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

Research on Cannabis and Aging

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 been working intimately with these issues for many years, Americans for Safe Access has 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 about ASA and the work we do, please see our website at 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 Amend-ment.[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 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 1991. Membership in the Society has more than tripled from about 50 members in the first year to over 300 in 2005. The International Association for Cannabis as Medicine (IACM) was founded in March 2000. It publishes a bi-weekly newsletter and the IACM-Bulletin, and holds a bi-annual symposium to highlight emerging research in cannabis therapeutics. The University of California established the Center for Medicinal Cannabis Research in 2001. As of June 2006, the CMCR has 17 approved studies, including research on cancer pain, nausea control in chemo-therapy, general analgesia and a proposed study on refractory cancer pain.

In the United Kingdom, GW Pharmaceuticals has been granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury.

GW has completed Phase III studies in patients with MS neuropathic pain and spasticity, and Phase II trials on perioperative pain, rheumatoid arthritis, peripheral neuropathy secondary to diabetes mellitus or AIDS, and patients with neurogenic symptoms.

These trials have provided positive results and confirmed an excellent safety profile for cannabis-based medicines. In 2002, GW conducted five Phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing THC in more than 100 patients with cancer pain. In total, more than 1,000 patients are currently involved in phase III trials in the UK.

In 2002 GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury, and in April 2005 GW received regulatory approval to distribute Sativex in Canada for the relief of neuropathic pain in adults with Multiple Sclerosis. Following meetings with the FDA, DEA, the Office for National Drug Control Policy, and the National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the U.S., and in January of 2006 was granted permission to begin Phase III clinical trials into cancer pain.

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 common types of arthritis, rheumatoid arthritis and osteoarthritis, but both affect the joints, causing pain and swelling, and limiting movement. Rheumatoid arthritis 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. Osteoarthritis, or arthritis of the bones, is also found primarily among the elderly, whose cartilage has been worn away through use. Arthritis may also manifest as chronic inflammation of the joints as the result of injuries.

Recent research is accumulating evidence that cannabis therapies are effective for arthritis and the other rheumatic and degenerative hip, joint and connective tissue disorders. Since these are frequently extremely painful conditions, the ability of cannabis to combat chronic pain makes it useful for that aspect, both on its own and as an adjunct therapy that enhances the efficacy of opiod painkillers. The use of cannabis as a treatment for musclo-skeletal pain in western medicine dates to the 1700s.[12-13]

But cannabis has also been shown to have powerful immune-modulation and anti-inflammatory properties,[14-17] indicating it may treat chronic inflammatory diseases directly. In fact one of the earliest records of medical use of cannabis—a Chinese text dating from ca. 2000 BC—notes that cannabis is effective in treating rheumatism, suggesting that ancient societies long ago recognized its anti-inflammatory and analgesic properties.[18]

Modern research on cannabidiol (CBD)—one of the non-psychoactive 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.[19-20]

Human studies have shown cannabis to be an effective treatment for rheumatoid arthritis, and it is one of the recognized 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 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) when using cannabis as an adjunct therapy.[21-22]

Medical researchers investigating Cannabidiol at Hebrew University in Jerusalem discovered an acid with potent anti-inflammatory action comparable to the drug indomethacin, but without the considerable gastrointestinal side effects associated with that drug.[23]

In addition, when the body metabolizes tetrahydrocannabinol (THC,  one of the primary components of cannabis) it produces a number of related chemicals. At least one of these metabolites has anti-inflammatory and pain-relieving effects. By modifying this metabolite, researchers at the University of Massachusetts Medical Center have produced a synthetic carboxylic acid known as CT-3 (also called DMH-11C, chemical name dimethylheptyl-THC-11 oic acid), which is more powerful than the natural metabolite and can be given in smaller doses. Animal tests found CT-3 effective against both chronic and acute inflammation; it also prevented destruction of joint tissue from chronic inflammation. The long safety record of marijuana (no one has ever died of an overdose) and the discovery that a metabolite with the desired anti-inflammatory effect is produced in the body when marijuana is used, strongly suggest that safe and effective anti-inflammatory drugs may be developed from cannabinoids.[24]

In addition, CT3 has demonstrated 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.[25-26] In contrast to the NSAIDs commonly prescribed arthritis sufferers, CT3 did not cause ulcers at therapeutically relevant doses. Moreover, it does not depress respiration, produce dependence, induce body weight loss or cause mutations. Studies on its mechanism of action are currently underway, and cytokine synthesis is one of the pathways being investigated.[27]

Cannabis may also help combat rheumatoid arthritis by way of its established immune-modulation properties.[28] 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, which typically 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 fueling 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.[29-32] 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 is effective in controlling the dysfunctional auto-immune response.

Similarly, another non-psychoactive cannabinoid, ajulemic acid, has been found by UMass Medical Center researchers to reduce joint tissue damage in rats with adjuvant arthritis.[33] Tests on human tissue done in vitro showed a 50% suppression of one of the body chemicals (interleukin-1beta) central to the progression of inflammation and joint tissue injury in patients with rheumatoid arthritis.[34]

Cannabis and Chronic Pain

Many older patients suffer from persistent and disabling pain, which can have numerous and sometimes multiple causes. These include cancer; arthritis and other rheumatic and degenerative hip, joint and connective tissue disorders; diabetes; AIDS; sickle cell anemia; multiple sclerosis; defects or injuries to the back, neck and spinal cord; and severe burns. Pain is not a primary condition or injury, but is 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.

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 opiod 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 pain-control properties when taken in combination than THC alone.

Research on cannabis and pain management

Cannabis has historically been used as an analgesic,[35-36] and patients often report significant pain relief from marijuana.[37-42] Some of the most encouraging clinical data on the effects of cannabinoids on chronic pain are from studies of intractable cancer pain and hard-to-treat neuropathic pain.[43-44]

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."[45]

A 1999 study commissioned by the White House and conducted by the Institute of Medicine recognizes the role that cannabis can play in treating chronic pain. "After nausea and vomiting, chronic pain was the condition cited most often to the IOM study team as a medicinal use for marijuana."[46]

The study 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 report, a number of brain areas that have an established role in sensing and processing pain respond to the analgesic effect of cannabis, such that cannabinoids have been used successfully to treat cancer pain, which is often resistant to treatment with opiates.

The Report further notes that cannabinoids serve as an anti-inflammatory agent, and so have therapeutic potential in preventing and reducing pain caused by the swelling of body tissues (such as arthritis).

In addition to its analgesic properties, the Report indicates that cannabis, like its synthetic cousin Marinol, can help treat the nausea often induced by opiate therapy, especially when other antiemetics prove ineffective. In short, the IOM Report 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 post-stroke pain.

· Patients with chronic pain and insomnia.

· AIDS patients with cachexia, AIDS neuropathy, or any significant pain problem.

Britain's House of Lords reached similar conclusions and called for legalized cannabis by prescription.[47]

Several studies have found that cannabinoids have analgesic effects in animal models, sometimes equivalent to codeine.[48-52] Cannabinoids also seem to synergize with opiods, which often lose their effectiveness as patients build up tolerance. One study in rats found morphine was 15 times more active with the addition of a small dose of THC. Codeine was enhanced on the order of 900 fold.[53]

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.[54] Their findings confirmed the analgesic effects of THC being "equivalent to codeine." A 1997 study made similar findings related to morphine.[55]

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."[56]

In 2001, British researchers reported that cannabis extract sprayed under the tongue was effective in reducing pain in 18 of 23 patients who were suffering from intractable neuropathic pain.[57]

CANNABIS and CANCER

Cannabis has been found to help cancer patients with pain and nausea, and recent research indicates it has tumor-reducing and anti-carcinogenic properties as well. It has proven highly effective at controlling the nausea associated with chemotherapy, and its appetite-stimulation properties help combat wasting. Cannabis can also help control the pain associated with some cancers, as well as that resulting from radiation and chemotherapy treatment.

Cannabis and chemotherapy side effects

One of the most widely studied therapeutic applications for cannabis and the pharmaceutical drugs derived from cannabinoids is in the treatment of nausea and vomiting associated with cancer chemotherapy. Numerous clinical studies have reported that the use of cannabis reduces nausea and vomiting and stimulates appetite, thereby reducing the severity of cachexia, or wasting syndrome, in patients receiving chemotherapy treatment.

The 1999 Institutes of Medicine report concluded: "In patients already experiencing severe nausea or vomiting, pills are generally ineffective, because of the difficulty in swallowing or keeping a pill down, and slow onset of the drug effect. Thus an inhalation (but, preferably not smoking) cannabinoid drug delivery system would be advantageous for treating chemotherapy-induced nausea."[58]

A 1997 inquiry by the British Medical Association found cannabis more effective than Marinol, and a 1998 review by the House of Lords Science & Technology Select Committee concluded that "cannabinoids are undoubtedly effective as anti-emetic agents in vomiting induced by anti-cancer drugs. Some users of both find cannabis itself more effective."[59, 60]

In the last three years, there have been major advances in both cannabinoid pharmacology and in understanding of the cancer disease process. In particular, research has demonstrated the presence of numerous cannabinoid receptors in the nucleus of the solitary tract, a brain center important in control of vomiting.

Although other recently developed anti-emetics are as effective or more effective than oral THC, nabilone or smoked cannabis, for certain individuals unresponsive to conventional anti-emetic drugs, the use of smoked cannabis can provide relief more effectively than oral preparations which may be difficult to swallow or be vomited before taking effect, as the IOM report notes.

The psychoactive euphoriant effects of THC or inhaled cannabis may also provide an improvement in mood. By contrast, several conventional medications commonly prescribed for cancer patients, e.g. phenothiazines such as haloperidol (known as "major tranquillizers"), may produce unwanted side effects such as excessive sedation, flattening of mood, and/or distressing physical "extrapyramidal" symptoms such as uncontrolled or compulsive movements.

While clinical research on using cannabis medicinally has been severely limited by federal prohibition, the accumulated data speaks strongly in favor of considering it as an option for most cancer patients, and many oncologists do. Survey data from a Harvard Medical School study in 1990, before any states had approved medical use, shows that 44% of oncologists were then recommending cannabis to at least some of their patients. Nearly half said they would do so if the laws were changed. According the American Cancer Society's 2003 data, more than 1,300,000 Americans are diagnosed with cancer each year.[61] At least 300,000 of them will undergo chemotherapy, meaning as many as 132,000 patients annually may have cannabis recommended to them to help fight the side effects of conventional treatments.

As the Institutes of Medicine report concluded, "nausea, appetite loss, pain and anxiety … all can be mitigated by marijuana."

Research on cannabis and chemotherapy

Cannabis is used to combat pain caused by various cancers and nausea induced by chemotherapy agents. Over 30 human clinical trials have examined the effects of cannabis or synthetic cannabinoids on nausea, not including several U.S. state trials that took place between 1978 and 1986.[62] In reviewing this literature, Hall et al. concluded that ". . . THC [delta-9-tetrahydrocannabinol] is superior to placebo, and equivalent in effectiveness to other widely-used anti-emetic drugs, in its capacity to reduce the nausea and vomiting caused by some chemotherapy regimens in some cancer patients."[63] A 2003 study found "Cannabinoids—the active components of Cannabis sativa and their derivatives—exert palliative effects in cancer patients by preventing nausea, vomiting and pain and by stimulating appetite. In addition, these compounds have been shown to inhibit the growth of tumor cells in culture and animal models by modulating key cell-signaling pathways. Cannabinoids are usually well tolerated, and do not produce the generalized toxic effects of conventional chemotherapies."[64] Authors of the Institute of Medicine report, "Marijuana and Medicine: Assessing the Science Base," found that there are many cancer patients for whom cannabis should be a valid medical option.[65]

A random-sample anonymous survey conducted in the spring of 1990 measured the attitudes and experiences of oncologists concerning the antiemetic use of cannabis in cancer chemotherapy patients. Of the respondents expressing an opinion, a majority (54%) thought cannabis should be available by prescription.[66]

Cancer-fighting properties of cannabis

Recent scientific advances in the study of cannabinoid receptors and endocannabinoids have produced exciting new leads in the search for anti-cancer treatments. More than twenty major studies published between 2001 and 2006 have shown that the chemicals in cannabis known as cannabinoids have a significant effect fighting cancer cells. We now know cannabinoids arrest many kinds of cancer growths (brain, breast, leukemic, melanoma, phaeochromocytoma, etc.) through promotion of apoptosis (programmed cell death) that is lost in tumors, and by arresting angiogenesis (increased blood vessel production).

There is growing evidence of direct anti-tumor activity of cannabinoids, specifically CB1 and CB2 agonists, in a range of cancer types including brain (gliomas), skin, pituitary, prostate and bowel. The anti-tumor activity has led in laboratory animals and in-vitro human tissues to regression of tumors, reductions in vascularisation (blood supply) and metastases (secondary tumors), as well as the direct destruction of cancer cells (apoptosis). Indeed, research on the complex interactions of endogenous cannabinoids and receptors is leading to greater scientific understanding of the basic mechanisms by which cancers develop.

The findings of these studies are borne out by the anecdotal reports of such patients as Steve Kubby, whose cannabis use is credited with keeping rare, terminal cancers in a state of remission for decades beyond conventional expectations.

Research on Tumor Reduction

Although cannabis smoke has been shown to have precancerous-causing effects in animal tissue, epidemiological studies have failed to link cannabis smoking with cancer.[67-68] If smoke inhalation is a concern, cannabis can be used with a vaporizer, orally in baked goods, and topically as a tincture or a suppository.

Cannabinoids, the active components of cannabis, have been shown to exhibit anti-tumor properties. Multiple studies published between 2001 and 2003 found that cannabinoids inhibit tumor growth in laboratory animals.[69-73] In another study, injections of synthetic THC eradicated malignant brain tumors in one-third of treated rats, and prolonged life in another third by as much as six weeks.[74] Other journals have also reported on cannabinoids' antitumoral potential.[75-81] Italian research teams reported in 1998 and 2001 that the endocannabinoid anandamide, which binds to the same brain receptors as cannabis, "potently and selectively inhibits the proliferation of human breast cancer cells in vitro" by interfering with their DNA production cycle.[82-84] Cannabis has been shown in recent studies to inhibit the growth of thyroid, prostate and colorectal cancer cells.[85-87] THC has been found to cause the death of glioma cells.[88-89] And research on pituitary cancers shows cannabinoids are key to regulating human pituitary hormone secretion.[90-93]

In 2004 an Italian research team demonstrated that the administration of the non-psychoactive cannabinoid cannabidiol (CBD) to nude mice significantly inhibited the growth of subcutaneously implanted U87 human glioma cells. The authors of the study concluded that "… CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent (an agent that inhibits the growth of malignant cells.)"[94]

More recently, investigators at the California Pacific Medical Center Research Institute reported that the administration of THC on human glioblastoma multiforme cell lines decreased the proliferation of malignant cells and induced apoptosis (programmed cell death) more rapidly than did the administration of an alternative synthetic cannabis receptor agonist.[95]

Cannabis and Movement Disorders

Movement disorders and neuro-degenerative diseases, which are sometimes interlinked, are among the conditions cannabis is particularly well suited to treat.

The therapeutic use of cannabis for treating muscle problems and movement disorders has been known to western medicine for nearly two centuries. In 1839, Dr. William B. O'Shaughnessy noted the plant's muscle relaxant and anti-convulsant properties, writing that doctors had "gained an anti-convulsive remedy of the greatest value."[96] In 1890 Dr. J. Russell Reynolds, physician to Queen Victoria, noted in an article in The Lancet that for "organic disease of a gross character in the nervous centers . . . India hemp (cannabis) is the most useful agent with which I am acquainted."[97]

Muscular spasticity is a common condition, affecting millions of people in the United States. It afflicts individuals who have suffered strokes, as well as those with multiple sclerosis, cerebral palsy, paraplegia, quadriplegia, and spinal cord injuries. Conventional medical therapy offers little help for spasticity problems. Phenobarbital and diazepam (Valium) are commonly prescribed, but they rarely provide complete relief, and many patients develop a tolerance, become addicted, or complain of heavy sedation. These drugs also cause weakness, drowsiness and other side effects that patients find intolerable.

Extensive modern studies in animals and various clinical states have shown that cannabis can treat movement disorders affecting older patients, such as tremors and spasticity, because cannabis has antispasticity, analgesic, antitremor, and antiataxia actions.[98-110]

In the federal court brief they filed in support of physicians' right to recommend cannabis, the American Public Health Association stated that "Marijuana is effective in treating muscle spasticity." They point out that the government's own Institutes of Medicine report on medical use of cannabis found that "current treatments for painful muscle spasms . . . have only limited effectiveness and their use is complicated by various adverse side effects." They go on to note that "a survey of British and American MS patients reports that after ingesting marijuana a significant majority experienced substantial improvements in controlling muscle spasticity and pain. An extensive neurological study found that herbal cannabis provided relief from both muscle spasms and ataxia (loss of coordination), a multiple benefit not achieved by any currently available medications" (amicus brief in Conant v. McCaffrey, 2001 filing).

Cannabis also has enormous potential for protecting the brain and central nervous system from the damage that creates various movement disorders. Researchers have found that cannabinoids fight the effects of strokes, as well as brain trauma, spinal cord injury, and multiple sclerosis. More than 100 research articles have been published on how canna-binoids act as neuroprotective agents to slow the progression of such neurodegenerative diseases as Huntington's, Alzheimer's and particularly Parkinson's, which affects more than 52% of people over the age of 85.

The contemporary understanding of the actions of cannabis was spurred by the discovery of an endogenous cannabinoid system in the human body. This system appears to be intricately involved in normal physiology, specifically in the control of movement.[111-115] Central cannabinoid receptors are densely located in the basal ganglia, the area of the brain that regulates body movement. Endogenous cannabinoids also appear to play a role in the manipulation of other transmitter systems within the basal ganglia—increasing transmission of certain chemicals, inhibiting the release of others, and affecting how still others are absorbed. Most movement disorders are caused by a dysfunction of the chemical loops in this part of the brain. Research suggests that an endo-genous cannabinoid tone participates in the control of movements.[116-120]

Endocannabinoids have paradoxical effects on the mammalian nervous system: Sometimes they block neuronal excitability and other times they augment it. As scientists are developing a better understanding of the physiological role of those natural cannabinoids, or endocannabinoids, it is becoming clear that these chemicals may be involved in the pathology of several neurological diseases. Researchers are identifying an array of potential therapeutic targets within the human nervous system. They have determined that various cannabinoids found in the cannabis plant interrupt the synthesis, uptake or metabolism of the endocannabinoids that drive the progression of Huntington's disease, Parkinson's disease, and tremor.[121-122]

Parkinson's disease has been linked to dysfunction in the body's dopamine system, specifically the production of too much of the neurotransmitter glutamate and oxidative damage to dopaminergic neurons. Studies have found a tight association between cannabinoids and dopamine, and recent research has produced anatomical, biochemical and pharmacological evidence supporting a role for the endogenous cannabinoid system in the modulation of dopaminergic transmission. Cannabinoid receptors switch between blocking and enhancing dopamine signaling. Cannabinoids neuroprotective action appears to result from their ability to inhibit reactive oxygen species, glutamate and tumour necrosis factor.

Cannabis and Alzheimer's Disease

Alzheimer's disease is another neuro-degenerative condition for which cannabis and cannabinoid therapies show promise, both for treating the symptoms and the underlying disease.

Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of beta-amyloid peptide aggregates. A laboratory study published in 2004 indicates that one of the cannabis plant's primary components, cannabidiol (CBD), exerts a combination of neuroprotective, anti-oxidative and anti-apoptotic effects by inhibiting the release of the toxic beta-amyloid peptide.[123]

Another cannabinoid, THC, has also has been shown to reduce the agitation common to Alzheimer's sufferers, according to findings presented in 2003 at the American Society of Consultant Pharmacists' 34th annual meeting.[124] Agitation is the most common behavioral management problem in patients with Alzheimer's and affects an estimated 75 percent of people with the disease. It may lead to a variety of symptoms ranging from physical and/or verbal abusive postures, physically non-aggressive conduct including pacing and restlessness, as well as verbally disturbed behaviors such as screaming and repetitive requests for attention.

This study and the Institutes of Medicine report also show THC to be effective in combating the anorexia or wasting syndrome common to Alzheimer's sufferers, since food refusal is a common problem in patients who suffer from Alzheimer's-type dementia. The appetite-stimulation properties of cannabis are some of the most well established in clinical research.[125]

This new research on cannabis and Alzheimer's disease, coupled with the extensive work done on other neuroprotective qualities of cannabis and its components, indicates that cannabis may become the source of the most effective treatments for battling the Central Nervous System diseases that afflict millions of elderly Americans.

Page 2 ⇒