specialspack said:
I didn't realise it was possible to bypass the BBB via insufflation..? I assume that snorting powdered substances of any kind deposits quite a bit on the olfactory mucosa - so by that logic wouldn't we see that insufflation gave faster onset than smoking? I'm not aware of any substance that behaves like that.
Good question.
I'm way out of my league here, so this is just speculation...
First of all, most of an insufflated substance
will enter the bloodstream. Even if dropped directly onto the olfactory mucosa, I'm willing to bet that the majority will diffuse into the rich capillary beds and get carried in the venous system back to the right side of the heart. From there, it will have to take the conventional route through the pulmonary circulation back to the left side of the heart, and then into the systemic arterial circulation. A small portion of the systemic circulation gets routed through the internal carotid arteries, and a small portion of that circulation actually has the ability to diffuse though the BBB and get into the brain. The onset of insufflation is limited by particulate size, absorptive surface area, lipid solubility, molecular size, and no doubt many other factors. In most cases, the infamous drip will also result in some being absorbed (or not) via the GI tract. In comparison, vaporized or aerosolized drugs have a shorter route since they start their journey in the lungs, plus there's a huge surface area for absorption and very small particulate size. That's my (probably naive) understanding of the basics of insufflation vs. inhalation.
In addition, however, insufflation allows lipid soluble drugs to enter via a more direct route. In the case of 2C-C-NBOMe, its lipid solubility likely allows some of the drug to diffuse directly into the CNS via the olfactory neurons. Maybe only 10% takes this route, but it is enough to feel an effect very quickly. Because it's diffusing locally, I think it's possible that you could achieve higher peak levels of the drug in the CNS via this method than with I.M. admin.
"Multiple authors demonstrate that the nose-brain pathway leads to nearly immediate delivery of some nasal medications to the cerebral spinal fluid, by-passing the blood brain barrier (
Source)."