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Endnotes

1 Marinol is produced and marketed by Unimed Pharmaceuticals, a subsidiary of Solvay Pharmaceuticals.

2 The FDA approved Marinol in 1985 as a Schedule II controlled substance. By definition, Schedule II drugs adhere to the following criteria: (A) The drug has a high potential for abuse; (B) The drug has a currently accepted medical use in treatment in the United States; (C) Abuse of the drug may lead to severe psychological or physical dependence. In 1999, Marinol was downgraded to a Schedule III controlled substance. By definition, Schedule III drugs adhere to the following criteria: (A) The drug has a potential for abuse less than Schedule I and Schedule II drugs; (B) The drug has a currently accepted medical use in treatment in the United States; (C) Abuse of the drug may lead to moderate or low physical dependence or high psychological dependence.

3 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. National Academy Press: Washington, DC. p. 25: Table 1.5: Cannabinoids Identified in Marijuana.

4 R. Mechoulam et al. 2003. Cannabidiol: an overview of some pharmacological aspects. Neuroscience Letters 346: 61-64; J. McPartland and E. Russo. 2002. Cannabis and cannabis extracts: greater than the sum of their parts. Journal of Cannabis Therapeutics 1: 103-132; A. Zuardi and F Guimaraes. Cannabidiol as an anxiolytic and antipsychotic. In: M. Mathre (Ed): Cannabis in medical practice: a legal, historical and pharmacological overview of therapeutic use of marijuana. McFarland Press: 1997: 133-141.

5 P. Consroe and S. Snider. Therapeutic Potential of Cannabinoids in Neurological Disorders. In: R. Mechoulam (Ed): Cannabinoids as Therapeutic Agents. CRC Press: 1986 21-51; E. Carlini and J. Cunha. 1981. Hypnotic and antiepileptic effects of cannabidiol. Journal of Clinical Pharmacology. 21: 417S-427S; J. Cunha et al. 1980. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21: 175-185.

6 D. Wade et al. 2004. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Multiple Sclerosis 10: 339-340; D. Wade et al. 2003. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Journal of Clinical Rehabilitation 17: 21-29.

7 A. Hampson et al. 1998. Cannabidiol and THC are neuroprotective antioxidants. Proceedings of the National Academy of Sciences 95: 8268-8273.

8 K. Mishima et al. 2005. Cannabidiol Prevents Cerebral Infarction. Stroke 36: 1077-1082.

9 C. Hamelink et al. 2005. Comparison of cannabidiol, antioxidants, and diuretics in reversing binge ethanol-induced neurotoxicity. Journal of Pharmacology and Experimental Therapeutics (electronically published May 5, 2005, ahead of printing).

10 A. Hampson, et al. 1998. Cannabidiol and THC are neuroprotective antioxidants. Proceedings of the National Academy of Sciences.

11 H. Patsos et al. 2005. Cannabinoids and cancer: potential for colorectal cancer therapy. Biochemical Society Transactions. 33: 712-714; M. Guzman. 2003. Cannabinoids: potential anticancer agents. Nature Reviews Cancer 3: 745-755.

12 P. Massi et al. 2004. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. Journal of Pharmacology and Experimental Therapeutics 308: 838-845; G. Carter et al. 2004. Medical marijuana: emerging applications for the management of neurologic disorders. Physical Medicine and Rehabilitation Clinics of North America 15: 943-954.

13 C. Turner et al. 1980. Constituents of Cannabis sativa L.: A review of the natural constituents. Journal of Natural Products 43: 169-304.

14 F. Evans. 1991. Cannabinoids; the separation of central from peripheral effects on a structural basis. Planta Medica 57: S60-S67.

15 P. Wirth et al. 1980. Anti-inflammatory properties of cannabichromene. Life Science 26: 1991-1995.

16 R. Deyo and R. Musty. A cannabichromene (CBC) extract alters behavioral despair on the mouse tail suspension test of depression. In: International Cannabinoid Research Society (Ed.) 2003 Symposium on the Cannabinoids. ICRS: 2003.

17 S. Baek et al. 1998. Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. Archives of Pharmacal Research 21: 353-356.

18 J. McPartland and E. Russo. 2002. Cannabis and cannabis extracts: greater than the sum of their parts. Journal of Cannabis Therapeutics.

19 Ibid.

20 Ibid.

21 Society for Neuroscience. "Marijuana-like compound may aid array of debilitating conditions ranging from Parkinson's Disease to pain." October 26, 2004.

22 G. Pryce et al. 2003. Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain. 126: 2191-2202.

23 C. Raman et al. 2004. Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders 5: 33-39.

24 I. Lastres-Becker et al. 2003. Effects of cannabinoids in the rat model of Huntington's disease generated by an intrastraital injection of malonate. Neuroreport 14: 813-816.

25 E. Williamson. 2001. Synergy and other interactions in phytomedicines. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 8: 401-409.

26 A. Holdcroft. 2001. Cannabinoids: from plant to patient. Investigative Drugs Journal. 4: 773-775. (See specifically: Abstract: "The active constituents of cannabis, predominantly cannabinoids and possibly flavonoids, are more effective than a single cannabinoid. ... Government ... clinical trials of cannabis ... should enable evidence to be presented to regulatory bodies documenting the medicinal uses of standardized cannabis plant material.")

27 J. McPartland and E. Russo. 2002. Cannabis and cannabis extracts: greater than the sum of their parts. Journal of Cannabis Therapeutics. p. 103.

28 The Pharmaceutical Journal. "Cannabis herb may have advantages over THC in epilepsy." July 19, 2003.

29 Comparison of results from: D. Wade et al. 2004. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Multiple Sclerosis (See specifically: Abstract: Spasticity VAS scores were significantly reduced by cannabis-based medicinal extracts in comparison with placebo.) and J. Zajicek et al. 2003. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis. Lancet. 362: 1517-26 (See specifically: Abstract: Treatment with [oral cannabis extract or THC] did not have a beneficial effect on spasticity.)

30 http://www.drugdevelopment-technology.com/projects/sativex/

31 Canada News Wire. "Sativex: Novel cannabis derived treatment for MS pain now available in Canada by prescription." June 20, 2005.

32 Physician’s Desk Reference: 43rd edition. Medical Economics Company. 1989: 1859-1860.

33 Physician’s Desk Reference: 52nd edition. Medical Economics Company. 1998: 2353-2355.

34 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and medicine: Assessing the Science Base. p. 203.

35 J. Morgan and L. Zimmer, Marijuana Myths, Marijuana Facts: A Review of the Scientific Evidence. The Lindesmith Center. 1997: 18-19.

36 L. Lemberger et al. 1973. Comparative pharmacology of delta-9-THC and its metabolite 11-0H-Delta-9-THC. Journal of Clinical Investigation 54: 2411-2417 and M. Perez-Reyes et al. 1972. Intravenous injection in man of delta-9-tetrahydrocannabinol and 11-hydroxy-delta-9-tetrahydrocannabinol. Science 177: 633-635 as cited by J. Morgan and L. Zimmer, Marijuana Myths, Marijuana Facts: A Review of the Scientific Evidence.

37 L. Growing et al. 1998. Therapeutic use of cannabis: clarifying the debate. Drug and Alcohol Review. 17: 445-452.

38 Ibid; J. Morgan and L. Zimmer, Marijuana Myths, Marijuana Facts: A Review of the Scientific Evidence, 19.

39 G. Carter et al. 2004. Medical marijuana: emerging applications for the management of neurologic disorders. Physical Medicine and Rehabilitation Clinics of North America; L. Growing et al. 1998. Therapeutic use of cannabis: clarifying the debate. Drug and Alcohol Review; A. Zuardi et al. 1982. Action of cannabidiol on the anxiety and other effects produced by delta-9-THC in normal subjects. Psychopharmacology 76: 245-250; G. Karinol et al. 1974. Cannabidiol interferes with the effects of delta-9-tetrahydrocannabinol in man. European Journal of Pharmacology 28: 172-177.

40 D. Gieringer et al. 2004. Cannabis vaporizer combines efficient delivery of THC with effective suppression of pyrolytic compounds. Journal of Cannabis Therapeutics 4: 7-27.

41 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. p. 199; See also: M. Hashibe et al. 2005. Epidemiologic review of marijuana use and cancer risk. Alcohol 35: 265-275; K. Rosenblat et al. 2004. Marijuana use and risk of oral squamous cell carcinoma. Cancer Research 64: 4049-4054; D. Ford et al. 2001. Marijuana use is not associated with head, neck or lung cancer in adults younger than 55 years: Results of a case cohort study. In: National Institute on Drug Abuse (Eds) Workshop on Clinical Consequences of Marijuana: Program Book. National Institutes of Health: Rockville, MD: p. 10.

42 M. Polen et al. 1993. Health care use by frequent marijuana smokers who do not smoke tobacco. Western Journal of Medicine 158: 596-601; D. Tashkin. 1993. Is frequent marijuana smoking hazardous to health? Western Journal of Medicine 158: 635-637.

43 D. Gieringer et al. 2004. Cannabis vaporizer combines efficient delivery of THC with effective suppression of pyrolytic compounds. Journal of Cannabis Therapeutics.

44 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. p. 203; L. Growing et al. 1998. Therapeutic use of cannabis: clarifying the debate. Drug and Alcohol Review.

45 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. p. 203.

46 S. Calhoun et al. 1998. Abuse potential of dronabinol. Journal of Psychoactive Drugs. 30: 187-196; J. Morgan and L. Zimmer, Marijuana Myths, Marijuana Facts: A Review of the Scientific Evidence, p. 19.

47 Ibid; National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. "The poor solubility of Marinol in aqueous solutions and its high first-pass metabolism in the liver account for its poor bioavailability; only 10-20% of an oral dose reaches the systemic circulation. The onset of action is slow; peak concentrations are not attained until two to four hours after dosing. In contrast, inhaled marijuana is rapidly absorbed. ... Variations in individual responses is highest for oral THC and bioavailability is lowest."

48 L. Growing et al. 1998. Therapeutic use of cannabis: clarifying the debate. Drug and Alcohol Review.

49 Of Marinol's patient population, only about 10 percent use it to combat cancer-related nausea. National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. p. 204.

50 E. Woolridge et al. 2005. Cannabis use in HIV for pain and other medical symptoms. Journal of Pain and Symptom Management 29: 358-67.

51 R. Schwartz and R. Beveridge. 1994. Marijuana as an antiemetic drug: how useful today. Opinions from clinical oncologists. Journal of Addictive Diseases 13: 53-65.

52 R. Doblin and M. Kleiman. 1991. Marijuana as an anti-emetic medicine: a survey of oncologists' attitudes and experiences. Journal of Clinical Oncology 19: 1275-1290.

53 National Institutes of Health. 1997. Report of the Workshop on the Medical Utility of Marijuana. Washington, DC as cited by L. Growing et al. 1998. Therapeutic use of cannabis: clarifying the debate. Drug and Alcohol Review.

54 Medical News Today. "New synthetic delta-9-THC Inhaler offers safe, rapid delivery, Phase I study." April 17, 2005.

55 Ibid.

56 Presentation of Unimed Pharmaceuticals Senior Vice President Robert Dudley before the National Academy of Sciences, Institute of Medicine. Washington, DC: February 24, 1998.

57 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. p. 207; Morgan and L. Zimmer, Marijuana Myths, Marijuana Facts: A Review of the Scientific Evidence, p. 21; Medical Marijuana ProCon.org

58 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. p. 206.

59 L. Growing et al. 1998. Therapeutic Uses of Cannabis. Drug and Alcohol Services Council: South Australia.

60 National Academy of Sciences, Institute of Medicine. 1999. Marijuana and Medicine: Assessing the Science Base. p. 207; Medical Marijuana ProCon.org

61 State research trials regarding natural cannabis were discontinued by 1985, after the FDA approved Marinol.

62 The cannabis distributed in these trails was manufactured and provided by the US National Institute on Drug Abuse (NIDA). Cannabis was provided to patients in the form of a cigarette.

63 R. Musty and R. Rossi. 2001. Effects of smoked cannabis and oral delta-9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: a review of state clinical trials. Journal of Cannabis Therapeutics. 1: 29-56. "The data reviewed here suggested that the inhalation of THC appears to be more effective than the oral route. ... Patients who smoked marijuana experienced 70-100% relief from nausea and vomiting, while those who used THC capsules experienced 76-88% relief."

64 Board of Pharmacy, State of Tennessee. 1983. Annual Report: Evaluation of Marijuana and Tetrahydrocannabinol in Treatment of Nausea and/or Vomiting Associated with Cancer Therapy Unresponsive to Conventional Anti-Emetic Therapy: Efficacy and Toxicity. p. 5.

65 Behavioral Health Services Division. 1983. The Lynn Pierson Therapeutic Research Program: A Report on Progress to Date. Health and Environment Department: New Mexico. p. 4.

66 Research Advisory Panel. 1986. Seventeenth Annual Report of the Research Advisory Panel, p. 9-10.

67 V. Vinciguerra et al. 1988. Inhalation marijuana as an antiemetic for cancer chemotherapy. New York State Journal of Medicine 88: 525-527.

68 E. Woolridge et al. 2005. Cannabis use in HIV for pain and other medical symptoms. Journal of Pain and Symptom Management.

69 D. Prentiss et al. 2004. Patterns of marijuana use among patients with HIV/AIDS followed in a public health care setting. Journal of Acquired Immune Definiciency Syndromes 35: 38-45

70 R. Gorter et al. 2005. Medical use of cannabis in the Netherlands. Neurology 64: 917-919.

71 Ibid.

72 Reuters News Wire. "Marijuana helps MS patients alleviate pain, spasms." August 19, 2002.

73 Ibid.

74 S. Page et al. 2003. Cannabis use as described by people with multiple sclerosis. Canadian Journal of Neurological Sciences 30: 201-205.

75 Ibid.

76 A. Clark et al. 2004. Patterns of cannabis use among patients with multiple sclerosis. Neurology 62: 2098-2100.

77 D. Gross et al. 2004. Marijuana use and epilepsy. Neurology 62: 2095-2097.

78 Ibid.

79 News Wire. "Pot may ease Parkinson's symptoms -- Czech study." November 13, 2002.