Aging and Medical Marijuana

A Note from Americans for Safe Access

We are committed to ensuring safe, legal availability of marijuana for medical uses. This brochure is intended to help doctors, patients and policymakers better understand how marijuana-or "cannabis" as it is more properly called-may be used as a treatment for people with serious medical conditions. This booklet contains information about using cannabis as medicine. In it you'll find information on:

Why Cannabis is Legal to Recommend

Overview of the Scientific Research on Medical Cannabis

Cannabis and Arthritis

Cannabis and Chronic Pain

Cannabis and Cancer

Cannabis and Movement Disorders

Cannabis and Neurological Disorders

Comparison of Medications: Efficacy and Side-Effects

Why Cannabis is Safe to Recommend

Testimonials of Patients and Doctors

History of Cannabis as Medicine

Scientific and Legal References

We recognize that information about using cannabis as medicine has been difficult to obtain. The federal prohibition on cannabis has meant that modern clinical research has been limited, to the detriment of medical science and the wellness of patients. But the documented history of the safe, medical use of cannabis dates to 2700 B.C. Cannabis was part of the American pharmacopoeia until 1942 and is currently available by prescription in the Netherlands and Canada.

Testimonials from both doctors and patients reveal valuable information on the use of cannabis therapies, and supporting statements from professional health organizations and leading medical journals support its legitimacy as a medicine. In the last few years, clinical trials in Great Britain, Canada, Spain, Israel, and elsewhere have shown great promise for new medical applications.

This brochure is intended to be a starting point for the consideration of applying cannabis therapies to specific conditions; it is not intended to replace the training and expertise of physicians with regard to medicine, or attorneys with regard to the law. But as patients, doctors and advocates who have worked intimately with these issues for many years, we have seen firsthand how helpful cannabis can be for a wide variety of indications. We know doctors want the freedom to practice medicine and patients the freedom to make decisions about their healthcare. For more information, please see AmericansForSafeAccess.org or call 1-888-929-4367.

Is Cannabis Legal to Recommend?

In 2004, the United States Supreme Court upheld earlier federal court decisions that doctors have a fundamental Constitutional right to recommend cannabis to their patients.

The history. Within weeks of California voters legalizing medical cannabis in 1996, federal officials had threatened to revoke the prescribing privileges of any physicians who recommended cannabis to their patients for medical use.[1] In response, a group of doctors and patients led by AIDS specialist Dr. Marcus Conant filed suit against the government, contending that such a policy violates the First Amendment.[2] The federal courts agreed at first the district level,[3] then all the way through appeals to the Ninth Circuit and then the Supreme Court.

What doctors may and may not do. In Conant v. Walters,[4] the Ninth Circuit Court of Appeals held that the federal government could neither punish nor threaten a doctor merely for recommending the use of cannabis to a patient.[5] But it remains illegal for a doctor to "aid and abet" a patient in obtaining cannabis.[6] This means a physician may discuss the pros and cons of medical cannabis with any patient, and issue a written or oral recommendation to use cannabis without fear of legal reprisal.[7] This is true regardless of whether the physician anticipates that the patient will, in turn, use this recommendation to obtain cannabis.[8] What physicians may not do is actually prescribe or dispense cannabis to a patient[9] or tell patients how to Angel Raich & Dr. Frank Lucido use a written recommendation to procure it from a cannabis club or dispensary.[10] Doctors can tell patients they may be helped by cannabis. They can put that in writing. They just can't help patients obtain the cannabis itself.

Patients protected under state, not federal, law. In June 2005, the U.S. Supreme Court overturned the Raich v. Ashcroft Ninth Circuit Court of Appeals decision. In reversing the lower court's ruling, Gonzales v. Raich established that it is legal under federal law to prosecute patients who possess, grow, or consume medical cannabis in medical cannabis states. However, this Supreme Court decision does not overturn or supersede the laws in states with medical cannabis programs.

For assistance with determining how best to write a legal recommendation for cannabis, please contact ASA at 1-888-929-4367.

Scientific Research Supports Medical Cannabis

Between 1840 and 1900, European and American medical journals published more than 100 articles on the therapeutic use of the drug known then as Cannabis Indica (or Indian hemp) and now simply as cannabis. Today, new studies are being published in peer-reviewed journals that demonstrate cannabis has medical value in treating patients with serious illnesses such as AIDS, glaucoma, cancer, multiple sclerosis, epilepsy, and chronic pain.

The safety of the drug has been attested to by numerous studies and reports, including the LaGuardia Report of 1944, the Schafer Commission Report of 1972, a 1997 study conducted by the British House of Lords, the Institutes of Medicine report of 1999, research sponsored by Health Canada, and numerous studies conducted in the Netherlands, where cannabis has been quasi-legal since 1976 and is currently available from pharmacies by prescription.

Recent published research on CD4 immunity in AIDS patients found no compromise to the immune systems of patients undergoing cannabis therapy in clinical trials[11].

The use of medical cannabis has been endorsed by numerous professional organizations, including the American Academy of Family Physicians, the American Public Health Association, and the American Nurses Association. Its use is supported by such leading medical publications as The New England Journal of Medicine and The Lancet.

Recent Research Advances

While research has until recently been sharply limited by federal prohibition, the last few years have seen rapid change. The International Cannabinoid Research Society was formally incorporated as a scientific research organization in 1991with 50 members; as of 2010, there are nearly 500 around the world. The International Association for Cannabis as Medicine (IACM), founded in March 2000, publishes a bi-weekly bulletin and holds international symposia to highlight emerging research in cannabis therapeutics. In 2001, the State of California established the Center for Medicinal Cannabis Research to coordinate an $8.7million research effort at University of California campuses. As of 2010, the CMCR had completed six of 14 approved studies. Of those, five published double-blind, placebo-controlled studies studied pain relief; each showed cannabis to be effective.

In the United Kingdom, GW Pharmaceuticals has been conducting clinical trials with its cannabis-based medicine for the past decade. GW's Phase II and Phase III trials of cannabis-based medicine show positive results for the relief of neurological pain related to: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury (including peripheral neuropathy secondary to diabetes mellitus or AIDS), central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident, and spina bifida. They have also shown cannabinoids to be effective in clinical trials for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury.

As of December 2010, the company has obtained regulatory approval in Spain, New Zealand, and the UK for Sativex® Oromucosal Spray, a controlled-dose whole-plant extract. Sativex® was approved in Canada for symptomatic relief of neuropathic pain in 2005, in 2007 for patients with advanced cancer whose pain is not fully alleviated by opiods, and in 2010 for spasticity related to multiple sclerosis. Sativex has been made available either for named patient prescription use or for clinical trials purposes in a total of 22 countries.

In the US, GW was granted an import license for Sativex® by the DEA following meetings in 2005 with the FDA, DEA, the Office for National Drug Control Policy, and the National Institute for Drug Abuse. Sativex® is currently an investigational drug in FDA-approved clinical trials as an adjunctive analgesic treatment for patients with advanced cancer whose pain is not relieved by opioids.

CANNABIS AND AGING

Cannabis has been found to help many patients suffering from conditions that afflict older patients, including arthritis, chronic pain, cancer, Alzheimer's disease, diabetes, and spasticity associated with such diseases as Parkinson's.

Cannabis and Arthritis

More than 31 million Americans suffer from arthritis. There are two main types of arthritis: rheumatoid arthritis and osteoarthritis. Both affect the joints, causing pain and swelling, and limiting movement.

Rheumatoid arthritis (RA) is caused by a malfunction of the immune system. Instead of fighting off intruders such as bacteria or viruses, the body attacks the synovial membranes, which facilitate the movement of joints, eventually destroying cartilage and eroding bones. Rheumatoid arthritis is most common among the aged, whose immune systems are no longer as robust or efficient as they were when younger.

Osteoarthritis (OA), or arthritis of the bones, is also found primarily among the elderly, where cartilage has been worn away through many years of use. Arthritis may also manifest as chronic inflammation of the joints as the result of injuries. OA is the most common form of arthritis, affecting more than 10 million people worldwide. Currently, no drugs are available to treat or modify this disease, and treatment is primarily focused around the use of pain killers, which often have limited benefits and hazardous side effects.

An important aspect of arthritis pathology relates to maintaining healthy bone. As people age, bones undergo extensive remodelling, which can lead to destruction or functional degradation of synovial joints. Drugs which can not only modulate pain from arthritis but also protect bones are of great importance.

Cannabis and cannabinoids represent a promising treatment which can reduce arthritic pain and inflammation and positively modulate bone growth and maintenance. It has already been demonstrated that cannabinoids can effectively treat some types of arthritic pain, but recent evidence suggests that the cannabinoids are also important for bone growth and maintenance throughout life.[12-17]

The importance of cannabinoids in bone health has been established in trans genic mice that are missing either the CB1 or CB2 receptor. These mice develop osteoporosis much more quickly than normal or wild mice. Research has recently shown that mice missing both cannabinoid receptors have extremely weak bones, a condition that underlies osteoporosis and osteoarthritis pathology.[18-20]

Based on genetic screening techniques, a correlation between cannabinoids and bone is emerging in humans as well. Three studies in three distinct ethnic groups have demonstrated that mutations in the type 2 cannabinoid receptor correlate to bone diseases. One study even showed that hand bone strength weakness is very well correlated with dysfunctional/mutant CB2 receptors.

Arthritis of any type can be an extremely painful and debilitating condition that presents challenges for pain management. The use of cannabis as a treatment for musclo-skeletal pain in western medicine dates to the 1700s.[21-22] Evidence from recent research suggests that cannabis-based therapies are effective in the treatment of arthritis and the other rheumatic and degenerative hip, joint and connective tissue disorders. Since these are frequently extremely painful conditions, the well-documented analgesic properties of cannabis make it useful in treating the pain associated with arthritis, both on its own and as an adjunct therapy that substantially enhances the efficacy of opioid painkillers.

Cannabis has also been shown to have powerful immune-modulation and antiinflammatory properties,[23-26] suggesting that it could play a role not just in symptom management but treatment of arthritis. In fact, one of the earliest records of medical use of cannabis, a Chinese text dating from ca. 2000 BC, notes that cannabis "undoes rheumatism," suggesting its anti-inflammatory and immune modulating effects were known even then[27].

Modern research on cannabidiol (CBD), one of the non-psychoactive cannabinoid components of cannabis, has found that it suppresses the immune response in mice and rats that is responsible for a disease resembling arthritis, protecting them from severe damage to their joints and markedly improving their condition.[28-29]

Human studies have repeatedly shown cannabis to be an effective treatment for rheumatoid arthritis, and it is one of the enumerated conditions for which many states allow legal medical use. Cannabis has a demonstrated ability to improve mobility and reduce morning stiffness and inflammation. Research has also shown that patients are able to reduce their usage of potentially harmful NonSteroidal Anti-Inflammatory drugs (NSAIDs) when using cannabis as an adjunct therapy.[30-31]

Medical researchers at Hebrew University in Jerusalem found that when cannabidiol is metabolized, one result is the creation of a compound with potent anti-inflammatory action comparable to the drug indomethacin, but without the considerable gastrointestinal side effects associated with that drug.[32]

In addition, when the body metabolizes tetrahydrocannabinol (THC), one of the primary cannabinoid components of cannabis, it produces a number of related chemicals. At least one of these metabolites has anti-inflammatory and painrelieving effects. By modifying this metabolite, researchers have produced a synthetic carboxylic acid known as CT-3 (also calleddimethylheptyl-THC-11 oic acid or DMH-11C ), which is more powerful than the natural metabolite itself, and thus can be given in smaller doses. Animal tests found CT-3 effective against both chronic and acute inflammation, and it also prevented destruction of joint tissue from chronic inflammation.

The remarkable 5,000-year safety record of cannabis-there has never been a recorded death from an overdose-and the fact that a metabolite with the desired anti-inflammatory effect is produced in the body when cannabis is used, indicates that the development of targeted, safe, and effective antiinflammatory drugs in this class are possible.[33] CT3 has also demonstrated considerable analgesic effects in animals. In some cases, the dose-dependent effect of THC was equivalent to morphine, but with a much greater duration of action and far less toxicity[34-35].

In contrast to the NSAIDs commonly prescribed arthritis sufferers, CT3 did not cause ulcers at therapeutically effective doses. Moreover, it does not depress respiration, produce dependence, induce body weight loss, or cause mutations, as many commonly prescribed drugs do. Studies on its mechanism of action are currently underway, with cytokine synthesis one of the pathways being studied.[36]

Cannabis may also help combat rheumatoid arthritis through its well-recognized immune-modulation properties.[37] Rheumatoid arthritis is characterized by dysregulation of the immune system in response to an initial infection or trauma. Over-activity of the immune system's B-cells causes antibodies to attack and destroy the synovial tissues located in the joint.

The immuno-modulatory properties of a group of fats found in cannabis, known as sterols and sterolins, have been used as natural alternatives to conventional rheumatoid arthritis treatments that employ highly toxic drugs to either suppress the entire immune response of the body or to palliate pain and the inflammatory process without correcting the underlying immune dysfunction.

Cytokines play a role in either fuelling or suppressing the inflammation that causes damage in rheumatoid arthritis and some other diseases. The release of selected cytokines is impaired by cannabis, but the findings differ by cell type, experimental conditions, and especially the concentration of the cannabinoids examined.[38-41] A sterol/sterolin combination has been experimentally demonstrated to reduce the secretion of the pro-inflammatory cytokines controlled by the TH2 helper cells and to increase the number of TH helper cells that regulate the secretion of antibodies from the B cells. This selective activation and inhibition of the immune system results is an effective control of the dysfunctional autoimmune response.

Similarly, ajulemic acid (another non-psychoactive cannabinoid) has been found to reduce joint tissue damage in rats with adjuvant arthritis.[42] Tests on human tissue done in vitro showed a 50% suppression of one of the body's chemicals (interleukin-1beta) central to the progression of inflammation and joint tissue injury in patients with rheumatoid arthritis[43].

Cannabis and Chronic Pain

Persistent and disabling pain can have numerous and sometimes multiple causes. Among them are cancer; AIDS; sickle cell anemia; multiple sclerosis; defects or injuries to the back, neck and spinal cord; arthritis and other rheumatic and degenerative hip, joint and connective tissue disorders; and severe burns. Pain is not a primary condition or injury, but rather a severe, frequently intolerable symptom that varies in frequency, duration, and severity according to the individual. The underlying condition determines the appropriate curative approach, but does not determine the proper symptom management. It is the character, severity, location and duration of the pain that determines the range of appropriate therapies.

Chronic pain is a public health issue that is widespread across the aging populations of industrialized nations. Epidemiological statistics are alarming: In Europe, it is estimated that one in four adults has a chronic pain condition.[44] In the US, it is estimated that at least 38 million adults suffer from chronic pain, and at least 12 million have used cannabis as a treatment.

For patients in pain, the goal is to function as fully as possible by reducing their pain as much as possible, while minimizing the often-debilitating side effects of the pain therapies. Failure to adequately treat severe and/or chronic pain can have tragic consequences. Not infrequently, people in unrelieved pain want to die. Despair can also cause patients to discontinue potentially life-saving procedures (e.g., chemotherapy or surgery), which themselves cause severe suffering. In such dire cases, anything that helps to alleviate the pain will prolong these patients' lives.

Cannabis can serve at least two important roles in safe, effective pain management. It can provide relief from the pain itself (either alone or in combination with other analgesics), and it can control the nausea associated with taking opioid drugs, as well as the nausea, vomiting and dizziness that often accompany severe, prolonged pain.

Opioid therapy is often an effective treatment for severe pain, but all opiates have the potential to induce nausea. The intensity and duration of this nausea can cause enormous discomfort and additional suffering and lead to malnourishment, anorexia, wasting, and a severe decline in a patient's health. Some patients find the nausea so intolerable that they are inclined to discontinue the primary pain treatment, rather than endure the nausea.

Inhaled cannabis provides almost immediate relief for this with significantly fewer adverse effects than orally ingested Marinol. Inhalation allows the active compounds in cannabis to be absorbed into the blood stream with greater speed and efficiency. It is for this reason that inhalation is an increasingly common, and often preferable, route of administration for many medications. Cannabis may also be more effective than Marinol because it contains many more cannabinoids than just the THC that is Marinol's active ingredient. The additional cannabinoids may well have additional and complementary antiemetic qualities. They have been conclusively shown to have better paincontrol properties when taken in combination than THC alone.

Research on cannabis and pain management

Cannabis has been used as an analgesic for thousands of years[45-47] and patients often report significant pain relief from cannabis, even in cases where conventional pain therapies have failed[48-53].

After reviewing a series of trials in 1997, the U.S. Society for Neuroscience concluded that "substances similar to or derived from marijuana could benefit the more than 97 million Americans who experience some form of pain each year."[54] A 1999 study commissioned by the White House and conducted by the Institute of Medicine recognized the role that cannabis can play in treating chronic pain.[55]

"After nausea and vomiting, chronic pain was the condition cited most often to the IOM study team as a medicinal use for marijuana." From 1975 to February 2011, there have been nearly 300 studies showing that cannabinoids and cannabis can help patients experiencing chronic pain.[56, 57]

Some of the most encouraging clinical data on effects of cannabinoids on chronic pain are from studies of intractable cancer pain and hard-to-treat neuropathic pain.[58] The effectiveness of cannabis and cannabinoids in relieving neuropathic pain has been demonstrated in more than three dozen preclinical and clinical trials.[59] A trial of cannabis cigarettes to treat HIVassociated daily neuropathic pain in 50 patients showed an average reduction of pain by 30% over a treatment course of only 5 days.[60] In 2001, researchers reported that cannabis extract sprayed under the tongue (Sativex®) was effective in reducing pain in patients suffering intractable neuropathic pain.[61] A review of over 20 clinical trials on cannabis and cannabinoids found that whole plant cannabis and extracts are superior to oral THC for the treatment of pain. Health Canada approved Sativex® for prescription in the treatment of HIV-associated neuropathic pain in 2005 and cancer pain in 2007.

The activity of the more than 100 cannabinoids and other components on the plant may explain its superiority in reducing pain when comparing whole plant cannabis and extracts to THC alone. For instance, the cannabinoid cannabichromene (CBC), the third most common ingredient on the plant, exhibits anti-inflammatory and analgesic actions, although weaker than THC.[62] Similarly, beta-sitosterol, a non-cannabinoid ingredient found in cannabis, was able to decrease inflammation and edema in skin treatment.[63] And a unique flavanoid found only in cannabis, cannaflavin A, inhibits the inflammatory molecule PGE-2, thirty times more potently than aspirin.[64] Lastly beta-caryophyllene, a cannabinoid found in many plants besides cannabis, has strong anti-inflamma tory properties but no noticeable side effects.[65] Beta-caryophyllen is the most commonly consumed FDA-approved cannabinoid in food.

The IOM report found that "basic biology indicates a role for cannabinoids in pain and control of movement, which is consistent with a possible therapeutic role in these areas. The evidence is relatively strong for the treatment of pain and intriguingly, although less well established, for movement disorder." According to the IOM Report and numerous independent research articles, a number of areas in the brain that have an established role in sensing and processing pain respond to the analgesic effect of cannabis, adding that cannabinoids have been used successfully to treat cancer pain, which is often resistant to treatment with opiates. The effectiveness of cannabinoids in treating intractable cancer pain has been demonstrated in several subsequent clinical trials of a dosage-controlled sublingual spray.

Several studies have found that cannabinoids have analgesic effects in animal models, sometimes equivalent to codeine.[66-70] Cannabinoids also seem to synergize with opioids, which often lose their effectiveness as patients build up tolerance. One study found morphine was 15 times more active in rats with the addition of a small dose of THC. Codeine was enhanced on the order of 900 fold.[71] In 1990, researchers conducted a double-blind study comparing the antispasmodic and analgesic effects of THC, oral Codeine, and a placebo on a single patient suffering from a spinal cord injury.[72] Their findings confirmed the analgesic effects of THC being "equivalent to codeine." A 1997 study made similar findings related to morphine.[73]

A 1999 article reviewing the body of scientific animal research concerning the analgesic effects of marijuana concludes that "[t]here is now unequivocal evidence that cannabinoids are antinociceptive [capable of blocking the appreciation or transmission of pain] in animal models of acute pain."[74] The report notes that multiple cannabinoids and noncannabinoid components can serve as antiinflammatory agents, and so have potential in preventing and reducing pain caused by swelling (such as arthritis). In short, the research community recognizes the potential benefits of cannabis for certain patients, including:

• Chemotherapy patients, especially those being treated for mucositis, nausea, and anorexia.
• Postoperative pain patients (using cannabinoids as an opioid adjunct to reduce the nausea and vomiting).
• Patients with spinal cord injury, peripheral neuropathic pain, or central poststroke pain.
• Patients with chronic pain and insomnia.
• AIDS patients with cachexia, AIDS neuropathy, or any significant pain.

Britain's House of Lords reached similar conclusions and called for making cannabis available by prescription[75].

Page 2 ⇒