Forewarning About Opiate Potentiators
Before we get started, its really important to note that. Opiate potentiation is not the same as tolerance reversal or prevention. The two are often mistaken for each other because they both can increase opiates effects (hence also described as potentiators).
However traditional potentiators are different in that they do not reverse or prevent tolerance, they work by merely increasing the amount of opiates in your blood plasma or they work by having similar analgesic effect which complements the opiates effects.
This means that potentiators will increase your tolerance to opiates, in the long run, unlike proglumide or memantine which would decrease it. The effect of true tolerance reversal agents like Proglumide also serves as potentiating opiates at the same time, but reduces tolerance at the same time (as long as doses are not going up).
Therefore, a highly advised strategy is to take tolerance preventative measures like Memantine and Proglumide with opiate potentiators to prevent tolerance developing, whilst achieving increased pain relief or other opiate effects.
Do not recklessly mix and match potentiators as this can bring opiate levels up to dangerous or even fatal levels.
In general opiate potentiators usually fall into one of these categories:
- CYP enzymes inhibitors
- NMDA antagonists
- Other CNS depressants
The Big List
There are literally dozens of chemicals that can potentiate opiates, many with similar mechanisms. We will start with the most well-known ones slowly move into the more novel ones as we go down the list.
Grapefruit Juice – The classic. Works by blocking the enzymes that metabolize opioids, thus increasing opiate concentration and duration. Usually, a 500ml of real 100% grapefruit juice will work fine. This is simple and works modestly for most people.
Cimetidine (also known as Tagamet) – Works by occupying CYP enzymes that metabolize opioids (and other drugs), may not be great for the liver as it increases the workload on in. Anecdotally dosage is 800mg. Available over the counter. Works for about an hour. This is the choice for most people, but may affect the metabolization of codeine to morphine.
Diphenhydramine (Benadryl) – Less itchy and better effects. Inhibits histamine and increases the analgesic and mood properties of opiates to a small degree. In addition, they also inhibit a subset of CYP2D6.
Clonidine – Dosages 0.1mg to 0.3 mg. Stronger rush of effects. Sometimes quoted as the strongest potentiators also known as Catapres.
Benzos – Not potentiation and a dangerous combination, but can be complementary to changing the effects of opiates at a low dose.
Quinine (Tonic Water) – makes opiates last longer and act stronger. It inhibits the CYP450 set, more specifically, CYP2D6. It doesn’t attach to as many enzymes as Cimetidine does, but it strongly attach to CYP2D6, which is the MAIN enzyme for opiates like oxycodone, heroin, hydromorphone, etc. A large glass of straight tonic water is plenty.
Promethazine – Any other sedative anticholinergic antihistamine will work to reduce opiate side effects and potentiate analgesia. Take after administration of opiate not before.
CPM (Chlorpheniramine maleate) – Same as above.
Cyclizine – Same as above.
Anafranil –A Tricyclic antidepressant that could potentiate opiates. Antidepressants pop up in patents for potentiation, but there doesn’t seem to be many anecdotal experiences on the web.
DXM – Actually a tolerance reversal and prevention agent, since it’s also an NMDA Antagonist, but we will pile it on this list. DXM is a whole potent analgesic drug itself. Dosage is 30mg of DXM a good half hour. This chemical is highly illegal in some countries (only available as cough syrup in some) due to potential for abuse. There is ample scientific evidence on this one but remains controversial.
Proglumide and Memantine – Proglumide naturally enhances opiate effects as well as reverses tolerance over time. Memantine is like DXM an NMDA antagonist, only its non-competitive so it doesn’t have any strong effects like DXM on its own. These are tolerance reversal and prevention agents and I would not classify them as strictly potentiators though they can be used in that way.
Magnesium – Efficacy is unknown as there are multiple forms of Magnesium. Magnesium also acts as an NMDA antagonist. Magnesium Maleate is usually the one quoted as having effects. If anything it is good at calming nerves and reducing things like bruxism.
Loperamide (Immodium) – 2mg. A little unclear whether this works or not. The theory is that loperamide occupy gut opiate receptors, thus freeing up more opiates to act on the brain. Seems to enhance analgesic effects more than mood effects, though.
Doxylamine Succinate (Active Ingredient in Nyquil) – Works to enhance effects, commonly used.
Orphenadrine – Anticholinergic used to treat muscle spasms, potentiator because it is strong anticholinergics. Acts on ALOT of mechanisms including being a moderate NMDA receptor antagonist.
Cyclobenzaprine – Same as above
Carisoprodol (Soma) – Same as above.
Propoxyphene – Huge potentiator of opium, but for other opiates it is unknown.
Naproxen – Non-selective COX inhibitor. Adds analgesia and increases mood effects. COX inhibitors reliably have shown in studies and patents to potentiate opiate effects. Other drugs of the same class may have effects also.
Cat’s Claw – Increases Duration, specifically for Methadone. Also an NMDA antagonist too.
Baking Soda – Only necessary for oral ingestion affects PH of the stomach to allow more opiates to be absorbed into the blood.
Rhodiola and Ashwagandha – Clinical studies show potentiation and tolerance reversal. We have some other herbs listed in this blog post.
And there are probably others that can potentiate opiates, its hard to include everything ever. These other ones have reports of working, but don’t have confirmed mechanisms.
– Black Seed Oil (cumin seed)
– Hordenine (very minute amounts, 5 – 20mg, even. MAO-B inhibitor – works
great if you don’t use too much)
– Tribulus Terrestris (a milder MAO-B inhibitor. This is also great as it
boosts testosterone and brings the ‘libido’ back which opiates can diminish)
– DLPA (this is great unless your tolerance is high, then it doesn’t do
– Curcumin (around 2g taken with Piperine – this potentiates the
DMSO = yup, it’s a potentiator and it seems to feel similarly to how Hordenine & Tribulus bring the ‘magic’ back to strains when tolerance is being a ‘bitch’ so to speak. We are using this stuff for the soaps and lotions, that’s how rubbing the lotion = pain relief and relaxation. It’s an interesting product, look it up: DMSO (organic)
Example Extreme Opiate Potentiation Regiment
Taking a combination of the CYP450 set inhibitors can drastically increase blood plasma levels of opiates.
45 Minutes before administration – 10mg Memantine + 600mg Proglumide would be good to combine with a regiment to prevent further tolerance and withdrawal developing.
45 Minutes before administration – 600mg Tagamet HB(Cimetidine HCl), a large glass of tonic water (or another source of quinine), and a large glass of (white) Grapefruit juice, preferably from concentrate.
35 Minutes before administration – 30mg DXM, 25mg Benadryl(Diphenhydramine HCl), 330mg Naproxen(Aleve).
20 Minutes before administration – 2 Tums OR 1.5 Tbsp. of Baking SODA. (Obviously this step only applies if you are eating your opes)
* T-0) Administrate your opiateopioid.
You can see how having a tolerance prevention regiment in place can pay off in big ways later, because you can continually use potentiation as needed instead of developing straight up tolerance to higher doses. This means better effects for longer, less side effects, less withdrawals, and a much longer sustainable usage of opiates in the long run.
The above is not medical advice, and should not be taken as a recommendation from a professional.