Potentiating Benzodiazepines

[Benzhead]

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

[aMorphius]

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!

[blackwolf]

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

[Benzhead]

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

[jesusfreak666er]

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

[philoscybin]

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).

[namidua]

cit H? vivodid? isn't htat synthetic and can kill you? sorry if I'm wrong but don't want nyone from mis info.



pj,. vit H. goy it, never mind, it is 6am..

[enquirewithin]

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

[raven3davis]

The obvious one, alcohol. To be honest SWIM and friends 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.

[tinogsx]

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 (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dSah i%2bJ%255BAuthor%255D';), Reyner EL (javascript ol'http://www.n++cbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dRey ner%2bEL%255BAuthor%255D';), Bauman JN (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dBau man%2bJN%255BAuthor%255D';), Gueneva-Boucheva K (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dGue neva%252DBoucheva%2bK%255BAuthor%255D';), Burleigh JE (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dBur leigh%2bJE%255BAuthor%255D';), Thomas VH (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dTho mas%2bVH%255BAuthor%255D';).

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]

[tinogsx]

Interaction between grapefruit juice and diazepam in humans.

Ozdemir M (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dOzd emir%2bM%255BAuthor%255D';), Aktan Y (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dAkt an%2bY%255BAuthor%255D';), Boydag BS (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dBoy dag%2bBS%255BAuthor%255D';), Cingi MI (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dCin gi%2bMI%255BAuthor%255D';), Musmul A (javascript ol'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db%3dpubmed%26cmd%3dSearch%26term%3dMus mul%2bA%255BAuthor%255D';).

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]

[Richard_smoker]

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...?

[Nahbus]

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)

[amnesia]

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

[amnesia]

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

[csharpprogrammer]

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

[geophagus]

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 SWIM is aware that his post doesn't actually detail any "legals that make benzos stronger," however, SWIM feels strongly that the "legal" he's pointing out here certainlly deserves an honorable mention. ;)

[neuroplastic]

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 SWIM is 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

[Jatelka]

For more on benzodiazepines and grapefruit juice: See here...

http://www.drugs-forum.co.uk/forum/showthread.php?t=26819&highlight=grapefruit

And some stuff in the archive...

http://www.drugs-forum.co.uk/forum/local_links.php?action=jump&id=1272&catid=27

http://www.drugs-forum.co.uk/forum/local_links.php?action=jump&id=1321&catid=27

[amnesia]

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?

[Daytona71]

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

You don't care? Maybe that is part of the reason you are banned? Grapefruit juice works wonders so why try to mix something that could damage your health, is being 18 that bad? Go ask Alice.....Cooper that is about being 18 as that seems to be the issue here!

[neuroplastic]

Not sure what you mean about being 18...profile says age is 54.

To get into more depth regarding liver enzyme inhibition and effect on benzos read Jatelka's links. Certain benzos are metabolized by specific enzymes, so if SWIM is taking diazepam grapefruit/cimetidine works great but not so much for other benzos. In summary, UTFSE to optimize SWIM's stash.

[Ididnotinhale]

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. Swim 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?

[outriderx]

HI SWIM has a few prazepam and a few medazepam (later being rather weak, first apparently similar to diazepam just twice as high of a dosage)
he wants to get as much out of it

are there any potentiators? would it be worth it to combine normale strenght prazepam with a little of the (rather useless) medazepam in order for some enzymes to work slower or the effects to be slightly better?

other things (like grapefruit juice maybe?)??

thanks in advance

[radiometer]

White grapefruit juice taken awhile prior to the benzodiazepine. One should be very careful to slowly titrate the benzo dose, as the effects of WGFJ on metabolism are unpredictable from one individual to the next, and obviously overdose could result.

Drug companies are starting to do interesting research on the active ingredients of WGFJ, with the goal of more effective drug administration.

I think personal research with disabling important enzymes is not worth the risk.

[outriderx]

yes, SWIM is aware of that and even with no tolerance will just go in the really low-dosage areas, since he doesnt have much and wants to enjoy it (thats why he asks about potentiation via medazepam or other things..)

anyhting besides grapefruit juice, easier things? anything about the medazepam combi?

[Laudaphun]

Other substances besides grapefruit juice which are CYP3A4, and CYP3A5 (which is generally less active than CYP3A4) inhibitors are Azamulin, diltiazam, erythromycin, fluconazole, itraconazole, ketoconazole, ritonavir, and troleandomycin.

It's actually a group of compounds present in grapefruit juice called furanocoumarins which are responsible for the enzyme inhibition. These are produced naturally by various plants.

But becareful because the CYP34A enzyme alone which is responsible for metabolism of over 50% of clinically prescribed drugs which are metabolized by the liver, therefore use caution as if you are consuming any other drugs, as there is a good chance that you are affecting their metabolism as well... acetaminophen metabolism is inhibited as well, so becareful if you have a APAP-painkiller habit. Also the metabolism of antibiotics is generally increased by the above substances, for whatever that's worth.

There are a lot of other common and rather interesting enzyme inducers and inhibitors of some of the most commonly used substances... but they are not necessarily important when it comes to benzos so that is for another topic in another forum.