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Should I Stop Using Antidepressants For Psychedelic Therapy?

Research institutions, universities, media and news reportings have paraded psychedelics as powerful therapeutic agents in the eyes of the public—and for good reason. Studies repeatedly prove how influential these substances are. 

Promising conclusions regarding psychedelics for depression and anxiety—specifically in treatment-resistant cases—are leading many people toward guided psychedelic therapy as a healing modality or last resort.

According to a CDC review, antidepressants are the third most common prescription drug taken by US citizens of all ages (Pratt et al., 2005-2008), but over 30 million citizens have used psychedelic drugs in their lifetime (Krebs and Johansen, 2013).

Psychedelics may indeed have a particular allure that regular talk therapy or prescription medications don’t have, but did you know that certain medications and antidepressants can affect the experience?

For many mental health conditions, deep and transcendent change is certainly needed to address the complex mechanisms at play. However, it is important to understand the potential interactions for antidepressants and psychedelics.

In this article, we’ll explore the effects of antidepressants on the psychedelic experience and the brain, as well as the best way to approach a therapeutic psychedelic experience if you are on SSRIs. 

Antidepressants & Therapeutic Psychedelics in The Depressed Brain

While there is still much unknown about how antidepressants and psychedelics interact with neural mechanisms and processes, let’s explore what science has shown us so far.

How Depression and Antidepressants Affect The Brain

In the medical community, there seems to be two opposing theories on if depression originates from a chemical imbalance or from a “disorder of the hardwiring of the brain” (Andrade and Rao, 2010).

While there are less reductionist theories, antidepressants are believed to work by possibly adjusting chemical imbalances in the brain, increasing neuroplasticity, or counteracting the effects of prolonged exposure to stress. 

Antidepressants inhibit or increase the reuptake and breakdown of monoamine neurotransmitters, which are essentially the communicative molecules passed between electrically excitable cells.

Examples of monoamine neurotransmitters are dopamine (motivation), norepinephrine (arousal), and serotonin (mood and cognition) and are responsible for modulating the faculties of emotion, memory, and behavior. 

Depression medication treatment is founded on the idea that depression and other disorders and conditions are a result of physical or biological abnormalities of the brain, but many find this view to be overly simplistic.

This medical model often ignores the complexity of the human body and mind and does one thing that science warns us not to do: assumes causation when only correlation has been confirmed. Addressing observable chemical imbalances via antidepressants can be beneficial but is not a guaranteed, long term solution to the mysterious manifestation of symptoms.  

To bring it back to the topic at hand, the purpose of this article is not to criticize antidepressants or discourage anyone from taking them. Instead, we merely want to highlight that it is still up for debate how these drugs really work.

Antidepressants are important and beneficial tools for many people to manage their mental health issues, and we encourage you to listen to your healthcare professionals and utilize the tools available to you. 

The Different Types of Antidepressants and Their Processes

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Serotonin-noradrenaline reuptake inhibitors (SNRIs)
  • Serotonin antagonists and reuptake inhibitors (SARIs)
  • Norepinephrine-dopamine reuptake inhibitors (NDRIs)
  • Noradrenaline and specific serotonergic antidepressants (NASSAs)
  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)

The most well-known and commonly prescribed antidepressant category is SSRIs, because they have relatively low side effects, are more selective than other types, and have a higher threshold for overdose. 

These drugs block nerve cells from reabsorbing serotonin and/or norepinephrine after use, which allows those monoamines to be more readily available for transmitting information between neurons.

MAOIs are interesting in comparison to the other types for a few reasons. Firstly, MAOIs are not selective and act on multiple neurotransmitters. Secondly, while it is hardly used in comparison to SSRIs nowadays, it is commonly believed to be the most effective form of antidepressants. 

Monoamine oxidase is the enzyme that breaks down serotonin, dopamine, and norepinephrine, so an MAOI blocks the enzyme rather than the neurons themselves. Lastly, MAOIs are found in a wide variety of plant species and are actually the primary component of the ayahuasca brew, which is made of the MAOI-containing vine and a secondary, DMT-containing plant.

The reason behind this is that DMT (the spirit molecule) is too quickly broken down when ingested orally for it to be active. MAOIs block the breakdown of DMT so that it reaches the serotonin receptors.

How Psychedelics Work in the Brain

Let’s dive into this idea that both antidepressants and psychedelics increase neurotransmitters or neurotransmitter agonists in the brain, leading to higher levels of serotonin, dopamine, and norepinephrine. Interesting studies on the brain while on psychedelics have provided insight into what happens to the neurology of the human brain when on substances like psilocybin.

Serotonergic psychedelics, such as psilocybin, act as agonists for the serotonin 2A receptor (5-HT2AR), in other words, mimicking sensations of high levels of endogenous serotonin. 

Like antidepressants, serotonergic psychedelics also potentially increase synaptic density and neuroplasticity which decrease with age, but the topic isn’t as simple as increasing neurotransmitters in the brain. 

Psychedelics may help alleviate suffering through restraining overactive parts of the brain, allowing for feelings of oneness, expansiveness, and profound interconnectedness with the universe. 

In 2013, results from fMRI scans of participants administered with intravenous psilocybin showed profound evidence that psychedelics may turn down activity in parts of the brain associated with constructs of individualism (Turton et al., 2014).

The brains of participants had a reduction in blood flow in both cortical and subcortical locations, and, most notably, the medial prefrontal cortex—which is overactive in people with depression—showed decreases in activity. 

Decreased blood flow and activity were shown in the parts of the brain associated with the Default Mode Network, consciousness, and ordered cognition. This could suggest that depression and similar cognitive conditions are a result of too much filtering and self-construction, and not enough “zooming out” and tuning in.

Simply put, serotonergic psychedelics mimic endogenous neurotransmitters and flood our neurons with information, drastically altering blood flow and brain activity.

Should You Taper Off Antidepressants Before a Psychedelic Journey?

Now that we have established the interesting and intrinsically linked mechanisms that fuel the effects of both psychedelics and antidepressants, let’s move on to the real questions at hand. There are a lot of moving parts when it comes to combining psychotropic medications with psychedelic substances, but there are two primary issues with combining the two.

Firstly and the most common, antidepressants can block neurons from receiving the active components of the psychedelic, dampening the effects, and therefore requiring larger doses usually.

Conversely, combining certain psychotropic medications with psychedelics could lead to serotonin syndrome in which the brain is essentially flooded with serotonin and cannot metabolize it quickly enough. One outcome can be extremely disappointing if you were hoping for a mind blowing trip, and the other can be serious and require medical attention.

For this reason, if you are dedicated to having an intentional psychedelic experience, you may consider tapering off of medications, always first consulting your doctor or psychiatrist before decreasing dosing of an antidepressant. 

For serotonergic antidepressants, the general rule of thumb is to take 5 days to 2 weeks for tapering, but this varies based on your specific medication’s half life. For non-serotonergic psychotropic medications, you should consider having a fully clear system before approaching psychedelic medicines, but many of these medications luckily only require a few days of tapering. 

It is also important to note that not all psychedelics interact with antidepressants in the same way. For instance, 5-MeO-DMT, ayahuasca, and MDMA are generally not recommended and can be problematic if mixed with serotonergic psychedelics, whereas LSD and psilocybin mushrooms are generally safe.

When it comes to any psychedelic experience, preparation is an important part of the journey, and for those on prescription medications, consulting a doctor and creating a game plan for tapering off is part of that preparation.

Resources for Safely Tapering Off Antidepressants

In a past article, we provide a more in-depth guide for if and when you should stop taking antidepressants leading up to a therapeutic psychedelic journey. We also have other posts to help you navigate the complexity of having a safe trip, such as how to safely dose and how to speak with your doctor about wanting to take psychedelics.

While there are many reasons you might not trip that don’t involve antidepressants, consulting with a professional or expert can mitigate risks and also increase the likelihood of having a meaningful experience.

If the thought of stopping your medications is scary to you, this resource on how to taper may offer helpful tips, and microdosing may also help fill in the gaps while you wane off, since both act on the serotonin receptors. 

Overall, it is best to approach psychedelic medicines with reverence and caution, and practicing a diet beforehand—not just with foods but also with medications and mindful lifestyle habits—can help ensure a safe and transformative journey.

All these factors—the type of antidepressant, the particular psychedelic substance, the strain of mushroom, and individual variations in body composition—make it hard to predict and ensure the desired type of journey.

Having a professional guide during the preparation process as well as during the journey itself can provide an element of harm-reduction, expert consulting, and insight knowledge on how to benefit from psychedelic medicine generally.

Ready to Embark on Your Healing Journey? 

Are you ready to voyage into the mysterious and powerful realm of psychedelics, whether out of pure curiosity or a yearning for deep healing and metamorphosis? We at Psychedelic Passage connect seekers with a network of pre-vetted psychedelic guides who offer not only in-the-moment ceremonial assistance but also specialize in preparation, integration, and harm-reduction support.

If you feel called to journey in a safe and supported way, book a consultation with our call takers to get started. We also have a resources page with more information and articles on a wide variety of psychedelic-relevant topics. 

Frequently Asked Questions About Antidepressants & Psychedelics

Is it safe to take psychedelics if I’m on antidepressants?

Certain psychedelics, like psilocybin and LSD, are generally safer than others for someone with a history of antidepressant use. It can be unsafe to take psychedelic substances while on certain antidepressant medications. 

Tapering off of medications for a period of time prior to a psychedelic experience is the best way to ensure a safe trip. However, tapering off of medications can also be problematic and is best done in the guidance of a medical professional. 

Do antidepressants impact the effectiveness of psychedelic therapy?

Yes, antidepressants often block the effects of psychedelics and require larger dosing in order to feel the effects. 

When should I stop taking antidepressants leading up to psychedelic therapy?

For many psychotropic medications, the half life ranges anywhere from 1 day to 2 weeks. Consulting a half life calculator and a professional will be helpful in understanding the specific timeline for tapering off medications.




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At Psychedelic Passage, we offer professional 1-on-1 guidance and companionship on your journey of healing. We simply can't sit back and let Americans continue to sit in silent suffering trying to battle mental health issues within a broken health care system, all while knowing that effective alternatives exist. We stand for the sacred, at-home, ceremonial use of psychedelics for consciousness exploration, which we believe to be a fundamental human right.

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