CBD and melatonin are natural substances that have long been recognised for re-establishing restorative sleep and promoting relaxation. Now for the first time, SuperSmart is combining them in an exceptional formulation, probably the best alternative to sleeping tablets for re-establishing restorative sleep naturally and durably …

Who is CBD + Melatonin aimed at??

This highly-innovative formulation is for anyone affected by the following:

• repeated problems with falling asleep at conventional times;
• difficulty getting up in the morning;
• waking frequently in the night;
• waking up too early in the morning;
• feeling tired on waking;
• feeling anxious about going to bed;
• chronic lack of sleep that impacts on daily life;
• insomnia;
• muscle or joint pain on waking or at bedtime;
• jet lag.

It is suitable for men and women of all ages. It’s particularly good for anyone with an unhealthy lifestyle, or who spends too much time in front of a screen, who works in an office or who has low levels of physical activity.

Why melatonin?

Melatonin is a hormone derived from serotonin, which is secreted by the pineal gland, primarily during the hours of darkness. Often referred to as the ‘sleep hormone’, it is crucial for regulating our circadian rhythms, particularly the sleep/wake cycle. It signals to the body where it is in the day/night cycle and promotes sleepiness at appropriate times.

Unfortunately, production of this hormone is nowadays significantly impaired by artificial light. At the end of the day, when the retina senses the decrease in light levels, a neural signal is sent to stimulate production of melatonin and the start of the sleep process. Exposure to artificial light during these key hours thus has a deeply negative effect: melatonin secretion falls dramatically, only to resume later, causing an untimely peak in its production which results in fatigue and sleepiness in the morning (1). This is exacerbated by exposure to the blue light emitted by screens.

Melatonin production also declines with age, due to calcification of the pineal gland (2) and decreased melatonin receptor sensitivity. Indeed studies have shown that after the age of 60, the deep and REM (or paradoxical) phases of sleep decline sharply and night-time waking increases.

Taking an external source of melatonin before bed is a recognised natural solution to correcting impaired melatonin secretion. Its effects have been demonstrated in people with and without sleep problems (3-4). Unlike drugs, it works without disrupting the different stages of sleep and causes no residual effects the following morning.

Various studies show that to obtain maximum efficacy, you need to take melatonin for a minimum of 3-4 days. However, use of this hormone at low doses (as is the case here) should not be prolonged indefinitely, 4 weeks at most, by which time things will be back to normal.

Does it produce any side-effects?

No particular adverse side-effects have been demonstrated in oral supplementation toxicology studies using a wide range of doses (from 1 to 300mg) over moderate treatment periods (5).

Why add CBD?

CBD does not induce sleep per se, but it helps promote relaxation, vasodilation and pain relief. It is a phytocannabinoid molecule found in hemp (Cannabis sativa) along with the well-known psychotropic substance tetrahydrocannabinol (THC). But unlike THC, CBD has no psychoactive effect – it will not get you ‘high’.

CBD is very similar to the endocannabinoid messengers produced by the body to trigger various responses (pain modulation (6-7), reduction in spontaneous locomotion (8-9), relaxation, hypothermia… (10)). Such is its similarity, it is (to varying degrees) able to bind to the same receptors and trigger the same sort of chain reactions. These receptors are primarily found on cell surfaces in the brain, central nervous system and immune system tissues.

What are the main elements of the chain reaction triggered?

• reduction in the inflammatory response (pain relief) (11-13) ;
• triggering of vasodilation (14) ;
• decreased intensity and impact of symptoms associated with anxiety or chronic stress (15-16) (stress being a common cause of sleep problems);
• effect on other brain receptors, particularly serotonin, a neurotransmitter that controls mood and sleep;
• reduction in reactive oxygen species (ROS) and lipid peroxidation (17).

It’s an important element of the formulation as lack of sleep is very often linked to stress.

How is CBD produced?

The CBD in this formulation is extracted from the leaves of Cannabis sativa, using supercritical carbon dioxide (sCO₂). This is an alternative mode of extraction to the organochlorine solvents normally used in such processes but which are potentially harmful to the environment. Very eco-friendly, sCO₂ both ensures the final product is free from solvent residues and helps maintain the chemical integrity of the heat-sensitive molecules. It is odourless, colourless, non-toxic and non-inflammable and is completely safe for our health and our environment.

Are there any side-effects?

CBD is very different from THC, the psychoactive substance found in the same plant. It has an excellent safety profile in humans and is in no way associated with the public health problems posed by cannabis. Its half-life is around nine hours, after which it is excreted in urine in a metabolised form.

Five good reasons to take CBD + Melatonin

1. CBD perfectly complements the effects of melatonin: one deals with the hormonal disruption caused by environmental factors, while the other tackles anxiety and stress, which are recognised factors in insomnia.
2. Scientific studies show that melatonin’s mechanism of action is radically different from that of benzodiazepines. Unlike sleeping pills which enforce drowsiness and disrupt cognitive performance and the architecture of sleep, melatonin induces a form of ‘calm sleep’ (18-19).
3. Western populations generally get less sleep than they need to stay on top form (20).
4. Good quality sleep is essential for long-term health, as it has an effect on cognitive faculties, rebuilding damaged cells, neural synapse plasticity, the immune defences, tissue repair, efficacy of endogenous antioxidants, mental health, and maintenance of muscle and bone tissue.
5. CBD and melatonin offer numerous other health benefits, particularly antioxidant, immune-stimulant and anti-inflammatory effects.

Additional steps for enhancing the efficacy of CBD + Melatonin

To maximise the effects of supplementing with this formulation, you can also follow the steps below:

1) Try to maintain a healthy lifestyle, particularly by avoiding frequent changes to your sleep habits, smoking, excess alcohol consumption, and using electronic devices in bed (mobile phones, tablets, computers …) Instead, establish a calm routine before you go to sleep - listen to soothing music, read, practise yoga or do breathing exercises, for example.

2) Restrict intense visual, physical auditory or mental stimulation in the two hours before bed.

3) Eat dinner at least two hours before you go to bed, and prioritise foods high in tryptophan, an amino acid involved in the production of melatonin and which encourages drowsiness. Good sources are seeds, wholegrain rice, dairy products, eggs, pulses, chocolate and brewer’s yeast.

In addition, light therapy can be valuable, potentially boosting the effects of melatonin, especially in people who spend a lot of time indoors.

One capsule taken 30 minutes before bed is generally enough to obtain this supplement’s benefits.
It’s worth noting that melatonin receptors are usually more sensitive between the hours of 7pm and 8pm (21).

This expertly-dosed formulation is not designed to replace the many plant-based combinations already available (such as the highly-effective Advanced Sleep Formula); it does, however, offer a more powerful alternative if you take into account the impact stress and pain can have on sleep problems.

Precautions: Do not exceed the recommended dose. This product should not be used as a substitute for a varied, balanced diet. Keep out of children’s reach. Protect from light, heat and humidity. Not recommended for women who are pregnant or breastfeeding, or for those suffering from mental disorders or auto-immune diseases. Consult a health professional before taking this product if you have any health problems. Do not take melatonin before driving or using machinery.

Written: October 2018.

Références

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3. Zhdanova IV. Melatonin as a hypnotic: Pro. Sleep Med Rev. févr 2005;9(1):51 65.
4. Turek FW, Gillette MU. Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med. nov 2004;5(6):523 32.
5. Bonnefont-Rousselot D, Collin F. Melatonin: Action as antioxidant and potential applications in human disease and aging. Toxicology. 28 nov 2010;278(1):55 67.
6. Hill KP. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems: A clinical review. JAMA. 2015;313:2474–83
7. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005;65:812–9
8. Portella G, Laezza C, Laccetti P, De Petrocellis L, Di Marzo V, Bifulco M. Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: Actions on signals involved in angiogenesis and metastasis. FASEB J. 2003;17:1771–3
9. Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev. 2003;83:1017–66.
10. Venance L, Maldonado R, Manzoni O. Le système endocannabinoïde central. Med Sci (Paris) 2004 ; 20 : 45-53.
11. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;34:13–25
12. Wang Q, Shao F, Wang W. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats. Front Mol Neurosci. 2015;8:49
13. Wee N, Kandiah N, Acharyya S, Chander RJ, Ng A, Au WL, et al. Depression and anxiety are co-morbid but dissociable in mild Parkinson's disease: A prospective longitudinal study of patterns and predictors. Parkinsonism Relat Disord. 2016;23:50–6
14. Hillard CJ. Endocannabinoids and vascular function. J Pharmacol Exp Ther. 2000;294:27–32.
15. Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci. 2012;367:3364–78.
16. Bergamaschi MM, Queiroz RHC, Chagas MHN, de Oliveira DCG, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011;36:1219–26.
17. Iuvone T, Esposito G, Esposito R, Santamaria R, Di Rosa M, Izzo AA. Neuroprotective effect of cannabidiol, a non-psychoactive componentpCannabis sativa, on ß-amyloid-induced toxicity in PC12 cells. J Neurochem. 2004;89:134–41.
18. Attenburrow ME, Cowen PJ, Sharpley AL. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl). juill 1996;126(2):179 81.
19. Zhdanova IV, Wurtman RJ, Lynch HJ, Ives JR, Dollins AB, Morabito C, et al. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. mai 1995;57(5):552 8.
20. Beck F, Richard J-B, Léger D. [Insomnia and total sleep time in France: prevalence and associated socio-demographic factors in a general population survey]. Rev Neurol (Paris). déc 2013;169(12):956 64.
21. Van den Heuvel CJ, Ferguson SA, Macchi MM, Dawson D. Melatonin as a hypnotic: con. Sleep Med Rev. févr 2005;9(1):71 80.

A natural and bioavailable form of GABA

PharmaGABA® is an innovative formulation containing gamma-aminobutyric acid, or GABA, as it’s more commonly known. This neurotransmitter is recognised for its calming, anxiolytic effects in the body and is thus available in nutritional supplement form for fighting stress and anxiety. While a number of dietary supplements are formulated from synthetic GABA, PharmaGABA® offers a natural alternative. This new stress-fighting supplement contains natural GABA obtained from Lactobacillus hilgardii, a bacteria used for fermenting vegetables. This unique formulation process produces a form of GABA with excellent bioavailability in the body.

GABA, a neurotransmitter with calming effects

With its content in natural, bioavailable GABA, PharmaGABA® offers a way of obtaining the benefits of this neurotransmitter. Gamma-aminobutyric acid is the body’s main inhibitory neurotransmitter, helping to regulate neuron activity by reducing neuronal excitability and preventing prolonged over-excitation. GABA’s neuron-modulating role is essential for inducing a state of physical and mental relaxation. In other words, GABA acts as both as powerful anxiolytic and a natural stress-buster.

GABA, anti-stress and anxiolytic effects

While neuronal excitation is essential in certain situations, prolonged over-excitation can be damaging to health, leading to problems with sleep, behaviour and mood, as well as increased blood pressure (hypertension). These symptoms are typical of a state of stress or anxiety. In the nervous system, this manifests as an imbalance between excitatory neurotransmitters such as acetylcholine, and inhibitory neurotransmitters such as GABA. PharmaGABA® has been developed specifically to maintain or restore such balance. In delivering natural GABA, this new dietary supplement helps relax the body and reduce the many negative effects of stress and anxiety.

PharmaGABA®, a pharmaceutical grade anti-stress supplement

Adhering to high quality standards, PharmaGABA® has seen rapid growth in demand, particularly in Japan. Both in nutritional supplements and as a functional drink ingredient, it is popular with Japanese people for reducing stress and inducing a state of relaxation. This innovative formulation provides 125mg of natural GABA per capsule, with a suggested dose of one capsule a day, although this can be adapted to your needs and the advice of your therapist. You may also be interested in other supplements that help combat stress and maintain general well-being. N-acetyl L-tyrosine and 5-hydroxytryptophan (5-HTP) , for example, are two amino acid derivatives which can be converted in the body into various neurotransmitters such as noradrenaline, dopamine and serotonin. The latter two are so-called ‘happiness hormones’, while noradrenaline acts as a natural brain stimulant.