Esketamine vs. Psychedelics: What’s the Difference in Experiential States?

We have been waiting for psychedelic-assisted therapy, journalists have been talking about its arrival for years, so is it here yet?

Interest and demand for psychedelic states as a means of psychological healing continues to grow – but does the only FDA-approved medicine of this type, Esketamine (Spravato), deliver a psychedelic experience and relief from depression? And is it the expanded state of consciousness itself that causes the relief? We’ll get into this and more here.

Is Esketamine a psychedelic?

That depends on what we mean by the word “psychedelic.” Does Esketamine deliver an altered state of consciousness? Yes. Is Esketamine a “classic psychedelic” working on the 5-HT2A receptor? No. Is it the psychedelic experience that causes the healing or the neurochemical changes? The answer to this depends on who you talk to.

If we examine both what we mean by psychedelic and what we are hoping for when we ask this question, we can get a better understanding of what to expect from Esketamine, experientially and in terms of healing depression.

At Sub Rosa Therapy and Sub Rosa Behavioral Health, we work with Esketamine (Spravato) as part of a medically supervised treatment for depression. This post will look at how Esketamine fits into the broader conversation around psychedelics, and how it can be combined effectively with therapy to create lasting change.

What Is Esketamine?

Esketamine is a fast-acting antidepressant derived from ketamine, a dissociative anesthetic that’s been used safely in medical settings for decades. Esketamine, delivered as a nasal spray under the brand name Spravato, is FDA-approved for treatment-resistant depression and depression with suicidal ideation.

At Sub Rosa, Esketamine is administered in a controlled, clinical setting under the supervision of trained medical professionals, as required. But our focus is different than many other Spravato clinics because we protect the non-ordinary awareness of Esketamine as an essential part of the healing process, not just a side-effect.

We believe that results can last long beyond the timeframe in which neuroplasticity is enhanced by Esketamine when we engage in anti-depressive behaviors and integrate the meaning from the psychedelic state. We do this by holding space for each Spravato experience (set + setting), integrating the experience in the immediate aftermath (taking notes) and participating in the work of therapy (deepening our understanding of ourselves and others).

While Esketamine produces profound states of consciousness in many people, these states tend to be deeper at the first session and in the beginning or “induction phase” of treatment. Subsequently the effects taper or are less intense. At Sub Rosa, one of our staff is always with you in the room to talk, take notes, or just be there to hold space for you.

What Are Classic Psychedelics?

Back to the initial thought: What do we mean by psychedelic? Let’s review the “classic psychedelics,” which are: 5-MeO-DMT, psilocybin (magic mushrooms), LSD, ayahuasca, and mescaline. These substances act primarily on serotonin (5-HT2A) receptors, and reliably induce vivid visual or auditory hallucinations, deep spiritual or existential insights, and maybe even Ego Death.

While there is promising early clinical research, these substances remain Schedule I under federal law in the U.S., meaning they are not currently available in most therapeutic settings outside of clinical trials—with the notable exception of Oregon, which has established a regulated, non-medical psilocybin services program allowing supervised use by trained facilitators at licensed centers.

A Side-by-Side Comparison:

Although Esketamine and the classic psychedelics can both induce transformative states of mind, they differ significantly in their mechanisms of action, legal status, therapeutic context, and the nature of the experiences they provide.

Esketamine (marketed as Spravato) is FDA-approved for treatment-resistant depression and depression with suicidal ideation. It works through a different neurochemical pathway—as an NMDA receptor antagonist—unlike the classic psychedelics, mentioned above.

While the experience of Esketamine tends to be dissociative, inward-facing, and dreamlike, the classic psychedelics often produce hallucinations, expansive perceptions, and mystical or visionary states. They are very different experientially, but both provide shifts in consciousness (both during and after the acute experience).

Even when Esketamine starts to wane in its intensity, after the first month’s induction period of twice a week treatments, it still provides an important inner state to be explored. The lighter shift in awareness offers deeper ability to bond and heal attachment patterns and a greater ease with talking about defenses and patterns that no longer serve us.

At Sub Rosa, your note-taking sitter is there to ensure that these changes in awareness are captured on paper and that you feel felt and seen in your new ways of being and knowing. This is the beginning of the process of psychedelic integration, as well as the important containment principle of set and setting. We believe the sitter who holds space without judgment or interpretation is essential to how the medicine works. Psychedelics alone are not magic – but people are magic when they are present for each other (and psychedelics can help with that).

It is in this state that we unfold the pain of the past and heal it, and we do this together.

Is Esketamine Still Transformative?

Yes. Esketamine’s dissociative effects can create distance from habitual thought patterns (the “default mode network”) allowing clients to observe their emotional landscape from a new vantage point. At Sub Rosa, clients lie down comfortably on a mat with blankets and a pillow, they wear a blackout eyeshade, and they listen to instrumental music through headphones and/ or a speaker in the room.

Many clients describe feeling a renewed sense of possibility, emotional relief, and insight. While far less visually commanding than the classic psychedelics, Esketamine often feels like a transformative emotional journey through space (guided by music) ending with a gentle landing into a more spacious awareness. This spacious awareness is the feeling of enhanced neuroplasticity – a tool that can be used in therapy to create ongoing change.

When paired with skilled integration therapy, Esketamine sessions can be a powerful catalyst for trauma healing, identity work, and nervous system regulation. Our clinical team integrates modalities such as Somatic Experiencing, Internal Family Systems, and Acceptance and Commitment Therapy to support this process.

Choosing the Right Path for You

If you’re seeking a legal, structured, and trauma-informed way to access non-ordinary states of consciousness in therapy, Esketamine may be an ideal option. Keep in mind that while the treatment is covered by insurance, only those with treatment-resistant depression are eligible for Spravato. (On the other hand, generic ketamine, which Sub Rosa Therapy also offer where clinically and medically appropriate, has a wider range of clinical indications including PTSD, OCD and depression. The drawback is that as an off-label generic it is not covered by any insurance.)

At Sub Rosa Therapy, we conduct thorough psychiatric and medical evaluations to ensure each client is a good candidate. We also provide preparation, therapeutic support during sessions, and post-session integration, all of which are essential to create meaningful and lasting change.

In conclusion, Esketamine is not a classic psychedelic, but it does offer a powerful opportunity for transformation. At Sub Rosa, we honor its unique potential by combining medical oversight with deep and immediate therapeutic integration. If you’re looking to move through depression, trauma, or long-standing emotional patterns that keep you in avoidance or turmoil, Esketamine-assisted therapy might be the next right step on your healing journey.