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Combinations - Potentiating Benzodiazepines

Discussion in 'Benzodiazepines' started by Benzhead, Feb 12, 2005.

  1. Benzhead

    Benzhead Titanium Member

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    Jatelka EDIT: This is a combined thread and the earlier posts in it where made before the "No self-incrimination" came into play

    Hello,

    I've been on 4mg/day Clonazepam for what seems like forever. I have a script for these.

    My issue is tolerance. I have developed enough tolerance to Clonazepam that I am unable to discern any effect from an 8mg dose. Hence the 1mg four times per day is utterly impotent.

    I am wondering in anyone has any good reports of a good easily attainable benzo potentiator.

    At this juncture a simple return to the anxiolytic(anxiety reducing) qualities would be greatly beneficial.

    A bit more background: The novel anti-depressant Mirtazapine(Remeron) did restore the anxiolytic properties of Clonazepam for a short while, but this was a short lived respite.

    Thanks for reading,

    T
     
    Last edited by a moderator: May 20, 2009
  2. aMorphius

    aMorphius Newbie

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    Benzhead, my X used to take Xanax and an MAOI (maybe Parnate for
    depression). Both Rx from her Psych. This lasted about a year. She was
    definitely zoned to the max on the xanax for the whole year! Another odd
    thing was that when she quit the xanax after a year, she did it nearly cold
    turkey! And seemed to suffer no withdrawel symptoms. Those MAOI's are
    pretty strange meds!
     
  3. blackwolf

    blackwolf Newbie

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    Try grapefruit juice, some antihistamines, and other cyp4 inhibitors.
    be carefull though
     
  4. Benzhead

    Benzhead Titanium Member

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    Thanks for both responses.


    I'm not really keen on MAOis. Dietary restrictions would be an issue...I love tyramine rich foods.


    I'll look into the relative safety of your suggestions, blackwolf.


    I'll not do anything without knowing the risks involved.


    Thanks again,


    T
     
  5. jesusfreak666er

    jesusfreak666er Newbie

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    legals that make benzodiazepines stronger

    im just wondering if there are legal drugs otc that i can take to make benzo highs better, other than alc... i hear grapefruit juice does something, but anything else like otc sleeping pills?... im aware of the dangers of mixing alc and benzos so dont bother telling me cuz i dont care, but any recomendations would be appreciated thanks


    -#1 benzo fan jeyez63
     
  6. philoscybin

    philoscybin Newbie

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    I love benzos - clonazepam being my personal favorite - so I'm always looking for combinations to potentiate or synergize my experience. OTC sleeping pills may help add to the sedation effect but aren't all that great compared with legal herbs you can buy such as kratom or fixing up some nicekava tea. I've recently purchased amanitas muscaria25x extract which hasboth depressant and psychedelicproperties - I can't wait totry this out.Other than that there reallyisn't anything else legal out therethat's worth your money. Opiates although illegal unless you'refortunate enough to get a scriptas you're probably awareare your best bet in achieving the best high imaginable. For me, there's nothing compared to popping a couple benzos and blowing, plugging,or shooting up a nice batch of vitamin H (not recommended for obvious reasons).
     
  7. enquirewithin

    enquirewithin Gold Member

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    You can mix kratom with benzos but I have only done this with SMALL quantities of both. You would need to be careful. Edited by: enquirewithin
     
  8. raven3davis

    raven3davis R.I.P. Palladium Member

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    The obvious one, alcohol. To be honest My friends and I have enjoyed this combo several times but it does increase the risks drastically. Drink a beer on top of a benzo dose, that should be a nice little potentiator. I know many people do not recommend this combo because it is quite dangerous, but as long as you play it safe with the doses you should be fine.
     
  9. tinogsx

    tinogsx Newbie

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    try taking large amounts of grapefruit juice. Studies taken from pubmed





    The effect of bergamottin on diazepam plasma levels and P450 enzymes in beagle dogs.

    Sahi J, Reyner EL, Bauman JN, Gueneva-Boucheva K, Burleigh JE, Thomas VH.

    Pfizer Global Research and Development, Ann Arbor , Michigan 48105, USA. jasminder.sahi@pfizer.com

    Bergamottin, a furanocoumarin isolated from grapefruit juice, was investigated for the ability to increase diazepam bioavailability and for its effect on cytochrome P450 (P450) enzymes in the beagle dog liver and intestine. To study the effect of bergamottin on diazepam pharmacokinetics, male beagle dogs were dosed with bergamottin (1 mg/kg) p.o. 0 or 2 h before p.o. diazepam (10 mg). In a second experiment, bergamottin (0.1 mg/kg) was dosed i.v. or p.o. 1 h before p.o. diazepam (10 mg). Plasma samples were collected over 24 h postdose, analyzed by liquid chromatography/mass tandem spectrometry, and diazepam pharmacokinetic parameters were determined. To study the effect of bergamottin on P450 enzymes, beagle dog liver and jejunum was harvested after a 10-day dosing regimen of bergamottin (1 mg/kg) p.o. per day; microsomes were prepared and analyzed for CYP3A12, CYP2B11, CYP1A1/2, and tolbutamide hydroxylase activity. Bergamottin predosing increased the plasma levels of diazepam as observed by C(max) (278.75 ng/ml versus 5.49 ng/ml) and the area under the curve [AUC((0-TLDC))] (247.69 versus 2.79 ng x hr/ml) in bergamottin versus placebo groups, respectively, indicating P450 enzyme inhibition. Diazepam plasma concentrations were increased to a similar level in the presence of i.v. and p.o. administered bergamottin. In hepatic microsomes, bergamottin treatment for 10 days reduced the activity of CYP3A12 by 50% and CYP1A1/2 by 75%. Tolbutamide hydroxylase activity did not change, and CYP2B11 activity was moderately induced. In jejunal microsomes, CYP3A12 activity doubled with bergamottin treatment. CYP2B11, CYP1A1/2 activity and tolbutamide hydroxylation was not detected. In conclusion, bergamottin is both an inhibitor and an inducer of P450 enzymes.

    PMID: 11792681 [PubMed - indexed for MEDLINE]
     
  10. tinogsx

    tinogsx Newbie

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    Interaction between grapefruit juice and diazepam in humans.

    Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A.

    Department of Pharmacology, Medical Faculty, University of Osmangazi, Eskisehir, Turkey.

    Grapefruit juice has been reported to markedly improve the bioavailability of triazolam, midazolam, terfenadine, cyclosporine and several dihydropyridine calcium channel blockers including felodipine, nifedipine, nitrendipine and nisoldipine. Because these drugs are metabolized by the hepatic cytochrome P450 isozyme (CYP) 3A4, the inhibitory effect of grapefruit juice is thought to results from inhibition of CYP3A4. In this study, our aim was to investigate the effects of grapefruit juice on plasma concentrations of diazepam. Eight healthy male and female subjects participated in this study. Oral (5 mg) diazepam was administered with either 250 ml water and grapefruit juice. Blood samples were collected for a 24 h period, and whole blood concentrations of diazepam were measured enzyme immunoassay. The mean AUC(0-24) of diazepam was increased 3.2-fold (P < 0.001) and Cmax was increased 1.5-fold (P < 0.05) by the grapefruit juice. Grapefruit juice postponed the tmax of diazepam from 1.50 h to 2.06 h (P < 0.01).

    Publication Types:
    <UL>
    <LI><A>Clinical Trial</A>
    <LI><A>Randomized Controlled Trial</A> </LI>[/list]
    PMID: 9625273 [PubMed - indexed for MEDLINE]
     
  11. Richard_smoker

    Richard_smoker Gold Member

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    Sorry if this is common knowledge, but according to something my friend heard at a biomedical conference on the liver and various enzymes, it is RUBY RED grapefruit juice that provides that liver-enzyme effects generally attributed to grapefruit juice. I'm not sure why... only speculation, but perhaps the canning process of the Ruby Red preserves more of the natural enzyme substrate...?
     
  12. Nahbus

    Nahbus Gold Member

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    Valium + Kava Kava extract. Very fun. Very mellow and happy. Highly recommended (not super strong, but if you appreciate kava and benzos on their own I believe you will love it)
     
  13. forumdude

    forumdude Newbie

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    Re: legals that make benzos stronger

    ive just optained 20 pills 5mg diazepam for back problems

    i am experioenced with valium but onlu at high doses....)i had several 10 mg tablet boxes, cant count them anymore. also a while back

    im also a lucky owner of kava tablets, grolsch beer cans, amnesia haze(nice some grams left) and some home grown powerrplant, nice but a exhousting high:( very tired stoned

    also catmint calamus guarana and daminana belong to my inventory

    how you think i can potentiate some valium pills to its optimumperformance by my inventory?

    thanks dudes, and ladys ofcourse

    not to forget my premium kratom250 and my high quality kratom half an ounce :D

    a
     
  14. forumdude

    forumdude Newbie

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    Re: legals that make benzos stronger

    not as swim ment dunno what gone wrong but swim geusses you swiys would get the message
    :confused::joint:
     
  15. csharpprogrammer

    csharpprogrammer Titanium Member

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    Re: legals that make benzos stronger

    If You is aiming for being real fucked up, then go for 25-50 diphenhydramine. It produces great effects for SWIM. I say the absolute BEST potentiator(illegal) is marijuana. Pop a few Xans then roll a blunt 20 mins later, and You will love the effects.
     
  16. geophagus

    geophagus Newbie

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    Re: legals that make benzos stronger

    Cimetidine (Tagamet in the USA) which is sold OTC as an acid blocker/heartburn medication can have a very interesting effect on benzos.

    It will not make benzos any stronger (from SWIM's experience anyway), but what it will do is greatly impact the time it takes for the benzos to be cleared from the body. There are a couple of benzos (oxazepam "Serax," and lorazepam "Ativan") which are both immune to the effects of cimetidine, but the rest of the benzos are not immune.

    "The effect of cimetidine on the metabolism of benzodiazepines is discussed. Studies of cimetidine's inhibition of benzodiazepine metabolism by liver microsomal enzyme pathways are described. Cimetidine is known to have this effect on the metabolism of diazepam and chlordiazepoxide, and because chlorazepate and prazepam are similarly metabolized, cimetidine is likely to have the same effect on the metabolism of these drugs. Oxazepam and lorazepam are two benzodiazepines not metabolized by liver microsomal enzymes, but are thought to be glucuronidated in peripheral tissue by glucuronyl transferase. Cimetidine has been shown not to alter the pharmacokinetics of lorazepam or oxazepam when administered concurrently with either of these benzodiazepines. When it is necessary to treat a patients receiving cimetidine with a benzodiazepine, oxazepam or lorazepam may be the drug of choice. "

    "Cimetidine/Benzodiazepines: This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment. Medical warning: Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.
    How the interaction occurs: When these two medicines are taken together, your body may not process benzodiazepines properly. What might happen: The effects of benzodiazepines may increase and cause excessive drowsiness. What you should do about this interaction: If you experience excessive drowsiness, contact your doctor. It may be necessary to change one or both of your medicines.Your healthcare professionals (e.g. doctor or pharmacist) may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

    References:

    1.Desmond PV, Patwardhan RV, Schenker S, Speeg KV Jr. Cimetidine impairs elimination of chlordiazepoxide (Librium) in man. Ann Intern Med 1980 Aug; 93(2):266-8.
    2.Klotz U, Reimann I. Delayed clearance of diazepam due to cimetidine. N Engl J Med 1980 May 1;302(18):1012-4.
    3.Klotz U, Reimann I. Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam. Eur J Clin Pharmacol 1980 Nov; 18(6):517-20.
    4.Patwardhan RV, Yarborough GW, Desmond PV, Johnson RF, Schenker S, Speeg KV Jr. Cimetidine spares the glucuronidation of lorazepam and oxazepam. Gastroenterology 1980 Nov;79(5 Pt 1):912-6.
    5.Ruffalo RL, Thompson JF, Segal J. Cimetidine-benzodiazepine drug interaction. Am J Hosp Pharm 1981 Sep;38(9):1365-6.
    6.Patwardhan RV, Johnson RF, Sinclair AP, Schenker S, Speeg KV Jr. Lack of tolerance and rapid recovery of cimetidine-inhibited chlordiazepoxide (Librium) elimination. Gastroenterology 1981 Sep;81(3):547-51.
    7.Klotz U, Reimann I. Elevation of steady-state diazepam levels by cimetidine. Clin Pharmacol Ther 1981 Oct;30(4):513-7.
    8.Divoll M, Abernethy DR, Greenblatt DJ. Cimetidine impairs drug oxidizing capacity in the elderly. Clin Pharmacol Ther 1982 Feb;31(2):218.
    9.Gough PA, Curry SH, Araujo OE, Robinson JD, Dallman JJ. Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change. Br J Clin Pharmacol 1982 Nov;14(5):739-42.
    10.Hiss J, Hepler BR, Falkowski AJ, Sunshine I. Fatal bradycardia after intentional overdose of cimetidine and diazepam. Lancet 1982 Oct 30; 2(8305):982.
    11.Divoll M, Greenblatt DJ, Abernethy DR, Shader RI. Cimetidine impairs clearance of antipyrine and desmethyldiazepam in the elderly. J Am Geriatr Soc 1982 Nov;30(11):684-9.
    12.Abernethy DR, Greenblatt DJ, Divoll M, Moschitto LJ, Harmatz JS, Shader RI. Interaction of cimetidine with the triazolobenzodiazepines alprazolam and triazolam. Psychopharmacology (Berl) 1983;80(3):275-8.
    13.Greenblatt DJ, Abernethy DR, Morse DS, Harmatz JS, Shader RI. Clinical importance of the interaction of diazepam and cimetidine. N Engl J Med 1984 Jun 21;310(25):1639-43.
    14.Greenblatt DJ, Abernethy DR, Morse DS, Harmatz JS, Shader RI. The diazepam-cimetidine interaction: is it clinically important?. Clin Pharmacol Ther 1984 Feb;35(2):245.
    15.Greenblatt DJ, Abernethy DR, Koepke HH, Shader RI. Interaction of cimetidine with oxazepam, lorazepam, and flurazepam. J Clin Pharmacol 1984 Apr;24(4):187-93.
    16.Greenblatt DJ, Locniskar A, Scavone JM, Blyden GT, Ochs HR, Harmatz JS, Shader RI. Absence of interaction of cimetidine and ranitidine with intravenous and oral midazolam. Anesth Analg 1986 Feb;65(2):176-80.
    17.Locniskar A, Greenblatt DJ, Harmatz JS, Zinny MA, Shader RI. Interaction of diazepam with famotidine and cimetidine, two H2-receptor antagonists. J Clin Pharmacol 1986 Apr;26(4):299-303.
    18.Friedman H, Greenblatt DJ, Burstein ES, Scavone JM, Harmatz JS, Shader RI. Triazolam kinetics: interaction with cimetidine, propranolol, and the combination. J Clin Pharmacol 1988 Mar;28(3):228-33.
    19.Andersson T, Andren K, Cederberg C, Edvardsson G, Heggelund A, Lundborg P. Effect of omeprazole and cimetidine on plasma diazepam levels. Eur J Clin Pharmacol 1990;39(1):51-4.
    20.Sanders LD, Whitehead C, Gildersleve CD, Rosen M, Robinson JO. Interaction of H2-receptor antagonists and benzodiazepine sedation. A double-blind placebo-controlled investigation of the effects of cimetidine and ranitidine on recovery after intravenous midazolam. Anaesthesia 1993 Apr;48(4):286-92."


    PS I am aware that his post doesn't actually detail any "legals that make benzos stronger," however, I feel strongly that the "legal" he's pointing out here certainlly deserves an honorable mention. ;)
     
    Last edited by a moderator: Jun 11, 2008
  17. neuroplastic

    neuroplastic Newbie

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    Re: legals that make benzos stronger

    Hi! First post, glad to join the party ;)

    I'll give a basic explanation...let me know if you want to know more. Benzo's are metabolized by enzymes in the liver and colon. Grapefruit juice (both white and red) contains a compound which inhibits the functioning of these enzymes resulting in a net increase in the amount of the benzo in the system. Cimetidine and the other acid reducers are also potent hepatic enzyme inhibitors. So, basically, right now I am popping 10mg valiums with a cimetidine/grapefruit juice cocktail. It certainly does work, I guarantee it. Suggestions are to take the cimetidine/juice a bit before the benzo so it has time to work it's magic, and to supplement the action by sipping juice along the way. Also, grapefruit/vodka isn't half bad either (not that I advocate mixing sedatives);) . Let me know if you have any more q's

    np
     
  18. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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    Last edited: Jun 11, 2008
  19. forumdude

    forumdude Newbie

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    Re: legals that make benzos stronger

    damn amnesia again:p
    swim forgot posting this but his email reminded him,
    his valium is al gone, damn this morning he was searching but only found 20 empty packages:( X!XQQ~!!ZZXX1!!#WQQ$!!!!
    geu%s he h&d fun
    :D

    does anybody perhaps know a benzodiazepine which produces none or light amnesia?
     
  20. Ididnotinhale

    Ididnotinhale Newbie

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    Re: legals that make benzodiazepines stronger

    As said before, grapefruit juice, but make sure that a monkey drinks it atleast an hour and a half to metabolize it. Also, the monkey should "chase" the grapefruit juice with tums to correct the acidity for better metabolism, and finally some monkeys have found that tagamet has worked, but generally they work better for opiates.

    If you are very very very..etc careful a monkey can take a tiny tiny tiny bit of opiates and that should really help the effects. I would not suggest this because it is very dangerous.

    Finally, plugging works great and hits a monkey hard and fast.

    Does anyone know if cimetadine(tagemet) and grapefruit will help if the benzos are plugged? Also, if one is to use the same mix and plug opiates will that help?