"By design CMCR [Center for Medicinal Cannabis Research] clinical studies focused on conditions identified by the Institute of Medicine for which cannabis might have potential therapeutic effects, based on current scientific knowledge (Institute of Medicine, 1999). To date, four CMCR-funded studies have demonstrated that cannabis has analgesic effects in pain conditions secondary to injury (e.g. spinal cord injury) or disease (e.g. HIV disease, HIV drug therapy) of the nervous system ... This suggests that cannabis may provide a treatment option for those individuals who do not respond or respond inadequately to currently available therapies. The efficacy of cannabis in treatment-refractory patients also may suggest a novel mechanism of action not fully exploited by current therapies. In addition to nerve pain, CMCR has also supported a study on muscle spasticity in Multiple Sclerosis (MS). Such spasticity can be painful and disabling, and some patients do not benefit optimally from existing treatments. The results of the CMCR study suggest that cannabis reduces MS spasticity, at least in the short term, beyond the benefit available from usual medical care."

Synopsis of CMCR Published Clinical Study Results

“The Effect of Cannabis on Neuropathic Pain in HIV-Related Peripheral Neuropathy”
Donald I. Abrams, M.D., University of California, San Francisco
"The primary objective of this study was to evaluate the efficacy of smoked cannabis when used as an analgesic in persons with neuropathic pain from HIV-associated distal sensory polyneuropathy (DSPN) ... In a double blind, randomized, five-day clinical trial patients received either smoked cannabis or placebo cannabis cigarettes .... The full results of this study appear in the journal Neurology (Abrams, et al., 2007– see reference list) ... The study concluded that a significantly greater proportion of patients who smoked cannabis (52%) had a greater than 30% reduction in pain intensity compared to only 24% in the placebo group."

“Placebo-Controlled, Double Blind Trial of Medicinal Cannabis in Painful HIV Neuropathy”
Ronald J. Ellis, M.D., Ph.D., University of California, San Diego
"The primary objective of this study also was to evaluate the efficacy of smoked cannabis when used as an analgesic in persons with HIV-associated painful neuropathy. In a double-blind, randomized, clinical trial of the short-term adjunctive treatment of neuropathic pain in HIV-associated distal sensory polyneuropathy, participants received either smoked cannabis or placebo cannabis cigarettes ... The full results of this study were published in the journal Neuropsychopharmacology (Ellis, et al., 2008 – see reference list) ... It was concluded that smoked cannabis was generally well-tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV-associated neuropathy."

“A Double-Blind, Placebo-Controlled Crossover Trial of the Antinociceptive Effects of Smoked Marijuana on Subjects with Neuropathic Pain“
Barth Wilsey, M.D., University of California, Davis
"This study’s objective was to examine the efficacy of two doses of smoked cannabis on pain in persons with neuropathic pain of different origins (e.g., physical trauma to nerve bundles, spinal cord injury, multiple sclerosis, diabetes). In a double-blind, randomized clinical trial participants received either lowdose, high-dose, or placebo cannabis cigarettes ... The full results of this study have been published in the Journal of Pain (Wilsey, et al., 2008 – see reference list) ...The study concluded that both low and high cannabis doses were efficacious in reducing neuropathic pain of diverse causes."

“Analgesic Efficacy of Smoked Cannabis”
Mark Wallace, M.D., University of California, San Diego
"This study used an experimental model of neuropathic pain to determine whether pain induced by the injection into the skin of capsaicin, a compound which is the 'hot' ingredient in chili peppers, could be alleviated by smoked cannabis. Another aim of the study was to examine the effects of 'dose' of cannabis, and the time course of pain relief. In a randomized double-blinded placebo controlled trial, volunteers smoked low, medium, and high dose cannabis (2%, 4%, 8% THC by weight) or placebo cigarettes ... The full results of this study were published in the journal Anesthesiology (Wallace, et al., 2007 – see reference list) ...In summary, this study suggested that there may be a 'therapeutic window' (or optimal dose) for smoked cannabis: low doses were not effective; medium doses decreased pain; and higher doses actually increased pain. These results suggest the mechanism(s) of cannabinoid analgesia are complex, in some ways like non-opioid pain relievers (e.g., aspirin, ibuprofen) and in others like opioids (e.g., morphine)."

“Short-Term Effects of Cannabis Therapy on Spasticity in Multiple-Sclerosis”
Jody Corey-Bloom, M.D., University of California, San Diego
"This objective of this study was to determine the potential for smoked cannabis to ameliorate marked muscle spasticity (chronic painful contraction of muscles), a severe and disabling symptom of multiple sclerosis ... In a placebo-controlled, randomized clinical trial spasticity and global functioning was examined before and after treatment with smoked cannabis ... Initial results were presented at the meeting of the American College of Neuropsychopharmacology in 2007 ... This study concluded that smoked cannabis was superior to placebo in reducing spasticity and pain in patients with multiple sclerosis, and provided some benefit beyond currently prescribed treatments."

“Vaporization as a ‘Smokeless’ Cannabis Delivery System”
Donald Abrams, M.D., University of California, San Francisco
"The aim of this study was to evaluate the use of a vaporization system (the Volcano; VAPORMED® Inhalatoren; Tüttlingen, Germany) as a 'smokeless' delivery system for inhaled cannabis ... The full results of this study have been published in the journal Clinical Pharmacology & Therapeutics (Abrams, et al., 2007 – see reference list) ... In summary, vaporization of cannabis was found to be a safe mode of delivery, and participants had a preference for vaporization over smoking as a delivery system in this trial."

"Evidence not only supports the use of medical marijuana in certain conditions but also suggests numerous indications for cannabinoids. Additional research is needed to further clarify the therapeutic value of cannabinoids and determine optimal routes of administration. The science on medical marijuana should not be obscured or hindered by the debate surrounding the legalization of marijuana for general use."

"Cannabinoids have been found to have antioxidant properties, unrelated to NMDA [(N-methyl-D-aspartic acid] receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention."

"Cannabinoids, the active components of Cannabis sativa and their derivatives, act in the organism by mimicking endogenous substances, the endocannabinoids, that activate specific cannabinoid receptors. Cannabinoids exert palliative effects in patients with cancer and inhibit tumour growth in laboratory animals.

"The best-established palliative effect of cannabinoids in cancer patients is the inhibition of chemotherapy-induced nausea and vomiting. ....

"Other potential palliative effects of cannabinoids in cancer patients — supported by Phase III clinical trials — include appetite stimulation and pain inhibition. ....

"Cannabinoids inhibit tumour growth in laboratory animals. They do so by modulating key cell-signalling pathways, thereby inducing direct growth arrest and death of tumour cells, as well as by inhibiting tumour angiogenesis and metastasis.

"Cannabinoids are selective antitumour compounds, as they can kill tumour cells without affecting their non-transformed counterparts. It is probable that cannabinoid receptors regulate cell-survival and cell-death pathways differently in tumour and nontumour cells.

"Cannabinoids have favourable drug-safety profiles and do not produce the generalized toxic effects of conventional chemotherapies. ... "

"On September 6, 1988, the Drug Enforcement Administration's [DEA] Chief Administrative Law Judge, Francis L. Young, ruled, "Placement [of a drug] in Schedule II would mean, essentially, that physicians in the United States would not violate Federal law by prescribing marijuana for their patients for legitimate therapeutic purposes. It is contrary to Federal law for physicians to do this so long as marijuana remains in Schedule I. ...

"Marijuana, in its natural form, is one of the safest therapeutically active substances known to man. By any measure of rational analysis, marijuana can be safely used within a supervised routine of medical care. ...

"The administrative law judge recommends that the Administrator [of the DEA] conclude that the marijuana plant considered as a whole has currently accepted medical use in treatment in the United States, that there is no lack of accepted safety for use of it under medical supervision and that it may lawfully be transferred from Schedule I to Schedule II."

The DEA's Administrative Law Judge, Francis Young concluded: "In strict medical terms marijuana is far safer than many foods we commonly consume. For example, eating 10 raw potatoes can result in a toxic response. By comparison, it is physically impossible to eat enough marijuana to induce death. Marijuana in its natural form is one of the safest therapeutically active substances known to man. By any measure of rational analysis marijuana can be safely used within the supervised routine of medical care.:

Medical and scientific organizations based in the United States that support access to therapeutic cannabis include: the American Academy of Family Physicians (1989, 1995); American Academy of HIV Medicine (2003); American College of Physicians (2008); American Medical Association's Council on Scientific Affairs (2001); American Medical Students Association (1993); American Nurses Association (2003); American Preventive Medical Association (1997); American Public Health Association (1995); Association of Nurses in AIDS Care (1999); Federation of American Scientists (1994); HIV Medicine Association (2006); Institute of Medicine (1982 & 1999); Kaiser Permanete (1997); Lymphoma Foundation of America (1997); National Association for Public Health Policy (1998); National Nurses Society on Addictions (1995); and Physicians Association for AIDS Care.

Medical and scientific organizations not based in the United States that support access to therapeutic cannabis include: Australian National Task Force on Cannabis (1994); Australian Medical Association (New South Wales) Limited (1999); British Medical Association; Bundesverband Poliomyelitis (Federal Union for Polio), Germany (1998); Canadian AIDS Society (2004); Canadian Medical Association (2001); Deutsche Epilipsievereinigung (German Association for Epilesy - 1998); Deutsche Gesellschaft fur Algesiologie (German Society for Algesiology - 1998); Deutsche Gesellschaft fur Drogen-und Suchtmedizin (German Society for Drug and Addiction Medicine - 1998); French Ministry of Health (1997); Health Canada (1997); House of Lords (UK) Select Committee on Science and Technology (1999); Medical Association of Jamaica (2001); Preventive Medical Center, Netherlands (1993); and Schmerztherapeutisches Kolloquium (Society for Pain Therapists), Germany (1998).

Medical and scientific organizations based in the United States that support research concerning therapeutic cannabis include: American Academy of Addiction Psychiatry (2000); American Academy of Family Physicians (1977); American Cancer Society (1997); American Nurses Association (2003); American Society of Addiction Medicine (2000); Association of Nurses in AIDS Care (1999); Council of Health Organizations (1971); Federation of American Scientists (1995); HIV Medicine Association (2006); and National Institute of Health Workshop on the Medical Utility of Marijuana (1997).

A few of the editorial boards that have endorsed medical access to marijuana include: Boston Globe; Chicago Tribune; Miami Herald; Denver Post; Los Angeles Times; New York Times; Orange County Register; and USA Today.

Since 1996, fourteen states have enacted laws that allow the cultivation of medical marijuana and protect patients who possess medical marijuana (with their doctors' recommendations or certifications) from criminal penalties: Alaska, California, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, and Washington. Nine of the thirteen did so through the initiative process. Hawaii's law was enacted by the legislature and signed by the governor in 2000; Vermont's was enacted by the legislature and passed into law without the governor's signature in 2004; Rhode Island's was passed into law over the governor's veto in 2006; New Mexico's legislation was signed into law by Governor Bill Richardson in 2007; and on January 18, 2010, Governor Jon Corzine signed New Jersey's bill into law. In mid-December 2009, the United States Senate passed an omnibus appropriations bill that removed restrictions on the implementation of a marijuana initiative passed by District of Columbia voters in 1998; President Obama subsequently signed this bill into law on December 13, 2009.

Despite its medical value, cannabis (marijuana) remains in Schedule I of the 1970 Controlled Substance Act where it is categorized as "(A) The drug or other substance has a high potential for abuse. (B) The drug or other substance has no currently accepted medical use in treatment in the United States. (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision."

Since 1978, thirty-six states have enacted some form of medicinal cannabis legislation, most of which has never been operable because of the federal Controlled Substances Act (CSA).

These laws and the states that currently have them include:

Therapeutic Research Programs (allow patients to use cannabis through state-run therapeutic research programs; not operable because of federal obstruction): Alabama, California, Georgia, Illinois, Massachusetts, Minnesota, New Jersey, New York, South Carolina, Texas.

Symbolic Pseudo-Prescriptions (allow patients to possess cannabis if obtained through a prescription; not operable because the CSA bars physicians from writing prescriptions for Schedule I drugs like cannabis): Arizona, California, Connecticut, District of Columbia, Iowa, New Hampshire, Tennessee, Virginia, Wisconsin.

Rescheduling (some states have their own CSA which often mirrors federal scheduling, but can vary; not operable because federal scheduling supersedes state schedules): Alaska, Iowa, Montana, Tennessee, and the District of Columbia.

Non-binding Resolutions (legislation that urges the federal government to reschedule cannabis; largely symbolic): California, Michigan, Missouri, New Hampshire, New Mexico, Rhode Island, Washington.

"The prosecution of significant traffickers of illegal drugs, including marijuana, and the disruption of illegal drug manufacturing and trafficking networks continues to be a core priority in the Department's efforts against narcotics and dangerous drugs, and the Department's investigative and prosecutorial resources should be directed towards these objectives. As a general matter, pursuit of these priorities should not focus federal resources in your States on individuals whose actions are in clear and unambiguous compliance with existing state laws providing for the medical use of marijuana. For example, prosecution of individuals with cancer or other serious illnesses who use marijuana as part of a recommended treatment regimen consistent with applicable state law, or those caregivers in clear and unambiguous compliance with existing state law who provide such individuals with marijuana, is unlikely to be an efficient use of limited federal resources. On the other hand, prosecution of commercial enterprises that unlawfully market and sell marijuana for profit continues to be an enforcement priority of the Department. To be sure, claims of compliance with state or local law may mask operations inconsistent with the terms, conditions, or purposes of those laws, and federal law enforcement should not be deterred by such assertions when otherwise pursuing the Department's core enforcement priorities.

"Typically, when any of the following characteristics is present, the conduct will not be in clear and unambiguous compliance with applicable state law and may indicate illegal drug trafficking activity of potential federal interest:
• unlawful possession or unlawful use of firearms;
• violence;
• sales to minors;
• financial and marketing activities inconsistent with the terms, conditions, or purposes of state law, including evidence of money laundering activity and/or financial gains or excessive amounts of cash inconsistent with purported compliance with state or local law;
• amounts of marijuana inconsistent with purported compliance with state or local law;
• illegal possession or sale of other controlled substances; or
• ties to other criminal enterprises."

(2003 - The Netherlands) "In 2003, the Opium Act was amended to legalise the medical use of cannabis. Since September 2003, prescribed medical cannabis is available at pharmacies for patients with indicated disorders."

According to a review by the General Accounting Office (GAO) of medical cannabis programs in four states, "Most medical marijuana recommendations in states where data are collected have been made for applicants with severe pain or muscle spasticity as their medical condition. Conditions allowed by the states' medical marijuana laws ranged from illnesses such as cancer and AIDS, to symptoms, such as severe pain. Information is not collected on the conditions for which marijuana has been recommended in Alaska or California. However, data from Hawaii's registry showed that the majority of recommendations have been made for the condition of severe pain or the condition of muscle spasticity. Likewise, data from Oregon's registry showed that, 84 percent of recommendations were for the condition of severe pain or for muscle spasticity."

"Short-term use of smoked cannabis did not affect viral load in 15 HIV-positive patients and also is associated with adherence to therapy and reduced viral loads in 16 patients with hepatitis C infections."

Medical Marijuana - Studies

"Eighty five percent of the BPG [Berkeley Patients Group] sample reported that cannabis has much less adverse side effects than their prescription medications. Additionally, the top two reasons listed by participants as reasons for substituting cannabis for one of the substances previously mentioned were less adverse side effects from cannabis (65%) and better symptom management from cannabis (57.4%).

"Conclusion
"The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs."

"Nevertheless, when considering all 15 studies (i.e., those that met both strict and more relaxed criteria) we only noted that regular cannabis users performed worse on memory tests, but that the magnitude of the effect was very small. The small magnitude of effect sizes from observations of chronic users of cannabis suggests that cannabis compounds, if found to have therapeutic value, should have a good margin of safety from a neurocognitive standpoint under the more limited conditions of exposure that would likely obtain in a medical setting."

"The use of a vaporizing device may mitigate some of these symptoms. Cannabis vaporization is a technique aimed at suppressing the formation of irritating respiratory toxins by heating cannabis to a temperature where active cannabinoids are volatilized, but below the point of combustion where smoke and associated toxins form. The use of a vaporizer is associated with higher plasma THC concentrations than smoking marijuana cigarettes, little if any carbon monoxide production, and significantly fewer triggered respiratory symptoms."

"In conclusion, a cannabinoid-based therapeutic strategy for neural diseases devoid of undesired psychotropic side effects could find in CBD [a cannabinoid] a valuable compound in cancer therapies along with the perspective of evaluating a synergistic effect with other cannabinoid molecules and/or with other chemotherapeutic agents as well as with radiotherapy. Whatever the precise mechanism underlying the CBD effects, the present results suggest a possible application of CBD as a promising, nonpsychoactive, antineoplastic agent."

In an ethnographic study of adolescents who were regular marijuana users, researchers at the University of British Columbia, concluded, "Thematic analysis revealed that these teens differentiated themselves from recreational users and positioned their use of marijuana for relief by emphasizing their inability to find other ways to deal with their health problems, the sophisticated ways in which they titrated their intake, and the benefits that they experienced. These teens used marijuana to gain relief from difficult feelings (including depression, anxiety and stress), sleep difficulties, problems with concentration and physical pain. Most were not overly concerned about the risks associated with using marijuana, maintaining that their use of marijuana was not 'in excess' and that their use fit into the realm of 'normal.'

Conclusion: Marijuana is perceived by some teens to be the only available alternative for teens experiencing difficult health problems when medical treatments have failed or when they lack access to appropriate health care."

"Conclusions: Smoked and oral cannabinoids did not seem to be unsafe in people with HIV infection with respect to HIV RNA levels, CD4+ and CD8+ cell counts, or protease inhibitor levels over a 21-day treatment."

"... we show that cannabinoid administration selectively down-regulates MMP-2 [matrix metalloproteinases] expression in mice bearing gliomas as well as in two patients with recurrent glioblastoma multiforme. Cannabinoid-induced inhibition of MMP-2 expression was also evident in cultured glioma cells, indicating that the changes observed in gliomas in vivo reflect—at least in part—the direct effect of cannabinoids on tumor cells. MMP-2 expression is upregulated in almost all human cancers, including gliomas, and this has been shown to be closely associated with negative prognosis."

"As MMP-2 up-regulation is associated with high progression and poor prognosis of gliomas and many other tumors, MMP-2 downregulation constitutes a new hallmark of cannabinoid antitumoral activity."

"Cannabinoids have a favourable drug safety profile. Acute fatal cases due to cannabis use in humans have not been substantiated, and median lethal doses of THC in animals have been extrapolated to several grams per kilogram of body weight. Cannabinoids are usually well tolerated in animal studies and do not produce the generalized toxic effects of most conventional chemotherapeutic agents. For example, in a 2-year administration of high oral doses of THC to rats and mice, no marked histopathological alterations in the brain and other organs were found. Moreover, THC treatment tended to increase survival and lower the incidence of primary tumours. Similarly, long-term epidemiological surveys, although scarce and difficult to design and interpret, usually show that neither patients under prolonged medical cannabinoid treatment nor regular cannabis smokers have marked alterations in a wide array of physiological, neurological and blood tests."

"This study provides evidence that short-term use of cannabinoids, either oral or smoked, does not substantially elevate viral load in individuals with HIV infection who are receiving stable antiretroviral regimens containing nelfinavir or indinavir. Upper confidence bounds for all estimated effects of cannabinoids on HIV RNA level from all analyses were no greater than an increase of 0.23 log10 copies/mL compared with placebo. Because this study was randomized and analyses were controlled for all known potential confounders, it is very unlikely that chance imbalance on any known or unknown covariate masked a harmful effect of cannabinoids. Study participants in all groups may have been expected to benefit from the equivalent of directly observed antiretroviral therapy, as well as decreased stress and, for some, improved nutrition over the 25-day inpatient stay."

Institute of Medicine - Marijuana and Medicine: Assessing the Science Base - 1999

"At this point, our knowledge about the biology of marijuana and cannabinoids allows us to make some general conclusions:

· Cannabinoids likely have a natural role in pain modulation, control of movement, and memory.

· The natural role of cannabinoids in immune systems is likely multi-faceted and remains unclear.

· The brain develops tolerance to cannabinoids.

· Animal research demonstrates the potential for dependence, but this potential is observed under a narrower range of conditions than with benzodiazepines, opiates, cocaine, or nicotine.

· Withdrawal symptoms can be observed in animals but appear to be mild compared to opiates or benzodiazepines, such as diazepam (Valium)."

The Institute of Medicine's 1999 report on medical marijuana examined the question of whether marijuana could diminish patients' immune system - an important question when considering marijuana use by AIDS and cancer patients. The report concluded that, "the short-term immunosuppressive effects are not well established but, if they exist, are not likely great enough to preclude a legitimate medical use."

The Institute of Medicine's 1999 report on medical marijuana stated, "The accumulated data indicate a potential therapeutic value for cannabinoid drugs, particularly for symptoms such as pain relief, control of nausea and vomiting, and appetite stimulation."

In the Institute of Medicine's report on medical marijuana, the researchers examined the physiological risks of using marijuana and cautioned, "Marijuana is not a completely benign substance. It is a powerful drug with a variety of effects. However, except for the harms associated with smoking, the adverse effects of marijuana use are within the range of effects tolerated for other medications."

The Institute of Medicine's 1999 report on medical marijuana examined the question whether the medical use of marijuana would lead to an increase of marijuana use in the general population and concluded that, "At this point there are no convincing data to support this concern. The existing data are consistent with the idea that this would not be a problem if the medical use of marijuana were as closely regulated as other medications with abuse potential." The report also noted that, "this question is beyond the issues normally considered for medical uses of drugs, and should not be a factor in evaluating the therapeutic potential of marijuana or cannabinoids."

"Advances in cannabinoid science of the past 16 years have given rise to a wealth of new opportunities for the development of medically useful cannabinoid-based drugs. The accumulated data suggest a variety of indications, particularly for pain relief, antiemesis, and appetite stimulation. For patients such as those with AIDS or who are undergoing chemotherapy, and who suffer simultaneously from severe pain, nausea, and appetite loss, cannabinoid drugs might offer broad-spectrum relief not found in any other single medication."

"The abundance of CB1 receptors in basal ganglia and reports of animal studies showing the involvement of cannabinoids in the control of movement suggest that cannabinoids would be useful in treating movement disorders in humans. Marijuana or CB1 receptor agonists might provide symptomatic relief of chorea, dystonia, some aspects of parkinsonism, and tics."