Sublingual administration

Because the connective tissue beneath the epithelium contains a profusion of capillaries, the substance then diffuses into them and enters the venous circulation.

[1] In contrast, substances absorbed in the intestines are subject to first-pass metabolism in the liver before entering the general circulation.

Being more direct, it is often faster onset of action, and it ensures that the substance will risk degradation only by salivary enzymes before entering the bloodstream, whereas orally administered drugs must survive passage through the hostile environment of the gastrointestinal tract, which risks degrading them, by either stomach acid or bile, or by enzymes such as monoamine oxidase (MAO).

One drawback, however, is tooth discoloration and decay caused by long-term use of this method with acidic or otherwise caustic drugs and fillers.

LSD, MDMA, morphine, alprazolam, clonazepam, diazepam, and many other substances including the psychedelic tryptamines and phenethylamines, and even recreational cannabis edibles (THC) are all viable candidates for administration via this route.

This may be a preferred method to simple oral administration, because MAO is known to oxidize many drugs (especially the tryptamines such as DMT) and because this route translates the chemical directly to the brain, where most psychoactives act.

Increased efforts are underway to deliver macromolecules (peptides, proteins and immunotherapies) by sublingual route, by companies such as Novo Nordisk, Sanofi and BioLingus.