If you’ve been to a psychiatrist or physician for anxiety or depression, chances are you’re familiar with drugs like Celexa, Zoloft, and Xanax; the former two are selective-serotonin reuptake inhibitors (SSRIs), while the latter is a benzodiazepine (we wrote a guide to natural Xanax alternatives if you’re interested).
While those three drugs are highly popular for treating depression and anxiety, there has recently been an uprising in a prescription drug cocktail called “California Rocket Fuel”, a colloquial term for combination therapy with Effexor (venlafaxine) and Remeron (mirtazapine).
California Rocket Fuel Explained
This antidepressant/anti-anxiety cocktail was popularized a psychiatrist Stephen Stahl.
You might be wondering what’s up with the name California Rocket Fuel?
It does sound a little pretentious and over-the-top, especially considering it’s a rather simple combination of drugs.
However, many physicians (and patients) insist that this duo-drug therapy packs one heck of a punch.
From a scientific standpoint, Effexor and Remeron do indeed have quite a synergy.
This is due to their selective mechanisms as both serotonin and norepinephrine modulators.
Effexor and Remeron: Are they Rocket Fuel for Your Brain?
Effexor is a potent SSNRI, which means it inhibits reuptake (recycling) of serotonin and norepinephrine in your brain cells/neurons.
Neurotransmitters, like serotonin, have to cross a small space/junction to get from one neuron to the next (and communicate messages).
Reuptake is when a neurotransmitter is released from a neuron and then taken back up by the same neuron, thus the message never gets across to the next neuron.
By blocking the reuptake process, SSRIs allow serotonin to build up in the brain and work its antidepressive mojo; remember.
Serotonin is often thought of as the “happy” neurotransmitter since individuals with depression often lack nominal serotonin production.
Remeron, on the other hand, works as noradrenergic and specific serotonergic antidepressant (NaSSA).
We realize that’s a mouthful of scientific mumbo-jumbo for most people. But don’t worry, we will make Remeron simple to understand.
Remeron works well with Effexor because rather than blocking the reuptake of serotonin, it actually stimulates serotonin release (by modulating serotonin receptors throughout the brain).
In fact, Remeron works to block certain serotonin receptors (such as 5-HT2A and 5-HT3) but stimulate others (primarily 5-HT1A).
Thus it is a “specific serotonergic” antidepressant and is thought to reduce unwanted side effects thanks to this unique mechanism.
Why Norepinephrine is Essential
Both Remeron and Effexor have similar effects on norepinephrine as well, albeit to a lesser degree than serotonin.
Nevertheless, the role of norepinephrine in the California Rocket Fuel cocktail is crucial.
Norepinephine works primarily to increase arousal, cognitive function, attention, and alertness.
One of the main drawbacks to drugs like Remeron and Effexor is that they make users drowsy and may even cause brain fog; but, when you combine the two drugs, their actions on norepinephrine fend off those side effects.
It’s no wonder the idea of rocket fuel (for the brain) came about from this drug combo.
Is California Rocket Fuel Best for Depression and Anxiety?
After reading that, chances are you can’t wait to get your hands on some California Rocket Fuel to kick depression and anxiety right out the door; before you jump the gun there are a few things to consider.
First of all, SSRIs and NaSSAs should not be your first line of attack for mental health, especially not both of them at once.
California Rocket Fuel was implemented largely for individuals who are severely depressed and had already tried many single-drug therapies with no positive response.
As such, it would seem a little hasty for a physician to prescribe California Rocket Fuel right off the bat, and you should be wary of accepting such treatment.
Moreover, you need to realize that with drugs like SSRIs and NaSSAs comes the risk of dependence and side effects.
Should you choose to take these drugs, there is a chance you will have an extremely hard time discontinuing use of them, as the withdrawals become too much to bear.
Drugs like Effexor and Remeron are potent, and since they are synthetic compounds that alter your neurophysiology, it skews your brain chemistry in an unnatural manner.
Don’t get us wrong, just because these drugs aren’t “natural,” doesn’t mean they can’t have positive effects, but there are drawbacks.
It’s sort of like a seesaw; the greater the benefits, the more drastic the side effects and risks of dependency tend to be.
You also need to be careful to avoid serotonin syndrome should you choose to go the California Rocket Fuel route.
Serotonin syndrome is a potentially life-threatening condition where your brain has chronically elevated serotonin levels.
While your physician should never prescribe a dose high enough to cause serotonin syndrome, the risk of it is higher when using combo therapy like California Rocket Fuel.
California Rocket Fuel Alternatives
After weighing all the pros and cons of Remeron and Effexor, it stands to reason that most people should try natural alternatives to California Rocket Fuel first (or even as a way to come off both drugs).
Thankfully, there are several nootropics that mimic the mechanisms by which California Rocket Fuel works.
In fact, research contends that 5-HTP is a clinically effective antidepressant supplement, with therapeutic effects on par with pharmaceutical antidepressants.
As such, both 5-HTP and L-tryptophan present potential substitutes for drugs like Remeron.
Secondly, you’ll want a nootropic that reduces reuptake of serotonin in neurons.
Arguably the best nootropic for this is St. John’s wort, which contains active compounds called hypericin and hyperforin that appear to act as natural serotonin reuptake inhibitors.
Combining St. John’s wort with 5-HTP will closely mimic the effects of California Rocket Fuel, except you’ll still want a nootropic that acts on norepinephrine to ward off side effects of higher serotonin levels.
While L-DOPA is a potent nootropic for increasing catecholamine production (e.g. norepinephrine and epinephrine), it may be a little too strong for some individuals.
We suggest starting with a milder norepinephrine enhancer, such as acetyl-L-carnitine (ALCAR) or even Rhodiola rosea extract.
If you find you still face side effects like drowsiness and lack of energy, then L-DOPA might be the better option to finish off your natural California Rocket Fuel stack.
- California Rocket Fuel is a duo-drug “cocktail” using Effexor and Remeron; it is a highly effective depression/anxiety treatment.
- Combining Effexor and Remeron appears to be more effective than using either drug on its own. However, by using both drugs, the risk of dependency and serotonin syndrome increases.
- Effexor works as a selective-serotonin reuptake inhibitor (SSRI), meaning it blocks the recycling of serotonin into a neuron (allowing it to communicate with other neurons).
- Remeron is a noradrenergic and specific serotonergic antidepressant (NaSSA) and works to inhibit certain serotonin receptors while activating others. It also enhances the activity of norepinephrine in a similar manner.
- If you’re currently taking California Rocket Fuel, you can slowly taper off by using a nootropic cocktail with supplements such as 5-HTP, St. John’s wort, and Rhodiola.
- For those facing depression and chronic anxiety, there are a variety of nootropic combinations that closely mimic the effects of California Rocket Fuel. We recommend trying 5-HTP, St. John’s wort, and Rhodiola/ALCAR to start.
- 5-HTP, St. John’s Wort, and Rhodiola are just some of many over the counter supplements that can help your anxiety, to find out about others get our free Anxiety Supplement Guide by clicking the button below!
Author Note: Please be advised, as with all content on Anxiety Hack, that none of this constitutes medical advice and we are not physicians. If you are currently taking prescription antidepressants, always consult with your prescribing physician before beginning any supplement/nootropic regimen.