The scene: a twenty year old junkie rushes back to his hell-hole of his apartment, buzzing with anxiety to get his fix. Contraband in hand, he opens his door, and even as he makes contact with the doorknob he knows. Fuck…I’m short. This isn’t going to get me high…He rushes in, prepares his shot, hits his favorite vein, sinks to the floor as the rush hits him. Five minutes later, our junkie is raging, fuming - a veritable wild-fire of opiod rage. Slowly, he sinks to the floor, wondering what to do, in fact, what is there to do? That is, besides…
Opiod Potentiation
Now that we’ve set the scene and have got some opium-based-alkaloid drama going. Follow this formula and rest assured, you will be hypothetically nodding, but of course you won’t since no one does drugs if they aren’t prescribed to you by a qualified physician. Right? Good.
But before the climatic new edition of N0 W4RN1NG’s “patented” opiod potentiating recipe, first let’s engage in a bit of foreplay. Explanation time, divided into classes:
AntihistaminesAntihistamines are common drugs that have been well-known to enhance the effects of opiods. By definition, an antihistamine is any drug that inhibits the release of, or the actions of histamine. They tend to increase sedation in most and euphoria in some, and have the added benefit of reducing itching. This is because histamines are released as a response to allergens and other itch-causing sources. There is, however, some debate over which type of histamine is superior for combating itch. H1 receptor antagonists (classic antihistamines) are generally believed to be the best for combating itch and inducing sedation – our current goal. H2 receptor antagonists are thought to have, at most, a slight effect on both itch & sedation, whereas H3 actually has an opposite effect. Apparently, the superiority of H1 receptor antagonists lies in its mechanism of action, which was studied over a decade ago:
These effects of neuronal histamine upon cortical neurons are likely to affect synaptic transmission in several ways. The depolarization per se should increase the likelihood that excitatory synaptic potentials will evoke an action potential. The increase in whole-cell input resistance evoked by H1 receptor activation should make the cell more electrotonically compact, thereby altering its integrative properties. We hypothesize that these mechanisms would allow histamine, acting at cortical H1 receptors, to enhance behavioral arousal. During waking when histamine release is highest, blockade of H1 receptors by systemically administered H1 receptor antagonists would be sedating.
- Reiner PB, Kamondi A, “Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current.” Neuroscience. 1994 Apr;59(3):579-88.In the realm of personal experience, I would have to say that, as a general principle, the ethanolamine class of antihistamines is the most effective at boosting the desired effects. Particularly, phenyltoloxamine is my personal favorite of the over-the-counter antihistamines. You won’t find it a solitary drug – it only appears in combination formulations with aspirin or other salicylates (or acetaminophen), but a dose of 60-90 mgs of phenyltoloxamine is a solid way to boost any opiate experience. Unlike other antihistamines (*coughCPMcough*), it doesn’t dominate the opiate high as much.
Other prominent antihistamines include the classic diphenhydramine (at a dose of 25-50 mgs) and DPH’s mother, dimenhydrinate. As a slight digression, dimenhydrinate is cleaved into the caffeine relative, theophylline, so it in theory might be more useful than diphenhydramine alone – this could counteract the drowsiness to some extent. Besides those prescription antihistamines, doxylamine and elemastine are the other options, however they’re nothing special.
As far as the prescription antihistamines go, ophenadrine is (in my opinion) the best, although it is not that much better than OTC phenyltoloxamine – it does seem to be a good bet, though. Coming in a close second and third place, hydroxyzine and promethazine are damn good non-enthanolamine prescription antihistamines. On a related note, the piperzine Meclizine is over-the-counter and very useful at combating nausea (cannabis will always be the best at this, though). It’s a good drug to take if you’re not sure of your tolerance and are prone to opiate-induced projectile vomiting. Bleeeechhhhh. Lunch, all over the walls. No one wants this…
The other commonly found antihistamines are chlorpheniramine (CCC) and Brompheniramine (Dimetapp). I have personally come to dislike chlorpheniramine, but if it’s all you have than it is better than nothing. Do yourself a favor, though, and cap your max dose at 4 mgs. Brompheniramine is nice, but not nearly as effective as the ethanolamine staples.
Dextromethorphan (DXM)Sigma agonist, NMDA antagonist, nicotinic receptor antagonist, serotonin releaser, dissociative anesthetic, tolerance reducer, and high potentiatior – dextromethorphan is all that and probably more. Brain chemistry is complicated, to say the least. DXM is however, also the easiest way to turn a smooth and clean oxycodone buzz and drench it in dirty weirdness. I usually recommend only taking 30 mgs of DXM, and would definitely cap the dose at 60 mgs. At 30 mgs the effect is barely noticeable, but at double the dose one might begin to feel slightly different, detached. A small warning: DXM does synergistically depress respiratory functions when used along with opiods. Taking 60 mgs with an already strong dose can be a bit dangerous, although it isn’t very likely.
AntacidsHaving a basic(high) pH in your stomach has been shown to enhance opiod bioavailability when consumed orally, as well as the rate of absorption. Taking a tums or two, baking soda or even magnesium oxide/hydroxide an hour or so before you ingest your opiate of choice will have possibly dramatic effects on your experience, depending on the usual pH of your stomach. And, speaking of magnesium…
MagnesiumWhile magnesium oxide is a great agent for basifying the stomach, but as a sole source of magnesium, it’s fairly – excuse the technical jargon – shitty. Taking approximately 400-600 mgs of magnesium citrate, taurate, glycinate, or as a chelate will enhance the experience. Like DXM, magnesium is an NMDA antagonist, which can mean many things, but in this case it means that it can aid in preventing the build up of the much dreaded opiate tolerance. Also, high doses of magnesium can have a mild sedating effect, which of course blends in nicely with any opiate buzz. Expectt mild laxative effects, as well.
Carisoprodol (soma)For whatever reason, Soma, (and its active metabolite, meprobamate) are extremely useful in enhancing the opiate experience. A dose even as low as 200 mg of meprobamate or 350 mg of carisoprodol will have a very positive effect on your high. Take them at the same time if you are eating your opiate, or twenty minutes before hand if you’re railing it or shooting it. They have a pretty long half life, but the sought-after-effects seems to only last four hours, max. They are Rx only, and meprobamate is rarely prescribed these days – but Soma is easy to find on the streets and the internet of course contains anything and everything. If you know where to look…
Dopamine Precursors
The amino acids phenylalanine and tyrosine are necessary to create dopamine in the brain. One of the wonderful effects of opiates is that they indirectly raise dopamine levels in the brain. That means that, theoretically, having some of dopamine’s direct precursors abundant in your brain will lead to increased plasma concentrations of dopamine in the presence of a dopaminergenic drug.
DL-phenylalaline at a dose of 1000 mg seems to really ramp up the energy and euphoria when taken at 500 mg, 30 minutes before ingestion) and then another 500 mgs ten to fifteen minutes later. Also, 250-500 mg of n-acetyl-tyrosine has similar effects.
I’ve found that, similar to how MDMA connoisseurs will preload with 5-HTP or l-tryptophan, noticeable effects can be achieved with opiates by preloading for a day or two beforehand with DLPA. Tyrosine should work as well, although I have no personal experience with it.
Caffeine
In addition to offsetting drowsiness, a modest dose of caffeine will prep the brain for optimum dopamine production. This is especially important if you took dopamine precursors, and as such taking energy drinks full of strange herbs is advised against [who knows what interactions are possible - maybe impotency, or chemical lobotomies – ED]. A cup of coffee or tea should do the trick. Now on to the real fun stuff…
Enzyme Inhibition & Manipulation:Before diving in, some basic primers on the subject: codeine and codeinones (hydrocodone, oxycodone, etc) are generally handled by two main cytochrome P450 enzymes: CYP3A4 and SYP2D6 (as well as glucoronidation). CYP3A4 processes your fun little friends into boring geeks like (mostly) inactive norcodeine. CYP2D6 metabolizes the goods into some really wild stuff like hydromorphone, oxymorphone, and such. So with codeine related drugs, you’re going to want to “clog” up the enzyme CYP3A4 to ensure that as much oxycodone or what have you is A) not processed into an active metabolite and B) come up on a little extra oxymorphone.
White Grapefruit Juice (Concentrate)
Yes, the cheap stuff. Make sure it’s 100% juice and that all of said juice is white grapefruit juice. A few studies have shown there to be significantly higher levels of 6-hydroxy-bergamottin, the main CYP34A inhibitor in white grapefruit, which is in the ghetto-cheap-concentrated juices as versus the freshly squeezed kind. I’m certainly not complaining…
Additionally, white grapefruit juice is, for whatever counter-intuitive reason, actually a base once inside your stomach. Which means it actually raises pH once inside you, similar to what a Tums would do. A tall glass or two of this stuff an hour before ingesting some opiates should suffice.
Tagamet
Tagamet HB (cimetidine HCl) is an OTC broad range CYP450 inhibitor. It inhibits 3A4 and 2d6 fairly well, although not nearly as well on 3A4 as well as white grapefruit does. This makes it ideal not only for oxycodone and hydrocodone, but also morphine & its relatives. Miss morphine and her brothers and sisters heroin, hydromorphone, etc, get converted into inactives by 2D6 and also by a process known as glucuronidation. Tagamet and white grapefruit juice work very well with oxycodone and hydrocodone, together they prolong the high and intensify the peak. With heroin and hydromorphone, white grapefruit juice doesn’t seem to effect it much at all, and tagamet has an effect similar to but lacking in the intensity as with hydro or oxy. The sweet spot in my experiences has been 600 mg, an hour before dosing.
Quinine & Quinidine:Quinine is the ingredient that gives tonic water that taste that’s so bitter and well, toniclicious. Did I mention that fact that it’s a mild inhibitor of CYP2D6? A couple of glasses of tonic water an hour or so before your heroin/morphine/hydromorphone will lengthen the buzz, especially combined with tagamet. Because tonic water is acidic, if you plan on eating your morphine/heroin/hydromoprhone (which is stupid – the oral bioavailability on all of those blows), you need to take Tums with your drink to counteract the acidity.
Wellbutrin (bupropion)Wellbutrin is, in this writer’s opinion, one of the best fucking morphine potentiators out there. It is an extremely strong CYP2D6 inhibitor , and it also has some mild dopamine reuptake inhibitor and stimulant properties of its own. Approximately 100 mg taken orally before your morphine or morphone will significantly lengthen the effects as well as adding a bit of stimulation and extra euphoria to the experience.
GlucoronidationHere we have something brand new, as far as I know no one has yet attempted to inhibit glucoronidation in an effort to enhance opiate effects. I've thrown around CYP450 inhibition for a while now, but it always bothered me that whil eeffects are definitely present, they are not as strong as they theoretically should be if you were really clogging all exit paths for the opiate. Then I realized that a good portion of most opioids (especially morphine) is handled by a separate set of enzymes, enzymes that conjugate opiates to an inactive glucoronic acid salt. I didn't know much about these at the time, so I lost interest and forgot about them; recently, however, I stumbled upon the concept of glucoronidation inhibitors - theoretically, in combination with CYP450 inhibitors, glucoronidation inhibitors would provide extreme lengthening of the opiate high.
And yes, they do exist.
Opiods like oxycodone are primarily glucoronized through a fun little guy called UGT2B7, unfortunately there are not too many OTC inhibitors of our friend. Or at least, that I’ve found [submit anything you find to
dosezine@gmail.com if you please – ed] – though the two that I found are laughably enough quinine and naproxen. Apparently, super human dosages of naproxone and quinine would be necessary to precipitate a noticeable effect on UGT2B7 inhibition. The inhibition would be synergistic so both should be used at once. Based on preliminary research, you would have to drink something like a bottle of tonic water along with roughly 800 mg of Aleve. This amount of naproxen is sometimes prescribed for acute pain management, but may not be safe for everyone. Do not drink alcohol with this combo and avoid APAP (acetaminophen) out of principle.
[but if you do, take a cold shower.]
That said, to get the ABSOLUTE MOST out of your opiate, try N0 W4RN1NG's (brand fuckin' new) patented opioid potentiation formula:
* T-60) 600mg Tagamet HB(Cimetidine HCl), 1000mg DLPA OR 500mg N-Acetyl-Tyrosine and a large glass of (white) Grapefruit juice, preferably from concentrate. Add in an extra strength tums or 1.5tbsp. of baking soda if you are going to be eating your opiates.
* T-45) 30mg DXM HBr, 90mg phenyltolaxamine citrate, 600mg Magnesium citrate\taurate\glycinate\chelate
* T-20 A bottle of tonic water (quinine), 880mg Naproxen Sodium. A cup of coffee, or a strong black tea. Take another tums now if you're eating your opiate to counteract the tonic water
* T-0) Parachute\chew\rail\bang your opiate
* T+10) Smoke a bowl or two. Not more, you don't want to over power it.
