Hi Lady Pharmacopeia,

First off I want to say I have tremendous admiration for your courage and the fact that you want to understand what is happening with you. You seem to educate yourself very well about the medication you are using

I am a student in pharmacology (the science that seeks to understand the different mechanisms of action of drugs and their influence on biological systems, as well as the design of novel drugs), so your story was interesting to me from the beginning

I am not a pharmacist though, so I don't know a lot of medications, just the basic mechanism underlying their action. Anyway, after looking up all your meds so I knew in which category they belong (benzos aka GABA modulators, histamine receptor inverse agonist, antipsychotic, SSRI, alpha1 blocker, etc.), I have some pieces of advice for you.

But first, a little story about myself. I have been mentally healthy almost all my life, except for a whole year which ended about 2 months ago. To cut a long story short, I was suffering from depression (very light compared to what you're going through) without knowing it. The problem was when I smoked the strongest weed I have ever smoked (possibly laced with PCP, I will never know - side note: I had been a regular smoker prior to this with no ill effects) and went into full-blown psychosis. Total paranoia lasting 3 days (during which I had virtually no sleep), ending at the emergency room with a high dose of antipsychotics. 20 minutes later I was back to reality, but it was a painful return. I felt immense shame and guilt for putting my family through this. Anyway, I took the antipsychotic (Zyprexa if you have any interest, I think it was 5mg in the morning and 15mg in the evening) for a week, then went for a follow-up. Since it was my first episode of mental illness (they did not detect the underlying depression), the final diagnostic was "toxic THC or PCP-induced psychosis". 3 months later, as the result of foolish alcohol-induced behaviour, I smoked another joint. The result: a far worse psychosis, with way more paranoia, resistant to treatment and ending in a 3-week stay at the hospital for psychiatric observation and evaluation. The doctors basically told me I was schizophrenic, and I believed them. As it turns out though, I am far from it and I am still an enigma to my psychiatrist. I still ended up being on both a SSRI (selective-serotonin reuptake inhibitor) and an antipsychotic for 10 months. My story was a little longer than I intended, I'm sorry for that and I hope you read through, because I want to offer you some info (both scientific and from personal experiences) about the specific combination of these two medications I was taking and psychedelic drugs.

Now, let me make myself clear: as long as you're not on a high dose of SSRI (Paxil in your case), it is perfectly safe to use psychedelics (IMPORTANT: AS OTHER MEMBERS HAVE MENTIONED, STAY VERY CLEAR OF MAOIS aka MONOAMINE OXIDASE INHIBITORS AS LONG AS YOU TAKE AN SSRI - THIS MEANS AYAHUASCA IS NO). But what I'm about to explain will probably make you face a dilemma, and leave you a little disappointed. As you probably know, to combination of Seroquel and a SSRI is the key element to treating the symptoms of your major depressive disorder. It is currently the best widely approved pharmacological treatment for this condition. But, these two drugs also dramatically blunt the effects of psychedelic drugs. This explains why you have to take very high doses of psilocybin-containing mushrooms to attain a desirable effect. Basically, and you can do your own research on the subject, the antipsychotic acts as an "antagonist" on many neuroreceptors (receptor proteins on the membranes of neurons, concentrated in the post-synaptic part of each synapse, that bind to various neurotransmitters). I apologize if you already know all of this, but maybe someone will be interested in this very rough explanation. Anyway, quetiapine, the active molecule in Seroquel, among other receptors, binds to the serotonin or 5-HT class of receptors. But remember, it is an antagonist so it binds to the receptor without activating it. You can see it as effectively "blocking" the receptor. And it does so with very high affinity, meaning that at the dose you are taking almost all of the target receptors are occupied, preventing their activation. Among the 5-HT receptors it "deactivates" are 5-HT1A, 5-HT2A and 5HT-2C. These are the same three receptors that DMT, or dimethyltryptamine (and any other "classical" psychedelic) is an agonist for. This means the DMT molecule binds to the same receptors, but activates them, producing a cascade of very rapid cellular responses quickly leading to the psychedelic state cherished by so many. In your case, this is virtually impossible because of the blockade of the receptors by the quetiapine molecules. I can confirm this from both a physiological point of view, and from personal experiences of trying various psychedelics while on antipsychotics. This means that for a standard dose of DMT, you would get very minimal effects. Don't get me wrong though, you will still get some effects, quite possibly interesting, but never the full-blown experience. Furthermore, SSRIs contribute to a lesser extent to the diminishing of psychedelic experiences by a mechanism I won't explain in detail as I feel my post is already pretty long.

Ok, now we've got the basic theory covered. It's now time for determining your options: the active metabolite of quetiapine has a half-life of 12 hours. This means that your body eliminates half of the drug in 12 hours, then half of the remaining half in another 12, and so on. To have optimal psychedelic effects you would need to have virtually no drug in your system. This means about 5 half-lives, or a 60-hour cessation. Personally, I cannot recommend that you do this. Abrupt antipsychotic cessation can have all kinds of nasty rebound effects and doctors are usually very careful about it: they taper off the dose gradually over months. This part is pure speculation unsupported by facts as abrupt cessation of antipsychotics is not well documented: However, you're not psychotic or schizophrenic, so your case is a little different. You might be able to get through it, and might even feel more "awake" and have more energy. What I'm trying to say is that it may be actually worth the try. If you decide to do it though, stop the Paxil 4 days before the Seroquel, and if you have strong reactions resume your medication regimen as before (the reason for stopping the Paxil before is that it has a longer half-life and, as I said earlier, will also diminish the effects of DMT).

To inform you the best I can, I have to say a word or two about the actual DMT experience. The first times I tried it, I was under the influence of both an antipsychotic and a SSRI. The effects were nonetheless unique and very interesting, but I had to go as high as 60mg (vaporized - I did not lose any) to get some decent closed-eyes visuals. No open-eyes visuals, no ego death, no out-of-body experience. Just a feeling of euphoria with, this I have to admit, pretty trippy visuals. Dosage-wise, 60mg is usually a full-blown rocket launch into multidimensional hyperspace with the possibility of communicating with some "entities" from that realm (people have many different explanations for these, but from my reductionist, scientific view, they are constructs of your unconscious made available to your everyday (altered in that moment) conscience via a change of neural activity in the prefrontal cortex.

As I said, I have stopped my medications about two months ago. I did it cold turkey, although my psychiatrist strongly disapproved, but it was risky. And there is a BIG difference between aripiprazole, the antipsychotic I was taking, and quetiapine: the half-life. Mine had nearly 6 times your half-life, meaning my withdrawal was way more gradual. So I want to repeat it one more time: going off your meds for a DMT trip is, from a clinical point of view, a VERY VERY BAD idea. It is, however, feasible, and you won't die from it. Now when I was sure I had no drugs left in my system, I treated myself to a nice 65mg DMT trip. My intention was to experience the full-blown DMT experience and learn as much as I could from it. And I have learned so much in those 5 minutes, it is almost impossible to put into words. Basically, I left my body and was shot into a reality constructed entirely of what I can describe as "futuristic organic moving and communicating, highly geometric circuitry". I was in such awe that I completely forgot who I was or what I had done. Then I realized that I had come from a "lower plane of reality" and that I had much to learn. As soon as I formulated that thought, a community of "entities" that inhabited that realm contacted me and told me they were going to teach me something. They were not visible through what I would call "standard vision", but their presence was more real than anything. We started communicating on all sorts of levels simultaneously, exchanging what I can best describe as sounds resembling those emitted by dolphins, only more percussive. Another layer was the exchange of geometrical patterns. I soon found out, with their help, that I could generate any geometrical object I wanted. There was also a transfer of "energy" or "electricity", a general pulsating feeling that we could pass around. And all of this was trivial compared to the exchange of instant thoughts and emotions. As I recall it, they pretty much made me understand on a telepathic level that they knew all my thoughts. Or was it the other way around? Did I upload all my thoughts to them? I don't know, but the feeling was one of true connectedness. Keep in my mind I still had no idea I was a human being, I was just accepted as one of "them", even though I knew I was different. I then started coming down, and they took me on a trip through space and back to Earth. We circled it a few times and they made me understand I was from there. They used their telepathic abilities to show me how to appreciate the inter-connectedness of the fragile world we live in. They made me understand how it is a jewel in the Universe that we must preserve. That was the less fun part of the trip: when they showed me I was a human being, along with all the harm we are causing to this fragile planet that is in no way ours. Things were not too dark though as they left me with the assurance that I could do something positive in this world if I wanted to. This is when they left and when I opened my eyes in reality, reintegrating my body and remembering all at once who I was, what I had done, etc. I was filled with unconditional love for every living creature, and especially for my family and friends. I was still affected by the DMT (my room was pulsating with light) and could think really fast, so I could see every single person I care about in my mind. No more than 10 minutes had passed, but I felt as if I had gained a century's wisdom.

For me, this is the experience that made a clear distinction between the dark period that had just passed, and the days that were to come. I viewed them with an optimism I had long lost. And this is just a personal fantasy (not in any way supported by sound scientific evidence), but I am convinced that there was significant psychiatric healing during this experience. This is consistent with what Ayahuasca clinics around the world are reporting. Some physicians involved with those alternative clinics postulate that the DMT experience does something to "reset" or "recalibrate" the limbic system, the part of the brain responsible for our emotions. According to current models of neuroscience, this is where a lot of depressive/negative emotions originate from (logical because it is the center of ALL emotion). This is also where a lot of the changes depression induces would take place. This explanation is strongly coherent with my personal experiences, and with some of the scientific litterature I have been reading. I believe that strong DMT trip I had may have been the last nail on the coffin of my relatively short-lived psychiatric problems.

Now back to you. Your case is obviously very different than mine. Your depression is deeply rooted in a physiological lack of production of key neurotransmitters, probably due to genetic or epigenetic causes, or a trauma very early during your foetal development. Mine was contextual, and although resulting in similar physiological effects, was completely reversible using standard SSRI medication and psychotherapy. I have no doubt that the future of modern medicine will be filled with discoveries beyond our imagination that will cure more and more diseases. I am confident that someday, you will find the right researcher who will be working on a cure specifically tailored to treat your condition. You seem to have hope, and that is what matters the most!

So the dilemma, in my opinion, is as follows:

A) You find the information you read about DMT experiences too intriguing and full of possibilities and you ABSOLUTELY have to try it. You cannot stand the thought of dying without having experienced this blissful state. This is the risky route. You stop your medication like I suggested, and you listen very carefully to what your body tells you. You will feel side effects, that is a certainty. However you will be the only judge of what is tolerable and what is not. Always keep the door open for taking the meds again if you start feeling very bad. After you are clear of the 2 drugs I mentioned (but continued with the others unchanged), you take the ride into your inner self (DMT). You see how beautiful your brain is, despite what you may sometimes believe. You see how your mind is immensely creative and vast, and almost God-like in those moments. You transcend everything for 5 of our terrestrial minutes, but you touch to a fraction of what can only be described as eternal bliss. You then come back to reality and you have to deal with it again. You start taking your medications again, and everything goes back to normal. Except you remember what you saw, what you felt, what you lived, and you'll keep this with you for the rest of your life. I must strongly advise against that route, as it can be a direct threat to your physical well-being. But you already know that. I just want you to have all the information you need to make an enlightened choice.

B) You think about it, and you don't want to take the risk. You feel as though learning about those experiences is fulfilling enough, and to be honest, it scares you a little. You decide to skip on DMT. This is what I would suggest, from a clinical point of view. However, I have to reinstate that choosing A) may actually IMPROVE your condition PERMANENTLY, if some of the actual experts on Ayahuasca treatments are right.

I'm guessing it will be a pretty though choice, so I left you a third option (I know, it's not a dilemma anymore...):

C) Although the effects will be greatly diminished, you can try a DMT trip while still on all your meds. There is no interaction between them and the DMT (the opposite effect I described is just some kind of equilibrium, this is not what physicians or pharmacists refer to as "drug interactions" ). An interesting thing about DMT is that you never build any tolerance to it, so if you have a large enough amount you can keep elevating the dose in successive sessions until you feel a satisfactory effect. I would advise, if taking this route, against taking more than 80mg for one single trip (I really mean one trip, you can exceed this during the whole session as DMT is broken down very rapidly to inactive products). With this option, you may satisfy your curiosity while minimizing the health risks.

Ok, I'm done. This is my first post apart from my Introduction Essay, I think I overdid it a little. I'll blame it on the 260mg of pure caffeine I ingested upon waking up...

Good luck!

^

Hiya! Sorry it's taken me so long to respond. I actually have a detailed response for you but as of now, both myself and my fiancé have terrible flu/colds that started kicking in the day before yesterday and now seem to be peaking at their most unpleasant today --sniffle-- I'll get back to you/this thread when I get to feeling better - as of now I need to rest.

Take care everyone,

Thanks for the very informative post everyone. Welcome to the nexus as well.

The night before last, one of my best friends committed suicide. For reasons of mourning and so forth, I will be MIA for, well, however long I need. Just wanted staff to know that I didn't make an account and then intend to not use the site - just a lot of things going on right now IRL. Thank you in advance to any well-wishers. :'(

Thanks for the image... It's very beautiful. Surprisingly, I'm starting to feel better and am back online. I've still got a bit of a nose cold though. Thank you to everyone who sent any positive energy this way because I'm pretty sure I felt it and things are getting easier as each day passes