Institute of medicine

Index
Appendices

APPENDIX A
Workshop Agendas
INSTITUTE OF MEDICINE
NATIONAL ACADEMY OF SCIENCES
Division of Neuroscience and Behavioral Health
Medical Used of Marijuana: Assessment of the Science Base
Workshop on
Perspective on the Medical Use of Marijuana: Basic and Clinical Science
December 14-16, 1997
Beckman Center, Irvine, California
WORKSHOP AGENDA
Sunday, December 14, 1997 2:00 Introduction Constance Pechura, IOM Division Director, Neuroscience and Behavioral Health 2:30 Public input session, 5 minutes per person Moderator, Stanley Watson, Jr., IOM Study Investigator University of Michigan 5:30 ADJOURN Monday, December 15, 1997 Cannabinoid Neuroscience 8:30 Moderator Stanley Watson, IOM Study Investigator University of Michigan 8:45 Neuropharmacology of Cannabinoids and Their Receptors Steven R. Childers, Wake Forest University School of Medicine
Appendix A
9:15 Precipitated Cannabinoid Withdrawal and Sensory Processing of Painful Stimuli J. Michael Walker, Brown University 9:45 Role of Cannabinoids in Movement Clara Sanudo, Brown University 10:15 Tolerance and Cannabinoid-Opioid Interactions Sandra P. Welch, Medical College of Virginia 10:45 BREAK Medical Uses of Marijuana: Clinical Data and Basic Biology 11:10 John A. Benson, Jr., IOM Study Investigator Oregon Health Sciences University 11:15 Profile of Medical Marijuana Users John Mendelson, University of California at San Francisco 11:45 Immune Modulation by Cannabinoids Norbert KaminskI, Michigan State University 12:15 Psychological Effects of Marijuana Use Charles R. Schuster, Wayne State University 12:45 LUNCH 1:45 Marijuana and Glaucoma Paul Kaufman, University of Wisconsin 2:15 Effects of Marijuana and Cannabinoids in Neurological Disorders Paul Consroe, University of Arizona Health Sciences Center 2:45 Neural Mechanisms of Cannabinoid Analgesia Howard Fields, University of California at San Francisco 3:15 Pain Management. Michael Rowbotham, University of California at San Francisco 3:45 Wasting Syndrome Pathogenesis and Clinical Markers Donald Kotler, St. Lukes'-Roosevelt Hospital 4:15 Clinical Experience with Marijuana Stephen O'Brien, East Bay AIDS Center 4:45 ADJOURN
Appendix A
Tuesday. December 16, 1997 Medical Uses of Marijuana: Clinical Data and Basic Biology 8:30 Moderator John A. Benson, Jr., IOM Study Investigator Oregon Health Sciences University 8:45 Marijuana in AIDS Wasting: Tribulations and Trials Donald I. Abrams, University of California at San Francisco 9:l5 Nausea and Vomiting: Underlying Mechanisms and Upcoming Treatments Alan D. Miller, The Rockefeller University 9:45 Post-chemotherapy Nausea and Anti-emetics Richard J. Gralla, Ochsner Cancer Center 10:15 BREAK Summary Views 10:30 Marijuana is Different from THC: A Review of Basic Research and State Studies of Anti-emesis Richard E. Musty, University of Vermont 11:00 Medical Uses of Crude Marijuana: Medical and Social Issues Eric A. Voth, The International Drug Strategy Institute 11:30 General Questions Moderator, John A. Benson, Jr., IOM Study Investigator 12:00 ADJOURN
Appendix A
INSTITUTE OF MEDICINE
NATIONAL ACADEMY OF SCIENCES
Division of Neuroscience and Behavioral Health
Medical Use of Marijuana: Assessment of the Science Base
Workshop on
Acute and Chronic Effects of Marijuana Use
January 22-23, 1998
New Orleans Marriott Hotel
New Orleans, LA
WORKSHOP AGENDA
Thursday, January 22, 1998 2:00 Introduction Constance Pechura, IOM Division Director Neuroscience and Behavioral Health 2:30 Public Input Session, 5 minutes per person Moderator, Stanley Watson, Jr, IOM Study Investigator University of Michigan 4:30 ADJOURN Friday. January 23. 1998 8:30 Moderator John A. Benson, Jr., IOM Study Investigator Oregon Health Sciences University Health Consequences of Marijuana Use 9:00 Health Consequences of Marijuana Use: Epidemiologic Studies Stephen Sidney, Kaiser Permanente, Oakland, CA 9:30 Immunity, Infections, and Cannabinoids Thomas Klein, University of South Florida 10:00 Pulmonary Effects of Smoked Marijuana Donald Tashkin, Unversity of California at Los Angeles 10:30 BREAK

Appendix A
Tuesday, December 16, 1997 Medical Uses of Marijuana: Clinical Data and Basic Biology 8:30 Moderator John A. Benson, Jr., IOM Study Investigator Oregon Health Sciences University 8:45 Marijuana in AIDS Wasting: Tribulations and Trials VC Donald I. Abrams, University of California at San Francisco 9.15 Nausea and Vomiting: Underlying Mechanisms and Upcoming Treatments Alan D. Miller, The Rockefeller University 9:45 Post-chemotherapy Nausea and Anti-emetics Richard J. Gralla, Ochsner Cancer Center 10:15 BREAK Summary Views 10:30 Marijuana is Different from THC: A Review of Basic Research and State Studies of Anti-emesis Richard E. Musty, University of Vermont 11:00 Medical Uses of Crude Marijuana: Medical and Social Issues Eric A. Voth, The International Drug Strategy Institute 11:30 General Questions Moderator, John A. Benson, Jr., IOM Study Investigator 12:00 ADJOURN
Appendix A
10-45 Is Marijuana Carcinogenic? Epidemiological evidence for and against biological evidence for and against Panel Discussion Stephen Sidney Donald Tashkin 12:00 LUNCH Effects of Marijuana on Behavior 1:30 Marijuana: Addictive and Amotivational States, the Scientific Evidence John Morgan, City University of New York Medical School 2:00 Marijuana's Acute Behavioral Effects in Humans Richard Foltin' Columbia University 2:30 Tolerance and Dependence Following Chronic Administration of oral THC or smoked marijuana to humans Margaret Haney, Columbia University 3:00 Patterns of Continuity and Discontinuity of Marijuana Use in Relationship to Other Drugs Robert Pandina, Rutgers University 3:30 ADJOURN
Appendix A
INSTITUTE OF MEDICINE
NATIONAL ACADEMY OF SCIENCES
Division of Neuroscience and Behavioral Health
Medical Use of Marijuana: Assessment of the Science Base
Workshop on
Prospects for Cannabinoid Drug Development
February 23-24, 1998
National Academy of Sciences Building
Washington, D.C.
WORKSHOP AGENDA
Monday. FEBRUARY 23 , 1998 1:30 Introduction CONSTANCE PECHURA, IOM Division Director Neuroscience and Behavioral Health 2:00 Public Input Session, 5 minutes per person Moderator: JoHN A. BENSON, JR., IOM Study Investigator Oregon Health Sciences University 5:30 ADJOURN TUESDAY. FEBRUARY 24. 1998 8:30 Introduction CONSTANCE PECHURA, IOM Division Director Neuroscience and Behavioral Health Moderator: STANLEY J. WATSON, Jr., IOM Study Investigator University of Michigan Overviews of Preceding Workshops 8:45 Acute and Chronic Effects of Marijuana BILLY R. MARTIN, Medical College of Virginia 9:25 Perspectives on the Medical Use of Marijuana ERIC B. LARSON, University of Washington Medical School 9:55 The Neurobiology of Cannabinoid Dependence GEORGE F. Koob, Scripps Research Institute 10:25 BREAK

Appendix A
TUESDAY. FEBRUARY 24, 1998 Drug Development 10:45 Regulatory Requirements Affecting Marijuana J. RICHARD CROUT, Crout Consulting 11:15 Marinol and the Market Robert E. DUDLEY, Unimed Pharmaceuticals, Inc. l1:45 Development of Cannabis-based Therapeutics DAVE PATE, HortaPharm, B.V. 12:15 LUNCH Drug Delivery 1:30 Alternative Drug Delivery Technologies for the Therapeutic Use of Marijuana PHYLLIS I. GARDNER, ALZA Corporation, Stanford University 2:00 Delivery of Analgesics via the Respiratory Track REID M. RUBSAMEN, Aradigm Corporation 2:30 Current Concepts for Delivery of THC MAHENDRA G. DEDHIYA, Roxanne Laboratories, Inc. 3:00 D9-THC-Hemisuccinate in Suppository Formulation: An Alternative to Oral and Smoked THC MAHMOUD A. ELSOHLY, University of Mississippi, ElSohly Laboratories, Inc. 3:30 Concluding Remarks JOHN A. BENSON, JR., IOM Study Investigator Oregon Health Sciences University 3:45 ADJOURN

APPENDIX AA
Individuals and Organizations that Spoke or Wrote to the Institute of Medicine A complete list will appear in the published report

APPENDIX B
Scheduling Definitions
Scheduling Definitions Established by the Controlled Substances Act of 1970
Schedule I (includes heroin, LSD, and marijuana)

(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 the use of the drug or other substance under medical supervision.
Schedule II (includes Marinol® methadone, morphine, methamphetamine, and cocaine)

(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.
Schedule III (includes anabolic steroids)

(A) The drug or other substance has a potential of 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.
Schedule IV (includes Valium(R) and other tranquilizers)

(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.
Schedule V (includes codeine-containing analgesics)

(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.
Sources: LeCraw (1996) and 21 U.S.C. 812.

APPENDIX C
Statement of Task
The study will assess what is currently known, and not known about the medical use of marijuana. It will include a review of the science base regarding the mechanism of action of marijuana, an examination of the peer-reviewed scientific literature on the efficacy uses of marijuana, and the costs of using various forms of marijuana versus approved drugs for specific medical conditions (e.g., glaucoma, multiple sclerosis, wasting diseases, nausea, and pain).
The study will also include an evaluation of the acute and chronic effects of marijuana on health and behavior; a consideration of the adverse effects of marijuana use compared with approved drugs; an evaluation of the efficacy of different delivery systems for marijuana (e.g., inhalation vs. oral); and an analysis of the data concerning marijuana as a gateway drug, and an examination of the possible differences in the effects of marijuana due to age and type of medical condition.
Specific Issues
Specific issues to be addressed fall under three broad categories: the science base, therapeutic use, and economics.
Science Base

Review of neuroscience related to marijuana, particularly relevance of new studies on addiction and craving
Review of behavioral and social science base of marijuana use, particularly assessment of the relative risk of progression to other drugs following marijuana use
Review of the literature determining which chemical components of crude marijuana are responsible of possible therapeutic effects and for side effects
Therapeutic Use

Evaluation of any conclusions on the medical use of marijuana drawn by other groups
Efficacy and side-effects of various delivery systems for marijuana compared to existing medications for glaucoma, wasting syndrome, pain, nausea, or other symptoms
Differential effects of various forms of marijuana that relate to age or type of disease.
Economics

Costs of various forms of marijuana compared with costs of existing medications for glaucoma, wasting syndrome, pain, nausea, or other symptoms
Assessment of differences between marijuana and existing medications in terms of access and availability
These specific areas, along with the assessments described above will be integrated into a broad description and assessment of the available literature relevant to the medical use of marijuana.
APPENDIX D
Recommendations made in Recent Reports on the Medical Use of Marijuana
Recommendations from five recent key reports pertaining to the medical use of marijuana are listed by subject. Recommendations made on issues outside the scope of his report, such as drug law and scheduling clecisions, are not included here. The following reports were reviewed:

Health Council of the Netherlands, Standing Committee on Medicine. 1996. Marihuana as medicine. Rijswikj, the Netherlands: Health Council of the Netherlands.
Report of the Council on Scientific Affairs. 1997. Report to the AMA House of Delegates. Subject: Medical Marijuana.
British Medical Association. 1997. Therapeutic uses of cannabis. Harwood Academic Publishers, United Kingdom.
National Institutes of Health. 1997. Workshop on the medical utility of marijuana. Bethesda, MD: National Institutes of Health.
World Health Organization. 1997. Cannabis: a health perspective and research agenda.
November 1998, the British House of Lords Science and Technology Committee published, Medical Use of Cannabis, in which they reported their conviction that "cannabis almost certainly does have genuine medical applications." The House of Lords report was released too late in the preparation of the IOM report to permit careful analysis, and is not summarized here.
It is available on the internet at: www.parliament uk.
Appendix D
General recommendations
Health Council of the Netherlands
In order to assess the efficacy of marihuanaand cannabinoids, the committee studied literature published during the past 25 years. Based on their findings, the committee concluded that there was insufficient evidence to justify the medical use of marijuana.
AMA House of Delegates
Adequate and well-controlled studies of smoked marijuana be conducted in patients who have serious conditions for which preclinical, anecdotal, or controlled evidence suggests possible efficacy including AIDS wasting syndrome, severe acute or delayed emesis induced by chemotherapy, multiple sclerosis, spinal cord injury, dystonia, and neuropathic pain.
British Medical Association
Further research is required to establish suitable methods of administration, optimal dosage regimens and routes of administration for the above indications.
National Institutes of Health
For at least some potential indications, marijuana looks promising enough to recommend that there be new controlled studies done for the following indications: appetite stimulation and wasting, chemotherapy-induced nausea and vomiting, neurological and movement disorders, analgesia, glaucoma (but see note below). Until studies are done using scientifically acceptable clinical trial design and subjected to appropriate statistical analysis, the question concerning the therapeutic utility of marijuana will likely remain largely unanswered.
World Health Organization
Therapeutic uses of cannabinoids warrant further basic pharmacological and experimental investigation and clinical research into their effectiveness. More research is needed on the basic neuropharmacology of THC and other cannabinoids so that better therapeutic agents can be found.
Analgesia
Health Council of the Netherlands
No recommendations
AMA House of Delegates
Controlled evidence does not support the view that THC or smoked marijuana offer clinically effective analgesia without causing significant adverse events when used alone Preclinical evidence suggests that cannabinoids can potentiate opioid analgesia and that cannabinoids may be effective in animal models of neuropathic pain. Further research into the use of cannabinoids in neuropathic pain is warranted.
British Medical Association
The prescription of nabilone, THC and other cannabinoids should be permitted for patients with intractable pain. Further research is needed into the potential of cannabidiol as an analgesic in chronic, terminal and post-operative pain.
National Institutes of Health

Appendix D
Evaluation of cannabinoids in the management of neuropathic pain, including HIV-associated neuropathy, should be undertaken.
World Health Organization
No recommendations, although the report notes that some newly synthesized cannabinoids are extremely potent analgesics, however, separation of the analgesia and side effects remains to be demonstrated.
Nausea and vomiting
Health Council of the Netherlands
No recommendations
AMA House of Delegates
Research involving THC and smoked marijuana should focus on their possible use in treating delayed nausea and vomiting, and their adjunctive use in patients who respond inadequately to 5-HT3 antagonists. The use of an inhaled substance has the potential for benefit in ambulatory patients who are experiencing the onset of nausea, and are thus unable to take oral medications.
British Medical Association
Further research is needed on the use of A8-THC as an anti-emetic, the use of cannabidiol in combination of THC, and the relative effectiveness of cannabinoids compared with 5-HT3 antagonists. Further research is needed in other cases, such as post-operative nausea and vomiting.
National Institutes of Health
Inhaled marijuana merits testing in controlled, double-blind, randomized trials for nausea and vomiting.
World Health Organization
More basic research on the central and peripheral mechanisms of the effects of cannabinoids on gastrointestinal function may improve the ability to alleviate nausea and emesls.
Wasting syndrome and appetite stimulation
Health Council of the Netherlands
No recommendations
AMA House of Delegates
THC is moderately effective in the treatment of AIDS wasting, but its long duration of action and intensity of side effects preclude routine use. The ability of patients who smoke marijuana to titrate their dosage according to need and the lack of highly effective, inexpensive options to treat this debilitating disease create the conditions warrants formal clinical trial of smoked marijuana as an appetite stimulant in patients with AIDS wasting syndrome.

Appendix D
National Institutes of Health
There is a need for further research where long term administration of marijuana might be considered for therapeutic purposes. individuals who are HIV-positive or who have tumors or diseases where immune system function may be important in the genesis of the disease.
Areas of study for the potential appetite-stimulating properties of marijuana include the cachexia of cancer, HIV/AIDS symptomatology, and other wasting syndromes. Investigations should be designed to assess long-term effects on immunology status, the rate of viral replication, and clinical outcomes in participants as well as weight gain . In therapeutic trials of cachexia, research should attempt to separate out the effect of marijuana on mood versus appetite. Some questions need to be answered in the studies: (1) Does smoking marijuana increase total energy intake in patients with catabolic illness. (2) Does marijuana use alter energy expenditure? (3) Does marijuana use alter body weight, and to what extent? (4) Does marijuana use alter body composition and to what extent?
World Health Organization
No specific recommendation, although the report notes that dronabinol is an effective appetite stimulant for patients with AIDS wasting syndrome.
Muscle spasticity
Health Council of the Netherlands
No recommendations
AMA House of Delegates
Considerably more research is required to identify patients who may benefit from THC or smoked marijuana, and to establish whether responses are primarily subjective in nature. A therapeutic trial of smoked marijuana or THC may be warranted in patients with spasticity who do not derive adequate benefit from available oral medications, prior to their considering intrathecal baclofen therapy or neuroablative procedures.
British Medical Association
A high priority should be given to carefully controlled trials of cannabinoids in patients with chronic spastic disorders which have not responded to other drugs are indicated. In the mean time, there is a case for the extension of the indications for nabilone and THC for use in chronic spastic disorders unresponsive to standard drugs.
National Institutes of Health
Few available therapies provide even partial relief for the neuropathic pain that complicates many diseases affecting the central nervous system. Cannabinoid drugs are potentially valuable in these areas, especially if deivered by other than the smoked route. More research is needed.
Movement disorders
Health Council of the Netherlands
No recommendations

Appendix D
AMA House of Delegates
Considerably more research is required to identify dystonic patients who may benefit from THC or smoked marijuana, and to establish whether responses are primarily subjective in nature.
British Medical Association
The potential of (+) 210 for neruodegenerative disorders should be explored through further research
National Institutes of Health
More studies are needed in movement disorders
World Health Organization
No recommendations, although the report notes that cannabinoids have not yet been proven useful in the treatment of convulsant or movement disorder or in treating multiple sclerosis.
Epilepsy
Health Council of the Netherlands
No recommendations
AMA House of Delegates
No recommendations
British Medical Association
Trials with cannabidiol (which is non-psychoactive) used to enhance the activity of other drugs in cases not well controlled by other anticonvulants are needed.
National Institutes of Health
No recommendations
World Health Organization
No recommendations
Glaucoma
Health Council of the Netherlands
No recommendations
AMA House of Delegates
Neither smoked marijuana nor THC are viable approaches in the treatment of glaucoma, but research on their mechanism of action may be important in developing new agents that act in an additive or synergistic manner with currently available therapies
British Medical Association
Cannabinoids do not at present look promising for these indications, but much further basic and clinical research is needed to develop and investigate cannabinoids which lower intraocular pressure, preferably by topical application (ea. eye drops, inhalant aerosols), without producing unacceptable systemic and central nervous system effects.
National Institutes of Health
Further studies to define the mechanism of action and to determine the efficacy of delta9-tetrahydrocannabinol and marijuana in the treatment of glaucoma are justified.
Appendix D
World Health Organization
No recommendations
Physiological harms
Health Council of the Netherlands
No recommendations
AMA House of Delegates
No recommendations
British Medical Association
Further research is needed to establish the suitability of cannabinoids for immunocompromised patients, such as those undergoing cancer chemotherapy or with HIV/AIDS.
National Institutes of Health
Additional studies of long term marijuana use are needed to determine if there are or are not important adverse pulmonary, central nervous system (CNS), or immune system problems. The suggested design for clinical studies is to add marijuana, oral THC, or placebo to standard therapy under double-blind conditions: (1) Establish dose-response and dose-duration relationships for IOP and CNS effects. (2) Relate IOP and blood pressure measurements longitudinally to evaluate potential tolernce development to cardiovascular effects. (3) Evaluate CNS effects longitudinally for tolerance development.
World Health Organization
Further studies are required of marijuana use on fertility effects, respiratory function and disease, immunological function, and cardiovascular effects.
Psychological harms
Health Council of the Netherlands
No recommendations
AMA House of Delegates
No recommendations
British Medical Association
No recommendations
National Institutes of Health
No recommendations
World Health Organization
There is a need for controlled studies investigating the relationships between cannabis use, schizophrenia and other serious mental disorders. Insufficient research has been undertaken on the 'amotivational' syndrome which may or may not result from heavy cannabis use. It is not clear that the syndrome exists, even though heavy cannabis use is sometimes associated with reduced motivation to succeed in school and work. New research is needed to show whether the reduced motivation seen in some cannabis users is due to other psychoactive substance use and whether it precedes cannabis use. Further
Appendix D
development of cognitive and psychomotor tests for controlled studies that are sensitive to the performance effects of cannabis use and that reflect the complexity of specific daily functions (e.g., driving, learning, reasoning) also need additional research. More research in examining the relationship between THC concentrations in blood and other fluids and the degree of behavioral impairment produced.
Physiological harms
Health Council of the Netherlands
No recommendations
AMA House of Delegates
No recommendations
British Medical Association
No recommendations
National Institutes of Health
There significant health risks associated with smoked marijuana that must be considered not only in terms of immediate adverse effects, but also long-term effects in patients with chronic diseases. The possibility that frequent and prolonged marijuana use might lead to clinically significant impairments of immune system function is great enough that relevant studies should be part of any marijuana medication development research.
World Health Organization
Research on chronic and residual cannabis effects is also needed. The lack of knowledge restricts the ability of researchers to relate drug concentrations in blood or other fluids and observed effects.
More studies are needed on the fertility effects in cannabis users, in view of the high rate of use during the early reproductive years.
More research is required on the effects of cannabis on respiratory function and respiratory diseases. More studies on whether cannabis affects the risk of lung malignancies and what level of use that may occur. More studies are needed to clarify the rather different results of pulmonary histopathological studies in animals and man.
More clinical and experimental research is needed on the effects of cannabis on the immunological function. More clarity should be sought concerning the molecular mechanisms responsible for immune effects, including both cannabinoid receptor and non-receptor events.
The possibility that chronic cannabis use has adverse effects on the cardiovascular system.
Smoked marijuana and use of plants as medicine
Health Council of the Netherlands
Not recommended. The committee believes that physicians cannot accept responsibility for a product of unknown composition that has not been subjected to quality control
Appendix D
AMA House of Delegates
NIH should use its resources to support the development of a smoke-free inhaled delivery system for marijuana or THC to reduce the health hazards associated with the combustion and inhalation of marijuana.
British Medical Association
Prescription formulations of cannabinoids or substances acting on the cannabinoid receptors should not include either cigarettes or herbal preparations with unknown concentrations of cannabinoids or other chemicals.
National Institutes of Health
NIH should use its resources and influence to rapidly develop a smoke-free inhaled delivery system for marijuana or THC. This will also bring this research effort in line with other Government initiatives to curtail cigarette smoking. "Taking the smoke" out of an inhaled dosage form of marijuana or THC would remove an important obstacle to the accurate determination of inhaled marijuana's beneficial and deleterious effects.
World Health
Not discussed in the context of medical use, although many health hazards associated with chronic marijuana smoking are noted.
Drug development
Health Council of the Netherlands
Not discussed
AMA House of Delegates
NIH should use its resources to support the development of a smoke-free inhaled delivery system for marijuana or THC to reduce the health hazards associated with the combustion and inhalation of marijuana.
British Medical Association
Pharmaceutical companies should undertake basic laboratory investigations and develop novel cannabinoid analogues which may lead to new clinical uses.
National Institutes of Health
NIH should use its resources and influence to rapidly develop a smoke-free inhaled delivery system for marijuana or THC. This will also bring this research effort in line with other Government initiatives to curtail cigarette smoking. "Taking the smoke" out of an inhaled dosage form of marijuana or THC. would remove an important obstacle to the accurate determination of inhaled marijuana's beneficial and deleterious effects.
World Health Organization
Not discussed.

APPENDIX E
Rescheduling Criteria
DEA's Five Factor Test for Rescheduling
(Formulated in 1992 in Response to Court Challenge to Scheduling)
(1) The Drug's Chemistry Must Be Known and Reproducible
The substance's chemistry must be scientifically established to permit it to be reproduced in dosages which can be standardized. The listing of the substance in a current edition of one of the official as defined by section 201 (I) of the Food, Drug and Cosmetic Act, 21 USC 321(f), is sufficient generally to meet this requirement.
(2) There Must be Adequate Safety Studies
There must be adequate pharmacological and toxicological studies done by all methods reasonably applicable on the basis of which it could be fairly and responsibly concluded, by experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, that the substance is safe for treating a specific, recognized disorder.
(3) There Must Be Adequate and Well-Controlled Studies Proving Efficacy
There must be adequate, well-controlled, well-designed, well-conducted, and well documented studies, including clinical investigations, by experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs on the basis of which it could fairly and responsibly be concluded by such experts, that the substance will have its intended effect in treating a specific, recognized disorder.
(4) The Drug Must Be Accepted by Qualified Experts
The drug must have a New Drug Application (NDA) approved by the Food and Drug Administration...Or, a consensus of the national community of experts, qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, accepts the safety and effectiveness of the substance for use in treating a specific, c, recognized disorder. A material conflict of opinion among experts precludes a finding of consensus.
(5) The Scientific Evidence Must Be Widely Available
In the absence of NDA approval, information concerning the chemistry, pharmacology, toxicology and effectiveness of the substance must be reported, published, or otherwise widely available in sufficient detail to permit experts, qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, to fairly and responsibly conclude the substance is safe and effective for use in treating a specific, recognized disorder.
Sources: LeCraw (1996) and 57 Fed. Reg. 10499- (1992).

NATIONAL ACADEMY PRESS The National Academy Press publishes the reports issued by the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council, all operating under a charter granted by the Congress of the United Stares.
www.nap.edu

UKCIA does not encourage anyone to grow or use cannabis. The aim of the site is as an information resource which will help people fight the injustice of prohibition with the strongest of weapons: Knowledge.