UNITED STATES DISTRICT COURT
SAN JOSE DIVISION
I, Dr, Harvey L. Rose, declare as follows:
1. I am a physician licensed to practice medicine in the State of California. I received my undergraduate degree from the University of California at Los Angeles, where I graduated cum laude in 1954. I received my M.D. in 1958 from the University of Southern California School of medicine. I subsequently completed a Rotating Internship at Harbor General Hospital in Torrance, California (1958-1959), where I received the Medical Director's Award; followed by a General Practice Residency at Sacramento County Hospital (1959-1960), where I received the Mead Johnson Award for Family Practice Residents.
2. From 1960 through 1962, I served in the United States Air Force as a Family Practice Medical Officer, stationed at Iraklion Air Station in Crete, Greece. Since that time, I have been a Board-certified Family Practitioner. In 1978, I became a Fellow of the American Academy of Family Physicians. For many years, I was also an Assistant Clinical Professor of Family Practice, at the University of California-Davis School of Medicine.
3. In my more than 40 years of practice, I have devoted the majority of time to the study and treatment of chronic pain. I have served as a consultant to state legislative bodies in California, Idaho, Nevada, Washington and Oregon on issues of pain management and the appropriate role of regulatory agencies. From 1988 through 1992, I was an active member of the American Pain Society's Special Committee on Analgesic Regulatory Issues. In 1990, I was consultant to California State Senator Leroy Greene, the author of Senate Bill 1802, signed into law as the Intractable Pain Treatment Act. In 1993, I testified before the Medical Board of California task force on appropriate prescribing. In March of 1994, I was an invited participant in Governor Wilson's "Summit on Effective Pain Management: Removing Impediments to Appropriate Prescribing. Later that year, I was honored with an Award/Resolution from the Union of American Physicians and Dentists for efforts and leadership in legislation and education for proper chronic pain relief. In November of 1996, the California State Senate Rules Committee passed Resolution #2136, commending me for significant contributions in the compassionate treatment of chronic pain. I am a founding director of The National Foundation for the Treatment of Pain on whose board I served.
4. Both my research and my many years as a clinician have convinced me that marijuana can serve at least two important roles in safe and effective pain management. Ample anecdotal evidence and clinical observations, as well as significant research findings, strongly indicate that marijuana, for whatever reason, is often effective in relieving pain. This is true across a range of patient populations, including the elderly, the terminally ill seeking comfort in their final days, young adults stricken with life-threatening conditions, and cancer patients unable to tolerate the devastating effects of potentially life-saving therapies. Marijuana is also widely recognized as an antiemetic that reduces the nausea and vomiting often induced by powerful opioid analgesics prescribed for chronic, severe pain, as well as the nausea, vomiting and dizziness which often accompany severe and/or prolonged pain. I have had the benefit of consultations on this subject over many years with a range of treatment providers, including physicians, oncologists, pharmacologists, family practitioners, hospice workers, and pain specialists. Although many have lamented the relative paucity of scientific data available, the premise that marijuana has, or likely has, beneficial analgesic qualities has been consistently confirmed. The problem was summed up quite succinctly in a published case report:
"Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their clinical use has been restricted by legislation." (Holdcroft, A., et al. "Pain relief with oral cannabinoids in familial Mediterranean fever," Anaesthesia 52:483-488 (1997).)
5. The scientific evidence accumulated by clinicians and researchers, especially when considered in light of the historical role of marijuana in medical care, is more than sufficient to warrant extensive study. Unfortunately, because of marijuana's legal status and the stigma surrounding this particular substance, research has been extremely limited by governmental restrictions, especially research involving human subjects. Nonetheless, there does exist a small yet compelling body of research demonstrating the effectiveness and safety of medical marijuana in conjunction with palliative care.
The research published to date certainly indicates that the chemical compound tetrahydrocannabinol (THC), one of the chief active components of marijuana (but by no means the only one), has analgesic properties in both animals and humans. The benefits of marijuana in reducing pain have been clinically observed and documented in laboratory animals. Numerous animal studies confirm that intravenous or spinal cord injection of THC is clearly effective in relieving pain. These include the following:
•Wilson, R.S., & May, E.L., "Analgesic Properties of the Tetrahydrocannabinols, their Metabolites, and Analogs," 18 Journal of Medical Chemistry 700 (1975);
•Moss, D.E. & Johnson, R.L., "Tonic Analgesic Effects of Delta-9-Tetrahydrocannabinol as Measured with the Formalin Test," 61 European Journal of Pharmacology 313 (1980);
•Welch, S.P. & Stevens, D.L., "Antinociceptive Activity of Intrathecally Administered Cannabinoids Alone, and in Combination with Morphine, in Mice," 262 Journal of Pharmacological Experimental Therapy 10 (1992);
•Reche, I. et al., "A Role for Central Cannabinoid and Opioid Systems in Peripheral Delta-9-Tetrahydro Cannabinol-Induced Analgesia in Mice," 301 European Journal of Pharmacology 75 (1996); and
•Smith, P.B. & Martin, B.R., "Spinal Mechanisms of Delta-9-Tetrahydrocannabinol-Induced Analgesia," 578 Brain Research 8 (1992).
6. The Wilson and May study provides extremely compelling evidence that cannabinoids do in fact have analgesic properties. In that study, researchers tested the analgesic properties of delta-9-THC, as well as several metabolites and analogs (comparable compounds) found in marijuana. In addition to their findings regarding THC's analgesic properties, the authors saw strong indications that some of the metabolites of THC may be more effective at relieving pain than the compound itself:
"Examination of the naturally occurring THC's, many of their metabolites, and some synthetic analogs has suggested that in mice the active analgesic form may be the 11-hydroxy metabolites." (Wilson & May, supra, at 702.)
A study conducted in Switzerland reached similar conclusions:
"(I)t might be possible that not only delta-9-THC but also its metabolites, especially 11-OH-delta-9-THC, have an antispastic and analgesic effect." (Maurer, M., Henn, V., Dittrich, A. & Hofmann, A., "Delta-9-tetrahydrocannabinol Shows Antispastic and Analgesic Effects in a Single Case Double-blind Trial," 240 European Archives of Psychiatry & Clinical Neuroscience 1-4 (Spring 1990).)
The relative importance of these THC metabolites may account for the widely documented reports by many human patients that smoked marijuana is more effective than synthetic THC (“Marinol”) at relieving pain and nausea. The promising metabolites identified in these studies are not found in Marinol.
7. The 1980 research of Moss and Johnson expanded upon the Wilson and May study, demonstrating that oral administration of THC also produced an analgesic effect in laboratory animals. Numerous other animal studies have since confirmed that THC -- either alone or in combination with opioid analgesics -- does indeed reduce pain in laboratory animals. These studies have begun to refine our understanding of the mechanisms by which THC functions as an analgesic. A recent study concluded that THC is apparently not blocked by opioid antagonists, suggesting that THC and the other components of marijuana utilize different receptors than those used by most opiates commonly prescribed to treat pain in humans. There is also reason to believe that the chemical components of THC and its metabolites produce alterations in the transmissions of neurons. In an important and related finding, studies also suggest that THC and opiates can work synergistically to alleviate pain:
"(T)he antinociceptive effects of i.t.-administered morphine are enhanced by the pretreatment with the cannabinoids." (Welch, S.P. & Stevens, D.L., "Antinociceptive Activity of Intrathecally Administered Cannabinoids Alone, and in Combination with Morphine, in Mice." Journal of Pharmacological and Experimental Therapies 262:1 (1992).)
8. A 1999 article reviewing the body of scientific animal research concerning the analgesic effects of marijuana concludes that “[t]here is now unequivocal evidence that cannabinoids are antinociceptive [capable of blocking the appreciation or transmission of pain] in animal models of acute pain.” William J. Martin, Basic Mechanisms of Cannabinoid-Induced Analgesia, IASP Newsletter (International Association for the Study of Pain) Summer 1999, at 89.
9. Clinical trials of THC among human subjects have yielded results consistent with the earlier studies of laboratory animals. Two studies conducted in the mid-1970's indicated that THC was an effective analgesic for cancer pain. In the first study, conducted with 10 cancer patients, the subjects were administered either a placebo, or varying doses (5-20 mg.) of THC in a double blind, random manner. Pain symptoms were assessed by patient interviews and observations by clinical staff. Side effects were measured through a patient questionnaire. The study revealed:
". . .(A) significant trend toward progressive relief of pain with increasing doses of the drug . . . This preliminary trial of THC on a limited number of patients has demonstrated an analgesic effect of the drug."
Also significant was their finding that "the reduction in pain (with THC) appears to be independent of the compound's euphoric and antianxiety effects." (Noyes, R. et al., “Analgesic Effect of Delta-9-Tetrahydrocannabinol,” Journal of Clinical Pharmacology 15:139-143 (1975).)
10. This study was later repeated as part of a project conducted with support from the National Institutes of Health. The resulting report is notable for its analysis of the analgesic properties of marijuana, as compared with Codeine. The sample group consisted of patients suffering prolonged and at least "moderately severe" pain attributable to advanced stages of cancer. The researchers concluded that: "This trial has demonstrated an analgesic effect of THC in patients with cancer pain." (Noyes, R., et al., "The analgesic properties of delta-9-tetrahydrocannabinol and codeine." Clinical Pharmacology and Therapeutics 18:1 (1975).) Even acknowledging some limitations of the study -- none of the patients had previously taken long-term opioid therapies, and mechanisms were not in place to measure relief from either drug with respect to relative dosages -- the authors nonetheless believed that the analgesic properties of marijuana could not be dismissed.
11. Interestingly, although the analgesic qualities of marijuana appeared in some respects to be similar to those of Codeine, in other respects they differed. It appeared from this limited study that the analgesic effects of THC developed more gradually and were more prolonged than those of Codeine. However, when dosages were adjusted, the effects of THC were "roughly comparable" to those of Codeine. Administering a 20 mg. dose of THC, however, produced the equivalent analgesic effect as a 120-mg does of codeine; and both had statistically significant analgesic effects as compared to the placebo.
12. This research left open the possibility that the mechanisms underlying THC's analgesic effects might well differ from those of opiate-based analgesics, yet this possibility in no way detracts from its possible benefits in combating pain. If anything, the writers suggested that used in combination, THC and codeine might each enhance the properties of one another:
"If the mechanism of THC's analgesic effect differs from that of other mild analgesics . . ., the drug may prove useful in combination with one or more of these drugs. Such an additive effect is suggested by the results with THC and aspirin in the preliminary comparison."
13. (Noyes, R. et al., “The Analgesic Properties of Delta-9-Tetrahydrocannabinol and Codeine,” Clinical Pharmacology and Therapeutics 18-84 (1975).) Other human studies similarly point to the synergistic potential of cannabinoids to bolster the analgesic effect of prescription medications. See e.g., Maurer, M., et al, “Delta-9-Tetrahydrocannabinol Shows Anti-Spastic and Analgesic Effects in a Single Case Double-Blind Trial,” European Archives of Psychiatry & Clinical Neuroscience 240:1 (1990) (double blind study of single patient suffering from spinal cord injury wherein THC and codeine both showed analgesic effects over placebo, but only THC decreased spasticity); Holdcroft, A., et al., “Pain Relief with Oral Cannabinoids in Familial Mediterranean Fever,” Anaesthesia 52:483 (1997) (double blind study of patient wherein patient self-administered more than twice as much morphine to control pain during period in which he was given a placebo than period during which he was administered THC.)
14. In 1990, researchers conducted a double-blind study comparing the antispastic and analgesic effects of THC, oral Codeine, and a placebo on a single patient suffering from a spinal cord injury. Their findings confirmed the analgesic effects of THC:
"The analgesic effects of THC corresponded with the results of Noyes et al. (1975) in a study of THC, codeine and placebo in cancer patients suffering from pain. These authors reported that THC is equivalent to codeine in its analgesic effect." (Maurer, et al., "Delta-9-tetrahydrocannabinol Shows Antispastic and Analgesic Effects in a Single Case Double-Blind Trial," European Archives of Psychiatry and Clinical Neuroscience 240:1-4 (Spring 1990).)
Also significant was their finding that "a dosage of 5 mg. THC p.o. (orally) was sufficient to improve most of the symptoms...without causing an altered state of consciousness." (Ibid., at 2 (emphasis added).) Additionally, while THC and codeine were found to be comparable as analgesics, "THC was then only substance to show an antispastic effect, which lasted longer than 12 (hours)." (Ibid., at 3.)
15. More recently, both the United States and British governments convened top-level research commissions to examine the scientific research and clinical experience concerning marijuana’s therapeutic uses and effects. Both commissions found that patients with various pain syndromes claim significant relief from marijuana. In 1999, the U.S. National Institute of Medicine of the National Academy of Sciences ("IOM") published an extensive review of the scientific evidence of the therapeutic applications of cannabis. Institute of Medicine Marijuana and Medicine: Assessing the Science Base, (Janet E. Joy, et al., eds., National Academy Press 1999) ("IOM Report") (available at http://www.nap.edu/books/0309071550/html). The IOM's 250-plus-page report conditionally endorsed the short-term clinical use of marijuana under certain conditions, IOM Report at 179, and concluded that "[s]cientific data indicate the potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation." IOM Report at 15, 179. In 1998, Great Britain’s House of Lords also undertook a comprehensive review of the medical uses of marijuana. Select Committee on Science and Technology, House of Lords, Sess. 1997-98, 9th Report, Cannabis: The Scientific and Medical Evidence: Report (Nov. 4, 1998), available at http://www.publications.parliament.uk/pa/ld199798/ldselect/ldsctech/151/15101.htm (“Lords Report”). The Lords Report concludes that "cannabis almost certainly does have genuine medical applications, especially in treating the painful muscular spasms and other symptoms of MS and in the control of other forms of pain." Lords Report § 8.2, at 41.
16. In 2001, British researchers reported that cannabis extract sprayed under the tongue was effective in reducing pain in 18 of 23 patients who were suffering from intractable pain. Clive Cookson, High Hopes for Cannabis to Relieve Pain: British Association Science Festival in Glasgow, Financial Times, September 4, 2001, at National News pg. 4, available at http://news.ft.com/ft/gx.cgi/ftc?pagename=View&c=Article&cid=FT3WWJOM6RC&live=true&query=cannabis. The studies being conducted in Great Britain and other countries are of great value to medical practitioners in the United States. Unlike the field of law, where reports from foreign jurisdictions typically carry little precedential value, scientific research – including medical research – applies across political boundaries. Thus, it is appropriate (and often essential) for researchers and clinicians to remain informed of therapeutic advances both at home and abroad.
17. Attached as Exhibit A is the affidavit of Irvin Rosenfeld filed in In the Matter of Rescheduling Petition, Department of Justice, U.S. Drug Enforcement Administration, Docket 86-22, September 6, 1988, before the DEA's Chief Administrative Law Judge, Francis L. Young. From the age of 10, Mr. Rosenfeld has suffered from Multiple Congenital Cartilaginous Exostosis and/or the related condition Psuedo Hypoparathyroidism, both of them rare and intensely painful diseases which cause bone tissue to branch into buds or spurs and grow rapidly into surrounding muscle tissue and nerve fibers. As an adult, Mr. Rosenfeld discovered that he could control his pain with marijuana while drastically reducing his medical dependence on opioid analgesics. Those medications – including Dilaudid (4 mg per day? for 19 years), Demerol, and Percocet -- had provided minimal relief while saddling him with unpleasant debilitating side effects. In 1982, the Food and Drug Administration (FDA) approved Mr. Rosenfeld’s application to use medical marijuana as part of his medically-monitored pain management regimen. That year, he began receiving marijuana cigarettes from the National Institute on Drug Abuse, under the joint auspice of the federal Drug Enforcement Administration and the Food and Drug Administration. Mr. Rosenfeld continues to receive his supply of medical marijuana from the federal government to this day. In the published Opinion and Recommended Ruling, Findings of Fact, Conclusions of Law and Decision of Administrative Law Judge in the Matter of Marijuana Rescheduling Petition, Docket No. 86-22 (Dep't Justice D.E.A., Sept. 6, 1988) (hereinafter, “ALJ Opinion”), Judge Young concluded that “[t]he evidence in this record clearly shows that marijuana has been accepted as capable of relieving the distress of great numbers of very ill people, and doing so with safety under medical supervision.” ALJ Opinion at 68.
18. Mr. Rosenfeld’s experience and the data from the human studies mentioned above track my clinical observations in at least one-half dozen of my serious chronic pain patients. Specifically, I have found that cannabis can have an important opioid-sparing effect for pain patients. That is to say, that patients who are prescribed high doses of opioid analgesics can significantly reduce their reliance on these medications and improve their daily functioning by incorporating cannabis into their pain care regimen.
19. Marijuana not only has important analgesic properties but it also is an effective and important adjuvant therapy for patients suffering acute and/or chronic pain. No experienced and respected physician will deny that for such patients opioid therapy is central to palliative care. By the same token, the same experienced physicians will readily acknowledge that opioids often induce nausea and vomiting. For a number of pain patients, standard prescription antiemetics (e.g., Compazine, Zofran and Reglan) simply do not substantially reduce their nausea. For many, those medications are substantially less effective, or produce more debilitating side effects, than marijuana.
20. The anti-emetic properties of marijuana are well-documented in research studies, scholarly articles, and testimony before state and federal legislative and regulatory bodies. (See e.g., Report of the Research Advisory Panel to the California State Legislature, "Cannabis Therapeutic Research Program" (January 24, 1989); Vincent Vinciguerra et al., Inhalation Marijuana as an antiematic for cancer chemotherapy, N.Y.S.J. Med. 525 (Oct. 1988) (New York State-sponsored study examining the effects of herbal cannabis on cancer chemotherapy patients who were unresponsive to standard antiemetics and finding that 78% responded positively to cannabis); Lords Report § 5.12, at 21 (finding cannabis effective in alleviating acute nausea and vomiting).
21. Quite simply, marijuana can serve much the same function for pain patients undergoing opiate therapy that it does for cancer patients undergoing chemotherapy: it suppresses the nausea and vomiting associated with treatment, and reduces the pain associated with prolonged nausea and retching, thereby increasing the chances that the patient will remain compliant with the primary treatment. With both chemotherapy and long-term pain management, failure to obtain and continue proper palliative and adjutant care can have dire, even fatal, consequences. One study acknowledged these risks in very unambiguous terms:
"it should be recognized that in part, fear of uncontrolled pain due to cancer and other debilitating conditions propels the current interest in euthanasia, physician assisted suicide and suicide."
Joranson, et al., supra (citing Foley, K.M. (1991) "The relationship of pain and symptom management to patient requests for physician-assisted suicide," J. of Pain and Symptom Management 6(5):289-297; and Connolly, M.E. "Alternative to Euthenasia: Pain management," Issues in Law and Medicine 4(4):497-507 (1989)). The report concludes:
"It should be recognized that chronic pain, regardless of it source, is debilitating; unrelieved chronic nonmalignant pain may even lead to suicide."
Id. (citing Fishbain, D.A., et al., "Case report: Completed suicide in chronic pain," The Clinical Journal Of Pain 7:29-36 (1991).
22. Finally, it is important to note that in my clinical experience observing patients who ingest cannabis for relief from pain and nausea and/or to stimulate appetite, I have witnessed no adverse complications. By contrast, many of the first-line pharmaceuticals used to combat cancer, HIV/AIDS, and pain associated with these and other illnesses can induce a variety of iatrogenic effects, including, in some instances, death. While patients may face serious legal implications related to their use of medical marijuana, as a physician I have yet to encounter a medical downside to their cannabinoid therapy. Nearly fifteen years ago, Administrative Law Judge Francis Young similarly found that “there is accepted safety for use of marijuana under medical supervision,” ALJ Opinion at 66, and that "[t]here was no record in the extensive medical literature describing a proven, documented cannabis-induced fatality." Id. at 58. To be sure, as a practicing clinician and lecturer in the field of pain care, I fully endorse what virtually every study in the field of cannabinoid and pain research has emphasized, namely that "further study of THC's analgesic effect is warranted." (Noyes, R. et al., “The Analgesic Properties of f Delta-9-Tetrahydrocannabinol and Codeine,” Clinical Pharmacology and Therapeutics 18-84 (1975).) But against the backdrop of a growing body of scientific research, the reports of myriad pain patients, and the burgeoning clinical experience of physicians like myself, it is my considered opinion that cannabis can constitute an acceptable and sometimes necessary medicine to alleviate the immediate suffering of certain patients.
I declare under penalty of perjury under the laws of the United States of America and the State of California that the foregoing is true and correct to the best of my knowledge and that this declaration was executed this _____ day of April, 2003 in ____________________, California.
HARVEY L. ROSE, M.D
Copyright Women's Alliance for Medical Marijuana 2007 - 2008