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

[paranoid android]

^Fact on only being able to fit 60mg's into one ml..... I had to argue this alot as ppl would wanna do 100-200mg shots. (Myself included) and I would sware 100mgs hit harder than 60 in a 1ml syringe -- suppose this is because I was not getting the full 60 out of a 60 where as a 100, def getting the 60 ---- all ER morphine has a rinse. (That you shouldnt do ....but does contain a good percent of your product unless you got morphine powder or IR's)

oh no one shot is not going to make anyone an addict -- may be hard to not want to repeat the experience though. Hydromorphone is alot "more-ish" as it only lasts about 2 hours but the rush is better than heroins, in most peoples opinion.

Still one shot of dilly you will not be an addict, but it will be more-ish in a couple hours, morphine you got more like 6 and you prolly falling asleep buzzed.

Needles are fuckin bad news though -- save that shit for when you are super old and in pain

Lol on dilly i became a human pin cushion for awile. I happened into a steady supply for awile and was banging 3 18mg hydromorph contind about every 4 hours sometimes. I was so hooked id be sick already by the 6 hour mark.

I get the mscontins and theres a trick to getting all the morphine out. It takes abit

 

[lost weekend]

Would it not be the case that genuine pharmaceutical morphine could be stronger and cleaner than say heroin you would buy on the street ?

 

[Psychonauticunt]

After having experimented for a while with Diclazepam, I never really quite understood why it wasn't marketed. For me, it's like diazepam - just a vastly improved one. It has a similarly balanced effects profile as a benzodiazepine. If you take into account its active metabolites, its duration becomes rather long.

Diazepam is metabolized mainly into desmethyldiazepam, which is weak (being a partial agonist), and produces temazepam and oxazepam (also weaksauce) in smaller amounts.
Diclazepam produces delorazepam as its main active metabolite, which is further metabolized into lorazepam and lormetazepam.

Diclazepam and its metabolites are infinitely better than diazepam's.

 

[placebonaut]

After having experimented for a while with Diclazepam, I never really quite understood why it wasn't marketed. For me, it's like diazepam - just a vastly improved one. It has a similarly balanced effects profile as a benzodiazepine. If you take into account its active metabolites, its duration becomes rather long.

never tried it and don't know much about it so I took a "quick look" (ok so I have a fixation problem with some things, fucking OCD brain or something ffs), ended up having to wrestle quite a lot with chatGPT to do this as it seems there's not very much research for Diclazepam sadly so no-one should trust this chatGPT produced info on it!


seems that the key take out is "The important difference is that diazepam's acute phase is better characterized and tends to be more prominent relative to its later metabolite phase, whereas diclazepam has a particularly significant long-lived delorazepam component. The original diclazepam human experiment found an approximately 42-hour parent half-life and active delorazepam, lorazepam and lormetazepam metabolites."

I know you say that its duration becomes rather long, but looking at the crap below and to me (who doesn't understand enough about benzo metabolites) it doesn't seem that different to diazepam to be honest, just a different profile. Maybe the major risk with Diclazepam to your duration point is with abusing it and taking it too frequently given the 48h window, though I tend to leave a good 3-4 days between doses of Diazepam when I do use it

other thing is that Diazepam has stronger anxiolysis/relaxation effects which is for me 1 the main reasons I like it.

hmm, i'm tempted to see if i can find some to give it a go!

Time after dose	5 mg Diclazepam	10 mg Diazepam
0–2 h	Building: anxiolysis, relaxation and sedation begin; impairment may develop	Building: diazepam rises relatively quickly; noticeable relaxation/sedation and psychomotor impairment
2–6 h	Moderate → strong: parent diclazepam is the main contributor; sedation, slowed reactions, impaired coordination and amnesia possible	Strongest period: parent diazepam dominates; pronounced anxiolysis/relaxation, sedation and impairment possible
6–12 h	Moderate: still substantial parent-drug effect; active metabolites beginning to contribute	Moderate → declining: noticeable effects generally declining, although impairment can remain
12–24 h	Moderate: diclazepam remains present; delorazepam increasingly contributes	Mild–moderate: parent drug declining, while nordazepam begins becoming increasingly relevant
24–48 h	Mild–moderate, persistent: delorazepam becomes increasingly important; residual sedation/impairment possible	Mild–moderate, persistent: diazepam + nordazepam; residual anxiolysis and sedation possible
2–3 days	Mild but persistent: delorazepam is now a major contributor; subjective effects may be subtle while pharmacological activity remains	Mild/persistent: nordazepam increasingly dominates residual exposure
3–5 days	Residual: mainly long-lived delorazepam; obvious subjective effects may be largely gone, but residual CNS effects are possible	Residual: nordazepam becomes particularly important; lingering sedation/psychomotor effects possible
5–7 days	Low residual activity: delorazepam can still be present	Low–moderate residual activity: nordazepam can still contribute substantially
7–14 days	Usually little/no obvious subjective effect, but metabolites may remain detectable	Usually little/no obvious subjective effect, although long-lived metabolites can remain
Overall profile	Long, relatively smooth tail driven heavily by delorazepam	Strong initial effect + very long tail, with nordazepam becoming increasingly important

The visual takeaway​

5 mg diclazepam

Moderate → strong → moderate → mild → long residual tail
████████ → ██████ → ████ → ██ → █ → ···

10 mg diazepam

Strong → moderate → mild → long residual tail
██████████ → ██████ → ███ → ██ → █ → ···

Feature	Diclazepam — 5 mg	Diazepam — 10 mg
Parent drug half-life	~42 h terminal	~20–70 h; ~24–48 h commonly cited
Main active metabolite	Delorazepam	Nordazepam / desmethyldiazepam
Major metabolite half-life	~78 h delorazepam	~40–120 h nordazepam
Other active metabolites	Lorazepam; lormetazepam	Temazepam; oxazepam
Metabolic pathway	Diclazepam → delorazepam → lorazepam / lormetazepam	Diazepam → nordazepam → oxazepam; separate branch → temazepam → oxazepam
Approx. parent amount administered	5 mg	10 mg
Estimated major-metabolite amount	Delorazepam: ~0.2–2 mg crude modeling range	Nordazepam: ~0.4–4 mg crude modeling range
Other metabolite amounts	Lorazepam: ~0.1–0.7 mg; lormetazepam: ~0.05–0.5 mg	Temazepam: ~0.2–1 mg; oxazepam: ~0.1–1 mg
Confidence in metabolite-mass estimates	Very low	Low, but better supported than diclazepam
Early dominant compound	Diclazepam	Diazepam
Later dominant compound	Delorazepam	Nordazepam
Approx. strongest subjective period	Roughly 5–12 h	Roughly 4–12 h
Residual active exposure	Several days	Several days to >1 week
Particularly long-lived component	Delorazepam	Nordazepam
Typical key effects	Anxiolysis, sedation, muscle relaxation, amnesia, impaired coordination	Anxiolysis, sedation, muscle relaxation, amnesia, anticonvulsant effects
Relative certainty of PK data	Low	High
Overall profile	Long-acting benzodiazepine with long-lived active metabolites	Long-acting benzodiazepine with exceptionally well-characterized active-metabolite accumulation

Spoiler: Diclazepam

Best directional estimate for a 5 mg dose​

Compound	Approx. terminal half-life​	Relative amount expected from 5 mg diclazepam	Very rough mass-equivalent estimate*​	Relative contribution to overall effect	Key effects
Diclazepam	~42 h​	100% initially	5 mg parent​	High initially	Anxiolysis, sedation, muscle relaxation, amnesia, impaired coordination
Delorazepam	~78 h​	Largest metabolite	~0.5–2 mg equivalent, very uncertain​	High and prolonged	Strong anxiolysis/sedation, muscle relaxation, anticonvulsant activity
Lormetazepam	~13 h​	Smaller	~0.05–0.5 mg equivalent, very uncertain​	Moderate, relatively shorter-lived	Sedation/hypnosis, anxiolysis, muscle relaxation
Lorazepam	~12 h​	Smaller than delorazepam but potentially substantial later	~0.1–0.7 mg equivalent, very uncertain​	Moderate, particularly in later phase	Anxiolysis, sedation, muscle relaxation, anticonvulsant activity

* Important: those ranges are not experimentally established amounts of metabolite actually produced. They are deliberately broad directional estimates based on the observed serum concentration relationships and the known pharmacology of the metabolites. I would not interpret “0.5–2 mg delorazepam” as literally meaning that a 5-mg dose generates 0.5–2 mg of isolated delorazepam.
The reason I'm putting delorazepam substantially ahead of the others is that in the original experiment its peak concentration was ~2.0 ng/mL, versus ~0.40 ng/mL for lorazepam and ~0.34 ng/mL for lormetazepam. Delorazepam also has the longest half-life of the three, around 78 h, compared with ~12 h for lorazepam and ~13 h for lormetazepam.

A more useful way to think about the 5 mg dose​

If what you're ultimately trying to estimate is “how much benzodiazepine activity does 5 mg diclazepam turn into over time?”, I'd model it qualitatively like this:

Time after 5 mg	Dominant contributors	What I'd expect directionally
0–12 h	Diclazepam	Parent drug dominates; sedation/anxiolysis and impairment
12–48 h	Diclazepam + increasing delorazepam	Parent still important, while the long-lived active metabolite becomes increasingly relevant
2–4 days	Delorazepam + lorazepam/lormetazepam	Delorazepam increasingly dominates residual pharmacological exposure
4–7 days	Delorazepam	Much of the remaining active benzodiazepine burden is likely attributable to the long-lived metabolite
>1 week	Delorazepam/residual metabolites	Pharmacological exposure can persist, although this does not mean someone remains intoxicated for that entire period

This fits the actual analytical observations: after the ~1-mg experiment, diclazepam itself was measurable in serum for about 99 hours, while delorazepam was measurable for up to 10 days; in urine, delorazepam, lormetazepam and lorazepam were detectable for approximately 6, 11 and 19 days, respectively. Detection is obviously not equivalent to impairment.

The three I'd prioritize​

If you're specifically interested in the 5-mg diclazepam → metabolite → duration analysis we've been doing, I'd read them in this order:

1. Moosmann et al. 2014 — the fundamental human PK/metabolism study.
   
   https://doi.org/10.1002/dta.1628
2. WHO Diclazepam Critical Review — the most comprehensive compilation and interpretation of the available evidence.
   
   DSpace
3. Organ distribution study (2019) — useful for seeing how dramatically parent/metabolite concentrations can differ in actual human toxicology cases.
   
   Redirecting

One correction to keep in mind from our earlier tables: the 2014 paper is much stronger evidence for which metabolites exist and how long they can be detected than for estimating how many milligrams of each metabolite are produced. The latter estimates we discussed were extrapolations, not quantities measured by the study.

Spoiler: Diazepam

10 mg diazepam — parent drug and major metabolites​

Compound	Relationship	Approx. half-life​	Approx. persistence	Key effects	Very rough amount / exposure from 10 mg diazepam​
Diazepam	Parent	~20–70 h; ~30–50 h is a reasonable central estimate​	Parent remains measurable for several days	Anxiolytic, sedative, muscle relaxant, anticonvulsant, amnestic	10 mg administered​
Nordazepam / desmethyldiazepam	Major N-demethylated metabolite	~40–120 h, commonly ~50–100 h​	Several days to >1 week	Long-lasting anxiolysis, sedation, muscle relaxation, anticonvulsant effects	~0.4–4 mg as a deliberately broad modeling range​
Temazepam	3-hydroxydiazepam	~8–20 h​	Roughly 1–2 days	Sedative/hypnotic, anxiolytic, muscle relaxation	~0.2–1 mg as a crude modeling range​
Oxazepam	Downstream metabolite of nordazepam/temazepam	~5–15 h​	Roughly 1–3 days pharmacologically, although conjugates persist longer	Anxiolytic, sedative, muscle relaxation	~0.1–1 mg as a crude modeling range​

The major metabolic routes are diazepam → nordazepam → oxazepam and diazepam → temazepam → oxazepam. Nordazepam is the major circulating metabolite and has a substantially longer half-life than diazepam.

What I would actually use as a "best guess"​

If you want one set of numbers for a rough conceptual model rather than a range:

From 10 mg diazepam	Crude working estimate​
Diazepam administered	10 mg​
Nordazepam	~1–2 mg​
Temazepam	~0.5 mg​
Oxazepam	~0.25 mg​

I'd attach at least a several-fold uncertainty to those metabolite quantities. They should not be interpreted as measured quantities of metabolites physically generated.
Why? In a human study after a 4-mg dose, urinary recovery over 96 hours was only about 3.9% as nordazepam, 6.6% as temazepam and 2.8% as oxazepam. Those percentages represent urinary recovery, not total formation, so they cannot simply be treated as the percentage of diazepam converted into each metabolite.

Expected time course after 10 mg​

Time after dose	Most relevant contributors	Directional picture
0–6 h	Diazepam	Parent drug overwhelmingly important; strongest acute effects
6–24 h	Diazepam + emerging nordazepam	Parent still dominant, but nordazepam is accumulating
1–3 days	Diazepam + nordazepam	Nordazepam increasingly important
3–7 days	Nordazepam + residual diazepam	Long-lived active metabolite becomes increasingly important
7–14+ days	Nordazepam + downstream metabolites	Residual drug/metabolites can remain detectable; this doesn't imply continuous intoxication

A particularly interesting finding is that after 5 mg, nordazepam's urinary concentration peaked around 100 hours after dosing, compared with about 2 hours for diazepam. The same study found that diazepam and its metabolites remained detectable for at least 15 days.

A useful correction to the earlier 5-mg table​

I would now characterize the metabolite amounts more cautiously:

Dose	Diazepam​	Nordazepam​	Temazepam​	Oxazepam​
5 mg	5 mg​	~0.2–2 mg​	~0.1–0.5 mg​	~0.05–0.5 mg​
10 mg	10 mg​	~0.4–4 mg​	~0.2–1 mg​	~0.1–1 mg​

These are modeling ranges, not experimentally measured metabolite yields. The particularly large uncertainty for nordazepam is intentional: about 50–60% of diazepam undergoes N-demethylation, but that does not mean 50–60% of the administered mass appears as free nordazepam—the metabolite is subsequently distributed, metabolized and conjugated.
Also, 10 mg isn't necessarily exactly twice the subjective effect of 5 mg. Plasma exposure generally increases with dose, but pharmacodynamics, tolerance, age, CYP2C19 genetics, liver function and drug interactions can produce substantial individual differences.
For perspective, controlled human testing has specifically examined 10 mg diazepam and found measurable acute impairment shortly after dosing, while older overnight testing found much less measurable next-morning impairment in healthy subjects. That illustrates why "half-life" and "duration of noticeable impairment" shouldn't be treated as the same number.

 

[Psychonauticunt]

That all seems to check out, sure. Also, diazepam is well-known for being one of the most rapidly absorbed and peaking benzos, which has obvious therapeutic benefits.

A lot of it, for me, just boils down to the fact that I like delorazepam, lorazepam and lormetazepam (one of my absolute favourites of like, almost 40) more than I like temazepam, nordazepam or oxazepam, the last two being particularly and emphatically meh.

Diazepam's duration of action isn't all that long, though - at least not as many people make it out to be. Says in the table that the approximate strongest subjective period for diazepam is roughly 4–12 h. That's an unnecessarily wide range to accommodate for some slow metabolizers or those who are super sensitive to even mild effects from metabolites, but diazepam has a biphasic action and the stronger therapeutic one is rather short, in fact. For most people, the strongest subjective period of activity is about 4-6 hours.

When people take diazepam for anxiety, it is typically administered THREE times a day. It is not especially known for producing next-day grogginess.

In a hospital setting, lorazepam is often given because if it takes hours, a second dose of diazepam is usually needed. It reaches its peak rapidly, but is then distributed around the body, and is no longer as active. Lorazepam, despite it's WAY shorter half-life, has a longer duration of principal action.

Diazepam's half-life due to its metabolites, especially with cumulated doses, is what makes it great for tapering, but after 10 hours of taking a Valium, you've got the benzo equivalent of half a sip at the bottom of your beer.

EDIT: Massive thanks for the info dump. You say OCD brain - are you sure it's not autism brain?

 

[placebonaut]

EDIT: Massive thanks for the info dump. You say OCD brain - are you sure it's not autism brain?

I thought ADHD but Dr GPT thinks it's "Very high openness/High novelty/sensation seeking" not sure if these are real medical terms but I need loads of mental stimulation to keep me sane, otherwise I sedate myself