Medical marijuana: The conflict between scientific evidence and political ideology. Part one of two

Journal of Pain and Palliative Care Pharmacotherapy

Volumn 23, Issue 1, 2009, Pages 4-25

  Cohen, Peter J ^a  

^a GEORGETOWN UNIVERSITY LAW CENTER   (United States)

Author keywords

Cannabis; Law; Marijuana; Medical; Nausea; Pain; Policy

Indexed keywords

ACETYLSALICYLIC ACID; BARBITURIC ACID DERIVATIVE; BELLADONNA ALKALOID; CANNABIS; DIAZEPAM; DONNATAL; DRONABINOL; EPHEDRINE; FENTANYL; MORPHINE; OPIATE; PACLITAXEL; PETHIDINE; PHENOBARBITAL; THALIDOMIDE; UNCLASSIFIED DRUG;

ANXIETY DISORDER; ATROPA BELLADONNA; BREAST CANCER; CANNABIS ADDICTION; COGNITION; COGNITIVE DEFECT; CONFUSION; DEATH; DELUSION; DEPERSONALIZATION; DEPRESSION; DIGESTIVE SYSTEM CANCER; DISEASE ASSOCIATION; DRUG APPROVAL; DRUG EFFICACY; DRUG FATALITY; DRUG LEGISLATION; DRUG SAFETY; DRUG SCREENING; EPHEDRA SINICA; FOOD AND DRUG ADMINISTRATION; GOVERNMENT REGULATION; HALLUCINATION; HEALTH CARE POLICY; HUMAN; HYPOTENSION; IRRITABLE COLON; LUNG CANCER; MEDICAL ETHICS; MEDICAL PRACTICE; MEDICOLEGAL ASPECT; MENTAL DISEASE; NONHUMAN; PAIN; PANIC; PAPAVER SOMNIFERUM; PARANOIA; PHYSICAL DISABILITY; POLITICS; PSYCHOSIS; RESPIRATION DEPRESSION; REVIEW; RISK; SCHIZOPHRENIA; SIDE EFFECT; SMOKING; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; EVIDENCE BASED MEDICINE; LUNG TUMOR; PHYTOTHERAPY; POLICY; UNITED STATES;

CANNABIS; COGNITION DISORDERS; EVIDENCE-BASED MEDICINE; HUMANS; LEGISLATION, DRUG; LUNG NEOPLASMS; PHYTOTHERAPY; POLITICS; PUBLIC POLICY; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 67649535493     PISSN: 15360288     EISSN: 15360539     Source Type: Journal    
DOI: 10.1080/15360280902727973     Document Type: Review

References (130)

1. AND NOTES 1. Morphine and some other opioids may be extracted from the opium poppy. Additional opioids possessing similar pharmacologic effects, but not found in the opium poppy, are the products of synthesis.
2. Jerome H. Jaffe,William R. Martin. Opioid analgesics and antagonists. In: Louis S. Goodman, Alfred Gilman, editors. The Pharmacological Basis of Therapeutics, 6th ed. New York: MacMillan Publishing Company, Inc. [herein after Goodman and Gilman]; 1980:494, 502. Morphine is a primary and continuous depressant of respiration . . . The respiratory depression is discernible even with doses too small to disturb consciousness, and increases progressively as the dose is increased. In man, death from morphine poisoning is nearly always due to respiratory arrest.
3. See, e.g., Jerome H. Jaffe,WilliamR. Martin.Opioid analgesics and antagonists. In Goodman and Gilman, 494, 499: In man, morphine [derived from opium] produces analgesia, drowsiness, changes inmood, andmental clouding . . . When therapeutic doses of morphine are given to patients with pain, they report that the pain is less intense, less discomforting, or entirely gone . . . In addition to relief of distress, some patients experience euphoria.
4. Although "marijuana" and "cannabis" refer to the same compound, I will refer to "marijuana" rather than "cannabis" unless "cannabis" was used in a quotation.
5. See, e.g., Carlton K. Erickson. Epidemiology of dependence: understanding the population. Addiction Professional. 2003;6:6-7: Anewstudy by researchers at Johns Hopkins University (FA Wagner and JC Anthony, From the First Drug Use to Drug Dependence: Developmental Periods of Risk forDependence upon Marijuana, Cocaine, and Alcohol, 26 Neuropharmacology 479 (2002)) gives us some [useful] numbers. Based upon data from the National Comorbidity Survey with 8,100 people (men and women ages 15 to 54) who were interviewed for when they first used drugs and for when they became dependent, it was found that 12 to 13 percent became dependent on alcohol in a 10-year period.
6. About 15 to 16 percent of people who used cocaine became dependent in the 10-year period [5-6% during their first year of use], and about 8 percent of marijuana users became dependent during the same period . . . . [These data] are very close to previously published incidence numbers for dependence: alcohol (10 percent of users); cocaine (17 to 18 percent of users); marijuana (4 percent of users) . . . nicotine (40 percent); heroin (40 percent). See also Sandra P.Welch and Billy R. Martin. The pharmacology of marijuana. In: Allan W. Graham, Terry K. Schultz, Michael E. Mayo-Smith, Richard K. Ries, Bonnie B. Wilford, editors. Principles of Addiction Medicine, 3rd ed. Chevy Chase, MD: American Society of Addiction Medicine [hereinafter Principles of Addiction Medicine]; 2003:249, 260: Clinical and epidemiologic evidence indicates that a cannabis dependence syndrome occurs in heavy chronic users, as exhibited by a lack of control over use and continued use of the drug despite adverse personal consequences . . . The risk of becoming dependent on cannabis probably is more like the risk for alcohol than for nicotine or the opioids, with around 10% of those who ever use cannabis eventually meeting the criteria for dependence.
7. Sandra P.Welch, Billy R. Martin. The pharmacology of marijuana. In Principles of Addiction Medicine, 249, 261-263.
8. While cannabis is not devoid of harm, there are no data suggesting that it can cause death. ("In healthy young users, [its] cardiovascular effects are unlikely to be of clinical significance.") See also Jerome H. Jaffe. Drug addiction and drug abuse. In Goodman and Gilman, 535, 561. Jaffe suggests that marijuana's effects on circulation and respiration are not lethal in nature: The most consistent effects on the cardiovascular system are an increase in heart rate [and] an increase in systolic blood pressure . . . The increase in heart rate is dose related, and its onset and duration correlate well with the concentration of-9- THC in blood . . . There are no consistent changes in respiratory rate.
9. Controlled Substances Act (CSA): 21 U.S.C. § 812(c).
10. Physicians may prescribe only those drugs that have been approved by the Food and Drug Administration.
11. Pearson v. McCaffrey, 139 F. Supp. 2d 113 (D.D.C. 2001).
12. ARS Report for Congress: Medical Marijuana: Review and Analysis of Federal and States Policies, Congressional Research Service, Updated May 15, 2007, Order Code RL33211, pages 17-18: "Twelve states, covering about 22% of the U.S. population, have enacted laws to allow the use of cannabis for medical purposes."
13. These states are: Alaska, California, Colorado, Hawaii, Maine, Montana, Nevada, New Mexico, Oregon, Rhode Island, Vermont, and Washington. (Last accessed August 24, 2008 at http:// static.scribd.com/docs/8b5xppyclqpes.swf? INITIALVIEW=width).
14. See also Dawson Bell, Proposal 1: Voters Support Letting Severely Ill Grow Own Pot, Detroit Free Press, November 5, 2008 at News 1. (Michigan voters favored sanctioning the use of medical marijuana to treat debilitating illness [November 4, 2009], apparently rejecting arguments that doing so would increase crime and juvenile drug use. The marijuana measure, Proposal 1, led 63% to 37%, with half of all precincts tallied . . . When it goes into effect-10 days after the vote is certified later this month-patients suffering from cancer, glaucoma, HIV/AIDS and other conditions can be authorized to cultivate, possess and use marijuana without fear of prosecution under state law. Michigan becomes the 13th state to approve medical marijuana, meaning that one in four Americans will live in a place where the use of the herb for medical purposes will be legal, according to advocates for legalization.)
15. The Controlled Substances Act, Pub. L. No. 91- 513, 84 Stat. 1236 (October 27, 1970), codified at 21 U.S.C. §801 et seq.
16. Gonzales v. Raich, 545 U.S. 1, 17 (2005): Our case law firmly establishes Congress' power to regulate purely local activities that are part of an economic "class of activities" that have a substantial effect on interstate commerce. . . As we stated in Wickard (317 U.S. 111, 125 (1942)), "even if appellee's activity be local and though it may not be regarded as commerce, it may still, whatever its nature, be reached by Congress if it exerts a substantial economic effect on interstate commerce.". . . We have never required Congress to legislate with scientific exactitude. When Congress decides that the "total incidence" of a practice poses a threat to a national market, it may regulate the entire class. (Some citations omitted.)
17. Advocates of medical marijuana claim (with some pharmacologic justification) that smoking allows easy titration and rapid onset of its therapeutic effects, thereby allowing its users to inhale the minimal dose necessary to achieve the desired medical effects while avoiding the frequently undesired psychological attributes of marijuana.
18. Weldon Angelos, a first-time offender, was convicted in federal court of selling marijuana in 2004 and received a mandatory minimum sentence of 55 years in prison. Although this harsh sentence was based on Weldon's possession of a gun during the drug deals (although the weapon was never used), a sentence of 6 to 8 years would have been required even in the absence of a gun. On December 4, 2005, the Supreme Court refused to hear Angelos' appeal. Angelos v. United States, 127 S. Ct. 723 (2006, cert. denied).
19. Although this may be an extreme example, the imposition of significant incarceration is by no means an isolated phenomenon: conviction of possession of more than 1 kg of marijuana in Rhode Island carries a mandatory minimum sentence of 10 years. Possession of larger amountsmay result in a maximum sentence of life in prison, whereas the highest mandatory minimum sentences imposed by Connecticut and Massachusetts is 5 years. See Elizabeth Gudrais, State May Revise Guidelines forDrug Sentences,Rhode Island News June 14, 2007. (Last accessed July 22, 2008 at http://www.projo.com/news/content/mandatory minimums 06-14-107 9H60LMB.34c74a9.html.)
20. However, even a short period of incarceration can have an extraordinary impact. Jonathan Magbie received a sentence of only 10 days in prison for marijuana possession although he was a quadriplegic and first-time offender. Unfortunately, failure of the prison to provide essential medical care resulted in his death during his incarceration. See Henri E. Cauvin, Care Provided by Hospital, Corrections Dept. in Question, Washington Post, October 1, 2004, B1.
21. Recreational marijuana has not always been a drug subject to opprobrium. For the history of federal marijuana control, see David F. Musto. Opium, cocaine and marijuana in American history. Sci Am. 1991;265:40. Unlike opiates and cocaine, marijuana was introduced during a period of drug intolerance. Consequently, it was not until the 1960s, 40 years after marijuana cigarettes had arrived in America, that it was widely used. The practice of smoking cannabis leaves came to the U.S. with Mexican immigrants, who had come North during the 1920s to work in agriculture, and it soon extended to white and black musicians. As the Great Depression of the 1930s settled over America, the immigrants became an unwelcome minority linked with violence and with growing and smoking marijuana. Western states pressured the federal government to control marijuana use. The first official response was to urge adoption of a uniform state Narcotics law. Then a new approach became feasible in 1937, when the Supreme Court upheld the National Firearms Act. This act prohibited the transfer of machine guns between private citizens without purchase of a transfer tax stamp-and the government would not issue the necessary stamp. Prohibition was implemented through the taxing power of the federal government. Within a month of the Supreme Court's decision, the Treasury Department testified before Congress for a bill to establish a marijuana transfer tax. The bill became law, and until the Comprehensive Drug Abuse Act of 1970, marijuana was legally controlled through a transfer tax for which no stamps or licenses were available to private citizens.
22. Ismail Serageldin. Science in Muslim Countries. Science. 2008;321:745 (quoting Ibn Al-Haytham [10th century]. The scientific method should operate through observation, measurement, experiment, and conclusion, the purpose being to "search for truth, not support of opinions.")
23. Note, however, that the "recreational" use [I will not use quotations to distinguish between "recreational" and "medical" marijuana in the remainder of this article] of marijuana far exceeds its legal (under state law) incorporation into the practice of medicine, the focus of the remainder of this article. For example, although 11.1 million individuals (80% of those reporting any illicit drug use) used marijuana during a 1-month survey period in 1997 (NationalHousehold Survey onDrug Abuse for 1997; America'sDrugUse Profile, inNational Drug Control Strategy, Office of National Drug Control Policy, The White House, 1999), a 2005 report estimated that only 115,000 people had made use of medical marijuana in the 10 states in which the cultivation, possession, and use of marijuana for medical purposes was legal at the time (Susan Okie. Medical marijuana and the Supreme Court. New Engl J Med. 2005;353:648). Although this number probably increased as legalization was extended to a total of 13 states by 2009 (supra note 10), it is clear that the number of people using marijuana for therapeutic purposes will continue to be miniscule in comparison to its recreational use.
24. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 321 et. seq. (2000).
25. Safety and efficacy must be demonstrated by "evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience." 21 U.S.C. §355(d)(7).
26. J. M. Campbell: Note on The Religion of Hemp British Indian Drugs Commission Report 1839-1894. Quoted in Famous Quotes about Cannabis, April 19, 2007 (Last accessed on August 2, 2008 at http://www.woyano.com/view/2073/ Famous-Quotes-About-Cannabis): This book is dedicated to: The Sun and Mother Nature for conspiracy to cultivate medical marijuana . . . Those being sought after and prosecuted while utilizing and cultivating this planet's most valuable natural resource. Some day understanding will come about, laws will change andMother Nature's most precious gift and its users will be released from tyranny. 21.
27. U.S.C. §§ 301(g)(1)(B) and (C).
28. U.S.C. § 355(a). "No person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application . . . is effective with respect to such drug."
29. Supra note 19.
30. Jacobson v. Massachusetts, 197 U.S. 11, 26 (1905).
31. United States v. Rutherford 442 U.S. 544, 557-558 (1979).
32. See, e.g., Peter J. Cohen, Science, Politics, and the Regulation of Dietary Supplements-It's Time to Repeal DSHEA, 31 Amer. J. Law & Med. 175, 178 (2005). [Hereinafter Cohen and DSHEA.]
33. Upton Sinclair, The Jungle (Gene DeGruson, ed., Peachtree Publishers, 1988) (first published serially in 1905 and then as a complete book in 1906).
34. Id. at 121-122
35. See Peter Barton Hutt, Richard A. Merrill. Food and Drug Law, Cases and Materials, 2nd edition. Westbury, NY: Foundation Press; 1991: Chapter 1.
36. FDA, The Long Struggle for the 1906 Law, FDA Consumer, June 1981 (U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition). (Last accessed on July 22, 2008 at http://www.cfsan.fda.gov/?lrd/history2.html.)
37. Taste of Raspberries, Taste of Death: The 1937 Elixir Sulfanilamide Incident, FDA Consumer Magazine, June 1981. (Last accessed on August 29, 2008 at http://www.fda.gov/oc/history/elixir.html.)
38. Arthur H. Hayes, Jr. Food and drug regulations after 75 years JAMA. 1981;246:1223, 1224.
39. -21 U.S.C. § 355(b)(1).
40. Kefauver-Harris Amendment of 1962, Pub. L. No.87-781, 76 Stat. 780 (codified in scattered sections of 21 U.S.C. §§ 301-399 (2000)).
41. C. Frederick Beckford III, The FDA's War on Drugs, 82 Geo. L.J. 529, 529-530 (1993) (explaining the effect of the Kefauver-Harris Amendment).
42. Beckford, supra note 34, at 530 (describing market failures that demonstrate the need for consumer protection in the pharmaceutical industry).
43. The Commerce Clause encompasses virtually all aspects of drug marketing and advertising, as they are "part of an economic 'class of activities' that have a substantial effect on interstate commerce." Gonzales v. Raich, 545 U.S. 1 (2005). Supra note 14.
44. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 321 et. seq. (2000).
45. Supra note 19.
46. See, e.g., Robert Temple, Susan S. Ellenberg. Placebo-controlled trials and active-control trials in the evaluation of new treatments. Ann Intern Med. 2000;133:455, 460.
47. P. B. Hutt, R. A. Merrill. Food and drug law, Cases and Materials, 2nd edition. Westbury, NY: Foundation Press, 1991:527:"The history of the 1962 Amendments clearly reveals Congress' intention that FDA not refuse to approve a drug on the ground of 'relative efficacy,' i.e., that a more effective drug is available."
48. Jerome H. Jaffe, William R. Martin. Opioid analgesics and antagonists. In Goodman and Gilsman, 494, 509: "Powdered opium is a light brown powder. The official morphine content of opium is 10.0 to 10.5% by weight. Paregoric, U.S.P. (camphorated opium tincture) is a hydroalcoholic preparation in which there is also benzoic acid, camphor, and anise oil. The usual adult dose is 5 to 10 ml, which corresponds to 2 to 4 mg of morphine."
49. Physicians' Desk . Montvale, NJ: Thompson PDR; 2005:2493.
50. Marcel P. Vercauteren, Hilde C. Coppejans, Vincent H. Hoffmann, Els Mertens, Hugo A. Adriaensen, Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal anesthesia in prehydrated cesarean delivery patients. Anesth. Analg. 2000;90:324.
51. S. Chrubasik, E. Eisenberg, E. Balan, T. Weinberger, R. Luzzati, C. Conradt. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am. J. Med. 2000;109:9.
52. Parenthetically, the multibillion dollar "dietary supplement" industry depends on the use of a wide variety of botanical agents that are exempt from the strict FDA premarket review demanded for pharmaceutical agents. Dietary Supplement Health and Education Act of 1994, Pub. L. No. 103-417, 108 Stat. 4325 (codified as amended in scattered sections of 21 U.S.C. §§ 301-399 (2000)).
53. See, e.g., DavidM. Eisenberg, Roger B. Davis, Susan L. Ettner, Scott Appel, Sonja Wilkey, Maria van Rompay, Ronald C. Kessler. Trends in alternative medicine use in the united states, 1990-1997: results of a follow-up national Study. JAMA. 1998;280:1569, 1575. ("Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% [of those surveyed] in 1990 to 42.1% in 1997. The therapies increasing themost included herbalmedicines . . . [and] megavitamins. . . [A]lternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches.") I have previously proposed (Cohen and DSHEA) that the majority of these dietary supplements should be subject to premarket review identical to that required for new pharmaceutical agents. In this article, I suggest that a similar approach to the evaluation of medical marijuana would be both good science and rational policy.
54. In setting forth the FDA's review process, I have made use of a recent excellent review. See James L. Zelenay, Jr. The prescription drug user fee act: is a faster food and drug administration always a better Food and Drug Administration? Food Drug L J. 2005;60:261.
55. Supra note 19.
56. -21 C.F.R. § 312.21(a).
57. -21 C.F.R. § 312.21(b).
58. -21 C.F.R. § 312.21(c).
59. -21 U.S.C. § 355(b)(1)(A).
60. -21 U.S.C. §355(b)(1)
61. -21 C.F.R. §§314.50-314.90.
62. Hutt, Supra note 39.
63. -21 U.S.C. § 352.
64. -21 U.S.C. § 321(n).
65. -21 U.S.C. § 321(n).
66. See, e.g., Peter J. Cohen. "Off-label" use of prescription drugs: legal, clinical and policy considerations. Eur J Anaesthesiol 1997;14:231, 233. Acquisition of information concerning drug action does not stop at the time of FDA approval. Invaluable information, not available during the limited phase of clinical investigation, is gleaned only through postmarket surveillance. Newly approved drugs are administered to patients with a variety of diseases, and who may be taking a panoply of othermedications.Adverse effects occurring with extremely low frequency, unlikely to have been noted during the phase of clinical investigation, may only become manifest after approval. Often, clinical studies designed to gather data to support the NDA do not include members of every group who will eventually receive the medication.
67. -21 U.S.C. § 355(e).
68. See, e.g., Cohen and DSHEA at 211-213.
69. Id.
70. See infra notes 180, 196, 197, 198
71. See, e.g., Cohen and DSHEA, 179. (The FDA's oversight was responsible for averting a major disaster by prohibiting the use of thalidomide in the United States after its widespread distribution in Europe had led to the catastrophe of malformed infants born after maternal use of the compound.)
72. Pub. L. No.91-513, 84 Stat. 1236 (October 27, 1970), codified at 21 U.S.C. § 801 et seq.
73. Petitions may also be filed by any other interested parties such as the pharmaceutical sponsor, public interest group, or concerned physicians.
74. The scheduling process is described in detail by John H. King, Federal regulations for the prescription of controlled substances. In: GabrielG.Nahas,Kenneth M. Sutin, David J. Harvey, Stig Agurell, editors. Marihuana and Medicine. Totowa, NJ: Humana Press, 1999:745.
75. Once the FDA recommends that the drug be scheduled, the DEA is responsible for assigning the level of scheduling. In doing so, however, the scientific findings presented by the FDA and NIDA are binding on the DEA.
76. The Controlled Substances Act (Pub. L. No. 91-513, 84 Stat. 1236 (October 27, 1970), codified at 21 U.S.C. § 801 et seq.) (Last accessed on July 22, 2008 at http://www.law.cornell.edu/uscode/21/812.html and http://www.usdoj.gov/ dea/pubs/csa/812.htm.) Title 21, § 812. Schedules of controlled substances (a) Establishment There are established five schedules of controlled substances, to be known as schedules I, II, III, IV, and V. Such schedules shall initially consist of the substances listed in this section. The schedules established by this section shall be updated and republished on a semiannual basis during the 2-year period beginning one year after October 27, 1970, and shall be updated and republished on an annual basis thereafter. (b) Placement on schedules; findings required Except where control is required by United States obligations under an international treaty, convention, or protocol, in effect on October 27, 1970, and except in the case of an immediate precursor, a drug or other substance may not be placed in any schedule unless the findings required for such schedule are made with respect to such drug or other substance. The findings required for each of the schedules are as follows: (1) Schedule I.- (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. (2) Schedule II.- (A) The drug or other substance has a high potential for abuse. (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence. (3) Schedule III.- (A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II. (B) The drug or other substance has a currently accepted medical use in treatment in the United States. (C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence. (4) Schedule IV.- (A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III. (B) The drug or other substance has a currently accepted medical use in treatment in the United States. (C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III. (5) Schedule V.- (A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV. (B) The drug or other substance has a currently accepted medical use in treatment in the United States. (C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV.
77. -21 U.S.C. § 812(b)
78. See, e.g., Gonzales v. Raich, 545 U.S. 1, 14 (2005). "In enacting the CSA, Congress classified marijuana as a Schedule I drug." (Emphasis added.)
79. See Cruel and Unusual Punishment: The Juvenile Death Penalty. Adolescence, Brain Development and Legal Culpability (Juvenile Justice Center, American Bar Association January 2004). (Last accessed on July 22, 2008 at http://www.abanet.org/crimjust/juvjus/ Adolescence.pdf.): Scientists are now utilizing advances in magnetic resonance imaging (MRI) to create and study three-dimensional images of the brain without the use of radiation (as in an x-ray).
80. This breakthrough allows scientists to safely scan children over many years, tracking the development of their brains. Researchers at Harvard Medical School, the National Institute of Mental Health, UCLA, and others, are collaborating to "map" the development of the brain from childhood to adulthood and examine its implications . . . This discovery gives us a new understanding into juvenile delinquency. The frontal lobe is "involved in behavioral facets germane to many aspects of criminal culpability," explains Dr. Ruben C. Gur, neuropsychologist and Director of the Brain Behavior Laboratory at the University of Pennsylvania. "Perhaps most relevant is the involvement of these brain regions in the control of aggression and other impulses . . . If the neural substrates of these behaviors have not reached maturity before adulthood, it is unreasonable to expect the behaviors themselves to reflect mature thought processes. The evidence now is strong that the brain does not cease to mature until the early 20s in those relevant parts that govern impulsivity, judgment, planning for the future, foresight of consequences, and other characteristics thatmake peoplemorally culpable . . . Indeed, age 21 or 22 would be closer to the 'biological' age of maturity." See also Roper v. Simmons, 543 U.S. 551, 569- 70; 125 S. Ct. 1183 (2005) (citations omitted): Three general differences between juveniles under 18 and adults [are recognized under our laws].First, as any parent knows and as the scientific and sociological studies respondent and his amici cite tend to confirm, "[a] lack of maturity and an underdeveloped sense of responsibility are found in youth more often than in adults and are more understandable among the young. These qualities often result in impetuous and ill-considered actions and decisions." It has been noted that "adolescents are overrepresented statistically in virtually every category of reckless behavior." In recognition of the comparative immaturity and irresponsibility of juveniles, almost every State prohibits those under 18 years of age from voting, serving on juries, or marrying without parental consent. The second area of difference is that juveniles are more vulnerable or susceptible to negative influences and outside pressures, including peer pressure. This is explained in part by the prevailing circumstance that juveniles have less control, or less experience with control, over their own environment. ("[A]s legal minors, [juveniles] lack the freedom that adults have to extricate themselves from a criminogenic setting"). The third broad difference is that the character of a juvenile is not as well formed as that of an adult. The personality traits of juveniles are more transitory, less fixed.
81. Adults are more likely candidates for medical marijuana than patients in the pediatric age group.
82. Jerome H. Jaffe, William R. Martin. Opioid analgesics and antagonists. In Goodman and Gilman, 494, 502.
83. Sandra P. Welch, Billy R. Martin. The pharmacology of morphine. In Principles of Addiction Medicine, 249, 261-263.
84. Jerome H. Jaffe. Drug addiction and drug abuse. In Goodman and Gilman, 535, 561.
85. Thomas M. Garrett, Harold W. Baillie, Rosellen M. Garrett. Health Care Ethics, 2nd edition. Upper Saddle River, NJ: Prentiss Hall; 1993:54-55. "Unless there is a sufficient reason not to, one has an obligation do those acts that are likely to do more good than harm."
86. Sandra P. Welch, Billy R. Martin. The pharmacology of marijuana. In Principles of Addiction Medicine, 249, 260.
87. JC Anthony, LA Warner, RC Kessler. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic findings from the National Comorbidity Study. Clin Exp Psychopharmacol. 1994;2:244.
88. Keith Stroup, Paul Armentano, The Problem is Pot Prohibition, Washington Post, May 4, 2002, A19.
89. Denise B. Kandel. Does marijuana use cause the use of other drugs? JAMA. 2003;289:482.
90. Physical dependence and tolerance, a normal consequence of opioid administration, differs significantly from addiction. See, e.g., Charles P. O'Brien. A 50- year-old woman addicted to heroin: review of treatment for heroin addiction, JAMA. 2008;300:314, 315: "[I]t is essential to distinguish between addiction, which involves a [pathologic] compulsion to take drugs, and simple tolerance with physical dependence, which is a normal phenomenon seen in everyone treated with opiates over the long term. In fact, tolerance begins with the first dose of opiates . . . "
91. Neil Irick. Practical issues in the management of pain. In Principles of Addiction Medicine, 1475, 1480.
92. Mark S. Gold. The pharmacology of marijuana. In: Allan W. Graham, Terry K. Schultz, editors. Principles of Addiction Medicine, 2nd ed. Chevy Chase, MD: American Society of Addiction Medicine; 1998:163-171.
93. Lambros Messinis, Anthoula Kyprianidou, Sonia Malefaki, Panagiotis Papathanasopoulos. Neuropsychological deficits in long-term frequent cannabis users. 66 Neurology. 2006;66:737.
94. Harrison G. Pope, Jr., Deborah Yurgelon-Todd. The residual cognitive effects of heavy marijuana use in college students. JAMA 1996;275:521.
95. Robert I. Block, Daniel S. O'Leary, Richard D. Hichwa, Jean C. Augustinack, Laura L. Boles Ponto, MM Ghoneim, Stephan Arndt, Richard R. Hurtig, G. Leonard Watkins, James A. Hall, Peter E. Nathan, Nancy C. Andreasen. Effects of frequent marijuana use on memory-related regional cerebral blood flow. Pharmacol Biochem Behav. 2002;72:237-250.
96. Id.
97. GK Tzilos, CB Cintron, JB Woods, AD Young, HG Pope, DA Yurgelun-Todd. Lack of hippocampal volume change in long-term heavy cannabis users. Am J Addict. 1005;14:64.
98. Bernard Laumon, B. Gadegbeku, JL Martin, MB Biechler, S.A.M. Group. Cannabis intoxication and fatal road crashes in france: population based case-control study. BMJ. 2005;331:1371. (While 2.5% of fatal crashes were attributed to the use of marijuana, at least 28.6% were caused by the use of alcohol.)
99. Summerlin v. Stewart, 341 F.3d 1082, 1084 (9th Cir. 2003).
100. -341 F.3d at 1087.
101. Id. at 1090.
102. Id. at 1090.
103. Constantine G. Lyketsos, Elizabeth Garrett, Kung-Yee Liang, James C. Anthony. Cannabis use and cognitive decline in persons under 65 years of age. Am J Epidemiol. 1999;149:794.
104. Keith Stroup, Paul Armentano, The Problem is Pot Prohibition, Washington Post, May 4, 2002, A19.
105. See, e.g., MarkWallace, Gery Schulteis, J Hampton Atkinson, Tanya Wolfson, Deborah Lazzaretto, Heather Bentley, Ben Gouaux, Ian Abramson. Dosedependent effects of smoked cannabis on capsaicininduced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007;107:785. Smoked marijuana in appropriate doses relieved pain in healthy volunteers but did not appear to produce significant decrements in mental performance (discussed infra, Part IV).
106. Jerome H. Jaffe. Drug addiction and drug abuse. In Goodman and Gilman, 535, 561.
107. Ćecile Henquet, Lydia Krabbendam, Janneke Spauwen, Charles Kaplan, Roselind Lieb, Hans-Ulrich Wittchen, Jim van Os. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ. 2005;330:11.
108. Louise Arseneault, Mary Cannon, Richie Poulton, Robin Murray, Avshalom Caspi, Terrie E. Moffitt. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 2002;325:1212.
109. George C. Patton, Carolyn Coffey, John B. Carlin, Louisa Degenhardt, Michael Lynskey. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325:1195.
110. Stanley Zammit, Peter Allebeck, Sven Andreasson, Ingvar Lundberg, Glyn Lewis. Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 2002;325:1199.
111. Mark S. Gold. The pharmacology of marijuana. In: Allan W. Graham, Terry K. Schultz, editors. Principles of Addiction Medicine, 2nd ed. Chevy Chase, MD: American Society of Addiction Medicine; 1998:163-171.
112. Reena Mehra, Brent A. Moore, Kristina Crothers, Jeanette Tetrault, David A. Fiellin. The Association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006;166:1359.
113. David Moir, William S. Rickert, Genevieve Levasseur, Yolande Larose, Rebecca Maertens, Paul White, Suzanne Desjardins. A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke produced under two machine smoking conditions. Chem Res Toxicol. ASAP Article, 10.1021/tx700275p, December 7, 2007.
114. Id.
115. S. Aldington, M. Williams, M. Nowitz, M. Weatherall, A. Pritchard, A. McNaughton, G. Robinson, R. Beasley. The effects of cannabis on pulmonary structure, function and symptoms. Thorax 2007;62:1058.
116. Id.
117. Id.
118. Mia Hashibe, Hal Morgenstern, Yan Cui, Donald P Tashkin, Zuo-Feng Zhang, Wendy Cozen, Thomas M Mack, Sander Greenland. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol Biomarkers Prev. 2006;15:1829.
119. Id.
120. See, e.g., Marc Kaufman, Study Finds no Cancer-Marijuana Connection, Washington Post, May 26, 2006, A3. The largest study of its kind has unexpectedly concluded that smoking marijuana, even regularly and heavily, does not lead to lung cancer. The new findings "were against our expectations," said Donald Tashkin [the senior author] of the University of California at Los Angeles, a pulmonologist who has studied marijuana for 30 years. "We hypothesized that there would be a positive association between marijuana use and lung cancer, and that the association would be more positive with heavier use," he said. "What we found instead was no association at all, and even a suggestion of some protective effect." . . . While no association between marijuana smoking and cancer was found, the study findings, presented to the American Thoracic Society International Conference this week, did find a 20-fold increase in lung cancer among people who smoked two or more packs of cigarettes a day.
121. Peter J. Cohen. Drugs, Addiction, and the Law: Policy, Politics, and Public Health Durham: North Carolina Academic Press; 2004:Chap. 3. [Hereinafter Drugs, Addiction, and the Law.] 111. See, e.g., America's Drug Use Profile, in National Drug Control Strategy (Office of National Drug Control Policy, The White House, 1999). In a 1-month period during 1997, approximately 11.1 million individuals self-reported having used marijuana; however, during the same period of time, only 1.5 million (13.5%) reported using either powdered or crack cocaine.
122. Salvatore Mannuzza, Rachel G. Klein, Nhan L. Truong, John L. Moulton III, Erica R. Roizen, Kathryn H. Howell, Francisco X. Castellanos. Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry. 2008;165:604.
123. If both identical and fraternal twins have the same environmental background and identical twins share the same genetic makeup why did only one of the twins voluntarily begin to use marijuana? Does this suggest that an individual's behavior does not depend solely upon genetic and environmental influences?
124. Michael T. Lynskey, Andrew C. Heath, Kathleen K. Bucholz, Wendy S. Slutzke, Pamela A. Madden, Elliott C. Nelson, Dixie J. Statham, Nicholas G. Martin. Escalation of drug use in early-onset cannabis users vs. co-twin controls. JAMA. 2003;289:427.
125. Denise B. Kandel. Does marijuana use cause the use of other drugs? JAMA. 2003;289:482.
126. See, e.g., CA Patten, JE Martin, N Owen. Can psychiatric and chemical dependency treatment units be smoke free? J Subst Abuse Treat. 1996;13:107
127. AC Collins, MJ Marks. Animal models of alcohol-nicotine interactions. In: JB Fertig, JP Allen. Alcohol and Tobacco: From Basic Science to Clinical Practice. NIAAA Research Monograph No. 30. NIH Publication No. 95-3931. Washington, DC: Superintendent of Documents, US Government Printing Office, 1995, pp. 129-144. ("Between 80 and 95 percent of alcoholics smoke cigarettes, a rate that is three times higher than among the population as a whole. Approximately 70 percent of alcoholics are heavy smokers (i.e., smoke more than one pack of cigarettes per day), compared with 10 percent of the general population.") I should also note that my work with drug-dependent physicians suggests that alcohol use often precedes the abuse of and addiction to illegal drugs.
128. See also Keith Stroup, Paul Armentano, The Problem is Pot Prohibition, Washington Post, May 4, 2002, A19: [It is reasonable to suggest] that marijuana, like other drugs, is not for kids. We permit adults to do many activities that we forbid children to do, such as motorcycle riding, skydiving, signing contracts, getting married, drinking alcohol and smoking tobacco. But we do not condone arresting adults who responsibly engage in these activities in order to dissuade our children from doing so. Nor can we justify arresting adult marijuana smokers at the pace of some 734,000 per year on the grounds of sending a message to children.
129. Supra note 115.
130. See, e.g., Peter J. Cohen. Medical marijuana, compassionate use, and public policy: expert opinion or vox populi? Hastings Center Report. 2006;36:19, 20. ("As an anesthesiologist, I have legally administered more narcotics (in the course of providing medical care) than many low-level illegal drug dealers".)