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Why patients suffer from insomnia?

Sometimes a patient lack a progress despite a proven protocol? Perhaps they do not get a  quantity and quality of their sleep. Up to one third of the population struggles with insomnia.5 Research indicates that poor sleep is inflammatory,6 disrupts the blood brain barrier7, and causes irritability, fatigue, poor memory and difficulty concentrating.8Furthermore, insomnia is associated with many health problems including cardiovascular,9 psychiatric,10  neurological,11 digestive, metabolic and rheumatological12 dysfunction. Insomnia is a complex condition, arising from multiple environmental, medical, behavioural and cognitive disorders.13

GABA is a Key Piece of the Sleep Puzzle

Despite the complexity surrounding insomnia, there are some key clues that can help us help patients catch those elusive ‘zzz’s. We know that glutamatergic neurotransmission excites the neurons, promotes alertness, and when elevated (e.g. by stress), reduces the quality and duration of sleep.14 Nature’s answer to glutamate is gamma amino butyric acid (GABA), as it antagonises glutamate signalling and is crucially involved in the regulation of sleep and wakefulness.15 Research shows that patients living with insomnia have reduced levels of GABA, and that GABA receptor activation improves sleep in these individuals.16 This explains why benzodiazepines, which act on GABA pathways, are effective at improving sleep in insomniacs. The addictive nature and undesirable side effects of benzodiazepines, however, lead us to look for GABAergic alternatives that may improve sleep without the negative effects.

 Magic GABA will put you to sleep

relaxed women in lavender

Oral administration of 80 mg per day of lavender essential oil improved sleep quality and quantity in adults suffering from anxiety disorder in a randomised, double-blind comparison study.24

Herbs like zizyphus, passion flower and California poppy, which act on the GABA pathway to improve sleep quality in your patients. In vitro, zizyphus was found to support GABA neurotransmission by causing an increased expression of GABA-A receptors, and by stimulating the synthesis of glutamic acid decarboxylase (GAD), which converts glutamate into GABA.17 In animal models, zizyphus was shown to increase sleep time and improve circadian cycle.18 Passion flower has been found to bind to and stimulate GABA and benzodiazepine receptors and enhance GABA uptake, producing an anxiolytic effect.19,20 California poppy also has an affinity for GABA receptors, resulting in sedating effects.21

Dial Glutamate Down for a Good Night’s Sleep

Dampening down the stimulating effects of the excitatory neurotransmitter, glutamate, may help your patients get the quality sleep they are craving. Zizyphus has been found in animal studies to effectively inhibit glutamate signalling.22  Several herbs and  lavender essential oil, which has been found to be a competitive antagonist of glutamate binding in neuronal membranes.23 Oral administration of 80 mg per day of lavender essential oil improved sleep quality and quantity in adults suffering from anxiety disorder in a randomised, double-blind comparison study.24

Anxiety may cause Insomnia 

Anxiety and depression are closely associated with insomnia.25 Interestingly, the neuroplastic, maladaptive changes that occur with these conditions are also seen in insomnia,26suggesting they share similar pathophysiological processes. Passion flower has been shown to reduce symptoms of anxiety in as little as ten minutes,27 and has demonstrated similar efficacy to benzodiazepine medication (Figure One).28

Figure One: Hamilton anxiety score for passion flower vs. benzodiazepine in generalised anxiety disorder.29

 

Lavender essential oil has also been found to reduce anxiety,30 and to do so more effectively than SSRI medication (Figure Two).31 Addressing potential drivers of insomnia, such as anxiety, may be another mechanism by which you can improve sleep in your insomniac patients.

Figure Two: Hamilton anxiety scale total score change over 10 weeks.32

No Pain May Lead to Sleep Gains

Pain certainly is never welcome, but this is particularly true when it exacerbates insomnia. Persistent pain is characterised by long-term increases in synaptic glutamate signalling in nociceptive pathways,33 as well as a lack of inhibition from GABA.34 Therapeutic interventions that stimulate GABA and inhibit glutamate signalling  may be useful in the management of insomnia accompanied by chronic pain. This formula targets pain as a driver of sleep disturbances with the aid of Jamaica dogwood, traditionally used as an analgesic, spasmolytic and mild sedative. California poppy may be particularly useful for pain-associated insomnia as it was found to reduce pain with comparable efficacy as a common, pain-relieving pharmaceutical medication.35

Don’t Lose Sleep Over Insomnia

Sleep is a common concern that may be contributing to a number of your patients’ health problems. Thankfully, nature has provided some potent answers to the sleep puzzle. Don’t lose sleep over insomnia  as Nature has provided us with a diversity of herbs  to provide powerful sleep support, aiding sleep onset and reducing night-time waking.

 

Source: Metagenics 2016

References

5. Cunnington D, Junge, M, Fernando A. Insomnia: prevalence, consequences and effective treatment. Med J Australia. 2013;199(8):S36-S40.

6. Irwin E, Olmstead R, Carroll J. Sleep disturbance, sleep duration, and Inflammation: A systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biological Psychiatry. [Online]. 2015. Available from: URL:http://escholarship.org/uc/item/1jq9h1jp#page-1 [Cited 17/06/16].

7. Shehata A, Rizk H. Total sleep deprivation compromises blood-brain barrier integrity and impairs learning and memory: A protective effect of glibenclamide and recovery sleep. Journal of Global Biosciences. [Online]. 2015. Available from: URL:http://www.mutagens.co.in/jgb/vol.04/4/03.pdf [Cited 17/06/16].

8. Cunnington D, Junge, MF, Fernando AT. Insomnia: prevalence, consequences and effective treatment. Med J Australia. 2013;199(8):S36-S40.

9. Chien K, et al. Habitual sleep duration and insomnia and the risk of cardiovascular events and all-cause death: report from a community-based cohort. Sleep. [Online]. 2010. Available from: URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817905/ [Cited 17/06/16].

10. Spiegalhalder K, Baglioni C. Comorbid sleep disorders in neuropsychiatric disorders across the life cycle. Current Psychiatry Reports. [Online]. 2013. Available from: URL: https://www.researchgate.net/profile/Dieter_Riemann/publication/236603404_Comorbid_sleep_disorders_in_neuropsychiatric_disorders_across_the_life_cycle/links/0c96051f2df9a9fa7e000000.pdf [Cited 17/06/16].

11. Chen JC, et al. Sleep duration, cognitive decline, and dementia risk in older women. Alzheimer’s and Dementia. [Online]. 2016. Available from: URL:http://aanddjournal.net/article/S1552-5260(15)00195-8/fulltext [Cited 17/06/16].

12. Sutton D, Moldofsky H, Badley E. Insomnia and health problems in Canadians. Sleep. [Online]. 2001. Available from: URL:http://www.journalsleep.org/Articles/240603.pdf [Cited 17/06/16].

13. Drake CL, Roehrs T, Roth T. Insomnia causes, consequences, and therapeutics: an overview. Depress Anxiety. 2003;18(4):163-76.

14. Gao J, Zhang JX, Xu TL. Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala on sleep-waking cycle of rats. Brain Res. 2002 Jul 26;945(1):60-70.

15. Riemann D, et al. The neurobiology, investigation, and treatment of chronic Insomnia. Lancet Neurol. 2015;14(5):547-58.

16. Winkelman JW, Buxton OM, Jensen JE, et al. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). Sleep. 2008 Nov;31(11):1499-506.

17. Han H, et al. Anxiolytic-like effects of sanjoinine A isolated from Zizyphi Spinosi Semen: Possible involvement of GABAergic transmission. Pharmacology, Biochemistry and Behavior. 2009;92:206–213.

18. Cao JX, et al. Hypnotic effect of jujubosides from Semen Ziziphi Spinosae. J Ethnopharmacol. 2010 Jul 6;130(1):163-6.

19. Aslanargun P, et al. Passiflora incarnata Linneaus as an anxiolytic before spinal anesthesia. J Anesth. 2012;26:39-44.

20. Grundmann O, Wang J, McGregor GP, Butterweck V. Anxiolytic activity of a phytochemically characterized Passiflora incarnata extract is mediated via the GABAergic system. Planta Med. 2008 Dec;74(15):1769-73.

21. Rolland A, et al. Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae). Phytotherapy Research 2001;15:377-381.

22. Zhang M, Ning G, Shou C, et al. Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med. 2003;69(8):692-5.

23. World Health Organisation. “Aetheroleum Lavandulae”. WHO Monographs on Selected Medicinal Herbs. 2007;3:219-28.

24. Woelk H, Schläfke S. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine. 2010 Feb;17(2):94-9.

25. Spiegalhalder K, Baglioni C. Comorbid sleep disorders in neuropsychiatric disorders across the life cycle. Current Psychiatry Reports. [Online]. 2013. Available from: URL: https://www.researchgate.net/profile/Dieter_Riemann/publication/236603404_Comorbid_sleep_disorders_in_neuropsychiatric_disorders_across_the_life_cycle/links/0c96051f2df9a9fa7e000000.pdf [Cited 17/06/16].

26. Riemann D, et al. The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol. 2015;14(5):547-58.

27. Movafegh A, et al. Preoperative oral Passiflora Incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study. Anesth Analg. Jun 2008;106(6):1728-32.

28. Akhondzadeh S, et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26(5):363-7.

29. Akhondzadeh S, et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26(5):363-7.

30. Kasper S. An orally administered lavandula oil preparation (Silexan) for anxiety disorder and related conditions: an evidence based review. Int J Psychiatry Clin Pract. 2013;17(Suppl 1):15–22. Available from: URL:http://infekt.ch/content/uploads/2014/11/jc_november14_rudolf.pdf [Cited 17/06/16].

31. Kasper S, et al. Lavender oil preparation Silexan is effective in generalized anxiety disorder – a randomized, double-blind comparison to placebo and paroxetine. International Journal of Neuropsychopharmacology. 2014 Jun;17(6):859-69.

32. Kasper S, et al. Lavender oil preparation Silexan is effective in generalized anxiety disorder – a randomized, double-blind comparison to placebo and paroxetine. International Journal of Neuropsychopharmacology. 2014 Jun;17(6):859-69.

33. Bleakman D, et al. Glutamate receptors and pain. Seminars in Cell and Developmental Biology 2006;17:592-604.

34. Jasmin L, et al. GABA puts a stop to pain. Current Drug Targets. CNS & Neurol Disord. 2004;3(6):487-505.

35. Rolland A, et al. Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae). Phytotherapy Research 2001;15:377-381.

 

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