Benzos lorazepam (Ativan) seems much 'harder to handle' than other benzos

[4DQSAR]

@Syntherize - Good point well made. around here we have a hospital ward where alcoholics who pass out in public are sent to. In essence all the hospital does is to feed them Librium until their hand's stop shaking, give them something akin to Stoss therapy (huge doses of IV vitamins), feed them up and after 24 hours of observation, push them out of the door.

It's always sad to watch someone you care for drink themselves to death. Upsetting when it's someone young enough to be your own child. MGTG did just that and Tom was just a kid. We got him a TV, bought him food, took him to the cinema and other places where alcohol wasn't available & ensured he always had someone to phone 24/7 - but all we know is that on one Friday evening he bought 1.5L of cheap whiskey, drank the lot in a few hours and his body wasn't discovered until the following week. I believe it took a couple of white-lies to get the Police to perform a welfare check. His GF was in bits. Both were lovely people. I mean two of the nicest people it's ever been my privilage to know.

For many years there was a [P] benzodiazepine only used in Spain (bentazepam/Tiadiona™), similarly in Russia phenazapam (феназепама™) and in India eitzolam (Etilaam™) and from what I can gather, in each case the idea was that a pharmacist could suggest them for the treatment of alcoholism. I don't think for a moment that an inebirated person would ever be served. It seemed more like a concerned family member or friend could buy them on the basis that they wouldn't provide the patient more the stated dose. Certainly a friend who visited Spain related how they had to have the medicaton explained to them, provide ID and so on - I assume this was intended to prevent smurfing. A bit like how Valoid™ (cyclizine) was sold in the UK.

Now, I've never tasted phenazepam but I suspect onset is quite slow and it isn't much fun. The other two I have tasted and really cannot imagine anyone thinking them 'fun'. Again, can's speak for phenazepam but the other two both have a plateau dose i.e. taking more may increase duration but will not subjectively be 'stronger'.

In a better world clobazam would become a [P] medication. It's an odd one. Uniquely it's a 1,5-benzodiazepine; all the others are 1,4-benzodiazepines. So by defintion clobazam cannot bind to the α1 or α5 subunits. The former subunit being the target of the Z-drugs, both subunits being targetted by alcohol i.e. clobazam is no 'fun' at all if alcohol-like intoxication is the goal. But far more importantly, alcohol doesn't 'amplify' it's effects AND clobazam demonstrates a plateau at 40mg/day which is 20mg [BID] i.e. even if someone ate a whole box, it may sedate for many days but will not render them unconscious.

The LD50 of clobazam has been measured as 100mg/kg in canine models and 6,000mg/kg in rodent models. However you look at it, it's the safest benzodiazepine in use. In a study of patients with refractive epilepsy, so called 'supertheraputic' doses of clobazam were prescribed and from every metric, the patients prescribed 160mg/day were no more sedated/disoriented or liable to physical side-effects than the patent prescribed 40mg/day. The cohort size was 241 patients i.e. 80 were given a placebo, 80 were given the official maximum dose of 40mg/day and 81 given 160mg/day.

It's even the case that neither clobazam nor any 1,5-benzodiazepine would be attractive targets for someone developing novel RCs. It seems no amount of complex modification produces a compound much more potent than clobazam itself. I belive CP-1414S is no more potent than clobazam - it's simply more sedating, but more akin to how first-generation antihistamines sedate i.e. in no way pleasent.

 

[notsmokeymcpot42088]

ativan never hit hard for me. I do remember tales of it being the only benzo you could hallucinate off of --- I do not know if there is any truth to this however

*edit* ^ I can vouch for phenazepam not being much fun and I think that is a good system to have. Of course as americans we try and import both as of course we do... but that could be fixed if we had the same system.

I can also vouch for how much it sucks to watch someone young drink themselves to death ... lost a close friend at 34. Very talented musician but had a very crazy life that I am sure drove him to drink..

 

[Jnowhere]

I have a fair bit of experience with a variety of benzos. Fortunately, I have only become dependent once (and the WDs from that scared me so much I never allowed myself to get in that deep again).

Anyway, this post concerns some experiences I have had (both in recent weeks and also when taken years ago) with lorazepam. I have a bottle of 2.5mg Ativan tablets. I also have a bottle of Pfizer (alprazolam) Xanax, which means I've got a convenient point of comparison.

To get straight to the point, I have found the lorazepam to be 'tricky' to use. Generally, half of a 2.5mg tablet provides a reduction in anxiety and some useful sedation at bed time. However, a full 2.5mg tablet can cause significant balance issues and blackouts. This is not consistent (if it was, I woudn't keep taking a full tablet). Sometimes a full tablet just feels like more of the same effect as a half tablet, as you might expect. However, other times it leads to symptoms of minor benzo OD, with things like balance impairment which is sudden and strong enough to send me head first into closets, door frames, or backwards into ... whatever is behind me.

Additionally, a full tablet at night before bedtime often leads to "morning surprises" such as a full plate of food prepared nicely and then left on the kitchen floor, untouched. Or food and other consumables "disappearing", where I've presumably taken them in a blackout. I've also built up a collection of some nasty looking bruises, mostly on my limbs, presumably from doing the Ativan waltz and then having no memory of it.

At this point, some readers are probably thinking "yeah dipshit, you're taking too much than you can handle, so just stick to the half tablet, you dumbass, stupid cunt, piece of shit, I'll fucking kill you..." ahem

However, I'm somewhat familiar with benzos and have over the years built up some idea of my tolerance and reaction to certain types of benzos. As mentioned I also currently have a bottle of 2mg Xanax bars (real ones), and these I can consistently take 4 -6mg without any issues. Over many years, I've taken tonnes of diazepam, etizolam, temazepam in the past without issues, and also navigated moderate doses of some heavier benzos like flubromazepam, bromazolam, phenazepam, phenazolam, and others without waking up naked in a jail cell (or any issues, really - except for one time where I woke up with a dodgy haircut I had no memory of getting).

I understand that benzos can be highly unpredictable and it would be foolish to think I'd "mastered" them or could predict the outcome of dosing every time. But I am just wondering if anyone can relate to my situation specifically with lorazepam or perhaps know one of its particular mechanisms of action which might be causing these unexpected midnight food making (and abandoning) incidents, and crashing into walls and furniture like a gridiron player, from what seems to be a very standard dose (2.5mg - a single tablet).

"Lo-raz-e-PAM!
Baby don't hurt me,
Don't hurt me,
No more"

I guess you are not in America. I used 2mg lorazepam 3x a day for years and no problems and even after losing my temper and going into a rage I took about 4 or so 2mg Ativan tablets and they only mild calmed me down.


You have experience with benzos, I find it very odd that only 2.5mg would do anything but keep you emotional sort of numb,( as in no aniety).

I like Diazepam better. Weaker, but very relaxing. Or it was.

I find it odd that you would have that kind of reation if you can handle a fair amount of xanax.


I never, even at first, had any issues with the types of things you say they do. Yeah, only 2mg ones here but even 2x2mg at first never made do anything like that. That was on top of two strong opiods( all prescribed)
Morphine and oxycodone.

Are you only on just taking one? Because it should at the most sedate you. I had 3 family members also prescribed it and well they, at least 2 were using more than you are and non of that happened.

What else are you taking? Also are you mixing it with xanax?


I personally felt gypted, and that 2mg was not enough, even when naive to benzos and opiods( sort of for the opiods)

Are you drinking with them? They are best on an empty stomach and even for a while I drank a bit while on them and never had an issue.


So, what else do take with them? I also opiods and mixed with alcohol a few times and nothing like that happened.

Is this just a case of ones own bodily chemistry reaction being different?

 

[Dextro .45]

ativan never hit hard for me. I do remember tales of it being the only benzo you could hallucinate off of --- I do not know if there is any truth to this however

*edit* ^ I can vouch for phenazepam not being much fun and I think that is a good system to have. Of course as americans we try and import both as of course we do... but that could be fixed if we had the same system.

I can also vouch for how much it sucks to watch someone young drink themselves to death ... lost a close friend at 34. Very talented musician but had a very crazy life that I am sure drove him to drink..

How much did u take? ….did u eat prior…..any other substances? Little coke? Some factors can alter effects

After accurately gauging its potency, I must say its impressive.

I just took 2mg Lorazepam on a fasted state, 2 weeks no sedatives, and it hit hard, but manageable….I would take 4mg of Lorazepam MAX and that might be too much…..in 35min everything hit instantly, nicely. 0.5mg & 1mg tab are common…..so I took Ativan 2mg and Wow……for 240lbs 6’ empty stomach & baseline. I give Lorazepam an A

I have Alprazolam 0.5mg tablets coming Monday and more Lorazepam ha ha ha

I honestly wouldn’t take more than 4mg …..I’d be Rocked !

I’m going to take 1mg of Ativan and 1.5mg of Xanax together and see those effects lol. The Alprazolam will add a pleasant mood-lift on top of Lorazepams tranquilizer dart like effects l …then the rest I’ll hoard away…..ya, until I bar out and it’s all gone lol. Fuuuuuk

 

[Jnowhere]

Really you got hit hard by one 2mg Ativan. Huh. I never hardly even noticed them. I Got off them and onto 10mg Valiums 3 x a day. My plan was to quit using benzos but that was almost 3 years ago, opps.

I always took them on an empty stomach. I admit that when I was first prescibed benzos when there there was a whole lotta bad things going on in my life which was supposed to over.( I just passed the 1 year mark doctors had given me to live, opps the doctors were wrong). I didn't even really quit drinking till after being put on Ativan. At least for a while. Not really my choice,lol.


I was also on Morphine and Oxycodone but I didn't die and I still am on benzos which kinda sucks but valium I suppose might still relax me.

I am amazed because most have said Ativan( lorazepam ) is rather mediocre.

I have never mixed benzos except maybe, valium and a leftover Ativan and well after years I got what expected, basically nothing. On an empty stomach.

I know of one or two people who switched to k-pins or clonazepam( mis?) and said it was the best.


But then again they tend to become benzo, lifers and I actually intend on getting off Valium. It just has been scary, being on even a relatively moderate dose for so long.


Hopefully the Xanax is real. I have read stories of fake shit being passed off as Xanax. Well good luck, bro and be safe.

Sincerely
J

 

[notsmokeymcpot42088]

How much did u take? ….did u eat prior…..any other substances? Little coke? Some factors can alter effects

1 mg usually. No other drugs - well pot. But that was the first benzo I was ever took actually. (Was like 13-14). Lol once cuz hockey practice was at like midnight to 1 AM and school was 7 am --- and another time cuz I was trippin balls and had to get to school and just broke down and was honest about it. Than a handful of times after that but not really much since I got ahold of about any other benzo.

Maybe it is just me -- something strange may be going on with my system regarding benzos. I remember just about being a damn case study for awhile there.

All you guys said go directly to the hospital youll never survive blah blah blah --- scared the shit out of me. Thank you for that.

I did end up fine and never went to no damn hospital as that felt like sure death.....but the scare is appreciated anyways.

After accurately gauging its potency, I must say its impressive.

I just took 2mg Lorazepam on a fasted state, 2 weeks no sedatives, and

it hit hard, but manageable….I would take 4mg of Lorazepam MAX and that might be too much…..

How much xanax do yo take max? I always figured lorazepam at about 1/2 potency.

in 35min everything hit instantly, nicely. 0.5mg & 1mg tab are common…..so I took Ativan 2mg and Wow……for 240lbs 6’ empty stomach & baseline. I give Lorazepam an A

I have Alprazolam 0.5mg tablets coming Monday and more Lorazepam ha ha ha

I honestly wouldn’t take more than 4mg …..I’d be Rocked !

Is lorazepam still prescribed sublingually? I remember I thought that was neat, only drug (at the time, way before sub) that had 'melt under tongue' on the bottle that I ever saw.

I’m going to take 1mg of Ativan and 1.5mg of Xanax together and see those effects lol. The Alprazolam will add a pleasant mood-lift on top of Lorazepams tranquilizer dart like effects l …then the rest I’ll hoard away…..ya, until I bar out and it’s all gone lol. Fuuuuuk

Hope you enjoyed your evening! Perhaps incomplete cross tolerance is what *Why* is happening with the lorazepam hitting harder.

I should prolly switch my benzo up but I dont think my shrink would love me being concerned about getting a little more out of an equivalent dose of something else lol

PS - Does lorazolam exist? Sounds like a banger based on what (NOTHING) I know

PPS - Jnowho has a decent point, about half (if not more havent checked lately) of the xanax being sold on the street is bromazolam. Which by almost all accounts is not as 'good' as alp but about equipotent.

 

[notsmokeymcpot42088]

@Syntherize -

The LD50 of clobazam has been measured as 100mg/kg in canine models and 6,000mg/kg in rodent models.

This matters -- the LD50 I always get is in mice. How do you find canine LD50's!? and are they generally more accurate if so?

Not that I want to approach the LD50 of anything but I had a friend come over talking about how they were thinking about doing that thing we dont talk about by taking a bottle of benzos --- knowing the person and that was not what they really wanted I told them to look up the LD50 of they benzo and it was a similar # ---- happened again recently on BL (or maybe there was a different reason someone asked) different benzo, both in thousands of mgs/kg IN MICE.

Nitrazepam is the benzo that people can feasibly overdose and die on correct? By feasibly I mean like under 100 pills of the largest size. (just so there is some standard for ya)

However you look at it, it's the safest benzodiazepine in use. In a study of patients with refractive epilepsy, so called 'supertheraputic' doses of clobazam were prescribed and from every metric, the patients prescribed 160mg/day were no more sedated/disoriented or liable to physical side-effects than the patent prescribed 40mg/day. The cohort size was 241 patients i.e. 80 were given a placebo, 80 were given the official maximum dose of 40mg/day and 81 given 160mg/day.

It's even the case that neither clobazam nor any 1,5-benzodiazepine would be attractive targets for someone developing novel RCs. It seems no amount of complex modification produces a compound much more potent than clobazam itself. I belive CP-1414S is no more potent than clobazam - it's simply more sedating, but more akin to how first-generation antihistamines sedate i.e. in no way pleasent.

Addiction potential aside, in my humble opinion 1.4 benzos are some of the safest drugs prescribed. I do love that you are looking for ways to make them safer for those damn supertheraputic users though!

PS - Dont take 100 benzos, you MAY DIE. You DEFINITELY will not enjoy it any more than 5.

 

[BadBoy377]

This matters -- the LD50 I always get is in mice. How do you find canine LD50's!? and are they generally more accurate if so?

Not that I want to approach the LD50 of anything but I had a friend come over talking about how they were thinking about doing that thing we dont talk about by taking a bottle of benzos --- knowing the person and that was not what they really wanted I told them to look up the LD50 of they benzo and it was a similar # ---- happened again recently on BL (or maybe there was a different reason someone asked) different benzo, both in thousands of mgs/kg IN MICE.

Nitrazepam is the benzo that people can feasibly overdose and die on correct? By feasibly I mean like under 100 pills of the largest size. (just so there is some standard for ya)



Addiction potential aside, in my humble opinion 1.4 benzos are some of the safest drugs prescribed. I do love that you are looking for ways to make them safer for those damn supertheraputic users though!

PS - Dont take 100 benzos, you MAY DIE. You DEFINITELY will not enjoy it any more than 5.

What's your favourite benzo?

 

[4DQSAR]

It seems all of the nitrobenzodiazepines are more toxic than the others. When designing a novel benzodiazepine (pyrazolam) one thing that was looked into was any examples of fatal overdoses involving benzodiazepines alone. We happened upon the Swedish government's data on suicide and nitrazepam, nimetazepam and flunitrazepam were all leading methods with a few cases involving clonazepam. The important bit being that in over 70% of cases, no other drug was found in body fluids.

Now we couldn't get the appropriate data to know if clonazepam was less toxic or if it was simply prescribed less frequently but what struck us was that flunitrazepam being far more potent than nitrazepam should in theory have made it safer because the amount prescribed and thus the amount imbibed would be much lower. But the opposite was true.

There are two toxic metabolites of nitrobenzodiazepines AND all nitrobenzodiazepines increase extracellular serotonin levels but which (if any) of these is responsible for the fatalities isn't clear.

But what we do know is that every nitrobenzodiazepine used medically is potentially fatal in overdose in the absence of other drugs.

There are quite regularly case studies of individuals who have consumed frankly insane amounts of diazepam (20 GRAMS in one case) and the important bit it that all survived. I'm sure there are examples of people passing out and dying from exposure, drowning, falls and so on but unless consumed with other drugs, they are incredibly safe. Certainly a 28 day supply of them would not provide a dose that could be fatal.

Sadly, the trials with 'supertheraputic' doses of clobazam didn't last long enough to test if physical dependence became an issue. Yes, it's still entirely possible to develop physical dependence to clobazam but from limited experimentation, it does seem that above the plateau, increasing the dose does not increase physical dependence. Clobazam is generally listed as being around half the potency of diazepam so assuming a person takes the maximum dose i.e. 20mg [BID], that's akin to 20mg of diazepam/day. Nasty, but the extreme half-life of clobazam (36-42 hours) and that of it's active metabolite norclobazam (71-82 hours) will at least mean that any reduction is easier than with short-acting benzodiazepines.

It just strikes me that of all the benzodiazepines, clobazam is the most benign by a large margin. Being no fun, it seems unlikely someone would continue to take them for long enough for physical dependence to become an issue as the anxiolytic activity only lasts about four weeks and of course taking more won't alter that fact.

We DID design a frustrated α1 ligand to test if a nitrobenzodiazepine that ONLY increased extracellular serotonin was possible. It was and it's action was nigh on identical to unrelated compounds that increased extracellular serotonin. None of us was keen to discover what 'supertheraputic' doses might do but we did wonder if it might be used as a novel antidepressant - one that simply bridged the gap between a patient presenting with unipolar depression and a typical antidepressant actually working i.e. only to be prescribed for upto 28 days. Not a profitable business model, but it could have been of value.

I look back and realize that as a rule benzodiazepines really are not much fun when consumed alone. When young we would mix dexedrine and diazepam (a sidewinder) which initially makes the user alert but the longer duration of the diazepam means that as time goes on, the subjective effects change from being stimulating to being sedating. Never more than to dexedrine and to blues - we were still quite conservative.