From a pharmacological standpoint, this is an interesting question. Most of the effects of psychedelic drugs are mediated via interaction with serotonin receptors. Recent evidence seems to suggest, however, that the strongest "mystical" or "spiritual" effects subjectively induced by psychedelic drugs may be more closely associated with a different receptor entirely, called Imidazoline 1.

The psychedelic drugs that are most strongly associated with spiritual experiences (such as DMT, DPT, or Psilocin) all have high affinities for this receptor. Of all of the psychedelics that have been evaluated for this property, however, the one that binds to Imidazoline 1 strongest of all is Mescaline. LSD, in contrast, has a much lower affinity for this receptor. Perhaps this is the answer to your question, at least from a neurochemical perspective.

The I1 receptor appears to be a G protein-coupled receptor that is localized on the plasma membrane.[6] It may be coupled to PLA2 signalling and thus prostaglandin synthesis.[6][7] In addition, activation inhibits the sodium-hydrogen antiporter and enzymes of catecholamine synthesis are induced, suggesting that the I1 receptor may belong to the neurocytokine receptor family, since its signaling pathways are similar to those of interleukins.[7] It is found in the neurons of the reticular formation, the dorsomedial medulla oblongata, adrenal medulla, renal epithelium, pancreatic islets, platelets, and the prostate.[6] They are notably not expressed in the cerebral cortex or locus coeruleus.[6]

Animal research suggests that much of the antihypertensive action of imidazoline drugs such as clonidine is mediated by the I1 receptor.[6][8][9] In addition, I1 receptor activation is used in ophthalmology to reduce intraocular pressure.[6] Other putative functions include promoting Na+ excretion and promoting neural activity during hypoxia.[6]

While doing some research online I came across this question. What was interesting was a response (quoted below), if anyone is familiar with the information found in the citation I would very much appreciate it if you added to this thread.

I am not a pharmocologist and maybe be very wrong but I am skeptical to think that "spiritualness" of an experience comes down to one receptor, especially a receptor which function is of the sort of this:



It is my intuition to think that spiritualness is more likely to be found within the integration of the neural patterns as well as the difference in receptor affinities of all the different receptors activated. The fact that lsd has a 5ht2c receptor affinity of 23nM while Mescaline is 17μM and DMT is 0.424μM may play a large part in the difference of the experience, not to mention its effect on brainwave frequencies (rate of firing, beta, alpha etc).