California Poppy (Eschscholzia californica) as a tool for helping with Anxiety

Objective To assess the clinical efficacy of a neurotonic component containing fixed quantities of two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium versus placebo in mild-to-moderate anxiety disorders with associated functional disturbances, under usual general practice prescription conditions. Research design and methods A total of 264 patients (81% female; mean age: 44.6 years) presenting with generalised anxiety (DSM-III-R) of mild-to-moderate intensity (total Hamilton anxiety scale score between 16 and 28) were included in a double-blind, randomised, placebo-controlled trial. Patients were randomly assigned to two groups: 130 received the study drug (Sympathyl), and 134 a placebo (two tablets twice daily for 3 months). Efficacy and safety data were recorded before first administration and 7, 14, 30, 60 and 90 days after start of treatment. Main outcome measures Efficacy was assessed by (a) change in Hamilton anxiety scale total and somatic scores; (b) change in patient self-assessment; (c) number and percentage of responsive subjects (reduction of at least 50% in Hamilton or self-assessment score); and (d) the physician's clinical global impression. Tolerance was assessed by undesirable events spontaneously reported by the patients over the study period. Results Total and somatic Hamilton scale scores and subjective patient-rated anxiety fell during treatment, indicating clinical improvement. The decrease was greater in the study drug than in the placebo group. End of treatment clinical improvement, as measured by the mean difference between final and pre-treatment scores, was, for the study drug and placebo groups respectively: -10.6 and -8.9 on the total anxiety score (p = 0.005); -6.5 and -5.7 on the somatic score (p = 0.054); and -38.5 and -29.2 for subjectively assessed anxiety (p = 0.005). The risk/benefit ratio as judged by the investigating physicians was also significantly greater in the study drug than in the placebo group. In all, 15 patients (11.5%) in the study drug group and 13 patients (9.7%) in the placebo group experienced 22 and 15 adverse events, respectively. Undesirable events were mainly mild or moderate digestive or psychopathological disorders. Conclusions The preparation containing fixed quantities of Crataegus oxyacantha, Eschscholtzia californica, and magnesium proved safe and more effective than placebo in treating mild-to-moderate anxiety disorders. Sympathyl is produced and marketed by Laboratoire Innotech International, Arcueil, France.

The California poppy (Eschscholzia californica Cham.) contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understanding of these biological effects at the molecular level is still lacking. Alkaloids detected in E. californica could be hypothesized to act at GABAA receptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinant α 1 β 2 γ 2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at the α 3, α 5, and α 6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S)-reticuline at the α 3 β 2 γ 2 and α 5 β 2 γ 2 GABAA receptors. Interestingly, α 1, α 3, and α 5 were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine-suspected (S)-reticuline metabolites in the rodent brain.