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Cannabis & Pain
What to Know
Last Updated: 11.22.22

Key Benefits
Managing pain is still a significant challenge for the medical community and many patients can end-up cycling through multiple treatments over years of trial and error.

Fortunately, there’s growing evidence that guided cannabis can offer effective control for chronic pain associated with musculoskeletal conditions1, cancer, and fibromyalgia.2-4 This is thanks to the analgesic and anti-inflammatory compounds in cannabis, which play a key part in reducing inflammation and recurrent pain.5

Newer areas of promise include the management of neuropathic/nerve and migraine pains. 11,12 While only a limited number of migraine studies have been conducted focusing on full-spectrum cannabis as a unique source of relief, most have focused on either a combination of CBD and THC rather or CBD by itself.

Anecdotally, cannabis has been reported to be effective in the treatment of pain caused by a wide range of other physical and psychological maladies, from fleeting muscle and bone pains to chronic nerve and degenerative changes associated with years of progressive disease. Both young and older consumers report meaningful improvement from cannabinoid therapies. Psychological pain, both distinct from and attributable to physical pain, also regularly meets relief with cannabis-based therapies.

Importantly, cannabis has been shown to effectively temper and even replace many prescription pain medications, such as opioids and sedatives. In fact, a growing number of studies report that cannabis has abetter side effect profile compared to narcotics and a lower risk of dangerous addiction.6,7 The clinical evidence confirms these preliminary findings; thousands of regular cannabis consumers find that cannabis therapies help to prevent the need for more addictive pharmaceuticals.

Cannabis has also shown potential as a pain reliever when used instead of, or together with, anti-inflammatory drugs (e.g. Advil, Motrin, etc.) as these medications all amplify the body’s production of anti-inflammatory prostaglandins, which can be associated with risk to sensitive organs such as the kidneys and digestive tract, particularly when taken consistently over long periods.

Key Risks
First, it’s important to know that cannabis products contain compounds such as THC and CBD which may interact with prescribed medications. The result can be potentially dangerous impact, and increased or decreased efficacy of those prescription medications, as well as unpleasant side effects.  

These medications include antibiotics such asErythromycin, cardiac medications such as Diltiazem and Verapamil, seizure medications such as Clobazam, antiviral medications such as Ritonavir, and life-saving blood-thinning medications such as Warfarin. Potential medication interactions are just one reason cannabis care should always be provided by an expert cannabis clinician.

Other possible side effects of cannabis can include fatigue, diarrhea, changes in appetite, and changes in weight.8 For some medical patients, these symptoms can be alarming and confusing, as they can be often in association with both chronic conditions and as concerning side effects of some acute illnesses.

While relatively benign relative to other pharmaceuticals and over-the-counter medications, the presence of cannabis medications in the bloodstream can have other  measurable impacts. Cannabis can cause reversible liver enzyme increases, both alone and in combination with pharmaceuticals. When consumed in large amounts, cannabis can impact cognitive function in the short-run, including memory and processing capabilities. For those who consume cannabis by inhalation, a European Academy report found that cannabis use may lead to more frequent bronchitis if smoked on a regular basis.

Another common impact and potential concern is cannabis can increase the heart rate and either raise or lower blood pressure. These effects may impact frail, older adults with balance issues, who may have an increased risk of dizziness and falling when using cannabis.18

Some research has also shown that long-term cannabis use may affect the gray matter in the brain. Teenagers in particular should only use cannabis in specific clinical situations due to its potential negative long-term neurological effects.22

The persistent and sustained excessive use of cannabis can also have longer-term effects. Many people consuming cannabis daily and in large volumes report that they feel slower, think less clearly, and can recall information less effectively than when they consumed less or none at all.

And of course, anyone using THC/intoxicating cannabis products should refrain from driving, operating heavy machinery, or any other activities in which intoxication might pose a health or safety risk to themselves or others.

Who Should Avoid Using Cannabis for Pain?
Adolescents, individuals with a history of psychotic symptoms, and pregnant women should only consider cannabis care in consultation with a licensed cannabis clinician.

How Cannabis Works to Relieve Pain
Cannabis helps to suppress pain on multiple levels of pain reception, transportation, and processing. Both CBD and THC affect CB1 and CB2 receptors directly or indirectly. CB1 receptors are found in the brain, while CB2 receptors are found in the peripheral nervous system. THC is known to work on the CB1 receptors, with the potential for euphoric effects, whereas CBD is known to work on CB2 receptors, which is not associated with euphoric effects.

First, THC and CBD can regulate pain thresholds at the site of pain origin, to help manage the strength of pain signals propagated by the receptors responsible for detecting pain. In addition, cannabinoids function as anti-inflammatories, inhibiting pain messenger production. Moreover, cannabis can change how pain signals are transported to and received by the brain, at so-called mu-opioid receptors, which is one reason cannabis can be used to replace opioids.

In addition to its effects on nerves and signal transmission, cannabis also modulates other aspects of the endocannabinoid system, including regulating stress levels, encoding long-term memory, and promoting physical and emotional homeostasis.

Other, more minor cannabinoids may also have pain-killing properties, with a similar  contribution to relief as THC and CBD provide.If the body isn't making enough cannabinoids or if the innate cannabinoid receptors (CB1 and CB2) aren't functioning optimally, pain signals may not be adequately inhibited, and pain and suffering will thrive.

About the Endocannabinoid System
What is the endocannabinoid system? It’s complex—and rarely taught in medical school. But it can be helpful to think of the endocannabinoid system as one of the body’s master regulators.

Briefly stated, it’s a neuroregulatory system that keeps physiologic functions in balance, or homeostasis. It plays a crucial role in inflammation, immune response, pain detection, the sleep-wake cycle, mood, memory, appetite regulation, reproduction, and fertility. It consists of three major components: naturally produced chemicals (self-made endocannabinoids acting as transmitters), the receptors those endocannabinoids bind to (located on neurons, immune cells, etc.), and the enzymes which synthesize and degrade these components.  

The human body uses two naturally derived signaling molecules, called endocannabinoids: anandamide (aka the blissmolecule) and 2-arachidonoylglycerol. Endocannabinoids are structurally similar to, but distinct from, the cannabinoids found in cannabis plants, though they act on the same receptors.

Cannabinoids derived from plants are usually referred to as phytocannabinoids. These plant-based cannabinoids consist of awide variety of active cannabinoid molecules, with nearly 150 discovered to date. The most popular molecules are tetrahydrocannabinol (THC), tetrahydrocannabinol acid (THCA), cannabidiol (CBD), cannabigerol (CBG), orcannabinol (CBN).

In addition to these 150 cannabinoids, the cannabis plant produces organic compounds called terpenes. These unsaturated hydrocarbons may not activate the endocannabinoid receptors directly, but they modulate and fine-tune the functions of the activated receptors. This effect (of interaction with the receptors and molecules is known as the "entourage effect."

The second component of the endocannabinoid system is the cannabinoid receptor. The biological effects of cannabinoids are controlled by dozens of known cannabinoid receptors, including the most popular, simply named cannabinoid receptor 1 and 2. Cannabinoid receptor 1 is primarily located in the brain, while cannabinoid receptor 2 is present exclusively in immune cells throughout the body. If an endocannabinoid binds toa cannabinoid receptor 1 in the brain, it may help to relieve pain. In contrast, an endocannabinoid that attaches to the cannabinoid receptor 1 in the immune system might help relieve symptoms of inflammation; it can tone down pro-inflammatory markers like cytokines and interleukin. 24

The third component of the endocannabinoid system are the enzymes, which synthesize and break down endocannabinoids. While many enzymes keep the endocannabinoid system balanced, the ones of therapeutic interest are the fatty acid amide hydrolase (FAAH) and the monoacylglycerollipase (MAGL). The body's endocannabinoid response can be improved for therapeutic purposes by modulating these enzymes.25 As a result, the endocannabinoid system keeps our body balanced, and cannabis can help support its natural function.

How Cannabis Care Should Work
As the evidence grows, it’s increasingly clear: An ongoing partnership with a clinician is essential in order to use cannabis safely and optimally in the treatment of anxiety.

An eo clinician or other expert cannabis clinician with a thorough understanding of your goals, medical record, current medications, and cannabis use history should be involved in formulating initial and ongoing product recommendations, doses, and times of use.

Questions?
Schedule a free consult with an eo team member today. Or email us at members@eo.care.

The content on this page is for informational purposes. Do not attempt to self-diagnose or prescribe treatment based on the information provided. Always consult a physician before deciding on the treatment of a medical condition.

Sources

Key Benefits
Managing pain is a significant challenge for the medical community. In the US, more people are affected by pain than cancer, heart disease, and diabetes, combined and many patients can end-up cycling through multiple treatments over years of trial and error. Aside from the physical discomfort, pain can also cause secondary symptoms like anxiety and depression.

It's not easy to treat such a complex condition because pain is generally used as a catch-all term for many different physiological problems. Fortunately, there’s growing evidence that guided cannabis care can offer effective control for pain associated symptoms such as: chronic pain, pain from musculoskeletal conditions [1], cancer pain, and fibromyalgia.[2-4]

Cannabis can be effective against those various types of pain due to its analgesic and anti-inflammatory compounds, which can reduce pain sensations directly or indirectly by interaction with various receptors throughout the body.[5]

Newer areas of promise include the management of neuropathic/nerve and migraine pains.[6, 7] Cannabis effectively reduces pain and sensitivity but doesn’t target vessels in the head as traditional migraine medication does. Instead, cannabinoids interact with nerves and receptors in the brain to reduce migraine symptoms. Additionally, cannabis was successful in relieving neuropathic pain from a variety of causes (e.g. diabetes, chemotherapy, or post-traumatic stress). A recent meta-analysis provided additional evidence of cannabis's effectiveness in relieving neuropathic pain.[8]

Moreover, patients with cancer pain whose symptoms could not be adequately relieved by traditional painkillers seem to respond well to supplemental cannabis treatment.[9]

Anecdotally, cannabis has been reported to be effective in the treatment of pain caused by a wide range of other physical and psychological maladies, from fleeting muscle and bone pains to chronic nerve and degenerative changes associated with years of progressive disease. Both young and older patients report meaningful improvement from cannabinoid therapies. Psychological pain, both distinct from and attributable to physical pain, also regularly meets relief with cannabis-based therapies.

Importantly, cannabis has been shown to effectively temper and even replace many prescription pain medications, such as opioids and sedatives. Recent US data demonstrated that opioid-related mortality is lower, and prescriptions for opioids have declined more significantly in states with legal access to cannabis.[10] [11] In addition, a growing number of studies report that cannabis has a better side effect profile compared to narcotics and a lower risk of dangerous addiction.[4, 12, 13] The clinical evidence confirms these preliminary findings; thousands of regular cannabis consumers find that cannabis therapies help to prevent the need for more pharmaceuticals with higher addictive potential.

Cannabis has also shown potential as a pain reliever when used instead of, or together with, common anti-inflammatory drugs (e.g. Advil, Motrin, etc.) as these medications all amplify the body’s production of anti-inflammatory prostaglandins, which can be associated with risk to sensitive organs such as the kidneys and digestive tract, particularly when taken consistently over long periods.

Key Risks
Current evidence suggests that pain treatment with cannabis is less habit-forming and non-lethal compared to traditional medical alternatives.[14] Unlike other drugs, cannabinoids don't suppress the receptors that control essential lung and heart function, so there's less risk of fatal overdoses.

However, it’s important to know that cannabis products contain compounds such as THC and CBD, which may interact with prescribed medications.[15,16] Those interactions can be potentially dangerous, increase or decrease prescription medication efficacy, and might have adverse effects as a result. 

These medications include antibiotics such as Erythromycin, cardiac medications such as Diltiazem and Verapamil, seizure medications such as Clobazam, antiviral medications such as Ritonavir, and life-saving blood-thinning medications such as Warfarin. Potential medication interactions are just one reason an expert cannabis clinician should always provide cannabis care. 

Other possible side effects of cannabis can include fatigue, diarrhea, changes in appetite, and changes in weight.[17] For some patients, these symptoms can be alarming and confusing, as they can often occur in association with symptoms of both chronic and acute illnesses.

While relatively benign relative to other pharmaceuticals and over-the-counter medications, the presence of cannabis medications in the bloodstream can have other  measurable impacts. Cannabis can cause reversible liver enzyme increases, both alone and in combination with pharmaceuticals. When consumed in large amounts, cannabis can impact cognitive function in the short run, including memory and processing capabilities. For those who consume cannabis by inhalation, a recent European report found that cannabis use may lead to more frequent bronchitis if smoked on a regular basis.

Another common impact and potential concern is cannabis can increase heart rate and either raise or lower blood pressure. These effects may impact frail, older adults with balance issues, who may have an increased risk of dizziness and falling when using cannabis.[18]

The persistent and sustained excessive use of cannabis can also have longer-term effects. Many people consuming cannabis daily and in large volumes report that they feel slower, think less clearly, and can recall information less effectively than when they consumed less or none at all.

And of course, anyone using THC/intoxicating cannabis products should refrain from driving, operating heavy machinery, or any other activities in which intoxication might pose a health or safety risk to themselves or others.

Who Should Avoid Using Cannabis for Pain?
Adolescents, individuals outside of active medical care with a history of psychotic, mood or anxiety disorders, women who are pregnant, or planning to be pregnant, and people with cardiovascular diseases should only consider cannabis care in consultation with a licensed cannabis clinician.[18]

How Cannabis Works to Relieve Pain
Cannabis helps to suppress pain on multiple levels of pain reception, transportation, and processing. Both CBD and THC affect CB1 and CB2 receptors directly or indirectly. CB1 receptors are found in the brain, while CB2 receptors are found in the peripheral nervous system. THC is known to work on the CB1 receptors, with the potential for euphoric effects, whereas CBD is known to work on CB2 receptors, which is not associated with euphoric effects.

First, THC and CBD can regulate pain thresholds at the site of pain origin to help manage the strength of pain signals propagated by the receptors responsible for detecting pain. In addition, cannabinoids function as anti-inflammatories, inhibiting pain messenger production. Moreover, cannabis can change how pain signals are transported to and received by the brain, at so-called mu-opioid receptors, which is one reason cannabis can be used to replace opioids.

In addition to its effects on nerves and signal transmission, cannabis also modulates other aspects of the endocannabinoid system, including regulating stress levels, encoding long-term memory, and promoting physical and emotional homeostasis. If the body isn't making enough cannabinoids or if the innate cannabinoid receptors (CB1 and CB2) aren't functioning optimally, pain signals may not be adequately inhibited, and pain and suffering may increase.

Besides THC and CBD, other minor cannabinoids (such as CBN,CBC, THCA or CBG), may also have pain-killing properties and make an equal contribution to overall pain relief.

About the Endocannabinoid System
What is the endocannabinoid system? It’s complex—and rarely taught in medical school. But it can be helpful to think of the endocannabinoid system as one of the body’s master regulators.

Briefly stated, it’s a neuroregulatory system that keeps physiologic functions in balance or homeostasis. It plays a crucial role in inflammation, immune response, pain detection, the sleep-wake cycle, mood, memory, appetite regulation, reproduction, and fertility. It consists of three major components: naturally produced chemicals (self-made endocannabinoids acting as transmitters), the receptors those endocannabinoids bind to (located on neurons, immune cells, etc.), and the enzymes which synthesize and degrade these components.

The human body uses two naturally derived signaling molecules called endocannabinoids: anandamide (aka the bliss molecule) and 2-arachidonoylglycerol (2-AG). Endocannabinoids are structurally similar to, but distinct from, the cannabinoids found in cannabis plants, though they act on the same receptors.

Cannabinoids derived from plants are usually referred to as phytocannabinoids. These plant-based cannabinoids consist of a wide variety of active cannabinoid molecules, with nearly 150 discovered to date. The best known molecules are tetrahydrocannabinol (THC), tetrahydrocannabinol acid (THCA), cannabidiol (CBD), cannabigerol (CBG), or cannabinol (CBN).

In addition to these 150 cannabinoids, the cannabis plant produces hundreds more organic compounds called terpenes and flavonoids. These unsaturated hydrocarbons may not activate the endocannabinoid receptors directly, but they modulate and fine-tune the functions of the activated receptors. This effect (of interaction with the receptors and molecules is known as the "entourage effect."

The second component of the endocannabinoid system is the cannabinoid receptor. The biological effects of cannabinoids are controlled by dozens of known cannabinoid receptors, the most relevant being receptors 1 and 2. Cannabinoid receptor 1 is primarily located in the brain, while cannabinoid receptor 2 is present exclusively in immune cells throughout the body. If an endocannabinoid binds to a cannabinoid receptor 1 in the brain, it may help to relieve pain. In contrast, an endocannabinoid that attaches to the cannabinoid receptor 2 in the immune system might help relieve symptoms of inflammation; it can tone down pro-inflammatory markers like cytokines and interleukin.[19]

The third component of the endocannabinoid system are enzymes, which synthesize and break down endocannabinoids. While many enzymes keep the endocannabinoid system balanced, the ones of therapeutic interest are the fatty acid amide hydrolase (FAAH) and the monoacylglycerol lipase (MAGL). The body's endocannabinoid response can be improved by modulating these enzymes for therapeutic purposes.[20] As a result, the endocannabinoid system keeps our body balanced, and cannabis can help support its natural function.

How Cannabis Care Should Work
As the evidence grows, it’s increasingly clear: An ongoing partnership with a clinician is essential in order to use cannabis safely and optimally in the treatment of pain.[2, 21-25]

An eo clinician or other expert cannabis clinician with a thorough understanding of your goals, medical record, current medications, and cannabis use history should be involved in formulating initial and ongoing product recommendations, doses, and times of use.

Questions?
Schedule a free consult with an eo team member today. Or email us at members@eo.care.

The content on this page is for informational purposes. Do not attempt to self-diagnose or prescribe treatment based on the information provided. Always consult a physician before deciding on the treatment of a medical condition.

Sources

  1. Mangual-Pérez, D., et al., Patient Experience and Perspective on Medical Cannabis as an Alternative for Musculoskeletal Pain Management. JAAOS Global Research & Reviews, 2022. 6(7): p. e22.00055.
  2. Balu, A., et al., Medical Cannabis Certification Is Associated With Decreased Opiate Use in Patients With Chronic Pain: A Retrospective Cohort Study in Delaware. Cureus, 2021. 13(12): p. e20240.
  3. Whiting, P.F., et al., Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA, 2015. 313(24): p. 2456-2473.
  4. Vučković, S., et al., Cannabinoids and Pain: New Insights From Old Molecules. Front Pharmacol, 2018. 9: p. 1259.
  5. Nagarkatti, P., et al., Cannabinoids as novel anti-inflammatory drugs. Future Med Chem, 2009. 1(7): p. 1333-49.
  6. Review: Weak evidence of benefits of cannabis for chronic neuropathic pain; moderate to weak evidence of adverse effects. Annals of Internal Medicine, 2017. 167(12): p. JC62.
  7. Mücke, M., et al., Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev, 2018. 3(3): p. Cd012182.
  8. Nugent, S.M., et al., The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med, 2017. 167(5): p. 319-331.
  9. Johnson, J.R., et al., Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage, 2010. 39(2): p. 167-79.
  10. Shi, Y., Medical marijuana policies and hospitalizations related to marijuana and opioid pain reliever. Drug Alcohol Depend, 2017. 173: p. 144-150.
  11. Bradford, A.C., et al., Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population. JAMA Intern Med, 2018. 178(5): p. 667-672.
  12. Piper, B.J., et al., Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. Journal of Psychopharmacology, 2017. 31(5): p. 569-575.
  13. Vigil, J.M., et al., Associations between medical cannabis and prescription opioid use in chronic pain patients: A preliminary cohort study. PLOS ONE, 2017. 12(11): p. e0187795.
  14. Kvamme, S.L., et al., Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample. Harm Reduction Journal, 2021. 18(1): p. 72.
  15. Arellano, A.L., et al., Neuropsychiatric and General Interactions of Natural and Synthetic Cannabinoids with Drugs of Abuse and Medicines. CNS Neurol Disord Drug Targets, 2017. 16(5): p. 554-566.
  16. Anderson, G.D. and L.N. Chan, Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. Clin Pharmacokinet, 2016. 55(11): p. 1353-1368.
  17. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis and Cannabinoid Research, 2017. 2(1): p. 139-154.
  18. Ebbert, J.O., E.L. Scharf, and R.T. Hurt, Medical Cannabis. Mayo Clin Proc, 2018. 93(12): p. 1842-1847.
  19. Zou, S. and U. Kumar, Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci, 2018. 19(3).
  20. Basavarajappa, B.S., Critical enzymes involved in endocannabinoid metabolism. Protein Pept Lett, 2007. 14(3): p. 237-46.
  21. Saeed, O.B., B. Chavan, and Z.T. Haile, Association between e-cigarette use and depression in US adults. Journal of Addiction Medicine, 2020. 14(5): p. 393-400.
  22. Reed, M.K., et al., A Failure to Guide: Patient Experiences within a State-Run Cannabis Program in Pennsylvania, United States. Subst Use Misuse, 2022. 57(4): p. 516-521.
  23. Ware, M.A., et al., Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). The Journal of Pain, 2015. 16(12): p. 1233-1242.
  24. Asselin, A., et al., A description of self-medication with cannabis among adults with legal access to cannabis in Quebec, Canada. Journal of Cannabis Research, 2022. 4(1): p. 26.
  25. Slawek, D., et al., Medical Cannabis for the Primary Care Physician. J Prim Care Community Health, 2019. 10: p. 2150132719884838.
  26. Reed MK, Kelly EL, Wagner B, Hajjar E, Garber G, Worster B. A Failure to Guide: Patient Experiences within a State-Run Cannabis Program in Pennsylvania, United States. Subst Use Misuse. 2022;57(4):516-521. doi:10.1080/10826084.2021.2019780
  27. Ware MA, Wang T, Shapiro S, et al. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). The Journal of Pain. 2015/12/01/ 2015;16(12):1233-1242. doi:https://doi.org/10.1016/j.jpain.2015.07.014
  28. Asselin A, Lamarre OB, Chamberland R, McNeil S-J, Demers E, Zongo A. A description of self-medication with cannabis among adults with legal access to cannabis in Quebec, Canada. Journal of Cannabis Research. 2022/05/26 2022;4(1):26. doi:10.1186/s42238-022-00135-y
  29. Slawek D, Meenrajan SR, Alois MR, Comstock Barker P, Estores IM, Cook R. Medical Cannabis for the Primary Care Physician. J Prim Care Community Health. Jan-Dec 2019;10:2150132719884838. doi:10.1177/2150132719884838
  30. The use of cannabis products may carry unique risks for those who  “self-medicate” without professional guidance and could worsen subjective symptoms. 25 {Omar Saeed} [J Addict Med]
  31. A lack of healthcare professional guidance can result in inadequate symptom relief and frustrating patient-reported outcomes after cannabis use as adjuvant therapy. 26 {Megan K Reed} [Subst Use Misuse]
  32. Among patients suffering from chronic pain, certification in medical cannabis is associated with a decrease in opiate use along with physician intervention. 2 {Alan Balu} [Cureus]
  33. Experts agree; a physician should handle treatment prescriptions and follow-ups to ensure safety.). 27{Mark A.Ware} [The Journal of Pain].
  34. Self-medicating with recreational cannabis is not a safe substitute for supervised care by a doctor or nurse practitioner. 28 {Antoine Asselin} [Journal of Cannabis Research]
  35. Health care providers should monitor for health consequences of medical cannabis use, while also considering how medical cannabis could affect other prescription medications. 29 {Deepika Slawek} [J Prim Care Community Health]

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