When engaging in any kind of sexual activity, orgasm and stressed induced inflammatory hormone prostaglandin E2 will excite mast cells and subsequently activate central histaminergic nerves. Histamine itself plays an important role in the body – through its H1, H2, H3, and H4 receptors is involved in inflammatory and immune responses, vasodilation, proper gastric functioning, chemataxis, separation of endothelial cells, and through its H3 receptor influences neurotransmitter concentrations in the brain. Any form of stress, especially sex induced stress, will lead to significant alterations in the synthesis and concentrations of histamine in a number of brain regions. Immediate autoimmune sensitivity or any histamine related overreaction will be observed if high amounts of histamine are to be used to process any specific stress induced reaction, which is usually the case with sex-induced stress. This may result in any of the following symptoms or combinations – allergic responses, circadian rhythm, itchiness, headache, asthma, premature ejaculation, scalp burning sensation, difficulty breathing and a very specific gut feeling of uneasiness which can be highly intensified under the influence of even low-level stress. Histamine also plays role in the atherosclerosis, coronary inflammation and cardiac ischemia.

H3 receptors are very useful in providing negative feedback control over the release of certain neurostransmitters such as acetylcholine, dopamine, serotonin, GABA, histamine, and norepinephrine. However, excessive sexual activities should be examined on their own due to the highly unique internal neurohormonal-hormonal-neurotransmitter relations during and after. Frequently, under the influence of inflammatory prostaglandin E2 and to some degree norepinephrine, the system fails to suppress its own histamine and norepinephrine release, but successfully blocks acetylcholine, serotonin, dopamine, and GABA release in the nervous terminals. This alone leads to extreme state of imbalance for a different set of symptoms ranging from irritability to full blown panic attacks. Of course, the severity of the specific symptoms observed will be highly dependent on the overall state of exhaustion.