How Each Major Cannabinoid Interacts with the CB Receptors Within the Endocannabinoid System.
Grains of Salt:
Before we get started, we want to mention that we are not scientists and we do not have science degrees, but we do our best to vet scientific papers and articles for scientific cannabis information.
We are still in the beginning stages of cannabis research and much of what we “know” could shift in time.
Cannabinoids:
Cannabinoids are natural chemical compounds found in cannabis plants (phytocannabinoids) and in most animals (endocannabinoids). Cannabinoids work with the endocannabinoid system found in most animals by interacting with CB receptors (CB1 and CB2) and specific enzymes. These pharmacological interactions between phytocannabinoids and CB receptors are why cannabis users feel a “high” and experience medical benefits.
Some of the more important phytocannabinoids are THC (tetrahydrocannabinol), CBD (cannabidiol), CBN (cannabinol), THCV (tetrahydrocannabivarin), CBG (cannabigerol).
This is an oversimplified version of how phytocannabinoids work within our endocannabinoid system. Phytocannabinoids (and terpenes) interact with other receptors unrelated to CB receptors or the endocannabinoid system, that influence the entourage effect, so this is not the whole picture behind how we get high.
Endocannabinoid System:
The endocannabinoid system is a biological system that helps to regulate many functions within the human brain and body, such as mood, appetite, pain perception, memory, anxiety, depression, and sleep among many others, as well as having a neuroprotective role when a traumatic brain injury occurs.
CB Receptors:
CB receptors (CB1 and CB2) are G protein-coupled receptors (GPCRs) that help to, in combination with specific enzymes, mediate the psychotropic effects of endo- and phytocannabinoids.
CB Receptor Locations:
CB1: Found primarily in the brain, central and peripheral nervous systems, spinal cord, GI Tract, and peripheral organs.
CB2: Found in immune cells and tissue, with higher concentrations when inflammation occurs. They are also found in the cardiovascular system, GI tract, liver, bones, and the reproductive system.
Defining agonism, affinity, antagonism, allosteric modulator:
Phytocannabinoids interact with CB receptors via varying affinities of agonism and/or antagonism to said receptors.
Agonist:
A drug or substance that binds to a receptor inside a cell or on its surface and causes the same action as the substance that normally binds to the receptor.9 Some phytocannabinoids can have full, partial, or poor agonism when reacting with CB receptors AKA they poorly, partially, or fully bind the CB receptors.
Affinity:
The strength of the attraction between two substances, such as two chemicals, or an antigen and an antibody. Some phytocannabinoids can have high-to-low affinity to want to bind with CB receptors AKA they have varying degrees of ”wanting” to bind to CB receptors.
Antagonist:
A substance that stops the action or effect of another substance. Some phytocannabinoids can inhibit other phytocannabinoids from binding or adjust how much they bind.
Allosteric Modulator
A drug that binds to non-primary site thus affecting other molecule binding at the primary site.
Cannabinoids and their agonism, affinity, and antagonism qualities:
Delta-9-THC:
This isomer of THC is the biological form which, when inhaled or ingested, offers the user the expected euphoria or high associated with cannabis usage. To calculate true THC percentage, THCa (the acidic form of delta-9-THC) is multiplied by .877 and the raw THC percentage is then added onto that, i.e. THCa percentage*.877+THC percentage=true THC percentage.
Delta-9 THC is a partial agonist with high affinity at CB1 receptors.
What does this mean? Due to THC binding with moderate capability and often to CB1 receptors, intaking THC alone or with terpenes inundates the user with the significant cerebral euphoria most often associated with cannabis.
Delta-9 THC is a partial agonist with moderate affinity at CB2 receptors.
What does this mean? Due to THC binding with moderate capability and somewhat often to CB2 receptors, intaking THC alone of with terpenes inundates the user with moderate physical euphoria.
High THC products are best suited for:
Folks seeking the most potent cerebral effects
Those who work in artistic and creative fields
People suffering traumatic brain injuries
Nerve pain relief
Suggested Products:
Almost everything we sell! (90% of what we sell has minimal-no-phytocannabinoid presence that is not THC)
CBD:
CBD is a negative allosteric modulator with no orthosteric binding affinity at CB1.
What does this mean? When you ingest THC and CBD together, CBD dampens the cerebral euphoria that THC provides, causing you to feel less of a ”head high”.
CBD is a partial agonist with low affinity at CB2.
What does this mean? Because CBD partially binds to CB2 receptors, taking CBD and THC together provides a more physical euphoria than THC alone.
High CBD (10:1 and above) products are best suited for:
Folks seeking less intense cerebral euphoria
People who work high stress and/or fast-paced jobs
May be effective as relief from those with epilepsy
Those looking to titrate THC (gradually increase THC in conjunction with CBD to utilize the benefits of THC without experiencing more potent cerebral qualities or too much of a ”head high”)
Suggested Products:
Kiwi Melon Gummies by Revolution
Wild Blueberry Surp by Spring Lake & Revolution
Blood Orange and Strawberry Gummies by Wana & Grassroots
Oromucosal Spray & Canna-Drops Options by Spectra & Revolution
Various RSOs
Near equal CBD:THC (1:4 through 9:1) ratioed products are best suited for:
Folks seeking more potent physically relaxing euphoria that THC often offers
Self care/spa days
Arthritis symptom relief
Athletes and others looking for musculoskeletal pain relief and/or recovery
Suggested Products:
Orange Herijuana Flower, Joints, Disposable Pens, Pods, and Cartridges by Rhythm, PAX, & GTI
2:1 Limonene and 2:1 Myrcene Flower by Revolution
Buddha’s Smile Pods by Airo & Ascend
Day Off Disposable Pens by Good News & Cresco
Cherry Limeade Disposable Pens & Cartridges by Pure & PTS
1:1, 2:1, and 4:1 V-RSO by Spectra & Revolution
All Drop Options by 1906 & Ascend
Harmony & Relief Tablets by Avexia & Verano
Downtime Pastilles & Gummies by Beboe & GTI
Amarena Cherry, Peach Nectarine, and Pink Pomegranate Gummies by The Botanist & In Grown Farms
Every Drink Option by Cann & GTI
Various Harmony Chocolate (Dark or Milk) and Gummy Options (Mandarin, Strawberry Peach, etc.) by Encore & Verano
Tangerine Mints by Encore & Verano
Strawberry Gummies by Incredibles & GTI
Black Cherry Chocolate Bar by Incredibles & GTI
Caramelized Chocolate Marshmallow Bar from Mindy’s Edibles & Cresco
Black Cherry & Honey Sweet Melon Gummies by Mindy’s Edibles & Cresco
2:1 Capsules by Pure & PTS
Black Cherry Lime Gummies by Revolution
Orange Pineapple Guava Surp by Spring Lake & Revolution
Dark or Milk Chocolate Dose Bar Options by Sweet Releaf & PTS
Citrus Lime & Tropical Punch Drinks by Tonic & PTS
Grapefruit & Lemon Lime Fizz Drinks by Tonic & PTS
Strawberry Lemonade & Yuzu Gummies by Wana & Grassroots
Cherry Tincture by Pure & PTS
Oromucosal Spray & Canna-Drops Options by Spectra & Revolution
Bee Eaze Honey by Innocent & In Grown Farms
Kiwi Strawberry & Orange Gummies by Matter & PharmaCann
Orange Sweet Stones by Encore & Verano
Various RSOs
CBN:
CBN is a poor agonist.
What does this mean? Because CBN doesn’t bind well but does bind to CB1 receptors, taking CBN in with THC creates a more cerebral euphoria than taking THC alone.
CBN is a poor agonist with moderate affinity at CB2.
What does this mean? Even though CBN doesn’t bind very well to CB2 receptors, it binds better to CB2 than it does to CB1 receptors which causes the effects of taking CBN in conjunction with THC to be felt in a more physical euphoria or “body high”.
CBN:THC ratioed products are best suited for:
Those looking for a sleep aid
Folks in need of more physical pain relief than found when taking THC alone
Suggested Products:
Cresco Counting Sheep Disposable Pen by Good News & Cresco
Sleep V-RSO Disposable Pen by Spectra & Revolution
Snoozeberry Gummies or Chocolate by Incredibles & GTI
Sweet Dreams Pastilles or Gummies by Beboe & GTI
Kiwi Strawberry Gummies by The Botanist & In Grown Farms
CBN Belgium Chocolatier Chocolates by Encore & Verano
Pomegranate Punch Gummies by & Encore & Verano
Blackberry Mints from Kiva & Cresco
Milk & Cookies Terrabites from Kiva & Cresco
THCV:
THCV is potentially an antagonist at low doses and an agonist at high doses at CB1 receptors.
What does this mean? With low doses, THCV blocks THC from binding to CB1 receptors which is why taking low doses of THCV in conjunction with THC creates less of a cerebral euphoria than felt with THC alone.
At high doses, the opposite effect happens and THCV binds easily to CB1 receptors. Taking high doses of THCV in conjunction with THC creates more of a cerebral euphoria or “head high” than felt with THC alone.
THCV is an antagonist with unknown affinity at CB2 receptors.
What does this mean? Because THCV blocks THC from binding to CB2 receptors, intaking THCV in conjunction with THC creates less physical euphoria or ”body high” than felt with THC alone.
THCV:THC ratioed products are best suited for:
Folks looking to suppress appetite
Those looking for less lethargy with their cannabis experience
Suggested Products:
Lemon Lime Boost Gummies by Incredibles & GTI
CBG:
CBG is a poor agonist with very low affinity at CB1 receptors.
What does this mean? Because CBG doesn’t bind very well or often to CB1 receptors, intaking CBG in conjunction with THC creates a slightly more cerebral euphoria than felt with THC alone.
CBG is a partial agonist at CB2 receptors.
What does this mean? Because CBG only partially binds sometimes to CB receptors, intaking CBG in conjunction with THC creates a physical euphoria than felt with THC alone.
CBG:THC ratioed products are best suited for:
Folks looking for slightly more physical euphoria than presented with THC alone
Athletes and physical laborers
Suggested Products:
Sour Blue Razzberry Gummies by Incredibles & GTI
Green Apple Gummies by The Botanist & In Grown Farms
Ascend Tablets by Avexia & Verano
Find any of the suggested products at our West Loop or Andersonville location.
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Silver RJ. The Endocannabinoid System of Animals. Animals (Basel). 2019 Sep 16;9(9):686. doi: 10.3390/ani9090686. PMID: 31527410; PMCID: PMC6770351.
Kendall, D. and Yudowski, G., 2017. Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Frontiers in Cellular Neuroscience, 10.
Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018 Mar 13;19(3):833. doi: 10.3390/ijms19030833. PMID: 29533978; PMCID: PMC5877694.
Mackie K. Cannabinoid receptors: where they are and what they do. J Neuroendocrinol. 2008 May;20 Suppl 1:10-4. doi: 10.1111/j.1365-2826.2008.01671.x. PMID: 18426493.
Mackie K. Cannabinoid receptors: where they are and what they do. J Neuroendocrinol. 2008 May;20 Suppl 1:10-4. doi: 10.1111/j.1365-2826.2008.01671.x. PMID: 18426493.
Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018 Mar 13;19(3):833. doi: 10.3390/ijms19030833. PMID: 29533978; PMCID: PMC5877694.
Bie B, Wu J, Foss JF, Naguib M. An overview of the cannabinoid type 2 receptor system and its therapeutic potential. Curr Opin Anaesthesiol. 2018 Aug;31(4):407-414. doi: 10.1097/ACO.0000000000000616. PMID: 29794855; PMCID: PMC6035094.
Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018 Mar 13;19(3):833. doi: 10.3390/ijms19030833. PMID: 29533978; PMCID: PMC5877694.
National Cancer Institute. 2022. NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/agonist [Accessed 18 August 2022].
National Cancer Institute. 2022. NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/affinity [Accessed 18 August 2022].
National Cancer Institute. 2022. NCI Dictionary of Cancer Terms. [online] Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/antagonist [Accessed 18 August 2022].
Nussinov R, Tsai CJ. The different ways through which specificity works in orthosteric and allosteric drugs. Curr Pharm Des. 2012;18(9):1311-6. doi: 10.2174/138161212799436377. PMID: 22316155; PMCID: PMC7458136.
Mackie, K., 2008. Cannabinoid Receptors: Where They are and What They do. Journal of Neuroendocrinology, 20(s1), pp.10-14.
Vučković, S., Srebro, D., Vujović, K., Vučetić, Č. and Prostran, M., 2018. Cannabinoids and Pain: New Insights From Old Molecules. Frontiers in Pharmacology, 9.
Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. PMID: 28120232; PMCID: PMC5345356.
Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. PMID: 28120232; PMCID: PMC5345356.
Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. PMID: 28120232; PMCID: PMC5345356.
Raïch, I., Rivas-Santisteban, R., Lillo, A., Lillo, J., Reyes-Resina, I., Nadal, X., Ferreiro-Vera, C., de Medina, V., Majellaro, M., Sotelo, E., Navarro, G. and Franco, R., 2021. Similarities and differences upon binding of naturally occurring Δ9-tetrahydrocannabinol-derivatives to cannabinoid CB1 and CB2 receptors. Pharmacological Research, 174, p.105970.
Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. PMID: 28120232; PMCID: PMC5345356.
Filipiuc, L., Ababei, D., Alexa-Stratulat, T., Pricope, C., Bild, V., Stefanescu, R., Stanciu, G. and Tamba, B., 2021. Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?. Pharmaceutics, 13(11), p.1823.
Navarro G, Varani K, Reyes-Resina I, Sánchez de Medina V, Rivas-Santisteban R, Sánchez-Carnerero Callado C, Vincenzi F, Casano S, Ferreiro-Vera C, Canela EI, Borea PA, Nadal X, Franco R. Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1-CB2 Heteroreceptor Complexes. Front Pharmacol. 2018 Jun 21;9:632. doi: 10.3389/fphar.2018.00632. PMID: 29977202; PMCID: PMC6021502.
Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. PMID: 28120232; PMCID: PMC5345356.
