A short series on CBD for post-operative pain relief begins…. Does CBD provide pain relief in the immediate post-operative period for patients who have undergone an arthroscopic rotator cuff repair?
Yes, according to the results of a double-blinded randomized controlled trial involving 99 patients. Patients who had undergone an arthroscopic rotator cuff repair and had received CBD post-operatively experienced significantly less pain on post-operative day 1 compared to the control group that did not receive CBD. However, the difference in pain scores between the CBD group and the control group was no longer present on post-operative day 2. Of note, on both post-operative days 1 and 2, patient satisfaction with pain control was significantly higher in the CBD group than in the control group. In this study, the CBD was administered via an oral, buccally absorbed (absorbed through the cheek) tablet containing 25 mg of CBD 3x/day if <80 kg, or 50 mg of CBD 3 times a day if >80 kg, post-operatively, while the control group received an identical placebo. On days 7 and 14, there were no statistically significant differences in VAS pain scores, or patient satisfaction with pain control between the CBD and control groups. (Note: the investigational CBD tablet used was ORAVEXX manufactured by Orcosa, Inc.) More on this study in future “The Answer of the Day” questions and answers.
Alaia MJ, Hurley ET, Vasavada K, et al. Buccally Absorbed Cannabidiol Shows Significantly Superior Pain Control and Improved Satisfaction Immediately After Arthroscopic Rotator Cuff Repair: A Placebo-Controlled, Double-Blinded, Randomized Trial. The American Journal of Sports Medicine. July 2022. doi:10.1177/03635465221109573
The delta-8-THC series continues… Have any US states banned delta-8-THC?
Yes…14 US states have banned either delta-8-THC or ALL federally-unregulated forms of THC. (Delta-9-THC and delta-8-THC are not the only forms of THC; for example, delta-10-THC also exists.) Of note, some of the recreational legal US states, such as Colorado and New York have banned delta-8-THC.
Smith, D. G. (2022, July 1). How Delta-8 THC Works, and Why Experts Are Worried About It. New York Times.
The delta-8-THC series continues… Are high concentrations of delta-8-THC produced in the hemp plant? In the marijuana plant?
Actually, only trace amounts of delta-8-THC are detectable in hemp plants and in marijuana plants, but delta-8-THC can be produced from the cannabinoid cannabidiol (aka CBD).
Smith, D. G. (2022, July 1). How Delta-8 THC Works, and Why Experts Are Worried About It. New York Times.
The delta-8-THC series continues… Why did delta-8-THC products become more accessible in 2018 in the US?
“Delta-8’s rise started with the passing of the 2018 Farm Bill, which made hemp legal. Hemp and marijuana are both types of cannabis plants, but marijuana produces delta-9-THC and hemp doesn’t…The Farm Bill stated that hemp could be grown legally as long as it contained less than 0.3 percent THC. But,…the authors of the bill made an oversight: They defined THC specifically as delta-9-THC, which is still illegal federally. With that definition, a market for delta-8 was born.”
Smith, D. G. (2022, July 1). How Delta-8 THC Works, and Why Experts Are Worried About It. New York Times.
The delta-8-THC series continues… How do the effects of delta-8-THC compare to those of delta-9-THC?
According to the results of an online survey of delta-8-THC consumers ( N= 521 participants), “most delta-8-THC users experienced a lot or a great deal of relaxation (71%); euphoria (68%) and pain relief (55%); a moderate amount or a lot of cognitive distortions such as difficulty concentrating (81%), difficulties with short-term memory (80%), and alerted sense of time (74%); and did not experience anxiety (74%) or paranoia (83%). Participants generally compared delta-8-THC favorably with both delta-9-THC and pharmaceutical drugs, with most participants reporting substitution for delta-9-THC (57%) and pharmaceutical drugs (59%). Participant concerns regarding delta-8-THC were generally focused on continued legal access.”
Jessica S Kruger 1 , Daniel J Kruger. Delta-9-THC’s nicer younger sibling? J Cannabis Res. 2022 Jan 4;4(1):4. doi: 10.1186/s42238-021-00115-8.
The next several “The Answer of the Day” questions and answers will review the literature on Δ8 -THC… Are the pharmacokinetics and the pharmacodynamics of Δ8 -THC and Δ9 -THC similar?
According to a recent review of delta-8-tetrahydrocannabinol (Δ-8-THC) pharmacology, “overall, the pharmacokinetics and pharmacodynamics of Δ-8 -THC and Δ9 -THC are very similar. Δ8 -THC is a partial agonist of the cannabinoid CB1 receptor and has cannabimimetic activity in both animals and humans. The reduced potency of Δ-8 -THC in clinical studies compared with Δ-9 -THC can be explained by weaker cannabinoid CB1 receptor affinity, although there are other plausible mechanisms that may contribute.”
Michael Tagen 1, Linda E Klumpers. Review of delta-8-tetrahydrocannabinol (Δ 8 -THC): Comparative pharmacology with Δ 9 -THC. Review Br J Pharmacol. 2022 Aug;179(15):3915-3933. doi: 10.1111/bph.15865. Epub 2022 Jun 1.
Yes. Cannabidiol inhibits some liver enzymes (specifically CYP3A4 and CYP2C19), both of which are involved in the metabolism of methadone. As a result, the co-administration of CBD and methadone may lead to increased sedation.
Some patients apply CBD topically. Does CBD easily penetrate the skin?
Due to CBD’s large size and hydrophobic properties, CBD does not penetrate the skin very efficiently, however, permeation-enhancing gels have been developed. Currently, CBD-containing gels are being evaluated for the treatment of several pediatric disorders, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies.
Does pretreatment with CBD prevent the transient psychotic symptoms induced by THC?
According to a study in humans, pretreatment with CBD does diminish THC’s psychotic effects. This particular study involved 6 healthy volunteers who were given THC intravenously on two separate occasions – once with a placebo pretreatment and once with a CBD pretreatment.
Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol 2012 Dec; 2(6):241-254. doi:10.1177/2045125312457586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736954/
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Author Bio
The COVID epidemic has accelerated research of the immune system’s integrated response to viral diseases. This 30-minute video sponsored by the American Osteopathic Association discusses cannabinoids’ impact on optimal immune function. It is presented by physician author, Jeffrey S. Block, MD – founder and principal partner of an independent professional consultancy providing client organizations with advanced scientific guidance. Dr. Block’s industry-wide expertise provides insight by translating the evolving science’s objective evidence-based data into clinical applications.
About the Author
Jeffrey Sherwood Block, M.D.. is a Board-certified physician anesthesiologist and adjunct Professor at the University of Miami Miller School of Medicine. Additionally, he is a highly awarded horticulturist and certified Master Gardener educator with the University of Florida’s UF/IFAS Extension Program. Dr. Block’s textbook chapter “Endocannabinoid Receptors and Medical Cannabis” (Advanced Therapeutics in Pain Medicine – CRC Press 2020) is a sentinel work on integrated pain management. Block served as the Florida Medical Association’s “Designated Expert on Botanical Medicines” authoring mandated physician education; and in 2014 was appointed by Florida’s Surgeon General to determine the rules for Florida’s first cannabis law. His consultancy’s demonstrated insight and responsible leadership are valued by both allied professionals and new industries seeking knowledge of future uses for Cannabinoid medicines.
Cannabinoids and Adaptive Immuno-Modulation References
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Block, Jeffrey S., 2019. Endogenous Cannabinoid Receptors and Medical Cannabis. (pre-publication chapter) Advanced Therapeutics in Pain Medicine, January 2021. CRC Press.
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References
Perioperative Considerations for the Patients Utilizing Cannabinoid-based Medicines and Products
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References
What is the endocannabinoid system?
Atakan, Z. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic advances in psychopharmacology 2012; 2(6): 241-54
Battista, Natalia; Meccariello, Rosaria; Cobellis, Gilda; Fasano, Silvia; Di Tommaso, Monia; Pirazzi, Valentina; Konje, Justin C; Pierantoni, Riccardo;Maccarrone, Mauro The role of endocannabinoids in gonadal function and fertility along the evolutionary axis. Molecular and Cellular Endocrin. Vol 355, issue 1, May 2012;1-14
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What are the components of the endocannabinoid system?
Atakan, Z. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic advances in psychopharmacology 2012; 2(6): 241-54.
Di Marzo V and De Petrocellis L. Endocannabinoids as regulators of transient receptor potential (TRP) channels: A further opportunity to develop new endocannabinoid-based therapeutic drugs. Curr Med Chem, 2010; 17(14): 1430-49.
Mackie K, Stella N. Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J. 2006;8(2):E298-306.
What are the two most well studied endocannabinoids?
Di Marzo V and De Petrocellis L. Endocannabinoids as regulators of transient receptor potential (TRP) channels: A further opportunity to develop new endocannabinoid-based therapeutic drugs. Curr Med Chem, 2010; 17(14): 1430-49.
Freund TF, Katona I, and Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev, 2003; 83(3): 1017-66.
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What are the receptors of the endocannabinoid system?
Atakan, Z. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic advances in psychopharmacology 2012; 2(6): 241-54.
Di Marzo V and De Petrocellis L. Endocannabinoids as regulators of transient receptor potential (TRP) channels: A further opportunity to develop new endocannabinoid-based therapeutic drugs. Curr Med Chem, 2010; 17(14): 1430-49.
Describe cannabinoid receptor -1.
Aggarwal SK. Cannabinergic pain medicine: A concise clinical primer and survey of randomized-controlled trial results. Clin J Pain 2012 02/23;29(1536-5409; 0749-8047; 2):162-71.
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Burns HD, Van Laere K, Sanabria-Bohorquez S, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci USA. 2007;104:9800–9805.
Freund TF, Katona I, and Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev, 2003; 83(3): 1017-66.
Howlett AC, Blume LC, Dalton GD. CB(1) cannabinoid receptors and their associated proteins. Curr Med Chem. 2010;17(14):1382-93.
Ibrahim BM, Abdel-Rahman AA. Cannabinoid receptor 1 signaling in cardiovascular regulating nuclei in the brainstem: A review. J Adv Res. 2013;5(2):137-45.
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Serrano A, Parsons LH. Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol Ther. 2011;132(3):215-41.
Describe cannabinoid receptor -2.
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Respiratory depression is associated with the overdose of opioids or benzodiazepines. Is respiratory depression associated with the overdose of cannabinoids?
Herkenham M, Lynn AB, Little MD, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA. 1990; 87:1932–1936.
What are phytocannabinoids?
Atakan Z. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic advances in psychopharmacology 2012; 2(6): 241-54
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The terms cannabis, marijuana and hemp are often used interchangeably; however, the terms actually have different meanings. What is cannabis? What is marijuana? What is hemp? Is the hemp plant a cannabis plant?
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What are terpenes (terpenoids)?
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Briefly describe the health effects of delta-9-tetrahydrocannabinol.
ElSohly, M. A. and W. Gul. 2014. Handbook of cannabis (Chapter 2). Oxford, UK: Oxford University Press: P.20.
In 2017, the National Academies of Sciences, Engineering and Medicine(NASEM) published the Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Did the results of the research indicate that cannabis-based products are effective?
National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625.