Hypericum perforatum (St. John's Wort)

Safety data 
St. Johns Wort has been used to treat nervous conditions since the Ancient Greeks. Hypericum perforatum is not advocated for severe depression, psychotic indications, or suicidal threat. It is not recommended to use it in place of conventional care without professional advise prior or in replacement of seeing a health care provider. 

Depression
The major constituents in Hypericum perforatum, especially hyperforin, act to alleviate depression and display mechanisms that both relate and differ from standard antidepressants e.g. selective serotonin reuptake inhibitors (SSRIs). Hyperforin has shown to delay the neuronal uptake of serotonin, monoamines, dopamine, norepinephrine, amino acid neurotransmitters glutamate and GABA (Nathan, 2001). This occurs in a non-competitive manner via intracellular Na+ ion concentration enhancement, providing anti-depressant action. The constituent hyperforin also acts as an anxiolytic and enhances cognition (Zanoli, 2004). Studies have shown that Hypericum perforatum acts indirectly with pH gradients, causing a pH reduction through the synaptic membrane creating the diffusion of uncharged monoamines into the cytoplasm. This surge in concentration reduces the transmembrane gradient of neurotransmitters inhibiting the uptake by hyperforin (Braun & Cohen, 2018). Other constituents such as adhyperforin and hypericin demonstrate a strong inhibitory effect on neurotransmitter intake. Evidence shows that Hypericum perforatum is extremely helpful during all phases of depression and is on par with common SSRI drugs (Braun & Cohen, 2018). Within a 26-week clinical trial that involved 124 people, Hypericum perforatum and a standard antidepressant (sertraline), alongside with placebo were both just as effective in treating major depression. Hypericum perforatum also proved to have fewer side effects than orthodox antidepressants (National Centre for Complementary & Integrative Health, 2012). Further studies of 426 patients in 2008 show that Hypericum perforatum use reduces the possibility of relapses after 6 to 12-months during a maintenance period than common pharmaceuticals (Kasper et al, 2008)
 
Anxiety & Obsessive-Compulsive disorder
Hypericum perforatum binds to GAB-A and –B receptors reducing GABA uptake which promotes an anxiolytic effect. A 2010 study involving 21 patients with anxiety showed that 71% had positive effects on lowering their anxiety rating after being prescribed the herb at a therapeutic level. This came without a high risk of unwanted side effects that occur from conventional anxiety medication (Lakhan, 2010). Thus, Hypericum perforatum is moderately helpful in reducing anxiety. OCD is an anxiety disorder affecting 2% of Australians and is characterised by the necessity to frequently check or partake activities with an irrational and impulsive nature (SANE, 2019). A study of 12 individuals with OCD over a 12-week duration showed that Hypericum perforatum had a positive effect on symptoms of OCD. After the study, 5 out of 12 patients were rated “very much improved” by clinicians and 6 were pronounced “minimally improved” thus presenting the significant impact of Hypericum perforatum on OCD anxiety conditions (LH et al, 2000). Historically, Hypericum perforatum has been recognised for 2,000 years, especially for its ability to assist hysteria and nervous imbalances especially with depression (King, 1876).
 
Dementia
Cognition-enhancing herbs assists in improving learning and memory. Dementia involves symptoms that affect the brain via memory and behaviour. Hypericum perforatum is indicated in prevention of this condition due to its ability to decrease oxidative stress within the brain (Sanchez-Reus, 2007). Hyperforin proves to help the release of acetylcholine in the hippocampus thus proving its cognition-enhancing effect on humans as well as providing protection from developing dementia (Klusa, 2001). Acetylcholine receptors provide a role in encoding new memories in the brain and improves cognition, learning and object recognition (Hasselmo, 2006).