Rizzo The Nihilizo

Monday, October 9, 2006

Rizzo the mythbuster: Snorting benzos DOES work

In this post, I will not only conclusively show that administering benzodiazepines such as diazepam, lorazepam, and alprazoram work, but also work effectively.

It is a common perception among people who consider themselves knowledgeable about drugs that benzodiazepines such as diazepam can not be taken intranasal. The idea is that since benzos are not water soluble, they can not be absorbed in the mucous membranes in the nose, and thus only the drip (see: phlegm, a water based gel substance) gets you high, when it eventually reaches your stomach. This perception is fairly widespread, and so-called "n00bs" are lambasted for snorting any type of benzo outside of midazolam, a water soluble benzo. Considering there has been no scientific proof brought forth that to take benzos intranasal they have to be water soluble, I think it is safe to say for many people this is a matter of ego. Since there has been no scientific proof linking water solubility to benzo inefficiently in the nasal mucosa, I would like to point out that this should not be considered the de facto truth.

First of all, absorption of drugs commonly takes place in one of the many mucous membranes in the body. These places include the nose, the anus, the lips, under the tongue, the ears, and the genital area. (Wikipedia article on mucous membranes.) Drugs (among other things) are absorbed through the mucous membranes, into the local veins, into a main artery, and then soon after are to the brain. The advantage of taking drugs this way is that it bypasses first pass metabolism of the liver, which is extremely destructive to drugs, and it reaches the brain much quicker. This is why intranasal, sublingual, and anal administration is usually preferred to oral.

Bioavailability is a term used to describe the fraction of a dose that reaches the systemic circulation, or in more basic terms, how much of drug X that is actually reaching your brain. It is a basic description for determining how effective a certain method of administration is. One of the most important of these is lipid solubility. Lipids are a group of naturally occurring organic compounds that are related by their solubility in nonpolar organic solvents, and generally their insolubility in water. Although bioavailability also depends on a number of other factors, including but not limited to pH, molecular weight, etc, lipid solubility is the most important and the one I will be focusing on. Molecular weight does not matter that much seeing as how cocaine is a substance taken intranasal with a molecular weight of 303.353 g/mol, and diazepam has a molecular weight of 284.7 g/mol. The pH of a substance can be modified through different methods, and thus is not that important.

The intranasal bioavailability of diazepam in dogs is a whopping 80%, according to this study which states:

Mean bioavailability of BDZ following IN administration was 80 +/- 9%. CONCLUSIONS AND CLINICAL RELEVANCE: Diazepam is rapidly and efficiently absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 microg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available.

Obviously dogs are different than humans, but the nasal mucous membranes of mammals does not differ that much. Taken alone, this bit of information might not be conclusive, but there is more:

The purpose of this study was to evaluate the pharmacokinetic profile of intranasal lorazepam in comparison to currently established administration routes. Eleven healthy volunteers completed this randomized crossover study. On three occasions, each separated by a 1-week washout, subjects received a 2 mg dose of lorazepam via the intranasal, intravenous, or intramuscular route. Blood samples were collected serially from 0 to 36 hours. Noncompartmental methods were used to determine pharmacokinetic parameters. Lorazepam was well absorbed following intranasal administration with a mean (%CV) bioavailability of 77.7(11.1). Intranasal administration resulted in a faster absorption rate than intramuscular administration. Elimination profiles were comparable between all three routes. The concentration-time profile for intranasal delivery demonstrated evidence of a double peak in several subjects, suggesting partial oral absorption. Females were found to have significantly higher AUC values than males for all three delivery routes. Overall, this study demonstrated favorable pharmacokinetics of intranasal lorazepam in relation to standard administration methods. Intranasal delivery could provide an alternative, noninvasive delivery route for lorazepam.

Taken from this study. Not only is intranasal administration an efficient method, but my personal favorite method, sublingual, is also efficient:

Ten healthy volunteers received single 2-mg doses of lorazepam on five occasions in random sequence. Modes of administration were: A, intravenous injection; B, deltoid intramuscular injection; C, oral tablets in the fasting state; D, sublingual dosage of oral tablets in the fasting state; and E, sublingual dosage of specially formulated tablets in the fasting state. Kinetic variables were determined from multiple plasma lorazepam concentrations measured during 48 hr postdose. After intravenous lorazepam, mean (+/- SE) values were: elimination half-life (t 1/2 beta), 12.9 (+/- 0.8) hr; volume of distribution, 1.3 (+/- 0.07) liters/kg; total clearance, 1.21 (+/- 0.1) ml/min/kg. Absorption of intramuscular lorazepam was rapid. Peak plasma levels were reached at 1.15 hr after dosage, with absorption half-life averaging 14.2 (+/- 4.7) min. Absorption or oral and sublingual lorazepam tended to be less rapid than intramuscular injection, although differences were not significant. Times of peak concentration were 2.37, 2.35, and 2.25 hr postdose for trials C,D, and E, respectively; values of absorption half-life were 32.5, 28.5, and 28.7 min. Absolute systemic availability for trials B, C, D, and E averaged 95.9, 99.8, 94.1, and 98.2%, respectively; none of these differed significantly from 100%. Values of t1/2 beta were highly replicable within individuals regardless of the administration route. Thus, sublingual lorazepam is completely absorbed and is a suitable administration route in clinical practice.

From here. Here are some more studies that further prove my point:

Intranasal lorazepam is effective, safe, and provides a less invasive alternative to intramuscular paraldehyde in children with protracted convulsions. The ease of use of this drug makes it an attractive and preferable pre-hospital treatment option.

http://tinyurl.com/or2zo

Intranasal benzodiazepines produce rapid and effective sedation in canaries. Intranasal alpha(2) agonists produce sedation but not sustained recumbency. Specific antagonists are also effective when used by this route. Clinical relevance Intranasal sedative drug administration is an acceptable alternative method of drug delivery in canaries.

http://tinyurl.com/o56df

Not only is intranasal administration of benzodiazepines an efficient method in the medical community, it has been shown that it is widespread in the drug (ab)using community:

Two cases of intranasal benzodiazepine use are presented. The methods of preparation and administration of the powder and accounts of the pharmacological effects of the drugs used are described. The pattern of development and progress of the habit and its associated features are delineated. Snorting benzodiazepines appears to be more common than is currently appreciated, and the clinical complications and implications of this habit are discussed.
http://tinyurl.com/qtfaf

In conclusion, intranasal administration of benzodiazepines is not only an extremely efficient method of use, but is also prevalent in the recreational drug community. I have shown that drug absorption in the mucous membranes relies on lipid solubility, not water solubility, and that drugs that are lipid soluble are very often water insoluble. There is no scientific evidence whatsoever to give the impression that water-insoluble benzodiazepines can not be taken intranasal, and thus it is a 100% positive fact that it is a myth. Water insoluble benzos can be snorted, are snorted, and if one so desires, should be snorted.

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