Medical Marijuana

1. More Than 148 Million Americans Live In a State With Effective Medical Marijuana Laws

"In all, more than 148 million Americans — about 47% of the U.S. population — now live in the 23 states, or the federal district, with effective medical marijuana laws. Eighty-five percent live in a state that has some form of medical cannabis legislation on the books."

Marijuana Policy Project, "State by State Medical Marijuana Laws 2015 with a December 2016 Supplement - How to Remove the Threat of Arrest," (Washington, DC: MPP, March 2017), p. 10, last accessed April 26, 2017.

2. Number of Approved Medical Cannabis Patients in the US

"Determining exactly how many patients use medical marijuana with state approval is difficult. According to a 2002 study published in the Journal of Cannabis Therapeutics, an estimated 30,000 California patients and another 5,000 patients in eight other states possessed a physician’s recommendations to use cannabis medically.67 More recent estimates are much higher. The New England Journal of Medicine reported in August 2005, for example, that an estimated 115,000 people have obtained marijuana recommendations from doctors in the states with programs.68
"Although 115,000 people may be approved medical marijuana users, the number of patients who have actually registered is much lower. A July 2005 CRS telephone survey of the state programs revealed a total of 14,758 registered medical marijuana users in eight states.69 (Maine and Washington do not maintain state registries, and Rhode Island, New Mexico, and Michigan had not yet passed their laws.) This number vastly understates the number of medical marijuana users, however, because California’s state registry was in pilot status, with only 70 patients so far registered."

Eddy, Mark, "Medical Marijuana: Review and Analysis of Federal and State Policies," Congressional Research Service (Washington, DC: March 31, 2009), p. 19.

3. Impact of Medical Marijuana Laws on Adolescent Marijuana Use

"Concerns about laws and policy measures that may inadvertently affect youth drug use merit careful consideration. Our study does not show evidence of a clear relationship between legalization of marijuana for medical purposes and youth drug use for any age group, which may provide some reassurance to policymakers who wish to balance compassion for individuals who have been unable to find relief from conventional medical therapies with the safety and well-being of youth. Further research is required to track the trends in marijuana use among adolescents, particularly with respect to different types of marijuana laws and implementation of laws in each state."

Choo, Esther K. et al. (2014), "The Impact of State Medical Marijuana Legislation on Adolescent Marijuana Use," Journal of Adolescent Health, Volume 55, Issue 2, p. 160 - 166.

4. Potential Therapeutic Uses of Cannabidiol (CBD)

"Recent developments suggest that non-psychotropic phytocannabinoids exert a wide range of pharmacological effects (Figure 1), many of which are of potential therapeutic interest. The most studied among these compounds is CBD, the pharmacological effects of which might be explained, at least in part, by a combination of mechanisms of action (Table 1, Figure 1). CBD has an extremely safe profile in humans, and it has been clinically evaluated (albeit in a preliminary fashion) for the treatment of anxiety, psychosis, and movement disorders. There is good pre-clinical evidence to warrant clinical studies into its use for the treatment of diabetes, ischemia and cancer. The design of further clinical trials should: i) consider the bell-shaped pattern of the dose–response curve that has been observed in pre-clinical pharmacology, and ii) establish if CBD is more effective or has fewer unwanted effects than other medicines. A sublingual spray that is a standardized Cannabis extract containing approximately equal quantities of CBD and D9-THC (Sativex®), has been shown to be effective in treating neuropathic pain in multiple sclerosis patients [76].
"The pharmacology of D9-THCV (i.e. CB1 antagonism associated with CB2 agonist effects) is also intriguing because it has the potential of application in diseases such as chronic liver disease or obesity—when it is associated with inflammation—in which CB1 blockade together with some CB2 activation is beneficial.
"The plant Cannabis is a source of several other neglected phytocannabinoids such as CBC and CBG. Although the spectrum of pharmacological effects of these compounds is largely unexplored, their potent action at TRPA1 and TRPM8 might make these compounds new and attractive tools for pain management."

Izzo,Angelo A.; Borrelli, Francesca; Capasso, Raffaele; Di Marzo, Vincenzo; and Mechoulam, Raphael, "Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb," Trends in Pharmacological Sciences (London, United Kingdom: October 2009) Vol. 30, Issue 10, pp. 525-526.

5. Known Therapeutic Benefits From Medicinal Cannabinoids

"Cannabis preparations exert numerous therapeutic effects. They have antispastic, analgesic, antiemetic, neuroprotective, and anti-inflammatory actions, and are effective against certain psychiatric diseases. Currently, however, only one cannabis extract is approved for use. It contains THC and CBD [cannabidiol] in a 1:1 ratio and was licensed in 2011 for treatment of moderate to severe refractory spasticity in multiple sclerosis (MS). In June 2012 the German Joint Federal Committee (JFC, Gemeinsamer Bundesausschuss) pronounced that the cannabis extract showed a 'slight additional benefit' for this indication and granted a temporary license valid up to 2015.
"The cannabis extract, which goes by the generic name nabiximols, has been approved by regulatory bodies in Germany and elsewhere for use as a sublingual spray. In the USA, dronabinol has been licensed since 1985 for the treatment of nausea and vomiting caused by cytostatic therapy and since 1992 for loss of appetite in HIV/Aids-related cachexia. In Great Britain, nabilone has been sanctioned for treatment of the side effects of chemotherapy in cancer patients (Box 1).
"In addition to these confirmed indications, there is solid evidence from a large number of small controlled trials that cannabinoid receptor agonists have an analgesic action, particularly in neuropathic pain; however, no country has yet approved their use for this purpose."

Franjo Grotenhermen, Dr. med., and Kirsten Müller-Vahl, Prof. Dr. med., "The Therapeutic Potential of Cannabis and Cannabinoids," Deutsch Arzteblatt International, 2012 July; 109(29-30): 495–501. doi: 10.3238/arztebl.2012.0495

6. Known Therapeutic Benefits From Medicinal Cannabinoids

"Evidence is accumulating that cannabinoids may be useful medicine for certain indications. Control of nausea and vomiting and the promotion of weight gain in chronic inanition are already licensed uses of oral THC (dronabinol capsules). Recent research indicates that cannabis may also be effective in the treatment of painful peripheral neuropathy and muscle spasticity from conditions such as multiple sclerosis [58]. Other indications have been proposed, but adequate clinical trials have not been conducted. As these therapeutic potentials are confirmed, it will be useful if marijuana and its constituents can be prescribed, dispensed, and regulated in a manner similar to other medications that have psychotropic effects and some abuse potential. Given that we do not know precisely which cannabinoids or in which combinations achieve the best results, larger and more representative clinical trials of the plant product are warranted. Because cannabinoids are variably and sometimes incompletely absorbed from the gut, and bioavailability is reduced by extensive first pass metabolism, such trials should include delivery systems that include smoking, vaporization, and oral mucosal spray in order to achieve predictable blood levels and appropriate titration. Advances in understanding the medical indications and limitations of cannabis in its various forms should facilitate the regulatory and legislative processes."

Igor Grant, J. Hampton Atkinson, Ben Gouaux and Barth Wilsey, "Medical Marijuana: Clearing Away The Smoke," The Open Neurology Journal, 2012, 6:18-25. doi: 10.2174/1874205X01206010018.

7. Impact of State-Legal Medical Marijuana on Adolescent Marijuana Use

"In conclusion, our study of self-reported marijuana use by adolescents in states with a medical marijuana policy compared with a sample of geographically similar states without a policy does not demonstrate increases in marijuana use among high school students that may be attributed to the policies."

Choo, Esther K. et al., "The Impact of State Medical Marijuana Legislation on Adolescent Marijuana Use," Journal of Adolescent Health, August 2014, Volume 55, Issue 2, p. 160 - 166.

8. Cannabinoids and the Chemical Composition of Cannabis

"Essentially a herbal cannabinoid drug, the resin-secreting flowers of select varietals of the female cannabis plant contain approximately 6 dozen of different phytocannabinoids or plant-derived cannabinoids; these compounds are generally classified structurally as terpenophenolics with a 21-carbon molecular scaffold.24 Other compounds, such as terpenoids, flavonoids, and phytosterols, which are common to many other botanicals, are also produced by cannabis and have some demonstrated pharmacologic properties.25,26 The best known naturally produced analgesic cannabinoids generally found in highest concentrations are THC and cannabidiol. They occur in their acid forms in herbal cannabis and must be decarboxylated to become activated. Five minutes of heating at 200 to 210°C has been determined as the optimal conditions for maximal decarboxylation; with a flame, where temperatures of 600°C are achieved, only a few seconds are needed.27"

Aggarwal, Sunil K., "Cannabinergic Pain Medicine: A Concise Clinical Primer and Survey of Randomized-controlled Trial Results," Clinical Journal of Pain (Philadelphia, PA: February 23, 2012), p. 2.

9. Safety of Cannabis

"Generally, as analgesics, cannabinoids have minimal toxicity and present no risk of lethal overdose.48 End-organ failure secondary to medication effect has not been described and no routine laboratory monitoring is required in patients taking these medications."

Aggarwal, Sunil K., "Cannabinergic Pain Medicine: A Concise Clinical Primer and Survey of Randomized-controlled Trial Results," Clinical Journal of Pain (Philadelphia, PA: February 23, 2012), p. 3.

10. Lower Opioid Overdose Mortality Rates In States With Medical Cannabis Laws

"Although the mean annual opioid analgesic overdose mortality rate was lower in states with medical cannabis laws compared with states without such laws, the findings of our secondary analyses deserve further consideration. State-specific characteristics, such as trends in attitudes or health behaviors, may explain variation in medical cannabis laws and opioid analgesic overdose mortality, and we found some evidence that differences in these characteristics contributed to our findings. When including state-specific linear time trends in regression models, which are used to adjust for hard-to-measure confounders that change over time, the association between laws and opioid analgesic overdose mortality weakened. In contrast, we did not find evidence that states that passed medical cannabis laws had different overdose mortality rates in years prior to law passage, providing a temporal link between laws and changes in opioid analgesic overdose mortality. In addition, we did not find evidence that laws were associated with differences in mortality rates for unrelated conditions (heart disease and septicemia), suggesting that differences in opioid analgesic overdose mortality cannot be explained by broader changes in health. In summary, although we found a lower mean annual rate of opioid analgesic mortality in states with medical cannabis laws, a direct causal link cannot be established."

Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.

11. Impact of Medical Marijuana Laws on Crime Rates

"The central finding gleaned from the present study was that MML is not predictive of higher crime rates and may be related to reductions in rates of homicide and assault. Interestingly, robbery and burglary rates were unaffected by medicinal marijuana legislation, which runs counter to the claim that dispensaries and grow houses lead to an increase in victimization due to the opportunity structures linked to the amount of drugs and cash that are present. Although, this is in line with prior research suggesting that medical marijuana dispensaries may actually reduce crime in the immediate vicinity [8]."

Robert G. Morris, Michael TenEyck, JC Barnes, and Tomislav V. Kovandzic, "The Effect of Medical Marijuana Laws On Crime: Evidence From State Panel Data, 1990-2006," PLoS ONE 9(3): e92816. March 2014. doi: 10.1371/journal.pone.0092816

12. Effect of Medical Marijuana Legalization On Crime Rates

"In sum, these findings run counter to arguments suggesting the legalization of marijuana for medical purposes poses a danger to public health in terms of exposure to violent crime and property crimes. To be sure, medical marijuana laws were not found to have a crime exacerbating effect on any of the seven crime types. On the contrary, our findings indicated that MML precedes a reduction in homicide and assault. While it is important to remain cautious when interpreting these findings as evidence that MML reduces crime, these results do fall in line with recent evidence [29] and they conform to the longstanding notion that marijuana legalization may lead to a reduction in alcohol use due to individuals substituting marijuana for alcohol [see generally 29, 30]. Given the relationship between alcohol and violent crime [31], it may turn out that substituting marijuana for alcohol leads to minor reductions in violent crimes that can be detected at the state level. That said, it also remains possible that these associations are statistical artifacts (recall that only the homicide effect holds up when a Bonferroni correction is made)."

Robert G. Morris, Michael TenEyck, JC Barnes, and Tomislav V. Kovandzic, "The Effect of Medical Marijuana Laws On Crime: Evidence From State Panel Data, 1990-2006," PLoS ONE 9(3): e92816. March 2014. doi: 10.1371/journal.pone.0092816

13. Effect Of Medical Marijuana Legalization On Crime Rates

"Given that the current results failed to uncover a crime exacerbating effect attributable to MML, it is important to examine the findings with a critical eye. While we report no positive association between MML and any crime type, this does not prove MML has no effect on crime (or even that it reduces crime). It may be the case that an omitted variable, or set of variables, has confounded the associations and masked the true positive effect of MML on crime. If this were the case, such a variable would need to be something that was restricted to the states that have passed MML, it would need to have emerged in close temporal proximity to the passage of MML in all of those states (all of which had different dates of passage for the marijuana law), and it would need to be something that decreased crime to such an extent that it ‘‘masked’’ the true positive effect of MML (i.e., it must be something that has an opposite sign effect between MML [e.g., a positive correlation] and crime [e.g., a negative correlation]). Perhaps the more likely explanation of the current findings is that MML laws reflect behaviors and attitudes that have been established in the local communities. If these attitudes and behaviors reflect a more tolerant approach to one another’s personal rights, we are unlikely to expect an increase in crime and might even anticipate a slight reduction in personal crimes."

Robert G. Morris, Michael TenEyck, JC Barnes, and Tomislav V. Kovandzic, "The Effect of Medical Marijuana Laws On Crime: Evidence From State Panel Data, 1990-2006," PLoS ONE 9(3): e92816. March 2014. doi: 10.1371/journal.pone.0092816

14. Harm Reduction and Alternative Delivery Methods for Cannabis Consumption

"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."

American Medical Association, Council on Science and Public Health, "Report 3 of the Council on Science and Public Health: Use of Cannabis for Medicinal Purposes" (December 2009), p. 15.

15. Safety of Medicinal Cannabis According to DEA Administrative Law Judge Francis Young

In 1988, 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."

US Department of Justice, Drug Enforcement Administration, "In the Matter of Marijuana Rescheduling Petition," [Docket #86-22], (September 6, 1988), p. 57.

16. Medicinal Cannabis and HIV-Related Neuropathic Pain

“Placebo-Controlled, Double Blind Trial of Medicinal Cannabis in Painful HIV Neuropathy”
Ronald J. Ellis, M.D., Ph.D., University of California, San Diego
(cannabis and HIV neuropathy) "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. A structured dose escalation-titration protocol was used to find an individualized, effective, safe, and well-tolerated dose for each subject. Participants continued on their usual analgesic medications throughout the trial, with the dose and amount of these medications being recorded daily.
"The full results of this study were published in the journal Neuropsychopharmacology (Ellis, et al., 2008 – see reference list). In brief, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among completers, pain relief was significantly greater with cannabis than placebo. The proportion of subjects achieving at least 30% pain relief was again significantly greater with cannabis (46%) compared to placebo (18%). 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."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 10.

17. Cannabis and Cancer Pain

"• 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. Today, capsules of ?9-tetrahydrocannabinol (dronabinol (Marinol)) and its synthetic analogue nabilone (Cesamet) are approved for this purpose.
"• Other potential palliative effects of cannabinoids in cancer patients — supported by Phase III clinical trials — include appetite stimulation and pain inhibition. In relation to the former, dronabinol is now prescribed for anorexia associated with weight loss in patients with AIDS.
"• 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 non-tumour cells.
"• Cannabinoids have favourable drug-safety profiles and do not produce the generalized toxic effects of conventional chemotherapies. The use of cannabinoids in medicine, however, is limited by their psychoactive effects, and so cannabinoid-based therapies that are devoid of unwanted side effects are being designed.
"• Further basic and preclinical research on cannabinoid anticancer properties is required. It would be desirable that clinical trials could accompany these laboratory studies to allow us to use these compounds in the treatment of cancer."

Guzman, Manuel, "Cannabinoids: Potential Anticancer Agents." Nature Reviews: Cancer (October 2003), p. 746.

18. Medical Cannabis Laws and Opioid Overdose Mortality Rates

"In an analysis of death certificate data from 1999 to 2010, we found that states with medical cannabis laws had lower mean opioid analgesic overdose mortality rates compared with states without such laws. This finding persisted when excluding intentional overdose deaths (ie, suicide), suggesting that medical cannabis laws are associated with lower opioid analgesic overdose mortality among individuals using opioid analgesics for medical indications. Similarly, the association between medical cannabis laws and lower opioid analgesic overdose mortality rates persisted when including all deaths related to heroin, even if no opioid analgesic was present, indicating that lower rates of opioid analgesic overdose mortality were not offset by higher rates of heroin overdose mortality. Although the exact mechanism is unclear, our results suggest a link between medical cannabis laws and lower opioid analgesic overdose mortality."

Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.

19. cannabis and neuropathic pain

“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. As customary in CMCR trials, participants were allowed to continue their usual regimen of pain medications (e.g., codeine, morphine, and others).
"The full results of this study have been published in the Journal of Pain (Wilsey, et al., 2008 – see reference list). Thirty-eight patients underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis; of these, 32 completed all three smoking sessions. The study demonstrated an analgesic response to smoking cannabis with no significant difference between the low and the high dose cigarettes. The study concluded that both low and high cannabis doses were efficacious in reducing neuropathic pain of diverse causes."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 11.

20. Cannabis and Neuropathic Pain

"In this randomized clinical trial, smoked cannabis at maximum tolerable dose (1–8% THC), significantly reduced neuropathic pain intensity in HIV-associated DSPN [distal sensory predominant polyneuropathy] compared to placebo, when added to stable concomitant analgesics. Using verbal descriptors of pain magnitude from DDS [Descriptor Differential Scale], cannabis was associated with an average reduction of pain intensity from ‘strong’ to ‘mild to moderate’. Also, cannabis was associated with a sizeable (46%) and significantly greater (vs 18% for placebo) proportion of patients who achieved what is generally considered clinically meaningful pain relief (eg X30% reduction in pain; Farrar et al, 2001). Mood disturbance, physical disability, and quality of life all improved significantly for subjects during study treatments, regardless of treatment order."

Ellis, Ronald J; Toperoff, Will; Vaida, Florin; van den Brande, Geoffrey; Gonzales, James; Gouaux, Ben; Bentley, Heather; and Atkinson, J. Hampton, "Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial," Neuropsychopharmacology (Nashville, TN : American College of Neuropsychopharmacology, 2009), Vol. 34, p. 678.

21. Cannabis and Fibromyalgia

"We observe significant improvement of symptoms of FM [fibromyalgia] in patients using cannabis in this study although there was a variability of patterns. This information, together with evidence of clinical trials and emerging knowledge of the endocannabinoid system and the role of the stress system in the pathopysiology of FM suggest a new approach to the suffering of these patients. The present results together with previous evidence seem to confirm the beneficial effects of cannabinoids on FM symptoms."

Fiz, Jimena; Dura´n, Marta; Capella, Dolors; Carbonel, Jordi; Farre, Mag?, "Cannabis Use in Patients with Fibromyalgia: Effect on Symptoms Relief and Health-Related Quality of Life," PLoS Medicine (Cambridge, United Kingdom: Public Library of Science, April 2011) Vol. 6, Issue 4, p. 4.

22. The Effect of Cannabis on Neuropathic Pain in HIV-Related Peripheral Neuropathy

"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. Patients continued on any concurrent analgesic medications (e.g., gabapentin, amitriptyline, narcotics, NSAIDs) which they were prescribed prior to the trial; the dose and amount of the medications were recorded daily.
"The full results of this study appear in the journal Neurology (Abrams, et al., 2007– see reference list). In brief, 55 patients were randomized and 50 completed the entire trial. Smoked cannabis reduced daily pain by 34% compared to 17% with placebo. 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."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 10.

23. Pain and Medical Cannabis Use

"By providing a medical geographic patient utilization 'snapshot' of 236.4 patient-years of the use of MC [Medical Cannabis] at a regional pain clinic, this study provides further insight into the applicability of cannabinoid botanicals in the management of a broad range of refractory chronic pain conditions in adults, from myofascial pain and discogenic back pain to neuropathic pain and central pain syndromes. With physicians employing proper chart documentation of appropriate use, efficacy, and side effects at patient visits, in a manner similar to that used in opioid management of pain, there will hopefully be additional reports in the future on MC use in pain management to add to the clinical database.
"Such a literature can grow only if certain stereotypes and myths about MC use are dispelled amongst pain management specialists and their regulators. The results presented here should help to deconstruct mythologies about the kinds of patients accessing MC treatment, including their young age or their propensity to malinger or feign disease. One prominent mythology is that patients who receive treatment with MC are not 'truly sick.'45 An examination of the chart review data, which includes both subjective and objective diagnostic data substantiating patients’ chronic pain illnesses, helps to deflate this concern."

Aggarwal, Sunil K.; Carter, Gregory T.; Sullivan, Mark D.; ZumBrunnen, Craig; Morrill, Richard; and Mayer, Jonathan D., "Characteristics of patients with chronic pain accessing treatment with medical cannabis in Washington State," Journal of Opiod Management, (Weston, Massachusetts: September/October 2009), Vol. 5, p. 264.

24. Medicinal Cannabis and Neuropathic Pain

"We found that 25 mg herbal cannabis with 9.4% tetrahydrocannabinol, administered as a single smoked inhalation three times daily for five days, significantly reduced average pain intensity compared with a 0% tetrahydrocannabinol cannabis placebo in adult participants with chronic post-traumatic or postsurgical neuropathic pain. We found significant improvements in measures of sleep quality and anxiety. We have shown the feasibility of a single-dose delivery method for smoked cannabis, and that blinding participants to treatment allocation is possible using this method."

Ware, Mark A.; Wang, Tongtong; Shapiro, Stan; Robinson, Ann; Ducruet, Thierry; Huynh,Thao; Gamsa, Ann; Bennett, Gary J.; and Collet, Jean-Paul,"Smoked cannabis for chronic neuropathic pain: a randomized controlled trial" (Ottawa, ON: Canadian Medical Association, October 5, 2010), p. E697-E700.

25. Analgesic Efficacy of Smoked Cannabis

"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). Nineteen healthy volunteers were enrolled, and 15 completed all four smoking sessions. In brief, five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 minutes after cannabis exposure there was a significant decrease in capsaicin-induced pain with the medium dose (4%) and a significant increase in pain with the high dose (8%). There was no significant effect seen with low dose (2%). There was a significant inverse relationship between pain perception and plasma THC. 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)."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), pp. 11.

26. Medicinal Cannabis and Migraines

"The information reviewed above indicates that cannabis has a long established history of efficacy in migraine treatment. Clinical use of the herb and its extracts for headache has waxed and waned for 1200 years, or perhaps much longer, in a sort of cannabis interruptus. It is only contemporaneously that supportive biochemical and pharmacological evidence for the indication is demonstrable. Cannabis’ unique ability to modulate various serotonergic receptor subtypes, inhibit glutamatergic-mediated toxicities, simultaneously provide antiinflammatory activity and provide acute symptomatic and chronic preventive relief make it unique among available treatments for this disorder."

Russo, Ethan, "Hemp for Headache: An In-Depth Historical and Scientific Review of Cannabis in Migraine Treatment," Journal of Cannabis Therapeutics (September 2000) Vol. 1, pp. 73-74.

27. Cannabinoids and Gastrointestinal Functions

"The role of the endocannabinoid system in the control of GI functions under physiological and pathological conditions has recently received increased interest. Within the last 5 years, more than half of all studies on the roles of the endocannabinoid system in the GI tract have been published. The current state of knowledge of the physiology and pharmacology of cannabinoids has largely increased, providing new potential tools for the treatment of several GI diseases. The symptoms of the most common GI disorders, IBS and inflammatory bowel disease, affect more than 20% of the population in Western countries and cause great discomforts [106]. Intestinal cramping, nausea, chronic diarrhoea and inflammation are all symptoms onto which the cannabinoids may be effective. Cannabis derivatives and other newly developed cannabinoids may represent promising tools for the treatment of different GI disorders because they can act at multiple sites, covering a wide spectrum of symptoms."

Massa, Federico; Storr, Martin; and Lutz, Beat, "The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract," Journal of Molecular Medicine (Berlin, Germany: August 26, 2005) Vol. 83, p. 951.

28. Medicinal Cannabis and Nausea

"This study was designed to determine how therapeutic users of cannabis rate its effectiveness as an anti-emetic, and particularly as a treatment for nausea and vomiting of pregnancy. In general (not specific to pregnancy), the vast majority of our respondents considered cannabis to be extremely effective or effective as a therapy for nausea (93%) and vomiting (75%), and as an appetite stimulant (95%). In the context of pregnancy, cannabis was rated as extremely effective or effective by 92% of the respondents who had used it as a therapy for nausea and vomiting (morning sickness)."

Westfall, Rachel E.; Janssen, Patricia A.; Lucas, Philippe; and Capler, Rielle, "Survey of medicinal cannabis use among childbearing women: Patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness'," Contemporary Therapies in Clinical Practice (United Kingdom: November 2009) Vol. 15, Issue 4, p. 32.

29. Cannabinoids and Multiple Sclerosis

Cannabis and Multiple Sclerosis

"Using an objective measure, we saw a beneficial effect of inhaled cannabis on spasticity among patients receiving insufficient relief from traditional treatments. Although generally well-tolerated, smoking cannabis had acute cognitive effects. Larger, long-term studies are needed to confirm our findings and determine whether lower doses can result in beneficial effects with less cognitive impact."

Corey-Bloom, Jody; Wolfson, Tanya; Gamst, Anthony; Jin, Shelia; Marcotte, Thomas D.; Bentley, Heather; and Gouaux, Ben, "Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial," Canadian Medical Association Journal (Ottawa, Ontario: May 14, 2012), p. 7.

30. Medical Marijuana - Research - 6-5-10

(Cannabinoids and Multiple Sclerosis) "We found evidence that combined extracts of THC and CBD [cannabidiol] may reduce symptoms of spasticity in patients with MS. Although the subjective experience of symptom reduction was generally found to be significant, objective measures of spasticity failed to provide significant changes. In a previous study of spasticity-related pain, MS patients also reported a subjective perception of symptom reduction with cannabinoids [10]. However, since at least one past animal study has provided objective, physiological evidence for the antispastic properties of cannabinoids [7], the distinction between perceived symptom relief and objective physiological changes in humans should therefore be primary in future research efforts.
"Given that adverse events occurred in each reviewed trial, we also encourage future comparison studies of cannabis treatments at a wide range of dosage in order to balance potential side effects with maximum therapeutic benefit.
"Finally, there is evidence that cannabinoids may provide neuroprotective and anti-inflammatory benefits in MS. Neuroinflammation, found in autoimmune diseases such as MS, has been shown to be reduced by cannabinoids through the regulation of cytokine levels in microglial cells [25]. The therapeutic potential of cannabinoids in MS is therefore comprehensive and should be given considerable attention."

Lakhan, Shaheen E and Rowland, Marie, "Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review," BMC Neurology (Los Angeles, CA: Global Neuroscience Initiative Foundation, December 2009) Vol. 9, p. 63.

31. Medical Marijuana - Research - 11-9-12

“Short-Term Effects of Cannabis Therapy on Spasticity in Multiple-Sclerosis”
Jody Corey-Bloom, M.D., University of California, San Diego
(cannabis and muscle spasticity) "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. Patients were allowed to continue their usual treatments for spasticity and pain while participating in the research.
"The full results of this study are being submitted for publication. Initial results were presented at the meeting of the American College of Neuropsychopharmacology in 2007. Thirty patients with multiple sclerosis were enrolled. Compared to placebo cigarettes, cannabis was found to significantly reduce both an objective measure of spasticity, and pain intensity. 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."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 12.

32. Medical Marijuana - Research - 12-16-09

Cannabis and HIV/AIDS

(Medical Cannabis and HIV Treatment) "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."

Abrams, Donald I., MD, et al., "Short-Term Effects of Cannabinoids in Patients with HIV-1 Infection - A Randomized, Placebo-Controlled Clinical Trial," Annals of Internal Medicine, Aug. 19, 2003, Vol. 139, No. 4 (American College of Physicians), p. 264.

33. Medical Marijuana - Research - 12-16-09

(Medical Cannabis and HIV) "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."

Abrams, Donald I., MD, et al., "Short-Term Effects of Cannabinoids in Patients with HIV-1 Infection - A Randomized, Placebo-Controlled Clinical Trial," Annals of Internal Medicine, Aug. 19, 2003, Vol. 139, No. 4 (American College of Physicians), p. 258.

34. Cannabis and Viral Load in HIV-Positive Patients and Patients with Hep C Infections

"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."

American Medical Association, Council on Science and Public Health, "Report 3 of the Council on Science and Public Health: Use of Cannabis for Medicinal Purposes" (December 2009), p. 15.

35. Medical Marijuana - Research - 1-6-10

(Safety of Cannabis During Treatment) "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."

Guzman, Manuel, "Cannabinoids: Potential Anticancer Agents." Nature Reviews: Cancer (October 2003), p. 752.

36. Number of Published Journal Articles on Potential Therapeutic Uses of Medical Cannabis

Potential Therapeutic Uses and Benefits from Medical Cannabis

"The length of this review, necessitated by the steady growth in the number of indications for the potential therapeutic use of cannabinoid-related medications, is a clear sign of the emerging importance of this field. This is further underlined by the quantity of articles in the public database dealing with the biology of cannabinoids, which numbered ~200 to 300/year throughout the 1970s to reach an astonishing 5900 in 2004. The growing interest in the underlying science has been matched by a growth in the number of cannabinoid drugs in pharmaceutical development from two in 1995 to 27 in 2004, with the most actively pursued therapeutic targets being pain, obesity, and multiple sclerosis (Hensen, 2005)."

Pacher, Pal; Batkai, Sandor; and Kunos, George, "The Endocannabinoid System as an Emerging Target of Pharmacotherapy," Pharmacological Reviews (Bethesda, MD: American Society for Pharmacology and Experimental Therapeutics, September 2006), Vol. 58, No. 3. p. 441.

37. Effect of CBD on Learned Fear and Potential in Treatment of Post Traumatic Stress Disorder (PTSD)

"A growing body of literature provides compelling evidence that CBD has anxiolytic effects and recent studies have established a role for CBD in regulating learned fear by dampening its expression, disrupting its reconsolidation, and facilitating its extinction. The opposing effects of CBD on fear memory reconsolidation and extinction make it particularly attractive as a potential adjunct to psychological therapy as both may lead to lasting reductions in learned fear expression. Our novel data also suggests that CBD reduces the expression of fear memory related to both discrete and contextual cues. Although we found no effect of CBD on auditory fear extinction, decreasing fear expression during extinction without interfering in its encoding is still a useful property that has clinical implications. In this respect CBD might be an improvement over other available drugs used for treating the fear-related symptoms of phobias and PTSD, which can impair extinction (e.g., benzodiazepines) or have a less favorable side effect profile (e.g., antidepressants)."

Jurkus R, Day HLL, Guimarães FS, Lee JLC, Bertoglio LJ, Stevenson CW. Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders. Frontiers in Pharmacology. 2016;7:454. doi:10.3389/fphar.2016.00454.

38. Medical Marijuana - Research - 5-21-10

(Endocannabinoid Deficiency) "Baker et al. have described how endocannabinoids may demonstrate an impairment threshold if too high, and a range of normal function below which a deficit threshold may be crossed [112]. Syndromes of CECD [Clinical Endocannabinoid Deficiency] may be congenital or acquired. In the former case, one could posit that genetically-susceptible individuals might produce inadequate endocannabinoids, or that their degradation is too rapid. The same conditions might be acquired in injury or infection."

Russo, Ethan, "Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?," Neuroendocrinology Letters (Stockholm, Sweden: Society of Integrated Sciences, Feb-Apr 2004) Nos.1/2, Vol.25, p. 38.

39. Medical Marijuana - Research - 8-23-10

Anti-Tumor Properties

(Cannabinoids and Skin Cancer) "The present data indicate that local cannabinoid administration may constitute an alternative therapeutic approach for the treatment of nonmelanoma skin cancer. Of further therapeutic interest, we show that skin cells express functional CB2 receptors. The synergy between CB1 and CB2 receptors in eliciting skin tumor cell apoptosis reported here is nonetheless intriguing because it is not observed in the case of cannabinoid-induced glioma cell apoptosis (21, 22). In any event, the present report, together with the implication of CB2- or CB2-like receptors in the control of peripheral pain (40–42) and inflammation (41), opens the attractive possibility of finding cannabinoidbased therapeutic strategies for diseases of the skin and other tissues devoid of nondesired CB1-mediated psychotropic side effects."

Casanova, M. Llanos; Blázquez,Cristina; Martínez-Palacio, Jesús; Villanueva, Concepción; Fernández-Aceñero, Jesús; Huffman, John W.; Jorcano, José L.; and Guzmán, Manuel, "Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors," Journal of Clinical Investigation (Ann Arbor, MI: American Society for Clinical Investigation, January 2003), p. 49.

40. Medical Cannabis Use Among Patients Receiving Substance Abuse Treatment

"It is clear, however, that cannabis use did not compromise substance abuse treatment amongst the medical marijuana using group. In fact, medical marijuana users seemed to fare equal to or better than non-medical marijuana users in every important outcome category. Movement from more harmful to less harmful drugs is an improvement worthy of consideration by treatment providers and policymakers. The economic cost of alcohol use in California has been estimated at $38 billion [30]. Add to this the harm to individuals, families, communities, and society from methamphetamine, heroin, and cocaine, and a justification can be made for medical marijuana in addictions treatment as a harm reduction practice. As long as marijuana use is not associated with poorer outcomes, then replacing other drug use with marijuana may lead to social and economic savings."

Swartz, Ronald, "Medical marijuana users in substance abuse treatment," Harm Reduction Journal (London, United Kingdom: March 2010) Vol. 7, p. 7-8.

41. Medical Marijuana - Research - 8-23-10

(Cannabis and Mantle Cell Lymphoma) "In conclusion, our study demonstrates that the cannabinoid receptor agonists R(+)-MA and Win55 induce a sequence of signaling events leading to cell death of MCL [Mantle Cell Lymphoma] cells. The requirement of ligation of both CB1 and CB2 [receptors] raises the possibility that cannabinoids may be used to selectively target MCL cells to undergo apoptosis."
Note: According to the study authors: "MCL is a malignant B-cell lymphoma with an aggressive course and generally a poor clinical outcome. MCL tumors respond to chemotherapy, but the remissions are short and the median survival is only 3 years."

Gustafsson, Kristin; Christensson, Birger; Sander, Birgitta; and Flygare, Jenny, "Cannabinoid Receptor-Mediated Apoptosis Induced by R(+)-Methanandamide and Win55,212-2 Is Associated with Ceramide Accumulation and p38 Activation in Mantle Cell Lymphoma," Molecular Pharmacology (Bethesda, MD: The American Society for Pharmacology and Experimental Therapeutics, August 2006), p. 1619.

42. Medical Marijuana - Research - 6-20-10

(Potential Antitumor Properties of Cannabinoids) "In conclusion, our data indicate that cannabidiol, and possibly Cannabis extracts enriched in this natural cannabinoid, represent a promising nonpsychoactive antineoplastic strategy. In particular, for a highly malignant human breast carcinoma cell line, we have shown here that cannabidiol and a cannabidiol-rich extract counteract cell growth both in vivo and in vitro as well as tumor metastasis in vivo. Cannabidiol exerts its effects on these cells through a combination of mechanisms that include either direct or indirect activation of CB2 and TRPV1 receptors and induction of oxidative stress, all contributing to induce apoptosis."

Ligresti, Alessia; Moriello, Aniello Schiano; Starowicz, Katarzyna; Matias, Isabel; Pisanti, Simona; De Petrocellis, Luciano; Laezza, Chiara; Portella, Giuseppe; Bifulco, Maurizio; and Di Marzo, Vincenzo, "Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma," The Journal of Pharmacology and Experimental Therapeutics (Bethesda, MD: The American Society for Pharmacology and Experimental Therapeutics, March 2004) Vol. 318, No. 3, pp. 1386-1387.

43. Medical Marijuana - Research - 1-11-10

(Potential of Cannabinoids in Cancer Therapy) "The use of cannabinoids in medicine is limited by the psychoactive effects mediated by neuronal CB1 receptors (1, 2). Although these adverse effects are within the range of those accepted for other medications, especially in cancer treatment, and tend to disappear with tolerance upon continuous use, it is obvious that cannabinoid-based therapies devoid of side effects would be desirable (3–5). Because glioma cells express functional CB2 receptors (7), we tested the effect of the nonpsychoactive, CB2 receptor-selective agonist JWH-133 and found that it indeed depresses MMP-2 expression in vivo. Likewise, the use of CB receptor type–selective antagonists indicates that CB2 receptors participate in THC-induced inhibition of MMP-2 expression in glioma cells. As selective CB2 receptor activation to mice has been shown to inhibit the growth and angiogenesis of gliomas (11, 13, 27), skin carcinomas (8) and melanomas (15), our observations further support the possibility of finding cannabinoid-based antitumoral strategies devoid of nondesired psychotropic side effects."

Cristina Bla´zquez, Mar?´a Salazar, Arkaitz Carracedo, Mar Lorente, Ainara Egia, Luis Gonza´lez-Feria, Amador Haro, Guillermo Velasco, and Manuel Guzman, "Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression," Cancer Research (March 2008), p. 1951.

44. Medical Marijuana - Research - 10-27-10

(Cannabidiol (CBD) and Breast Cancer) "Our results, which were obtained in a clinically relevant animal model of ErbB2-positive breast cancer, suggest that these highly aggressive and low responsive tumors could be efficiently treated with nonpsychoactive CB2-selective agonists without affecting the surrounding healthy tissue."

Caffarel, María M; Andradas, Clara; Mira, Emilia; Pérez-Gómez, Eduardo; Cerutti; Camilla; Moreno-Bueno, Gema; Flores, Juana; García-Realm, Isabel; Palacios, José; Mañes, Santos; Guzmán, Manuel; Sánchez, Cristina, "Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition," Molecular Cancer (London, United Kingdom: July 22, 2010), p. 1 and P. 8.

45. Medical Marijuana - Research - 6-5-10

(Cannabinoids and Cancer Cells) "Cannabinoids, the active components of marijuana and their other natural and synthetic analogues have been reported as useful adjuvants to conventional chemotherapeutic regimens for preventing nausea, vomiting, pain, and for stimulating appetite. Before the discovery of specific cannabinoid systems and receptors, it was speculated that cannabinoids produced their effects via nonspecific interaction with cell membranes. Cannabinoids are proving to be unique based on their targeted action on cancer cells and their ability to spare normal cells. Variation in the effects of cannabinoids in different cell lines and tumor model could be due to the differential expression of CB1 and CB2 receptors. Thus, overexpression of cannabinoid receptors may be effective in killing tumors, whereas low or no expression of these receptors could lead to cell proliferation and metastasis because of the suppression of the antitumor immune response."

Sarfaraz, Sami; Adhami, Vaqar M.; Syed, Deeba N.; Afaq, Farrukh; and Mukhtar, Hasan, "Cannabinoids for Cancer Treatment: Progress and Promise," Cancer Research (Philadelphia, PA: American Association for Cancer Research, January 2008) Vol. 68, pp. 341-342.

46. Medical Marijuana - Research - 1-6-10

(Cannabidiol (CBD) and Cancer Therapy) "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."

Massi, Paola; Vaccani, Angelo; Ceruti, Stefania; Colombo, Arianna; Abbracchio, Maria P., and Parolaro, Daniela, "Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines," The Journal of Pharmacology and Experimental Therapeutics (Bethesda, MD: The American Society for Pharmacology and Experimental Therapeutics, March 2004) Vol. 308, p. 845.

47. Medical Marijuana - Research - 12-22-10

Cannabis and Diabetes

(Cannabinoids and Diabetic Cardiomyopathy) "Remarkably, CBD [Cannabidiol] attenuated myocardial dysfunction, cardiac fibrosis, oxidative/nitrative stress, inflammation, cell death, and interrelated signaling pathways. Furthermore, CBD also attenuated the high glucose-induced increased reactive oxygen species generation, nuclear factor-

Rajesh, Mohanraj; Mukhopadhyay,Partha; Batkai, Sandor; Patel, Vivek; Patel, Keita; Matsumoto, Shingo; Kashiwaya, Yoshihiro; Horvath, Béla; Mukhopadhyay, Bani; Becker, Lauren; Hasko, György; Liaudet, Lucas; Wink, David A.; Veves, Aristidis; Mechoulam, Raphael; Pacher, Pal, "Cannabidiol Attenuates Cardiac Dysfunction, Oxidative Stress, Fibrosis, and Inflammatory and Cell Death Signaling Pathways in Diabetic Cardiomyopathy," Journal of the American College of Cardiology (San Diego, CA: American College of Cardiology Foundation: December 2010) Vol. 56, No. 25, p. 2115.

48. Medical Marijuana - Research - 6-12-10

(Cannabidiol (CBD) and Diabetic Retinopathy) "Drugs that enhance extracellular adenosine signaling have been of clinical interest in treatment of inflammation after myocardial or cerebral ischemia.25,26 CBD as an anti-inflammatory drug is an attractive alternative to smoking marijuana because of its lack of psychoactive effects.27 CBD is known to be nontoxic in humans,28 which has previously been a problem for other nucleoside inhibitor drugs.29,30"

Liou, Gregory I.; Auchampach, John A.; Hillard, Cecilia J.; Zhu, Gu; Yousufzai, Bilal; Salman, Mian; Khan, Sohail; and Khalifa, Yousuf, "Mediation of Cannabidiol Anti-inflammation in the Retina by Equilibrative Nucleoside Transporter and A2A Adenosine Receptor," Investigative Ophthalmology & Visual Science (Rockville, MD: Association for Research in Vision and Ophthalmology, December 2008), Vol. 49, No. 12, p. 5531.

49. Medical Marijuana - Research - 6-12-10

(Cannabidiol (CBD) and Diabetic Retinopathy) "Recent evidence suggests that local inflammation plays a major role in the pathogenesis of diabetic retinopathy. The function of CBD as an antioxidant to block oxidative stress and as an inhibitor of adenosine reuptake to enhance a self-defense mechanism against retinal inflammation represents a novel therapeutic approach to the treatment of ophthalmic complications associated with diabetes."

Loiu, George, " Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation, " World Journal of Diabetes (Beijing, China: Beijing Baishideng BioMed Scientific Co., March 15, 2010), p. 15.

50. Cannabidiol (CBD) As Antipsychotic

"Our results provide evidence that the non-cannabimimetic constituent of marijuana, cannabidiol, exerts clinically relevant antipsychotic effects that are associated with marked tolerability and safety, when compared with current medications."

Leweke, FM; Piomelli, D; Pahlisch, F; Muhl, D; Gerth, CW; Hoyer, C; Klosterkotter, J; Hellmich, M; and Koethe, D, "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia," Translational Psychiatry (New York, NY: Nature Publishing Company, March 2012), p. 6.

51. Medical Marijuana - Research - 8-12-10

Substance Abuse and Mental Health Treatment

(Cannabidiol's (CBD's) Potential in Substance Abuse Treatment) "The current study has revealed unique properties of the phytocannabinoid CBD and underscores the contrasting characteristics of the main constituents of cannabis in relation to addiction vulnerability. Compared with the documented effects of THC to enhance heroin self-administration (Solinas et al., 2004; Ellgren et al., 2007), the present data demonstrated that CBD specifically inhibited reinstatement of cue-induced heroin seeking. The specificity of CBD to cue-induced reinstatement was also emphasized by the observation that the compound still inhibited drug relapse behavior in animals extinguished to the environmental context (self-administration chamber) previously associated with heroin. The results are striking given the very selective and protracted effects of CBD."
"Overall, the observations of this study suggest the potential for CBD as a treatment strategy given its specificity to attenuate cue-induced drug-seeking behavior, preferential impact on mesolimbic neuronal populations, and enduring neural actions. Clearly, greater attention needs be given to the potential role of CBD in the treatment of addiction and other mental health disorders."

Ren, Yanhua; Whittard, John; Higuera-Matas, Alejandro; Morris, Claudia V.; and Yasmin L. Hurd, "Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances," The Journal of Neuroscience (Washington, DC: Society for Neuroscience, November 25, 2009), Vol. 29, No. 47, pp. 14767 and 14768.

52. Medical Marijuana - Research - 11-14-10

(Cannabidiol (CBD) and Schizophrenia Treatment) "These studies suggest, therefore, that CBD has an antipsychotic-like profile in healthy volunteers and may possess antipsychotic properties in schizophrenic patients, but not in the resistant ones. Confirming this suggestion, a preliminary report from a 4-week, double-blind controlled clinical trial, using an adequate number of patients and comparing the effects of CBD with amisulpride in acute schizophrenic and schizophreniform psychosis, showed that CBD significantly reduced acute psychotic symptoms after 2 and 4 weeks of treatment when compared to baseline. In this trial CBD did not differ from amisulpride except for a lower incidence of side effects (49).
"In conclusion, results from pre-clinical and clinical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients. Future trials of this cannabinoid in other psychotic conditions such as bipolar disorder (50) and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly needed."

"Zuardi, A.W.; Crippa, J.A.S.; Hallak, J.E.C.; Moreira, F.A.; and Guimarães, F.S., "Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug," Brazilian Journal of Medical and Biological Research (Ribeirão Preto, Brazil: April 2006), Volume 39, Issue 4, p. 427-428.

53. Cannabinoids and PTSD

"A chart review of patients diagnosed with PTSD who were referred to a private psychiatric clinic suggests that the synthetic cannabinoid, nabilone, has beneficial effects beyond its official indication in regard to abolishing or greatly reducing nightmares that persisted in spite of treatment with conventional PTSD medications.
"The subjects concomitantly received nabilone in addition to the one or more psychiatric medications that they were already taking for 2 years or more. No tolerance to nabilone was observed among the patients. This may indicate its potential longer-term safety and efficacy.
"The author recognizes the limits of this study (e.g., there was no placebo control, the measurements were limited to subjective reports to nightmare changes, the study was on a small number of patients, and there was a selective bias by nature of referrals to a specific clinic from which the patients were selected). Nonetheless, on the basis of these retrospective findings, nabilone appears to be a significant treatment for nightmares in the PTSD population."

Fraser, George A., "The Use of a Synthetic Cannabinoid in the Management of Treatment-Resistant Nightmares in Posttraumatic Stress Disorder (PTSD)," CNS Neuroscience & Therapeutics (Hoboken, NJ: Wiley-Blackwell, Winter 2009), p. 87.

54. Substitution of Cannabis for Other Drugs

"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%).
"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."

Reiman, Amanda, "Cannabis as a Substitute for Alcohol and Other Drugs," Harm Reduction Journal (London, United Kingdom: December 2009).

55. Medical Marijuana - Law - 4-11-10

Medical Cannabis and Young People

(Adolescent Use in Medical Marijuana States) "Indeed, all 11 states that have passed medical marijuana laws ranked above the national average in the percentage of persons 12 or older reporting past-month use of marijuana in 1999, as shown in Table 2. It is at least possible, however, that this analysis confuses cause with effect. It is logical to assume that the states with the highest prevalence of marijuana usage would be more likely to approve medical marijuana programs, because the populations of those states would be more knowledgeable of marijuana’s effects and more tolerant of its use.
"It is also the case that California, the state with the largest and longest-running medical marijuana program, ranked 34th in the percentage of persons age 12-17 reporting marijuana use in the past month during the period 2002-2003, as shown in Table 1. In fact, between 1999 and 2002-2003, of the 10 states with active medical marijuana programs, five states (AK, HI, ME, MT, VT) rose in the state rankings of past-month marijuana use by 12- to 17-year-olds and five states fell (CA, CO, NV, OR, WA).111 Of the five states that had approved medical marijuana laws before 1999 (AK, AZ, CA, OR, WA), only Alaska’s ranking rose between 1999 and 2002-2003, from 7th to 4th, with 11.08% of youth reporting past-month marijuana use in 2002-2003 compared with 10.4% in 1999. No clear patterns are apparent in the state-level data. Clearly, more important factors are at work in determining a state’s prevalence of recreational marijuana use than whether the state has a medical marijuana program."

Eddy, Mark, "Medical Marijuana: Review and Analysis of Federal and State Policies," Congressional Research Service (Washington, DC: March 31, 2009), p. 32.

56. Impact of Medical Marijuana Laws (MMLs) on Cannabis Use by Youth

"We replicated the findings of Wall et al. (2) that marijuana use was higher in states that have passed MMLs, and our analysis suggests this is unlikely to be a causal association. Our difference-in-differences estimates suggest little detectable effects of passing MMLs on marijuana use or perceived riskiness of use among adolescents or adults, which is consistent with some limited prior evidence on arrestees and emergency department patients (17). Future analyses that take advantage of additional policy changes may provide further evidence on this question, but our results suggest that such analyses should adequately control for potential confounding by unmeasured state characteristics."

Sam Harper, Erin C. Strumpf, and Jay S. Kaufman, "Do Medical Marijuana Laws Increase Marijuana Use? Replication Study and Extension," Annals of Epidemiology, March 2012 (Vol. 22, Issue 3, Pages 207-212, DOI: 10.1016/j.annepidem.2011.12.002).

57. Adolescents - Usage - 12-24-09

(Non-Recreational Adolescent Marijuana Use) "The findings of this study provide one of the first in-depth descriptions of youths' use of marijuana for non-recreational purposes, adding to the growing body of research on the use of drugs to self-medicate among young people. Teens involved in regular and long-term use of marijuana for relief constructed their use of marijuana as essential to feeling better or 'normal' in situations where they perceived there were few other options available to them. Unlike the spontaneity typically involved in recreational use, these youth were thoughtful and prescriptive with their marijuana use – carefully monitoring and titrating their use to optimize its therapeutic effect. The findings also point to important contextual factors that further support youth's use of marijuana for relief that extend beyond the availability of marijuana and dominant discourses that construct marijuana as a natural product with medicinal properties."

Bottorff, Joan L , Johnson, Joy L, Moffat, Barbara M, and Mulvogue, Tamsin, "Relief-oriented use of marijuana by teens," Journal of Substance Abuse Treatment, Prevention, and Policy (Vancouver, BC: April 2009), doi:10.1186/1747-597X-4-7.

58. Youth Medical Marijuana Use and Unmet Health Needs

"Of key importance in the findings are the unmet health needs of these youth. Health issues such as depression, insomnia, and anxiety were significant problems that interfered with these youths' ability to function at school, maintain relationships with family and friends, and feel that they could live a normal life. The level of distress associated with these health concerns, along with the lack of effective interventions by heath care providers and family members appeared to leave them with few alternatives. Researchers have reported that when adolescents in rural communities experience barriers to seeking health care, they think they can take care of the problems themselves [30]. Similarly, our study participants believed that their best option was to assume responsibility for treating their problems by using marijuana. Unpleasant side effects with prescribed medications and long, ineffective therapies resulted in little hope that the medical system could be counted on as beneficial. In contrast, marijuana provided these youth with immediate relief for a variety of health concerns. Nevertheless, the regular use of marijuana put youth at risk. Cannabis use has been identified as a risk factor for mental illness such as psychosis, schizophrenia [21,31,32] and psychiatric symptoms such as panic attacks [33]. Teens who smoked marijuana at least once per month in the past year were found to be three times more likely to have suicidal thoughts than non-users [34], and there is evidence that exposure to cannabis may worsen depression in youth [35]. Marijuana use among youth has also been associated with other substance use and school failure [36]. What is interesting is that the findings of this study suggest that youth have little awareness of some of these risks; rather, some are using marijuana to counteract these very problems (e.g., depression, school failure). Teens' perceptions that their health concerns were not addressed suggest that more attention is needed to assess these issues and ensure that other options are available to them. Parents and health care providers need to make a concerted effort to not only understand the pressures and influences on youth [37], but also gain a better understanding of the effect of youths' health problems on their ability to engage in healthy lifestyle choices."

Bottorff, Joan L , Johnson, Joy L, Moffat, Barbara M, and Mulvogue, Tamsin, "Relief-oriented use of marijuana by teens," Journal of Substance Abuse Treatment, Prevention, and Policy (Vancouver, BC: April 2009), doi:10.1186/1747-597X-4-7.

59. Youth Medical Marijuana Use and Reasons for Self-Medication

"Underlying problems related to youth health concerns also need to be addressed. In many situations, the participants' symptoms appeared to be directly related to their life circumstances. Along with the challenges inherent in being an adolescent in today's complex world, some teens were also trying to deal with significant losses (death of a close friend or family member), extremely difficult family relationships, disappointments with friends, school and sports, and a fragile family and peer support network. The risk of substance use increases substantially when youth are attempting to deal with these kinds of situations in isolation. Although marijuana provided the youth with temporary relief, the underlying situation often went unattended – leading the teens into a regular pattern of use. Appropriate guidance and targeted support from counselors and health care providers must be sensitive to meeting the needs of youth as they work through such situations and life altering events. In addition, adults working with youth must find better ways to talk with young people about how they are coping with their health issues, including their marijuana use. Based on the experiences of youth in this study, there is a wide range of support that may benefit youth including counseling, stress management, social skills training, anger management, study skills, pain management, and sleep hygiene. The youth in this study had minimal access to these types of resources."

Bottorff, Joan L , Johnson, Joy L, Moffat, Barbara M, and Mulvogue, Tamsin, "Relief-oriented use of marijuana by teens," Journal of Substance Abuse Treatment, Prevention, and Policy (Vancouver, BC: April 2009), doi:10.1186/1747-597X-4-7.

60. Effects of State Medical Marijuana Laws (MMLs) on Youth Marijuana Use

"We found no evidence of intermediate-term effects of passage of state MMLs on the prevalence or frequency of adolescent nonmedical marijuana use in the states evaluated, with 2 minor exceptions. From 2003 through 2009, adolescent lifetime prevalence of marijuana use and frequency of daily marijuana use decreased significantly in Montana, as compared with a more modest decrease in lifetime prevalence and an increase in daily frequency observed in Delaware (Ps = .03). These 2 statistically significant findings do not appear to represent real effects. Our difference-in-differences study design involved 40 planned comparisons (before---after differences in treatment vs comparison states), and naturally 2 significant results (at the P < .05 level) of a possible 40 can be expected according to chance alone.
"Moreover, the pattern is not consistent with an effect of MMLs. A significant effect was found for lifetime marijuana use but not past-month marijuana use. Self-reported lifetime use requires a much longer recall period than past-month use and is characterized by higher measurement error.13 Also, one would expect the 30-day use measure to be more sensitive than lifetime use to the effects of a change in MMLs, because most of the period covered by respondents’ lifetime reports occurred before passage of an MML.
"Finally, the significant increase in daily marijuana use was observed for the comparison state of Delaware, which had not enacted an MML during the years under evaluation, whereas the frequency of daily marijuana use in Montana decreased. This is the opposite of
what would be expected if MMLs had the deleterious effect of increasing the frequency of nonmedical marijuana use.
"Conversely, the significant effects observed were found between the 2 states that differed the most on the timing of MML enactment, maximizing the length of the follow-up period. Hence, it is reasonable to suspect that enacting an MML may influence the prevalence and frequency of adolescent nonmedical marijuana use half a decade later, despite no evidence of more proximal effects."

Sarah D. Lynne-Landsman, PhD, Melvin D. Livingston, BA, and Alexander C. Wagenaar, PhD, "Effects of State Medical Marijuana Laws on Adolescent Marijuana Use," American Journal of Public Health, June 13, 2013.
Abstract at: http://ajph.aphapublications.o...

61. Medical Marijuana - Dronabinol - 2-26-11

Marinol and Dronabinol

(Dronabinol) "Dronabinol (?-9-tetrahydrocannabinol [THC]) is an alternative treatment for nausea and vomiting caused by chemotherapy. THC is the principal psychoactive component of marijuana. Its mechanism of antiemetic action is unknown, but cannabinoids bind to opioid receptors in the forebrain and may indirectly inhibit the vomiting center. Dronabinol is administered in doses of 5 mg/m2 po 1 to 3 h before chemotherapy, with repeated doses q 2 to 4 h after the start of chemotherapy (maximum of 4 to 6 doses/day). However, it has variable oral bioavailability, is not effective for inhibiting the nausea and vomiting of platinum-based chemotherapy regimens, and has significant adverse effects (eg, drowsiness, orthostatic hypotension, dry mouth, mood changes, visual and time sense alterations). Smoking marijuana may be more effective. Marijuana for this purpose can be obtained legally in some states. It is used less commonly because of barriers to availability and because many patients cannot tolerate smoking."
1. "Dronabinol, the active ingredient in MARINOL® (dronabinol) Capsules, is synthetic delta-9-tetrahydrocannabinol (delta-9-THC). Delta-9-tetrahydrocannabinol is also a naturally occurring component of Cannabis sativa L. (Marijuana)."
2. "Dronabinol is a name of a particular isomer of a class of chemicals known as tetrahydrocannabinols (THC). Specifically, dronabinol is the United States Adopted Name (USAN) for the (-)-isomer of [Delta]\9\-(trans)- tetrahydrocannabinol [(-)-[Delta]\9\-(trans)-THC], which is believed to be the major psychoactive component of the cannabis plant (marijuana)."
3. "A United States Adopted Name (USAN) is the "US generic name for any compound to be used as a drug."
4. Dronabinol is the generic name for THC or tetrahydrocannabinol.

Chabner, Bruce A. and Thompson, Elizabeth Chabner, "Management of Adverse Effects," The Merck Manual (Whitehouse Station, N.J: Merck & Co. Inc., July 2009), Section: Hematology and Oncology, Chapter: Management of Adverse Effects, Nausea and Vomiting.
"MARINOL® (dronabinol) Capsules," (Abbott Laboratories: Abbott Park, IL, July 2006), pp. 11.
Federal Register, "Listing of Approved Drug Products Containing Dronabinol in Schedule III," Vol. 75, No. 210, Monday, November 1, 2010, pp. 67054 to 67059.
"United States Adopted Name," The Bantam medical dictionary, p. 685.

62. Medical Marijuana - Marinol - 3-23-10

MARINOL® (dronabinol) Capsules
"After oral administration, dronabinol has an onset of action of approximately 0.5 to 1 hours and peak effect at 2 to 4 hours. Duration of action for psychoactive effects is 4 to 6 hours, but the appetite stimulant effect of dronabinol may continue for 24 hours or longer after administration.
"MARINOL Capsules is indicated for the treatment of:
"1. anorexia associated with weight loss in patients with AIDS; and
"2. nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
"A cannabinoid dose-related “high” (easy laughing, elation and heightened awareness) has been reported by patients receiving MARINOL® Capsules in both the antiemetic (24%) and the lower dose appetite stimulant clinical trials (8%)
"MARINOL Capsules is one of the psychoactive compounds present in cannabis, and is abusable and controlled [Schedule III (CIII)] under the Controlled Substances Act. Both psychological and physiological dependence have been noted in healthy individuals receiving dronabinol, but addiction is uncommon and has only been seen after prolonged high dose administration.
"Chronic abuse of cannabis has been associated with decrements in motivation, cognition, judgement, and perception. The etiology of these impairments is unknown, but may be associated with the complex process of addiction rather than an isolated effect of the drug. No such decrements in psychological, social or neurological status have been associated with the administration of MARINOL Capsules for therapeutic purposes.
"In an open-label study in patients with AIDS who received MARINOL Capsules for up to five months, no abuse, diversion or systematic change in personality or social functioning were observed despite the inclusion of a substantial number of patients with a past history of drug abuse.
"Signs and symptoms following MILD MARINOL Capsules intoxication include drowsiness, euphoria, heightened sensory awareness, altered time perception, reddened conjunctiva, dry mouth and tachycardia; following MODERATE intoxication include memory impairment, depersonalization, mood alteration, urinary retention, and reduced bowel motility; and following SEVERE intoxication include decreased motor coordination, lethargy, slurred speech, and postural hypotension. Apprehensive patients may experience panic reactions and seizures may occur in patients with existing seizure disorders.
Note: Marinol® is now marketed by Abbott Laboratories.

"MARINOL® (dronabinol) Capsules," (Abbott Laboratories: Abbott Park, IL, July 2006), pp. 1, 2, 6, 9, 10, 11, and 13.
Abbott Marinol® pricing as of 2/27/11:

63. Rescheduling

Other Laws & Policies

"Medical experts emphasize the need to reclassify marijuana as a Schedule II drug to facilitate rigorous scientific evaluation of the potential therapeutic benefits of cannabinoids and to determine the optimal dose and delivery route for conditions in which efficacy is established.2 This research could provide the basis for regulation by the Food and Drug Administration. Current roadblocks to conducting clinical trials, however, make this more rational route of approval unlikely and perpetuate the development of state laws that lack consistency or consensus on basic features of an evidence-based therapeutic program."

Hoffman, Diane E., and Weber, Ellen, "Medical Marijuana and the Law," New England Journal of Medicine (Boston, MA: Massachusetts Medical Society, April 22, 2010), Vol. 362, No. 16, p. 1457.

64. Legalizing Without Congress

"Not surprisingly, the Obama Administration would have been more successful had it simply legalized medical marijuana.143 In fact, the CSA [Controlled Substances Act] authorizes the Attorney General to do so, in consultation with the Secretary of Health and Human Services and the DEA.144 In other words, the President would not need the consent of the Congress to make this, more fundamental change to federal law."

Miklos, Robert A., "A Critical Appraisal of the Department of Justice's New Approach to Medical Marijuana" (February 23, 2011). Stanford Law & Policy Review, Vol. 201, p. 101, 2011 ; Vanderbilt Public Law Research Paper No. 11-07, pp. 665-666.

65. Medical Marijuana - 4-11-10

(History) "For most of American history, growing and using marijuana was legal under both federal law and the laws of the individual states. By the 1840s, marijuana’s therapeutic potential began to be recognized by some U.S. physicians. From 1850 to 1941 cannabis was included in the United States Pharmacopoeia as a recognized medicinal.4 By the end of 1936, however, all 48 states had enacted laws to regulate marijuana.5 Its decline in medicine was hastened by the development of aspirin, morphine, and then other opium-derived drugs, all of which helped to replace marijuana in the treatment of pain and other medical conditions in Western medicine.6"

Eddy, Mark, "Medical Marijuana: Review and Analysis of Federal and State Policies," Congressional Research Service (Washington, DC: March 31, 2009), p. 1.

66. NIDA's Federal Medical Cannabis Program

"It is a judicial fluke that the National Institute on Drug Abuse has provided medical marijuana to a handful of patients (never more than 32, currently 4 surviving) as the outcome of the settlement in a lawsuit pressed in 1976 by a man with cannabis-responsive glaucoma. That settlement became the basis for the FDA’s Compassionate Investigational New Drug Study program for patients with marijuana responsive conditions. No patient has been enrolled since 1992, when the George H. W. Bush administration suspended new registration in reaction to a large influx of applications from AIDS patients."

Bostwick, J. Michael, "Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana," Mayo Clinic Proceedings (Rochester, MN: Mayo Clinic, February 2012), Vol. 87, No. 2, p. 182.

67. Current Scheduling of Cannabis

Cannabis (marijuana) is listed in Schedule I of the 1970 Controlled Substance Act. Schedule 1 classification is supposed to mean: "(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."

U.S. Code. Title 21, Chapter 13 -- Drug Abuse Prevention and Control -- Section 812, Schedules of Controlled Substances, p. 384.

68. Exceptions to Federal Ban

"Only two limited exceptions to the federal ban on marijuana have been made. The first, a compassionate use program created under President Carter, is superficially analogous to extant state medical use programs; it allows patients to use marijuana legally for therapeutic purposes. The marijuana for the program is supplied by a federally approved grow-site at the University of Mississippi (the only federally approved grow-site in the United States). However, the program stopped accepting new applications in 1992, and only eight (yes, eight) patients currently receive marijuana through it. Over its entire history, only thirty-six patients have been enrolled.52 The second and only other way to obtain marijuana legally under federal law is by participating in an FDA-approved research study. But since the federal government approves so few marijuana research projects—eleven since 200053—only a small fraction of the population that currently qualifies for state exemptions could participate."

Miklos, Robert A., "On the Limits of Supremacy: Medical Marijuana and the States’ Overlooked Power to Legalize Federal Crime," Vanderbilt Law Review (Nashville, TN: Vanderbilt University Law School, March 9, 2009), p. 113.

69. Medical Marijuana - Law & Policy - 7-13-12

"Although Raich established Congress’s constitutional authority to enact the existing federal prohibition on marijuana, principles of federalism prevent the federal government from mandating that the states support or participate in enforcing the federal law. While state resources may be helpful in combating the illegal use of marijuana, Congress’s ability to compel the states to enact similar criminal prohibitions, to repeal medical marijuana exemptions, or to direct state police officers to enforce the federal law remains limited. The Tenth Amendment likely prevents such an intrusion into state sovereignty."

Garvey, Todd, "Medical Marijuana: The Supremacy Clause, Federalism, and the Interplay Between State and Federal Laws," Congressional Research Service (Washington, DC: Library of Congress, March 6, 2012), p. 5.

70. Medical Marijuana - Law & Policy - 6-22-12

(Medical Cannabis and the Constitution's Commerce Clause) "Congress has exercised its Commerce Clause authority to categorically ban marijuana. The Supreme Court has upheld this plenary prohibition.19 In Gonzales v Raich, a divided Court held that the Commerce Clause enables Congress to prohibit the local cultivation and use of marijuana, despite more permissive regulations under California law.20 Writing for the majority, Justice Stevens found that precedent 'firmly established' Congress’ power under the Commerce Clause to regulate purely local activities that have a substantial effect on interstate commerce.21 The Raich majority held that Congress can prohibit local marijuana cultivation and use, because it was part of a 'class of activities' constituting the national black market for marijuana.22 The Court reasoned that local cultivation and use, even for limited medical purposes, affected supply and demand in the national black market, making regulation over local use 'essential' to undermining the broader underground industry nationwide.23 The majority distinguished Raich from earlier precedent that circumscribed Congress’ Commerce Clause power, finding that those earlier cases involved statutes that regulated purely non-economic activities, while this one aims to nullify a particular application of a valid statutory scheme.24"

Woods, Jordan Blair, "The Kingpin Act vs. Calfornia's Compassionate Use Act: The Dubious Battle Between State and Federal Drug Laws," University of the District of Columbia Law Review (Washington, DC: The University of the District of Columbia David A. Clarke School of Law, 2011) Volume 15, Number 1, p. 50.

71. Medical Marijuana - Legislation - 12-20-09

(Other State Laws) Since 1978, thirty-seven states have enacted some form of medicinal cannabis legislation other than effective laws. These include:
Therapeutic Research Programs (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 Prescriptions (patients allowed to possess cannabis only if obtained through prescription, not operable because the CSA bars physicians from writing prescriptions for Schedule I drugs): Arizona, California, Connecticut, District of Columbia, Iowa, New Hampshire, Tennessee, Virginia, Wisconsin.
State Rescheduling (not operable because federal scheduling supersedes state schedules): Alaska, Iowa, Montana, Tennessee, and the District of Columbia.
Non-binding Resolutions Urging Federal Rescheduling: California, Michigan, Missouri, New Hampshire, New Mexico, Rhode Island, Washington.

Marijuana Policy Project, "State by State Medical Marijuana Laws" (Washington, DC: 2013, p. 3, pp. 11-12, and Table 2, pp. A1-A18.

72. Medical Marijuana - Supporters - 5-15-11

(US Department of Veterans Affairs, Medical Marijuana, and Pain Management) "If a Veteran obtains and uses medical marijuana in manner consistent with state law, testing positive for marijuana would not preclude the Veteran from receiving opioids for pain management in the Department of Veteran Affairs (VA) facility. The Veteran would need to inform his provider of the use of medical marijuana, and of any other non-VA prescribed medications he or she is taking to ensure that all medications, including opioids, are prescribed in a safe manner. Standard pain management agreements should draw a clear distinction between use of illegal drugs, and legal medical marijuana. However, the discretion to prescribe, or not prescribe, opioids in conjunction with medical marijuana, should be determined on clinical grounds, and thus will remain the decision of the individual health care provider. The provider will take the use of medical marijuana into account in all prescribing decisions, just as the provider would for any other medication. This is a case-by-case decision, based on the provider's judgment, and the needs of the patient."

Petzel, Robert A., Letter to Michael Krawitz from the Dept. of Veterans Affairs concerning its postion on medical marijuana, (Washington, DC: Department of Veterans Affairs, Under Secretary for Health, July 6, 2010).

73. Medical Marijuana - Supporters - 5-15-11

(American Nurses Association Support for Medical Cannabis) "Summary: The evidence demonstrates a connection between therapeutic use of marijuana and symptom relief. The American Nurses Association actively supports patients' rights to legally and safely utilize marijuana for symptom management and health care practitioners’ efforts to promote quality of life for patients needing such therapy."

"In Support of Patients’ Safe Access to Therapeutic Marijuana," ANA Board of Directors (Silver Spring, MD: American Nurses Association, December 12, 2008), pp. 3-4.

74. Medical Marijuana - 5-29-10

(Categories of Cannabinoid Medicines) "They [cannabinoid medicines] fall into three categories: single molecule pharmaceuticals, cannabisbased liquid extracts, and phytocannabinoid-dense botanicals–the main focus of this article (Figure 2). The first category includes US Food and Drug Administration (FDA)-approved synthetic or semisynthetic single molecule cannabinoid pharmaceuticals available by prescription. Currently, these are dronabinol, a Schedule III drug and nabilone, a Schedule II drug. Though both are also used offlabel, dronabinol, a (-)trans-[delta]9-tetrahydrocannabinol (THC) isomer found in natural cannabis, has been approved for two uses since 1985 and 1992, respectively: the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments and the treatment of anorexia associated with weight loss in patients with AIDS.10,11 Nabilone, a synthetic molecule shaped similarly to THC, has also been approved since 1985 for use in the treatment of nausea and vomiting associated with cancer chemotherapy.12,13
"The second category of cannabinoid medicines being used in the United States includes a line of cannabis-based medicinal extracts developed by several companies. The industry leader is GW Pharmaceuticals, a UK-based biopharmaceutical company whose lead product is currently undergoing FDA-approved, multisite Phase IIb clinical trials for the treatment of opioid-refractory cancer pain in the United States14 and has received prior approval for Phase III clinical trials in the United States. This botanical drug extract which goes by the nonproprietary name nabiximols has already secured approval in Canada for use in the treatment of central neuropathic pain in multiple sclerosis (in 2005) and in the treatment of intractable cancer pain (in 2007).15 It is also available on a named patient basis in the United Kingdom and Catalonia,16,17 a scheme which allows a doctor to prescribe an unlicensed drug to a particular “named patient,” and has been exported to 22 countries to date.
"The third category of cannabinoid medicines currently being used in the United States includes the Schedule I medicinal plant Cannabis sativa L. itself, which, while currently unavailable for general prescription use in the United States, is in use in the context of two active controlled clinical trials,18,19 33 completed controlled clinical trials,20-52 and one on-going, yet essentially defunct, three-decade investigational clinical study.53,54"

Aggarwal, Sunil K.; Carter, Gregory T.; Sullivan, Mark D.; ZumBrunnen, Craig; Morrill, Richard; and Mayer, Jonathan D., "Medicinal use of cannabis in the United States: Historical perspectives, current trends, and future directions" Journal of Opioid Management, (Weston, Massachusettes: May/June 2009) Vol. 5:3, pp. 153-154.

75. Medical Marijuana - Law & Policy - 1-4-12

(Ethics of Recommending Medical Cannabis to Patients) "Portions of the American Medical Association’s Code of Medical Ethics, Opinion 1.02 – The Relation of Law and Ethics reads, 'Ethical values and legal principles are usually closely related, but ethical obligations typically exceed legal duties. In some cases, the law mandates unethical conduct.' 'In exceptional circumstances of unjust laws, ethical responsibilities should supersede legal obligations.'[56] An 'exceptional circumstance of unjust laws' may be interpreted as the federal ban on cannabis for medical use. Sixteen states and the District of Columbia found the federal government’s prohibition on prescribing and using medicinal cannabis so unjust as to create laws in direct violation of federal statute. Therefore, one could surmise that prescribing cannabis for the purpose of harm reduction is ethical even though it violates federal law. In addition, Hayry suggests that the idea of 'freedom' also provides an ethical reason for prescribing cannabis and he writes, '… whatever the legal situation, respect for the freedom of the individual would imply that requests like this (for medicinal cannabis) should be granted, either by health professionals, or by society as a whole.'[57]"

Collen, Mark, "Prescribing Cannabis for Harm Reduction," Harm Reduction Journal (London, United Kingdom: January 2012) Vol. 9, Issue 1, p. 5.

76. Medical Marijuana - Research - 11-9-12

“Vaporization as a ‘Smokeless’ Cannabis Delivery System”
Donald Abrams, M.D., University of California, San Francisco
(vaporization of cannabis) "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. Because of concerns regarding the practicality and palatability of using cannabis cigarettes as a standard treatment, there has been an interest in developing alternative delivery systems. Participants were randomly assigned to receive low, medium, or high dose (1.7, 3.4, or 6.8% tetrahydrocannabinol) cannabis cigarettes delivered by smoking or by the vaporization
system on six study days.
"The full results of this study have been published in the journal Clinical Pharmacology & Therapeutics (Abrams, et al., 2007 – see reference list). Eighteen healthy volunteers were recruited to participate in the research. The analysis indicated that the blood levels of vaporized cannabis are similar to those of smoked cannabis over a six hour period. However, blood concentrations of THC at 30 and 60 minutes after inhalation were significantly higher in vaporized cannabis as compared to smoked cannabis. In addition, carbon monoxide levels were significantly reduced with vaporization compared with smoked cannabis. Fourteen participants preferred vaporization, 2 preferred smoking, and 2 reported no preference. 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."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 12.

77. California Medical Association and Medical Cannabis

"CMA [California Medical Association] policy has acknowledged the criminalization of cannabis to be a failed public health policy (HOD 704a-09) and has recognized a public movement toward the legalization of cannabis (HOD 101a-10). Cannabis illegality has perpetuated the effective prohibition of clinical research on the properties of cannabis and has prevented the development of state and national standards governing the cultivation, manufacture, and labeling of cannabis products, similar to those governing food, tobacco and alcohol products, most of which are promulgated by federal agencies."

"Cannabis and the Regulatory Void: Background Paper and Recommendations," California Medical Association (Sacramento, CA: 2011), 11.

78. Medical Marijuana - Research - 6-14-12

(Dispensaries and Crime) "The cross-sectional results suggest that dispensaries are not associated with crime rates; however, current media and policy efforts have focused their attention on the place-based regulation of these dispensaries to protect the public against crime (California Police Chief’s Association, 2009; City of Los Angeles, 2010; Lopez, 2010). Based on the limited evidence presented by this study, it is unclear if place-based policies will be effective."

Kepple, Nancy J. and Freisthlere, Bridget, "Exploring the Ecological Association Between Crime and Medical Marijuana Dispensaries," Journal of Studies on Alcohol and Drugs (Piscataway, NJ: The State University of New Jersey Rutgers, July 2012) Volume 73, Issue 4, p. 529.

79. Medical Marijuana - Law and Policy - 5-17-11

(Federally-Subsidized Public Housing and Medical Cannabis) "In sum, PHAs [Public Housing Agencies] and owners may not grant reasonable accommodations that would allow tenants to grow, use, or otherwise possess, or distribute medical marijuana, even if in doing so tenants are complying with state laws authorizing medical marijuana-related conduct. Further, PHAs and owners must deny admission to those applicant households with individuals who are, at the time of consideration for admission, using marijuana. See 42 U.S.C. § 13661(b)(1)(A); Lester Memorandum at 2.
"We note, however, that PHAs and owners have statutorily-authorized discretion with respect to evicting or refraining from evicting current residents on account of their use of medical marijuana. See 42 U.S.C. § 13662(b)(1); Lester Memorandum at 5-7. If a PHA or owner desires to allow a resident who is currently using medical marijuana to remain as an occupant, the PHA or owner may do so as an exercise of that discretion, but not as reasonable accommodation. HUD regulations provide factors that PHAs and owners may consider when determining how to exercise their discretion to terminate tenancies because of current illegal drug use. See 24 C.F.R. § 966.4(1)(5)(vii)(B)(factors for PHAs); 5.852 (factors for PHAs and owners operating other assisted housing programs)."

Kanovsky, Helen, R. "Medical Use of Marijuana and Reasonable Accommodation in Federal Public and Assisted Housing," U.S. Department of Housing and Urban Development (Washington, DC: January 20, 2011), pp. 10-11.

80. Medical Marijuana - Orgs - 12-19-09

US-Based Medical and Scientific Organizations Which Support Access to Medical Cannabis:
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.

Patients out of Time, "Organizations Supporting Access to Therapeutic Cannabis," (Howardsville, VA: January 2009).

81. Medical Marijuana - 5-19-10

(History) "Cannabis indica became available in American pharmacies in the 1850’s following its introduction to western medicine by William O'Shaughnessy (1839).6 In its original pharmaceutical usage, it was regularly consumed orally, not smoked. The first popular American account of cannabis intoxication was published in 1854 by Bayard Taylor, writer, world traveler and diplomat."

Geiringer, Dale, "Origins of Cannabis Prohibition in California" Contemporary Drug Problems," originally published as "The Forgotten Origins of Cannabis Prohibition in California," Contemporary Drug Problems, (Summer 1999 - substantially revised June 2006) Vol 26, #2, p. 4.

82. General Conclusions

IOM's 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)."

Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999), p. 3.

83. Therapeutic Value

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."

Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999).

84. Increased Use

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."

Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999). p. 99.

85. Movement Disorders

"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."

Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999), p. 169.

86. Tolerance

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."

Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999), p. 126-127.

87. Uses

"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."

Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999), p. 177.

88. Adverse Effects

"For most people, the primary adverse effect of acute marijuana use is diminished psychomotor performance. It is, therefore, inadvisable to operate any vehicle or potentially dangerous equipment while under the influence of marijuana, THC, or any cannabinoid drug with comparable effects."

Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999), p. 125-126.