect on adaptability. Proteins like SIRT1, dependent on NAD+, play a role in how the brain responds to stress, both at the cellular level and in broader regulatory systems. When those pathways are under-supported, the brain becomes more reactive and less flexible, which is a pattern that shows up across depression, anxiety, and trauma-related disorders.

What’s important here is not to reduce everything to NAD+, but to recognize that it sits at a point of convergence. Energy, inflammation, repair, stress response are not separate problems. They are overlapping systems, and NAD+ is involved in all of them. That’s why restoring it can have effects that feel disproportionate to how simple the intervention appears on the surface.

NAD+ and Depression: A Shift Beneath the Symptoms

One of the more interesting developments in recent research is the connection between NAD+ metabolism and depressive states, not just behaviorally, but at the level of brain function. In preclinical models, disruptions in NAD+ biosynthesis, particularly through the NAMPT pathway, are associated with changes in mood-related behavior and reduced function in the prefrontal cortex. When NAD+ levels are restored, those patterns begin to reverse: behavioral markers improve, and proteins associated with neuroplasticity, like BDNF, increase.

There’s a temptation to translate that directly into clinical claims, but that would be premature. Human data is still limited, and it’s important not to overstate what we know. What these findings do suggest, however, is that depression is not only a disorder of signaling. It is also a disorder of capacity.

If the brain does not have the metabolic support required to adapt, even effective therapies can have diminished impact or shorter duration. This is part of the reason some patients respond to ketamine but struggle to maintain the gains. The signaling shift occurs, but the underlying systems are still under strain.

NAD+ doesn’t replace antidepressant effects. It changes the conditions in which those effects have to operate.

NAD+ and Addiction: Where the Clinical Signal Is Strongest

If there is one area where NAD+ has moved beyond theory into observable clinical impact, it’s addiction. Substance use places sustained stress on the brain’s reward systems, energy metabolism, and stress regulation pathways. Over time, this creates a state where cravings are not just psychological, they are reinforced by underlying biological instability.

In a 2022 observational study of 50 patients undergoing IV NAD+ therapy for substance use disorder, researchers reported significant reductions in cravings, anxiety, and depression scores over the course of treatment.

The study design matters. It was not randomized or blinded, but the consistency of the signal is difficult to dismiss. What’s notable is not just symptom reduction, but the pattern: patients often report a decreased intensity of withdrawal and a greater sense of stability during early recovery.

That aligns with what we would expect mechanistically. If NAD+ helps restore cellular energy and reduces stress-related dysregulation, it may not eliminate cravings entirely, but it can lower the amplitude of the system generating them.

In practice, that can be the difference between constant internal friction and something more manageable.

NAD+ and Anxiety / PTSD: Regulation, Not Suppression

Anxiety and trauma-related conditions are often approached as problems of overactivation: too much signaling, too much reactivity. But underneath that is often a different issue: difficulty returning to baseline. The nervous system becomes efficient at activating, but inefficient at settling.

NAD+-dependent pathways, particularly those involving sirtuins, play a role in regulating this balance. They influence inflammation, stress signaling, and cellular resilience, factors that determine how quickly and effectively the system can recover after activation. This is why NAD+ is not experienced like an anxiolytic. It doesn’t blunt the response in the moment. Instead, over time, it can help recalibrate the system so that responses are less extreme and recovery is more complete.

Again, the clinical research here is still developing. But the biological rationale is consistent with what we see across related fields: improving baseline cellular function tends to improve system-level regulation.

What the Research Shows, And What It Doesn’t

There’s a way to talk about emerging treatments that sounds confident but avoids precision. It leans on phrases like “shown to help” or “clinically proven” without ever making clear what, exactly, has been proven and in what context. That approach is common. It’s also unnecessary.

The reality is more nuanced, and ultimately more useful. Ketamine is well-supported. Its antidepressant effects, particularly in treatment-resistant depression, have been demonstrated across multiple controlled studies. The mechanism is increasingly understood: NMDA receptor antagonism, a glutamate surge, downstream activation of BDNF and mTOR pathways, and rapid synaptogenesis. That part of the landscape is solid.

NAD+ sits in a different category. We have strong mechanistic evidence showing that NAD+ is central to mitochondrial function, DNA repair, and neuronal resilience. We also have growing literature linking NAD+ depletion to neurodegeneration, aging, and stress-related dysfunction in brain cells.

There are also early clinical signals. In addiction medicine, observational data has shown meaningful reductions in cravings, anxiety, and depressive symptoms following IV NAD+ infusions. But for mood disorders more broadly, and especially for the combination of NAD+ with ketamine, we do not yet have large randomized controlled trials.

That gap matters. It should be stated directly. At the same time, the absence of a combined trial does not make the approach speculative in the way people often assume. Medicine frequently advances by integrating well-understood mechanisms before formal combination studies catch up. What matters is whether the underlying logic is coherent and whether clinical outcomes align with that logic.

Here, the logic is straightforward. Ketamine increases the brain’s capacity for change. NAD+ supports the cellular systems that allow that change to stabilize. One operates at the level of signaling. The other at the level of function. The question is not whether they do the same thing - they don’t. The question is whether they address different constraints within the same system.

In practice, that is exactly how they are used.

Learn more:
https://www.fountainnyc.com/IV-Ketamine

What to Expect During IV NAD+ Therapy

The experience of NAD+ therapy is often misunderstood before a patient ever sits in the chair. It is not like ketamine. There is no perceptual shift, no dissociation, no altered state to navigate. If anything, the contrast is part of the design. Where ketamine is acute and nonlinear, NAD+ is steady and physiological.

A typical session lasts between two and three hours. The infusion is gradual by necessity—not because of inefficiency, but because the body responds to NAD+ in real time. At higher rates, patients can feel a distinct sense of pressure or discomfort: warmth moving through the chest, a tightening sensation, sometimes mild nausea. These effects are not dangerous, but they are informative. They reflect how actively the compound is interacting with metabolic pathways. When the infusion is slowed, those sensations ease almost immediately.

Over the course of a session, most patients settle into a rhythm. It becomes less about “getting through” the infusion and more about allowing the body to adjust to it. Some read, some listen to music, some simply rest. Afterward, the effect is rarely dramatic in the way ketamine can be. There is no sudden shift in mood or perspective. Instead, patients often describe something quieter: clearer thinking, less internal friction, a sense that energy is more available than it was before. It is not a peak experience. It is a recalibration. And like most recalibrations, it becomes more apparent over time rather than all at once.

Who This Is For, And Who It Isn’t

Not every intervention needs to be for everyone. In fact, the more precisely a treatment is used, the more effective it tends to be. IV NAD+ therapy is most relevant in a specific context: when the goal is not just to initiate change, but to support the systems that allow change to persist.

That includes patients who are already undergoing ketamine therapy and want to extend or stabilize their response. It also includes individuals with treatment-resistant depression, chronic anxiety, or PTSD, particularly when those conditions are accompanied by fatigue, cognitive slowing, or a sense of diminished resilience.

There is also a clear role in addiction recovery, where the combination of physiological stress and psychological instability creates a high-friction environment for healing. At the same time, this is not a universal solution. It is not designed as a standalone treatment for acute psychiatric symptoms. It does not replace therapy, medication, or other interventions when those are indicated. And it is not appropriate for every patient.

Certain medical conditions, such as pregnancy or specific kidney disorders, require exclusion or careful evaluation. A proper intake is not a formality; it is part of ensuring that the treatment is used in the right context, for the right reasons.

Precision matters here. More is not better. Better is better.

How Treatment Is Structured

If ketamine is episodic, administered in a defined series, NAD+ is more gradual in how it builds. Most protocols begin with a loading phase. This typically involves several infusions over the course of one to two weeks, allowing NAD+ levels to rise in a way the body can tolerate and adapt to. The emphasis is not on intensity, but on consistency.

From there, the approach shifts into maintenance. Maintenance is not a fixed schedule so much as a response to how the patient is doing. For some, that means weekly sessions for a period of time. For others, it becomes monthly or intermittent. The goal is not to maintain a number, but to maintain function.

This is where individualized care matters. Two patients can present with similar symptoms and respond very differently. One may stabilize quickly and require minimal follow-up. Another may need a longer runway before the effects become consistent. The protocol adjusts to that reality rather than forcing a standardized path.

In many cases, NAD+ is scheduled on separate days from ketamine to allow each intervention to do its work without overlap, while still supporting the same broader objective.

IV NAD+ vs. Oral Supplements

There’s a persistent assumption that IV NAD+ is simply a more intense version of taking a supplement. It isn’t.

Oral NAD+ precursors, such as NMN or nicotinamide riboside, rely on a multi-step process. They are absorbed through the digestive system, converted through metabolic pathways, and only then contribute to NAD+ levels in the body. That process is not inefficient, but it is limited. The amount that ultimately becomes available to brain tissue is constrained.

IV administration changes that equation. By delivering NAD+ directly into the bloodstream, it bypasses those conversion steps entirely. The concentration achieved is higher, the availability is immediate, and the effect is not dependent on how well the body processes a precursor.

This is why the two approaches serve different purposes. Oral supplementation can support baseline health over time. IV therapy is used when there is a need to intervene more directly, when the goal is not incremental support, but restoration under clinical supervision.

They are not interchangeable. They operate at different scales.

Questions Patients Actually Ask

Most questions about NAD+ are not technical. They’re practical, and often unspoken.

What will this actually do for how I feel?

It doesn’t create an immediate emotional shift. What it tends to do is reduce the underlying friction—mental, physical, and cognitive—that makes everything else harder. Over time, that can translate into more stable mood regulation.

How does this fit with ketamine?

Ketamine initiates change at the level of neural signaling. NAD+ supports the cellular systems that allow those changes to stabilize. They operate in different domains, but toward the same outcome.

Is there real evidence behind this?

There is strong mechanistic evidence and emerging clinical data, particularly in addiction recovery. Large-scale trials for mood disorders and combination therapy are still developing, and that should be understood going in.

Are there side effects?

During infusion, patients may experience warmth, pressure, or mild nausea. These are dose-dependent and resolve when the rate is adjusted. Serious adverse effects are rare under proper medical supervision.

How quickly will I notice a difference?

Some patients notice changes during the initial series, but the effect is typically cumulative. It’s less about a single moment and more about a shift in baseline over time.

Where This Fits in the Larger Picture

There is a tendency in mental health treatment to look for singular solutions, one intervention that resolves the problem completely. That model doesn’t reflect how the brain actually works. The brain is not a single system. It is a set of interdependent processes: signaling, structure, energy, repair. When one of those is addressed in isolation, the result can be meaningful but incomplete.

Ketamine addresses signaling and plasticity with unusual speed and effectiveness. That alone has changed the landscape. NAD+ addresses something quieter but just as necessary: whether the brain has the capacity to sustain what ketamine makes possible. Neither replaces the other. Neither stands alone. But when they are used with a clear understanding of what each is actually doing, not just what it’s called, the result is not just change, but the possibility of stability.

And in this context, stability is the harder problem. It’s also the one that matters most.

In Closing

If you are already exploring ketamine therapy, or if you have experienced partial relief but not lasting stability, it may be time to look at the systems underneath the symptoms.

NAD+ therapy is not a shortcut. It is a way of supporting the biological conditions that allow meaningful change to take hold.

To learn whether this approach is appropriate for you, schedule a clinical consultation with our team.

Start here:
https://www.fountainnyc.com/contact/

References

Kolotyeva NA et al. Pathobiochemistry of Aging and Neurodegeneration.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673498/

Blum K et al. NAD+ Infusions in Substance Use Disorder.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9474872/

Krystal JH et al. Ketamine and rapid antidepressant action.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700627/

Lv S et al. NMDA receptors in depression treatment.
https://pubmed.ncbi.nlm.nih.gov/36539011/

Mou NH et al. Mechanisms of ketamine antidepressant effects.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9082546/

Chen C et al. BDNF and ketamine mechanisms.
https://www.mdpi.com/1422-0067/25/23/13098

Xu J et al. SIRT1 and neuroprotection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265504/

Jesko H et al. Sirtuins in brain aging.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357501/

Zhang X et al. NAD+ biosynthesis and depression.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775136/

Bogan KL, Brenner C. NAD+ precursor metabolism.
https://pubmed.ncbi.nlm.nih.gov/18429699/

Authorship

Editorial Staff
Fountain Health

This article was developed by the clinical and research team at Fountain Health, an interdisciplinary practice specializing in interventional psychiatry and treatment-resistant mood disorders. Content is informed by current peer-reviewed research and clinical protocols used in patient care, including ketamine infusions and adjunctive therapies such as NAD+.

Our approach emphasizes evidence-based care, biological precision, and long-term outcomes for patients who have not responded to traditional treatments.

All medical content is reviewed for accuracy, clinical relevance, and alignment with evolving evidence in neurobiology, psychiatry, and metabolic health.

IV NAD+ Therapy: What It Does in Your Brain and How It Works With Ketamine