• At a physiological level, the synergy resulting from the combinations of cannabinoids, terpenes, and flavonoids amplifies the activity of endogenous cannabinoids interacting with the body’s endocannabinoid system(1).
  • Researchers believe that cannabinoids or cannabis compounds have a symbiotic action, like cannabidiol (CBD)’s action mitigating the psychoactive effects of tetrahydrocannabinol (THC).
  • In the medical setting, the entourage effect is recognized for its proclivity to alleviate symptoms of specific medical conditions like gastrointestinal, autoimmune, and mood disorders(2).

What Is CBD? What Is the Entourage Effect?

There are  86 cannabinoids identified in Cannabis sativa. The majority can be categorized as analogs of delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), cannabicyclol (CBL), cannabielsoin (CBE), and cannabitriol (CBT)(3)

Users consuming Cannabis sativa may experience the entourage effect resulting from integrating cannabinoids THC and CBD and different compounds such as phytocannabinoids, terpenes, and flavonoids(4).

When numerous substances work together synergistically, the psychoactive and medicinal properties are enhanced. This chemical teamwork or harmonic interplay between the compounds leads to a maximal pharmaceutical effect. In addition, the entourage effect may broaden the range of therapeutic applications of cannabis products(5).

What Does Research Say?

The study Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects shows how THC has been the main interest of cannabis research since 1964(6). 

In 1998, Professors Shimon Ben-Shabat and Raphael Mechoulam explained how the endocannabinoid system demonstrated the entourage effect. 

These synergistic effects show how closely related molecules and inactive metabolites significantly enhance the activity of the primary endogenous cannabinoids, 2-arachidonoylglycerol (2-AG), and anandamide. 

2-AG functions as a signaling lipid in the central nervous system(7). On the other hand, anandamide is synthesized in the areas of the brain important in thought processes, memory, and control of movement(8).

Many body processes, including immunological response, cell communication, sleep cycles, and memory, are regulated and balanced by these receptors, interacting with the ECS(9).

Experts stated that CBD has the most influence on the entourage effect. This theory was supported by Ethan Russo, a psychopharmacologist and cannabis researcher in Washington State(10). 

How Does the Entourage Effect Work in the Brain?

Cannabinoids and terpenoids (another term for isoprenoids or terpenes) in cannabis may interact with one another and with the brain receptors, resulting in an entourage effect.

CBD is believed to have an inhibitory effect when endocannabinoids are disabled within the endocannabinoid system. This effect enhances the action of these endogenous molecules on cannabinoid receptors(11)

The neuroprotective properties of CBD do not appear to be exerted by the activation of essential targets within the ECS for plant-derived cannabinoids like CB1 and CB2 receptors(12).

A scientific trial showed how Δ9-THC acts as a partial agonist at type 1 cannabinoid receptors (CB1), primarily located in the central and peripheral nervous system (13)

Proponents argued that non-THC cannabinoids could interact with cannabinoid receptors in the central nervous system. CBD, whether full-spectrum or broad-spectrum, may possess the ability to modulate the stoning and anxiety effects of THC by inhibiting some cannabinoid receptors(14).

Cannabis produces a wide range of phytocannabinoids alongside a vast array of terpenes. However, while known to modulate neuroendocrine function, the specific acute and chronic dose-related impact of cannabinoids in humans still needs to be studied with care(15).

What Does the Entourage Effect Do for the User?

The entourage effect has been investigated in combination with a variety of conditions. 

Numerous clinical studies have demonstrated that distinct therapeutic effects can significantly contribute to the entourage effects of cannabis-based medical extracts. 

Studies show how multiple sclerosis causes pain, fatigue, inflammation, muscle spasticity, and depression. Many individuals with multiple sclerosis look for alternative and complementary therapies such as cannabis(16)

Complementing studies demonstrate a marked improvement in subjective sleep parameters in patients with various pain conditions, including peripheral neuropathic pain, multiple sclerosis, rheumatoid arthritis, and intractable cancer pain(17).

Medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing THC, CBD, or a 1: 1 combination of the two (Sativex)(18)

Sleep-laboratory results show a mild activating effect of CBD and slight residual sedation with THC-predominant extracts(19)

Around 40-50% of subjects achieved excellent sleep quality. Lack of sleep is a primary source of disability in chronic pain syndromes. This sleep quality may help in an individual’s quality of life(20).

Ways to Experience the Entourage Effect

The type of product becomes essential when considering ways to experience the advantages of the entourage effect and the therapeutic potential using the different kinds of CBD. 

Full-Spectrum CBD Products

Full-spectrum CBD products contain most of the components found in the cannabis plant. 

These products keep the full cannabinoid spectrum of the plant and its compounds unaltered. 

  • Fiber
  • Chlorophyll
  • Phytocannabinoids,
  • Flavonoids
  • Proteins
  • Fatty acids
  • Terpenes
  • THC

These CBD products derived from hemp and THC-rich cannabis can contain up to 0.3% THC can contain up to 0.3% THC(21).  These components are contained in full-spectrum CBD oil.

Full-spectrum CBD contains various cannabinoid chemicals derived from the cannabis plant and trace amounts of THC. The entourage effect is enhanced as full-spectrum products have components other than CBD, such as THC.

This low concentration of THC is unlikely to produce the euphoria associated with cannabis use.

Broad Spectrum CBD Products

Broad-spectrum products contain a wide range of cannabinoids without THC, meaning users will not feel high. 

THC is found in trace amounts in most broad-spectrum products but is classified as non-detectable (ND) on the certificate of analysis(22). 

Below are ways to examine how cannabinoids may be administered to get the entourage effect:

  • Ingesting edible CBD products result in the slowest onset of action. CBD passes through the stomach and is processed by the liver. Its therapeutic effects can persist the longest.
  • Applying CBD-rich products beneath the tongue or against the cheek tissues promotes absorption slowly. The therapeutic effects, however, may last longer.
  • Vaping or smoking CBD-rich products results in rapid action since the cannabinoid is absorbed into the blood through the lungs. The therapeutic effects typically last many hours.
  • CBD-containing medicines can be prepared for topical administration. In this method, CBD is absorbed locally, such as topical products, applied directly on the skin like a balm to experience targeted relief.

It is essential to consult healthcare experts as directed by the FDA (Food and Drug Administration) relative to the beneficial effects of CBD. Consulting medical experts will protect every user of cannabis-derived products.

What Is the Best Ratio of THC to CBD?

CBD is highly correlated to another significant medically active phytocannabinoid, THC, the psychoactive component of cannabis. 

CBD and THC are the critical components of cannabis extracts that have been the subject of many pharmacology and scientific investigations.

CBD and THC both have substantial medicinal properties. However, unlike THC, CBD does not cause “stoning” or intoxication. CBD and THC operate differently on the brain and human body receptors.

CBD can potentially mitigate or eliminate the intoxicating effects of THC based on the quantity consumed(23). Individuals may prefer the medical benefits of cannabis without experiencing a euphoric high or with a reduced level of intoxication.

While THC and CBD may perform better together than they do individually, it is crucial to remember that cannabis affects everyone uniquely(24).

Taking Advantage of CBD Safely

Phytocannabinoid-terpenoid entourage effect can create synergy in treating depression, anxiety, pain, inflammation, epilepsy, cancer, addiction, and bacterial and fungal infections(25)

While there are numerous CBD products available, not all of them, despite the rigorous research, are guaranteed to be of acceptable quality.  

CBD consumers must understand the various forms of CBD and take measures to identify third-party standards. 

It is essential to consider the following to obtain a high-quality CBD product.

  • Safety and purity are guaranteed.
  • The milligrams of CBD are included in each dose.
  • Lab testing was done following strict standards.
  • CBD products, whether edibles, oil, or tinctures, are distributed only through state-licensed dispensaries
  • The manufacturer uses only USDA (United States Department of Agriculture) organic CBD(26).

Individuals interested in using and consuming CBD and THC for their potential anti-inflammatory health benefits and other therapeutic effects on pain, inflammation, anxiety, addiction, epilepsy, cancer, bacterial and fungal infections should consult a healthcare provider or medical professional(27). This decision is crucial if an individual is currently taking other medications.

Additionally, one should keep in mind that THC and CBD may induce side effects. 

THC is psychotropic, and in specific individuals, it may cause dry mouth, slowed reaction times, weariness, short-term memory loss, and anxiety(28)

On the other hand, CBD may have side effects such as nausea, diarrhea, and weight loss(29).

Furthermore, it is essential to consider that while medical marijuana is prohibited at the federal level, it is permitted under some state laws.

Anyone wanting to explore a THC-containing product needs to check local laws and FDA regulations.

How Does The Entourage Effect Apply To Consumer Products?

Terpenes, flavonoids, and other lesser-known medical cannabis are different compounds that contribute to the entourage effect. 

However, individuals who are sensitive to the psychoactive effects of THC, even in fractional amounts required by law, may prefer a CBD isolate. 

CBD isolates are flavorless and odorless CBD products characterized by the lack of terpenes. 

Terpenes are constituents of essential oils. This compound plays a vital role in realizing the potential benefits of cannabinoids(30)

Beta-caryophyllene, beta-pinene, humulene, limonene, and linalool myrcene are among the most common terpenes(31).

Scientific investigations revealed that cannabis terpenes replicate the effects of cannabinoids and produce similar pain-relieving benefits. These effects were heightened without increasing adverse reactions(32).

Is CBD Still Beneficial Without THC?

Evidence indicates that CBD works best when combined with THC and the full spectrum of other cannabis components(33). In recent years, it has been unfolding state-by-state and country-by-country.

So while some individuals experiment with CBD but abstain from THC, others are interested in CBD. 

  1. The Entourage Effect https://caclinics.com.au/australia-medicinal-cannabis-news/the-entourage-effect/ 
  2. ibid
  3. Cannabichromene https://www.sciencedirect.com/topics/medicine-and-dentistry/cannabichromene 
  4. ibid
  5. The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7324885/ 
  6. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/
  7. 2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain https://www.sciencedirect.com/science/article/pii/S0163782717300619
  8. Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/ 
  9. The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6334252/
  10. Some of the Parts: Is Marijuana’s “Entourage Effect” Scientifically Valid? https://www.scientificamerican.com/article/some-of-the-parts-is-marijuana-rsquo-s-ldquo-entourage-effect-rdquo-scientifically-valid/ 
  11. The Endocannabinoid System as an Emerging Target of Pharmacotherapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/ 
  12. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? https://pubmed.ncbi.nlm.nih.gov/22625422/ 
  13. Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors https://www.frontiersin.org/articles/10.3389/fphar.2020.00359/full 
  14. Does Cannabidiol Protect Against Adverse Psychological Effects of THC? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797438/ 
  15. The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7324885/ 
  16. Cannabidiol to Improve Mobility in People with Multiple Sclerosis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874292/ 
  17. Ibid
  18. THC and CBD oromucosal spray (Sativex®) in the management of spasticity associated with multiple sclerosis https://pubmed.ncbi.nlm.nih.gov/21456949/ 
  19. ibid
  20. Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine https://pubmed.ncbi.nlm.nih.gov/17712817/ 
  21. Patients Guide to CBD https://american-safe-access.s3.amazonaws.com/Patients_Guide_to_CBD.pdf 
  22. ibid
  23. Does Cannabidiol Protect Against Adverse Psychological Effects of THC? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797438/ 
  24. Cannabis, a complex plant: different compounds and different effects on individuals https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736954/ 
  25. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/ 
  26. ibid
  27. ibid
  28. Patient-Reported Negative Effects from Medical Cannabis page https://www.health.state.mn.us/people/cannabis/docs/about/ipappendixj.pdf 
  29. What are the benefits of CBD — and is it safe to use? https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700# 
  30. Study shows Cannabis terpenes provide pain relief, contribute to ‘entourage effect’ https://www.sciencedaily.com/releases/2021/07/210714110455.htm# 
  31. ibid
  32. ibid
  33. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01238.x
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