California Poppy

Papaveraceae

Eschscholzia californica

Also known as: Golden Poppy, Copa de Oro, Gold Poppy

Pregnancy C
Lactation C

clinical_notes Clinical Summary

California Poppy (Eschscholzia californica) is a Western North American herb from the Papaveraceae family containing unique isoquinoline alkaloids (californidine, escholtzine, protopine) that modulate GABA-A receptors and possibly opioid receptors, producing gentle sedative, anxiolytic, and analgesic effects.

Unlike its distant relative the opium poppy, it contains no morphine or codeine and is non-addictive.

Clinical evidence from one double-blind RCT (264 patients) supports use for mild-to-moderate anxiety.

Traditional and observational data support insomnia, nervous agitation, and pain applications.

Dose-dependent effects range from anxiolytic (lower doses) to sedative/analgesic (higher doses).

Pregnancy Safety

C

No published safety studies in pregnancy. Contains alkaloids with unknown fetal safety profile. Avoid during pregnancy as a precaution despite low opiate content.

Lactation Safety

C

Insufficient safety data. Alkaloids may pass into breast milk. Avoid during lactation as a precaution.

warning Contraindications

  • Concurrent use with CNS depressants, sedatives, opioids, benzodiazepines (avoid)
    Theoretical
  • Pregnancy (avoid)
    Theoretical
  • MAO inhibitors (MAOIs) (avoid)
    Theoretical

vital_signs Clinical Profile

Primary Indications

  • check_circle insomnia
  • check_circle anxiety
  • check_circle neuralgia
  • check_circle pain
  • check_circle migraine
  • check_circle stress
  • check_circle nervous agitation
  • check_circle bed-wetting in children
  • check_circle muscle spasm

Therapeutic Actions

nervineanxiolyticsedativeanalgesicantispasmodichypnoticmild analgesicantidepressant

System Affinities

  • check_circle nervous system
  • check_circle cardiovascular
  • check_circle musculoskeletal

labs Active Constituents

californidine

escholtzine

protopine

allocryptopine

sanguinarine

chelerythrine

reticuline

N-methyllaurotetanine

aporphine alkaloids

history_edu Traditional Use

No TCM data available for this herb yet.

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Traditional Uses Across Healing Systems

While many herbs lack controlled clinical trials, centuries of traditional practice across cultures provide valuable insight into their therapeutic applications.

Indigenous Western North America (California, Oregon)
Pre-European settlement; documented from Ohlone, Yokuts, and other California indigenous peoples

Roots chewed for oral and dental pain; plant used as tea for headaches, anxiety, insomnia, and fever

Roots were applied as poultice to wounds for topical pain relief. Plant was used as a gentler pain remedy than related Papaver species.

Western Herbal North America
Included in Parke-Davis catalogue in 1890 as soporific and analgesic; popularized in 19th-20th century naturopathic medicine

Nervine sedative and analgesic for insomnia, anxiety, neuralgia, and pain; safe alternative to stronger sedative herbs

Health Canada authorizes a product standardized to 0.8% isoquinoline alkaloids for use as analgesic and mild sedative. Considered a gentler and non-addictive alternative to opium poppy.

spa Parts Used

aerial parts

Constituents
californidineescholtzineprotopineallocryptopinesanguinarinereticuline
Indications
  • insomnia
  • anxiety
  • pain
  • nervous agitation
Preparation

Aerial parts (leaves, flowers, stems) harvested during flowering. Used as tincture (1:5, 60% ethanol), infusion (tea), or powder. Health Canada approves standardized 0.8% isoquinoline alkaloid extract as analgesic and sedative.

root

Constituents
californidineprotopinehigher alkaloid concentrations
Indications
  • toothache (topical)
  • stronger analgesic and sedative action
Preparation

Root contains higher alkaloid concentrations than aerial parts. Traditionally chewed by Native Americans for dental pain. Not generally used in commercial preparations due to higher potency.

shield Safety

Contraindications — Evidence Basis

Concurrent use with CNS depressants, sedatives, opioids, benzodiazepines
avoid Theoretical

Additive CNS depressant effects. Alkaloids have demonstrated GABA-A modulation and possible opioid receptor activity. May prolong sedation or enhance respiratory depression.

Pregnancy
avoid Theoretical

Contains alkaloids with potential opioid activity. No safety studies in pregnancy. Best avoided as a precaution.

MAO inhibitors (MAOIs)
avoid Theoretical

Theoretical interaction - alkaloids may interact with MAO inhibition. Caution advised though not clinically documented.

Toxicity

Toxic Dose

Generally considered safe at 500 mg-2 g/day dried herb. No significant toxicity documented at therapeutic doses. Aqueous extracts non-toxic in mouse studies.

Symptoms

Drowsiness, impaired coordination at high doses. No reports of serious toxicity at therapeutic doses in adults.

Management

Reduce dose. For severe sedation: standard supportive care. Not known to cause respiratory depression at therapeutic doses.

Adverse Effects

drowsinessimpaired alertnessavoid drivingmild GI upset in some individuals

CYP Metabolism

Limited CYP data. Alkaloids may be substrates or inhibitors of CYP enzymes; clinical significance unknown. Use caution with narrow therapeutic index drugs.

swap_horiz Interactions

CNS Depressants / Sedatives (Benzodiazepines, Zolpidem, Barbiturates)

Synergistic moderate

Class: CNS Depressants

Mechanism

California poppy alkaloids — including (S)-reticuline and protopine — modulate GABA-A receptors as positive allosteric modulators and may have partial opioid receptor agonist activity. Additive CNS depression with benzodiazepines, barbiturates, or non-benzodiazepine sedatives can result in excessive sedation or respiratory depression.

Clinical Guidance

Avoid combining California poppy supplements with CNS depressant medications. If a patient insists on use, reduce CNS depressant doses cautiously and monitor for excessive sedation, respiratory depression, and impaired psychomotor function. Use with caution in elderly patients.

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Evidence Source Rolland A, Fleurentin J, Lanhers MC, et al. Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae). Phytother Res 2001;15(5):377-381. View source open_in_new

Opioid Analgesics (Morphine, Codeine, Oxycodone, Tramadol)

Increased Effect moderate

Class: Opioid Analgesics

Mechanism

California poppy alkaloid (S)-reticuline can be biotransformed to morphine-like alkaloids that bind mu-opioid receptors. Protopine's analgesic effects are partially reversible by naloxone, indicating opioid receptor interaction. Additive opioid receptor stimulation increases risk of excessive analgesia, sedation, and respiratory depression.

Clinical Guidance

Do not combine California poppy with opioid medications without medical supervision. Advise patients on opioid therapy to avoid California poppy products. Monitor for signs of opioid toxicity (excessive sedation, respiratory rate <12/min, miosis). Naloxone may reverse effects.

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Evidence Source Fedurco M, Gregorova J, Sebrlova K, et al. Modulatory effects of Eschscholzia californica alkaloids on recombinant GABAA receptors. Biochem Res Int 2015;2015:617620. View source open_in_new

CYP3A4 / CYP2C9 / CYP2C19 Substrates (Warfarin, Midazolam, Alprazolam, Tacrolimus)

Increased Effect moderate

Class: CYP-metabolized Drugs

Mechanism

Ethanolic extracts of California poppy and isolated alkaloids escholtzine and allocryptopine show strong time-dependent inhibition of CYP3A4, CYP2C9, and CYP2C19 in vitro, while protopine reversibly inhibits CYP2D6. This can reduce clearance of drugs metabolized by these enzymes, raising plasma levels.

Clinical Guidance

Exercise caution when combining California poppy extracts (particularly ethanolic tinctures) with drugs having narrow therapeutic indices and CYP3A4/2C9/2C19 metabolism. Aqueous tea preparations appear to have lower CYP interaction risk. Monitor for signs of drug toxicity.

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Evidence Source Gafner S, Dietz BM, McPhail KL, et al. Alkaloids from Eschscholzia californica and their inhibitory capacity on CYP enzymes and PXR. J Nat Prod 2016;79(4):1033-1043. View source open_in_new

MAO Inhibitors (Phenelzine, Tranylcypromine, Selegiline, Moclobemide)

Caution moderate

Class: MAO Inhibitors

Mechanism

California poppy alkaloids act on serotonin (5-HT1A) receptors, and N-methyllaurotetanine (NMT) has demonstrated antidepressant-like serotonergic activity. Combining with MAO inhibitors may increase serotonergic activity, raising theoretical risk of serotonin syndrome and hypertensive crisis.

Clinical Guidance

Avoid combining California poppy with MAO inhibitors. Maintain a washout period of at least 14 days between MAO inhibitor treatment and California poppy use. Monitor for signs of serotonin syndrome (agitation, hyperthermia, tachycardia, myoclonus).

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Evidence Source Gafner S, Dietz BM, McPhail KL, et al. Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-hydroxy-2-DPAT to 5-HT1A receptors in vitro. J Nat Prod 2006;69(3):432-435. View source open_in_new

General Anesthetics / Perioperative Agents

Synergistic moderate

Class: Anesthetic

Mechanism

California poppy's GABAergic alkaloids can potentiate the CNS depressant effects of anesthetic agents, potentially prolonging anesthesia induction, recovery time, or causing unexpected hypotension. The multi-receptor pharmacology of its alkaloids makes preoperative interactions particularly unpredictable.

Clinical Guidance

Discontinue California poppy supplements at least 2 weeks before elective surgery. Inform anesthesiologist of any California poppy use. Monitor respiratory function closely during and after anesthesia in patients who have used this herb.

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Evidence Source Rolland A, Fleurentin J, Lanhers MC, et al. Behavioural effects of the American traditional plant Eschscholzia californica: sedative and anxiolytic properties. Planta Med 1991;57(3):212-216. View source open_in_new

hub Combinations

info

Synergistic pairings can enhance therapeutic outcomes, while knowing suitable substitutes helps when specific herbs are unavailable or contraindicated.

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Synergistic Combinations

3
Hawthorn
Strong Evidence
Rationale

The validated clinical combination (with magnesium) demonstrated efficacy for anxiety. Hawthorn cardiovascular support complements California Poppy nervine effects for cardiac manifestations of anxiety.

Clinical Evidence

RCT: Hanus M et al. Curr Med Res Opin. 2004;20(1):63-71. E. californica + Crataegus + magnesium for mild-moderate anxiety in 264 patients.

Passionflower
Limited Evidence
Rationale

Both are nervine sedatives acting on GABA pathways. California Poppy is more analgesic while Passionflower has stronger antispasmodic and anxiolytic activity. Combined for anxiety with pain or insomnia.

Clinical Evidence

Traditional pairing in clinical herbalism; no direct RCT data for combination.

Valerian
Moderate Evidence
Rationale

Both herbs modulate GABA pathways with different alkaloid/valerenic acid mechanisms. Clinical trial showed combination reduced insomnia severity and increased sleep duration.

Clinical Evidence

Open-label observational study: 36 patients with insomnia showed significant improvement in sleep duration (+0.5h) and insomnia severity with E. californica + valerian combination.

science Studies

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Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California Poppy) and Its Alkaloids

In Vitro
2016 |Roby MHH et al. Phytother Res. 2016 Sep;30(9):1498-507.

This in vitro pharmacokinetic study investigated the effects of Eschscholzia californica ethanol extract, aqueous extract, and isolated alkaloids on cytochrome P450 enzymes, P-glycoprotein, and the pregnane X receptor. The ethanol extract and its fractions showed potent time-dependent inhibition of CYP3A4, CYP2C9, and CYP2C19, plus reversible inhibition of CYP2D6. The isolated alkaloids escholtzine and allocryptopine were identified as the key CYP inhibitors. Notably, the aqueous tea extract and californidine did not significantly affect these drug-metabolizing pathways, suggesting that tea preparations may be safer than ethanol-based supplements regarding drug interactions.

CYP-inhibitionPXR-activation
View source open_in_new

Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors

In Vitro
2015 |Abramson SN et al. Front Pharmacol. 2015 Oct;6:196.

This in vitro electrophysiology study investigated the molecular mechanisms underlying the sedative and anxiolytic effects of California poppy alkaloids using recombinant GABAA receptor isoforms expressed in Xenopus oocytes. The alkaloid (S)-reticuline was identified as a positive allosteric modulator at alpha3, alpha5, and alpha6 GABAA receptor isoforms, explaining the anxiolytic properties of the plant. N-methyllaurotetanine showed no significant effect at concentrations below 30 uM. The chloride-current modulation by (S)-reticuline at specific receptor subtypes provides a plausible molecular basis for California poppy's traditionally documented sedative and anxiolytic effects.

GABA-modulatinganxiolyticsedative
View source open_in_new

medication Dosing

tincture

Dose Range

30-60 drops (1.5-3 mL), 1:5 in 60% ethanol

Frequency

1-3x/day; higher dose at bedtime for insomnia

Notes

Lower doses (30 drops) for daytime anxiolytic use; higher doses (60 drops) for sedation and sleep. Can be combined with valerian for insomnia.

capsule

Dose Range

500 mg-2 g dried aerial parts powder

Frequency

1-2x/day; or as directed

Notes

Health Canada authorized product: 3 g dried herb standardized to 0.8% isoquinoline alkaloids as analgesic and mild sedative. Start with lower dose to assess individual sensitivity.

tea

Dose Range

1-2 tsp dried aerial parts per cup

Frequency

1-3x/day

Notes

Steep covered 10-15 min. Mild pleasant flavor. Suitable for evening use. For children: half adult dose under herbal supervision.

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Disclaimer: This information is largely AI-generated and reviewed by human experts at Evara Health. It is intended for educational and clinical reference purposes only and should not replace professional medical advice.

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