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Here is another research paper that I wrote during my masters degree. This paper examines the California poppy and some of its notable benefits.

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California poppy Eschscholzia californica and its Sedative, Analgesic, and Anxiolytic Effects

Written by Julie Howell

12/11/2023

This paper aims to see if the California poppy Eschscholzia californica is or is not effective in use for anxiety, pain, or sedation, as stated in the monograph found in Peterson (2020). Anxiety is a disabling diagnosis with comorbidity, and there is a need for phytotherapy to help treat it (Sarris et al., 2013). A systematic review by Lakhan et al. (2010) advised that 55 million people in the United States alone are affected by anxiety and depression, which are two of the most common mental disorders. Standard treatment for anxiety and pain is with addictive medications such as benzodiazepines or narcotics. Berro et al. (2023) discussed increased use of benzodiazepine abuse and that deaths are on the rise, which is a cause for concern. This adds to the need for a non-addictive alternative with the same desired beneficial effects for treatment. This review discusses the sedative, analgesic, and anxiolytic effects of California poppy Eschscholzia californica.

California poppy is found in the antispasmodic category of Peterson (2020). The Latin binomial of California poppy is Eschscholzia californica and is part of the Papaveraceae family. Eschscholzia californica is a flowering plant that grows about 2 feet tall. The above-ground parts are used for herbal remedies. Its primary therapeutic uses are analgesic, anodyne, diaphoretic, diuretic, hypnotic, and spasmolytic properties. The roots have noted narcotic and respiratory effects. The traditional uses are sedative, anxiolytic, to prolong sleep, spasmolytic, analgesic, for stomach cramps, and toothaches. Concerns for using California poppy Eschscholzia californica is that it binds with the same receptors as monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs). When taken with other sedatives, it may increase sedative activity. The dosing guidelines for Peterson (2020) are two grams of dried herb to 105 ml of water taken as tea up to 4 times daily. Mills et al. (2005) provided a standard dose of 3-6 ml daily at a 1:2 ratio of liquid extract or equivalent in tablet or capsule form. The active constituents in California poppy are alkaloids californine and protopine, and have benzodiazepine-like activity. It is recommended not to use this herb while pregnant or breastfeeding or if allergic to any herbs in the Papaveraceae family.

Drugs.com (2023) defines benzodiazepines as a medication that works on the central nervous system (CNS) by lessening stimulation and acts on the GABA A receptors. Benzodiazepines are used for various things, but a few diagnoses listed are anxiety, sedation, and sleep disorders. They are meant for short-term use and, if used long-term, can cause addiction and the need for higher doses due to tolerance. With California poppy, there are limited contraindications with the use, and it would be an excellent natural alternative to addictive benzodiazepines.

Methods

To find articles, the American College of Healthcare Sciences (ACHS) library database was utilized, and the research terms used were "California poppy for anxiety," "California poppy for pain," "California poppy as an analgesic," "Eschscholzia californica for pain," "Analgesic effects of California poppy," "Eschscholzia californica as a sedative," "California poppy as a sedative," and "Eschscholzia californica for anxiety." The articles searched for were clinical trials using California poppy Eschscholzia californica as a single or combination use for anxiety, sedation, and pain from 2004 to 2023, and are full-text and scholarly. Articles that did not use California poppy in the manner mentioned above and any articles outside the date ranges applied were not included. Studies were limited, many articles were duplicates, and most available articles were in vitro or done on animals. The article by Bilia et al. (2008) was found on Science Direct, and it had to be ordered through the ACHS librarian to read the full article.

Results

  In an observational, open-label, longitudinal study by Abdellah et al. (2019), 22 people diagnosed with insomnia participated, and the results were used for the final assessment and data. The participants had to have a diagnosis of insomnia with an insomnia severity index (ISI) score greater than 7. Participants took a combination supplement of Eschscholzia californica and valerian root. Participants were advised to take a max of up to 4 tabs of the supplement every night for four weeks. One supplement tablet had 80 mg of Eschscholzia extract and 32 mg of valerian root extract. The study assessed multiple aspects of sleep regarding anxiety, sleep latency, length, times awake throughout the night, and efficacy. Patients used sleep diaries to document self-assessments, which were then used to determine ISI. The final results showed that the supplement helped and showed a 30% decrease in the mean ISI score (a 5-point reduction) and a 36-minute increase in sleep duration.

Bilia et al. (2008) used a 70% v/v ethanol extract in rats to study the analgesic properties of California poppy. Several tests were completed by stimulated chemical, thermal, and pressure injury. They simulated neuropathy by chronic constriction injuries of the sciatic nerve, repeated treatment with the chemotherapeutic agent oxaliplatin, osteoarthritis caused by intra-articular injection of monoiodoacetate, and inflammation caused by carrageenan plantar injection. They used 100 mg/kg for injection or 300 mg/kg for oral dosing of California poppy for pain management. The results of all the simulated injuries showed a significant pain perception reduction. They noted that the dose peaked at 30 minutes and was uninterrupted by naloxone, indicating that California poppy does not use the same opioid neurotransmitters as traditional narcotics. During the experiments, they also noted that California poppy worked better than gabapentin in the simulated osteoarthritis experiment. The conclusion was that the California poppy exhibited characteristics that would be a good alternative for acute and chronic pain treatment.  

Fedurco et al. (2015) is a research study that focused on the actions of alkaloids, such as protopine and allocryptopine, found in Eschscholzia californica and their effects on the GABA receptor sites. They also isolated N-Methyllaurotetanine (NMT), an aporphine alkaloid that was a serotonin receptor site 5HT1a antagonist. They analyzed the percentage of alkaloids isolated and assessed their actions on the receptor sites. Their results showed that very minimal amounts of protopine and allocryptopine were found. They said they could not activate the GABA receptor sites due to their minute amounts. However, they discovered that NMT acts on the GABA A site and is likely responsible for the sedative action found in Eschscholzia californica. They also found that the S-reticuline may metabolize into morphine, reacting to opioid receptors and also initiating depression in the central nervous system. The conclusion was that the dosage of dried aerial parts of the plant would need to be increased to above 1 gram to work as intended, or combined with another herb promoting sedative effects.

Hanus et al. (2004) completed a double-blind, randomized, placebo-controlled study on the effects of a combination of two herbs and magnesium on anxiety. The study consisted of 264 patients with diagnosed mild to moderate anxiety. They compared the results of a drug that contained 75 mg of hydro-alcoholic dried flower head of Crataegus oxyacantha, 20 mg of a dried aqueous extract of Eschscholzia californica, and 75 mg of magnesium combination named Sympathyl, and compared it to a placebo. The participants in both groups received two tablets twice daily over three months. The results showed that both groups had improved anxiety symptoms; however, the change was more significant in the Sympathyl trial group.

The study by Lemoine et al. (2019) was a single-center, single-arm, open-label trial that used a combination mixture called Novanuit, which included vitamin B6, melatonin, Eschscholzia californica, lemon balm, and passionflower. The study was completed on 40 participants with mild to moderate sleep disorders/insomnia. The participants were given two capsules to be taken daily at the same time each day, 30-60 minutes before bedtime for two weeks. Each dose (2 capsules) contained 1 mg of melatonin, 0.42 mg of vitamin B6, 8.4 mg of California poppy extract, 150 mg of passionflower extract, and 240 mg of lemon balm extract. The results summarized showed a significant positive benefit and concluded that it would be a good alternative for insomnia treatment.

Sarris et al. (2013) reviewed preclinical studies that focused on using various herbal remedies for anxiety, including Eschscholzia californica. Their two-part review found 53 different herbs with anxiolytic activity and noted that only the animal studies are included in this review. The review contains 32 different animal studies that included a variety of herbs, while the second part of the review will consist of 21 human trials. The review noted that the primary mechanism of action for the beneficial herbs is that they involve GABA receptors to some extent, including direct receptor binding and cell membrane modulation. Saris et al. (2013) summarized each herb individually and noted that the California poppy had sedative and anxiolytic effects with oral doses over 100 mg/kg. They concluded that there was encouraging evidence but agreed that more research on human trials is needed.

Discussion

            The review with mice (Saris et al., 2013) (Bilia et al., 2008) used a higher dose of California poppy than the human trials (Lemoine et al., 2019) (Hanus et al., 2004). Both human trials used a combination medication, while the animal studies used California poppy alone, which could explain the need for a higher dose. The trials on animals and humans had similar results, showing positive sedative, analgesic, and anxiolytic effects. Bilia et al. (2008) compared the effects of gabapentin to California poppy and produced beneficial results for pain control in multiple types of induced pain diagnoses. The study by Lemoine et al. (2013) was not conducted in the lab, and the results were based on self-assessment questionnaires, Likert scales, and sleep diaries. While the study appears to have succeeded, the concern for a mind-over-matter effect would be present. It would be beneficial to complete this as a double-blind trial and compare it to a placebo or traditional sleep medications without any other sleep, dietary, or lifestyle changes. Similarly, the study by Abdellah et al. (2019) noted that some of the sleep diary and self-assessment information could have been skewed and suggested that another study be completed using actigraphy and not solely subjective assessment. Another concern noted in Abdellah et al. (2019) study is that there was no standard dose, and participants could have taken anywhere from 1 to 4 tabs. Having participants take a similar dose or a dose based on weight would have had more reliable study data.  

Conclusion

In summary, all the studies showed that there is supporting evidence that Eschscholzia californica helps treat anxiety, sleep, and pain as a single formula or synergistically in combination with other herbs. While the studies show promising results, they all agree that more research is necessary to understand its benefits fully and get it standardized for treatment. Based on the findings, using California poppy in the recommended doses should be a first-line treatment before advancing to more addictive medications such as benzodiazepines and or narcotics. California poppy has proven itself to have sedative, anxiolytic, and analgesic benefits.

References

Abdellah, S. A., Berlin, A., Blondeau, C., Guinobert, I., Guilbot, A., Beck, M., & Duforez, F. (2019). A combination of Eschscholtzia californica Cham. and Valeriana officinalis L. extracts for adjusting insomnia: A prospective observational study. Journal of traditional and complementary medicine, 10(2),116-123. https://doi.org/10.1016/j.jtcme.2019.02.003

Berro, L. F., Fidalgo, T. M., Rowlett, J. K., & Tardelli, V. S. (2023). Editorial: Benzodiazepine addiction: from lab to street. Frontiers in psychiatry, 14, 1287352. https://doi.org/10.3389/fpsyt.2023.1287352

Bilia, A.R., Norcini, M., Maidecchi, A., Vivoli, E., Galeotti, N., & Ghelardini, C. (2008). Antihyperalgesic effect of Eschscholzia californica in rat models of neuropathic pain.

Drugs.com. 2023. https://www.drugs.com/drug-class/benzodiazepines.html 

Fedurco, M., Gregorova, J., Sebrlova, K., Kantorova, J., Pes, O., Baur, R., Sigel, E., & Taborska, E. (2015). Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors. Biochemistry Research International, 2015.   https://doi.org/10.1155/2015/617620 

Hanus, M., Lafon, J., & Mathieu, M. (2004). Double-blind, randomized, 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. Current Medical Research and Opinion, 20(1), 63-71.   https://www.proquest.com/scholarly-journals/double-blind-randomisedplacebocontrolled-study/docview/207998821/se-2

Lakhan, S. E., & Vieira, K. F. (2010). Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutrition Journal, 9, 42.            https://doi.org/10.1186/1475-2891-9-42

Lemoine, P., Bablon, J.-C., & Da Silva, C. (2019). A combination of melatonin, vitamin B6, and medicinal plants in treating mild-to-moderate insomnia: A prospective pilot study. Complementary Therapies in Medicine, 45, 104–108. https://doi.org/10.1016/j.ctim.2019.05.024

Mills, S., & Bone, K. (2005). The essential guide to herbal safety. Churchill Livingston: An imprint of Elsevier Limited.

Peterson, D. (2020). Advanced Herbal Materia Medica II. Portland: American College of   Healthcare Sciences.

Sarris, J., McIntyre, E., & Camfield, D. A. (2013). Plant-Based Medicines for Anxiety Disorders, Part 1: A Review of Preclinical Studies. CNS Drugs, 27(3), 207–19.   https://www.proquest.com/scholarly-journals/plant-based-medicines-anxiety-disorders-part-1/docview/1466148100/se-2