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Management CBD: Pain

kosmobuff
18.06.2018

Content:

  • Management CBD: Pain
  • Boomers Fuel Boom in Popularity of CBD
  • What about NSAIDs?
  • Pain Management · News MONDAY, May 7, (HealthDay News) -- Cannabidiol (CBD) oil has become the hot new product in states that have legalized. Molecular structures of four cannabinoids employed in pain treatment. . It also exhibits GABA uptake inhibition to a greater extent than THC or CBD (Banerjee. You may have heard the term CBD pain relief associated with various methods for consuming the cannabinoid. Click here to learn how CBD.

    Management CBD: Pain

    In , the first cannabinoid receptor was identified CB 1 Howlett et al and in , a second was described CB 2 Munro et al Both are 7-domain G-protein coupled receptors affecting cyclic-AMP, but CB 1 is more pervasive throughout the body, with particular predilection to nociceptive areas of the central nervous system and spinal cord Herkenham et al ; Hohmann et al , as well as the peripheral nervous system Fox et al ; Dogrul et al wherein synergy of activity between peripheral and central cannabinoid receptor function has been demonstrated Dogrul et al CB 2 , while commonly reported as confined to lymphoid and immune tissues, is also proving to be an important mediator for suppressing both pain and inflammatory processes Mackie Following the description of cannabinoid receptors, endogenous ligands for these were discovered: These endocannabinoids both act as retrograde messengers on G-protein coupled receptors, are synthesized on demand, and are especially active on glutamatergic and GABA-ergic synapses.

    The endocannabinoid system parallels and interacts at many points with the other major endogenous pain control systems: Interestingly, our first knowledge of each pain system has derived from investigation of natural origin analgesic plants, respectively: Notably, no endocannabinoid has ever been administered to humans, possibly due to issues of patentability and lack of commercial feasibility Raphael Mechoulam, pers comm For an excellent comprehensive review of the endocannabinoid system, see Pacher et al , while Walker and Huang have provided a key review of antinociceptive effects of cannabinoids in models of acute and persistent pain Walker and Huang A clinical endocannabinoid deficiency has been postulated to be operative in certain treatment-resistant conditions Russo , and has received recent support in findings that anandamide levels are reduced over controls in migraineurs Sarchielli et al , that a subset of fibromyalgia patients reported significant decreased pain after THC treatment Schley et al , and the active role of the ECS in intestinal pain and motility in irritable bowel syndrome Massa and Monory wherein anecdotal efficacy of cannabinoid treatments have also been claimed.

    The endocannabinoid system is tonically active in control of pain, as demonstrated by the ability of SRA rimonabant , a CB 1 antagonist, to produce hyperalgesia upon administration to mice Richardson et al As mentioned above, the ECS is active throughout the neuraxis, including integrative functions in the periacqueductal gray Walker et al a ; Walker et al b , and in the ventroposterolateral nucleus of the thalamus, in which cannabinoids proved to be fold more potent than morphine in wide dynamic range neurons mediating pain Martin et al The ECS also mediates central stress-induced analgesia Hohmann et al , and is active in nociceptive spinal areas Hohmann et al ; Richardson et al a including mechanisms of wind-up Strangman and Walker and N-methyl-D-aspartate NMDA receptors Richardson et al b.

    It was recently demonstrated that cannabinoid agonists suppress the maintenance of vincristine-induced allodynia through activation of CB 1 and CB 2 receptors in the spinal cord Rahn et al The ECS is also active peripherally Richardson et al c where CB 1 stimulation reduces pain, inflammation and hyperalgesia. These mechanisms were also proven to include mediation of contact dermatitis via CB 1 and CB 2 with benefits of THC noted systemically and locally on inflammation and itch Karsak et al Recent experiments in mice have even suggested the paramount importance of peripheral over central CB 1 receptors in nociception of pain Agarwal et al Cannabinoid agonists produce many effects beyond those mediated directly on receptors, including anti-inflammatory effects and interactions with various other neurotransmitter systems previously reviewed Russo a.

    Briefly stated, THC effects in serotonergic systems are widespread, including its ability to decrease 5-hydroxytryptamine 5-HT release from platelets Volfe et al , increase its cerebral production and decrease synaptosomal uptake Spadone THC may affect many mechanisms of the trigeminovascular system in migraine Akerman et al ; Akerman et al ; Akerman et al ; Russo ; Russo The glutamatergic system is integral to development and maintenance of neuropathic pain, and is responsible for generating secondary and tertiary hyperalgesia in migraine and fibromyalgia via NMDA mechanisms Nicolodi et al Additionally, cannabinoids reduce hyperalgesia via inhibition of calcitonin gene-related peptide Richardson et al a.

    As for Substance P mechanisms, cannabinoids block capsaicin-induced hyperalgesia Li et al , and THC will do so at sub-psychoactive doses in experimental animals Ko and Woods These are all promising attributes for an adjunctive agent in treatment of clinical chronic pain states.

    The anti-inflammatory contributions of THC are also extensive, including inhibition of PGE-2 synthesis Burstein et al , decreased platelet aggregation Schaefer et al , and stimulation of lipooxygenase Fimiani et al THC has twenty times the anti-inflammatory potency of aspirin and twice that of hydrocortisone Evans , but in contrast to all nonsteroidal anti-inflammatory drugs NSAIDs , demonstrates no cyclo-oxygenase COX inhibition at physiological concentrations Stott et al a.

    Cannabidiol, a non-euphoriant phytocannabinoid common in certain strains, shares neuroprotective effects with THC, inhibits glutamate neurotoxicity, and displays antioxidant activity greater than ascorbic acid vitamin C or tocopherol vitamin E Hampson et al These activities reinforce the conception of CBD as an endocannabinoid modulator, the first clinically available Russo and Guy CBD additionally affects THC function by inhibiting first pass hepatic metabolism to the possibly more psychoactive hydroxy-THC, prolonging its half-life, and reducing associated intoxication, panic, anxiety and tachycardia Russo and Guy A new explanation of inflammatory and analgesic effects of CBD has recently come to light with the discovery that it is able to promote signaling of the adenosine receptor A2A by inhibiting the adenosine transporter Carrier et al Cannabichromene CBC is the third most prevalent cannabinoid in cannabis, and is also anti-inflammatory Wirth et al , and analgesic, if weaker than THC Davis and Hatoum Furthermore, CBG has more potent analgesic, anti-erythema and lipooxygenase blocking activity than THC Evans , mechanisms that merit further investigation.

    It requires emphasis that drug stains of North American ElSohly et al ; Mehmedic et al , and European King et al cannabis display relatively high concentrations of THC, but are virtually lacking in CBD or other phytocannabinoid content. Cannabis terpenoids also display numerous attributes that may be germane to pain treatment McPartland and Russo Myrcene is analgesic, and such activity, in contrast to cannabinoids, is blocked by naloxone Rao et al , suggesting an opioid-like mechanism.

    It also blocks inflammation via PGE-2 Lorenzetti et al It is anti-inflammatory comparable to phenylbutazone via PGE-1 Basile et al , but simultaneously acts as a gastric cytoprotective Tambe et al Cannabis flavonoids in whole cannabis extracts may also contribute useful activity McPartland and Russo Cannflavin A, a flavone unique to cannabis, inhibits PGE-2 thirty times more potently than aspirin Barrett et al , but has not been subsequently investigated.

    Very few randomized controlled trials RCTs have been conducted using smoked cannabis Campbell et al despite many anecdotal claims Grinspoon and Bakalar A recent brief trial of smoked cannabis 3. This short clinical trial also demonstrated prominent adverse events associated with intoxication.

    In Canada, 21 subjects with chronic pain sequentially smoked single inhalations of 25 mg of cannabis 0, 2. Even after political and legal considerations, it remains extremely unlikely that crude cannabis could ever be approved by the FDA as a prescription medicine as outlined in the FDA Botanical Guidance document Food and Drug Administration ; Russo b , due to a lack of rigorous standardization of the drug, an absence of Phase III clinical trials, and pulmonary sequelae bronchial irritation and cough associated with smoking Tashkin Although cannabis vaporizers reduce potentially carcinogenic polyaromatic hydrocarbons, they have not been totally eliminated by this technology Gieringer et al ; Hazekamp et al Two open label studies in France of oral dronabinol for chronic neuropathic pain in 7 subjects Clermont-Gnamien et al and 8 subjects Attal et al , respectively, failed to show significant benefit on pain or other parameters, and showed adverse event frequently requiring discontinuation with doses averaging 15— Dronabinol did demonstrate positive results in a clinical trial of multiple sclerosis pain in two measures Svendsen et al , but negative results in post-operative pain Buggy et al Table 1.

    Another uncontrolled case report in three subjects noted relief of intractable pruritus associated with cholestatic jaundice employing oral dronabinol Neff et al Some authors have noted patient preference for whole cannabis preparations over oral THC Joy et al , and the contribution of other components beyond THC to therapeutic benefits McPartland and Russo THC absorption orally is slow and erratic with peak serum levels in 45— minutes or longer.

    Systemic bioavailability is also quite low due to rapid hepatic metabolism on first pass to hydroxy-THC. A rectal suppository of THC-hemisuccinate is under investigation Broom et al , as are transdermal delivery techniques Challapalli and Stinchcomb The terminal half-life of THC is quite prolonged due to storage in body lipids Grotenhermen Nabilone Cesamet Figure 1 , is a synthetic dimethylheptyl analogue of THC British Medical Association that displays greater potency and prolonged half-life.

    Serum levels peak in 1—4 hours Lemberger et al It was also primarily developed as an anti-emetic in chemotherapy, and was recently re-approved for this indication in the USA. Prior case reports have noted analgesic effects in case reports in neuropathic pain Notcutt et al and other pain disorders Berlach et al Sedation and dysphoria were prominent sequelae. An RCT of nabilone in 41 post-operative subjects actually documented exacerbation of pain scores after thrice daily dosing Beaulieu Table 1.

    An abstract of a study of 82 cancer patients on nabilone claimed improvement in pain levels after varying periods of follow-up compared to patients treated without this agent Maida However, 17 subjects dropped out, and the study was neither randomized nor controlled, and therefore is not included in Table 1. Part of its analgesic activity may relate to binding to intracellular peroxisome proliferator-activator receptor gamma Liu et al Peak plasma concentrations have generally been attained in 1—2 hours, but with delays up to 4—5 hours is some subjects Karst et al Debate surrounds the degree of psychoactivity associated with the drug Dyson et al Current research is confined to the indication of interstitial cystitis.

    CBD ratios reviewed in Russo and Guy , generally approximately 2: Two pharmacokinetic studies on possibly related material have been reported Nadulski et al a ; Nadulski et al b. Both Marinol and Cannador produced reductions in pain scores in long-term follow-up Zajicek et al Cannador was assayed in postherpetic neuralgia in 65 subjects with no observed benefit Ernst et al Table 1 , and in 30 post-operative pain subjects CANPOP without opiates, with slight benefits, but prominent psychoactive sequelae Holdcroft et al Table 1.

    It was approved by Health Canada in June for prescription for central neuropathic pain in multiple sclerosis, and in August , it was additionally approved for treatment of cancer pain unresponsive to optimized opioid therapy. Sativex effects commence in 15—40 minutes, an interval that permits symptomatic dose titration.

    A very favorable adverse event profile has been observed in over patient years of exposure in over experimental subjects. Patients most often ascertain an individual stable dosage within 7—10 days that provides therapeutic relief without unwanted psychotropic effects often in the range of 8—10 sprays per day.

    In a Phase II double-blind crossover study of intractable chronic pain Notcutt et al in 24 subjects, visual analogue scales VAS were 5. During that time, there was no escalation of dose indicating an absence of tolerance to the preparation. Similarly, no withdrawal effects were noted in a subset of patients who voluntarily stopped the medicine abruptly.

    Upon resumption, benefits resumed at the prior established dosages. In a Phase II double-blind, randomized, placebo-controlled, 5-week study of 56 rheumatoid arthritis patients with Sativex Blake et al , employed nocturnal treatment only to a maximum of 6 sprays per evening In a study of spinal injury pain, NRS of pain were not statistically different from placebo, probably due to the short duration of the trial, but secondary endpoints were clearly positive Table 1.

    Finally, in an RCT of intractable lower urinary tract symptoms in MS, accompanying pain in affected patients was prominently alleviated Table 1. Common adverse events AE of Sativex acutely in RCTs have included complaints of bad taste, oral stinging, dry mouth, dizziness, nausea or fatigue, but do not generally necessitate discontinuation, and prove less common over time.

    While there have been no head-to-head comparative RCTs of Sativex with other cannabinoid agents, certain contrasts can be drawn. Sativex Rog et al and Marinol Svendsen et al have both been examined in treatment of central neuropathic pain in MS, with comparable results Table 1.

    However, adverse events were comparable or greater with Marinol than with Sativex employing THC dosages some 2. Similarly, while Sativex and smoked cannabis have not been employed in the same clinical trial, comparisons of side effect profiles can be made on the basis of SAFEX studies of Sativex for over a year and up to several years in MS and other types of neuropathic pain Russo b ; Wade et al , and government-approved research programs employing standardized herbal cannabis from Canada for chronic pain Lynch et al and the Netherlands for general conditions Janse et al ; Gorter et al over a period of several months or more.

    As is evident in Figure 2 Figure 2 , all adverse events are more frequently reported with herbal cannabis, except for nausea and dizziness, both early and usually transiently reported with Sativex see Russo b for additional discussion.

    Comparison of adverse events AE encountered with long term therapeutic use of herbal cannabis in the Netherlands Janse et al ; Gorter et al and Canada Lynch et al , vs that observed in safety-extension SAFEX studies of Sativex oromucosal spray Russo ; Wade et al Phytocannabinoids are lipid soluble with slow and erratic oral absorption.

    While cannabis users claim that the smoking of cannabis allows easy dose titration as a function of rapid onset, high serum levels in a short interval inevitably result. This quick onset is desirable for recreational purposes, wherein intoxication is the ultimate goal, but aside from paroxysmal disorders eg, episodic trigeminal neuralgia or cluster headache attack , such rapid onset of activity is not usually necessary for therapeutic purposes in chronic pain states.

    The vast majority of subjects in Sativex clinical trials do not experience psychotropic effects outside of initial dose titration intervals Figure 2 and most often report subjective intoxication levels on visual analogue scales that are indistinguishable from placebo, in the single digits out of Wade et al Thus, it is now longer tenable to claim that psychoactive effects are a necessary prerequisite to symptom relief in the therapeutic setting with a standardized intermediate onset cannabis-based preparation.

    Intoxication has remained a persistent issue in Marinol usage Calhoun et al , in contrast. Recent controversies have arisen in relation to non-steroidal anti-inflammatory drugs NSAID , with concerns that COX-1 agents may provoke gastrointestinal ulceration and bleeding, and COX-2 drugs may increase incidents of myocardial infarction and cerebrovascular accidents Fitzgerald ; Topol Frequent questions have been raised as to whether psychoactive drugs may be adequately blinded masked in randomized clinical trials.

    Internal review and outside analysis have confirmed that blinding in Sativex spasticity studies has been effective Clark and Altman ; Wright Sativex and its placebo are prepared to appear identical in taste and color.

    Great public concern attends recreational cannabis usage and risks of dependency. The addictive potential of a drug is assessed on the basis of five elements: Drug abuse liability DAL is also assessed by examining a drug's rates of abuse and diversion.

    US Congress placed cannabis in Schedule I of the Controlled Substances Act in , with drugs categorized as addictive, dangerous, possessing severe abuse potential and no recognized medical value.

    Marinol was placed in Schedule II, the category for drugs with high abuse potential and liability to produce dependency, but certain recognized medical uses, after its FDA approval in Marinol was reassigned to Schedule III in , a category denoting a lesser potential for abuse or lower dependency risk after documentation that little abuse or diversion Calhoun et al had occurred.

    Nabilone was placed and has remained in Schedule II since The degree to which a drug is reinforcing is determined partly by the by the rate of its delivery to the brain Samaha and Robinson Sativex has effect onset in 15—40 minutes, peaking in a few hours, quite a bit slower than drugs of high abuse potential.

    It has been claimed that inclusion of CBD diminishes psychoactive effects of THC, and may lower potential drug abuse liability of the preparation see Russo b for discussion. Prior studies from Sativex clinical trials do not support the presence reinforcement or euphoria as problems in administration Wade et al Certain facets of acute cannabinoid exposure, including tachycardia, hypothermia, orthostatic hypotension, dry mouth, ocular injection, intraocular pressure decreases, etc.

    No dose tolerance to the therapeutic effects of Sativex has been observed in clinical trials in over patient-years of administration. Additionally, therapeutic efficacy has been sustained for several years in a wide variety of symptoms; SAFEX studies in MS and peripheral neuropathic pain, confirm that Sativex doses remain stable or even decreased after prolonged usage Wade et al , with maintenance of therapeutic benefit and even continued improvement.

    Debate continues as to the existence of a clinically significant cannabis withdrawal syndrome with proponents Budney et al , and questioners Smith While symptoms recurred after 7—10 days of abstinence from Sativex, prior levels of symptom control were readily re-established upon re-titration of the agent Wade et al Overall, Sativex appears to pose less risk of dependency than smoked cannabis based on its slower onset, lower dosage utilized in therapy, almost total absence of intoxication in regular usage, and minimal withdrawal symptomatology even after chronic administration.

    No known abuse or diversion incidents have been reported with Sativex to date as of November Cognitive effects of cannabis have been reviewed Russo et al ; Fride and Russo , but less study has occurred in therapeutic contexts. Effects of chronic heavy recreational cannabis usage on memory abate without sequelae after a few weeks of abstinence Pope et al Studies of components of the Halstead-Reitan battery with Sativex in neuropathic pain with allodynia have revealed no changes vs placebo Nurmikko et al , and in central neuropathic pain in MS Rog et al , 4 of 5 tests showed no significant differences.

    While the Selective Reminding Test did not change significantly on Sativex, placebo patients displayed unexpected improvement. Slight improvements were observed in Hospital Anxiety and Depression Scales depression and anxiety scores were noted with Sativex in MS patients with central neuropathic pain Rog et al , although not quite statistically significant.

    No long-term mood disorders have been associated with Sativex administration. Debate continues with regard to the relationship between cannabis usage and schizophrenia reviewed Fride and Russo An etiological relationship is not supported by epidemiological data Degenhardt et al , but if present, should bear relation to dose and length of high exposure. It is likely that lower serum levels of Sativex in therapeutic usage, in conjunction with anti-psychotic properties of CBD Zuardi and Guimaraes , would minimize risks.

    Children and adolescents have been excluded from Sativex RCTs to date. SAFEX studies of Sativex have yielded few incidents of thought disorder, paranoia or related complaints. Adverse effects of cannabinoids on immune function have been observed in experimental animals at doses 50— times the psychoactive level Cabral In four patients using herbal cannabis therapeutically for over 20 years, no abnormalities were observed in leukocyte, CD4 or CD8 cell counts Russo et al Investigation of MS patients on Cannador revealed no major immune changes Katona et al , and similarly, none occurred with smoked cannabis in a short-term study of HIV patients Abrams et al Hematological measures have been normal in all Sativex RCTs without clinical signs of immune dysfunction.

    Concerns are frequently noted with new drug-drug interactions, but few have resulted in Sativex RCTs despite its adjunctive use with opiates, many other psychoactive analgesic, antidepressant and anticonvulsant drugs Russo a , possibly due to CBD ability to counteract sedative effects of THC Nicholson et al Thus, Sativex should be safe to use in conjunction with other drugs metabolized via this pathway.

    The Sativex product monograph in Canada http: Given that THC is the most active component affecting such abilities, and the low serum levels produced in Sativex therapy vide supra , it would be logical that that patients may be able to safely engage in such activities after early dose titration and according to individual circumstances, much as suggested for oral dronabinol. This is particularly the case in view of a report by an expert panel Grotenhermen et al that comprehensively analyzed cannabinoids and driving.

    Prior studies document that 4 rapid oromucosal sprays of Sativex greater than the average single dose employed in therapy produced serum levels well below this threshold Russo b. Sativex is now well established as a cannabinoid agent with minimal psychotropic effect. These include anti-emetic effects, well established with THC, but additionally demonstrated for CBD Pertwee , the ability of THC and CBD to produce apoptosis in malignant cells and inhibit cancer-induced angiogenesis Kogan ; Ligresti et al , as well as the neuroprotective antioxidant properties of the two substances Hampson et al , and improvements in symptomatic insomnia Russo et al The degree to which cannabinoid analgesics will be adopted into adjunctive pain management practices currently remains to be determined.

    Given their multi-modality effects upon various nociceptive pathways, their adjunctive side benefits, the efficacy and safety profiles to date of specific preparations in advanced clinical trials, and the complementary mechanisms and advantages of their combination with opioid therapy, the future for cannabinoid therapeutics appears very bright, indeed. National Center for Biotechnology Information , U. Ther Clin Risk Manag. Author information Copyright and License information Disclaimer.

    This article has been cited by other articles in PMC. Abstract This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Introduction Chronic pain represents an emerging public health issue of massive proportions, particularly in view of aging populations in industrialized nations.

    Cannabinoids and analgesic mechanisms Cannabinoids are divided into three groups. Open in a separate window. Molecular structures of four cannabinoids employed in pain treatment. Available cannabinoid analgesic agents and those in development Very few randomized controlled trials RCTs have been conducted using smoked cannabis Campbell et al despite many anecdotal claims Grinspoon and Bakalar Table 1 Results RCTs of cannabinoids in treatment of pain syndromes.

    Practical issues with cannabinoid medicines Phytocannabinoids are lipid soluble with slow and erratic oral absorption. Broad experience with pain sparks search for relief [online] Short-term effects of cannabinoids in patients with HIV-1 infection. A randomized, placbo-controlled clinical trial.

    Cannabis in painful HIV-associated sensory neuropathy: Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors.

    Cannabinoid CB1 receptor activation inhibits trigeminovascular neurons. J Pharmacol Exp Ther. Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception. Anandamide acts as a vasodilator of dural blood vessels in vivo by activating TRPV1 receptors. Are oral cannabinoids safe and effective in refractory neuropathic pain? Cannflavin A and B, prenylated flavones from Cannabis sativa L.

    Anti-inflammatory activity of oleoresin from Brazilian Copaifera. Effects of nabilone, a synthetic cannabinoid, on postoperative pain: Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: Molecular targets for cannabidiol and its synthetic analogues: Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine Sativex in the treatment of pain caused by rheumatoid arthritis.

    Rheumatology Oxford ; Therapeutic uses of cannabis. Harwood Academic Publishers; Analgesic and reinforcing proerties of delta9-THC-hemisuccinate in adjuvant-arthritic rats. Journal of Cannabis Therapeutics. Review of the validity and significance of cannabis withdrawal syndrome. Lack of analgesic efficacy of oral deltatetrahydrocannabinol in postoperative pain. Inhibition of biosynthesis by the naturally occurring cannabinoids.

    Russo EB, Grotenhermen F, editors. Pharmacology, toxicology and therapeutic potential. Abuse potential of dronabinol Marinol J Psychoactive Drugs. This viewpoint stands contrary to the idea of holistic medicine, where you take something in its entirety for medicinal purposes.

    The Cannabis sativa plant is one of the greatest present-day examples of this tug-of-war between Western medicine and traditional medicine. It has been found to have a variety of health-related benefits for the user. CBD is the second most well-known cannabinoid found in cannabis, and like most of the other phytocannabinoids, it is non-psychotropic.

    These are the two most abundant and well-studied cannabinoids in marijuana, and both have been found in numerous published studies to have pain-relieving properties in humans. While they may be the most abundant, THC and CBD are certainly not the only compounds found in cannabis that are known to exert positive effects on human health.

    In every cannabis plant, there is a unique mixture of hundreds of plant compounds, comprised of phytocannabinoids, terpenes, and flavonoids. Research suggests that these compounds too have an influence on our neurochemistry, and together they may work synergistically, producing better improvements in pain relief than anyone would produce on its own.

    This research supports the idea that it is best to use the whole cannabis plant, with CBD, THC, and the natural medley of additional compounds. This harmony between the various plant chemicals found in marijuana is colloquially referred to as the entourage effect. The most well-studied compounds found in the marijuana plant that support the idea of the entourage effect are THC and CBD, which have been found to work differently together than when separate.

    Using these two compounds in concert has been shown to help mitigate side effects and enhance efficacy, with CBD plus THC showing more benefit for some conditions than THC alone. It has also been found to extend the half-life of THC, which may help to extend the pain-relieving benefits.

    This has allowed the use of higher doses of THC in clinical trials for the treatment of pain caused by multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis. When used in concert, a greater efficacy in treating these types of pain have been observed.

    Every strain of bud that you can purchase at a dispensary will be labeled with its THC and CBD content, which can be helpful when choosing which strain to choose for pain relief.

    CBD has been found to exhibit enhancements in treating pain both when used on its own and when used in combination with THC. When used alone, CBD is largely best for inflammatory pain, such as that caused by arthritis or injuries.

    In one animal study on arthritis pain, it was found that the topical application of CBD led to a reduction in inflammation and pain. Another animal study found that CBD helps to reduce neuropathic pain through the suppression of chronic inflammation. CBD does not directly bind to the receptors found in the endocannabinoid system but rather works to modulate the effects of the endocannabinoids the cannabinoids found naturally in our bodies as well as working as a CB1 receptor antagonist.

    The main mechanism by which CBD is thought to help mediate pain is by reducing inflammation , largely by blocking inflammatory mediators. It is also believed to potentiate glycine receptors, which help to regulate pain at the spinal level.

    This suppresses both neuropathic and inflammatory pain. THC is used clinically for the treatment of pain and studies find it helps relieve central and neuropathic pain. It is also used to help reduce pain in cancer, AIDS, and fibromyalgia patients, for which resistance to other pain treatments have been found. The mode of action for THC is as a partial CB1 receptor agonist, which means that it will bind to these receptors but not fully which leads to the variability in effects documented when THC is present with other CB1 agonists, antagonists or both.

    It has been found to impact the serotonergic, dopaminergic, and glutamatergic systems — an action which may contribute to its pain-relieving benefits.

    Additionally, THC has been found to act as an anti-inflammatory agent. While human studies have found benefits from the use of THC, CBD, and whole-plant marijuana in relieving pain, much of the evidence for this use comes from user reports and surveys.

    When searching for the best cannabis strains for pain relief, you will first want to consider how much THC and CBD is found in the strain. This is because CBD can help to mediate the side effects of THC while also providing additional anti-inflammatory and analgesic properties. One example would be if you are experiencing inflammation, yet you are wanting to go about your day normally, without the psychotropic effects of THC. Other times you may be in enough pain that you would like something that takes your mind off the pain while also offering pain relief.

    In one survey , participants reported that indicas helped more than sativas when it came to headaches, joint pain, neuropathy, and spasticity. Users also reported indicas to be more helpful when it comes to sleep and sedation.

    Lastly, there are countless user reports on specific strains of weed that have been found to be powerful for relieving pain.

    While some of these strains are high CBD, indica strains, some strains of weed used for pain do not fall into this category. It may be that the other cannabinoids, terpenes, and flavonoids have come together in a harmonious balance that leads to strong pain-relieving properties. There are limited studies examining the effect of CBD alone on pain in humans.

    When it comes to CBD only studies, the majority are preclinical or animal studies. That said, the research conducted thus far, along with countless user reports, suggests that CBD itself may be able to help relieve pain. Activation of cannabinoid receptors has been linked to the inhibition of pain. The exact mechanisms of action are still being researched, however, CBD has been found to increase the levels of endocannabinoids in the body, specifically anandamide. It is plausible that this increase in endogenous endocannabinoids could have an impact on pain.

    Another study suggests that CBD in rats induced suppression of chronic inflammation and neuropathic pain through potentiating glycine receptors. Here we will examine the limited scientific evidence, along with theories relating to the use of CBD for pain. Neuropathic pain, also known as nerve pain, is a unique type of pain that is caused by injured, dysfunctional, or irritated nerves. This pain tends to be chronic and severe, and with no known cure or remedy, every individual is left to try numerous strategies to find something that works for them.

    Some of the most common sources of neuropathy include diabetes, injury, cancer, infections, alcoholism, and autoimmune disorders. In an animal study , researchers found that oral supplementation of CBD led to improvements in neuropathic pain in rats. Back pain is one of the most common forms of both acute and chronic pain. Acute back pain tends to be caused by an injury, such as by falling or lifting something heavy. Chronic back pain is that which lasts more than three months and is often caused by a ruptured or bulging disc, arthritis, osteoporosis, scoliosis, or nerve pain.

    Some back pain is partly caused by inflammation, and numerous preclinical and animal studies have found benefits of CBD for inflammation. Through possible reductions in both nerve and inflammatory pain, CBD may help relieve back pain. When it comes to localized pain, topical CBD lotion or creams may be a great option.

    While human studies on the efficacy of CBD lotion are lacking, there are plenty of animal studies and personal accounts to support this use. In one study , researchers found that rats with arthritis treated with transdermal CBD experienced reductions in pain-related behaviors and inflammation. Cannabis and CBD dosing for pain are highly individual.

    Studies have found a bell-shaped dose-response curve with cannabis extract, meaning that it slowly becomes more effective until it hits a certain point, and then the effectiveness decreases. To further complicate matters, the effective dose found in human studies varies greatly from one condition and one study to the next. However, doses of Sativex, an oral spray that delivers 2. CBD dosage for pain has not been examined in any human studies. Like the Cannabis sativa extract, studies have found that exceeding the optimal dose of CBD can lead to a reduction in efficacy.

    In a study examining the effect of CBD on anxiety, mg and mg were not effective, where mg was.

    Boomers Fuel Boom in Popularity of CBD

    Kyle Wright was used to living in pain. The year-old who lives in New York City regularly felt the repercussions of decades-old injuries from. Cannabidiol or CBD oil has become popular for pain treatment. People use it for arthritis, multiple sclerosis (MS), and other conditions. It also. By Winston Peki. With the widespread legalization of medical marijuana, many people turn to the drug for a more natural pain relief method. As a natural.

    What about NSAIDs?



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    aleks65654

    Kyle Wright was used to living in pain. The year-old who lives in New York City regularly felt the repercussions of decades-old injuries from.

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