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SSRIs, Antidepressants, and Psilocybin

In this episode transcript of the Psychedelic Passage podcast, co-founders Nick Levich and Jimmy Nguyen answer some of the most frequently asked questions about potential interactions between psychedelics and serotonergic medications. 

Should you stop taking your serotonergic medications if you’re looking to embark on a psychedelic journey? Who should consider tapering down and how long should you be off of your medications before working with psychedelics?

Episode 4: Psychedelics vs. Serotonergic Medications

Nicholas Levich: Welcome to the Psychedelic Passage podcast. My name is Nick Levich, and I’m here with my partner, Jimmy Nguyen. Thanks for joining us today. This week we are talking about SSRIs, antidepressants, psilocybin, and the interaction between all of these. 

And the reason this is such a popular topic is because one of the main impetus for people exploring intentional psilocybin use is that they have some form of depression. And the way that depression is treated in our Western culture most commonly is with SSRIs and other antidepressants. 

And so inevitably, folks who are taking these medications tend to want to know, do I need to come off the medication? Can I stay on it? I want to have this intentional psychedelic experience, but what do I do? 

Jimmy Nguyen: Yeah, likely the most frequent conversations we have with folks regarding psychedelics, pretty much what you just said, which is that psychotropic medications- and even it’s beyond just depression. 

I’ll say that there can be a wide range of psychotropic medications just prescribed for a lot of different mental health issues, and sometimes it’s even prescribed for just things like mood stability. So I wonder what the percentages of folks in America are who have a history with psychotropic medications? 

We’re talking about the Prozac, the Zolofts, the Effexor, Cymbalta, you name it. Let me just disclaim really quickly, though, that Nick and I are not medical professionals. We are not mental health professionals. We never claim to be. We have a deep respect for folks in the mental health field and in the medical field. 

And our organization just naturally is geared to that. We like working alongside your therapist, we like working alongside those folks. So what we’re going to be talking about today is more on the anecdotal side, I think, more on how to navigate your history with psychotropic medications in preparation for a psychedelic experience

Anything beyond that, we always say, talk to your prescribed professional, talk to your psychiatrist, talk to your mental health professional, talk to your family, like all those things. So I’ll just say this upfront, anything that you do with your own medications is your right. Your choice to do that includes getting prescribed a medication. 

And there are so many people who are like ‘I just got prescribed Prozac and it’s been sitting on my counter because I’m not sure whether to take it or not’, all the way to people who stay on their medication leading into a psychedelic experience. There’s people who go back on their medications afterwards. And we’re not here to shame anybody. 

You have your own right to whatever you do with your own body, and obviously that extends even beyond medications. Our world is crazy right now, but in this conversation we’ll be specifically talking about psychotropic medications and preparing for a psychedelic experience. So why is this important? Why is this even a thing, Nick? 

Nicholas Levich: I would say there’s two prongs that I want to make sure we address here. One is safety concerns and the other is around expectation management. 

Jimmy Nguyen: Yeah. 

Safety & Risks

Nicholas Levich: So we’re going to focus this discussion primarily on psilocybin because that is what most of our clients choose to sit with. It’s one of the safest and most accessible psychedelic medicines. And so we’re going to focus there. 

What I will say is that when we start to get into things like ayahuasca and 5-MeO DMT, some of the other psychedelics, there is a very serious safety concern. And so I want to be very clear for anyone that’s listening to this that we’re going to be addressing this primarily from the perspective of folks who are approaching an intentional psilocybin experience. 

Jimmy Nguyen: Yeah, and I’ll say directly that especially with ayahuasca, it’s because it contains an MAOI, a monoamine oxidase inhibitor, which is medically contraindicated for the vast majority of psychotropic medications. You can get serotonin syndrome, it can cause death.

Nicholas Levich: Same with MDMA. 

Jimmy Nguyen: Yes, that’s right. You just have to be very prudent here because there are some real health risks, health concerns, and this is where you have to go talk to your prescribing doctors and your prescribing folks. 

Nicholas Levich: If I could give a blanket warning, it’s be very cautious when combining psychotropic medication with either MDMA or ayahuasca. Very careful. When we talk about LSD, psilocybin, it’s a little bit different. 

We’re going to focus this on psilocybin in particular. Everything that we’ve seen anecdotally indicates that combining psychotropic medication with psilocybin is very rarely, if ever, a safety concern. 

Jimmy Nguyen: Meaning doesn’t pose an actual medical contraindication or medical issue. 

Expectation Management

Nicholas Levich: Correct. The flip side of that is there is a massive impact on expectations. So what I want to focus on to start is serotonergic medications. This includes SSRIs, SNRIs, anything that impacts serotonin in your system. 

These are typically prescribed for depression, anxiety, mood stabilization, bipolar, what else? I think those are the main ones. And so you can see why if you’re seeking a psychedelic experience to alleviate some of those diagnoses or concerns, then you have a high likelihood of being one of these drugs. 

And so typically one of two things happens here. If you choose to move forward with a psychedelic experience and you are on your Paxil. Let’s say I sat with a client who was taking Paxil and we did a psychedelic experience, knowing that Paxil was very hard to taper off, she wasn’t ready to do it. 

She gets brain zaps, all kinds of side effects and withdrawal symptoms and she was able to have an actual full blown psychedelic experience, granted at a much higher dose of psilocybin in order to kind of overcompensate for the impact that SSRI has on your serotonin receptors. 

The flip side of that is I’ve watched a woman eat 10 grams of penis envy, which are extremely strong psilocybin containing mushrooms while taking Effexor or had no psychedelic effect at all, like not even a minor altered state of consciousness. And so the reason I bring this up is because if you choose to stay on your medication and move towards a psilocybin experience, you’re basically rolling the dice. 

There’s no way to predict whether you’re going to have the experience or not. And for people that spend the time, the money and the effort preparing for something like this, the last thing they want is for it to not work, especially if they’re coming from a place of desperation. 

Jimmy Nguyen: Yeah. That’s what you mean by the expectation, I think. And I hope that science and research will catch up to really really study the psychedelic compounds, to really continue to study psychotropic medications. To figure out why somebody who fully tapers, walks into an experience, and they don’t elicit anything. 

And somebody who is a completely different individual tapers off for a couple of weeks and comes in and has an experience. And it’s not just whether you have an experience or don’t, there’s a lot more factors to it. Psychotropic medications can dull or dampen the experience. It can affect the duration and the timing of the experience. 

So I’ve worked with folks who are on a fairly high dose, that for an ‘average individual’, they would likely be under the influence of the mushroom for four to 6 hours and they pop out of their experience in 3 hours. Or folks who just generally feel like, oh, for the dosage that I took, I still felt like it was a little dampened or a little bit muted. 

And likely here we’re talking about large dose experiences. It’s also worth noting that psychotropic medications do also impact your tolerance for microdosing as well. There’s also a lot of folks who use microdosing either as a supplement or actually as a replacement to their antidepressants or anti-anxiety medications, or whatever they’re taking there. 

This is all in context, though, because for folks who are microdosing, I’ve also had people report, wow, on this particular microdose of psilocybin, I actually got a little bit of increased anxiety and a little bit of heightened things like that. And so this is me just saying that it’s so individualistic. 

And just because we’re hearing the results of microdosing, the results of macrodose experiences and all that, does not mean that is exactly what’s going to happen to you. Again, in this conversation, we’re expectation-setting. 

Nicholas Levich: Basically nothing here is cut and dry, right? So we’ve had clients who will literally link us to a study that was done on a specific SSRI and its interaction with psilocybin. I think it was acetyl azepam. And basically what it said was there were no diminished psychedelic effects on the perceptual rating scale of the participants in that study. 

And so we’ve had clients that link us to this and they say, well, see, look, this study says that I don’t need to taper and I’m going to be fine. That might be true. It also might not be and we have no way to predict how those drugs are going to interact. 

And there’s a lot of other varieties of SSRIs besides that particular medication. And so it’s really challenging for everyone to predict how this is all going to unfold. So this really is a gray area and it’s important for clients or journeyers to really consider what their motivations are, what their expectations are, and what does success look like for you as far as moving towards one of these journeys? 

Jimmy Nguyen: Yeah. And oftentimes folks who are on these types of medications, or at least the people that we chat with, they’re exploring their first psychedelic experience. And so you only get to do that once, you know what I mean? You don’t get to go back and have your first psychedelic experience again. 

And so I find that with folks who are really seeking the potential benefit of psychedelics, it can be rather heartbreaking to have prepared and to have done all the things and to have committed into finding a facilitator that you trust and finding the setting and procuring the substance and all that. 

Then you lead up into this event and nothing happens. Which by the way, I think there’s too much emphasis on just the magic around the psychedelic event anyways. And there should be more emphasis around prep and integration. 

That’s a whole side conversation, but you can imagine how heartbreaking that is for somebody who’s been on this journey, especially for folks who have been taking these medications for decades. There are so many people who are like, yeah, I’ve taken this for 20 years now I’m finding that the effects don’t work the same. 

Now I’m finding that my psychiatrist is cycling me through different medications and different things to try this and to try this in combination with wellbutrin, and I’m not feeling the effects. Well, likely there’s something that’s happening that’s modulating your serotonin receptors, which is the same thing that’s affecting your potential psychedelic experience. And I think my best guess is – as just a layman, a total amateur at this – is that you’re desensitizing your receptors and your system a little bit. 

Nicholas Levich: I mean, basically the challenge is if you go through all of this effort to prepare for an experience and then nothing happens, it perpetuates the narrative of ‘I’m broken, it doesn’t work for me, I’ve got no hope’. And that’s just not true. That’s just not true. 

I think it’s important that we discuss why, like generally as a company policy, we suggest people be tapered or give a very explicit warning as to the potential for a muted, negated, or dampened psychedelic journey. 

Jimmy Nguyen: Yeah, I mean, at a base level, I’ll say this at least for me, and then you can weigh in here. We don’t recommend people one way or another, we talk about the most common things that people do to prime themselves for the best possible outcome. But again, I assure the people that they can make their own choices 100%. 

But at least bringing up the conversation about their medications allows somebody to actually look at their relationship with those medications to really see how that has affected, altered or impacted their journey so far. And there are folks who are like, ‘Yes, this is what I need. This is helpful to me. This is the stabilizing factor’. Great. We love that. We fully support you in moving forward with the psychedelic experience if you choose to stay on your meds. 

The vast majority of other folks are like, ‘I feel like I’m spinning my wheels here’ and ‘I feel like this is not getting me anywhere. And these medications are basically starting to wear down.’ And then it comes into this conversation about, well, how much reliance are you putting on something external for your own internal state? 

And that in itself can open up a lot of conversations because I ask all of my clients two things. Do you believe that change and healing is actually possible? And I think everybody who’s listening to this can answer that in their own right. And then the second piece is, do you believe that you have all the tools inside of you already for that change to exist.

In any moment that somebody says no to either of those, that’s a whole different conversation outside of medications, outside of any of that. Because the medications, as Nick is very aptly pointing out, it’s a factor. It’s just one factor. But there’s this higher level of you having to believe that it’s inside of you. that all of this change is possible. 

Because the moment we look for any external thing, the moment we rely on the mushroom or LSD or ayahuasca to do the work for us, we missed the point. We missed the point. And then it sets you up for a hard drop off if you don’t meet that expectation. Also, that’s a big pedestal to fall off of if it doesn’t work that way for you. So I have a question for you, Nick. 

So what if there’s somebody who, and I think both of us have seen this, what if there’s somebody who feels like the antidepressant or the medication is actually helpful? 

Nicholas Levich: Right. 

Jimmy Nguyen: There’s some benefit, but then they are considering whether to taper off for a psychedelic experience, so they feel kind of stuck. They’re like, do I taper and possibly go through this little bit of instability? 

That part, because they might know that being in a solid set and setting is helpful for preparation, but at the same time, that’s a tricky spot for folks. How do those conversations go when you chat with folks in that particular situation? 

Should You Taper Off of Your Medications? 

Nicholas Levich: I always personally take the stance of empowering them to choose what’s best for themselves. I also give them explicit indication of the potential outcomes with either path forward. Because what I tend to find is that a lot of these doctors are better at prescribing the medications than they are helping folks taper. 

And so I think a lot of people feel helpless when it comes to tapering because they don’t have the adequate resources to work through that. And so the big thing for me is going back to expectations. We want to walk this fine line between keeping you stable enough to move forward towards an experience while also increasing the probability that the experience happens. 

Jimmy Nguyen: Yeah, it’s tricky. I do want to point out a resource for folks that we do send people to, which is

I just looked at the site. It’s down right now, but I hope that it comes up soon. And that is a huge forum, knowledge-based resource where people essentially just report their process of tapering off. Because the tapering process, as I find, not only is what we’re talking- about super variable, whether an individual has a psychic experience or not, but the tapering process for those who choose to do that also can be very variable. 

Where I’ve chatted with folks who have tapered off and they haven’t been on their medications for like six months, and they still have some of that brain zap, brain fog, some of those things that kick in. And then I’ve also had folks who have tapered off for a couple of weeks. ‘I feel great, no side effects at all’. So just be really careful here for anybody who is tapering and listen to your body. 

I really respect what you said, Nick, about just empowering people to make their own choice. And I want to highlight that also should be included when you have a psychedelic event on the calendar, if you have a ceremony coming up, or if you have a session coming up, or if you’re going on an international retreat and your tapering timeline is not right, or you’re actually feeling like, ‘oh, I need to reschedule’. Reschedule it, reschedule it. That’s how important it is. 

I’m working with a client right now who we rescheduled eight weeks because we’re dealing with Fluoxetine, and it just requires a longer tapering protocol for their prescribing doctor. I’m like, great, let’s just move this out because that’s what’s in the best benefit, in the best interest to you. 

So this is all about empowering folks to make the best decisions that’s right for them. There is no prescriptive part of this where if you do this, then this. It’s so individualized. 

Microdosing While Tapering

Nicholas Levich: So I want to talk about something for those that do choose to taper, because there’s a lot of people who are unhappy with the effects of their medication, right? They’re either emotionally muted, they’ve got side effects, they’re not actually getting the antidepressant relief that they seek. 

For those folks who elect to taper on their own or with the support of a doctor, but they’re committed to tapering. We’ve seen that supplementing with microdosing makes a massive difference. And so I’m curious anecdotally what you’ve seen in your clients, and I’m happy to share as well. How do you approach this kind of toggling of levers between tapering your psychotropic medication and increasing or adding a microdosing protocol? 

Jimmy Nguyen: Yeah, the first thing that comes up is for many of my clients who are doing this, exactly what you’re talking about. They’re ramping down on their traditional psychotropic medications, potentially with some overlap, ramping up on a microdosing protocol, which is likely psilocybin. 

Here, what I find with folks who do that are two things. One is they report not feeling any effect from the microdosing. And I see two schools of thought here. One is that their tolerance levels are too high, meaning that they’re not taking the minimum effective dosage for their microdosing. 

The second, which I think is actually more nuanced and more interesting, is that the microdosing actually is taking effect, but you’re so desensitized that you’re not like feeling it. This is really tricky because some of this is subjective. 

Nicholas Levich: Right.

Jimmy Nguyen: But I find that with folks who are microdosing- if a standard microdose of psilocybin, whether you’re doing a Fadiman protocol, Stamets protocol, intuitive microdosing, your own off days, on days, whatever, usually that’s somewhere between 50 milligrams to 250 and 300 mg. So we’re talking about on the scale, .05 all the way up to .25 or .3, 1000 mg in 1 gram. 

What I find with folks who are on these psychotropic medications is that their range is likely higher. And I’ve seen folks anywhere from 500 mg up to maybe 800 mg. We’re talking about half a gram here, all the way ranging up for them to get some of that sub perceptual, therapeutic benefit. And then the alternate side of this is also important, there is such a thing where you’re likely taking too much as well. 

So I would say that anybody who crosses that 1 gram threshold of a microdose, regardless of how desensitized you are because of your medications, that requires a real thoughtful conversation around that, because there are folks out there who can take a gram, a gram and a half and not feel anything. 

These are all moving targets. That’s where the benefit of having somebody there, likely weekly with you, assessing, adjusting week to week, working alongside your tapering protocol- that’s what I find is the most effective. I don’t know if you have thoughts on this too. 

Nicholas Levich: Yeah, I agree. To me, what you’re touching on and what I explicitly state to anyone I’m working with through this process, is that you don’t always have to feel the microdose for the effects to be working, because what we’re looking for here is an increase in neuroplasticity. An increase in neural connectivity. 

In other words, the brain is a malleable tool and we can adjust it to perform in a way that suits us. And so what I tend to find is that folks who have been on Paxil for 20 years and have tried to taper without microdosing and can’t get past a certain point due to brain zaps or fatigue or whatever headaches they’re experiencing, when they introduce microdosing (even if they’re not perceptually feeling the microdose) they’re still able to taper past where they were without the microdose. 

And once again, this is specifically psilocybin. What I want to make clear is that just because you can’t feel it, doesn’t mean it’s not working. It’s really important to pay attention to the withdrawal symptoms or lack thereof in an effort to really evaluate how the process is going. 

Jimmy Nguyen: Yeah, you bring up a good point because there’s never a time where I take a multivitamin and I’m like, ‘oh, I can really feel the B complex working and kicking in. I can really feel the zinc and the iron in that moment’. But if you were taking a multivitamin and getting the essential things in your body, likely over 20-30 days, you might potentially see a benefit there in combination with other stuff. 

Healthy habits, better eating, exercise, diet, sleep, all that stuff. So that’s kind of why I was giggling earlier because I was like, you’re so right. How many times do we take something and we’re like, ‘I’m not feeling that zinc that I just took a capsule of’. 

But that also is the prescriptive society that we live in, is that the majority of the medications that we take are here to alleviate some type of a symptom. And so therefore, if that symptom still exists, that’s usually our marker on whether it’s successful or not. And what I hear you say is there’s way more nuance to it than that. 

Nicholas Levich: 100%. And so not only have I been impressed, but clients of mine have been impressed with the progress they’re able to make when they choose to taper and choose to supplement with microdoses of psilocybin. And I want to be clear here again for anyone that’s just joining us, when we’re talking about tapering, we’re talking specifically about serotonergic medication. 

Drug Interactions With Non-Serotonergic Medications

So I think we should take a couple of minutes and just talk about non-serotonergic medications. So things like Xanax, Vicodin, Adderall, anything that’s not working through the serotonin pathways, how do you approach that? 

Jimmy Nguyen: Well, the whole goal for me in helping somebody prepare for a psychedelic experience, is to get them to as clean of a baseline as possible so that there’s less variables that can be the culprit of things. And so when we’re looking at stuff like sleep AIDS, anti-anxiety, stuff like Xanax or even Adderall, right, these are things that people are likely taking daily, a couple of times a week and whatnot.

Again, everybody’s choice here, but all of those things affect the nervous system and so does the psychedelic experience or the psychedelic event. So it’s not just the serotonergic kind of components of this. So I typically will recommend or suggest for folks to cease use, generally based on half life. And now half life is not a linear thing. Like, there can be different rates and gradients for folks. 

But if you can cease use so that compound is generally out of your system, then you can approach a psychedelic experience knowing that variable likely had a very little impact on it. And I think the same goes for caffeine. I think the same goes for sugar. 

It’s not just these medications that we’re talking about, but it goes back to what I’m saying about having the conversation on how these things affect your life. And I think that really it comes down simply to this. 

For me, it’s one of two options. Does this medication or things that I’m doing allow me to get closer to the real root of what’s going on? Or does it get me further away? Just as simple as that. And if you can ask yourself that question with all of the things that you’re doing. All the pills that you’re taking. All the food that you eat. 

You can just get a real clear idea. Your own kind of layout on ‘oh, this is maybe masking some stuff that I want to deal and address’, or ‘oh, this is actually helping me get some stability so that I can better address it. It’s so different per person, but if you just ask yourself that fundamental question, it can give you a pretty good roadmap on what’s going on with the stuff that we put in our bodies. 

Nicholas Levich: And I also want to share anecdotally that I have had clients who are on a cocktail of different medications. Uppers, downers, anti-anxiety, sleep, all the different stuff. And they make a very concerted effort to show up as clean and clear as possible for the ceremony. We have a beautiful psilocybin experience, and then afterwards, they try their medication again and realize how hypersensitive they are to it. 

And they either need to adjust dosage down or cut it out altogether. What they indicated was that a lot of those medications were used to mask symptoms of underlying issues. So the severe PTSD was actually causing a lack of focus. So then Adderall was prescribed. There’s this whole interconnectedness thing going on here. And it’s interesting to see that it also plays a role in the back end after the ceremony. 

Jimmy Nguyen: Right, because then the Adderall gets prescribed, and then you then have a sleep issue. Then you get prescribed sleep aid or let’s say you’re on a separate narcotic or opioid to address your pain, but then the pain also causes GI issues, and then you’re taking something for that, and then you’re a walking medicine cabinet basically trying to alleviate this. Alleviate this, and it becomes this whole foxtail of medication. 

Nicholas Levich: I hear you on that. I just think it’s really miraculous that people who are on three or four medications can either cut them out altogether or go down on dosage just by addressing the root issue, which a lot of times is psychosomatic. Basically. If I could sum up, what we’ve discussed today is that serotonergic medications have a certain probability of dampening, muting, or negating the psychedelic experience altogether. 

Other medications that are non-serotonergic, things like ADHD, anxiety meds, those kinds of things, don’t need such a long tapering process. But essentially we want to consider half life, which anyone can look up on Google and just make sure that those are generally out of your system. 

If you can tolerate it and stay balanced and stable leading up to the ceremony and then be very careful and slow with how you reintroduce medication after a journey because what you’ll likely find is your body is incredibly more sensitive to those pharmaceutical medications afterwards. 

Everything You Need Is Already Within

Jimmy Nguyen: I love all that. And maybe I’ll just add something a little bit more philosophical, potentially to wrap us up here. 

This is nothing wrong with you. Meaning that if you moved through, you’ve done your whole tapering, if you’ve done your whole stuff or you stay on your medication, you move through a psychedelic experience and it doesn’t match what you thought it was going to look like. Just know that a lot of people feel a lot of shame and guilt around that. 

They’re like, they’re like, ‘oh, now there’s something wrong with me and psychedelics will never be able to help me. And then I’m just stuck with where I’m at,’ and I just want to share with folks that there’s nothing wrong with you and that there will be some options because this is what I mean. 

Why there’s so much emphasis around one psychedelic event where I’ve had folks who work through and then maybe they don’t elicit an experience on their first event. But then they continue to do this process and then on their second event or the third event they do elicit an inexperience. And so this is one of those kinds of parts where the shame and the guilt doesn’t really serve you. 

And if you continue to make the choice on getting better, you continue to make the choice on taking responsibility for your own healing in whatever way, shape or form. Which by the way, can include medications or not include medications, totally up to you. 

But just having that earnestness just to know that you’re enough, you’re worthy of these things, even though you may not have that experience at that specific time because that heartbreak is like, oh man, I really feel for my clients who do all this stuff and they move into a ceremony and they don’t have that experience. 

I also am so triumphantly celebrating the clients that I do work with who have been on medications 20, 30 years and they have a psychedelic experience. They don’t even touch a single pill afterwards. Again, that choice has to be theirs, you know what I mean? 

Nicholas Levich: Yeah, 100%. Thanks for adding that. That brings us to the end of our episode for today. Thank you for listening. For those of you who joined us, you can download episodes of the Psychedelic Passage podcast on all of your major platforms Apple Podcast, Amazon, on Spotify and IHeartRadio or wherever you stream. Thanks for joining us this week and we’ll see you next week. 

Closing Thoughts

We hope that today’s discussion provided some clarity on how serotonergic medications should be approached in relation to psychedelics. If you have any more questions about potential drug interactions, we empower you to book a consultation with us today. Our blog page is another great resource for exploring the effects of altered states of consciousness. We wish you the best on your healing journey, our fellow psychonauts. Safe journeying!

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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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