Entourage effect of CBD from Traditional Chinese Medicine to Modern Pharmacology

1. ENTOURAGE EFFECT
OF
CANNABIDIOL (CBD)
FROM
TRADITIONAL CHINESE MEDICINE
TO
MODERN PHARMACOLOGY
By
Kevin KF Ng, MD, PhD.
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, FL., USA
Email: kevinng68@gmail.com
A Slide Presentation for HealthCare Provider Nov 2020

2. Lecture outline
▪ History of entourage effect
▪ Scientific basis
▪ Traditional Medicine
▪ Western Medicine
▪ Controversy

3. HISTORY

4. Endocannabinoid Discovery Timeline
https://www.projectcbd.org/science/endocannabinoid-discovery-timeline

5. Who first coined the term “Entourage Effect” ?
▪ It was Aristotle who first made the observation that
“The whole is more than the sum of its parts”
▪ The ”Entourage Effect” was first used by Shimon Ben-Shabat and Raphael
Mechoulam in 1998 when they suggested the biological synergy existed
among cannabinoids, terpenoids and flavonoids.
https://hampihemp.com/research/what-is-the-entourage-effect-and-how-does-it-work/

6. Evolution of the concept of “Entourage effect”
▪ The phrase “entourage effect” first appeared in the European Journal
of Pharmacology July 1998 by S. Ben-Shabat and several colleagues.
▪ The article focused on 2-AG and “a novel route for molecular
regulation of endogenous cannabinoid activity.”
▪ The authors reported that 2-AG’s binding affinity for CB1 and CB2 was
enhanced by the presence of other endogenous lipid compounds that
were not part of the cannabinoid framework.
▪ A subsequent paper that year in the same journal discussed “the
effects of ‘entourage’ compounds on the activities of anandamide and
2-arachidonoyl glycerol.”

7. What is Entourage Effect?
▪ The entourage effect is a proposed mechanism by which cannabis
compounds other than tetrahydrocannabinol (THC) act
synergistically with it to modulate the overall psychoactive effects
of the plant
▪ Cannabidiol (CBD) has been shown to modify the effects of THC
by mitigating the psychoactive effects of THC.
▪ Other bioactive compounds including terpenes and flavonoids
may also contribute to the entourage effects of CBD.
https://en.wikipedia.org/wiki/Entourage_effect

8. SCIENTIFIC BASIS

9. Difference between summation and synergism response
https://quizlet.com/317403373/agonists-and-antagonists-flash-cards/

10. Example of drug combinations producing
Summation vs. Synergistic effects.
http://tmedweb.tulane.edu/pharmwiki/doku.php/drug_receptor_theory

11. Examples of Combined Effects of Drugs in Therapeutics
Drug Synergism
▪ Additive effects (1 + 1 =2)
▪ Aspirin + piracetam ol
▪ Amlodipine + atenolol
▪ Nitrous oxide + halothane
▪ Supra-additive effect (1 + 1 = 4)
▪ Sulfamethoxazole + trimethoprim
▪ Levodopa + carbidopa
▪ Acetylcholine + physostigmine
▪ Multiple combination effect
▪ Lisinopril + HCTZ + atenolol + hydralazine

12. TRADITIONAL CHINESE MEDICINE (TCM)

13. Traditional Chinese Medicine (TCM)
over 300 herbs are in common use
TCM is based on herbal combinations and formulas of
many herbs
https://ars.els-cdn.com/content/image/1-s2.0-S0102695X17301011-fx1_lrg.jpg

14. Philosophical theory of how TCM herbs works
▪ 1 Monarch
▪ 2 Ministers
▪ 3 Assistants
▪ 4 Aids
▪ Combination of these herbs is thought to produce an
orchestral or ensemble effect thereby maximizing the
therapeutic effects of the herbs and minimizing their
side effects.

15. Western medicine view on how a drug works
▪ Agonist and antagonist
▪ Receptor activation
▪ Biologic response
▪ Metabolism
▪ Synthesis enzymes
▪ Degradation enzymes
https://psychonautwiki.org/wiki/File:Agonists_and_antagonists.png

16. Drugs used in the treatment of congestive heart failure:
Synergism with 4 classes of drugs

17. Additive and synergistic effects of two or more drugs:
Drugs for congestive heart failure
https://www.graphpad.com/support/faq/how-can-i-figure-out-if-two-drugs-are-additive-or-synergistic/

18. Summary of Effect of drug combination on response using a
Bliss independence dose-response surface model (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415926/

19. BIOACATIVE COMPOUNDS IN CANNABIS PLANT

20. Bioactive compounds in cannabis plant involved in
Entourage Effect
https://www.kindhealthflorida.com/terpenes/

21. Entourage Effect of cannabinoids and
other bioactive compounds

22. Orchestral (ensemble) effect of Traditional Chinese Medicine herbs
is similar to
Entourage effect of cannabinoids in cannabis plant
Synergy in Harmony
Ensemble effect of
Traditional Chinese Medicine herbs
Entourage effect of
Cannabinoids, terpenes and flavonoids
=

23. Common Features in The Ensemble and Entourage Effects
▪ Receptor mechanisms
▪ Antioxidant mechanism
▪ Anti-inflammatory mechanism
▪ Immuno-modulatory mechanism
▪ Antimicrobial mechanism
▪ Anticancer mechanism
▪ Various medical treatments

24. CONTROVERSY

25. Controversy of entourage effect of cannabinoids
▪ The entourage effect of cannabinoids was initially
discovered in isolated tissues and laboratory
animals.
▪ The results of entourage effect on human studies
are mixed.
▪ The concept of entourage effect in cannabinoids is
similar to the ensemble effect of multiple herbs in
Traditional Chinese Medicine which has stood the
test of time for thousands of years.

26. SUMMARY

27. Summary
“The whole is greater than the sum of its parts.”
Aristotle
384 BC – 322 BC

28. ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com