Best CBD for Pain

CBD is the acronym for cannabidiol, one of the 108 (at least) phytocannabinoids found in members of the cannabis plant. CBD has several different evidence based effects including anti-nausea, as an anticonvulsant, an anti-anxiety agent, anti-inflammatory agent, an immune modulator and an antioxidant. Importantly, CBD has also been shown to be an effective pain reliever. [1]

It is important to know that the effects of CBD are significantly different than those of THC, another cannabinoid with a similar chemical structure, but with different actions. One of the most important differences is that CBD is not an intoxicant and won’t get you high while THC is intoxicating. As an aside, most times you will hear or read that CBD is not a “psychoactive” agent. While this is true in the way most people think of psychoactive agents, CBD does have anti-anxiety and antidepressant effects and it does affect mood, so the more correct technical term is non-intoxicating).[2]

To understand how CBD relieves pain, let’s start first with the human endocannabinoid system: the ancient regulatory system on which the cannabinoids act.

The Endocannabinoid System

Cannabis is one of the oldest medicinal plants known to humans and the endocannabinoid system is an ancient, evolutionarily conserved system that plays a key role in homeostasis, the process that helps balance the body’s metabolic, immune and hormonal systems. The endocannabinoid system (ECS) plays vital roles in regulation of the stress response, mood, memory, reward systems that control appetite, libido, addictions and metabolic processes like the regulation of blood sugar levels and the balance of energy in the body. The fact that such a wide variety of systems can be regulated by the ECS gives us a clue as to how important it is.

Endocannabinoids are the signaling molecules for the ECS. Structurally, they don’t “look” like cannabinoids, which are phytocannabinoids but the endocannabinoids interact with receptors of the ECS in a way similar to a lock (the receptors) and key (the endocannabinoids or phytocannabinoids) The two main endocannabinoids found in humans are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These substances (the keys) bind to one of two receptors (the locks), either CB1 or CB2.

· AEA binds weakly to both the CB1 and CB2 receptors

· 2-AG binds strongly to both the CB1 and CB2 receptors

CB1 and CB2 Receptors

CB1 and CB2 receptors are found in different areas of the body. CB1 is found mostly in the brain, the spinal cord and on the nerves that run through the body. One current theory is that slight genetic changes in the CB1 receptor may help explain some mood disorders like depression and anxiety.[3]

CB2 receptors are found on cells of the immune, reproductive, digestive, cardiovascular and musculoskeletal systems.

THC, the intoxicating or psychoactive cannabinoid binds more strongly to CB1. CBD has a different profile;t binds weakly to both CB1 and CB2 receptors. More recent research indicates that THC can affect additional receptors (beyond the CB1 and CB2 receptors) in different ways that can result in various health benefits. Some of these different ways include:

• CBD may bind to serotonin receptors – This may help explain the anti-anxiety effect of CBD. This may also help explain other effects including alterations in pain perception and delivery of pain relief. [4]
• CBD also binds to a type of receptor known as transient receptor potential channels, of the vanilloid subtype usually abbreviated as TRPVs. The TRPVs act as “sensors” for pain, heat and pressure. [5] CBD binds to TRPV1. This receptor is specifically involved in the perception of pain. The endocannabinoid AEA also binds to the TRPV1 receptor as does the substance capsaicin derived from hot chili peppers. Capsaicin is used in several topical agents designed to decrease pain.
• CBD may also act as a natural Selective Serotonin Reuptake Inhibitor (SSRI). The SSRI’s are a class of drug used to treat anxiety and depression.[6]
  • • In addition to acting as an SSRI, CBD may also inhibit the reuptake of AEA. The end result is that AEA hangs around longer and exerts a greater effect.

Overall, the evidence is building that CBD acts as a – get ready for it—an indirect antagonist of cannabinoid agonists. Translation: CBD acts on parts of a number of different receptors to balance out the actions of other cannabinoids like THC. [7]

What Is Pain?

Pain is a subjective response to a sensory stimulus. That stimulus could be heat, pressure or some form of injury. Pain is difficult to measure because it is subjective. It all depends on who is experiencing the pain. We’ve all known people who seem to wince at the smallest pain while others seem to have a great deal of tolerance to pain.

Medically, two main types of pain are recognized:

· Nociceptive: pain that comes from damaged tissues

· Neuropathic: pain that comes from damaged nerves

There is also a third major form of pain recognized by many physicians and researchers. This is the pain that comes from some form of neurologic dysfunction that is not necessarily accompanied by any signs of damage. Fibromyalgia is a good example of this form of pain.

Some researchers, on the other hand, classify pain as nociceptive, neuropathic, inflammatory or due to cancer.

There are other ways to describe pain. It can be acute or chronic, but it can also be described as sharp, dull, achy, pressure, stabbing or in a number of other ways. Again, it is often how the person going through the pain perceives it.

Acute pain is sudden pain that usually signals an injury or sudden damage to tissues. It is meant to immediately notify you that you are in danger! Acute pain is carried by fast-acting “A” type nerve fibers. Chronic pain is pain that lasts longer and it is carried by the slower “C” fibers. The sections of the nervous system that perceive pain evolved to protect us from movement that might make the pain or injury worse. It also seems to encourage us to take it easy, to rest and recover from the injury.

How Does CBD Reduce Pain?

The quick answer is we don’t really know. We are in the early stages of CBD research. This is often difficult research to perform. Why? There are many technical, legal and cultural reasons, but the most complicated reasons may be technical. We are in possession of lots more information then we had, say 5 years ago, and more are being published all the time.

Here is some of the information we have now:

· CBD appears to have both some direct and some indirect effects at CB receptors and at other receptors such as the serotonin and the TRPV1 receptors that help regulate how pain is perceived. CBD may interact with even more receptors involved including nuclear receptors [8],[9],[10]

· CBD may increase the threshold for pain[11]

· CBD acts as an anti-inflammatory agent[12]

The current understanding of the actions of CBD in the context of pain relief is that “cannabinoids, both plant derived and endogenous, act simultaneously on multiple pain targets.”[10] That is part of the reason CBD research is complicated. It looks like CBD can act on multiple receptors and multiple targets at the same time.

Evidence Based Use of CBD for Chronic Pain Relief

While it is clear that much more research needs to be done, currently there is enough evidence to support at least a trial of CBD in several different pain related conditions including: [10], [13],[14],[15]

· Chronic non-cancer pain

· Neuropathic pain

· Abdominal pain

· Rheumatic and joint pain

· Chronic cancer pain

· Neurological pain

Not all the studies looked specifically at CBD. That is another area that needs to be expanded. Several studies examined medical cannabis and synthetic cannabinoids.

The side effects associated with CBD use tend to be mild, short-term, well tolerated and are often related to other uses of CBD;eg. drowsiness, fatigue, changes in appetite and diarrhea.

Overall, CBD research is in its infancy, but it is reasonable to expect that every year there will be a better understanding of how CBD may function to decrease pain levels. Currently, there is sufficient evidence and CBD has a good enough safety profile so that it is definitely worth of trial for most people suffering from chronic pain. It is recommended that you work with a knowledgeable healthcare professional when using CBD.

Evidence Based Use of CBD for Arthritis Pain Relief

Arthritis is common.- In fact, the term arthritis covers over 100 different conditions that all possess the common element of joint pain. Arthritis can take the form of:

• Degenerative arthritis is the most common type of arthritis and due, at least in part, to “wear and tear” of joints. During a lifetime, the cartilage of the joints accumulates damage, eventually often resulting in swelling, inflammation, stiffness and pain.
• Inflammatory arthritis is a somewhat redundant terminology because arthritis IS an inflammatory process. This is a class designation and includes rheumatoid arthritis (RA), psoriatic arthritis and other autoimmune processes like ankylosing spondylitis and lupus. Gout and Lyme disease can also produce arthritic syndromes. Gout and pseudogout are sometimes considered metabolic forms of arthritis.
• Infectious arthritis is caused by bacterial, viral or fungal infections that affect the joints. Bacterial infections may be due to Salmonella, Shigela, Chlamydia and Neisseria species. Hepatitis C can also cause infectious arthritis.

At this point, you won’t find it too surprising that there have not been many clinical studies using just hemp derived CBD for pain relief, either oral or topical, while managing the various forms of arthritis. However, some case studies were recently published [16] using CBD in various forms. One case involved a 50 year old woman with multiple autoimmune conditions including rheumatoid arthritis who was successfully assisted using 600mg CBD of isolate in MCT oil given by the sublingual (under the tongue) route. The doses were divided and given 3 times a day (200 mg each) and the woman reported significant improvement in her pain levels, quality of life, emotional well being and physical ability to function normally.

In a recent review cleverly titled “Joints for Joints”, one of the Key Points stated that “ CBD is effective in reducing inflammation and pain and might enhance the efficacy of therapeutic drugs. “[17] This finding suggests that oral CBD might reduce pain by reducing inflammation- and that it might be best used in conjunction with current medications. That is a conversation that you would need to have with your physician.

Topically, CBD has been anecdotally widely reported to reduce pain. Topical applications have the advantage of working directly on a painful joint and avoid first pass metabolism. There are no current recommendations regarding the quantity to use.-A reasonable rule of thumb is to fully cover the painful area with as small amount of topical CBD as possible and to repeat the process every 2-4 hours as needed. The temptation is often to go for the most “potent” topical CBD but, depending on the area and the degree of pain, it is often reasonable and cost-effective to start with a low dose and increase as needed.

Other studies have used synthetic cannabinoids or combinations of CBD and THC which make interpretation difficult- but it can be concluded from these studies that CBD alone is worth a try if you have any form of arthritis. A reasonable recommendation would be to start with a topical form of CBD if your arthritis is limited to one, two or three joints. If more joints are involved, oral CBD may represent a better approach. There will be some trial and error involved in finding your dose so be patient.

Evidence Based Use of CBD for Multiple Sclerosis

Most of the studies done on cannabinoids and multiple sclerosis (MS) have used Sativex in a mouth spray. Sativex is a synthetic mixture of THC and CBD in a 1:1 ratio. It has been shown to be safe and effective in controlling pain and muscle spasticity in MS.[18]

The evidence that CBD in oil or tincture form may benefit MS is mostly anecdotal. No clinical studies have been performed so far. The anecdotal information essentially boils down to “It works for some but not for others”. It may be worth a try but work with your physician and don’t try it on your own.

Evidence Based Use of CBD for Inflammation

CBD has been shown to have anti-inflammatory properties. A 2014 review indicated that in many mouse and rat studies, CBD had significant anti-inflammatory properties. [19]

In rat models of inflammatory arthritis, topical CBD reduced both inflammation and pain related behaviors. [20] In a mouse model of arthritis, CBD also reduced inflammation, but it was not clear how it was able to do this. [21] Other lab studies support this view. [22]

Overall, it is the same story. Anecdotally, CBD is believed to be effective at reducing inflammation. Clinical studies are lagging, but the studies that have been carried out using lab animals indicate that CBD reduces markers of inflammation. It is not yet clear how this happens. Again, the current evidence indicates that CBD can reduce inflammation and the pain often associated with it and is worth a try. The recommendations would include working with your physicians and starting at a low dose and slowly increasing the dose until you feel your goal has been reached.

Tips for Choosing a CBD Product for Pain

Always, always, always start at a low dose and slowly increase that dose until the pain has been effectively relieved. All the data indicates that CBD is safe over a wide range of doses but why buy or use more than you need?

We here at LeafReport are striving to help you make the best choice possible. The most important parameters to consider are:

• Make certain of the purity of the product and that the label gives accurate information. The best way to do this is by ensuring that the company you are looking to buy from has a good, professional reputation AND that they use 3rd party labs to test their product to ensure both purity and accuracy. We have done many different company and product reviews so you don’t have to!
• Human nature seems to want to have the most “potent” product around but you may not need that amount of product. You would be wasting money better spent on other needs. If you follow the adage “Start low and go slow” you will be able to determine your most effective dose. This may be quite different from your friend’s most effective dose so go through your own trial and error process to find it. You may, or may not, need to increase that dose, depending on your particular situation.
• When you are dealing with pain, it can be difficult to be patient and the trial and error process does require some patience! If you are using a topical product for pain, apply it and give it at least 20-30 minutes to be effective and then slowly increase the amount if required. If you find you need to apply a further amount every thirty minutes or so, you can likely go to a more potent product. That may be one that is more highly concentrated or one that contains more total CBD. If you are taking CBD by mouth, you should wait at least 1-2 hours before trying the same dose and a few days before you try increasing the dose. Oral products take longer to show their effectiveness than topical products do but the effects last hours longer.

References Cited

[1] Iffland, Kerstin, and Franjo Grotenhermen. “An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.” Cannabis and cannabinoid research vol. 2,1 139-154. 1 Jun. 2017, doi:10.1089/can.2016.0034

[2] Russo, Ethan B. “Cannabidiol claims and misconceptions.” Trends in pharmacological sciences 38.3 (2017): 198-201.

[3] Mechoulam R; Parker LA., The endocannabinoid system and the brain. Annu Rev Psychol. 2013; 64:21-47.

[4] de Mello Schier AR, et al, Antidepressant like and anxiolytic like effects of cannabidiol: a chemical compound of Cannabis sativa. CNS Neurol Disord Drug Targets. 2014;13(6):953-60.

[5] Baylie, R L, and J E Brayden. “TRPV channels and vascular function.” Acta physiologica (Oxford, England) vol. 203,1 (2011)

[6] Blessing, Esther M., et al. “Cannabidiol as a potential treatment for anxiety disorders.” Neurotherapeutics 12.4 (2015): 825-836.

[7] Meng, Howard, et al. “Selective cannabinoids for chronic neuropathic pain: a systematic review and meta-analysis.” Anesthesia & Analgesia 125.5 (2017): 1638-1652.

[8] Kress, Michaela, and R. Kuner. “Mode of action of cannabinoids on nociceptive nerve endings.” Experimental brain research 196.1 (2009): 79-88.

[9] O’Brien, Melissa, and Jason J. McDougall. “Cannabis and joints: scientific evidence for the alleviation of osteoarthritis pain by cannabinoids.” Current opinion in pharmacology 40 (2018): 104-109.

[10] Vučković, Sonja et al. “Cannabinoids and Pain: New Insights From Old Molecules.” Frontiers in pharmacology vol. 9 1259. 13 Nov. 2018, doi:10.3389/fphar.2018.01259

[11] do Nascimento, Glauce Crivelaro, et al. “Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson’s disease.” Neuropharmacology (2019): 107808.

[12] ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A., Phytochemistry of Cannabis sativa L. Prog Chem Org Nat Prod. 2017; 103():1-36.

[13] Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W., Cannabis based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2018 Mar 7; 3():CD012182.

[14] Andreae MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, Abrams DI, Prasad H, Wilsey B, Indyk D, Johnson M, Sacks HS, Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. J Pain. 2015 Dec; 16(12):1221-1232.

[15] NASEM (2017). National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: National Academies Press

[16] Shaw, Christian, L. L. C. Halcyon Therapeutics, and Jahan Marcu. “Cannabidiol in the Management of Comorbid Rheumatoid Arthritis, Lupus, and Raynaud’s Disease.” Endocannabinoid Medicine 2.30 (2016): 14.

[17] Lowin, Torsten, Matthias Schneider, and Georg Pongratz. “Joints for joints: cannabinoids in the treatment of rheumatoid arthritis.” Current opinion in rheumatology 31.3 (2019): 271-278.

[18] Zettl, Uwe K., et al. “Evidence for the efficacy and effectiveness of THC-CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis.” Therapeutic advances in neurological disorders 9.1 (2016): 9-30.

[19] Burstein, Sumner. “Cannabidiol (CBD) and its analogs: a review of their effects on inflammation.” Bioorganic & medicinal chemistry 23.7 (2015): 1377-1385.

[20] Hammell, D. C., et al. “Transdermal cannabidiol reduces inflammation and pain related behaviours in a rat model of arthritis.” European Journal of Pain 20.6 (2016): 936-948.

[21] Zurier, Robert B., and Sumner H. Burstein. “Cannabinoids, inflammation, and fibrosis.” The FASEB Journal 30.11 (2016): 3682-3689.

[22] Philpott, Holly T., Melissa O’brien, and Jason J. McDougall. “Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.” Pain 158.12 (2017): 2442.