Antihistamines
Antihistamines are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the histamine (H) receptor sites, responsible for immediate hypersensitivity reactions such as sneezing and itching. Histamine-releasing neurons are located in the tuberomammillary nucleus of the hypothalamus, and with ventral areas (hypothalamus, basal forebrain, and amygdala) receiving a particularly strong innervation. The histamine system is involved in many central nervous system functions: arousal; anxiety; activation of the sympathetic nervous system; the stress-related release of hormones from the pituitary and of central aminergic neurotransmitters; water retention and suppression of eating.
There are four known histamine receptors: H 1-4. The H1 receptor can be found in the tuberomammillary nucleus of the hypothalamus and the cortex of the "brain". It is also common in many other tissues of the body. The H2 receptor is found throughout the hypothalamus, thalamus and central nervous system including neurons (nerve cells). It stimulates formation of cAMP (a compound used to transport energy), protein formation, muscle contraction, blood pressure and much more. The receptor is found in neurons and when stimulated it acts to inhibit other neurotransmitter formation including dopamine, GABA, acetylcholine, noradrenaline, histamine and serotonin. The H4 receptor is expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea.
Increasing evidence supports a role for histamine in anxiety and depression. In most studies the anxiety is caused by stimulation of the histamine H1 receptor (H1R) or blockade of the histamine H2 receptor (H2R). These effects of histamine on anxiety and depression make histamine receptor ligands attractive therapeutic targets for anxiety and depression.
Diphenhydramine, (over the counter) also known as Benadryl, is an antihistamine and as such is not only used for allergies/colds but also as a sleep aide. It does have a mild anxiolytic effect. May lower blood pressure and cause irregular heartbeats. Long-term use of Benadryl often affects mental cognition, especially in the elderly. Your body does build up tolerance to it after a few weeks. There is evidence of dependence in cases of long-term heavy uses. It is a histamine H(1)R antagonist in the brain. Do not take this medicine with any other medicine that can cause sleepiness including benzos, most blood pressure medicines, ssri/snri, buspar and others. Please check for compatibility before using. This medicine has many drug interactions.
Begins working in 15 to 30 minutes
Peak levels - 2 to 2.5 hrs
Half Life – 4 to 6 hrs
https://www.ncbi.nlm...pubmed/24530460
Moderately effective
https://www.ncbi.nlm...pubmed/19415242
(50mg dose)
https://www.ncbi.nlm...pubmed/16156843
Effective
https://www.ncbi.nlm...pubmed/16111835
Effective
http://www.ncbi.nlm....pubmed/18308811
Can cause dependence with constant heavy use. Some moderate withdrawal symptoms possible.
Chlorpheniramine (over the counter) is an antihistamine {H(1)R antagonist} used to treat allergy symptoms. It does cause sleepiness like other antihistamines and has significant anxiolytic effects. It has also been shown to function as an ssri and snri. As such it should never be taken in combination with those medications as it can cause seratonin syndrome. Due to its anticholenergic effects it frequently causes constipation. As with diphenhydramine do not take with other medicines that can cause sleepiness. Recommended dose is 4 mg every 4 to 6 hrs not to exceed 32 mg/day. Widely sold as an allergy treatment.
Begins working in 30 minutes to an hour
Peak levels - 2 to 4 hrs
Half Life – 12 to 43 hrs
https://www.ncbi.nlm...les/PMC3854398/
(8mg dose)
https://www.ncbi.nlm...pubmed/16876927
https://www.ncbi.nlm...pubmed/16156843
https://www.ncbi.nlm...pubmed/12951198
https://www.ncbi.nlm...pubmed/10541737
Hydroxyzine, (Vistaril, Atarax) is an H(1)R antagonist, is very effective against anxiety in most people but some get no help from it at all. It is not addictive nor does it have withdrawal but it also can lower blood pressure some but that usually goes away with time. This medicine should be started slowly to give your body a chance to adjust to the blood pressure effect. Normal dose is 25 mg four times a day but can go as high as 400mg/day.
Begins working in 30 minutes or less
Peak levels - 2 hrs
Half Life – 15 to 20 hrs
https://www.ncbi.nlm...pubmed/21154375
https://www.ncbi.nlm...pubmed/12444816
https://www.ncbi.nlm.../pubmed/7875114
Anxiolytic, Sleepiness begins to subside after 1st week and no withdrawal.
https://www.ncbi.nlm.../pubmed/9809861
https://www.ncbi.nlm.../pubmed/2430410
Do not take with cimetidine as it increases hydroxyzine levels in the blood.
https://www.ncbi.nlm...les/PMC1512309/
Effective, sleepiness slowly decreases.
