Hops are also an ingredient in commonly OTC herbal-based sedatives. Typically in combination with valerian.
Mild, not overpowering, certainly not to somebody that like I do, takes a pharmaceutical sedative-hypnotic, in its antiseizure capacity here, but still tolerance is built. The valerian is much more of an interesting little devil however. I like to use, occasionally, those valerian/hop based (and pure valerian extract based without hops also, to which the effect appears to be due) an entire pack or sometimes two, for the pronounced and quite astonishingly..well...there just aren't words that do it justice.
Sedative effect is primary, but once asleep valerian, seems to be a really, really powerfully oneirogenic herb. Effect is via GABAa receptors, at least primarily, the same as are the targets of sleeping pills of many kinds, not including antihistamines, which are crap generally for that purpose. I mean the likes of the benzodiazepines (valium, librium, rohypnol/roofies [never had roofies myself but have had its close analog nitrazepam, and the nitrobenzodiazepines seem to be the best of the lot] and ativan/lorazepam. as well as the barbiturates, such as seconal, amytal sodium, phenobarbital, as well as the Z-drugs such as zolpidem and the highly atypical one, that is often used as the prototype ligand for defining, in the physiological sense, the GABAa receptor in radioligand binding assays, muscimol, which is the active substance in the fly agaric mushroom, long used in ritual and by siberian folk, as an intoxicant. And by me, especially as a tonic in the winter as it renders one insensitive to the bite of the cold, and to cook with, in small quantities its my favourite spice for cooking with meat. I will'nae suffer a chilli con carne to disgrace my bowl by arriving lacking in a spoonful of fly agaric powder added to the cookpot.
Anyhow, valerian. Small doses for a person's GABAa agonist tolerance if any, lead to sleep. Larger ones to the most powerfully vivid, ofttimes lucid and in-your-face episodes of constant, constant constant and intense dreaming. Its almost like a classic psychedelic in intensity, very very different mode of action from any of them, bar maybe muscimol. Its actives are similar in structure, or many are, to the anticonvulsant valproate, aka epilim. So it wouldn't surprise me one tiny bit if they were sodium channel modulators in a similar way, but also one at least, binds the GABAa receptor at the loreclezole allosteric binding site (an allosteric site is one that is situated on the receptor complex, but is also separate from the binding site of the main neurotransmitter, and is thus unable to displace radiolabelled neurotransmitter, at least not unless there is such an interaction as a change in receptor conformation that renders agonist-bound receptors susceptible to or directly inducing a conformational change that makes the agonist binding less favourable, and so would cause release. But classically speaking, its a separate site that doesn't directly bind neurotransmitter, but rather modulators of the action of that transmitter, either positively or negatively, in accordance with their facilitating or negating the amplitude of the effect of the neurotransmitter in question. For example, GABA, gamma-aminobutyric acid is the main inhibitory neurotransmitter in the brain, and an orthosteric agonist or antagonist, e.g the agonist muscimol binds at the same site GABA does and can displace radiolabelled GABA. However an allosteric positive modulator for example diazepam/valium binds at its allosteric regulatory site, and when in the presence of GABA, increases the flow of Cl- ions [GABA receptors are chloride channels, GABAa being a heteropentamer, that is composed of 5 different subunits forming various different subtypes of GABAa receptors, sensitive to different allosteric ligands, all sensitive to GABA itself. These arrange as a pentameric, cyclic structure forming the central pore of the receptor, that when opened, by GABA binding, inducing a conformational shift in the geometry of the GABAaR, which is situated upon/within the cell membrane, allows chloride ions to flow in and out, the influx, in exchange for sodium ions results in hyperpolarization of the cell, and renders it less likely towards being subject to excitation, and thus less likely to fire an action potential in response to stimuli.)
The loreclezole site intrigues me a lot, given the experiences I've had with valerian, christ its intense as hell, almost instant tolerance (tachyphylaxis, a rapidly induced, but short lived tolerance to the effects of a drug), to the point where it cannot be done for more than perhaps 2 nights in a row. This does not however produce withdrawal symptoms of any kind, although long term use presumably could do so. But it does prevent use as a dream inducer. I'd love some time to either buy a little, or synthesize a few grams of loreclezole for testing, because it was absolutely fucking incredible, every time I've used valerian extract at high doses, good god, went on all night, slight awakenings every so often, and more or less continuous (as perceived, non-stop dreaming, so strong was this effect that it almost felt, despite the absence of nightmarish scenery, like being on a rollercoaster, or tossed and turned and buffedted, thrown about on a stormy ocean current. Never felt anything like it, I honestly, have never known its like. Left me exhausted the next morning, although I'd had a good long sleep, but just from the constant, unceasing intensity of it all.
