Eschscholzia californica

California Poppy is a common plant in North and South America that has some traditional usage as a sedative and anxiolytic when made as a tea. Two rat studies have observed sedatory and anxiolytic actions, and one human study showed some promise to this claim but conclusions cannot be drawn since it also used another herb in conjunction with California Poppy.

In the preliminary stages of research, the unique alkaloid profile of California Poppy appears to interact with a variety of receptors in potent ways. The vast majority of these leads have not been further investgiated, and conclusions (especially on Serotonin) cannot be drawn at this point in time.

Currently, California Poppy is too preliminary to support any supplemental usage.

There is currently not enough evidence to support an optimal dose of California Poppy. The best bet may to simply make tea, which has been apparently used as an anxiolytic and sedative by some people.

California Poppy is a herb with the taxonomical designation of eschscholzia californica (genus and species, respectively) and is within the family of Papaveraceae.^[2] The Californian Poppy is deemed an invasive species in Chile^[3] similar to how Japanese Knotweed is also deemened an invasive species but in North America normally grows (and not deemed invasive) throughout California, usually below 5000 feet, and in parts of Oregon and Washington as well as the Mojave Desert where it has the densest population.^[4]

1.1Composition

California Poppy contains:

• Californidine^[4]

• Escholtzine^[4]

• The pavine alkaloid 6S,12S-neocaryachine-7-O-methyl ether N-metho salt^[4]

• N-methyllaurotetanine^[4]

• Caryachine and the O-methylcaryachine related structure^[4]

• Protopine^[4]

• Chelirubine, macarpine and sanguinarine as well as their dihydro- derivatives^[5]

• Benzophenanthridine alkaloids (10-hydroxysanguinarine, 12-hydroxychelirubine, 10-hydroxychelerythrine)^[5]

• Dihydrobenzophenanthridines 10-hydroxydihydrosanguinarine and 12-hydroxydihydrochelirubine^[5]

• Carotenoids (yellow-orange coloration of the petals)^[6]

2.1Metabolism

One study using rats as a model to study two alkaloids in California Poppy, Californine and Protopine, noted that both alkaloids were subject to metabolism by Catechol-O-Methyltransferase and subsequently conjugated in the urine.^[7]

2.2Enzymatic Interactions

A 70% ethanolic extract (1.82% alkaloids) appears to inhibit CYP3A4 with an IC₅₀ value of 128.6+/-61.8ug/mL, which was thought to be mediated by mostly Escholtzine with an IC₅₀ of 13.4 ± 4.7μM.^[4] Californidine and Protopine were not significantly active (over 80uM).^[4]

An ethanolic extract in general appears to possess MAO-B inhibitory potential.^[8]

3.1Anxiety

One study combining California Poppy with Crataegus oxyacantha in 264 patients with diagnosed General Anxiety Disorder of mild to moderate intensity over a period of three months given combination therapy (75mg dry hydroalcoholic extract of CO, 20mg dry water extract of CP; 75mg elemental Magnesium) or placebo showed statistically significant benefits associated with all parameters of Anxiety (assessed by Hamilton Anxiety Scores) on day 14, 60, and 90 with a dip at day 30 where placebo was effective enough to make no significant difference; side effects did not differ between groups.^[1]

Animal studies on anxiety with California Poppy (aqueous extract) show benefit with 25mg/kg daily.^[9] 200mg/kg of a 60% aqueous extract (injections) appears to have anxiolytic properties in animals as well with nonsignificantly different potency when compared to 2mg/kg Midozolam (although it trended to be weaker).^[10]

Appears to have moderate to weak anti-anxiety actions, but insufficient human testing (only current study is confounded with the inclusion of another herb)

3.2Sedation

100mg/kg of the aqueous extract of California Poppy in rats appears to accelerate the induction of sleep, which demonstrates sedative actions.^[9] These sedatory actions (in another test using 200mg/kg injections) were partially antagoniszed by flumazenil by about half, a benzodiazepine and GABA antagonist.^[10]

In Anticonvulsant and myorelaxant tests, the plant extract was ineffective at both up to 400mg/kg while reference benzodiazepines were effective.^[10] California Poppy also failed to protect against Amphetamine-induced death despite benzodiazepines being effective.^[10]

3.3Acetylcholine

An anticholinergic test with up to 400mg/kg of a 60% water extract of California Poppy failed to exert anticholinergic effects.^[10] These lack of effects may be due to using a water extract in this study, as an ethanolic extract of the roots and aerial parts (leaves) has two alkaloid components (reticuline 9 and 14) that inhibit acetylcholinesterase enzymes; no effect was noted on butyrylcholinesterase.^[11]

3.4Serotonin

A 70% ethanolic extract of California Poppy (1.82% alkaloids) was able to bind to both 5-HT_1A and 5-HT₇ receptors in vitro at 100mcg/mL.^[4] Specifically, when the 70% ethanolic extract was incubated at 9mcg/mL, it showed inhibition of 64 +/-4% of 5-HT_1A receptors and inhibition of 76 +/-1% of 5-HT₇ receptors. Binding on the 5-HT_1A was mostly due to N-methyllaurotetanine since it alone showed an EC₅₀ of 160+/-10nM and a K_i of 0.085 ± 0.001uM in preventing binding of 8-OH-DPAT to this receptor.^[4]

Highly potent interactions at the level of the receptor with the ethanolic extract, but it is not known whether this is an agonist (activator) or antagonist (inactivator), or whether it is biologically relevant

3.5Dopamine

California Poppy appears to inhibit Dopamine-B-Hydroxylase.^[8]

3.6Adrenergic

In human recombinant Sf9 cells, 9mcg/mL of the 70% ethanolic extract showed inhibition of 30+/-7% of Alpha-2-Adrenergic receptors; less potent than the active control of yohimbine with an EC₅₀ of 8.5nM.^[4]

Some beta-blocking potential exists, with this extract inhibiting 32 +/-3% of binding to Beta-1-Adrenergic receptors, but underperformed relative to the active control of Propanolol (1.8nM EC₅₀).^[4]

3.7Histamine

The 60% water extract of the plant has failed to exert antihistaminic effects in an animal ileum^[10] while the alkaloids in the ethanolic extract failed to show any significant affinity for Histamine receptors.^[4]

3.8Adenosine

Some inhibitory potential was noted against the Adenosine A1 receptor in vitro with 70% ethanolic extract of California Poppy, inhibiting 21 +/-5% of receptor binding; this was weaker than the active control Dipropylcyclopentylxanthine (1200nM EC₅₀).^[4]

3.9Cannabinoids

Californian poppy, at 9mcg/mL (a concentration seen as active) of the 70% ethanolic extract failed to show binding to the Cannabinoid CB₁ receptor.^[4]

1. ^ a b Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders.
2. ^ Cahlíková L, et al. Identification of pavinane alkaloids in the genera Argemone and Eschscholzia by GC-MS. Nat Prod Commun. (2012)
3. ^ Véliz D, Gauci R, Bustamante RO. Characterization of novel microsatellite markers for Eschscholzia californica (Papaveraceae), an invasive species in central Chile. Am J Bot. (2012)
4. ^ a b c d e f g h i j k l m n o p Gafner S, et al. Alkaloids from Eschscholzia californica and their capacity to inhibit binding of {3H}8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro. J Nat Prod. (2006)
5. ^ a b c Tanahashi T, Zenk MH. New hydroxylated benzo{c}phenanthridine alkaloids from Eschscholtzia californica cell suspension cultures. J Nat Prod. (1990)
6. ^ Barrell PJ, et al. Inheritance and epistasis of loci influencing carotenoid content in petal and pollen color variants of california Poppy (Eschscholzia californica Cham.). J Hered. (2010)
7. ^ Paul LD, Maurer HH. Studies on the metabolism and toxicological detection of the Eschscholtzia californica alkaloids californine and protopine in urine using gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. (2003)
8. ^ a b Kleber E, et al. Modulation of key reactions of the catecholamine metabolism by extracts from Eschscholtzia californica and Corydalis cava. Arzneimittelforschung. (1995)
9. ^ a b Rolland A, et al. Behavioural effects of the American traditional plant Eschscholzia californica: sedative and anxiolytic properties. Planta Med. (1991)
10. ^ a b c d e f Rolland A, et al. Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae). Phytother Res. (2001)
11. ^ Cahlíková L, et al. Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Eschscholzia californica (Papaveraceae). Nat Prod Commun. (2010)