Review Article
Volume 14 Issue 3 - 2022
A Desktop Primer and Practical Review of Cannabis-Containing Compounds and Their Entourage Effects
Nicholas A Kerna1,2*, John V Flores3,4, Sudeep Chawla5, Stephen M Brown6, Joseph Anderson II7, ND Victor Carsrud8, Hilary M Holets3,4, Rashad Roberson9, Uzoamaka Nwokorie10 and Kevn D Pruitt11,12
1SMC, Medical Research, Thailand
2First InterHealth Group, Thailand
3Beverly Hills Wellness Surgical Institute, USA
4Orange Partners Surgicenter, USA
5Chawla Health & Research, USA
6International University of Health Sciences, St. Kitts
7International Institute of Original Medicine, USA
8Lakeline Wellness Center, USA
9Georgetown American University, College of Medicine, Guyana
10University of Washington, USA
11Kemet Medical Consultants, USA
12PBJ Medical Associates, LLC, USA
*Corresponding Author: Nicholas A Kerna, (mailing address) POB47 Phatphong, Suriwongse Road, Bangkok, Thailand 10500.
Received: November 19, 2021; Published: February 28, 2022


Cannabis sativa is one of the first domesticated plants known to humankind for its numerous psychological, physical, and emotional benefits. Its first use was reported in 2600 BCE in Chinese Pharmacopoeias. Cannabis subspecies hemp and marijuana are widely studied extracts. It is a complex plant with specific constituents acting synergistically. The discovery of the plant’s numerous compounds led to another discovery—that of the endocannabinoid system (ECS), which is widely distributed in the human brain and body. The ECS is responsible for various physiological and psychological effects. However, an increase in epidemiological studies is associated with dose-increasing psychotic disorders, raising significant concern among researchers and physicians. Research began on hundreds of cannabinoids contained in the cannabis plant, leading to the detection of CB1 and CB2 receptors—following the characterization of the ECS in the human body. Specific chemicals express synergistic effects, known particularly as “entourage effects”. The concerted effect of chemical constituents of cannabis enhance the overall pharmacological properties of the plant. This entourage effect has been supported by various studies. However, a few studies debunk the construct of cannabis’ entourage effects. Recent changes in the US FDA Legalization and Scheduled Drug Act are facilitating research on the cannabis plant and compounds to explore therapeutic potential.

Keywords: Cannabidiol; Cannabinol; GABA; Phytocannabinoids; Sativa; Sleep Disorder; Terpenes; Tetrahydrocannabinol


  1. Maroon J and Bost J. “Review of the neurological benefits of phytocannabinoids”. Surgical Neurology International 1 (2018).
  2. Atakan Z. “Cannabis, a complex plant: different compounds and different effects on individuals”. Therapeutic Advances in Psychopharmacology 6 (2012): 241.
  3. Hanuš LO and Hod Y. “Terpenes/Terpenoids in Cannabis: Are They Important?” Medical Cannabis and Cannabinoids 1 (2020): 25-60.
  4. Crocq M-A. “History of cannabis and the endocannabinoid system”. Dialogues in Clinical Neuroscience 3 (2020): 223.
  5. Lancet JR-T. undefined. On the therapeutical uses and toxic effects of cannabis indica (1890).
  6. Final Act of The United Nations Conference.
  7. Small E and Cronquist A. “A Practical And Natural Taxonomy For Cannabis”. Taxon 4 (1976): 405-435.
  8. A H., et al. “The medicinal use of cannabis and cannabinoids--an international cross-sectional survey on administration forms”. Journal of Psychoactive Drugs 3 (2013): 199-210
  9. Wood T., et al. J of the, 1899 undefined. III.-Cannabinol. Part I (1899).
  10. R M LH. “A historical overview of chemical research on cannabinoids”. Chemistry and Physics of Lipids 1-2 (2000): 1-13.
  11. Mechoulam R., et al. “The structure of Cannabidiol”. Tetrahedron12 (1963): 2073-2078.
  12. Gaoni Y and Mechoulam R. “Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish”. Journal of the American Chemical Society8 (1964): 1646-1647.
  13. Ladha KS., et al. “Understanding the Medical Chemistry of the Cannabis Plant is Critical to Guiding Real World Clinical Evidence”. Molecules18 (2020).
  14. Maroon J and Bost J. “Review of the neurological benefits of phytocannabinoids”. Surgical Neurology International1 (2018).
  15. Radwan MM., et al. “Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis”. Molecules9 (2021): 2774.
  16. Bautista JL., et al. “Flavonoids in Cannabis sativa: Biosynthesis, Bioactivities, and Biotechnology”. ACS Omega8 (2021): 5119.
  17. Andre CM., et al. “Cannabis sativa: The Plant of the Thousand and One Molecules”. Frontiers in Plant Science (2016): 19.
  18. Worth T. “Cannabis’s chemical synergies”. Nature 7771 (2019): S12-S13.
  19. Ben-Shabat S., et al. “An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity”. European Journal of Pharmacology 1 (1998): 23-31.
  20. Cather JC and Cather JC. “Cannabidiol primer for healthcare professionals”. Proceedings (Baylor University Medical Center) 3 (2020): 376.
  21. Volkow ND., et al. “Adverse Health Effects of Marijuana Use”. The New England Journal of Medicine 23 (2014): 2219.
  22. Golombek P., et al. “Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature”. Toxics 2 (2020).
  23. Morales P., et al. “Molecular Targets of the Phytocannabinoids-A Complex Picture”. Progress in the Chemistry of Organic Natural Products 103 (2017): 103.
  24. Russo EB. “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects”. British Journal of Pharmacology7 (2011): 1344.
  25. Jakowiecki J., et al. “Allosteric modulation of the cb1 cannabinoid receptor by cannabidiol-a molecular modeling study of the n-terminal domain and the allosteric-orthosteric coupling”. Molecules9 (2021).
  26. Vučković S., et al. “Cannabinoids and Pain: New Insights From Old Molecules”. Frontiers in Pharmacology (2018): 1259.
  27. Reggio PH. “Endocannabinoid Binding to the Cannabinoid Receptors: What Is Known and What Remains Unknown”. Current Medicinal Chemistry14 (2010): 1468.
  28. Søes I., et al. “Cannabinoid CB1 and CB2 Receptor Signaling and Bias 2.1 (2017): 48-60.
  29. Whiting PF., et al. “Cannabinoids for Medical Use: A Systematic Review and Meta-analysis”. JAMA: The Journal of the American Medical Association 24 (2015): 2456-2473.
  30. Jugl S., et al. “A systematic review of evidence for cannabis and cannabinoids as adjuvant therapy in palliative and supportive oncology care 38.15 (2020): 12091-12091.
  31. V M., et al. “Topical cannabis-based medicines - A novel adjuvant treatment for venous leg ulcers: An open-label trial”. Experimental Dermatology9 (2021): 1258-1267.
  32. A practical approach to utilizing cannabis as adjuvant therapy in inflammatory bowel disease | GI and Hepatology News (2021).
  33. BG R., et al. “Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation”. The Journal of neuroscience: the official journal of the Society for Neuroscience8 (2005): 1904-1913.
  34. MM B., et al. “Safety and side effects of cannabidiol, a Cannabis sativa constituent”. Current Drug Safety4 (2011): 237-249.
  35. Johnson JR., et al. “Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC: CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain”. Journal of Pain and Symptom Management2 (2010): 167-179.
  36. Lewis MA., et al. “Pharmacological Foundations of Cannabis Chemovars”. Planta Medica04 (2017): 225-233.
  37. Baron EP., et al. “Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort”. The Journal of Headache and Pain1 (2018): 1-28.
  38. Fukumoto S., et al. “Effect of flavour components in lemon essential oil on physical or psychological stress”. Stress and Health1 (2008): 3-12.
  39. Some of the Parts: Is Marijuana’s “Entourage Effect” Scientifically Valid? - Scientific American (2021).
  40. Raup-Konsavage WM., et al. “Cannabidiol (CBD) Oil Does Not Display an Entourage Effect in Reducing Cancer Cell Viability in vitro”. Medical Cannabis and Cannabinoids2 (2020): 95-102.
  41. Santiago M., et al. “Absence of Entourage: Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Functional Activity of Δ9-THC at Human CB1 and CB2 Receptors”. Cannabis and Cannabinoid Research3 (2019): 165.
  42. Van Bakel H., et al. “The draft genome and transcriptome of Cannabis sativa”. Genome Biology10 (2011):1-18.
  43. Russo EB. “The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain”. Frontiers in Plant Science (2019): 1969.
  44. Booth JK., et al. “Terpene synthases from Cannabis sativa”. Plos One3 (2017): e0173911.
  45. SJ W JBJE J. “Marijuana and medicine: assessing the science base: a summary of the 1999 Institute of Medicine report”. Archives of General Psychiatry6 (2000): 547-552.
Citation: Kerna NA, Flores JV, Chawla S, Brown SM, Anderson II J, Carsrud NDV, Holets HM, Roberson R, Nwokorie U, Pruitt KD. “A Desktop Primer and Practical Review of Cannabis-Containing Compounds and Their Entourage Effects”. EC Neurology 14.3 (2022): 49-57.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

June Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the June issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before July 14, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.