The Endocannabinoid System

Discovered in the early 1990s by Dr. Raphael Mechoulam, the father of medical cannabis research, the endocannabinoid system forms the basis for understanding how cannabis affects our organism. The endocannabinoid system is a key regulator of various bodily functions.
There is hardly a functional process that is not influenced by it to some extent.
Despite the outstanding importance of the endocannabinoid system as a key regulatory mechanism in the biochemistry and physiology of the body, knowledge about this system is still quite limited, especially among German physicians.

This is exactly where we at canncura see a great need for education and training.
In the initial consultation, which you can conveniently carry out digitally from home, our trained doctors will not only inform you about cannabis as medicine, but also about the ECS and its tasks.

Structure of the ECS
What are cannabinoids?

Phytocannabinoids belong to the class of cannabinoids. These chemical compounds are found in the cannabis plant. They bind to the cannabinoid receptors and thus influence the release of messenger substances in the brain. The two most well-known phytocannabinoids are THC (tetrahydrocannabinol) and CBD (cannabidiol).

Endocannabinoids (the bodys own cannabinoids) also belong to the class of cannabinoids. These are made by our body and mimic the way phytocannabinoids work. The two primary endocannabinoids are AEA (arachdionylethanolamine), also called anandamide after the Sanskrit word for “bliss”, and 2-AG (2-arachidonylglycerol).

The role of endocannabinoids is to maintain homeostasis (balance). They ensure that our cells communicate with each other effectively, but not excessively.

Cannabinoid Receptors

There are two main receptors in the ECS – CB1 and CB2.
A receptor can be thought of as a lock to which a corresponding substance fits like a key (if it has the right structure). If the key gets into the lock, further chemical processes take place inside the cell.
CB1 receptors are predominant in the central nervous system, where they curb excessive transmission of messenger substances. As soon as nerve cells release an excessive amount of chemical messengers, the endocannabinoids act as a kind of brake to ensure a balance.

CB2 receptors are distributed throughout the body, particularly in the cells of the immune system and gastrointestinal tract.
Endocannabinoids activate CB2 receptors located on cell membranes. Once activated, CB2 receptors trigger numerous immune-altering effects that depend on the type of cell and its environment. The activation of CB2 receptors leads to a reduction in the release of inflammatory messengers (cytokines). This has positive clinical implications.


The ECS is largely under enzymatic control. The level of endocannabinoids is determined by the balance between making enzymes and breaking them down. They ensure that the endocannabinoids are used when they are needed.



1. Light, M. K., A. Orens, B. Lewandowski, and T. P. Market size and demand for marijuana in Colorado. (2014).

2. Ilgen, M. A. et al. Characteristics of adults seeking medical marijuana certification. Drug Alcohol Depend. 132, 654–659 (2013).

3. Boehnke, K. F., Litinas, E. & Clauw, D. J. Medical Cannabis Use Is Associated with Decreased Opiate Medication Use in a Retrospective Cross-Sectional Survey of Patients with Chronic Pain. J. Pain 17, 739–744 (2016).

4. Whiting, P. F. et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA - J. Am. Med. Assoc. 313, 2456–2473 (2015).

5. Ware, M. A. et al. Smoked cannabis for chronic neuropathic pain: A randomized controlled trial. Cmaj 182, (2010).

6. Mechtler, L. L., Gengo, F. M. & Bargnes, V. H. Cannabis and Migraine: It’s Complicated. Curr. Pain Headache Rep. 25, 1–13 (2021).

7. Rhyne, D. N., Anderson, S. L., Gedde, M. & Borgelt, L. M. Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population. Pharmacotherapy 36, 505–510 (2016).

8. Russo, E. Cannabis for migraine treatment: The once and future prescription? An historical and scientific review. Pain 76, 3–8 (1998).

9. Cuttler, C., Spradlin, A., Cleveland, M. J. & Craft, R. M. Short- and Long-Term Effects of Cannabis on Headache and Migraine. J. Pain 21, 722–730 (2020).

10. Baron, E. P. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science. Headache 58, 1139–1186 (2018).

11. Serpell, M. et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur. J. Pain (United Kingdom) 18, 999–1012 (2014).

12. Hoch, E. et al. How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review. Eur. Arch. Psychiatry Clin. Neurosci. 269, 87–105 (2019).

13. Bachhuber, M., Arnsten, J. H. & Wurm, G. Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary. J. Psychoactive Drugs 51, 400–404 (2019).

14. Shannon, S., Lewis, N., Lee, H. & Hughes, S. Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm. J. 23, 18–041 (2019).

15. Piper, B. J. et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. J. Psychopharmacol. 31, 569–575 (2017).

16. Corroon, J. M., Mischley, L. K. & Sexton, M. Cannabis as a substitute for prescription drugs - A cross-sectional study. J. Pain Res. 10, 989–998 (2017).

17. Duran, M. et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br. J. Clin. Pharmacol. 70, 656–663 (2010).

18. Hernandez, S. L., Sheyner, I., Stover, K. T. & Stewart, J. T. Dronabinol Treatment of Refractory Nausea and Vomiting Related to Peritoneal Carcinomatosis. Am. J. Hosp. Palliat. Med. 32, 5–7 (2015).

19. Merriman, A. R. & Oliak, D. A. Use of medical marijuana for treatment of severe intractable nausea after laparoscopic Roux-en-Y gastric bypass surgery. Surg. Obes. Relat. Dis. 4, 550–551 (2008).

20. Westfall, R. E., Janssen, P. A., Lucas, P. & Capler, R. Reprint of: Survey of medicinal cannabis use among childbearing women: Patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness’. Complement. Ther. Clin. Pract. 15, 242–246 (2009).

21. Gonzalez-Rosales, F. & Walsh, D. Intractable nausea and vomiting due to gastrointestinal mucosal metastases relieved by tetrahydrocannabinol (Dronabinol). J. Pain Symptom Manage. 14, 311–314 (1997).

22. Green, S., Nathwani, D., Goldberg, D. & Kennedy, D. Nabilone as effective therapy for intractable nausea and vomiting in AIDS [letter]. Br. J. Clin. Pharmacol. 28, 494–495 (1989).

23. Dejesus, E., Rodwick, B. M., Bowers, D., Cohen, C. J. & Pearce, D. Use of dronabinol improves appetite and reverses weight loss in HIV/AIDS-infected patients. J. Int. Assoc. Physicians AIDS Care 6, 95–100 (2007).

24. Zutt, M., Hänßle, H., Emmert, S., Neumann, C. & Kretschmer, L. Dronabinol zur supportiven Therapie metastasierter maligner Melanome mit Lebermetastasen. Hautarzt 57, 423–427 (2006).

25. Volicer, L., Stelly, M., Morris, J., McLaughlin, J. & Volicer, B. J. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int. J. Geriatr. Psychiatry 12, 913–919 (1997).

26. Cooper, R. E. et al. Cannabinoids in attention-deficit/hyperactivity disorder: a randomised-controlled trial. Eur. Neuropsychopharmacol. 26, S130 (2016).

27. Aharonovich, E. et al. Concurrent cannabis use during treatment for comorbid ADHD and cocaine dependence: Effects on outcome. Am. J. Drug Alcohol Abuse 32, 629–635 (2006).

28. Hupli, A. M. M. Medical Cannabis for Adult Attention Deficit Hyperactivity Disorder: Sociological Patient Case Report of Cannabinoid Therapeutics in Finland. Med. Cannabis Cannabinoids 1, 112–118 (2019).

29. Prentiss, D., Power, R., Balmas, G., Tzuang, G. & Israelski, D. M. Patterns of Marijuana Use among Patients with HIV/AIDS Followed in a Public Health Care Setting. J. Acquir. Immune Defic. Syndr. 35, 38–45 (2004).

30. Consroe, P. M. R. R. J. T. W. P. R. The Perceived Effects of Smoked Cannabis on Patients with Multiple Sclerosis. Eur. Neurol. (1997) doi:10.1159/000112901.

31. Linares, I. M. P. et al. No acute effects of Cannabidiol on the sleep-wake cycle of healthy subjects: A randomized, double-blind, placebo-controlled, crossover study. Front. Pharmacol. 9, 1–8 (2018).

32. Bonaccorso, S., Ricciardi, A., Zangani, C., Chiappini, S. & Schifano, F. Cannabidiol (CBD) use in psychiatric disorders: A systematic review. Neurotoxicology 74, 282–298 (2019).

33. Neubauer, D., Perkovic Benedik, M. & Osredkar, D. Cannabidiol for treatment of refractory childhood epilepsies: Experience from a single tertiary epilepsy center in Slovenia. Epilepsy Behav. 81, 79–85 (2018).

34. Devinsky, O. et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 15, 270–278 (2016).

35. Szaflarski, J. P. et al. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia 59, 1540–1548 (2018).

36. Hausman-Kedem, M., Menascu, S. & Kramer, U. Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents – An observational, longitudinal study. Brain Dev. 40, 544–551 (2018).