of interest in making this I have no conflicts of interest in making this presentation. presentation. The research referenced in this talk is largely pre- The research referenced in this talk is largely pre- clinical. clinical. This talk is NOT about marijuana. This talk is NOT about marijuana. Cannabis is a Schedule I Drug on the Federal level and Cannabis is a Schedule I Drug on the Federal level and is illegal for chiropractors to recommend it and for is illegal for chiropractors to recommend it and for physicians to prescribe it. Check your State and Local physicians to prescribe it. Check your State and Local Statutes. Statutes.
refers to interventions aimed Harm reduction refers to interventions aimed at reducing the negative effects of health at reducing the negative effects of health behaviors without necessarily extinguishing behaviors without necessarily extinguishing the problematic health behaviors completely the problematic health behaviors completely or permanently. or permanently. Hawk, M., Coulter, R. W. S., Egan, J. E., Fisk, S., Reuel Friedman, M., Tula, M., & Kinsky, S. (2017). Harm reduction principles for Hawk, M., Coulter, R. W. S., Egan, J. E., Fisk, S., Reuel Friedman, M., Tula, M., & Kinsky, S. (2017). Harm reduction principles for healthcare settings. Harm Reduction Journal, 14, 70. https://doi.org/10.1186/s12954-017-0196-4 healthcare settings. Harm Reduction Journal, 14, 70. https://doi.org/10.1186/s12954-017-0196-4
is furnished by Innate, the spirit, a segment of Universal Intelligence.” Palmer, DD. (1914). The Chiropractor. Press of Beacon Light Printing Company.
with Consciousness Wall, et. al. Wall, et. al. (2019) (2019) describe the reduction of the internodal describe the reduction of the internodal connectivity of both the DMN and the SAL network with the connectivity of both the DMN and the SAL network with the use of use of Δ Δ-9-THC. -9-THC. Wall, M. B., Pope, R., Freeman, T. P., Kowalczyk, O. S., Demetriou, L., Mokrysz, C., Hindocha, C., Lawn, W., Bloomfield, M. A., Freeman, A. Wall, M. B., Pope, R., Freeman, T. P., Kowalczyk, O. S., Demetriou, L., Mokrysz, C., Hindocha, C., Lawn, W., Bloomfield, M. A., Freeman, A. M., Feilding, A., Nutt, D., & Curran, H. V. (2019). Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity. Journal of Psychopharmacology M., Feilding, A., Nutt, D., & Curran, H. V. (2019). Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity. Journal of Psychopharmacology (Oxford, England), 33(7), 822–830. https://doi.org/10.1177/0269881119841568 (Oxford, England), 33(7), 822–830. https://doi.org/10.1177/0269881119841568 – Reductions in functional connectivity were seen in the DMN Reductions in functional connectivity were seen in the DMN and SAL networks for and SAL networks for Cann−CBD. Cann−CBD. – Cann−CBD had its greatest effects on the PCC and was Cann−CBD had its greatest effects on the PCC and was correlated with subjective drug effects such as feeling correlated with subjective drug effects such as feeling ‘stoned’ and ‘high’. ‘stoned’ and ‘high’. – Ego Death: Psychedelic enlightenment, Spiritual awakening, Ego Death: Psychedelic enlightenment, Spiritual awakening, Cosmic consciousness, Unitive experience, Non-duality, and Cosmic consciousness, Unitive experience, Non-duality, and No-self. No-self.
of REBUS. Carhart-Harris, R. L., & Friston, K. J. (2019). REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Pharmacological Reviews, 71(3), 316–344. https://doi.org/10.1124/pr.118.017160
in the River Lethe Purgatorio, Canto 31 : Dante submerged in the River Lethe, illustration from 'The Divine Comedy' by Dante Alighieri, 1885 (digitally colored engraving) Gustave Dore (1832-83) / French Matelda bathes Dante in the Lethe. Lethe is generally associated with the removal of painful memories or worries as opposed to the loss of cherished memories. https://www.encyclopedia.com/literature-and- arts/classical-literature-mythology-and-folklore/folklore-and- mythology/lethe
compound anandamide, often referred to as the body’s own often referred to as the body’s own marijuana, plays a role in erasing memories marijuana, plays a role in erasing memories of a traumatic event. of a traumatic event. News, N. (2020, May 12). Body’s own marijuana helps us forget traumatic memories. Neuroscience News. News, N. (2020, May 12). Body’s own marijuana helps us forget traumatic memories. Neuroscience News. https://neurosciencenews.com/endocannabinoids-ptsd-16361/ https://neurosciencenews.com/endocannabinoids-ptsd-16361/ Erasing Memories Erasing Memories
of the River Eunoe, illustration from 'The Divine Comedy' by Dante Alighieri, 1885 (digitally colored engraving) Dore, Gustave (1832-83) / French The word "eunoe" is one of Dante's many neologisms presumably derived from Greek "eu-," meaning "good" and "noe," meaning "mind." Drink of the River Eun Drink of the River Eunӧ ӧe e Suppression of Inhibition Suppression of Inhibition
Emotional Valence Cannabinoid receptor Cannabinoid receptor (CB1r) (CB1r) stimulation stimulation reduces the emotional charge during reduces the emotional charge during memory reconsolidation via hippocampal memory reconsolidation via hippocampal and amygdala mechanisms. and amygdala mechanisms. Ruehle, S., Rey, A. A., Remmers, F., & Lutz, B. (2012). The endocannabinoid system in anxiety, fear memory and habituation. Journal Ruehle, S., Rey, A. A., Remmers, F., & Lutz, B. (2012). The endocannabinoid system in anxiety, fear memory and habituation. Journal of Psychopharmacology (Oxford, England), 26(1), 23–39. https://doi.org/10.1177/0269881111408958 of Psychopharmacology (Oxford, England), 26(1), 23–39. https://doi.org/10.1177/0269881111408958
Bassir Nia, et. al. Bassir Nia, et. al. (2019) (2019) review the impact of trauma review the impact of trauma on the endocannabinoid system’s ligands and on the endocannabinoid system’s ligands and receptors. receptors. Bassir Nia, A., Bender, R., & Harpaz-Rotem, I. (2019). Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Bassir Nia, A., Bender, R., & Harpaz-Rotem, I. (2019). Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Accumulative Effects of Trauma. Chronic Stress, 3, 2470547019864096. https://doi.org/10.1177/2470547019864096 Review of Developmental and Accumulative Effects of Trauma. Chronic Stress, 3, 2470547019864096. https://doi.org/10.1177/2470547019864096 – Childhood trauma results in a reduction in Childhood trauma results in a reduction in BOTH eCB ligand production and CBr BOTH eCB ligand production and CBr expression. expression. – Adult trauma results in decreased levels of Adult trauma results in decreased levels of eCB ligands and increased expression of eCB ligands and increased expression of CBrs. CBrs.
the River Lethe What if you could drink from the River Lethe and “forget” how to be ill and then drink from and “forget” how to be ill and then drink from the River the River Eun Eunӧ ӧe to change your body’s e to change your body’s charge or valence toward illness? charge or valence toward illness? What If?
of the eCB System The first is to modulate pleasure, energy, The first is to modulate pleasure, energy, and well-being. The second is to slowly and well-being. The second is to slowly nudge the body back to health in the face of nudge the body back to health in the face of injury and disease. injury and disease. Leinow, Leonard & Birnbaum, Julianna. (2017). CBD: A Patient’s Guide to Medicinal Cannabis. North Atlantic Books. Leinow, Leonard & Birnbaum, Julianna. (2017). CBD: A Patient’s Guide to Medicinal Cannabis. North Atlantic Books.
Years Lost The Controlled Substances Act was The Controlled Substances Act was enacted by the 91st United States Congress enacted by the 91st United States Congress and signed into law by President Nixon in and signed into law by President Nixon in 1970 making marijuana a Schedule I 1970 making marijuana a Schedule I substance. substance. ( (Berman, D., & Kreit, A. (2020). Marijuana Law and Policy. Carolina Academic Press., p 145-7). Berman, D., & Kreit, A. (2020). Marijuana Law and Policy. Carolina Academic Press., p 145-7). Schedule I drugs, substances, or chemicals Schedule I drugs, substances, or chemicals are defined as drugs with no currently are defined as drugs with no currently accepted medical use and a high potential accepted medical use and a high potential for abuse. for abuse. (Drug Scheduling. (n.d.). Retrieved October 26, 2023, from https://www.dea.gov/drug-information/drug-scheduling). (Drug Scheduling. (n.d.). Retrieved October 26, 2023, from https://www.dea.gov/drug-information/drug-scheduling).
of eCB system is comprised of cannabinoid receptors, endocannabinoids, cannabinoid receptors, endocannabinoids, and the enzymes that synthesize and and the enzymes that synthesize and degrade them. degrade them. Lu, H.-C., & Mackie, K. (2021). Review of the Endocannabinoid System. Biological Psychiatry. Cognitive Neuroscience and Lu, H.-C., & Mackie, K. (2021). Review of the Endocannabinoid System. Biological Psychiatry. Cognitive Neuroscience and Neuroimaging, 6(6), 607–615. https://doi.org/10.1016/j.bpsc.2020.07.016 Neuroimaging, 6(6), 607–615. https://doi.org/10.1016/j.bpsc.2020.07.016 The eCB System The eCB System
eCBs, pCBs, sCBs bind to the CB1r and eCBs, pCBs, sCBs bind to the CB1r and CB2r which are members of the G-protein CB2r which are members of the G-protein coupled receptor coupled receptor (GPCR) (GPCR) which has an which has an inhibitory effect on cellular function by inhibitory effect on cellular function by blocking the influx of ionic calcium. blocking the influx of ionic calcium. Mackie, K. (2008). Cannabinoid Receptors: Where They are and What They do. Journal of Neuroendocrinology, 20(s1), 10–14. Mackie, K. (2008). Cannabinoid Receptors: Where They are and What They do. Journal of Neuroendocrinology, 20(s1), 10–14. https://doi.org/10.1111/j.1365-2826.2008.01671.x https://doi.org/10.1111/j.1365-2826.2008.01671.x
& c-AMP pCB and eCB inhibit adenylate cyclase. pCB and eCB inhibit adenylate cyclase. Cyclic AMP is a secondary messenger that plays Cyclic AMP is a secondary messenger that plays a role in many cellular processes, including the a role in many cellular processes, including the regulation of gene expression, neurotransmitter regulation of gene expression, neurotransmitter release, and cellular metabolism. release, and cellular metabolism. Bayewitch, M., Rhee, M.-H., Avidor-Reiss, T., Breuer, A., Mechoulam, R., & Vogel, Z. (1996). (—)-Δ9-Tetrahydrocannabinol Bayewitch, M., Rhee, M.-H., Avidor-Reiss, T., Breuer, A., Mechoulam, R., & Vogel, Z. (1996). (—)-Δ9-Tetrahydrocannabinol Antagonizes the Peripheral Cannabinoid Receptor-mediated Inhibition of Adenylyl Cyclase ( ). Journal of Biological Chemistry, ∗ Antagonizes the Peripheral Cannabinoid Receptor-mediated Inhibition of Adenylyl Cyclase ( ). Journal of Biological Chemistry, ∗ 271(17), 9902–9905. https://doi.org/10.1074/jbc.271.17.9902 271(17), 9902–9905. https://doi.org/10.1074/jbc.271.17.9902
in the central CB1rs are found predominantly in the central nervous system where they regulate learning, nervous system where they regulate learning, memory, appetite, stress, movement, nausea, memory, appetite, stress, movement, nausea, vomiting, higher level thinking, pain sensation, vomiting, higher level thinking, pain sensation, touch, temperature, and more. touch, temperature, and more. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books.
in the CB2rs are found predominantly in the immune system. immune system. They protect against age-related They protect against age-related bone loss. bone loss. Activation of CB2rs in the CNS Activation of CB2rs in the CNS reduce anxiety. reduce anxiety. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books.
and synthesized on-demand and act as retrograde inhibitors. act as retrograde inhibitors. Min, R., V. Di Marzo, and H.D. Mansvelder, DAG lipase involvement in depolarization-induced suppression of inhibition: does Min, R., V. Di Marzo, and H.D. Mansvelder, DAG lipase involvement in depolarization-induced suppression of inhibition: does endocannabinoid biosynthesis always meet the demand? Neuroscientist, 2010. 16(6): p. 608-13. endocannabinoid biosynthesis always meet the demand? Neuroscientist, 2010. 16(6): p. 608-13. Alger, B.E. and J. Kim, Supply and demand for endocannabinoids. Trends Neurosci, 2011. 34(6): p. 304-15. Alger, B.E. and J. Kim, Supply and demand for endocannabinoids. Trends Neurosci, 2011. 34(6): p. 304-15. On-Demand and Retrograde On-Demand and Retrograde
are two canonical endocannabinoids, N-arachidonoyl ethanolamine N-arachidonoyl ethanolamine (AEA, or anandamide) (AEA, or anandamide) and 2-arachidonoylglycerol and 2-arachidonoylglycerol (2-AG) (2-AG). . Foster, Denise. (2021). The Human Endocannabinoid System: Physiology. In Cannabis: A Handbook for Nurses. (pp. 44–114). Foster, Denise. (2021). The Human Endocannabinoid System: Physiology. In Cannabis: A Handbook for Nurses. (pp. 44–114). Wolters Kluwer. Wolters Kluwer. Canonical eCBs Canonical eCBs
discovered by Devane and Mechoulam in 1992 and is Devane and Mechoulam in 1992 and is often called the “bliss” molecule. often called the “bliss” molecule. Devane, W.A., et al., Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Devane, W.A., et al., Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 1992. 258(5090): p. 1946-9 Science, 1992. 258(5090): p. 1946-9 AEA Discovery AEA Discovery
synthesized from N-arachidonoyl phosphatidylethanolamine N-arachidonoyl phosphatidylethanolamine (NAPE) (NAPE) by phospholipase D by phospholipase D (NAPE–PLD) (NAPE–PLD) . . Di Marzo, V., et al., Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature, 1994. Di Marzo, V., et al., Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature, 1994. 372(6507): p. 686-91. 372(6507): p. 686-91. AEA Synthesis AEA Synthesis
AEA tonically activates CB1 and CB2 receptors at a significantly lower affinity receptors at a significantly lower affinity than does than does Δ Δ-9-THC -9-THC. . Kim, J. and B.E. Alger, Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses. Kim, J. and B.E. Alger, Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses. Nat Neurosci, 2010. 13(5): p. 592-600. Nat Neurosci, 2010. 13(5): p. 592-600. AEA Receptor Affinity AEA Receptor Affinity
eBCs require Fatty Acid Binding Proteins eBCs require Fatty Acid Binding Proteins (FABPs) (FABPs) for transport into the cell for hydrolysis. for transport into the cell for hydrolysis. Elmes, M. W., Kaczocha, M., Berger, W. T., Leung, K., Ralph, B. P., Wang, L., Sweeney, J. M., Miyauchi, J. T., Tsirka, S. E., Ojima, I., Elmes, M. W., Kaczocha, M., Berger, W. T., Leung, K., Ralph, B. P., Wang, L., Sweeney, J. M., Miyauchi, J. T., Tsirka, S. E., Ojima, I., & Deutsch, D. G. (2015). Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and & Deutsch, D. G. (2015). Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD). The Journal of Biological Chemistry, 290(14), 8711–8721. https://doi.org/10.1074/jbc.M114.618447 Cannabidiol (CBD). The Journal of Biological Chemistry, 290(14), 8711–8721. https://doi.org/10.1074/jbc.M114.618447
cell by After AEA is transported inside the cell by the FABPs, they are hydrolyzed by fatty acid the FABPs, they are hydrolyzed by fatty acid amide hydroxylase amide hydroxylase (FAAH) (FAAH) yielding AA and yielding AA and ethanolamine. ethanolamine. FAAHs are found in both the endoplasmic FAAHs are found in both the endoplasmic reticulum and cytoplasmic lipid droplets. reticulum and cytoplasmic lipid droplets. Kaczocha, M., S.T. Glaser, and D.G. Deutsch, Identification of intracellular carriers for the endocannabinoid anandamide. Proc Natl Kaczocha, M., S.T. Glaser, and D.G. Deutsch, Identification of intracellular carriers for the endocannabinoid anandamide. Proc Natl Acad Sci U S A, 2009. 106(15): p. 6375-80. Acad Sci U S A, 2009. 106(15): p. 6375-80. Degradation of AEA Degradation of AEA
& FAAH Acute stress triggers an increase FAAH- Acute stress triggers an increase FAAH- mediated hydrolysis of AEA especially seen mediated hydrolysis of AEA especially seen in the basolateral amygdala in the basolateral amygdala (BLA) (BLA) thus thus magnifying fear and pain respones. magnifying fear and pain respones. Paulus, M. P., Stein, M. B., Simmons, A. N., Risbrough, V. B., Halter, R., & Chaplan, S. R. (2021). The effects of FAAH inhibition on Paulus, M. P., Stein, M. B., Simmons, A. N., Risbrough, V. B., Halter, R., & Chaplan, S. R. (2021). The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: A randomized clinical trial. Neuropsychopharmacology, 46(5), the neural basis of anxiety-related processing in healthy male subjects: A randomized clinical trial. Neuropsychopharmacology, 46(5), 1011–1019. https://doi.org/10.1038/s41386-020-00936-w 1011–1019. https://doi.org/10.1038/s41386-020-00936-w
FAAH inhibition causes AEA to FAAH inhibition causes AEA to accumulate and activate more accumulate and activate more cannabinoid receptors resulting in cannabinoid receptors resulting in antidepressant, anti-anxiety and antidepressant, anti-anxiety and pain-relieving effects within pain-relieving effects within 1-4 weeks of treatment. 1-4 weeks of treatment. Piomelli, D., et al., Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev, 2006. 12(1): p. 21-38. Piomelli, D., et al., Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev, 2006. 12(1): p. 21-38.
FAAH Inhibition FAAH inhibition alters the emotional charge FAAH inhibition alters the emotional charge of aversive memories acting on the of aversive memories acting on the basolateral amygdala basolateral amygdala (BLA) (BLA) . . Gunduz-Cinar, O., et al., Amygdala FAAH and anandamide: mediating protection and recovery from stress. Gunduz-Cinar, O., et al., Amygdala FAAH and anandamide: mediating protection and recovery from stress. Trends Pharmacol Sci, 2013. 34(11): p. 637-44. Trends Pharmacol Sci, 2013. 34(11): p. 637-44. FAAH inhibition appears to be as effective at FAAH inhibition appears to be as effective at relieving pain and inflammation as THC. relieving pain and inflammation as THC. Schlosburg, J.E., et al., Inhibitors of endocannabinoid-metabolizing enzymes reduce precipitated withdrawal responses in THC- Schlosburg, J.E., et al., Inhibitors of endocannabinoid-metabolizing enzymes reduce precipitated withdrawal responses in THC- dependent mice. AAPS J, 2009. 11(2): p. 342-52. dependent mice. AAPS J, 2009. 11(2): p. 342-52.
NSAIDs can influence the eCB system by NSAIDs can influence the eCB system by inhibiting FAAH or by inhibiting FABP. inhibiting FAAH or by inhibiting FABP. Păunescu, H., Coman, O., Coman, L., Ghiţă, I., Georgescu, S., Drăia, F., & Fulga, I. (2011). Cannabinoid system and Păunescu, H., Coman, O., Coman, L., Ghiţă, I., Georgescu, S., Drăia, F., & Fulga, I. (2011). Cannabinoid system and cyclooxygenases inhibitors. Journal of Medicine and Life, 4(1), 11–20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056416/ cyclooxygenases inhibitors. Journal of Medicine and Life, 4(1), 11–20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056416/
Truffles have the major eCB Truffles have the major eCB metabolic enzymes and AEA. metabolic enzymes and AEA. Pacioni, G., Rapino, C., Zarivi, O., Falconi, A., Leonardi, M., Battista, N., Colafarina, S., Sergi, M., Bonfigli, A., Miranda, M., Barsacchi, Pacioni, G., Rapino, C., Zarivi, O., Falconi, A., Leonardi, M., Battista, N., Colafarina, S., Sergi, M., Bonfigli, A., Miranda, M., Barsacchi, D., & Maccarrone, M. (2015). Truffles contain endocannabinoid metabolic enzymes and anandamide. Phytochemistry, 110, 104–110. D., & Maccarrone, M. (2015). Truffles contain endocannabinoid metabolic enzymes and anandamide. Phytochemistry, 110, 104–110. https://doi.org/10.1016/j.phytochem.2014.11.012 https://doi.org/10.1016/j.phytochem.2014.11.012 What about chocolate? What about chocolate?
synthesized from 2-AG is synthesized from diacylglycerol diacylglycerol (DAG) (DAG) , which includes the , which includes the omega-6 fatty acid arachidonic acid. omega-6 fatty acid arachidonic acid. Diacylglycerol lipase turns DAG into 2-AG. Diacylglycerol lipase turns DAG into 2-AG. Bisogno, T., et al., Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in Bisogno, T., et al., Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol, 2003. 163(3): p. 463-8. the brain. J Cell Biol, 2003. 163(3): p. 463-8.
Cytokine Release 2-AG acting through the CB2r inhibits 2-AG acting through the CB2r inhibits the production of pro-inflammatory cytokines the production of pro-inflammatory cytokines by binding to the CB2 receptor thereby by binding to the CB2 receptor thereby reducing the activity of PPAR. reducing the activity of PPAR. O’Sullivan, S. E. (2016). An update on PPAR activation by cannabinoids. British Journal of Pharmacology, 173(12), 1899–1910. O’Sullivan, S. E. (2016). An update on PPAR activation by cannabinoids. British Journal of Pharmacology, 173(12), 1899–1910. https://doi.org/10.1111/bph.13497 https://doi.org/10.1111/bph.13497
2-AG is broken down by monoacylglycerol lipase lipase (MAGL) (MAGL) at the cell membrane. at the cell membrane. Nomura, D.K., et al., Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation. Nomura, D.K., et al., Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation. Science, 2011. 334(6057): p. 809-13. Science, 2011. 334(6057): p. 809-13. Savinainen, J.R., S.M. Saario, and J.T. Laitinen, The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2- Savinainen, J.R., S.M. Saario, and J.T. Laitinen, The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2- arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol (Oxf), 2012. 204(2): p. 267-76. arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol (Oxf), 2012. 204(2): p. 267-76. 2-AG Breakdown 2-AG Breakdown
Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Molecular Sciences, 19(3), Article 3. https://doi.org/10.3390/ijms19030833
pCBs and terpenes are synthesized pCBs and terpenes are synthesized in the trichomes of the cannabis flowers. in the trichomes of the cannabis flowers. Gülck, T., & Møller, B. L. (2020). Phytocannabinoids: Origins and Biosynthesis. Trends in Plant Science, 25(10), 985–1004. Gülck, T., & Møller, B. L. (2020). Phytocannabinoids: Origins and Biosynthesis. Trends in Plant Science, 25(10), 985–1004. https://doi.org/10.1016/j.tplants.2020.05.005 https://doi.org/10.1016/j.tplants.2020.05.005
pCB, cannabidiol, is known to modulate the activity of is known to modulate the activity of many cellular effectors, including CB1r, many cellular effectors, including CB1r, CB2r, 5HT1Ar, GPR55r, the μ and ‐ CB2r, 5HT1Ar, GPR55r, the μ and ‐ δ opioid receptors, the TRPV1 cation ‐ δ opioid receptors, the TRPV1 cation ‐ channels, PPAR, fatty acid binding protein, channels, PPAR, fatty acid binding protein, and fatty acid amide hydrolase. and fatty acid amide hydrolase. Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the ‐ Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the ‐ cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 4790–4805. https://doi.org/10.1111/bph.13250 cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 4790–4805. https://doi.org/10.1111/bph.13250
to an allosteric site on CB1rs CBD binds to an allosteric site on CB1rs. . CBD reduces the potency of CBD reduces the potency of Δ- Δ-9- 9-THC by THC by altering its binding affinity to the CB1r. altering its binding affinity to the CB1r. Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the ‐ Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the ‐ cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 4790–4805. https://doi.org/10.1111/bph.13250 cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 4790–4805. https://doi.org/10.1111/bph.13250
CBD raises the concentration of AEA CBD raises the concentration of AEA by competitively inhibiting the action of by competitively inhibiting the action of FABPs that shuttle CBD to FAAH. FABPs that shuttle CBD to FAAH. Elmes, M. W., Kaczocha, M., Berger, W. T., Leung, K., Ralph, B. P., Wang, L., Sweeney, J. M., Miyauchi, J. T., Tsirka, S. E., Ojima, I., Elmes, M. W., Kaczocha, M., Berger, W. T., Leung, K., Ralph, B. P., Wang, L., Sweeney, J. M., Miyauchi, J. T., Tsirka, S. E., Ojima, I., & Deutsch, D. G. (2015). Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and & Deutsch, D. G. (2015). Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD). The Journal of Biological Chemistry, 290(14), 8711–8721. https://doi.org/10.1074/jbc.M114.618447 Cannabidiol (CBD). The Journal of Biological Chemistry, 290(14), 8711–8721. https://doi.org/10.1074/jbc.M114.618447
Kaczocha, M., Sun, J., Balius, T. E., Rizzo, R. C., Haj-Dahmane, S., Ojima, I., & Deutsch, D. G. (2012). Targeting Fatty Acid Binding Protein (FABP) Anandamide Transporters – A Novel Strategy for Development of Anti-Inflammatory and Anti-Nociceptive Drugs. PLOS ONE, 7(12), e50968. https://doi.org/10.1371/journal.pone.0050968
Nuclear Receptors Nuclear receptors regulate gene expression Nuclear receptors regulate gene expression in response to hormones, vitamins, and in response to hormones, vitamins, and other small molecules. other small molecules. They bind to DNA and control the They bind to DNA and control the transcription of specific genes. transcription of specific genes. Khorasanizadeh, S., & Rastinejad, F. (2001). Nuclear-receptor interactions on DNA-response elements. Trends in Biochemical Khorasanizadeh, S., & Rastinejad, F. (2001). Nuclear-receptor interactions on DNA-response elements. Trends in Biochemical Sciences, 26(6), 384–390. https://doi.org/10.1016/S0968-0004(01)01800-X Sciences, 26(6), 384–390. https://doi.org/10.1016/S0968-0004(01)01800-X
Receptors Work Ligand binding Ligand binding: The specific ligand that : The specific ligand that activates a nuclear receptor determines the activates a nuclear receptor determines the type of gene that will be regulated. type of gene that will be regulated. DNA binding DNA binding: The receptor binds to specific : The receptor binds to specific sequences of DNA called hormone response sequences of DNA called hormone response elements elements (HREs) (HREs) . The HREs are located near . The HREs are located near the genes that the receptor regulates. the genes that the receptor regulates. Rastinejad, F., Huang, P., Chandra, V., & Khorasanizadeh, S. (2013). Understanding Nuclear Receptor Form and Function Using Rastinejad, F., Huang, P., Chandra, V., & Khorasanizadeh, S. (2013). Understanding Nuclear Receptor Form and Function Using Structural Biology. Journal of Molecular Endocrinology, 51(3), T1–T21. https://doi.org/10.1530/JME-13-0173 Structural Biology. Journal of Molecular Endocrinology, 51(3), T1–T21. https://doi.org/10.1530/JME-13-0173
PPAR PPAR (Peroxisome Proliferator-Activated Receptor) (Peroxisome Proliferator-Activated Receptor) is an is an important target of CBD. Several studies important target of CBD. Several studies have reported that PPAR agonists exhibit have reported that PPAR agonists exhibit neuroprotective effects via regulating gene neuroprotective effects via regulating gene transcription related to neurodegeneration. transcription related to neurodegeneration. Bhunia, S., Kolishetti, N., Arias, A. Y., Vashist, A., & Nair, M. (2022). Cannabidiol for neurodegenerative disorders: A comprehensive Bhunia, S., Kolishetti, N., Arias, A. Y., Vashist, A., & Nair, M. (2022). Cannabidiol for neurodegenerative disorders: A comprehensive review. Frontiers in Pharmacology, 13. https://www.frontiersin.org/articles/10.3389/fphar.2022.989717 review. Frontiers in Pharmacology, 13. https://www.frontiersin.org/articles/10.3389/fphar.2022.989717
& Morales, P. (2021). Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System. International Journal of Molecular Sciences, 22(3), 1001. MDPI AG. Retrieved from http://dx.doi.org/10.3390/ijms22031001 PPAR PPAR
κβ, & Inflammation PPAR reduces inflammation by inhibiting the PPAR reduces inflammation by inhibiting the activation of activation of NF- NF-κβ κβ. . This is beneficial in the treatment of This is beneficial in the treatment of diseases such as rheumatoid arthritis, diseases such as rheumatoid arthritis, asthma, and inflammatory bowel disease. asthma, and inflammatory bowel disease. Remels, A. H. V., Langen, R. C. J., Gosker, H. R., Russell, A. P., Spaapen, F., Voncken, J. W., Schrauwen, P., & Schols, A. M. W. J. Remels, A. H. V., Langen, R. C. J., Gosker, H. R., Russell, A. P., Spaapen, F., Voncken, J. W., Schrauwen, P., & Schols, A. M. W. J. (2009). PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle. American Journal of Physiology-Endocrinology (2009). PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism, 297(1), E174–E183. https://doi.org/10.1152/ajpendo.90632.2008 and Metabolism, 297(1), E174–E183. https://doi.org/10.1152/ajpendo.90632.2008
κβ, & Glucose PPAR can improve insulin sensitivity by PPAR can improve insulin sensitivity by inhibiting the activation of inhibiting the activation of NF- NF-κβ κβ. . This is beneficial in the treatment of This is beneficial in the treatment of Type 2 diabetes. Type 2 diabetes. Remels, A. H. V., Langen, R. C. J., Gosker, H. R., Russell, A. P., Spaapen, F., Voncken, J. W., Schrauwen, P., & Schols, A. M. W. J. Remels, A. H. V., Langen, R. C. J., Gosker, H. R., Russell, A. P., Spaapen, F., Voncken, J. W., Schrauwen, P., & Schols, A. M. W. J. (2009). PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle. American Journal of Physiology-Endocrinology (2009). PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism, 297(1), E174–E183. https://doi.org/10.1152/ajpendo.90632.2008 and Metabolism, 297(1), E174–E183. https://doi.org/10.1152/ajpendo.90632.2008
κβ, & Cancer PPAR can reduce cancer risk by PPAR can reduce cancer risk by inhibiting the activation of inhibiting the activation of NF- NF-κβ κβ. . This is because This is because NF- NF-κβ κβ is involved in is involved in the growth and progression of cancer cells. the growth and progression of cancer cells. Remels, A. H. V., Langen, R. C. J., Gosker, H. R., Russell, A. P., Spaapen, F., Voncken, J. W., Schrauwen, P., & Schols, A. M. W. J. Remels, A. H. V., Langen, R. C. J., Gosker, H. R., Russell, A. P., Spaapen, F., Voncken, J. W., Schrauwen, P., & Schols, A. M. W. J. (2009). PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle. American Journal of Physiology-Endocrinology (2009). PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism, 297(1), E174–E183. https://doi.org/10.1152/ajpendo.90632.2008 and Metabolism, 297(1), E174–E183. https://doi.org/10.1152/ajpendo.90632.2008
CBD at low physiological doses inhibits or CBD at low physiological doses inhibits or desensitizes neuronal TRPV-1 desensitizes neuronal TRPV-1 (Transient Receptor (Transient Receptor Potential Vanilloid) Potential Vanilloid) signaling. signaling. This mechanism underlies nociceptor This mechanism underlies nociceptor desensitization and the therapeutic effect in desensitization and the therapeutic effect in acute and chronic pain. acute and chronic pain. Anand, U., Jones, B., Korchev, Y., Bloom, S. R., Pacchetti, B., Anand, P., & Sodergren, M. H. (2020). CBD Effects on TRPV1 Anand, U., Jones, B., Korchev, Y., Bloom, S. R., Pacchetti, B., Anand, P., & Sodergren, M. H. (2020). CBD Effects on TRPV1 Signaling Pathways in Cultured DRG Neurons. Journal of Pain Research, 13, 2269–2278. https://doi.org/10.2147/JPR.S258433 Signaling Pathways in Cultured DRG Neurons. Journal of Pain Research, 13, 2269–2278. https://doi.org/10.2147/JPR.S258433
Disease states related to CECD are marked Disease states related to CECD are marked by chronic pain, dysfunctional immune by chronic pain, dysfunctional immune systems, fatigue, and mood imbalances. systems, fatigue, and mood imbalances. The endocannabinoid system regulates The endocannabinoid system regulates most of these physiological processes. most of these physiological processes. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books.
Migraine Migraine Fibromyalgia Fibromyalgia Irritable Bowel Syndrome Irritable Bowel Syndrome Russo, E. B. (2008). Clinical endocannabinoid deficiency (CECD): Can this concept explain therapeutic benefits of cannabis in Russo, E. B. (2008). Clinical endocannabinoid deficiency (CECD): Can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinology Letters, 29(2), 192– migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinology Letters, 29(2), 192– 200. 200.
Childhood trauma results in a reduction in BOTH Childhood trauma results in a reduction in BOTH eCB ligand production and CBr expression. eCB ligand production and CBr expression. Adult trauma results in decreased levels of eCB Adult trauma results in decreased levels of eCB ligands and increased expression of CBrs. ligands and increased expression of CBrs. Bassir Nia, A., Bender, R., & Harpaz-Rotem, I. (2019). Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Bassir Nia, A., Bender, R., & Harpaz-Rotem, I. (2019). Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Accumulative Effects of Trauma. Chronic Stress, 3, 2470547019864096. https://doi.org/10.1177/2470547019864096 Accumulative Effects of Trauma. Chronic Stress, 3, 2470547019864096. https://doi.org/10.1177/2470547019864096
the fatty acid amide of palmitic acid PEA is the fatty acid amide of palmitic acid and ethanolamine and is expressed widely and ethanolamine and is expressed widely in plant and animal tissue. in plant and animal tissue. PEA has powerful anti-inflammatory activity. PEA has powerful anti-inflammatory activity. PEA increases AEA concentrations. PEA increases AEA concentrations. PEA is metabolized by FAAH. PEA is metabolized by FAAH. Tsuboi, K., N. Takezaki, and N. Ueda, The N-acylethanolamine-hydrolyzing acid amidase (NAAA). Tsuboi, K., N. Takezaki, and N. Ueda, The N-acylethanolamine-hydrolyzing acid amidase (NAAA). Chem Biodivers, 2007. 4(8): p. 1914-25. Chem Biodivers, 2007. 4(8): p. 1914-25.
of PEA PEA is found in several foods, including egg PEA is found in several foods, including egg yolk, peanut oil, nuts, and soybeans. yolk, peanut oil, nuts, and soybeans. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books. Ross, Michele. (2018). Vitamin Weed: A 4-Step Plan to Prevent and Reverse Endocannabinoid Deficiency. GreenStone Books.
anti-inflammatory, analgesic, PEA has anti-inflammatory, analgesic, anticonvulsant, antimicrobial, antipyretic, anticonvulsant, antimicrobial, antipyretic, antiepileptic, immunomodulatory and antiepileptic, immunomodulatory and neuroprotective activities. neuroprotective activities. Clayton, P., Hill, M., Bogoda, N., Subah, S., & Venkatesh, R. (2021). Palmitoylethanolamide: A Natural Compound for Health Clayton, P., Hill, M., Bogoda, N., Subah, S., & Venkatesh, R. (2021). Palmitoylethanolamide: A Natural Compound for Health Management. International Journal of Molecular Sciences, 22(10), 5305. https://doi.org/10.3390/ijms22105305 Management. International Journal of Molecular Sciences, 22(10), 5305. https://doi.org/10.3390/ijms22105305
PEA does not activate either CB1r or CB2r. PEA does not activate either CB1r or CB2r. PEA inhibits fatty acid amide hydrolase PEA inhibits fatty acid amide hydrolase (FAAH) (FAAH) , , the major enzyme catalyzing AEA the major enzyme catalyzing AEA degradation. degradation. Di Marzo, V., Melck, D., Orlando, P., Bisogno, T., Zagoory, O., Bifulco, M., Vogel, Z., & De Petrocellis, L. (2001). Di Marzo, V., Melck, D., Orlando, P., Bisogno, T., Zagoory, O., Bifulco, M., Vogel, Z., & De Petrocellis, L. (2001). Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cells. Biochemical Journal, 358(Pt 1), 249–255. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222054/ in human breast cancer cells. Biochemical Journal, 358(Pt 1), 249–255. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222054/
thought to be the PPAR. This receptor is a regulator of gene networks which control pain and inflammation, probably by switching off the NF-κβ a key element in the transcription of genes for proinflammatory mediators (cytokine, chemokines, nitric oxide) . Hesselink, J. M. K., & Hekker, T. A. (2012). Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: A case series. Journal of Pain Research, 5, 437–442. https://doi.org/10.2147/JPR.S32143 PEA Main Target PEA Main Target
PEA exerts significant ‘entourage’ effects PEA exerts significant ‘entourage’ effects on 2 AG, by enhancing both its levels and ‐ on 2 AG, by enhancing both its levels and ‐ its actions at TRPV-1 channels. its actions at TRPV-1 channels. This helps to explain how PEA conveys This helps to explain how PEA conveys anti inflammatory and analgesic effects. ‐ anti inflammatory and analgesic effects. ‐ Petrosino, S., Schiano Moriello, A., Cerrato, S., Fusco, M., Puigdemont, A., De Petrocellis, L., & Di Marzo, V. (2016). The anti‐ Petrosino, S., Schiano Moriello, A., Cerrato, S., Fusco, M., Puigdemont, A., De Petrocellis, L., & Di Marzo, V. (2016). The anti‐ inflammatory mediator palmitoylethanolamide enhances the levels of 2 arachidonoyl glycerol and potentiates its actions at TRPV1 ‐ ‐ inflammatory mediator palmitoylethanolamide enhances the levels of 2 arachidonoyl glycerol and potentiates its actions at TRPV1 ‐ ‐ cation channels. British Journal of Pharmacology, 173(7), 1154–1162. https://doi.org/10.1111/bph.13084 cation channels. British Journal of Pharmacology, 173(7), 1154–1162. https://doi.org/10.1111/bph.13084
Mast Cells PEA is an endocannabinoid able to down- PEA is an endocannabinoid able to down- regulate mast cell degranulation by up- regulate mast cell degranulation by up- regulating the CB2r/2-AG axis. regulating the CB2r/2-AG axis. Cerrato, S., Brazis, P., della Valle, M. F., Miolo, A., & Puigdemont, A. (2010). Effects of palmitoylethanolamide on immunologically Cerrato, S., Brazis, P., della Valle, M. F., Miolo, A., & Puigdemont, A. (2010). Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFalpha release from canine skin mast cells. Veterinary Immunology and Immunopathology, 133(1), induced histamine, PGD2 and TNFalpha release from canine skin mast cells. Veterinary Immunology and Immunopathology, 133(1), 9–15. https://doi.org/10.1016/j.vetimm.2009.06.011 9–15. https://doi.org/10.1016/j.vetimm.2009.06.011
of rat PFC decreased RVT pre-treatment of rat PFC decreased lipoperoxidation while increasing PEA, CB1r lipoperoxidation while increasing PEA, CB1r and CB2r densities. and CB2r densities. Carta, G., Poddighe, L., Serra, M. P., Boi, M., Melis, T., Lisai, S., Murru, E., Muredda, L., Collu, M., Banni, S., & Quartu, M. (2018). Carta, G., Poddighe, L., Serra, M. P., Boi, M., Melis, T., Lisai, S., Murru, E., Muredda, L., Collu, M., Banni, S., & Quartu, M. (2018). Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion. International Journal of Molecular Sciences, 19(2), 426. by Bilateral Common Carotid Artery Occlusion and Reperfusion. International Journal of Molecular Sciences, 19(2), 426. https://doi.org/10.3390/ijms19020426 https://doi.org/10.3390/ijms19020426
An entourage effect occurs when several An entourage effect occurs when several compounds such as eCBs, terpenes, and compounds such as eCBs, terpenes, and flavonoids interact within the eCB system flavonoids interact within the eCB system to produce synergistic effects. to produce synergistic effects. Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M. H., Vogel, Z., Bisogno, T., De Petrocellis, L., Di Marzo, V., & Mechoulam, R. Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M. H., Vogel, Z., Bisogno, T., De Petrocellis, L., Di Marzo, V., & Mechoulam, R. (1998). An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. (1998). An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology, 353(1), 23–31. https://doi.org/10.1016/s0014-2999(98)00392-6 European Journal of Pharmacology, 353(1), 23–31. https://doi.org/10.1016/s0014-2999(98)00392-6
terpenes by interlinking chains Plants form terpenes by interlinking chains of isoprenes which are 5 carbon chains. of isoprenes which are 5 carbon chains. Terpenes are pharmacologically active, act Terpenes are pharmacologically active, act as antioxidants, and prenylate to flavonoids. as antioxidants, and prenylate to flavonoids. Prenylation is the covalent attachment of a hydrophobic molecule to a protein or a biomolecule. Prenylation is the covalent attachment of a hydrophobic molecule to a protein or a biomolecule. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. www.bigbookofterps.com. www.bigbookofterps.com.
components are myrcene, β-caryophyllene, limonene, α-pinene, β-pinene, terpinolene, and α-humulene. The general properties of these substances include antidepressant, relaxant, anxiolytic, sedative, antimicrobial, and antioxidants. Gulluni, N., Re, T., Loiacono, I., Lanzo, G., Gori, L., Macchi, C., Epifani, F., Bragazzi, N., & Firenzuoli, F. (2018). Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects. Evidence-Based Complementary and Alternative Medicine : eCAM, 2018, 1709182. https://doi.org/10.1155/2018/1709182
sesquiterpene β-CP is a sesquiterpene (15-C or 3-isoprenes units) (15-C or 3-isoprenes units) widely distributed in essential oils of various widely distributed in essential oils of various plants with biological attributes such as anti- plants with biological attributes such as anti- inflammatory, antibiotic, antioxidant, anti- inflammatory, antibiotic, antioxidant, anti- carcinogenic and local anesthetic activities. carcinogenic and local anesthetic activities. Legault, J., & Pichette, A. (2007). Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene Legault, J., & Pichette, A. (2007). Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel. The Journal of Pharmacy and Pharmacology, 59(12), 1643–1647. https://doi.org/10.1211/jpp.59.12.0005 and paclitaxel. The Journal of Pharmacy and Pharmacology, 59(12), 1643–1647. https://doi.org/10.1211/jpp.59.12.0005
is found in allspice, anise, basil, black β-CP is found in allspice, anise, basil, black pepper, cardamom, chamomile, cinnamon, pepper, cardamom, chamomile, cinnamon, citronella, clove, curry, eucalyptus, ginger, citronella, clove, curry, eucalyptus, ginger, lavender, lemongrass, mango, nutmeg, lavender, lemongrass, mango, nutmeg, oregano, peppermint, rosemary, sage, oregano, peppermint, rosemary, sage, thyme, turmeric, et al. thyme, turmeric, et al. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. www.bigbookofterps.com. www.bigbookofterps.com.
CB2r β-CP has a higher affinity for the CB2 β-CP has a higher affinity for the CB2 receptor than the CB1 receptor, and it is receptor than the CB1 receptor, and it is thought to exert its effects primarily through thought to exert its effects primarily through the CB2 receptor. the CB2 receptor. Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J.-Z., Xie, X.-Q., Altmann, K.-H., Karsak, M., & Zimmer, A. (2008). Beta- Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J.-Z., Xie, X.-Q., Altmann, K.-H., Karsak, M., & Zimmer, A. (2008). Beta- caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences, 105(26), 9099–9104. caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences, 105(26), 9099–9104. https://doi.org/10.1073/pnas.0803601105 https://doi.org/10.1073/pnas.0803601105
tend to have higher Indica strains tend to have higher concentrations of concentrations of β β-CP -CP than sativa strains. than sativa strains. Some strains high in Some strains high in β β-CP: -CP: Bubba Kush, Northern Lights, Bubba Kush, Northern Lights, Hindu Kush, Granddaddy Purple, OG Kush, Sour Diesel, Hindu Kush, Granddaddy Purple, OG Kush, Sour Diesel, Chemdawg, Do Si Dos, Gelato, Sherbet, Cookies and Chemdawg, Do Si Dos, Gelato, Sherbet, Cookies and Cream. Cream. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cannabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cannabis. www.bigbookofterps.com. www.bigbookofterps.com.
Cannabis in the Ancient Greek and Roman World. Lexington Books. “ “We see many references to psychotropic drug usage at the We see many references to psychotropic drug usage at the ancient Greek dramatic festivals and drinking symposiums” ancient Greek dramatic festivals and drinking symposiums” (Sumler, 2018, 67). (Sumler, 2018, 67).
a common ancestor 28 million years ago. Hops and cannabinoids. (2023). In Wikipedia. https://en.wikipedia.org/w/index.php?title=Hops_and_cannabinoids&oldid=1155664703
cannabis are both members of the Hops and cannabis are both members of the same Cannabaceae plant family. same Cannabaceae plant family. They both contain many of the same They both contain many of the same terpenes but sadly, hops do not contain terpenes but sadly, hops do not contain CBD, THC, or any of the psychoactive CBD, THC, or any of the psychoactive cannabinoids of cannabis. cannabinoids of cannabis. DiSorbo, Dan. (2022). The Book of Hops: A Craft Beer Lover’s Guide to Hoppiness. Ten Speed Press. DiSorbo, Dan. (2022). The Book of Hops: A Craft Beer Lover’s Guide to Hoppiness. Ten Speed Press.
The Saint of Suds (Sibyl of the Rhine: 1098-1179; canonized May 10, 2012, by Pope Benedict XVI) (Sibyl of the Rhine: 1098-1179; canonized May 10, 2012, by Pope Benedict XVI) Hoppho: Hoppho: It causes melancholy to It causes melancholy to increase, gives a sad mind, and increase, gives a sad mind, and makes the intestines heavy. makes the intestines heavy.(p. 36) (p. 36). . Hanff: Hanff: It is easy to digest, It is easy to digest, diminishes bad humors, and diminishes bad humors, and fortifies good humors … [if one] fortifies good humors … [if one] has a vacant brain, it easily afflicts has a vacant brain, it easily afflicts the head the head (p.14) (p.14). . Bingen, H., & Throop, P. (1998). Hildegard von Bingen’s Physica: The Complete English Bingen, H., & Throop, P. (1998). Hildegard von Bingen’s Physica: The Complete English Translation of Her Classic Work on Health and Healing. Healing Arts Press. Translation of Her Classic Work on Health and Healing. Healing Arts Press.
a wind-pollinated dioeciuos plant. Hops is a wind-pollinated dioeciuos plant. The mature female inflorescences The mature female inflorescences give it bitterness give it bitterness (alpha acids) (alpha acids) and aroma and aroma (terpenes) (terpenes) . . In folk medicine is has been used in the In folk medicine is has been used in the treatment of insomnia, anxiety, spasms, treatment of insomnia, anxiety, spasms, cough, fever, inflammation, liver, cough, fever, inflammation, liver, gynecological disorders, digestion issues, gynecological disorders, digestion issues, and others. and others. Ovidi, E., Laghezza Masci, V., Taddei, A. R., Torresi, J., Tomassi, W., Iannone, M., Tiezzi, A., Maggi, F., & Garzoli, S. (2022). Hemp Ovidi, E., Laghezza Masci, V., Taddei, A. R., Torresi, J., Tomassi, W., Iannone, M., Tiezzi, A., Maggi, F., & Garzoli, S. (2022). Hemp (Cannabis sativa L., Kompolti cv.) and Hop (Humulus lupulus L., Chinook cv.) Essential Oil and Hydrolate: HS-GC-MS Chemical (Cannabis sativa L., Kompolti cv.) and Hop (Humulus lupulus L., Chinook cv.) Essential Oil and Hydrolate: HS-GC-MS Chemical Investigation and Apoptotic Activity Evaluation. Pharmaceuticals, 15(8), 976. https://doi.org/10.3390/ph15080976 Investigation and Apoptotic Activity Evaluation. Pharmaceuticals, 15(8), 976. https://doi.org/10.3390/ph15080976
⍺ ( -caryophyllene) ⍺ is an isomer of is an isomer of β-caryophyllene that exhibits anti- β-caryophyllene that exhibits anti- inflammatory, anti-cancer, antibacterial, and inflammatory, anti-cancer, antibacterial, and appetite suppressing activity and is found appetite suppressing activity and is found in various spices and hops. in various spices and hops. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. www.bigbookofterps.com. www.bigbookofterps.com.
found in allspice, anise, basil, Humulene is found in allspice, anise, basil, black pepper, cardamom, chamomile, black pepper, cardamom, chamomile, cinnamon, citronella, clove, curry, cinnamon, citronella, clove, curry, eucalyptus, ginger, lavender, lemongrass, eucalyptus, ginger, lavender, lemongrass, mango, nutmeg, oregano, peppermint, mango, nutmeg, oregano, peppermint, rosemary, sage, thyme, turmeric, et al. rosemary, sage, thyme, turmeric, et al. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. www.bigbookofterps.com. www.bigbookofterps.com.
include Biological properties of β-Myrcene include anxiolytic, antioxidant, anti-ageing, anti- anxiolytic, antioxidant, anti-ageing, anti- inflammatory, and analgesic properties. inflammatory, and analgesic properties. There is potential for the formulation and There is potential for the formulation and production of non-alcoholic beers, functional production of non-alcoholic beers, functional foods and drinks, and cannabis extracts foods and drinks, and cannabis extracts (low in (low in Δ- Δ-9-THC 9-THC) ) rich in β-myrcene. rich in β-myrcene. Surendran, S., Qassadi, F., Surendran, G., Lilley, D., & Heinrich, M. (2021). Myrcene—What Are the Potential Health Benefits of This Surendran, S., Qassadi, F., Surendran, G., Lilley, D., & Heinrich, M. (2021). Myrcene—What Are the Potential Health Benefits of This Flavouring and Aroma Agent? Frontiers in Nutrition, 8, 699666. https://doi.org/10.3389/fnut.2021.699666 Flavouring and Aroma Agent? Frontiers in Nutrition, 8, 699666. https://doi.org/10.3389/fnut.2021.699666
be found in apricots, black β-Myrcene can be found in apricots, black currants, black pepper, blood orange, currants, black pepper, blood orange, blueberries, cherry, clove, fennel, ginger, blueberries, cherry, clove, fennel, ginger, guava, kiwi, mango, oregano, parsnip, guava, kiwi, mango, oregano, parsnip, tangerine, thyme, turmeric, et al. tangerine, thyme, turmeric, et al. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. www.bigbookofterps.com. www.bigbookofterps.com.
β-Myrcene is believed to increase the β-Myrcene is believed to increase the maximum saturation level* of the CB1r maximum saturation level* of the CB1r which means the effects of which means the effects of Δ- Δ-9-THC and 9-THC and other endocannabinoids can be potentiated other endocannabinoids can be potentiated. . *positive allosteric modulation *positive allosteric modulation Lupoi, Jason. (2019). The Cannabis Terpene Experience. MACE Media Group. Lupoi, Jason. (2019). The Cannabis Terpene Experience. MACE Media Group.
β-Myrcene may exert analgesic effects β-Myrcene may exert analgesic effects by desensitizing nociceptors via TRPV-1 by desensitizing nociceptors via TRPV-1 interactions. interactions. Jansen, C., Shimoda, L. M. N., Kawakami, J. K., Ang, L., Bacani, A. J., Baker, J. D., Badowski, C., Speck, M., Stokes, A. J., Small- Jansen, C., Shimoda, L. M. N., Kawakami, J. K., Ang, L., Bacani, A. J., Baker, J. D., Badowski, C., Speck, M., Stokes, A. J., Small- Howard, A. L., & Turner, H. (2019). Myrcene and terpene regulation of TRPV1. Channels, 13(1), 344–366. Howard, A. L., & Turner, H. (2019). Myrcene and terpene regulation of TRPV1. Channels, 13(1), 344–366. https://doi.org/10.1080/19336950.2019.1654347 https://doi.org/10.1080/19336950.2019.1654347
a group of plant-derived Flavonoids are a group of plant-derived polyphenolic compounds that are found polyphenolic compounds that are found in a wide variety of foods, including fruits, in a wide variety of foods, including fruits, vegetables, grains, and beverages. vegetables, grains, and beverages. They have antioxidant, pharmacological, They have antioxidant, pharmacological, and gene regulating properties. and gene regulating properties. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. www.bigbookofterps.com. www.bigbookofterps.com.
found in an enormous Kaempferol is found in an enormous varieties of common edible plants, fruits, varieties of common edible plants, fruits, vegetables, herbs, and spices such as nuts, vegetables, herbs, and spices such as nuts, legumes, and crucifery. legumes, and crucifery. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. Hudson, Russ. (2022). The Big Book of Terps: Understanding Terpenes, Flavonoids, and Synergy in Cnnabis. www.bigbookofterps.com. www.bigbookofterps.com.
Kaempferol has been shown to inhibit Kaempferol has been shown to inhibit FAAH in both in vitro and in vivo studies. FAAH in both in vitro and in vivo studies. Thors, L., Belghiti, M., & Fowler, C. J. (2008). Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring Thors, L., Belghiti, M., & Fowler, C. J. (2008). Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids. British Journal of Pharmacology, 155(2), 244–252. https://doi.org/10.1038/bjp.2008.237 flavonoids. British Journal of Pharmacology, 155(2), 244–252. https://doi.org/10.1038/bjp.2008.237
an isoflavone, mainly Biochanin-A is an isoflavone, mainly contained in legumes of the Fabaceae contained in legumes of the Fabaceae family family (soy and red clover) (soy and red clover) , peanuts, but , peanuts, but is the most is the most represented flavonoid in chickpeas. represented flavonoid in chickpeas. Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. https://doi.org/10.3390/biom11060790 https://doi.org/10.3390/biom11060790
Biochanin-A exerts a peripheral Biochanin-A exerts a peripheral antinociceptive effect driven antinociceptive effect driven by FAAH inhibition. by FAAH inhibition. Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. https://doi.org/10.3390/biom11060790 https://doi.org/10.3390/biom11060790
found widely in vegetables Apigenin is found widely in vegetables (parsley, onions, celery) (parsley, onions, celery) , herbs , herbs (chamomile, oregano, thyme, basil) (chamomile, oregano, thyme, basil) , , fruits fruits (oranges) (oranges) and plant-based beverages and plant-based beverages (tea, (tea, beer and wine) beer and wine) . . Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. https://doi.org/10.3390/biom11060790 https://doi.org/10.3390/biom11060790
PPAR, COX, & FAAH Apigenin interacts at micromolar Apigenin interacts at micromolar concentrations with PPAR, inhibits COX2, concentrations with PPAR, inhibits COX2, and is a potent competitive inhibitor of and is a potent competitive inhibitor of FAAH. It can also cross the BBB. FAAH. It can also cross the BBB. Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. https://doi.org/10.3390/biom11060790 https://doi.org/10.3390/biom11060790
2018 Farm Bill and the Code of According to the 2018 Farm Bill and the Code of Federal Regulations Federal Regulations hemp hemp is defined as is defined as The plant species Cannabis sativa L. and any part The plant species Cannabis sativa L. and any part of that plant, including the seeds thereof and all of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing acids, salts, and salts of isomers, whether growing or not, with a total or not, with a total delta-9 tetrahydrocannabinol delta-9 tetrahydrocannabinol concentration of concentration of not more than 0.3 percent not more than 0.3 percent on a on a dry weight basis. dry weight basis.
Moderately intense exercise increases Moderately intense exercise increases CB1r, AEA, and 2-AG and demonstrates CB1r, AEA, and 2-AG and demonstrates significant interactions between opioid and significant interactions between opioid and eCB systems. See the runners’ high. eCB systems. See the runners’ high. Amatriain-Fernández, S., Budde, H., Gronwald, T., Quiroga, C., Carreón, C., Viana-Torre, G., Yamamoto, T., Imperatori, C., Machado, Amatriain-Fernández, S., Budde, H., Gronwald, T., Quiroga, C., Carreón, C., Viana-Torre, G., Yamamoto, T., Imperatori, C., Machado, S., & Murillo-Rodríguez, E. (2021). The Endocannabinoid System as Modulator of Exercise Benefits in Mental Health. Current S., & Murillo-Rodríguez, E. (2021). The Endocannabinoid System as Modulator of Exercise Benefits in Mental Health. Current Neuropharmacology, 19(8), 1304–1322. https://doi.org/10.2174/1570159X19666201218112748 Neuropharmacology, 19(8), 1304–1322. https://doi.org/10.2174/1570159X19666201218112748 Crombie, K. M., Brellenthin, A. G., Hillard, C. J., & Koltyn, K. F. (2018). Endocannabinoid and Opioid System Interactions in Exercise- Crombie, K. M., Brellenthin, A. G., Hillard, C. J., & Koltyn, K. F. (2018). Endocannabinoid and Opioid System Interactions in Exercise- Induced Hypoalgesia. Pain Medicine: The Official Journal of the American Academy of Pain Medicine, 19(1), 118–123. Induced Hypoalgesia. Pain Medicine: The Official Journal of the American Academy of Pain Medicine, 19(1), 118–123. https://doi.org/10.1093/pm/pnx058 https://doi.org/10.1093/pm/pnx058
Fasting appears to increase the Fasting appears to increase the concentration of AEA in the gut which concentration of AEA in the gut which appears to convey an analgesic effect via appears to convey an analgesic effect via the vagal nerve. the vagal nerve. Lee, J.-Y., Lee, G. J., Nakamura, A., Lee, P. R., Kim, Y., Won, C. H., Furue, H., & Oh, S. B. (2020). Involvement of cannabinoid type 1 Lee, J.-Y., Lee, G. J., Nakamura, A., Lee, P. R., Kim, Y., Won, C. H., Furue, H., & Oh, S. B. (2020). Involvement of cannabinoid type 1 receptor in fasting-induced analgesia. Molecular Pain, 16, 1744806920969476. https://doi.org/10.1177/1744806920969476 receptor in fasting-induced analgesia. Molecular Pain, 16, 1744806920969476. https://doi.org/10.1177/1744806920969476
Hydroxybutyric Acid & FAAH β β- -Hydroxybutyric acid Hydroxybutyric acid (3-hydroxybutyrate, or BHB) (3-hydroxybutyrate, or BHB) may may inhibit FAAH in the limbic forebrain and inhibit FAAH in the limbic forebrain and hypothalamus of fasting rats. hypothalamus of fasting rats. Kirkham, T. C., Williams, C. M., Fezza, F., & Marzo, V. D. (2002). Endocannabinoid levels in rat limbic forebrain and hypothalamus in Kirkham, T. C., Williams, C. M., Fezza, F., & Marzo, V. D. (2002). Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: Stimulation of eating by 2-arachidonoyl glycerol. British Journal of Pharmacology, 136(4), relation to fasting, feeding and satiation: Stimulation of eating by 2-arachidonoyl glycerol. British Journal of Pharmacology, 136(4), 550–557. https://doi.org/10.1038/sj.bjp.0704767 550–557. https://doi.org/10.1038/sj.bjp.0704767
drinking Voluntarily stopping eating and drinking (VSED) (VSED) is a “an action of a competent, capacitated is a “an action of a competent, capacitated person, who voluntarily and deliberately person, who voluntarily and deliberately chooses to stop eating and drinking with the chooses to stop eating and drinking with the primary intention to hasten death because primary intention to hasten death because unacceptable suffering persists.” unacceptable suffering persists.” Lowers, J., Hughes, S., & Preston, N. J. (2021). Overview of voluntarily stopping eating and drinking to hasten death. Annals of Lowers, J., Hughes, S., & Preston, N. J. (2021). Overview of voluntarily stopping eating and drinking to hasten death. Annals of Palliative Medicine, 10(3), 3611–3616. https://doi.org/10.21037/apm-19-525 Palliative Medicine, 10(3), 3611–3616. https://doi.org/10.21037/apm-19-525
without the Handcuffs Cannabis benefits without the Handcuffs https://www.freepik.com/premium-photo/cannabis-leaves-marijuana-weapons-handcuffs-dark_9727606.htm
The high intake of different types of fruit, The high intake of different types of fruit, seasonal green leafy vegetables, extra-virgin olive seasonal green leafy vegetables, extra-virgin olive oil, fresh blue fish, whole grains, legumes, oil, fresh blue fish, whole grains, legumes, nuts, spices and a low intake of alcohol nuts, spices and a low intake of alcohol such as red wine, with small quantities of red such as red wine, with small quantities of red meat, eggs and dairy products, defines the meat, eggs and dairy products, defines the Mediterranean dietary pattern. Mediterranean dietary pattern. Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. https://doi.org/10.3390/biom11060790 https://doi.org/10.3390/biom11060790
Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. https://doi.org/10.3390/biom11060790
consumption of ω-6 rich foods is A chronic consumption of ω-6 rich foods is associated with an increase in eCB levels associated with an increase in eCB levels with desensitization and downregulation of CBrs. with desensitization and downregulation of CBrs. Dietary supplementation of ω-3 PUFAs enhances Dietary supplementation of ω-3 PUFAs enhances plasma and tissue concentrations of EPA and plasma and tissue concentrations of EPA and DHA, balancing AEA and 2-AG amounts. DHA, balancing AEA and 2-AG amounts. Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Armeli, F., Bonucci, A., Maggi, E., Pinto, A., & Businaro, R. (2021). Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. Neglected Role of Nutrition in the Modulation of the Endocannabinoid System. Biomolecules, 11(6), 790. https://doi.org/10.3390/biom11060790 https://doi.org/10.3390/biom11060790
Western diets the ratio of Western diets the ratio of ω-6:ω-3 is 15/1-16.7/1 ω-6:ω-3 is 15/1-16.7/1 A ratio of 2.5/1 reduced rectal cell proliferation in colorectal cancer. A ratio of 2.5/1 reduced rectal cell proliferation in colorectal cancer. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis. Simopoulos, A. P. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy = Simopoulos, A. P. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 56(8), 365–379. https://doi.org/10.1016/s0753-3322(02)00253-6 Biomedecine & Pharmacotherapie, 56(8), 365–379. https://doi.org/10.1016/s0753-3322(02)00253-6
Singing increased plasma levels of AEA Singing increased plasma levels of AEA by 42% by 42% (P < 0.05) (P < 0.05) and PEA by 53% and PEA by 53% (P < 0.01) (P < 0.01) and improved positive mood and improved positive mood and emotions and emotions (P < 0.01) (P < 0.01) . . Stone, N. L., Millar, S. A., Herrod, P. J. J., Barrett, D. A., Ortori, C. A., Mellon, V. A., & O’Sullivan, S. E. (2018). An Analysis of Stone, N. L., Millar, S. A., Herrod, P. J. J., Barrett, D. A., Ortori, C. A., Mellon, V. A., & O’Sullivan, S. E. (2018). An Analysis of Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers. Frontiers in Behavioral Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers. Frontiers in Behavioral Neuroscience, 12, 269. https://doi.org/10.3389/fnbeh.2018.00269 Neuroscience, 12, 269. https://doi.org/10.3389/fnbeh.2018.00269
AEA and 2-AG increased after AEA and 2-AG increased after meditation by > 70% meditation by > 70% (P < 0.001) (P < 0.001) . . Bhava Spandana Program (BSP), an experiential program leading to deep states of meditativeness in just a short period of time. Bhava Spandana Program (BSP), an experiential program leading to deep states of meditativeness in just a short period of time. In Sanskrit, “Bhava” means “sensation” and “Spandana” can be loosely translated as “resonance.” In Sanskrit, “Bhava” means “sensation” and “Spandana” can be loosely translated as “resonance.” Essentially, it means “resonance with life.” Essentially, it means “resonance with life.” Sadhasivam, S., Alankar, S., Maturi, R., Vishnubhotla, R. V., Mudigonda, M., Pawale, D., Narayanan, S., Hariri, S., Ram, C., Chang, Sadhasivam, S., Alankar, S., Maturi, R., Vishnubhotla, R. V., Mudigonda, M., Pawale, D., Narayanan, S., Hariri, S., Ram, C., Chang, T., Renschler, J., Eckert, G., & Subramaniam, B. (2020). Inner Engineering Practices and Advanced 4-day Isha Yoga Retreat Are T., Renschler, J., Eckert, G., & Subramaniam, B. (2020). Inner Engineering Practices and Advanced 4-day Isha Yoga Retreat Are Associated with Cannabimimetic Effects with Increased Endocannabinoids and Short-Term and Sustained Improvement in Mental Associated with Cannabimimetic Effects with Increased Endocannabinoids and Short-Term and Sustained Improvement in Mental Health: A Prospective Observational Study of Meditators. Evidence-Based Complementary and Alternative Medicine : ECAM, 2020, Health: A Prospective Observational Study of Meditators. Evidence-Based Complementary and Alternative Medicine : ECAM, 2020, 8438272. https://doi.org/10.1155/2020/8438272 8438272. https://doi.org/10.1155/2020/8438272
& eCB Tai Chi and eCB in Women Tai Chi and eCB in Women (TC-eCB) (TC-eCB) ClinicalTrials.gov ID ClinicalTrials.gov ID NCT03823157 NCT03823157 Texas Tech University Health Texas Tech University Health Sciences Center Sciences Center Start Date: August 1, 2019 Start Date: August 1, 2019 End Date: December 31, 2023 End Date: December 31, 2023 Study Record | Beta ClinicalTrials.gov. (n.d.). Retrieved July 2, 2023, from Study Record | Beta ClinicalTrials.gov. (n.d.). Retrieved July 2, 2023, from https://clinicaltrials.gov/study/NCT03823157?tab=table https://clinicaltrials.gov/study/NCT03823157?tab=table
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