These remarks were from a now-kaput forum I was in, and no I don't have any references. But I think it was discussed that the symptoms of 2C-E discomfort (which are nicely detailed on its wikipedia page) are caused by peripheral (i.e., non-brain) binding to serotonin receptors throughout the body and digestive system. And that somehow dihenhydramine (which also has its own wiki page with lots of interesting history as well as pharmacological info... fascinating substance) prevents this, thus relieving the body load. Seems to work for the majority of people, though not all.
You can find lots and lots of chat about the combo by googling
2c-e (benadryl OR diphenhydramine) ...so you might dig around those results and perhaps if you go back a ways you could find specifics mentioned once upon a time... I dont have time right now to do this, sorry.
I recall the body load was described as having "extra-pyramidal" like side effects (pyramidal is a type of serotonin responsive neuron that some LSD and 2C drugs bind to in the brain, which seems necessary for the psychedelic effects). "Extra" I think refers to sites not in the brain but around the body? ... not real clear on the terminology. So anyway searching for
dihenhydramine pyramidal I came across the following (and alot of other refs), which mentions treatment with diphenhydramine
Drug-Induced Extrapyramidal Reactions
http://jama.ama-assn.org/content/177/10/665.abstract
As to why 2C-E should be particularly strong in this "extra-pyramidal" side effect as compared to other drugs, I dunno, but some biomed folks at that old forum were saying that is exactly what the symptoms in the complex of 2C-E bodyload effects sounded like, like it binds to serotonin outside the brain stronger than other drugs, and this is what the benedryl is relieving.
As an aside there is a good description of the 2C-E bodyload here
http://en.wikipedia.org/wiki/2C-E
2C-E's chemical structure is fairly different from that of LSD, and while the both are serotonin agonists, 2C-E's body load is a highly unusual one. Several users have described it, roughly, as a "profound feeling of general discomfort". It is sometimes characterized by urges to shift the position of one's body, strong nausea at high doses leading often to vomiting, itching, prolonged tensing of unusual combinations of muscle groups which can occur without the user's knowledge over a long period of time, diarrhea, and an accompanying feeling of "disconnection from one's digestive tract". Other users report little or no body load on 2C-E, and experience instead a strong euphoria.
Following that page's link "body load"
http://en.wikipedia.org/wiki/Body_load you find this:
The causes of the subjective experience of body load are unknown. However, one proposed mechanism is the stimulation of serotonergic 5-HT receptors[1], particularly those involved in tactile sensation and, equally importantly in many cases where nausea is experienced, those located along the lining of the digestive tract. Serotonin is heavily involved in appetite control, and over-stimulation of serotonergic receptors has been shown to cause nausea in overdoses of SSRIs or MDMA. Many psychedelics which can cause body load are partial serotonin agonists, which work by mimicking the structure of serotonin to varying degrees.
[edit] Notes
^ PHARMACOLOGY OF SEROTONIN AND AGENTS ACTING AT SEROTONERGIC RECEPTORS. Goodman and Gilman, Chap. 11, pp. 249–263 and Chap. 38, pp. 928–934
Sorry I cant be of more help, but there are some hints to start looking at if you want a research project
Let us know if you find anything more exact.
