CBD interacts with the Endocannabinoid System (ECS). The ECS essentially consists of

• receptors (CB1, CB2, GPR55, etc.)
• ion channels (TRPV1, TRPA1, etc.)
• enzymes for formation from precursors enzymes for degradation (e.g. FAAH/Fatty Acid Amide Hydrolase, MAGL/Monoacylglycerolipase) transport proteins for the uptake of endocannabinoids into the cell
• endocannabinoids (anandamid/AEA, 2-arrachidonoylglycerol/2-AG, etc.)
• More than 65 binding sites for CBD have been described in the literature so far, but only about a dozen are likely to be relevant for physiologically achievable concentrations.

Contrary to popular belief, CBD does not primarily bind to the classical receptors CB1 and CB2, but interacts mainly with the G protein Coupled Receptor GPR55, the Peroxisome Proliferator-Activated Receprot gamma (PPARγ) and ion channels such as the vanilloids Transient Receptor Potential Channels (TRPV1, TRPA1). CBD is a complete agonist of Transient Receptor Potential Vanilloid Type 1 (TRPV1), which plays an important role in the reaction to hot (e.g. boiling water) and harmful substances. TRPV1 is a nociceptor: When the receptor is sufficiently stimulated, signals are sent to the brain. This triggers a series of automatic reactions, including pain sensation.

Various cannabinoids, including the endocannabinoids anandamide and N-arrachidonyl dopamine (an agonist of the CB1 receptor), affect the TRPV1 receptor. Conversely, several vanilloids affect cannabinoid receptors, including olvanil and pseudocapsaicin (nonivamide), but not capsaicin itself. The close chemical relationship between many vanilloids and cannabinoids has led researchers to conclude that research into vanilloid cannabimimetics (substances that mimic cannabinoids) has great therapeutic potential.
Furthermore, CBD has been shown to act as an agonist of the 5HT1a receptor ⁽²⁴⁾. This receptor controls the expression of serotonin (5HT) in the central nervous system, and this could explain many of the anxiety and depression relieving properties of CBD. CBD also has a regulating effect on the mu and delta opioid receptors, which are responsible for the anaesthetic and euphoric reaction during cannabis use, which may increase this effect in the user overall.

 

On CB1 and CB2 receptors (major sites of THC), CBD acts as a non-competitive nagative-allosteric modulator of CB1, CBD is neither an agonist nor an antagonist, but inhibits the binding of THC to these receptors⁽²³⁾. This explains the lack of psychoactive side effects and supports the thesis that CBD is the antagonist of THC in its mode of action.

 

⁽²³⁾ R B Laprairie, A M Bagher, M E M Ladle, E M Denovan-Wright. Cannabidiol is a negative allosteric modular of the cannabinoid CB1 receptor. British Journal of Pharmacology, July 27, 2015 Link

⁽²⁴⁾ Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochempcal Res. August 2005 Link

Cannabidiol is an enormously effective substance against anxiety. Firstly, CBD can suppress the appearance of anxiety. On the other hand, CBD can facilitate the forgetting or repressing of anxious and traumatic memories. This fact is particularly interesting for athletes who are under great pressure to perform and have problems with it in competitive situations. Post-traumatic stress disorders (PTSD) after accidents or injuries can also be relieved by CBD ⁽⁴⁾.

1.1 CBD can be helpful in anxiety conditions ⁽¹⁾

As one of the numerous studies shows, even small doses of CBD are sufficient to help with anxiety. A study with 49 participants showed that doses of 30mg CBD are already effective ⁽¹⁾

⁽¹⁾ RK, Kamboj SK, Ramadas M, Yogan K, Gupta V, Redman E, Curran HV, Morgan CJ. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology (Berl). 2013 Apr;226(4):781-92 Link

1.2 CBD can help regulate emotions and emotional memory processing ⁽²⁾⁽³⁾

CBD can suppress the occurrence of anxiety. Studies also show that CBD can facilitate the forgetting or repression of anxious and traumatic memories. ⁽²⁾

 

⁽²⁾ Lee JL, Bertoglio LJ, Guimarães FS, Stevenson CW. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. Br J Pharmacol. 2017 Mar 7 Link

⁽³⁾ Norris C, Loureiro M, Kramar C, Zunder J, Renard J, Rushlow W, Laviolette SR. Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System. Neuropsychopharmacology. 2016 Nov;41(12):2839-2850 Link

1.3 CBD can have positive effects in unforeseen stress situations ⁽⁴⁾

In a study in stressed mice, scientists observed that CBD causes the effects on behavior due to unpredictable stress "presumably due to an alleviation of endocannabinoid neurotransmission and subsequent CB1/CB2 receptor activation".

⁽⁴⁾Fogaça MV, et al. The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling. University of São Paulo, Ribeirão Preto, Brazil. Neuropharmacology. 2018;135:22-33. Link

1.4 CBD may be helpful in acute anxiety conditions ⁽⁵⁾

CBD can also be helpful in acute anxiety conditions. CBD seems to be particularly effective when anxiety is caused by negative memories. ⁽³⁾

⁽⁵⁾ Jurkus R, Day HL, Guimarães FS, Lee JL, Bertoglio LJ, Stevenson CW. Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders. Front Pharmacol. 2016 Nov 24;7:454 Link

CBD has antispasmodic and relaxing properties. In contrast to THC, however, CBD does not explicitly make people tired and is even stimulating for some people. However, there are studies that show that CBD seems to be helpful in sleep-through and sleep-in disorders.^(5)(27) These properties are mainly due to the anxiety-relieving and relaxing effects of CBD. Athletes who train hard until late into the night reported a relaxing effect and improved sleep.

⁽⁵⁾Babson KA, Sottile J, Morabito D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep. 2017 Apr;19(4):23 Link

⁽²⁷⁾Shannon S., Opila-Lehman J.: Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report.
The Permanente Journal 2016 Case; 20(4): 108-111 Link

CBD are assigned strong anti-inflammatory and analgesic properties. Cannabidiol and other cannabinoids are used in the treatment of cancer and chronic pain. Most of the studies published so far have been based on the entire cannabis plant including psychoactive THC. Studies have shown pain relief, but this was usually out of proportion to the side effects. In contrast, studies with pure CBD confirmed the analgesic effect without the typical cannabinoid side effects ⁽⁶⁾

⁽⁶⁾ Casey SL, Vaughawn CW, Plant-Based Cannabinoids for the Treatment of Chronic Neuropathic Pain Link

CBD has also been successfully used in chronic pain in clinical trials. For example, treatment of kidney transplant patients in Uruguay resulted in strong to temporary pain relief. ⁽⁷⁾

⁽⁷⁾ Cuñetti L1, Manzo L2, Peyraube R3, Arnaiz J4, Curi L2, Orihuela S2. Chrinic Pain Treatment with Cannabidiol in Kidney Transplant Patients in Uruguay Link

The anti-inflammatory properties are mainly attributed to the fact that CBD has very high potential as an agonist of the CB2 receptor. ⁽¹³⁾

⁽¹³⁾ Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007 Mar;150(5):613-23 Link

Competitive sports, especially high-performance sports, significantly increase oxidative stress. The oxistatus of a competitive athlete is often similar to that of a seriously ill person. This oxidative stress, which is caused by an increased concentration of free radicals, not only prevents proper regeneration, it is also dangerous. An excessive number of free radicals attacking the cells can trigger a premature aging process and sunbathe the development of chronic diseases. Studies and studies conducted in cancer patients during chemotherapy show that CBD has a protective effect on cells ^(9)(10) and even the genome ⁽⁸⁾.

 

⁽⁸⁾ Yamaori S, Kinugasa Y, Jiang R, Takeda S, Yamamoto I, Watanabe K. Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells. Life Sci. 2015 Sep 1;136:87-93 Link

⁽⁹⁾Santos NA, Martins NM, Sisti FM, Fernandes LS, Ferreira RS, Queiroz RH, Santos AC. The neuroprotection of cannabidiol against MPP⁺-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease. Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):231-40 Link

Unlike the most popular cannabiniodine THC, CBD is not psychoactive. In an animal study, scientists found increased neuregenesis and improved cognitive abilities in damaged animals ^(10). Especially in the American Football League (NFL), the pressure to release CBD according to the WADA code was great because they want to treat their players for concussions with cannabidiol. However, CBD is not only likely to have positive effects on cognitive abilities in sick and injured persons. Numerous feedback from our test subjects on increased concentration and slowed mental fatigue seem to confirm this assumption. However, scientific investigations are still pending at the moment.

⁽¹⁰⁾ Mori MA, Meyer E, Soares LM, Milani H, Guimarães FS, de Oliveira RM.Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3;75:94-105 Link

In various studies cannabidiol showed antidepressive properties. It has been shown that cannabidiol interferes with brain metabolism and increases the effect of serotinin ⁽¹¹⁾ and glutamate ⁽¹²⁾, which can lead to a noticeable improvement in mood. This can be of interest to athletes during injury breaks, among other things, as the reduced physical strain and the lack of endorphins can reduce serotonin levels. The use of CBD can also be helpful for mental lows and motivation problems.

⁽¹¹⁾ Shoval G, Shbiro L, Hershkovitz L, Hazut N, Zalsman G, Mechoulam R, Weller A. Prohedonic Effect of Cannabidiol in a Rat Model of Depression. Neuropsychobiology. 2016;73(2):123-9 Link

⁽¹²⁾ Linge R, Jiménez-Sánchez L, Campa L, Pilar-Cuéllar F, Vidal R, Pazos A, Adell A, Díaz Á. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuropharmacology. 2016 Apr;103:16-26 Link

The Journal of Bone and Mineral Research published a study ⁽¹³⁾ confirming the effectiveness of CBD in healing bone fractures. Israeli scientists from Tel Aviv and Hebrew universities have found that CBD can strengthen the bone in the healing process.

 

⁽¹³⁾ Kogan NM, J Bone Miner Res. 2015 Oct;30(10):1905-13. doi: 10.1002/jbmr.2513. epub 2015 May 10. cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. Link

Another study confirmed these results. This study found that CBD treatment increased serum levels of osteocalcin ⁽¹⁴⁾ and increased bone mineral density. The result was increased bone volume and compression load.

 

⁽¹⁴⁾ Eur J Pharmacol. 2017 Aug 15;809:13-19. doi: 10.1016/j.ejphar.2017.05.011. Epub 2017 May 4. Cannabidiol administration reduces sublesional cancellous bone loss in rats with severe spinal cord injury. Link

An extremely interesting property of CBD is its antispasmodic properties. In the treatment of epilepsy and severe spasticity, good results have already been achieved with CBD extracts⁽²⁸⁾. Our field trials also showed good results in muscular overexertion.

 

⁽²⁸⁾Hussain S.A., Zhou R., Jacobson C., Weng J., Cheng E., Lay J., Hung P., Lerner J.T., and Sankar R.: Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy & Behavior, Volume 47, June 2015, pp. 138-141 Link

⁽²⁹⁾Jones, N. A., Hill A. J., Smith I., Bevan S. A., Williams C. M., Whalley B. J., and Stephens G. J.: Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo. Journal of Pharmacology and Experimental Therapeutics, 2010 Feb; 332(2): 569-577 Link

β-Caryophyllene - also called BETA-Caryophyllen, abbreviated BCP, is a natural substance found in numerous plants. Studies show that BCP is able to interact with some of the receptor sites of the endocannabiniodine system, specifically the CB2 receptor important for CBD uptake ^(15). Through its function as CB2 agonist, BCP also achieves its anti-inflammatory, soothing, antibacterial, antispasmodic and antioxidant effects, making it a useful supplement to CBD. The ECB-Booster contains plants melissa and dstenkraut tinctures contain this important plant substance.

⁽¹⁵⁾Jürg Gertsch,Br J Pharmacol. 2010 Jun; 160(3): 523-529.Phytocannabinoids beyond the Cannabis plant - do they exist? Link

Two studies published in 2004 ⁽¹⁶⁾ and 2005 ⁽¹⁷⁾ show that the plant formerly considered a medicinal plant contains echinacea (coneflower) substances that act similarly to cannabinoids but have no pychoactive effects. It is shown that the alkylamides contained in echinacea are similar to the anandamides found in the body. These anandamides are ligands of the endocannabinoid receptors and bind to the CB receptors.

 

⁽¹⁶⁾ Juerg Gertsch, Roland Schoop, Urs Kuenzle, Andy Suter: Echinacea alkylamides modulate TNF-α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways Link

⁽¹⁷⁾ Karin Woelkart, Wei Xu, Ying Pei, Alexandros Makriyannis, Robert P. Picone, Rudolf Bauer: The Endocannabinoid System as a Target for Alkamides from Echinacea angustifolia Roots. Link

In the study ⁽¹⁸⁾ published in the Journal of Biological Chempstry in 2006, researchers at the Swiss Federal Institute of Technology in Zurich have shown that N-isobutylamides are a new class of cannabino mimetics that bind to the peripheral CB2 cannabinoid receptors on immune cells (T lymphocytes) but not to the CB1 receptors in the central nervous system. The frequently reported immunostimulatory effect associated with echinacea may be related to interaction with CB2 receptors.

 

⁽¹⁸⁾ Stefan Raduner, Adriana Majewska, Jian-Zhong Chen, Xiang-Qun Xie, Jacques Hamon, Bernard Faller, Karl-Heinz Altmann, Jürg Gertsch: Alkylamides from Echinacea Are a New Class of Cannabinomimetics: CANNABINOID TYPE 2 RECEPTOR-DEPENDENT AND -INDEPENDENT IMMUNOMODULATORY EFFECTS. Link

The isoflavonoid genistein contained in red clover plays a decisive role in fatty acid amide hydrolase (FAAH). FAAH is the enzyme responsible for the degradation of the endogenous CB receptor ligand anandamide. ⁽¹⁹⁾ Studies in this study show that genistein inhibits this enzyme and thus the enzymatic hydrolysis (degradation) of anandamide.

⁽¹⁹⁾ Thors L, Alajakku K, Fowler CJ. The'specific' tyrosine kinase inhibitor genistein inhibits the enzymic hydrolysis of anandamide: implications for anandamide uptake. Br J Pharmacol. 2007;150:S951-S960. Link

Black cumin (Nigella Sativa) is one of the most studied plants due to its manifold effects. Numerous studies prove the effect of black cumin.

4.1 Black cumin as an anti-inflammatory and painkiller

Already in 1995 the anti-inflammatory and analgesic mechanism was discovered in laboratory studies ^(20). The thymoquinone contained in black cumin prevents the formation of eicosanoids, which are involved in the development of inflammatory processes.

(20) Houghthon PJ, Fixed oil of Nigella Sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation Link

4.2 Black cumin in asthma

Especially in outdoor athletes, asthma symptoms typical of stress are not uncommon. The use of asthma sprays is always associated with a small portion of residual risk, especially for competitive athletes tested by Anti-Doping. Indian scientists tested in a study ⁽²¹⁾ over a period of three months nigella savita extract in asthma patients. Accurate analysis and lung function text showed a significant improvement in symptoms. It has also been observed that the effect of conventional asthma drugs has been improved.

⁽²¹⁾ Boskabady MH, The possible prohylactic effect of Nigella sativa seed extract in sthmatic patients Fundam Clin Pharmacol. 2007 Oct;21(5):559-66. Link

4.3 Black cumin in rheumatism

Also of interest are the results of a study of black cumin oil in patients with rheumatoid arthritis ⁽²²⁾ . In 2010, 40 patients with this diagnosis were initially treated with placebo, followed by 500 mg black cumin oil capsules twice daily. Pain and movement restrictions decreased rapidly in the treatment, in contrast to the comparative phase with the placebo: joint swelling and morning stiffness decreased, and also in the laboratory the indicator values decreased by over 40%.

 

⁽²²⁾ Gheita TA, Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study. Link

Several studies have shown that alcohol increases the concentration of cannabinoids in the body and increases their effect ^(25)(26). We take advantage of this fact with the ECS booster. The ECS booster is based on 66 percent alcohol. Only a few drops on the oral mucosa are absorbed by the receptors. In addition to the rapid absorption of the plant substances described above, the alcohol also ensures that the CBD drops taken afterwards enter the bloodstream more quickly and in a more concentrated form. This low alcohol absorption has no effect on driving ability. 10 drops of the ECS booster are comparable to 5.4ml beer or 2.3ml wine. In addition, it should be noted that the studies listed below were primarily focused on the concentration of THC. Clinical studies in connection with alcohol and pure CBD are not yet available. However, it can be assumed that the concentration and uptake of other cannabinoids is also favored.

⁽²⁵⁾ Hartman RL, Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol Clin Chem. 2015 Jun;61(6):850-69. doi: 10.1373/clinchem.2015.238287. Epub 2015 May 27. Link

⁽²⁶⁾ Hartman RL, Controlled vaporized cannabis, with and without alcohol; subjective effects and oral fluid-blood cannabinoid relationships, Drug Test Anal. 2016 Jul;8(7):690-701. doi: 10.1002/dta.1839. Epub 2015 Aug 10. Link