Psychedelics vs Antidepressants – What Your Doctor Won’t or Can't Tell You
- Brainz Magazine
- 6 hours ago
- 8 min read
Dr. Katie Simons, PharmD, is a clinical pharmacist, transpersonal hypnotherapist, psychedelic medicine facilitator, and coach specializing in nervous system regulation, personal transformation, and holistic healing. She is the founder of The Holistic Apothec, a resource for coaching and education on healing through altered states of consciousness.
Millions of people take antidepressants every day, often without ever questioning how these medications actually work, or how effective they really are. At the same time, psychedelics are making headlines as a promising tool for depression, anxiety, and trauma, despite being largely illegal in much of the world. From ketamine to psilocybin to ibogaine, the results continue to stack up. It’s no wonder people are starting to ask, Could psychedelics replace antidepressants? Could they help me get off my medication? Or even, can they fix my brain?
The answers might surprise you, and they could change the way you think about healing the mind altogether.
Antidepressants vs psychedelics: Two very different approaches
At a glance, both antidepressants and psychedelics act on serotonin in the brain. But how they do it, and what that means for healing, couldn’t be more different. Antidepressants are designed to create stability by dulling the emotional extremes. They smooth over symptoms, allowing you to function more easily. Psychedelics, on the other hand, don’t suppress, they open things up. They amplify emotion, loosen rigid thought patterns, and bring to the surface the unresolved issues that may be driving your symptoms.
One way to think about it, antidepressants help you cope, psychedelics help you process. Coping can be useful, especially during a crisis. But staying in that mode long term can lead to numbness, disconnection, and a sense of being stuck. You might be getting through the day, but not really living.
Many mental health symptoms, like anxiety, depression, or dissociation, aren’t signs of a broken brain. They’re often intelligent signals from your nervous system saying something’s not right. According to Polyvagal Theory, these symptoms can reflect different states of survival response. For example, anxiety and irritability often show up when your body is in fight-or-flight mode. Fatigue, numbness, or depression can reflect a freeze or shutdown response. In both cases, the nervous system is doing its job, trying to keep you safe.
But instead of listening to these signals, we often override them. We keep going. We take the edge off with medication so we can manage work, relationships, and responsibilities, even if something deep down still feels off.
This is where psychedelics offer a different path. They temporarily quiet the brain’s defense systems, making it easier to access what’s underneath. They bring buried stress patterns into awareness so they can be released and integrated. Rather than masking symptoms, psychedelics help you hear them and, often, heal them.
What you probably don’t know about antidepressants
Despite how commonly they’re prescribed, there are several important things most people don’t hear from their doctors before starting antidepressants.
First, while antidepressants like SSRIs and SNRIs can be helpful for some people, the data show that for mild to moderate depression, they perform no better than placebo. The most benefit tends to show up in people with severe depression, but even then, the effects are modest and take 4 to 6 weeks to fully kick in.
Second, antidepressants were originally studied for short-term use, yet many people end up taking them for years. We don’t have robust long-term data on their safety or effectiveness beyond the acute treatment window. What we do know is that coming off them can be difficult, and for people who have taken multiple courses, the likelihood of staying off after stopping gets lower with each relapse. One analysis found that after a second or third episode of depression, patients are more likely to be placed on maintenance medication, often indefinitely.
We also don’t fully understand how these medications work, or what causes depression in the first place. The long-standing “chemical imbalance” theory has been widely debunked in the scientific literature. Neurotransmitters like serotonin are certainly involved, but depression is now understood to be a complex interplay of genetics, environment, trauma, stress response, inflammation, and more. Simply increasing serotonin doesn’t necessarily fix the deeper imbalance.
How psychedelics actually help the brain heal
Psychedelics aren’t magic bullets, but they do create a unique window of opportunity in the brain. One of their most profound effects is promoting neuroplasticity, your brain’s natural ability to form new connections and reorganize old ones. This helps explain why people often report insights, emotional clarity, and even shifts in behavior after a psychedelic experience. It’s not just a feeling, your brain is, temporarily, more receptive to change.
These substances also temporarily quiet the default mode network (DMN), a system in the brain involved in self-referential thinking and rumination. In depression, the DMN tends to be overactive, keeping people stuck in cycles of worry, shame, or hopelessness. By disrupting this network, psychedelics stop these rigid thought loops and open the door for new perspectives.
But here’s the catch, this flexibility doesn’t last forever. The neuroplastic “window” gradually narrows in the days and weeks after the experience. That’s why integration, how you reflect, take action, and support your nervous system afterward, is essential. Without it, insights may fade. With it, they can catalyze meaningful and lasting change.
One major study highlighted this potential. In a head-to-head trial, researchers compared two high-dose psilocybin sessions with six weeks of daily escitalopram (a commonly prescribed SSRI). Both groups saw improvements, but the psilocybin group had twice the rate of remission. More than that, participants reported increased emotional connectedness, greater self-awareness, and improved overall well-being.
So while antidepressants may help you tread water, psychedelics, especially when combined with intentional integration, just might help you learn how to swim.
Microdosing vs. macrodosing: What's the difference?
As interest in psychedelics has grown, so has the conversation around microdosing, taking sub-perceptual doses of a psychedelic like psilocybin or LSD, often a few times per week. Unlike macrodosing, where the goal is to induce a full psychedelic journey, microdosing aims to create gentle shifts in mood, energy, and perspective without the altered state. Some people compare it to a “mood vitamin” that makes the day feel a little brighter, lighter, or more creative.
While the research is still catching up, thousands of anecdotal reports and small studies suggest that microdosing may support nervous system regulation, emotional awareness, and subtle shifts in ingrained patterns, especially when paired with practices like meditation, hypnotherapy, or breathwork. Over the course of a 6- to 8-week microdosing practice, these subtle shifts can add up to profound changes. There is also data showing that you get those neuroplasticity effects when using certain microdosing protocols. It’s not a replacement for deeper therapeutic work, but it can serve as a helpful support.
Macrodosing, by contrast, involves a larger, immersive experience that can bring deep subconscious material to the surface. For some, this kind of journey catalyzes big shifts, emotional breakthroughs, spiritual insights, and perspective changes that echo for weeks or even months. But that doesn’t make it better or more effective than microdosing, just different. Some nervous systems are ready for the depth that macrodosing offers, while others benefit more from the slower, steadier rhythm of microdosing.
Both approaches offer valuable tools and have their place. Microdosing can gently build awareness and create momentum, while macrodosing can shake things loose and show you what’s been running the show underneath the surface. And when used intentionally, both can support the larger process of healing, growth, and self-sovereignty.
Can I use psychedelics while I'm on antidepressants?
One of the most common questions people ask is whether it's safe to take psychedelics while still on antidepressants. The short answer? It depends on the medication, and the psychedelic.
Classical psychedelics like psilocybin and LSD do not carry a known risk of serotonin syndrome when used in combination with SSRIs or SNRIs. Unlike MDMA, which has a more complex interaction with serotonin and demands greater caution, psilocybin and LSD work via a different mechanism and have been co-used with antidepressants without serious complications.
That said, antidepressants may blunt the effects of psychedelics, particularly at the emotional or perceptual level. People often report that the experience feels muted or less immersive. So while the combination may be physically safe, it may not offer the full range of benefits unless the antidepressant is reduced or tapered.
This is where individual context matters. For some, a gentler experience is actually preferable, especially early in the healing process. For others, the medication may need to be addressed before deeper psychedelic work can unfold. Either way, consulting with a knowledgeable professional is critical.
Can psychedelics help me get off antidepressants?
By now, some of you are probably wondering whether psychedelics could help you get off antidepressants. You’re not alone in this question. More people are asking as studies show the potential of psychedelics to support emotional healing in ways antidepressants often don’t. But transitioning off medication isn’t something to do impulsively, especially if you’ve been on them for a long time.
Tapering is essential. Antidepressants alter your brain’s neurochemistry, and stopping suddenly can trigger withdrawal symptoms like mood swings, insomnia, anxiety, and brain zaps. A gradual, individualized taper allows your nervous system time to recalibrate. Many people find it takes months, not weeks, to taper safely and effectively.
This is where psychedelics, especially psilocybin, may offer support. While they are not meant to directly replace antidepressants, they can create the right conditions for change, increased emotional clarity, enhanced neuroplasticity, and a deeper sense of meaning or purpose. For some, this can make the emotional work of tapering more productive. For others, it can reignite a spark that’s been dulled by years of symptom suppression.
Professional guidance matters. Coming off antidepressants and working with psychedelics are both nuanced processes. When combined, they require even more care. Working with someone who understands both pharmaceuticals and psychedelic integration, ideally with trauma-informed training in nervous system regulation, can be the difference between a rough transition and a truly healing one.
The bigger picture: Can psychedelics fix your brain?
It’s tempting to hope for a silver bullet, especially when you’ve been struggling with anxiety, depression, or emotional numbness for a long time. And while the early research on psychedelics is exciting, here’s the truth, psychedelics can open the door, but they don’t do the work for you.
Lasting change doesn’t come from one powerful trip. It comes from what you do after. Psychedelics may help reset your brain’s default patterns and boost neuroplasticity, but it’s up to you to build the new pathways. That means creating safety in your body, setting boundaries in your life, and practicing habits that support mental and emotional health.
We know from earlier in this article that many symptoms of depression and anxiety are rooted in nervous system dysregulation. Psychedelics can help you access and process the subconscious material driving those patterns, but you still have to identify what’s triggering your system. You still need to do the work of creating safety signals and repatterning old beliefs. This is where somatic therapies, hypnotic work, and trauma-informed modalities like EMDR or bilateral stimulation can make a big difference.
In other words, psychedelics can amplify the healing process, but they’re not a fix-all. They will fix your brain only if you’re willing to participate in your own healing. The best part? You’re more powerful than you’ve been taught to believe. When you begin listening to your body and working with your nervous system, you start to reclaim that power.
This is what self-sovereignty looks like. Psychedelics can remind you of who you are, but you’re the one who has to live it.
Ready to take the next step?
If you’re exploring the role of psychedelics in your healing journey, or questioning whether antidepressants are still serving you, you don’t have to do it alone. This path is complex, personal, and full of potential. With the right support, you can navigate it safely and powerfully. Learn more about working with me through my Transformational Taper Coaching program, The Path to Self-Sovereignty Microdosing program, or grab my free guide to microdosing here.
Read more from Katie Simons
Katie Simons, PharmD, Personal Transformation and Medical Coach
Dr. Katie Simons, PharmD, is the founder of The Holistic Apothec, a platform for coaching, education, and healing transformation through altered states of consciousness. A clinical pharmacist turned transpersonal hypnotherapist, psychedelic medicine facilitator, and coach, she blends neuroscience, somatic practices, trance techniques, and spiritual wisdom to guide clients in creating lasting change. Drawing on a decade in academic medicine and years in holistic healing, Katie’s programs focus on nervous system regulation, trauma recovery, overcoming limiting beliefs, and medication tapering. Her work bridges science and mysticism, offering a grounded, accessible path to deep healing, authentic living, and personal freedom.
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