Analgesia

Analgesia is the medical term for pain relief. Medical research emphasizes the need for increased treatment of chronic and incurable pain. New models of pain clarify understanding. We now know that injured tissue sprouts new nerve fibers with even greater sensitivity to pain, a condition known as hyperalgia. [1] This increased level of sensitivity to pain after injury is a natural biological response that cannot be ignored. Sadly, the complaints of ill and aged people all too often go unanswered. A study of elderly cancer patients in nursing homes discovered that many cases are severely under-treated for pain relief. Of 4,003 cases studied, 26% received no pain medication at all, not even aspirin. [2] A similar finding that as many as 50% of all pain cases are under-treated prompted American medical experts to call for a “war on pain” with greater use of opiate painkillers. [3] In 1998, the Journal of the American Medical Association concluded that under-treatment of pain “is no longer acceptable and should be considered a first-line indicator of poor quality medical care.” [4] The US Drug Enforcement Administration (DEA) is also in support of the “war on pain,” actively endorsing and encouraging the use of “in particular, narcotic analgesics [that] may be used in the treatment of pain experienced by a patient with a terminal illness or chronic disorder.” [5] Physicians remain wary, however, due to the recent rise in government scrutiny of prescription practices. (Fishman 2006)

Regardless of the mixed messages sent by federal regulators, analgesic drugs have some seriously adverse side effects, including headaches, nausea, addiction, loss of coordination, deep sedation, severe gastrointestinal disturbances, liver disease, kidney disease, and death. In fact, as The New England Journal of Medicine points out:

It is also hypocritical to forbid physicians to prescribe marijuana while permitting them to use morphine and meperidine [Demerol], to relieve extreme dyspnea [shortness of breath] and pain. With both these drugs the difference between dose that relieves symptoms and the dose that hastens death is very narrow; by contrast, there is no risk of death from smoking marijuana. [6]

A poll taken by ABC News in 2005 indicated that 19% of adults in the US (38 million people) have chronic pain and 6% (12 million) have used cannabis to relieve their pain. Pain specialists note difficulties managing intractable (incurable) pain caused by cancer, neuropathy, as well as central nervous system pain caused by multiple sclerosis. conditions which are known to be inadequately treated by opiates and other pharmeceutical pain medications. [7] "For exploratory purposes, any patient with pain unrelieved by conventional analgesics should have access to medical marijuana if they so desire." (Hollister, 2000) A survey of patients at the Oakland Cannabis Buyer's Co-op in California shows that 46% of those patients use marijuana for pain relief. Modern understandings found in endocannabinoid physiology offer new hope to many, but the federal war on medical cannabis remains a serious concern to patients and physicians in most parts of the nation.

There greater share of historical reference to cannabis in medicine generally describe its analgesic actions. Specific citations on pain relief are common in most antiquated medical texts. [8], [9] Migraine headaches and neuralgic pain were treated with cannabis preparations in India as early as the sixth century AD. [10} Modern research has verified those historical observations. Cannabinoids are effective in treating intractable pain caused by a variety of conditions. In 1974, noted researchers Noyes and Baram studied five case histories and concluded, “There are indications that the active ingredient in marijuana may be a mild, though effective analgesic that is efficacious in functional pain.” [11] The anti-inflammatory effects of THC, the most prominent cannabinoid found in cannabis plants, have been demonstrated in laboratories since the early 1970's. In 1991 THC was cited to have 20 times the anti-inflammatory potency of aspirin and twice that of hydrocortisone. [12] But other cannabinoids are shown to have particular anti-inflammitory actions as well. Cannflavin A and B, compounds unique to cannabis, inhibit inflammation in human rhematoid cells 30 times better than aspirin. [13] "The activity of cannabichromene through the oral route, its safety and its lack of behavioral-type (psychotomimetic) activity characteristic of THC indicate its therapeutic potential for the treatment of inflammitory diseases." (Turner and Elsohly, 1981)

Cannabis is known to contain several other effective cannabinoid and noncannabinoid compounds that reduce painful inflammation. [14] A 1988 study found that cannabidiol, a cannabinoid not found in Marinol tablets, was also more effective than aspirin in reducing inflammation. [15] Another paper, entitled “Delta-9-tetrahydrocannabinol Shows Antispastic And Analgesic Effects in A Single Case Double Blind Trial,” reached a similar conclusion. [16] Research by the University of London School of Pharmacy also indicated that cannabinoids are not only effective pain relievers but would also be useful in the treatment of certain inflammatory disorders. [17] In 2008 the National Academy of Sciences published a report on a little-studied non-psychoactive compound found in cannabis, beta-caryophyllene, that binds with CB2 receptors located in the body, not the brain. beta-caryophyllene is shown to provide pronounced reduction of inflammation, providing a new and novel pathway to treat the pain of swelling and inflammation. [18]

Other cannabinoids are also receiving attention for their great potential to reduce pain. In November 1997, Dr. Ian Meng reported to the public on research he had recently presented at the Society for Neuroscience meeting in October, “A synthetic marijuana-like drug called WIN 55212 enhances the brain’s ability to suppress pain in rats, and probably in humans as well.” In an interview on the subject, Meng elucidated the findings of his research team:

People know that they [cannabinoids] are analgesic. But until fairly recently it hasn’t been proven in animal studies that cannabinoids affect sensation . . . I can actually look at the electrical impulses that travel down neurons to tell me how active a cell is. By doing that we’ve been able to show it’s not just motor effects; this cannabinoid has bery specific sensory effects. It affects the neurons in the pain pathway. [19]

The powerful opiate morphine relaced cannabis for the treatment of pain in the late 1800s, but now, 100 years later, moder research promises to reinstate cannabinoids as the premier relievers of physical pain. In that same 1997 Society for Neuroscience conference, researchers from eight respected universities, Wake Forest University Medical School, the University of Michigan Medical School, the University of California at San Francisco (Meng et al.), Brown University, the University of Minnesota, and the University of Texas, each presented their individual evidence demonstrating that cannabinoids have a direct effect on biochemical pain signals in the central nervous system. Scientists reported that these cannabinoid studies reveal the potential for a new class of pain-control drugs suprtior to addictive opiate-based narcotics. Cannabinoids were shown to reduce pain through the central nervous system and also prevent the condition of hyperalgia, increased sensitivity to pain caused by injury. Scientists believe, therefore, that cannabinoids may be particularly effective in the treatment of arthritic pain. [20], [21]

Researchers at the Medical College of Virginia reported that the presence of cannabinoid binding sites in the nervous system indicates that naturally occurring cannabinoids may govern the body’s basic threshold of pain. [22] Research by the American Association for the Advancement of Science has produced similar findings. [23] Some scientists believe that cannabis is a more effective pain killer that opiates because the number of cannabinoid receptor sites found in the spinal cord is 10 to 50 times greater than the number of opiate receptors. [24]

A 1998 Nature article detailed how anandamide receptors located outside the central nervous system are crucial to pain control in cases of injury. Also in 1998, studies at UCSF by Meng et al. showed that THC and morphine both affect the same cranial nerves located at the base of the skull. These studies were the first published evidence that cannabis has analgesic actions that work directly on the brain. [25]

When interviewed on cannabinoid analgesia, Dr. Ken Mackie, Professor of Anesthesiology at the University of Washington, replied, “Yes, marijuana does ease pain. As an analgesic, it is about as efficacious as codeine.” [27] Dr. Donald Abrams, Director of HIV Research at San Francisco General Hospital, explained why cannabis is actually superior to many common pharmaceutical painkillers:

"Cananbinoid-induced analgesia appears linked to the same system by which opioids [synthetic narcotics] produce pain relief. But different from opioids, cannabinoids are also effective in a rat model of neuropathic pain, which means pain cased by nerves. For those of us that care for people with HIV—we know about the painful, peripheral neuropathy they get—very painful numb tingling feet. We often start these patients on a trial of drugs that lead ultimately to morphine, because there isn’t anything effective." [26]

Dr. Abrams conducted a valuable human study of 50 HIV patients who used smoked marijuana cigarettes three times per day. Subjects showed positive results in daily pain, hyperalgesia, and a 30% reduction in pain. [27]

A research paper fone at Hammersmith Hospital in London confirmed cannabis’ analgesic effects in the first UK clinical trial. The paper’s abstract began, “Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their clinical use has been restricted by legislation.” That same abstract calling for further studies concluded, “Cannabis naïve patients would tolerate investigations but may generate medicolegal problems.” [28]

The use of cannabis for pain relief was widespread in the membership of legitimate medical marijuana groups under attack by the US government. [29] In 1998, federal law enforcers closed San Francisco Bay Area Cannabis Clubs, forcing over 10,000 seriously ill patients to support nefarious “street” sources and pay outrageous black market prices for non-medical grade marijuana. In the following year, the government sponsored Institute of Medicine report elevated pain relief to the top of the list of marijuana’s medical benefits. [30]

Due to cannabis prohibition and the bias of research regulation by the National Institutes on Drug Abuse, human studies of the pain relieving qualities of cannabis are limited. Grotenherman writes: " Few clinical studies of cannabinoids in painful conditions exist. In two trials, oral THC proved to be effective against cancer pain in doses of 15 and 20 mg, respectively. However, some patients experienced intolerable side effects. In a single case double-blind study a patient with familial Mediterranean fever clearly reduced his need for opiates while receiving THC (50 mg per day divided in five doses) in comparison to placebo."[31]

However, the fascinating new view of the body's endocannabinoid systems provide ample scientific evidence to justify the widespread popularity of cannabis as an analgesic, partivcularly in cases of nerve or neurological pain. Consider the following excerpts from a recent paper titled “Mechanisms of Cannabinoid Analgesia”:

“Within the central nervous system, cannabinoids, like opioids, act at both spine (intrathecal) and supraspinal (intracerebroventricular) levels to produce analgesia. Cannabinoid-induced analgesia is not mediated by opioid receptors because it is unaffected by opioid antagonists. However, cannabinoid and opioid agonists have synergistic analgesic affects.”

“In vivo electrophysiological studies indicate that, like opioids, cannabinoids suppress the activity of neurons involved in the ascending transmission of nociceptive information. Systemic administration of cannabinoid agonists inhibits noxious stimulus-evoked firing in neurons of the spinal cord dorsal horn and thalamus. Cannabinoids also inhibit windup (a neuronal correlate of hyperalgesia), which is the augmentation of the response of spinal neurons to repetitive noxious electrical stimuli.”

“It is now becoming apparent that, like opioids, cannabinoids act via specific receptors within pain pathways to produce analgesia. The distinct anatomical receptors within pain pathways suggests that they may be useful for management of different pain sites. The distinction between cannabinoids and opioids is emphasized by more recent electrophysiological studies and provides a cellular basis for their synergistic analgesic actions. These findings suggest that cannabinoids warrant urgent study as therapeutic agents, particularly with the emergence of novel cannabinoid drugs.”[32]

IN 2008, i nvestigators at the University of California at Davis, in conjunction with the University of California Center for Medical Cannabis Research (CMCR), assessed the efficacy of inhaled cannabis on pain intensity among 38 patients with central and/or peripheral neuropathic pain in a randomized, placebo-controlled, crossover trial. Researchers reported that smoking low-grade (3.5 percent THC) and mid-grade (7 percent THC) cannabis equally reduced patients’ perception of spontaneous pain.

They concluded: "In the present experiment, cannabis reduced pain intensity and unpleasantness equally. Thus, as with opioids, cannabis does not rely on a relaxing or tranquilizing effect, but rather reduces both the core component of nociception (nerve pain) and the emotional aspect of the pain experience to an equal degree."

The study is the second clinical trial conducted by CMCR investigators to conclude that inhaled cannabis significantly reduces chronic neuropathy, a condition that is typically unresponsive to both opioids and non-steroidal anti-inflammatory drugs such as ibuprofen.[33]

GW Pharmeceuticals is a company that has isolated canabinoid compounds in arosol sprays for medical use.  Another recent study shows that GW's product, Sativex,  sowed remarkable value in trating neuropathic pain.  Forty-one patients with multiple sclerosis and central neuropathic pain completed the double blind, placebo-controlled "randomized withdrawal" study. Volunteers in the study were administered either Sativex or a placebo daily for four weeks following their long-term use of the cannabis spray.  Previous trials of Sativex have reported that patients required fewer daily doses of the drug and reported lower median pain scores the longer they took it.[34]

Recent studies have located and determined exact mechanisms of cannabis analgesia through the body's endocannabinoid receptors.  The following is an excert from "Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy" from theInperial College of Science in London:

"Local administration, peptide release and electrophysiological studies support the concept of spinally mediated endocannabinoid-induced analgesia. Whilst a proportion of the peripheral analgesic effect of endocannabinoids can be attributed to a neuronal mechanism acting through CB(1) receptors expressed by primary afferent neurones, the antiinflammatory actions of endocannabinoids, mediated through CB(2) receptors, also appears to contribute to local analgesic effects." [35]

 Related sections: Addiction, Arthritis, Neuralgia, Psychoactivity, Replacement of Medications

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[1] “Doctor urges war on pain, more use of opium-based drugs.” Miami Hearald, January 29, 1998

[2] Stolberg, “Study Finds Elderly Receive Little Pain Treatment in Nursing Homes.” June 17, 1998

[3] “Doctor urges war on pain, more use of opium-based drugs.” Miami Hearald, January 29, 1998

[4] “Researchers say many cancer patients suffer needless pain.” Associated Press, June 17, 1998

[5] Drug Enforcement Administration, “Statement of policy for the use and handling of controlled substances in the treatment of pain.” 1998

[6] Kassirer, “Federal foolishness and marijuana.” Editorial, The New England Journal of Medicine, January 30, 1997

[7] Russo "Cannabinoids in the management of difficult to treat pain" Therapeutics and Clinical Risk Management" 2008-4(1) 245-259

[8] Mikuriya, Marijuana Medical Papers: 1839-1972. Oakland: Medi-comp Press, 1973

[9] Grinspoon, Marijuana Reconsidered. 3^rd ed. San Francisco: Quick American Archives, 1971

[10] Russo, "The Role of Cannabis and Cannabinoids in Pain Management" Weiner's Pain Mnagement Guide, 7th ed. American Academy of Pain Management 2006

[11] Noyes and Baram, “Cannabis analgesia.” Comprehensive Psychiatry. Vol. 15, No. 6, 1974

[12] Beltramo and Piomelli, “Functional role of high-affinity anandamide transport, as revealed by selective inhibition.” Science, Vol. 277, No. 5329, p1094(4), 1997

[13] Russo, "The Role of Cannabis and Cannabinoids in Pain Management" Weiner's Pain Mnagement Guide, 7th ed. American Academy of Pain Management 2006

[14] Formukong, Evans, and Evans, “Analgesic and anti-inflammatory activity of constituents of cannabis sativa L.” Inflammation, Vol. 12, No. 4, pp.361-371, 1988

[15] Maurer, Henn, Dittrich, and Hoffman, “Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double blind trial.” European Archive of Psychiatry and Neurological Science. Vol. 240, No. 1, pp. 1-4, 1990

[16] “Cannabidiol, Wonder drug of the 21^st century?” Source: Schaffer Library of Drug Policy, www.druglibrary.org

[17] “Pre-clinical studies show CT-3 reduces chronic and acute inflammation and reduces destruction of joints.” BW HealthWire, January 1998

[18] "Curative Leaf - Compound in marijuana reduces inflammation without the psychological effects", Amy Maxmen, Science News, June 23rd, 2008, www.sciencenews.com

[19] “Medical marijuana: Doing the science.” Synapse, 1998, www.itsa.ucsf.edu/synapse/

[20] Symposium Syllabus, Functional Role of Cannabinoid Receptors. Press Conference, August 26, 1998, Source: Medical Marijuana Magazine, www.marijuanamagazine.com

[21] “Study reveals pot chemicals can relieve serious pain.” Los Angeles Times, October 27, 1998

[22] Ibid.

[23] Morin, “Research into cannabinoids provides evidence that the use of marijuana to treat pain and nausea should not e so easily dismissed.” May 1998, Source: Morin@Brown.edu

[24] Cowen, “Science journal reports that cannabinoid receptors located outside the brain and spine are affected when the skin or flesh is cut or hurt.” July 16, 1998, www.marijuananews.com

[25] Widener, “Study: Marijuana, morphine work on same area of brain.” The Seattle Times, September 25, 1998

[26] “Diagnosis: Smoke Pot to Relieve Pain.” The University of Washington Daily, May 1997

[27] Abrams, Lindesmith Center Lecture, San Francisco, May 17, 1999

[28] Holdcroft et al., “Pain relief with oral cannabinoids in familial Mediterranean fever.” Anesthesia, Vol. 52, No. 5, pp. 483-486, May 1997

[29] San Francisco Chronicle, San Francisco Examiner, Associated Press, May 1998

[30] Institute of Medicine: Marijuana and Medicine: Assessing the Science Base. Washington DC: National Academy Press

[31] Grotenhermen, “Review of Therapeutic Effects.” Chapter 11, p. 126-128 (see Absracts and Studies section of this website)

[32] Vaughn and Christie, “Mechanisms of Cannabinoid Analgesia.” Chapter 8, p. 90-95

[33] Inhaled Cannabis Reduces Central And Peripheral Neuropathic Pain, Study Says, NORML News, May 3rd, 2008 See: www.NORML.org

[34] Cannabis Spray Demonstrates Long Term Efficacy In Neuropathic Pain, Study Says, NORML News, 9/11/08, See: www.NORML.org 

[35] “Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy”, Rice AS, Farquhar-Smith WP, Nagy I., Department of Anaesthetics, Pain Research Group, Inperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital Campus, 369 Fulham Road, London SW10 9NH, UK. a.rice@ic.ac.uk