Source: Antihistamine Aficionado Magazine
Date: July 2000

Using Antihistamines, Anticholinergics, and Depressants To Potentiate Opiates, And Dealing With Opiate Side Effects

Antihistamine Aficionado Magazine
No. 3 -- 30. July 2000
by "Dr. Ivo Sandor"

Disclaimer: The following is provided for educational and research purposes. The author or redistributors accept no liability for actions resulting from the misuse of this information and remind readers that the possession of several of the substances mentioned herein without a valid prescription order is a violation of various local, state/provincial, or national laws.

Table of Contents
Introduction
A. Dealing With Troublesome Side Effects of Opiates And/Or Anticholinergics
B. Tips For Ingestion
C. Boosting Opiates with Cytochrome P450 Inhibitors And Other Metabolism Issues
D. Mixtures of Narcotics With Other Substances
E. Appendix: Chemical Classes of Opioid Analgesics and Antihistamines.

Practically everyone who digs antihistamines and other anticholinergics is going to get an even bigger kick out of the various opiates if they have the chance to experience them. Here are, based on more than a decade of experiments conducted by myself and others, some recipes for enhancing the effects of oral doses of codeine and hydrocodone. Except as noted the same effects which are shown for hydrocodone also apply to oxycodone. The effects of dihydrocodeine (Synalgos DC) are to an extent like a half again stronger version of codeine, but the euphoria has some hydrocodone elements to it, about a 60-40 split. For example, it is a warm and fuzzy feeling in general but there is the potential for the speeding exhilaration of codeine as well, especially right as the drug is entering ones system. In this document, the term "normal dose" refers to the dose used to produce euphoria without boosters, and "therapeutic dose" refers to the recommended dose for medical use. I would not recommend trying these mixtures until you are familiar with the effects of the components by themselves, and as always, err on the side of caution when dosing.

A. Dealing With Troublesome Side Effects:

1. The "itchies" affect users of oral narcotics above moderate doses and can be reduced in intensity by taking a tablet of clemastine furmarate (Tavist), the new non-drowsy anti-histamines Allegra or Claritin, or meclizine hydrochloride (Dramamine II) an hour before taking the dose of opiates, then using an old fashioned drowsiness producing antihistamine with moderate to strong anticholinergic action like diphenhydramine (Benadryl), dimenhydrinate (Original Dramamine), or brompheniramine (Dimetapp) to boost the effect of the opiate, and using topical creams containing antihistamines to knock down the worst itching. The itchies can be intensified by the inert and non-psychoactive ingredients of cough syrups coming out of one's pores and being deposited on the skin, so having a shower if you are not too blasted to walk a straight line can be a good idea in the middle of a long hydrocodone run. Codeine is for most people the itchiest narcotic.

2. Constipation is best dealt with by having tomatoes, tomato juice, or Metamucil before the opiate session and taking a tablet of senna 90 or more minutes before ingesting the opiates. [Eating fruit regularly is also a great help.] Keeping hydrated by drinking lots of water and fluids with electrolytes, especially on hydrocodone, also helps the problem from getting as bad as it could. Particularly with hydrocodone, the user should either avoid acidic materials before the opiate session or consume a solution of sodium bicarbonate to send their system pH back up before consuming the opiates. Many people experience an initial bout of diarrhoea on codeine, although they and others almost invariably wind up dealing with constipation even worse than oxycodone in the end.

3. Nausea is best counteracted with a combination of a carbonated beverage such as 7up or Alka Seltzer, the long-acting anti-nauseant meclizine and a shorter-acting drug such as diphenhydramine or promethazine etc. If you somehow come upon the anti-nauseant Compazine you would do well to flush it down the toilet because it has about half a dozen different ways to kill you.

4. The hangover from a combined opiate and anticholinergic session is almost completely the result of the anticholinergics and is best chased away with nicotine, either a low dose for non-smokers or some chain-smoking for smokers, and its effectiveness ranges from moderate for dimenhydrinate to virtually complete for the muscle relaxant cyclobenzaprine, the normal dose of which is equivalent to the anticholinergic effect of 70 mg of diphenhydramine. The usual dental precautions for anticholinergics such as using ice chips or artificial saliva for cotton mouth and avoiding acidic beverages until a fair amount of saliva is back in the mouth apply.

B. Tips For Ingestion:

1. The efficacy of codeine, hydrocodone, oxycodone, and dihydrocodeine can be increased by at least 10% by taking them rectally. Inconclusive results have been obtained by heating hydrocodone and codeine cough syrups to 80 degrees Centigrade to boil off the alcohol, and it is suspected that these temperatures may result in the decomposition of the drug. On the other hand the best method for obtaining an opiate solution would be by using Cold Water Extraction on painkiller tablets. This liquid can be shot up the asshole with a plain syringe [no needle!] or medicine dropper or formed into colloids or solids for anal insertion by the addition of corn starch, oatmeal, or baking soda.

2. Purified powders of hydrocodone and oxycodone produced by evaporation (avoid boiling, see above) of the liquids generated by cold water extraction can be snorted (or the liquid put in a nasal sprayer), a concentrated solution or slurry added to chewing gum with a liquid centre, the liquid added to sugar cubes or antacid tablets for sublingual use or absorbed by other mucous membranes by other methods. Bulk can be added to these powders as needed by the addition of Nutrasweet, confectioner's sugar, or baby formula. Because of the way in which it is metabolised, oral administration is the optimal route for codeine. All of the oral codeine-based narcotics are bad news when used IV but can be skin-popped (injected subcutaneously) with effects marginally better than swallowing. If you are concentrating or boiling off solutions, diluting etc. it is imperative that you use precisely calibrated measuring equipment and keep some kind of record so there is no uncertainty about dosage.

Reports have circulated about a method for obtaining a smokable freebase form of codeine, but this has not been verified. Snorting powdered codeine is assumed to be ineffective for metabolic reasons. The above-listed methods are theoretically workable for hydromorphone (Dilaudid) and oxymorphone (Numorphan) to an equal or greater extent.

3. The orally effective narcotics have much in common with alcohol as far as absorption goes, and the following methods have been demonstrated to have at least some effectiveness in getting the drug into the system more quickly:
a. Mixing cough syrup or solutions of drug with carbonated beverages
b. Mixing cough syrup or solutions of drug with Gatorade
c. Mixing cough syrup or solutions of drug with warm brandy
d. Using one form or another of the opiate to fortify an over-the-counter cough syrup
e. Preparing a sodium bicarbonate solution or capsule containing the drug
f. Dissolving/mixing the drug in soup or chocolate pudding
g. Mixing codeine cough syrup or liquid into tonic water

4. Mixing liquid forms of the narcotics with antacids or sodium bicarbonate solution has proved to be effective at lengthening the high, although taking them separately has the same effect. There are bound to be tactical reasons for doing it this way -- for example, there are places where a bottle of Maalox is OK but a big bottle of cough syrup with a roman numeral five inside a C or a bottle of pills would raise suspicion.

5. Only so much codeine can be metabolised at one time - if you get above 400 mg, you are wasting it. This does not apply to hydrocodone, morphine, or the other natural or semi-synthetic opiates.

C. Boosting Opiates with Cytochrome P450 Inhibitors And Other Metabolism Issues

1. A dose of Tagamet an hour before a hydrocodone/oxycodone session will make the drug last longer and have a better effect. Antacids should be taken at least 45 minutes after the Tagamet otherwise absorption of the Tagamet will be impaired. Grapefruit juice also has the same type of impact on liver enzymes; use a Maalox chaser to neutralise any systemic acidification effect from the grapefruit juice. Tagamet should not be taken with codeine because it impairs the metabolism into morphine necessary for it to have any real effect.

2. Quinine and quinidine accentuate the buzz of opiates but only directly help with codeine metabolism by boosting the amount changed into morphine. The prescription antihistamine promethazine (Phenergan) helps out codeine even more, and is found with codeine in the Schedule V cough syrup Phenergan VC With Codeine. Quinine will tend to have its effect without impairing hydrocodone but does seem to burn off the buzz more quickly and may flatten the dose-to-response curve.

3. With all this liver magic going on and the acetaminophen content of a number of the drugs in question, the concurrent use of any alcohol at all with any of these mixtures should be thoroughly researched ahead of time. For example, washing down 5 Percocets with a vodka gimlet is not a good idea even if you have a massive tolerance to the narcotic. Also in many people moderate to large amounts of alcohol can change the subjective nature of the high for the worse and bring on sleep before the user intends. Anything more than 20 ml pure alcohol equivalent is likely to create trouble.

D. Mixtures of Narcotics With Other Substances

Note: Several other drugs are discussed under the headings below; if you do not see one you are looking for, use the find function on your reader to see if it is in the document.

1. Orphenadrine Citrate (Banflex, Norflex, Norgesic) -- This muscle relaxant works by much the same mechanism as scopolamine and the ethanolamine antihistamines and by itself is a mild euphoriant, although this euphoria is mainly appreciated by experienced anticholinergic users. Orphenadrine has many of the same systemic effects as cyclobenzaprine but tends to metabolise more quickly. It can be used, by itself or with a standard dose of a strong antihistamine like diphenhydramine, to enhance the euphoria of both codeine and hydrocodone to equal extents, and it is assumed oxycodone as well. A full dose of orphenadrine should be taken with an 80% dose of narcotic; if available, a half-dose of scopolamine, or 75 mg of diphenhydramine, provides a massive boost to the above mixture. Alcohol in low to moderate amounts does tend to increase the overall euphoria but should be added in small amounts after the full effect of the two or three other drugs is known.

2. Cyclobenzaprine (Flexeril) -- This muscle relaxant is generally a rotten medication but does have some impact on opiates and is a crucial ingredient in a late-afternoon snack involving Tylenol With Codeine. The user prepares for the set by taking a 200 mg caffeine tablet and an antacid and then about 30 minutes later taking a naproxen tablet, a effective dose of Tylenol (or aspirin or ibuprofen) with Codeine and the Cyclobenzaprine. If taken on an otherwise empty stomach the feeling of euphoria rapidly overtakes the user.

Cyclobenzaprine is a tricyclic and the usual interaction warnings apply. Vicodin had been substituted for codeine with less success and it is assumed oxycodone preparations will have a similar effect. Alcohol will cause stomach problems if consumed with this mixture. In general, Cyclobenzaprine has been found to steepen the dose-to-response curve of codeine but have a negligible impact on other opiates, and mixes very poorly with many synthetics such as Darvon.

3. Diazepam (Valium) & Other Benzodiazepines -- This drug and other benzodiazepine tranquillisers have the effect of making codeine, oxycodone and especially hydrocodone highs cosier and preventing the insomnia that moderate to high narcotic doses can cause. A full therapeutic dose of the benzodiazepine should be taken with a dose of the narcotic starting at 70% of the usual. Alcohol must not be consumed with benzodiazepine tranquillisers under any circumstances. Not only does alcohol in low doses spoil the positive effects of the drug, but practically all benzodiazepine-related deaths have something to do with alcohol. It is assumed that oxycodone, paregoric, and opium doses should be started even lower if taken with Valium, Xanax, Librium etc.

4. Meprobamate (Miltown) -- This sedative-hypnotic can be used to boost codeine pain pills into a much higher level of euphoria, and along with quinine the combination can approach the intensity of morphine. However, Meprobamate spoils a hydrocodone high by making it harsher although the onset is more intense. A usual therapeutic dose of 200-600 mg of Meprobamate combined with 60% of the usual narcotic dose is a good place to start, with booster doses of opiate following no sooner than an hour later. Alcohol of any type should not be combined with these.

5. Barbiturates & Other Depressants -- The only research I or others have done with barbiturates has involved the use of low doses of hydrocodone to lift the hangover remaining after the primary effects had worn off. It is assumed that practically nothing in the realm of narcotics, depressants, or anticholinergics can be safely mixed with barbiturates at any dose. Non-barbiturate sedative-hypnotics have lesser but still significant dangers and concomitant dosing should not be attempted unless one has a good deal of experience with the effects of the sedative by itself. A therapeutic dose of methyprylon (Noludar) combined with 60 mg of codeine significantly strengthened both. Another piperidine-derived drug reportedly sold with codeine for concurrent use, glutethemide (Doriden), could not be obtained and is apparently no longer manufactured for US distribution. The depressant ethchlorvynol (Placidyl) is similar in many respects to barbiturates.

Unconfirmed reports of a half dose of codeine cough syrup taking the rough edge of the recommended hypnotic dose of Chloral Hydrate have circulated, and codeine has the same effect on downer hangover that it does on alcohol hangover.

6. Promethazine (Phenergan) Phenergan VC With Codeine Cough Syrup is a pleasant night time substance which can be enhanced with the green-label Alka Seltzer Night-Time Cold Medicine or diphenhydramine. See notes under metabolic enhancers - this drug theoretically will burn off a hydrocodone/oxycodone buzz faster while increasing sedation.

7. Trazadone -- Effects are somewhat similar to cyclobenzaprine, both of which cannot be taken if the user has been taking MAO inhibitors in the last two weeks. Trazadone's anticholinergic activity is much less than Cyclobenzaprine and Trazadone has a horrible side effect profile including priapism or impotence and so forth.

8. Belladonna Alkaloids - These three alkaloids, scopolamine, hyoscyamine and atropine are used as antispasmodics and anticholinergics and have indirect additive effects on natural and semi-synthetic opiates when taken by mouth. The belladonna-paregoric mixture Donnagel PG has a crazy rushing high to it when taken at 150% of the therapeutic dose. Similar effects have resulted with combining the therapeutic dose with normal doses of codeine and dihydrocodeine.

Of the alkaloids considered singly, therapeutic doses of scopolamine help out the opiates, hyoscyamine theoretically would have no direct impact, and atropine has variable antagonist activity, and its impact on opiates generally is a wash with the exception of some synthetics, which it directly wipes out. Diphenhydramine is basically synthetic scopolamine, the anti-parkinsonism agent Trihexyphenidyl (Artane) is an atropine equivalent that does not appear to have the opiate-antagonist properties of atropine, and chlorpheniramine has many atropine-like effects (and a very similar dose-to-response curve) with no known opiate-antagonist activity. In all cases starting with the therapeutic dose of both the opiate and the anticholinergic are recommended, with increases in the anticholinergic needing to be capped at double the therapeutic dosage. In contrast to the belladonna alkaloids, the mentioned antihistamines have negligible gastro-intestinal effects, and Artane is closer to the antihistamines than atropine in this regard.

9. Diphenhydramine (Benadryl) -- This antihistamine increases the effects of opiates more or less evenly across the board, and the effect seems to be similar for all natural and semi-synthetic opiates. A normal dose of the opiate can be taken with 25 to 75 mg of diphenhydramine. This mixture should be taken with a bronchodialator/decongestant because diphenhydramine is also a cough suppressant. The green label version of Alka Seltzer cold medicine contains a sufficient dose of decongestant and sodium bicarbonate (which slows metabolism). If the diphenhydramine product contains alcohol, the loading dose of the opiate should be reduced by 30% and the any booster doses should be taken no sooner than an hour afterwards.

Those who take larger doses of antihistamines or other anticholinergics for the euphoriant properties should not take opiates along with them; needless to say, the mixing of opiates with the much higher deliriant doses of anticholinergics can be assumed to invariably have catastrophic effects because of the combination of respiratory depression and thickening of bronchial secretions caused by these drugs. It is assumed that any dose of diphenhydramine above 125 mg cannot be safely mixed with any quantity of opiate.

10. Dimenhydrinate -- Basically a pro-drug of diphenhydramine, see that section, doses are a 2:1 ratio.

11. Phenyltoloxamine Citrate - This is an antihistamine found in "enhanced pain relievers" available over-the-counter and has effects midway between brompheniramine and orphenadrine. It will make the euphoria of hydrocodone warmer and have a similar impact on codeine and dihydrocodeine. A normal dose of the opiate can be combined with up to 175% of the therapeutic dose of the phenyltoloxamine product (beware of total acetaminophen consumption) to start with.

12. Doxylamine Succinate -- This antihistamine is the active ingredient in NyQuil and some over-the-counter sleeping pills. Its sedative effects are similar to diphenhydramine and it has about 65-75% of the anticholinergic strength. It works nicely with codeine and about as well with hydrocodone. A normal dose of the opiate can be combined with a therapeutic dose of the doxylamine product to start out with, unless the doxylamine product contains a large amount of alcohol, in which case the opiate should be divided between a 70% dose initially and the other 30% no less than 30 minutes later with booster doses done at the usual interval but equal to or more than of the usual size.

13. Brompheniramine Maleate (Dimetapp) - This antihistamine is a drowsier version of Chlor-Trimeton which adds directly to most of the effects of opiates, with its contribution to codeine being the most significant. More than one person has reported a feeling of exhilaration similar to 150 mg of codeine when taking Dimetapp with 25 mg of hydrocodone. The sedative effect of brompheniramine is about 80% that of diphenhydramine with 75-80% of the anticholinergic potency. At therapeutic doses of brompheniramine the normal dose of the opiate can be taken; with anything above twice that (max should be four times) the initial dose of the opiate should be reduced by 20-35% and booster doses started no sooner than 45 minutes later, and then, at least initially, smaller than usual. Any brompheniramine product being used with opiates which contains alcohol should be taken at no more than 150% of the therapeutic dose with an initial dose of the opiate reduced by 25%.

14. Dextromethorphan Hydrobromide - Therapeutic doses of dextromethorphan tend to smooth out a codeine buzz and add calmness to the buzz of hydrocodone, oxycodone, and dihydrocodeine. Anything above this amount may not be a good idea because of the respiratory effects. Dextromethorphan is technically an opioid in the same chemical class as Levo-Dromoran, without a lot of the same effects, of course.

15. Meclizine (Dramamine II) - This is effective at reducing the nausea of opiates in a lot of people and at therapeutic doses will cause some across-the-board increase in the effects of opiates (about 35% that of diphenhydramine) and has been demonstrated to steepen or move out the dose-to-response curve of opiates, hydrocodone particularly. The antihistamines cyclizine (Marezine) and tripelennamine (PBZ, Pelamine) also have similar effects. The latter is a strong anticholinergic and was famous for being mixed with pentazocine (Talwin) back in the old days before they started mixing it with Narcan. All of these can be taken in the therapeutic doses along with the normal dose of the opiate.

16. Clemastine (Tavist) - This is an antihistamine in the same chemical class as diphenhydramine with a much longer half-life and about 55% of the sedative strength and 30% of the anticholinergic potency. The antihistamine triprolidine (Actifed) is a shorter acting antihistamine of the same type, albeit in another chemical category, that has stronger anticholinergic effects, about 60% those of diphenhydramine. Tavist is better ranked with Allegra and Claritin as being good medicines for pre-empting the itchies, although it has a similar effect to meclizine in compounding the effects of opiates, 35-45% that of diphenhydramine. These can be taken in the therapeutic doses along with the normal dose of the opiate.

17. NyQuil (Doxylamine & Dextromethorphan + other items) - See the dextromethorphan and doxylamine sections for details on how these act separately. This mixture is a good potentiator of practically all narcotics and has a particularly pleasing impact on hydrocodone. Because of the alcohol content, a therapeutic dose of NyQuil should be taken with an initial opiate dose reduced by 25% if it is the only item added or 25-45% if a third agent (the best are ONE of the following at one time):
a.Orphenadrine, therapeutic dose, best with any
b.Chlorpheniramine, therapeutic dose, best with codeine
c.Diazepam, no more than 50% of the therapeutic dose with a 5mg maximum, somewhat better with hydrocodone. In this case, the dose of NyQuil should also be cut by 25%, as well as basically halving the initial opiate dose and then taking the other half about 45 minutes later, and no more alcohol consumed in any form.

18. Valerian - This is a good agent for dealing with insomnia at the end of an opiate session but really doesn't do much for the opiate. Chamomile tea has similar effects.

19. St. John's Wort - This has seemed to help some of the stimulant effects of opiates, codeine in particular, along. The difference varies quite a bit from person to person, and the fact that St. John's Wort is reportedly a soft Monoamine Oxidase Inhibitor should be considered when getting ready to mix things.

20. Sljivovica (100 proof plum brandy) - Of the alcoholic beverages, this was the best to mix with opiates, although no more than about > of an ounce should be used by those with no tolerance, and probably not that much more for others. It had an across-the-board impact on codeine but tended to harshen hydrocodone and oxycodone buzzes. In matters other than flavour and aesthetics, vodka is interchangeable with this beverage.

21. Gin - The same 15-20 ml pure-alcohol equivalent limit applies for this, and it's negative effects on the hydrocodone and oxycodone buzzes seemed to be somewhat greater than vodka, Sljivovica, and pure reagent-grade ethanol (thus it can be assumed Everclear)

22. White Wine: The co-generics present in wine make it an all or nothing thing as far as how well it mixes with opiates. Red wine will generally be worse. For a lot of people it won't be an improvement. The same goes for beer and a lot of whiskey.

23. Naproxen (Aleve): This non-steroidal anti-inflammatory will increase the analgesia of all opiates and can add some warmth to a hydrocodone buzz.

It is very tough on the digestive system when taken on an empty stomach. 24. Multi-Narcotic Mixtures: The natural and semi-synthetic opiates by themselves steepen the dose-to-response curve of other opiates of the same class. Whether this is the most efficient use of them depends on one's supply situation.

25. Chlorpheniramine (Chlor-Trimeton) - This antihistamine with about 60% of the anticholinergic strength and less than a quarter of the sedative activity of diphenhydramine markedly increases the exhilaration of codeine. Both are taken at the normal dosages, and mixtures of chlorpheniramine and phenylpropanolamine (Ornade etc) seem to work even better. The mixture can in turn be mixed with a normal dose of orphenadrine for an enhanced body buzz. The effects of chlorpheniramine seem to go on independent of a hydrocodone buzz without much in the way of enhancement, subjective change, or metabolic changes.

26. Loperamide (Immodium): This drug is related to meperidine/pethidine (Demerol) but does not cross the blood-brain barrier in sufficient quantities to cause euphoria. However, the consumption of doses of 150-300% of the therapeutic dose when mixed with high doses of codeine or meprobamate have been reported to produce a weak Darvon-like buzz aside from the effects of the other drugs.

E. Chemical Classes of Opioid Analgesics and Antihistamines.

 Opioid Analgesics

 Opiates
  Opium (Paregoric, Laudanum, etc.)
  Morphine
  Codeine*
 Derivates or Analogues of Morphine & Codeine  Hydrocodone (Vicodin, Codiclear)
Hydromorphone (Dilaudid)
Oxycodone (Percodan)
Oxymorphone (Numorphan)
Diacetylmorphine (Heroin)
 Dihyhdrocodeine (Synalgos)

 Morphinian Derivates
 Levorphanol (Levo-Dromoran)
Dextromethorphan
Butorphanol (Stadol)

 Benzomorphan Derivatives
 Phenazocine
Pentazocine (Talwin)

 Piperidine Derivatives
  Meperidine/Pethidine
 Diphenoxylate (Lomotil)
Loperamide (Immodium)
Fentanyl (Duragesic, Sublimaze etc.)
Remifentanil (Ultiva)
Sufentanil (Sufenta)
Alfentanil (Alfenta)
Piminodine
Anileridine

 Methadone Class Compounds
 Methadone
Propoxyphene (Darvon)

 Antihistamines

 Ethanolamines
 Diphenhydramine (Benadryl)
Dimenhydrinate (Dramamine)
Clemastine (Tavist)
Carbinoxamine (Clistin)
Bromodiphenhydramine (Ambrodyl)

 Ethylenediamines
Tripelennamine (Pyrabenzamine, PBZ)
Pyrilamine (Allertoc)
Antazoline (Vasocon)
Methapyriline (Histadyl)

 Alkylamines
 Triprolidine (Actifed)
Chlorpheniramine (Chlor-Trimeton, Ornade)
Brompheniramine (Dimetapp)
Dexchlorpheniramine (Polaramine)
Dimethindene (Forhistal)
Pheniramine (Naphcon-A)

 Piperzines
 Cyclizine (Marezine)
Meclizine (Dramamine II, Bonine)
Hydroxyzine (Atarax)
Chlorcyclizine
Buclizine

 Phenothiazines
 Promethazine (Phenergan)
Methdilazine (Tacaryl)
Trimeprazine (Temaril)

 Related chemicals
 Chlorpromazine (Thorazine)
Prochlorperazine (Compazine)

Others  
 Cimetidine (Tagamet) -- H-2 Receptor Antagonist
 Orphenadrine (Norflex) -- Tertiary Amine
Anticholinergic Related Chemicals:Oxybutynin (Ditropan) and Trihexyphenidyl (Artane)
 Phenyltoloxamine (Percogesic)
 Doxylamine (NyQuil)
 Cyproheptadine (Periactin)
 Azatadine (Optimine)
 Terfenadine (Seldane)
  Fexofenadine (Allegra)
 Ketotifen (Zaditen)
 Astemizole (Hismanal)
 Loratadine (Claritin)



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