Psychopharmacology of Camellia sinensis Green tea: Green tea may reverse the development of depression through normalisation of the reward function [1] Attenuates a social isolation model of depression-induced dysfunction of dopaminergic reward pathways [2] ⦁ promising for neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders and is suggested as a prophylactic for Alzheimer's, Parkinson's etc ⦁ Epidemiological investigations have reported that drinking tea reduces the risk of dementia (higher consumption of green tea is associated with lower prevalence of cognitive impairment) and depression. ⦁ believed to lower the risk of dementia both through it's polyphenols and active metabolites that exhibit effects on nerve cell proliferation and neuritogenic properties. ⦁ Some evidence suggests that daily consumption of tea catechins may help in controlling type 2 diabetes ⦁ Green tea's theanine seems to have multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with major depression [3] It may be beneficial in schizophrenia [4] ⦁ Improves “cognitive functioning [through affecting]...working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto- frontal brain connections.” 1 ⦁ Green teas reduced memory deficits. G reen tea consump Ɵ on in subjects with cognitive dysfunction (2 g/day for 3 months, approximately equal to 2 to 4 cups of tea/day) significantly improved cognitive performance. ⦁ Promotes stress resistance, has neuroprotective and autophagy-promoting properties ⦁ beneficial effects in related areas such as work performance and creativity ⦁ A standard cup of green tea contains ~8mg theanine and ~70 mg EGCG per bag. [1] https://doi.org/10.1186/1475-2891-12-84 [2] https://doi.org/10.3390%2Fnu15030581 [3] https://www.ncbi.nlm.nih.gov/pubmed/27396868 [4] https://www.ncbi.nlm.nih.gov/pubmed/21208586 Black tea ⦁ posesses aphrodisiac properties [1] ⦁ strongly anti-inflammatory (Theaflavins from black tea have a stronger anti- inflammatory effect than many other polyphenols) ⦁ black tea polyphenols are promising functional food ingredients and medicines for improving insulin resistance-related disorders and improve postprandial glycemic control ⦁ A standard cup of black tea was found to contain L-theanine 24.2 ± 5.7 mg and mostly thearubigens [1] https://www.ncbi.nlm.nih.gov/pubmed/18565706 Other teas: Oolong contains more O-methylated catechins like (-)-epigallocatechin 3- O-(3- O-methyl) gallate with distinct physiological functions in animal models and humans compared to common tea, including antiallergy, antiobesity, the prevention of cardiovascular disease risks Pu-erh tea fermentation forms simple phenolic acids (gallic) and theogallin while epicatechin, epigallocatechin gallate and theanine decreased during fermentation It is reported that Pu-erh tea have a variety of pharmacologically activities, such as anti- hyperlipidemic, anti-diabetic, anti-oxidative, anti-tumor, anti-bacterial, anti-inflammatory, and anti-viral effects. It is promising for it's effects on metabolic syndrome through 2 remodelling the microbiome Pu-erh tea contains "biological compounds binding transcription factors and inhibiting the expression of mGluR5 and is a novel natural neuroprotective agent" as dysregulation of mGluR5 is implicated in multiple brain disorders particularly showing promise for pain, epilepsy, schizophrenia, drug addiction and Alzheimer’s disease Gallic acid in Pu-erh tea is reported to be a main constituent. Individual constituents Theanine: Several studies found that caffeine and L-theanine improve attentional performance but studies did not find any change in self-reported mood compared to caffeine. Some of the studies, even on more well-known combinations such as caffeine and L- theanine, failed at reproducing the same results as in other studies. L-theanine appears to be most beneficial in subjects that reported being more stressed and/or anxious during the study. "L-Theanine is a relaxing and nondietary amino acid found pretty much exclusively in teas from Camellia sinensis and is known to promote relaxation without sedation. It appears to be effective at this as well as reducing stress at standard dosages." One study suggests that chronic (8-week) L-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with depression [1] A dose of L-theanine (200mg) equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses. [2] Other results suggest that L-theanine is effective in ameliorating positive symptoms and sleep quality in schizophrenia [3] and beneficially impacts sensorimotor gating [4]. The intake of L-theanine might be a potential candidate for suppression of disadvantage under psychosocial stress. [5] [1] http://www.ncbi.nlm.nih.gov/pubmed/27396868 [2] http://www.ncbi.nlm.nih.gov/pubmed/26869148 [3] http://dx.doi.org/10.1017/neu.2015.22 [4] http://www.ncbi.nlm.nih.gov/pubmed/24372613 [5] http://www.ncbi.nlm.nih.gov/pubmed/21425911 3 Catechins: Tea catechins have GABAA modulatory [1] and cannabinoid affinity [2]. While the tea catechin EGCG is known to inhibit COMT enzymatic activity in vitro this may not be relevant in vivo. EGCG attenuates NMDA antagonist-stimulated behaviours ⦁ ligands for the GABAA receptor benzodiazepine site, the higher catechins like EGCG are PAMS at some sites. EGCG reversed the effects of GABAA receptor negative modulators - picrotoxin and methyl beta-carboline-3-carboxylate, EGCG and chlordiazepoxide fully generalised in substitution studies "Much of orally ingested EGCG is hydrolyzed to epigallocatechin (EGC) and gallic acid. In rats, EGC is then metabolized mainly to 5-(3',5'-dihydroxyphenyl)-γ-valerolactone" These metabolites may promote neurogenesis in the brain [3] ⦁ EGCG has sedative and hypnotic effects at the brain level, by acting partially at the level of GABA receptors moderating the response to the acute stress. In addition, a positive effect against anxiety in mice has been observed. The sedative effect is enhanced by the presence of L-theanine. The consump Ɵ on of green tea catechins is generally believed to suppress age -related cognitive dysfunction, The neuroprotective, antioxidant, anti-inflammatory, and iron- chelating properties of EGCG make it promising for neurorescue Research suggests that tea catechins, mainly EGCG, elicit cognitive effects as well. EGCG administration has been associated with self-reported calmness and reduced stress in healthy subjects. [1] https://www.ncbi.nlm.nih.gov/pubmed/16457806 [2] https://doi.org/10.1016/j.phymed.2009.10.001 [3] https://www.ncbi.nlm.nih.gov/pubmed/28891114 Teaflavins/thearubigens Oral administration with theaflavins can suppress neural inflammation and prevent inflammation-related brain disorders, improving memory impairment and depression-like behaviour [1]. Theaflavins from black tea have a stronger anti-inflammatory effect than many other polyphenols. Oral consumption of theaflavins induced anxiolytic effects via activation of the dopaminergic system in the frontal cortex [2]. Despite concerns about these reaching the CNS, oral doses are indeed CNS active in animal models. [1] https://www.ncbi.nlm.nih.gov/pubmed/30696093 [2] https://www.ncbi.nlm.nih.gov/pubmed/30806570 4