Galphimia glauca - An uncommon anxiolytic with a novel mechanism High-quality evidence was found to exist for the use of Galphimia glauca (galphimia) for anxiety disorders [1]. "0.175 mg of galphimine-B and administered for 15 weeks to patients with generalized anxiety disorder, showed greater anxiolytic effectiveness than that obtained with lorazepam, with high percentages of therapeutic tolerability and safety." [2, 3] Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases, particularly nervous hyperexcitability disorders. This plant contains galphimines which have been shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the ventral tegmental area [4]. Galphimine-B appears to be an allosteric modulator of 5HT1A receptors [5] It was capable of blocking positive and cognitive symptoms associated with psychosis induced by ketamine [6] Dose: Dried herb 0.6–1 g per day standardized to 0.175–0.348 mg of galphimine B Clinical trials showing equivalence to synthetic anxiolytics No adverse reactions found in studies Generalized anxiety, GAD While emerging data is encouraging, further placebo-controlled studies are needed. Galphimines have been identified as active compounds in galphimia, with the nor- secotriterpenes galphimine A and galphimine B, being shown to have the strongest anxiolytic activity. Galphimine B has been considered the primary active constituent for galphimia’s anxiolytic and sedative effect, and is the constituent standardized for clinical trials. Galphimine B has been shown to interact with serotonergic transmission in the dorsal hippocampus in rats. This occurs by increasing the frequency of neuronal discharge in CA1 cells, resulting in activation of 5HT(1A) receptors. One study in mice demonstrated that galphimines cross the blood–brain 1 barrier, with galphimine A found to have an effect on the central nervous system. 2.5.3 Evidence of Efficacy 2.5.3.1 Preclinical A number of galphimine constituents, including galphimine B, were evaluated for their anxiolytic effects in mice using the EPM. Mice were intraperitoneally administered 15 mg/kg of a galaphimine derivative 1 hour before testing. An anxiolytic-like effect in the mice was found for both galphimine A and galphimine B, with a significant increase in the time spent in and number of entries into the open arm in the EPM. A second study on mice used a methanolic extract (standardized for galphimine B, 8.3 mg/g) at different doses (125, 250, 500, 1000 and 2000 mg/kg), which were orally administered at three different times (24, 18 and 1 hour before the test). Significant anxiolytic-like effects were found in the light–dark paradigm test and the EPM, but not the forced swimming test. 2.5.3.2 Clinical Two clinical trials have found galphimia to be an effective anxiolytic. The first was a 4-week, positive-controlled double-blind RCT, with a cohort of 152 patients with a DSM-IV diagnosis of GAD and HAMA scores ≥ 19 . The two groups received either galphimia aqueous extract (310 mg standardized to 0.348 mg of galphimine B), or the benzodiazepine lorazepam (1 mg). Each treatment was administered in capsule form (identical in appearance) twice daily. Both groups demonstrated a significant reduction in anxiety symptoms. There were no significant side effects reported in the galphimia group, which contrasted with the lorazepam group, in which over 21 % of people reported excessive sedation. [ 1 ] https :// www ncbi nlm nih gov / pubmed / 29575228 [ 2 ] https :// www ncbi nlm nih gov / pubmed / 22828921 [ 3 ] https :// www ncbi nlm nih gov / pubmed / 17562493 [ 4 ] https :// www ncbi nlm nih gov / pubmed / 12567277 [ 5 ] https :// www ncbi nlm nih gov / pubmed / 21742023 [ 6 ] https :// www ncbi nlm nih gov / pubmed / 29710504 2