The Entourage Effect and Why It Matters
What is the Entourage Effect?
The hemp and marijuana plant are both defined as cannabis sativa. Although biologically identical, there is one glaring difference between these two plants – marijuana grows with higher percentages of THC, and lower percentages of CBD, and hemp is the reverse (higher percentages of CBD, and lower percentages of THC).
The cannabis plant is comprised of over 400 trace compounds to include cannabinoids, terpenes, and flavonoids, and many of these compounds offer individual therapeutic benefits. However, scientists have found many of these identified compounds work synergistically, meaning the medicinal effects of the whole plant (cannabinoids, terpenes, flavonoids) far outweigh the benefits of their individual parts. This synergistic relationship between the different compounds in cannabis is commonly referred to as the entourage effect.
Cannabinoids are complex chemical compounds that act on receptors in cells. This collection of receptors has been identified as the endocannabinoid system (ECS). The ECS is an extraordinary communication system in both the brain and body, which is responsible for a variety of functions, to include how we feel, move, and react. There are over 100 different cannabinoids found in the hemp and marijuana plant, however the two primary cannabinoids are CBD and THC.
Tetrahydrocannabinol (THC) has been the epicenter of cannabis research since 1964 when the Israeli organic chemist, Raphael Mechoulam, isolated and synthesized it. In more recent history, the pharmacological contributions of cannabidiol (CBD) have been demonstrated, and now other minor cannabinoids (i.e. CBDA, CBG, CBN, CBC) have captured scientific interest.
Tetrahydrocannabinol (THC): The most popular of the cannabinoids due to its psychoactivity (i.e. causes users to feel “stoned” or “high”). Uniquely binds with both CB1 and CB2 receptors of the endocannabinoid system, resulting in a range of effects on both the body and the mind. THC may help relieve nausea, pain, and stimulate appetite.
- Cannabis-based medicines for chronic neuropathic pain in adults
- How does cannabidiol (CBD) influence the acute effects of delta-9-tetrahydrocannabinol (THC) in humans? A systematic review
- The use of cannabinoids for sleep: A critical review on clinical trials
Cannabidiol (CBD): A highly therapeutic, yet non-psychoactive cannabinoid found in cannabis. CBD acts as an agonist to the 5-HT1A receptor, binds with various TRPV ion channels, and activates the GPR55 receptor, resulting in CBD’s myriad of medicinal benefits (i.e. may help relieve anxiety, pain, inflammation, stress, insomnia, depression, with antioxidant and neuroprotectant properties).
Cannabidiolic acid (CBDA): Once considered solely a precursor to CBD, CBDA actually offers a variety of medicinal and health benefits due primarily to its activation of the 5-HT1A serotonin receptors, as well as its affinity for the GPR55 receptor (both aiding in CBDA's anti-anxiety, antidepressant, and anti-nausea effects.
Additionally, research indicates CBDA inhibits cyclooxygenase-2 (COX-2) enzyme. There are two types of cyclooxygenase enzymes: COX-1 (maintains lining of both the stomach and intestines) and COX-2 (linked to inflammatory response and associated pain). Unlike NSAIDs like aspirin and ibuprofen, which inhibit both COX-1 and COX-2 enzymes, CBDA bypasses COX-1 enzymes, and only inhibits COX-2. By inhibiting COX-1, long-term use of NSAIDS can cause major issues in the gastrointestinal tract such as bleeding and ulceration. Because CBDA exclusively inhibits the COX-2 enzyme, it shows great potential as a safer anti-inflammatory compound.
- Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis
- Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice
- Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort
- What is CBDA and What is it good for?
- Acute oral cannabidiolic acid methyl ester reduces depression-like behavior in two genetic animal models of depression
Cannabigerol (CBG): The acidic form of CBGA, and a precursor to CBDA. This cannabinoid elicits medicinal benefits through direct interactions with the CB1 and CB2 receptors in the brain. THC produces its psychoactive effects through these two receptors, however CBG is non-psychoactive, therefore will not result in the sensation of feeling “high”. CBG may have anti-inflammatory, neuroprotectant, and anti-bacterial properties.
- In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid
- Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease
- Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol
Cannabinol (CBN): Best known as the precursor to THC, CBN is created as cannabis ages, and THC breaks down. Research suggests CBN has a greater affinity for the CB2 receptor of the endocannabinoid system (i.e. the immune system), and has been popularly associated with sedation. More recent studies suggest that CBN protects neurons from oxidative stress and cell death, thereby potentially treating age-related neurodegenerative diseases like Alzheimer's.
- Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function
- Novel cannabinol probes for CB1 and CB2 cannabinoid receptors
- Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol
- Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain
- Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors
Cannabichromene (CBC): Another non-intoxicating cannabinoid, formed when CBCA decarboxylates. This cannabinoid binds with the endocannabinoid receptors TRPV1 and TRPA1, both of which are linked to pain perception.
- Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action
- The effect of cannabichromene on adult neural stem/progenitor cells
- Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L
Terpenes are aromatic molecules, excreted from the minuscule glands of the hemp and marijuana plant. However, terpenes are not exclusive to the cannabis plant. They are responsible for both the scent and therapeutic benefits found in essential oils (ex: the terpene linalool is what gives lavender its floral scent and calming effects). In addition to providing cannabis and other plants with their pungent scent, terpenes are used to attract pollinators, and to repel pests and herbivores. They have also been used in beauty and pharmaceutical products for centuries. Roughly 200 different terpenes have been found in cannabis, however only a few are worth mentioning, as only concentrations above 0.05% are considered of pharmaceutical interest.
Beta-Caryophyllene (BCP): The most common terpene found in cannabis, and can also found in black pepper, clove, and oregano. BCP binds with the endocannabinoid system, specifically the CB2 receptor, which is unique to the caryophyllene family. This terpene is thought to have analgesic, antidepressant, anti-inflammatory, antioxidant, anxiolytic, and neuroprotectant properties.
- Beta-Caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain
- Polypharmacological properties and therapeutic potential of beta-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise
- Beta-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice
- Beta-caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats
Alpha and Beta-Pinene: Another common terpene found particularly in sativa-strains, pinene can be found in rosemary, basil, and most notably, pine trees. This terpene may have analgesic, antibacterial, anti-inflammatory, and antioxidant properties.
- Alpha-pinene exhibits anti-inflammatory activity through the suppression of MAPKs and NF-kB pathway in mouse peritoneal macrophages
- Therapeutic potential of alpha and beta-pinene: a miracle gift of nature
- Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential
- A review of the potential use for Pinene and Linalool as terpene-based medicines for brain health: discovering novel therapeutics in the flavours and fragrances of cannabis
D-Limonene and L-Limonene: These citrus-smelling terpenes are most commonly found in lemon rinds, orange rinds, and juniper, and assist in the absorption of other terpenes. This terpene may have antidepressant, anti-inflammatory, and anxiolytic properties.
- Neuroprotective effects of limonene
- Can limonene be a possible candidate of evaluation as an agent or adjuvant against infection, immunity, and inflammation in COVID-19?
- Anti-inflammatory and chondroprotective activity (+)-alpha-pinene: structural and enantiomeric selectivity
- Anxiolytic Terpenoids and Aromatherapy for Anxiety and Depression
- Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum
Myrcene: This sweet and hoppy terpene is most commonly found in (you guessed it) hops, as well as mangoes. This monoterpene may have analgesic with sedating properties, as well as powerful anti-inflammatory effects.
- Myrcene and terpene regulation of TRPV1
- Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes
- Effect of beta-myrcene on pentobarbital sleeping time
- Myrcene attenuates renal inflammation and oxidative stress in the adrenalectomixed rat model
Linalool: This mildly floral terpene is most commonly found in lavender and jasmine. For thousands of years, linalool has been used as a calmative, and may have anxiolytic and sedating properties.
- Linalool Odor-Induced Anxiolytic Effects in Mice
- Anxiolytic Terpenoids and Aromatherapy for Anxiety and Depression
- Inhaled linalool-induced sedation in mice
- Linalool attenuates oxidative stress and mitocondrial dysfunction medicated by glutamate and NMDA toxicity
Flavonoids are a diverse group of plant chemicals called phytonutrients, which are found in almost all fruits and vegetables. As previously mentioned, flavonoids are also found in cannabis, and account for roughly 10% of the plant’s known compounds. Flavonoids found exclusively in cannabis are called cannaflavins, and similar to terpenes, effect how we experience cannabis through our senses. Flavonoids are what give cannabis its pigmentation, odor, and flavor, while also providing various therapeutic benefits (namely antioxidant and anti-inflammatory).
- Flavonoids: an overview
- Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science
- Analysis of Phenolic Compounds in Commercial Cannabis sativa L. Inflorescences Using UHPLC-Q-Orbitrap HRMS
The Rx Remedies Difference
At Rx Remedies, we believe plant medicine is real medicine. And with all of the different compounds found within the cannabis plant (cannabinoids, terpenes, and flavonoids), we believe there is a significant amount of medicinal science to be understood and applied in product development.
We don’t just use whole-plant, full-spectrum CBD oil in our products. We further include concentrated terpene profiles, as well as additional plant-based, active ingredients, for the most comprehensive and effective plant-based medicine on the market. And all products are researched and formulated by our board-certified toxicologist and pharmacologist.
Research indicates inflammation in the body and anxiety can manifest through multiple ailments and symptoms. Although CBD is all-natural and our primary active ingredient, it is only one of the many plant-based compounds that we include in our products. We know when you are seeking relief, you just want a product that works for you. And you shoudn't have to spend hours of time researching to find that product. So, our promise is simple: to formulate the most effective, 100% plant-based remedies for optimal relief. It shouldn't get more complicated than making a product that works.
Have questions about cannabis? Not sure which CBD product is right for you?
Contact us at firstname.lastname@example.org today. We are here for you.