Benzos Which benzos are worth snorting? A systematic investigation

[Vesicle]

In my time hanging out in various drug circles, I've noticed the occasional mention of snorting various benzodiazepines, the most common of which being alprazolam. It is stated within these circles that benzodiazepines (in general) should not be insufflated due to their low water solubility, and that oral/sublingual administration is more viable. Poor water solubility is claimed to be a significant factor affecting the intranasal viability of benzodiazepines.

However, a couple of unique benzodiazepines are highly soluble in water and have therefore been deemed "snortable". The main ones that come to mind are midazolam, flurazepam, and triazolam (debatably).

I sought to investigate these claims by checking the available literature for the water solubility of various benzodiazepines and any reports of intranasal use, whether in a medical setting, anecdotally (e.g. via this forum), or in animal studies.

I encourage anyone to debate/discuss my findings as I most certainly missed important details on this complex topic. I understand other factors such as pH and individual pharmacokinetics will affect the intranasal bioavailability. But, I chose to focus on water solubility as it is still greatly important.

I have compiled my findings and sources in the table below. This table is a DRAFT, so do not take these results as hard evidence or fact. And please do not use this table as the basis for your next sniffing session XD.

Name	Common Brand	Solubility in Water @ 25°C (mg/L)	Worth snorting?
Alprazolam	Xanax	13.1	NO
Clonazepam	Klonopin	100	NO
Diazepam	Valium	50-66	NO
Etizolam	Etilaam	42*	NO
Flurazepam	Dalmane	500,000	YES
Lorazepam	Ativan	80	NO
Midazolam	Versed	>22**	YES
Triazolam	Halcion	4.53	UNCERTAIN

∗ - Estimated based on results from ALOGPS
∗∗ - Highly pH dependent. The solubility of Midazolam increases as pH decrease. This supposedly is the case for some other benzodiazepines as well.

Notes: I find it strange that midazolam has a relatively low water solubility yet it is the most commonly used benzodiazepine for intranasal administration in a medical setting. Also, I find it strange that flurazepam supposedly has a water solubility that is MAGNITUDES greater than all the others. This must be some kind of edge-case or poor estimate, but it was the main result I found. I am open to any and all corrections!

SOURCES:

Alprazolam

Alprazolam | C17H13ClN4 | CID 2118 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Clonazepam

Clonazepam | C15H10ClN3O3 | CID 2802 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Diazepam

Diazepam | C16H13ClN2O | CID 3016 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

T3DB: Etizolam

Flurazepam

Flurazepam | C21H23ClFN3O | CID 3393 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Lorazepam: Uses, Interactions, Mechanism of Action | DrugBank Online

Lorazepam is a short-acting benzodiazepine commonly used to treat panic disorders, severe anxiety, and seizures.

go.drugbank.com

Midazolam

Midazolam | C18H13ClFN3 | CID 4192 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Transmucosal nasal drug delivery : systemic bioavailability of nasally applied midazolam - edoc

edoc.unibas.ch

Pharmacokinetics and Pharmacodynamics of a New Intranasal... : Anesthesia & Analgesia

of a novel formulation into both naris. Blood samples were taken serially from 0 to 12 h after each dose. Plasma midazolam concentrations were determined by liquid chromatography/mass spectrometry/mass spectrometry. Noncompartmental analysis was used to estimate pharmacokinetic parameters. The...

journals.lww.com

Triazolam

Triazolam | C17H12Cl2N4 | CID 5556 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Intranasal absorption of flurazepam, midazolam, and triazolam in dogs - PubMed

Intranasal delivery of flurazepam, midazolam, and triazolam was studied in a dog model as a possible alternate route of drug administration for treatment of insomnia. Four beagles received each hypnotic by both intranasal and oral routes on two separate occasions. Plasma concentrations for each...

pubmed.ncbi.nlm.nih.gov

 

[RxVeritas]

Flurazepam has a pretty high oral bioavailability (83%) while the others are less than 50%.

The last study you mentioned is interesting and definitly seem to point to intranasal being the superior ROA for all of those drugs, at least in dogs (which I would guess can fairly accurately be extrapolatd to humans).

Very interesting stuff.

 

[Vesicle]

Flurazepam has a pretty high oral bioavailability (83%) while the others are less than 50%.

The last study you mentioned is interesting and definitly seem to point to intranasal being the superior ROA for all of those drugs, at least in dogs (which I would guess can fairly accurately be extrapolatd to humans).

Very interesting stuff.

Yeah i’m unsure if the canine nasal cavity is drastically different compared to humans, but it’s an interesting study nonetheless. As for the bioavailability, flurazepam is a very unique outlier and i wonder what properties make it such a potent drug for intranasal use .

 

[TUFKA-Sleepwalker]

When I saw the title, first thing that came to mind was some old friends getting massive nosebleeds after snorting crushed midazolam, not diluted in water.
Their noses should have been trained well enough by all the other drugs they snorted.
Might be very a-typical , but worth the mention.

 

[Vesicle]

When I saw the title, first thing that came to mind was some old friends getting massive nosebleeds after snorting crushed midazolam, not diluted in water.
Their noses should have been trained well enough by all the other drugs they snorted.
Might be very a-typical , but worth the mention.

Yeah midazolam is strange. From what I've read, pH plays a large role in it's ability to be absorbed, with lower pH levels resulting in greater bio-availability. Putting acidic solutions up your nose doesnt sound like the most pleasant experience thought...

Did your friends get affected or did they just get nose bleeds?

 

[TUFKA-Sleepwalker]

Not sure if snorting surpassed their 'normal' levels of weirdness on midazolam...
They had a massive tolerance to begin with.
But they snorted ounces of speed and coke, had no septum left, yet Dormicum made their noses bleed.

This benzos amnesia brought me in strange and stupid situations.
30 years ago the DSM mentioned Midazolam as an 'non-addictive' benzo.
And 'freely' uncontrolled available in liquid form at my job.
As the naive boy I was...yeah right...that turned out bad.
In the end I was taking a 10ml/30mg ampoule IM spread over a day.
Until the stash ran out and I went coldturkey through one of the most severe WDs ever.

Dormicum is excellent if you want to forget. Everything.
For passing out, great benzo.
For sleeping and resting, it doesn't work. You forget you slept, so only feel wasted.
When you use it IM, you will forget even 15 minutes BEFORE you took it.
I spent days looking for ampoules I had hidden the night before and were nowhere to be found.
Awful.
Just keep in mind, black holes in your memories don't ever go away.

Sorry, lil' off track, back to topic

 

[themediumlebowski]

Not sure if snorting surpassed their 'normal' levels of weirdness on midazolam...
They had a massive tolerance to begin with.
But they snorted ounces of speed and coke, had no septum left, yet Dormicum made their noses bleed.

This benzos amnesia brought me in strange and stupid situations.
30 years ago the DSM mentioned Midazolam as an 'non-addictive' benzo.
And 'freely' uncontrolled available in liquid form at my job.
As the naive boy I was...yeah right...that turned out bad.
In the end I was taking a 10ml/30mg ampoule IM spread over a day.
Until the stash ran out and I went coldturkey through one of the most severe WDs ever.

Dormicum is excellent if you want to forget. Everything.
For passing out, great benzo.
For sleeping and resting, it doesn't work. You forget you slept, so only feel wasted.
When you use it IM, you will forget even 15 minutes BEFORE you took it.
I spent days looking for ampoules I had hidden the night before and were nowhere to be found.
Awful.
Just keep in mind, black holes in your memories don't ever go away.

Sorry, lil' off track, back to topic

Some do, repressed memories are not uncommon, nor is sensory recall.

Drugs that punch holes in your brain might be a slightly different story though

If the synapse is blocked by a neurotransmitter that the benzo produces then that also would change things a bit.

 

[OntarioGuy]

I personally dont believe water solubility matters. they work fine nasally. the musous membranes in your nose seem to absorb benzos as well as the ones under your tongue. I think the "you cant snort benzos cause they arent water soluble" is one of those things on bluelight where ppl repeat it like its gospel without even trying it themselves. if they work sublingually, why not intranasally?

 

[german]

When I saw the title, first thing that came to mind was some old friends getting massive nosebleeds after snorting crushed midazolam, not diluted in water.
Their noses should have been trained well enough by all the other drugs they snorted.
Might be very a-typical , but worth the mention.

You should mix with water if you snort