Medical Marijuana

41. 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.

42. Cannabis 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. Safety of Medical 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.

48. Research Into Potential Therapeutic Uses of 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.

49. 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.

50. 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.

51. 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.

52. 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.

53. 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.

54. 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.

55. 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.

56. 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.

57. 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.

58. 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-B activation, and cell death in primary human cardiomyocytes.
"Conclusions: Collectively, these results coupled with the excellent safety and tolerability profile of CBD in humans, strongly suggest that it may have great therapeutic potential in the treatment of diabetic complications, and perhaps other cardiovascular disorders, by attenuating oxidative/nitrative stress, inflammation, cell death and fibrosis."

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.

59. 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.

60. 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.