• N&PD Moderators: Skorpio | thegreenhand

  • Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

California Rocket Fuel

S

somedud

Bluelighter
Joined
Dec 8, 2010
Messages
515
I've read about an interesting combo. Appearently they're extremely synergetic.

California rocket fuel (SNRI plus mirtazapine) is a combination that has a great degree of theoretical synergy, norepinephrine reuptake blockade plus aplha 2 blockade, serotonin reuptake plus 5HT2A and 5HT2C antagonism, and thus many 5HT actions plus norephinephrine actions.
Specifically, 5HT is quadruple-boosted (with reuptake blockade, alpha 2 antagonism, 5HT2A antagonism, and 5HT2C antagonism). Norepinephrine is quadruple-boosted (with reuptake blockade, aplha 2 antagonism, 5HT2A antagonism, and 5HT2C antagonism.) And there may even be a double boost of dopamine (with 5HT2A and 5HT2C antagonism.)

Now currently I'm taking Wellbutrin and remeron, I don't want to mess with my SERTs too much, so I'm avoiding SSRIs, due to my past MDMA (ab)use.

Remeron has some memory improving properties, and wellbutrin seems very goosfor motivation and focus. My goal is to obviously be happy, but also not impair my cognitive performance, which SSRIs tend to do. I also want to avoid emotional bluntness.

So comment on this CRF even though I highly doubt I'll start it, but "if" I did how do you think this would affect cognition/memory etc.. It sounds like this could cause some nasty downregulation long term as well?
 
It sounds like a messy, broad-spectrum cocktail to be taking. Personally I prefer to avoid such... drastic actions. Excessive elevation of monoamines is not pleasant, causing psychosis, hypertensive crises, or serotonin syndrome, depending on whgat you're taking.

5-HT2A/C antagonism is pretty standard in antidepressant/antipsychotics and I don't think it's due to a direct elevation of any monoamine that causes it... They control sensory gain as far as I can tell and are likely to be involved in the perception of "runaway" anxiety/fear. I am unsure whether agonism or antagonism of these receptors has a direct effect on dopamine release (Isn't 5-HT2a agonism responsible for dopamine release sometimes?) - but I believe that it may be a much more complex interaction than you explain it as.

Alpha-2 blockade will result in stimulation similar to yohimbine/kratom alkaloids. The alpha-2a receptor acts as a negative feedback mechanism that your body uses to sense the levels of adrenaline/noradrenaline and adjust the levels appropriately. I'm pretty sure any effect on 5-HT levels is secondary to any increases in NE. This competes with the NERT action of the SNRI and could cause unpleasant anxiety or stimulation.

SNRIs, however, still act at SERT - and NERT - directly increasing levels of both. I don't see a reason to combine them with the newer, more selevtive agents. They are much less refined and selective and lack efficacy in anything but major depression. This "california rocket fuel" seems like a rather brute-force approach to pharmacotherapy comparable to a speedball or candyflip.

I would expect a high incidence of side effects were this cocktail actually in medical usage.
 
I've taken remeron before for insomnia. In low dosages <30mg it acts as a sedative.
In this dosage regime, as with most sedatives, there are generally amnesiac effects. I'm not sure how this could be memory improving or beneficial to cognition.

However taking remeron in higher dosages for its anti-depressant properties may be a different scenario all together.

IMO, however, remeron doesn't seem like ti would help with either memory or cognition but again I've never used in in higher dosages >45mg
 
^ the higher the mirtazipime dose, the less sedation/histamine action.

Aswell, with respect to NE, in order to achieve this "California rocket fuel" combination, you must take <200 my Effexor, which is when the NE inhibition becomes most pronounced.

Mirtazapine doesn't negatively impact memory, as it for one induces better sleep, and also inhibits dopamine to an extent at higher doses.

Rats showed behavioral and memory enhancement when given mirtazapine.

The synergy would be quite stimulating, so people with psychosis, or varying degrees of mental issues other than depression would probably be set off by this combo.

But it's supposively VERY effective and even recognized by alot of psychiatrists itself as, California rocket fuel.

This is mainly due to it's double fold action on NE receptors.

Then again, some patients find themselves to edgy on this combo.

Optimally 30 mg of mirtazipne is the doseage for not to much next day sedation, along with good dopamine inhibition, as it also counteracts this systems "stimulation" to allow for a subtle sleep.
 
Last edited:
Stahl mentions it in his essential psychopharm book as a 'heroic combo'... SERT is blocked by the SNRI. If you don't wanna mess with SERT this is not a combo worth considering.
 
I'm hoping to start desvenlafaxine in a couple days and already take mirtazapine at night. Will keep you posted.
 
From what I understand its all a crap shoot with AD's. Either they help you, they do nothing, or they cause problems. And there's only one way to find out where you fit on the spectrum of things.
 
If anyone ever suggested I take a combination of drugs that promised to "quadruple-boost" my serotonin levels, I would make sure I never took their advice again. I imagine this combination is not particularly remarkable, though, or we'd hear warnings about it.

From what I understand its all a crap shoot with AD's.
Click to expand...

Indeed, patients respond to antidepressants with a caprice that is perhaps... depressing. Of course, if you've tried five antidepressants before one of them works, how do we know your depression didn't get better on its own? At some point it surely could, and obviously you'd be on something at the time, much like the sharpshooter who draws a target around his shot.

The liability of withdrawal is another fun problem; in theory you put a person on a drug, they turn their life around, and with a more stimulating lifestyle they don't need it anymore (hopefully!), but if long-term side-effects kick in you can end up starting all over.
 
I'll be starting 50mg of Pristiq tomorrow morning to go along with my 30mg of evening Remeron. I'll let you guys know what I think of the "rocket fuel."
 
I have access to Effexor-XR, Mirtazapine and Cymbalta. I'm yet to try this combination but I am extremely interested in hearing how it works for you, I hope it has a good outcome.

From what I understand you'll need to dose between 225mg-375mg of the Effexor, and 30mg-45mg of the Mirtazapine (Remeron).

Pristiq can also work as the rocket fuel combination but don't expect it to be as potent a result as straight venlafaxine.

Good luck!
 
thebigbenzobob said:
Pristiq can also work as the rocket fuel combination but don't expect it to be as potent a result as straight venlafaxine.

Good luck!
Click to expand...

Why would you say that? Pristiq is Effexor's more potent successor. Pristiq is desvenlafaxine and Effexor is Venlafaxine. Its like the difference between Celexa and Lexepro
 
No, it's not like that at all. The latter is a racemic to single isomer change. The pristiq and effexor are analogues
 
To be super nit picky, Pristiq is the major metabolite of Effexor. A little like nordazepam versus diazepam, or amphetamine versus methamphetamine.
 
I've developed severe tolerance to Venlafaxine (where I'm probably not alone with), by taking it for maybe two years at 150 mg/d - it worked the first weeks or months and slowly faded away. Some bad day I've started combining it with Dextromethorphan (50-100mg), this way it worked again - ok, way more euphoric than an antidepressant should - surprisingly strahight for these four or five months, maybe the first date with NMDA tolerance regulation. Stopped completely after an ugly coincidence that involved police and psychiatry (there I also discovered that I do not tolerate neuroleptic medication..... in the retrospective.)

Well, years passed by since then, and of course they tried to put me on Effexor and other antidepressants again. Every time there were less effects and more intense, prolonged withdrawal. Permanently rewired SERT connections, maybe. If I would just take ONE 75 mg ER capsule, I'd have a week of brain zaps and all that...

I do remember that while switching from Paroxetine to Mirtazapine, it gave me some days of energy and euphoria. This rocket fuel thing let me remember that, maybe there is really something going on.. but that name would fit better for some dirty black market drug bowl.

But after all, I have real doubts when it comes to S(N)RIs. There is too much differing evidence. And whilst my tolerance to Venlafaxine lasted, I discovered now that I do respond much better than thought to Moclobemide. Like I had no history of failing serotonergic AD pills... This makes me think it is less a problem of the serotonergic system / brain overall changing but more of a selective substance tolerance like with every other drug.
 
I have been on "California Rocket Fuel" some 10 years ago, and it worked somewhat, but I suspect my alprazolam was most effective back then. IIRC, my doses were 45 mg mirtazapine and 225 mg venlafaxine.

I couldn't continue with the combination of venlafaxine and mirtazapine for long though, since I got so severe side effects from venlafaxine. It seems it's the AD I've tolerated worst of all I've ever tried, while mirtazapine is the opposite.

Honestly "California Rocket Fuel" was less effective than 15 mg escitalopram (alone), I was very lethargic with this combination and don't think it deserves its nick name.
 
dopamimetic said:
I've developed severe tolerance to Venlafaxine (where I'm probably not alone with), by taking it for maybe two years at 150 mg/d - it worked the first weeks or months and slowly faded away. Some bad day I've started combining it with Dextromethorphan (50-100mg), this way it worked again - ok, way more euphoric than an antidepressant should - surprisingly strahight for these four or five months, maybe the first date with NMDA tolerance regulation. Stopped completely after an ugly coincidence that involved police and psychiatry (there I also discovered that I do not tolerate neuroleptic medication..... in the retrospective.)

Well, years passed by since then, and of course they tried to put me on Effexor and other antidepressants again. Every time there were less effects and more intense, prolonged withdrawal. Permanently rewired SERT connections, maybe. If I would just take ONE 75 mg ER capsule, I'd have a week of brain zaps and all that...

I do remember that while switching from Paroxetine to Mirtazapine, it gave me some days of energy and euphoria. This rocket fuel thing let me remember that, maybe there is really something going on.. but that name would fit better for some dirty black market drug bowl.

But after all, I have real doubts when it comes to S(N)RIs. There is too much differing evidence. And whilst my tolerance to Venlafaxine lasted, I discovered now that I do respond much better than thought to Moclobemide. Like I had no history of failing serotonergic AD pills... This makes me think it is less a problem of the serotonergic system / brain overall changing but more of a selective substance tolerance like with every other drug.
Click to expand...

I'd be very careful next time you decide to combine DXM with anything. It's known to have several potentially dangerous interactions with many drugs. I myself was on 275mg effexor and 150mg bupropion daily for last 6 months or so, and I got so fed up with the sexual side effects that I decided to quit the effexor (as I suspected it was the dopamine I needed rather than the serotonin or norepinephrine). Withdrawal was pretty nasty, but I got on a dose of Prozac to taper off of and it cut that shit down to nothing. Now I'm on 450mg bupropion and honestly I feel fantastic. Things seem enjoyable again and I'm a lot less hopeless and worried about what others think of me. A NDRI for anxiety might seem counterintuitive, but for me it's worked well.

Anyways I'm rambling. What dose of bupropion are you on? You might see if you can increase it rather than going on something totally different.
 
Hammilton said:
No, it's not like that at all. The latter is a racemic to single isomer change. The pristiq and effexor are analogues
Click to expand...

I wasn't being entirely literal, just making a lazy comparison. I'm aware of the chemical differences, which is why I chose Pristiq over Effexor. It doesn't inhibit CYP2D6 and this is important considering the other meds I'm on.

Effexor is metabolized into O-desmethylvenlafaxine, among other things. Pristiq is a synthetic version of this metabolite. Escitalopram is just the most potent isomer of Citalopram, so yeah the comparison is a week one.

I really like Pristiq and Remeron together so far!
 
I was taking 30mg's of mirtazapine everyday for a little less then a month i think. I certainly didn't find that it improved any of my cognitive functions though you won't forget where the fridge is because it is absolutely the worst drug i found for increasing appetite. Actually that's about all it did for me besides the whole nearly causing me to kill myself thing.

At 15mg's it was mostly just knocking me out but at 30mg's i started to notice less drowsiness and the sedative effect doesn't seem to last that long at any dose really.

Venlafaxine was perhaps the worst drug i have ever taken and no way in hell would i take either of these meds now. I would suggest just trying to find one anti-depressant that helps you. Selegiline is one that i know works for alot of people but you need to becareful with it as it is a MAOI even if it's not nearly as risky as say nardil or parnate.
 
and the sedative effect doesn't seem to last that long at any dose really.
Click to expand...

I'm finding 7.5 mg really useful for induction of sleep with few side-effects. It's not so strong as to overcome stimulants, but I no longer need to worry about random early waking messing up my day or sporadic difficulty inducing slumber. I'm on a pretty insane exercise regimen, so my hunger is set at maximum anyway, so I can't assess that side-effect. :p

ebola
 
You must log in or register to reply here.
Top