Pain relievers are medicines that reduce or relieve headaches, sore muscles, arthritis, or other aches and pains. There are many different pain medicines, and each one has advantages and risks. Some types of pain respond better to certain medicines than others. Each person may also have a slightly different response to a pain reliever.
Recent years have brought a wealth of new scientific understanding regarding how medical marijuana cannabis can be beneficial for treating Pain.
Over-the-counter (OTC) medicines are good for many types of pain. There are two main types of OTC pain medicines: acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin, naproxen (Aleve), and ibuprofen (Advil, Motrin) are examples of OTC NSAIDs.
If OTC medicines don’t relieve your pain, your doctor may prescribe something stronger. Many NSAIDs are also available at higher prescription doses. The most powerful pain relievers are narcotics. They are very effective, but they can sometimes have serious side effects. Because of the risks, you must use them only under a doctor’s supervision.
There are many things you can do to help ease pain. Pain relievers are just one part of a pain treatment plan.
Analgesic the Beauty of Cannabis PAIN Relief
Analgesia or pain relief, is an important part of any treatment for cancer, AIDs, multiple sclerosis, and many other serious illnesses. The drugs used in analgesia are called analgesics, and include common painkillers as well as medical marijuana. Medical marijuana is a legal alternative analgesic in many states including California, and for conditions that cause severe and persistent pain, it may even be a better treatment option than traditional pain relievers such as opiates.
How Medical Marijuana Works as an Analgesic
The chemicals in medical marijuana that are only found in the cannabis plant are known as cannabinoids. These compounds have been shown to significantly relieve pain by connecting to the pain receptors in the central nervous system of the human body, and are known to relieve pain in patients even when stronger painkillers derived from opiates are not effective. Findings from studies on medical marijuana and pain relief show:
- Less delta-9-THC, a cannabinoid, is needed for pain relief when compared to codeine, with the pain relief obtained from a 10 mg dose of delta-9-THC comparable to the pain relief obtained from a 60 mg dose of codeine (The analgesic properties of delta-9-tetrahydrocannabinol and codeine, Noyes R. Jr. et al.)
- Patients with access to medical marijuana extracts may decrease their use of opioid pain relievers, non-steroidal anti-inflammatory drugs (NSAIDs), and antidepressants (Adjunctive nabilone in cancer pain and symptom management, Maida V., et al.)
- Patients administered inhaled medical marijuana may achieve significant relief from peripheral neuropathy, a common symptom in patients undergoing chemotherapy or taking certain anticancer drugs that causes pain, tingling, or muscle weakness, especially in the hands or feet (Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial, Abrams D.I., et al.)
- If medical marijuana is taken before chemotherapy or anticancer drugs, peripheral neuropathy might be prevented entirely (Cannibidol Prevents the Development of Cold and Mechanical Allodynia in Paclitaxel-Treated Female Mice, Ward S., et al.)
- Those with extremely severe and/or chronic pain might be able to find relief by combining the use of medical marijuana with sustained-release morphine when neither drug alone provides sufficient pain relief (Cannabinoid-opioid interaction in chronic pain, Abrams D.I., et al.)
How Medical Marijuana is Used as an Analgesic
There are many forms in which patients can ingest medical marijuana for pain relief. Although the majority of patients report smoking their medicine, many studies use alternative delivery methods due to lingering negative perceptions about smoking cannabis. It should also be noted that while some studies have shown that although smoking cannabis is not as negative to health as smoking cigarettes, there may be dangers to smoking any type of drug. These alternative methods of medical marijuana delivery have all been shown to provide an analgesic effect:
- Vaporizing, through the use of specialized vaporizer equipment
- Oral ingestion in a solution, either of all parts of the cannabis plant or of scientifically isolated cannabinoids
- Oral ingestion through edibles
Medical marijuana studies are leading to more widespread legalization of cannabis as a treatment option for painful conditions. These are major steps to making cannabis and cannabinoids more widely available as analgesics and removing the stigma attached to using these effective methods of chronic pain relief. For patients living in areas where medical marijuana is already legal at the state level, the analgesic potential of cannabis may be an effective pain relief solution.
What You Don’t Know About Cannabis and Pain
Not all Analgesic is equal
Pain relief can be tricky, since not all pain is the same. Pain can be cancer-related or neuropathic. It can be central pain (related to multiple sclerosis) or it can be visceral (related to the gut). Pain can also be acute and short-lived or chronic, lasting for months or years. Normally for acute pain, such as the kind you may experience after an injury or an operation, or neuropathic pain which is related to a whole host of diseases such as diabetes or cancer, doctors will prescribe opiates or NSAIDS (non-steroidal anti-inflammatory drugs).
However, opiates and NSAIDS are less effective in treating chronic pain. Both have adverse side-effects, including nausea, stroke, erectile dysfunction, heart-attack, hepatoxicity. Opiates often cause sedation that make long-term opiate use burdensome to the user. Plus, long-term use of traditional pain relievers builds tolerance, meaning that for these analgesics to continue to be effective, users must consistently increase their dosage. This can also lead to accidental overdose.
However, there is a light at the end of the tunnel. Research has proven time and time again that cannabis can be employed to relieve pain without the adverse side-effects that come from synthetic analgesics.
A 2008 double-blind, randomized clinical trial at the University of California Davis found that both high and low doses of inhaled cannabis reduced neuropathic pain of various causes. The subjects who participated in the study were chosen for their unresponsiveness to standard pain therapies.
In another clinical trial conducted in 2013, researchers reported that both inhaled and oral THC decreased pain significantly. The trial exposed healthy subjects to painful stimuli and discovered that the subjects had decreased pain sensitivity and increased pain tolerance with the use of either smoked or orally-administered THC.
Also in 2013, a clinical trial provided evidence that vaporized cannabis had a strong impact on neuropathic pain. Low doses of vaporized THC (1.29%) “provided statistically significant 30% reductions in pain intensity when compared to placebo.”
There is also strong evidence that the compound THCa is highly effective in treating pain. THCa is the more commonly known compound THC before it’s dried and burned. In this raw state, THCa is non-psychoactive and has anti-proliferative, anti-spasmodic, and anti-inflammatory properties. It’s anti-inflammatory properties are responsible for reducing the pain of ailments from arthritis to endometriosis and even menstrual cramps.
Dr. William Courtney of Mendocino County is leading a growing number of patients and caregivers who believe that THCa has numerous medicinal qualities that are lost when cannabis is dried. He is a proponent of juicing raw cannabis for its many health benefits from THCa, including the relief his wife, Kristen Peskuski, experiences from her chronic Lupus.
While more studies need to be conducted, there is plenty of evidence that cannabis is highly effective in moderating pain. These studies have shown that smoking, vaporizing, and taking administering oral cannabis can all reduce various kinds of pain.
Not all strains are equal
But just like there are many different varieties of pain, the varieties of cannabis strains are vast. With over 400 active pharmacological compounds found in cannabis that can be used to treat a range of ailments, there are countless ways to mix and match components and create specific strains to treat an array of ailments, and of course, all kinds of pain.
I mentioned earlier that cannabis is almost too good to be true, and this becomes even more apparent when you see how many of the compounds in cannabis can be used to treat various ailments. Active components such as cannabinoids work alongside terpenoids (also known as terpenes) and flavonoids to offer a multiplicity of benefits for the human body. Some of the active compounds that work to fight pain are CBC, CBD, CBG4, D9-THC, THCA-C4, THCYA, CBLA, CBNA, Linalool, and Myrcene. By combining a number of these cannabinoids, terpenes, and flavonoids, you can create the perfect pain relief solution in your own backyard. Or, of course you can go down to your friendly neighborhood dispensary (if you reside in a legalized state) and purchase one of these pain-fighting strains:
Strains that fight Analgesic Problems
For wounds, muscle, and back pain, try Afghan Kush. This strain is nearly all indica, which means its effects will mostly be physical. It has a high dosage of THC which is notorious for pain relief as well as a number of analgesic terpenes such as Humulene, Caryophyllene, and Terpinoline.
If you’re experiencing neuropathic chronic pain due to either tissue damage or damage to the central nervous system, then the strain Jack Herer might be a good option for you. This strain is mostly sativa and has an energizing effect. Like Afghan Kush, Jack Herer also features high levels of THC, but has a host of other compounds and terpenes that make this strain specifically beneficial for treating neuropathic pain such as Pinene, Myrcene, Caryophyllene, and Humulene.
If arthritis and inflammation is what’s getting you down, try Harlequin. Harlequin is very high in CBD which interacts with the CB2 receptors in our bodies. In one study, it was found that mice who didn’t have CB2 receptors have weaker bones. From this it was determined that CBD is very beneficial in treating symptoms of arthritis, particularly the inflammatory and pain parts. Harlequin features a 5 to 2 ratio of CBD to THC as well as other anti-inflammatory, pain-relieving compounds and terpenes, including CBC, CBG, Myrcene, and Pinene. It’s also interesting to note that CBD is not a psychoactive component like THC is, which means that you won’t get the trippy effects of the other two.
It is becoming more and more evident that cannabis is a natural pain reliever that doesn’t have any of the nasty effects of traditional pain medications. With more research and more push back against the federal ban on marijuana, we may soon see a day when prescribing various strains of cannabis is the norm for treating all varieties of pain.
Cannabinoids in the management of difficult to treat pain.
- GW Pharmaceuticals Vashon, WA, USA.
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. Tetrahydrocannabinol (THC, Marinol((R))) and nabilone (Cesamet((R))) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex((R)), a cannabis derived oromucosal spray containing equal proportions of THC (partial CB(1) receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB(1) receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.
As many as one in five Americans lives with chronic pain. Many of these people suffer from neuropathic pain (nerve-related pain) — a condition that is associated with numerous diseases, including diabetes, cancer, multiple sclerosis, and HIV. In most cases, the use of standard analgesic medications such as opiates and NSAIDS (non-steroidal anti-inflammatory drugs) is ineffective at relieving neuropathic pain. Further, long-term use of most conventional pain relievers, including acetaminophen, opioids, and NSAIDs, is associated with a host of potential adverse side effects, including dependence, heart-attack, liver damage, and accidental overdose death.
Survey data indicates that the use of cannabis is common among patients with chronic pain and patients who use it for this indication typically report it to be an effective treatment. Majorities further report that cannabis possesses fewer side effects than conventional pain medications and that it provides greater symptom management than opioids.
In addition to these anecdotal claims, numerous clinical trials report that inhaled marijuana alleviates neuropathic pain. A recent review identifies 35 controlled studies specific to the use of cannabis or cannabinoids in pain treatment, involving over 2,000 subjects. These include a pair of randomized, placebo-controlled clinical trials demonstrating that smoking cannabis reduces neuropathy in patients with HIV by more than 30 percent compared to placebo.[6-7] (Additional details on these studies appear in the HIV section of this publication.) A University of California at San Diego double-blind, placebo-controlled trial reported that inhaled cannabis significantly reduced capsaicin-induced pain in healthy volunteers. A University of California at Davis double-blind, randomized clinical trial reported both high and low doses of inhaled cannabis reduced neuropathic pain of diverse causes in subjects unresponsive to standard pain therapies. A McGill University study reported that smoked cannabis significantly improved measures of pain, sleep quality and anxiety in participants with refractory pain for which conventional therapies had failed. Another clinical trial reported that both inhaled cannabis and oral THC significantly decreased pain sensitivity and increased pain tolerance in healthy subjects exposed to experimental painful stimuli.
Clinical trials also report that vaporized cannabis is effective at mitigating pain. A 2013 FDA-approved trial assessing the impact of vaporized cannabis on neuropathic pain reported that even low doses of THC (1.29 percent) “provided statistically significant 30% reductions in pain intensity when compared to placebo.” A 2014 Israeli open-label clinical trial reported that the administration of a single dose of whole-plant cannabis via a thermal-metered inhaler was effective and well tolerated among patients suffering from nerve pain. Placebo-controlled data published in 2015 in The Journal of Pain further reported that vaporized cannabis provides “a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain.” A 2016 placebo-controlled trial in a cohort of 42 subjects with spinal injury neuropathy reported that vaporizing cannabis with low to moderate levels of THC elicited a “significant analgesic response” in study participants.
A review of these and other trials published in the British Journal of Clinical Pharmacology concluded, “[I]t is reasonable to consider cannabinoids as a treatment option for the management of chronic neuropathic pain with evidence of efficacy in other types of chronic pain such as fibromyalgia and rheumatoid arthritis as well.” A separate review published in The Clinical Journal of Pain further concluded, “Overall, based on the existing clinical trials database, cannabinergic pain medicines have been shown to be modestly effective and safe treatments in patients with a variety of chronic pain conditions. … Incorporating cannabinergic medicine topics into pain medicine education seems warranted and continuing clinical research and empiric treatment trials are appropriate.” Another review of the data similarly reports, “[C]annabinoids are safe [and] demonstrate a modest analgesic effect and provide a reasonable treatment option for treatment chronic non-cancer pain.” Most recently, a review of over 10,000 scientific studies by the National Academies of Sciences, Engineering, and Medicine concluded that whole-plant cannabis is effective for the treatment of chronic pain in adults. “In adults with chronic pain, patients who were treated with cannabis or cannabinoids are more likely to experience a clinically significant reduction in pain symptoms,” they determined.
Longitudinal trials have also shown cannabis therapy to be safe and effective for pain treatment. A one-year assessment of Canadian chronic pain patients reported that daily use of herbal cannabis was associated with sufficient safety and efficacy. Compared to controls, patients in the cannabis use group experienced a significant reduction in average pain intensity while reporting no increased risk of adverse cognitive or pulmonary events. Authors concluded: “[T]his study suggests that the adverse effects of medical cannabis are modest and comparable quantitatively and qualitatively to prescription cannabinoids. The results suggest that cannabis at average doses of 2.5g/d in current cannabis users may be safe as part of carefully monitored pain management program when conventional treatments have been considered medically inappropriate or inadequate.”
Preclinical data indicates that cannabinoids, when administered in concert with one another, are more effective at ameliorating neuropathic pain than the use of a single agent — a phenomenon sometimes referred to as the entourage effect. Investigators at the University of Milan have reported that the administration of single cannabinoids such as THC or CBD produce limited relief compared to the administration of plant extracts containing multiple cannabinoids, terpenes (oils), and flavonoids (pigments). Researchers concluded: “[T]he use of a standardized extract of Cannabis sativa … evoked a total relief of thermal hyperalgesia, in an experimental model of neuropathic pain, … ameliorating the effect of single cannabinoids.” … “Collectively, these findings strongly support the idea that the combination of cannabinoid and non-cannabinoid compounds, as present in [plant-derived] extracts, provide significant advantages in the relief of neuropathic pain compared with pure cannabinoids alone.” Other studies have reported similar results.
Cannabis dosing also permits some chronic pain patients to significantly reduce their use of opioids. A 2011 clinical trial assessing the administration of vaporized plant cannabis in chronic pain patients on a daily regimen of morphine or oxycodone reported that inhaled “cannabis augments the analgesic effect of opioids.” Authors concluded, “The combination (of opioids and cannabinoids) may allow for opioid treatment at lower doses with fewer side effects.” A 2016 Israeli clinical trial of intractable pain patients similarly reported that inhaled cannabis reduced symptom severity and also was associated with 44 percent overall reduction in subjects’ use of opiates. A separate University of Michigan study of 244 chronic pain subjects similarly reported that cannabis use led to a 64 percent decrease in opioid consumption. Patient survey data published in 2017 reported that 97 percent of respondents “strongly agreed/agreed” that they are able to decrease the amount of opioids they consume when they also use cannabis.”
In jurisdictions that permit medical cannabis access, patients are using fewer opioids. According to the findings of a 2015 National Bureau of Economic Research study, “[S]tates permitting medical marijuana dispensaries experience a relative decrease in both opioid addictions and opioid overdose deaths compared to states that do not. The NBER findings are similar to those published in 2014 in the Journal of the American Medical Association (JAMA) Internal Medicine which also reported that the enactment of statewide medicinal marijuana laws is associated with a 24.8 percent lower mean annual opioid overdose mortality rate compared with states without medical cannabis laws. A 2016 study produced by Castlight Health similarly reports that rates of unauthorized opiate use is significantly lower in medical cannabis jurisdictions. Incidences of opioid-related hospitalizations and traffic-related fatalities have also fallen, as have overall prescription drug spending. (For a comprehensive summary of relevant studies finding that legal cannabis access is associated with decreases in opioid use, abuse, hospitalization, and mortality, please see NORML’s fact-sheet, Relationship Between Marijuana and Opioids.) Consequently, some pain experts are now advising that physicians recommend cannabis therapy in addition to or in lieu of opiate medications to “reduce the morbidity and mortality rates associated with prescription pain medications.”
Role of Cannabinoids in Pain Management
Ethan B. Russo and Andrea G. Hohmann
Key Points Cannabinoids are pharmacological agents of endog-• enous (endocannabinoids), botanical (phytocannabinoids), or synthetic origin. Cannabinoids alleviate pain through a variety of • receptor and non-receptor mechanisms including direct analgesic and anti-inﬂ a mmatory effects, modulatory actions on neurotransmitters, and interactions with endogenous and administered opioids. Cannabinoid agents are currently available in various • countries for pain treatment, and even cannabinoids of botanical origin may be approvable by FDA, although this is distinctly unlikely for smoked cannabis.
An impressive body of literature supports cannabinoid • analgesia, and recently, this has been supplemented by an increasing number of phase I–III clinical trials.
Plants and Pain
I t is a curious fact that we owe a great deal of our insight into pharmacological treatment of pain to the plant world [ 1 ] . Willow bark from Salix spp. led to development of aspirin and eventual elucidation of the analgesic effects of prostaglandins
and their role in inﬂ a mmation. The opium poppy ( Papaver somniferum ) provided the prototypic narcotic analgesic morphine, the ﬁ rst alkaloid discovered, and stimulated the much later discovery of the endorphin and enkephalin systems. Similarly, the pharmacological properties of cannabis ( Cannabis sativa ) prompted the isolation of D 9- tetrahydrocannabinol (THC), the major psychoactive ingredient in cannabis, in 1964 [ 2 ] . It is this breakthrough that subsequently prompted the more recent discovery of the body’s own cannabis-like system, the endocannabinoid system (ECS), which modulates pain under physiological conditions. Pro-nociceptive mechanisms of the endovanilloid system were similarly revealed by phytochemistry of capsaicin, the pungent ingredient in hot chile peppers ( Capsicum annuum etc.), which activates transient receptor potential vanilloid receptor-1 (TRPV1). Additional plant products such as the mints and mustards activate other TRP channels to produce their physiological effects.
The Endocannabinoid System
There are three recognized types of cannabinoids: (1) the phytocannabinoids [ 3] derived from the cannabis plant, (2) synthetic cannabinoids (e.g., ajulemic acid, nabilone, CP55940, WIN55, 212-2) based upon the chemical structure of THC or other ligands which bind cannabinoid receptors, and (3) the endogenous cannabinoids or endocannabinoids. Endocannabinoids are natural chemicals such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) found in animals whose basic functions are “relax, eat, sleep, forget, and protect” [ 4 ] . The endocannabinoid system encompasses the endocannabinoids themselves, their biosynthetic and catabolic enzymes, and their corresponding receptors [ 5 ] . AEA is hydrolyzed by the enzyme fatty-acid amide hydrolase (FAAH) into breakdown products arachidonic acid and ethanolamine [ 6] . By contrast, 2-AG is hydrolyzed primarily by the enzyme monoacylglycerol lipase (MGL) into breakdown products arachidonic acid and glycerol [ 7 ] and to a lesser extent by the enzymes ABHD6 and ABHD12. FAAH, a postsynaptic enzyme, may control anandamide levels near sites of synthesis, whereas MGL, a presynaptic enzyme [ 8 ] , may terminate 2-AG signaling following CB 1 receptor activation. These enzymes also represent therapeutic targets because inhibition of endocannabinoid deactivation will increase levels of endocannabinoids at sites with ongoing synthesis and release [ 9 ] . The pathways controlling formation of AEA remain poorly understood. However, 2-AG is believed to be formed from membrane phospholipid precursors through the sequential activation of two distinct enzymes, phospholipase C and diacylglycerol lipase- a . First, PLC catalyzes formation of the 2-AG precursor diacylglycerol (DAG) from membrane phosphoinositides. Then, DAG is hydrolyzed by the enzyme diacylglycerol lipase- a (DGL- a ) to generate 2-AG [ 199 ]
Fig. 18.1 Putative mechanism of endocannabinoid-mediated retrograde signaling in the nervous system. Activation of metabotropic glutamate receptors ( mGluR) by glutamate triggers the activation of the phospholipase C ( PLC) -diacylglycerol lipase ( DGL) pathway to generate the endocannabinoid 2-arachidonoylglycerol ( 2-AG ). First, the 2-AG precursor diacylglycerol ( DAG ) is formed from PLC-mediated hydrolysis of membrane phospholipid precursors ( PIPx ). DAG is then hydrolyzed by the enzyme DGL- a to generate 2-AG. 2-AG is released from the postsynaptic neuron and acts as a retrograde signaling m olecule. Endocannabinoids activate presynaptic CB 1 receptors which reside on terminals of glutamatergic and GABAergic neurons. Activation of CB 1 by 2-AG, anandamide, or exogenous cannabinoids (e.g., tetrahydrocannabinol, THC ) inhibits calcium in ﬂ ux in the presynaptic terminal, thereby inhibiting release of the primary neurotransmitter
(i.e., glutamate or GABA) from the synaptic vesicle. Endocannabinoids are then rapidly deactivated by transport into cells (via a putative endocannabinoid transporter) followed by intracellular hydrolysis. 2-AG is metabolized by the enzyme monoacylglycerol lipase ( MGL ), whereas anandamide is metabolized by a distinct enzyme, fatty-acid amide hydrolase ( FAAH ). Note that MGL co-localizes with CB 1 in the presynaptic terminal, whereas FAAH is localized to postsynaptic sites. The existence of an endocannabinoid transporter remains controversial. Pharmacological inhibitors of either endocannabinoid deactivation (e.g., FAAH and MGL inhibitors) or transport (i.e., uptake inhibitors) have been developed to exploit the therapeutic potential of the endocannabinoid signaling system in the treatment of pain (Figure by authors with kind assistance of James Brodie, GW Pharmaceuticals)
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