Whats special about California rocket fuel antidepressant mix?

[ColoradoBoy90]

Note/edit: This is NOT to get high. These are meds for psychiatric disorders under the care of a doctor! They do NOT get you high, in fact they very likely will make you VERY ILL if you do not need them and are not prescribed them. Definitely a very dumb idea to try to take Psychiatric meds like these to get High, you?ll get VIOLENTLY sick and mess up your brain chemistry.
I see a doctor and she even KNOWS I am online asking these kind of questions, as I want to get off all other drugs and get stabilized on a anti-depresssnt combo VS being on drugs like Benzos forever, and the Benzos they do not even work. My doctor admits she does not know why the mixture works together, only that it came from a popular CA psychiatrist. She encouraged me to look into it more and find out why it works so special (those doctors are rare) as she admits she does not know why they are special together, and is actually open to learning new information. But that is after she fact checks everything of course. But still cool I have a doctor who is at least willing to look at my research I do.

QUESTION:
What is special about Effexor + mirtazapine? I know it is called California rocket fuel. I also remember once reading that it quote ? gives a Quad boost to serotonin, a triple boost to Noradrenaline, and a double boost to dopamine? - no idea if that is true or not, I forgot where I read that.
I know that in high does Effexor starts to reuptake dopamine or so. Cannot remember if it is at 150mg or 300mg before Effexor works on dopamine, somewhat. Is that the reason why Effexor is special? If so, what about the couple of other SNRIs out there, would they work as well as Effexor+mirtazapine, or no? I kept reading that Effexor + mirtazapine = California rocket fuel and they work together in special ways that no other 2 antidepressants do. Not sure if that is true or not.
Do they really have some type of synergy that no other 2 antidepressants can do? Or is it just named that because Effexor is the most common SNRI? It also seems like an SSRI + mirtazapine would be better for most depression, but I am not sure.

Edit: I do not know why commas or question marks show up as question marks. Tried to retype it without any of them.

 

[d1nach]

My phones dying mitrazapine acts on adrenic and seritonin receptors effexor on sert and net transporter.

 

[Keif' Richards]

OP, I'm sorry to have to tell you this, but this is not something that we really want to address. I understand that it takes a little bit of time to understand what we are truly about. From the outside, it can look like we're just a bunch of fiends trying to get higher and higher. The thing is, that is not what we are about. We're not here to "get people high". We're not even here to encourage it. We only want to help our peers be safe in their experiences.

Given that we have a limited amount of space on our front page (think about the front page of a newspaper) we just really shouldn't dedicate it to some theoretical mix of antidepressants that will allegedly fuck you up. This will be closed in a bit, I'm sure, but you deciding to do this or not do this is on you.

 

[Scrofula]

State law says California Rocket Fuel™ is an appellation only allowed for raisins grown from a specific region of the San Joaquin Valley (specifically, McCall Ave South of Belmont, to just before the Selma city limits) intended for Mr. Elon Musk's morning bran flakes. The combination is often said to be a reference to SpaceX but in fact, these particular raisins merely facilitate propulsive evacuation.

OK, apparently this phrase has been used for at least four years now in reference to mirtazapine and venlafaxine. I can't figure out why, though. If anything, the two should be straight up dangerous together, and you should not combine them outside of a doctor's prescription.

These drugs are available world-wide, and LA trends are things to avoid anyway, especially for psychiatric medicines. No street-drug users with ready access to cheap and abundant crystal methamphetamine are going to rename a combo with potent anti-histamine action "rocket fuel" either, although the more literary ones might do so ironically.

And irony might be the case: venlafaxine's main mode of action is as a SERT and NET inhibitor. Mirtazapine is an antagonist at many serotonin and adrenergic receptors. So right away, you'd say, don't these two just counteract each other? Why boost synaptic serotonin and norepinephrine if you're going to block many of its receptors?

One thing mirtazapine does not inhibit is serotonin 1 receptors. So increased synaptic serotonin from venlafaxine might lead to increased HT1a activation, while HT2a remains silenced. Except, there are single-drug options that already do that, like aripiprazole, or similar like with buspirone. Nothing about that adds up to "rocket fuel".

Bottom line is these are powerful medications with overlapping and competing function, and while there may be some "synergistic" effects in terms of treating depression, it's not something to experiment with on your own.

 

[d1nach]

Im assuming you are not trying to get high and have depression or something. Also, if you were this wont get you high anyway. Do not try this without a doctor. I am not a doctor im 22.

Binding Sites[64] IC50(nM)
SERT 27
NET 535

Site Ki (nM) Species Ref

5-HT2A 6.3?69 Human [7][63][62]
5-HT2B 200 Human [7]
5-HT2C 8.9?39 Human [63][7][62]
5-HT3 7.9 Human [7]
5-HT5A 670 Human
5-HT7 265 Human [63][62]
α1A 316?1,815 Human [62][62]
α2A 20 Human [63][62]
α2B 88 Human [62]
α2C 18 Human [63][62]
H1 0.14?1.6 Human [64][63][7][62]

5 ht2a and 5 ht 2c may downregulate paradoxically to a antagonist (Gray and Roth, 2001)

Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked by chronic administration of selective serotonin reuptake inhibitors (SSRIs) Eison AS, Mullins UL (1996)

Blockade of alpha2 adrenic receptors may increase Norepinephrine and 5 ht signaling (The α2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo)

Basically, idk its confusing use scholar.google.com

 

[d1nach]

(sorry if that came off rude, have a splitting headache)

Also does anyone know why i cant add or edit my posts on my phone without it deleting everything ?

 

[RDP89]

(sorry if that came off rude, have a splitting headache)

Also does anyone know why i cant add or edit my posts on my phone without it deleting everything ?

If you're using the mobile version that is the problem. There's a stickied thread in the support forum where you can switch to the full version. I only ever use the full version on my phone because of that shitty problem.

 

[Scrofula]

You can also just "request desktop version" from your phone browser.

 

[CFC]

(sorry if that came off rude, have a splitting headache)

Also does anyone know why i cant add or edit my posts on my phone without it deleting everything ?

Scroll to the bottom of any thread you're reading and select 'Full Site'

 

[ColoradoBoy90]

I forgot to mention: no this is not to get high. My doctor will likely read this, lol. Or I will show her any research I find out, and she what she thinks. My doctor is cool like that and would like to see more research on why it works for depression, and she does not know how this mixture is really suppose to work either.
So for me being able to only take 2 antidepressants (under the care of a Doctor) VS popping Benzo?s and pain pills 24/7 to try and numb the pain? Well I am sure you all know which is the bad idea and more harmful compared to the better idea and less harmful route. My doctor agrees, I?m simply hoping to learn if this combo is truly special or not. Or any information that I could learn through research, as I have to ask my doctor anyways. But knowledge is power so I really am curiois to know.
I told her I want OFF Benzos, and she is having me do it slowly over a 1.5 to 2 year tamper. That?s how high my dose is. Also want to get off the pain-killers, and others.. But since I have Depression, Anxiety, and OCD my doctor wants to try to treat me with anti-depressants VS being on the Benzos and these other drugs for the rest of my life with no relief either. Which I agree is a less harmful and safer route.
I showed her research on Prozac she didn?t know. I was up to 80mg on Prozac and not helping. What I found out via google and asking online explained why Prozac didn?t help my OCD and kinda made my anxiety a little worse. I believe it involved the 5htc2 receptor but not certain. After she looked into it herself and fact checked it, she decided to put me on Paxil + mirtazapine instead, as Paxil supposedly causes the most sexual side effects, which actually is the goal. Long story short: I have insane love attachment issues that makes me depressed and anxious 24/7 along with obsessive thoughts about the person. Cannot function like without wanting to jump off a bridge.
And what my doctor said makes perfect sense: I cannot treat your extreme attachment love problem and extreme depression feelings, anxiety feelings, and obsessive thoughts it causes: but I can try to treat the symptoms or possible things that cause those feelings or can help lower or block them. Thus why I am currently on an SSRI and mirtazapine.
So when she mentioned trying Effexor and Mirtazapine I was confused as from my research it seems like Effexor and mirtazapine is meant more for people with depression and fatigue, as the extra noradrenaline action helps that. I don?t see anything that backs up the combo giving a Quad boost to serotonin - or a bigger boost to serotonin than any other 2 antidepressants could give.
If anything I thought say Paxil + mirtazapine mix/combo would work more on serotonin than an Effexor/SNRI + mirtazapine mix/combo would? At least that?s what I told my doctor, I told her I was going to research it myself and she just laughed and encouraged it.

 

[Scrofula]

I see, so you are currently on Minnesota 87 Octane, and you're curious/confused about California Rocket Fuel. It turns out they're roughly equivalent, it's mainly a regulatory issue.

So really, your question is about the difference between Paxil and Effexor; paroxetine and venlafaxine. Well, paroxetine is one of the "cleanest" of the SSRIs. Yes, if you look at its profile you'll see it has other targets, the closest being the muscarinic acetylcholine receptor, but at less than 100x the affinity it has for the serotonin transporter. So it's a very "pure" SSRI.

With that comes lowest efficacy for depression, highest tolerability, very slow onset (over a week), and a complete wipeout of your libido. Also a risk of discontinuation syndrome that mostly just involves "brain zaps".

Venlafaxine is much sloppier, by contrast. I can't even get good references, but I'm comparing it to its very close cousin Tramadol, which has targets including the opioid receptor, and does bad things with glutamate. That doesn't necessarily apply to venlafaxine. One thing though, is that the adrenergic effects of venlafaxine are pretty weak, over ten-fold less than its SERT inhibition. That means dosage is important. Another downside is its very short half-life. You would need to take divided doses, or use extended release forms, and be vigilant in your dosing.

Honestly, though, mirtazapine already inhibits the alpha2 adrenergic receptor, making it a kind of anti-clonidine. Alpha2 is the autoreceptor, and inhibiting it would promote the release of more norepinephrine, just as though you were taking a NET inhibitor. It's very potent at doing this. I'd expect it to drown out any added NRI function of the venlafaxine.

The main problem with mirtazapine is it's most potently an anti-histmaine, which means sleepy time. Adding venlafaxine will do dick in that regard.

But what matters to you right now, is clinical results, rather than speculation based on receptor affinities. I've heard for a long time that the one thing SSRIs are actually good for is treating OCD. With chlomipramine perhaps better, but with a more severe side effects profile.

I can't find a major trial for mirtazapine, but everything seems to indicate it'd be effective in its own right.

A lot depends on your actual pathology, and for that you need an actual doctor. Listen to her, and if it's the case that mirtazapine is keeping you sleepy or fat, there could be other adjuncts besides additional psychiatric meds.

 

[xbandit07x]

Anything that touches Nor epinephrine and serotonin usually sucks. Norepinephrine and serotonin deficiencys are from being unhealthy. Your gut is messed up and you have adrenal fatigue? Artificially fixing those aint gonna help.

Inb4 medicine is not just dopamine, gaba, endorphins.

 

[AlphaMethylPhenyl]

Something about both peripheral acting and pro-opioidergic agents somewhere down the line in metabolism.

 

[Scrofula]

You mean venlafaxine's shady tramadol family tree? Shady in a nefarious way, not in a "tree" way.


And xBandit's all about the dopamine-only drugs. NO TOUCHING her adrenergics or her serotonin. Eww, fucking serotonin.

 

[Hodor]

And xBandit's all about the dopamine-only drugs. NO TOUCHING her adrenergics or her serotonin. Eww, fucking serotonin.

XD

LSD? *ugh* MDMA?! *blech*
Amphetamine? Well, if you insist... *spits it out* ARE YOU KIDDING ME?! THIS IS ADDERALL! STOP POLLUTING MY D-AMPHETAMINE WITH YOUR LEVOROTATORY SWILL.

This is why I stick to Ropinirole and Amfonelic Acid!

 

[AlphaMethylPhenyl]

There are some studies out there that describe remeron as effective on mu and kappa formations, effexor on mu and delta receptors. It's downstream, though, and in the end, an antidepressant should function to enhance happiness. Maybe their actions are closer to the surface, never took time to curse through them.

 

[Hodor]

Seriously though:
Venlafaxine is a good antidepressant with strong serotonergic/mild noradrenergic effects und without the side-effects of other SNRI‘s that are less selective for serotonin over noradrenaline (ex. milnacipran).

Mirtazapine has a pretty weird pharmacology in that it mostly functions as a receptor antagonist, except instead of being a sedating antipsychotic like you'd expect from such a mechanism, it produces a strong antidepressant effect by antagonizing a number of receptors that would normally decrease the amount of neurotransmitters being released, resulting in *more* neurotransmitters (even some dopamine, I believe) getting released. It is still sedating enough to facilitate going to sleep in the evening though, which is also something many patients struggle with.

So while „California Rocket Fuel“ is a ridiculously stupid name (that I doubt anybody in the medical profession actually uses... it‘s like how people convinced the media that the slang term for Methoxetamine was „Roflcopter“), the combo is obviously worthwhile.

 

[mp44god]

Mirtazapine antagonizes 5ht2a/2c and 5ht3 receptors, which are responsible for a lot of the negative side effects from SSRIS/SNRIS. By antagonizing 2a/2c in theory it should reduce any anxiogenic effects induced by the Venlafaxine, and 2c means it disinhibits dopamine release in the prefrontal cortex.

 

[kangaroo]

Long time reader, first time poster. Finally had something to contribute.

OP probably isn't looking to get high off of psychiatric meds. Despite the name, the combination is not some fad from a celebrity Hollywood doctor. However, I am a bit curious why OP would be on Benzos and also think this is a useful replacement for symptoms.

What you and your doctor are looking for, OP, is a book called Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Not sure if links are OK on the topic, but you can find it on Amazon. Stahl is the psychiatrist your thinking of, and the cocktail is explained in the book. The book is very good and about as non-technical as you can get with neuroscience and psychopharmacology and takes a very symptom-oriented approach to treatment with medication. He also has a companion for practicing doctors, Prescriber's Guide: Stahl's Essential Psychopharmacology.

While the term for the cocktail may sound silly, there is a bit of a reason for it. California is just because it's where Stahl practices. The rocket fuel part is because it is meant to be a particularly "activating" combination. Some people have depression which has symptoms of feeling bad but still have normal levels of energy. Anything activating or boosting energy is bad for these people, since it doesn't address their symptoms while creating new problems. Others can barely drag their asses out of bed in the morning. For the people, some sort of activating anti-depressant is useful. For those with a particular combination of symptoms, California Rocket Fuel may be particularly useful.

By the way, I won't bother attempting to go into the details of why it can be useful. For that, you or your doctor should read the book. Messing around with these things can range from having no effect (two drugs with same effect on serotonin, so they don't "double-up") to having a high potential of problems up to and including death via serotonin syndrome. There are reasons this cocktail has a moderate level of danger, but it is best to educate yourself rather than trusting an internet forum.

 

[Scrofula]

Mirtazapine antagonizes 5ht2a/2c and 5ht3 receptors, which are responsible for a lot of the negative side effects from SSRIS/SNRIS. By antagonizing 2a/2c in theory it should reduce any anxiogenic effects induced by the Venlafaxine, and 2c means it disinhibits dopamine release in the prefrontal cortex.

Why not just trazadone then? Or lots of other atypical antipsychotics.

Some people have depression which has symptoms of feeling bad but still have normal levels of energy. Anything activating or boosting energy is bad for these people, since it doesn't address their symptoms while creating new problems. Others can barely drag their asses out of bed in the morning. For the people, some sort of activating anti-depressant is useful. For those with a particular combination of symptoms, California Rocket Fuel may be particularly useful.

Welcome to Bluelight.

No, haven't read his book. Like has been mentioned, there's nothing to combining these drugs that is stimulating or motivating or activating. Mirtazapine is a bit sedating. That wouldn't change just because venlafaxine has NRI activity at very large doses--mirtazapine still blocks those adrenergic receptors and hammers your histamine receptors.

I saw just now a thread on this combo from 2010. Which even if that was a just-released edition, means a decade of clinical studies since then. I'd hope he'd revisit the subject, to say, "yeah, no one got into orbit; or, switching to Adderall gave them the energy and mild happiness they'd wanted all along; or, Tesla refused to sponsor; or, I sold my shares before the metastudy results was released, I'm satisfied."