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Untreated Addiction Imposes an Ethical Bar to Recruiting Addicts for Non-Therapeutic Studies of Addictive Drugs

Published online by Cambridge University Press:  01 January 2021

Extract

The mental illness of substance dependence or addiction is responsible for major economic, social, and personal costs. If we are to elucidate its etiology, understand its mechanisms, and eventually bring it under control, scientific investigation is essential. Research in animals and humans has enhanced our understanding of this disease through examination of genetic, neurophysiological, biochemical, and behavioral factors. But because animals cannot verbalize their subjective responses to drugs and because significant symptoms of addiction (e.g., craving, impaired control, and compulsive use) cannot be observed in non-drug-dependent humans, it is not surprising that certain investigations of substance dependence have required the participation of addicted or substance-dependent humans.

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Article
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Copyright © American Society of Law, Medicine and Ethics 2002

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References

Nutt, D.J., “Addiction: Brain Mechanisms and their Treatment Implications,” Lancet, 347 (1996): 3136, at 32 (“Because addiction is an imprecise and potentially pejorative term, the WHO [World Health Organization] recommended in 1969 that it should be replaced by the term drug dependence.”). Since the term “addiction” is the more familiar term, I will use “addiction” interchangeably with “substance dependence,” as defined by the DSM-IV criteria, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (Washington, D.C.: American Psychiatric Association, 1994).CrossRefGoogle Scholar
In 1990, deaths attributed to drug use were estimated as follows: 400,000 from tobacco; 100,000 from alcohol; and 20,000 from “illegal” drugs. It was estimated that 3 million people in the United States had serious problems related to illegal drugs. McGinnis, J.M. and Foege, W.H., “Actual Causes of Death in the United States,” in Areen, J. et al., eds., Law, Science and Medicine, 2nd ed. (Westbury, New York: Foundation Press, 1996): 502–10. Overall lifetime prevalence of drug use disorders is 6.2 percent; overall lifetime prevalence of alcohol disorders is 13.5 percent. Crum, R.M., “The Epidemiology of Addictive Disorders,” in Graham, A.W. and Schultz, T.K., eds., Principles of Addiction Medicine, 2nd ed. (Chevy Chase, Maryland: American Society of Addiction Medicine, 1998): 3-15. In 1995, illegal drug use was estimated to have cost approximately $110 billion and to have resulted in approximately 9,300 deaths. Drug-related emergency room visits were over half a million annually. The social costs of drug and alcohol abuse in 1995 were estimated at $277 billion. National Drug Control Strategy (Washington, D.C.: Office of National Drug Control Policy, 1999): at 14-15. From 1990 to 1992, the National Comorbidity Survey of more than 8,000 Americans ages 15–54 demonstrated that 7.5 percent had developed dependence on illicit drugs. Injection drug use is the leading factor for new HIV infections in the United States. Institute of Medicine, Pathways of Addiction: Opportunities in Drug Abuse Research (Washington, D.C.: National Academy Press, 1996): at 102, 161.Google Scholar
The neurochemical mechanisms responsible for addiction to “legal” and “illegal” drugs are similar. The same ethical considerations apply to alcohol and nicotine dependence as illegal drug dependence because it is the impact of compulsive use and denial on an addict's competency to consent that are in question. That alcohol and cigarettes are “legal drugs” is not germane to the discussion.Google Scholar
See, for example, Adler, M.W., College on Problems of Drug Dependence, “Special Report: Human Subject Issues in Drug Abuse Research,” Drug and Alcohol Dependence, 37 (1995): 167–75; Leshner, A.I., “What We Know: Drug Addiction Is a Brain Disease,” in Graham, A.W. and Schultz, T.K., eds., Principles of Addiction Medicine, 2nd ed. (Chevy Chase, Maryland: American Society of Addiction Medicine, 1998):: xxix–xxxvi; Nutt, , supra note 1.Google Scholar
Gardner, E.L. and Lowinson, J.H., “Drug Craving and Positive/Negative Hedonic Brain Substrates Activated by Addicting Drugs,” The Neurosciences, 5 (1993): 359–68.Google Scholar
See Diagnostic and Statistical Manual of Mental Disorders, supra note 1.Google Scholar
See, for example, Gorelick, D.A., Pickens, R.W. and Bonkovsky, F.O., “Clinical Research in Substance Abuse: Human Subjects Issues,” in Pincus, H.A., Liberman, J.A. and Ferris, S., eds., Ethics in Psychiatric Research (Washington, D.C.: American Psychiatric Association, 1998): 177218; Adler, , supra note 4.Google Scholar
Ernst, M. and London, E.D., “Brain Imaging Studies of Drug Abuse: Therapeutic Implications,” Seminars in Neuroscience, 9 (1997): 120–30; Grant, S. et al., “Activation of Memory Circuits During Cue-Elicited Cocaine Craving,” Proceedings of the National Academy of Science, 93 (1996): 12040-45; London, E.D. et al., “Morphine-Induced Metabolic Changes in Human Brain. Studies with Positron Emission Tomography and [Fluorine 18]-Fluorodeoxy-glucose,” Archives of General Psychiatry, 47 (1990): 73-81; London, E.D. et al., “Cocaine-Induced Reduction of Glucose Utilization in Human Brain. Studies with Positron Emission Tomography and [Fluorine 18]-Fluorodeoxyglucose,” Archives of General Psychiatry, 47 (1990): 567-74; Volkow, N.D. et al., “Long-Term Frontal Brain Metabolic Changes in Cocaine Abusers,” Synapse, 11 (1992) 184-90; Volkow, N.D. et al., “Cocaine Addiction: Hypotheses Derived from Imaging Studies with PET,” Journal of Addictive Diseases, 15 (1996): 55-71; Volkow, N.D. et al., “Brain Glucose Metabolism in Chronic Marijuana Users at Baseline and During Marijuana Intoxication,” Psychiatry Research and Neuroimaging, 67 (1996): 29-38.CrossRefGoogle Scholar
Grant, et al., source>supra note 8; London, et al., “Cocaine-Induced Reduction of Glucose Utilization in Human Brain. Studies with Positron Emission Tomography and [Fluorine 18]-Fluorodeoxyglucose,” supra note 8.supra+note+8;+London,+et+al.,+“Cocaine-Induced+Reduction+of+Glucose+Utilization+in+Human+Brain.+Studies+with+Positron+Emission+Tomography+and+[Fluorine+18]-Fluorodeoxyglucose,”+supra+note+8.>Google Scholar
London, et al., “Morphine-Induced Metabolic Changes in Human Brain. Studies with Positron Emission Tomography and [Fluorine 18]-Fluorodeoxy-glucose,” supra note 8.Google Scholar
Volkow, et al., “Brain Glucose Metabolism in Chronic Marijuana Users at Baseline and During Marijuana Intoxication,” supra note 8.Google Scholar
Kreek, M.J., “Methadone-Related Opioid Agonist Pharmacotherapy for Heroin Addiction. History, Recent Molecular and Neurochemical Research and Future in Mainstream Medicine,” Annals of the New York Academy of Science, 909 (2000): 186216.CrossRefGoogle Scholar
Ernst, and London, , supra note 8; Volkow, et al., “Long-Term Frontal Brain Metabolic Changes in Cocaine Abusers,” supra note 8.Google Scholar
Cohen, P.J., “Immunization for Prevention and Treatment of Cocaine Abuse: Legal and Ethical Implications,” Drug and Alcohol Dependence, 48 (1997): 167–74.CrossRefGoogle Scholar
Beauchamp, T. and Childress, J.F., Principles of Biomedical Ethics, 4th ed. (New York: Oxford University Press, 1994); National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects in Research, DHEW Pub. No. (OS) 78–0012 (Washington, D.C.: U.S. Gov't Printing Office, 1978).Google Scholar
See, for example, Appelbaum, P.S., “Drug-Free Research in Schizophrenia: An Overview of the Controversy,” IRB: A Review of Human Subjects Research, 18 (1996): 15; Bor, J., “Mental Patients at Risk in Research,” Baltimore Sun, June 7, 1998, at A1; Hilts, P.J., “Agency Faults a U.C.L.A. Study for Suffering of Mental Patients,” New York Times, March 10, 1994, at Al; Hilts, P.J., “House Panel Told of More Tests Done Without Consent,” New York Times, May 24, 1994, at A13; Hilts, P.J., “Psychiatric Researchers Under Fire,” New York Times, May 19, 1998, at F1; Marshall, E., “NIMH to Screen Studies for Science and Human Risk,” Science, 283 (1999): 464-65; Pear, R., “Study Finds Risks to Patients in Drug Trials,” New York Times, May 30, 1998, at A9; Weiss, R., “Research Volunteers Unwittingly at Risk,” Washington Post, August 1, 1998, at Al.CrossRefGoogle Scholar
National Bioethics Advisory Commission, Research Involving Subjects with Mental Disorders That May Affect Decisionmaking Capacity (Rockville, Maryland: National Bioethics Advisory Commission, 1998) [hereinafter cited as NBAC Report]. The NBAC Report, facilitated by input from the bioethical, scientific, and public communities, was submitted to the President on January 8, 1999. On January 16, 2001, U.S. Department of Health and Human Services (DHHS) Secretary Donna, E. Shalala Sent the NBAC the Department's response: HHS Working Group on the NBAC Report, Analysis and Proposed Actions Regarding the NBAC Report: Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity (Washington, D.C.: DHHS Working Group, 2001) [hereinafter cited as DHHS Working Group Report]. The DHHS Working Group consisted of “representatives from all the relevant agencies within the Department, [and] was convened to review and address the specific recommendations of the NBAC Report.” See Secretary Shalala's January 16, 2001 letter to the NBAC Chair, Harold Shapiro. The NBAC's charter expired October 2001, at which time there had been neither a final response to nor implementation of the report.Google Scholar
See NBAC Report, supra note 17, at 9.Google Scholar
Mental status is likely to fluctuate as a result of either internal stimuli (e.g., altered level of craving or occurrence of drug-associated memories) or external stimuli (e.g., verbal, visual, or auditory). The conduct of a proposed study may also affect mental status, e.g., does it involve the subject's drug of choice or is it “neutral” with respect to substance dependence?.Google Scholar
See NBAC Report, supra note 17, at 21.Google Scholar
Id. at 8 (emphasis added).Google Scholar
Id. (emphasis added).Google Scholar
McLellan, A.T. et al., “Psychosocial Services in Substance Abuse Treatment?: A Dose-Ranging Study of Psychosocial Services,” JAMA, 269 (1993): 1953–59.CrossRefGoogle Scholar
See, for example, Kreek, M.J., “Rationale for Maintenance Pharmacotherapy of Opiate Dependence,” Research Publication — Association for Research in Nervous and Mental Diseases, 70 (1992): 205–30.Google Scholar
See NBAC Report, supra note 17, at 8.Google Scholar
Harrison, K. et al., “Medical Eligibility, Comprehension of the Consent Process, and Retention of Injection Drug Users Recruited for an HIV Vaccine Trial,” Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 10 (1995): 386–90.CrossRefGoogle Scholar
Id. at 390.Google Scholar
See NBAC Report, supra note 17, at 23.Google Scholar
High, D.M. et al., “Guidelines for Addressing Ethical and Legal Issues in Alzheimer Disease Research: A Position Paper,” Alzheimer Disease and Associated Disorders, 8 no. 4 (Supp. 1994): 6674. quoted in the NBAC Report, supra note 17, at 23).CrossRefGoogle Scholar
Elliott, C., “Caring About Risks: Are Severely Depressed Patients Competent to Consent to Research?,” Archives of General Psychiatry, 54 (1997): 113–16 (quoted in the NBAC Report, supra note 17, at 23).CrossRefGoogle Scholar
See Diagnostic and Statistical Manual of Mental Disorders, supra note 1.Google Scholar
Sugarman, J., “Toward Achieving Meaningful Informed Consent in AIDS Vaccine Trials with Injection-Drug Users,” AIDS and Public Policy Journal, 9 (1994): 167–72.Google Scholar
Leshner, , supra note 4.Google Scholar
Pope, T.M., “Balancing Public Health Against Individual Liberty: The Ethics of Smoking Regulations,” University of Pittsburgh Law Review, 61 (2000): 419–98 (quotations appear at pages 461 and 466–68).Google Scholar
Elliott, , supra note 31.Google Scholar
Denial is present even when craving is minimal or absent. Therefore, a fundamental biological and ethical issue — denial — must be confronted whether or not craving exists. The foundation of my thesis is that prospective subjects' failure to understand the nature of their disease or admit that they have the disease is prima facie evidence that they lack the information and decision-making competence necessary for making an informed consent to receive their drug of choice in non-therapeutic research. The presence of craving only exacerbates this situation.Google Scholar
I do not use the concept of coercion to imply that clinical investigators, those treating substance abuse, or any other individuals are compelling the addict (with money or any other type of inducement) to participate in clinical research. Rather, I am suggesting that coercion is internal, resulting from the state of addiction itself, such that the associated craving and denial are likely to interfere with the ability to make a rational decision.Google Scholar
Adler, , supra note 4, at 170.Google Scholar
Id. at 170–71.Google Scholar
Id. at 171.Google Scholar
O'Brien, C.P. and McLellan, T., “Myths About the Treatment of Addiction,” in Graham, A.W. and Schultz, T.K., eds., Principles of Addiction Medicine, 2nd ed. (Chevy Chase, Maryland: American Society of Addiction Medicine, 1998): 309–14.Google Scholar
Marwick, C., “Physician Leadership on National Drug Policy Finds Addiction Treatment Works,” JAMA, 279 (1998) 1149–50.Google Scholar
Ernst, and London, , supra note 8; Volkow, et al., “Long-Term Frontal Brain Metabolic Changes in Cocaine Abusers,” supra note 8.Google Scholar
See, for example, Faillace, L.A. et al., “Giving Alcohol to Alcoholics: An Evaluation,” Quarterly Journal of Studies of Alcohol, 33 (1972): 8590; Gorelick, D.A. et al., “Influence of Enforced Abstinence on Cocaine Use by Research Subjects,” Journal of Addictive Diseases, 18 (1999): 115; Kaufman, M.J. et al., “Illicit Cocaine Use Patterns in Intravenous-Naïve Cocaine Users Following Investigational Intravenous Cocaine Administration,” Drug and Alcohol Dependence, 58 (2000): 35-42; Kranzler, H.R., Dolinsky, Z. and Kaplan, R.F., “Giving Ethanol to Alcoholics in a Research Setting: Its Effect on Compliance with Disulfiram Treatment,” British Journal of Addiction, 85 (1990): 119-123; Modell, J.G., Glaser, F.B. and Mountz, J.M., “The Ethics and Safety of Alcohol Administration in the Experimental Setting to Individuals Who Have Chronic, Severe Alcohol Problems,” Alcohol and Alcoholism, 28 (1993): 189-197.CrossRefGoogle Scholar
Kirulis, K. and Zacny, J., “Do Healthy Volunteers Increase Drug Usage After Participation in Research Involving Opioids and Nitrous Oxide?,” Anesthesiology, 89 (1998): A-1222.CrossRefGoogle Scholar
Gorelick, et al., supra note 46.Google Scholar
Kaufman, et al., supra note 46.Google Scholar
Faillace, et al., supra note 46.Google Scholar
Kranzler, , Dolinsky, and Kaplan, , supra note 46.Google Scholar
Leshner, Alan, personal communication with author, October 6, 2001, at Smithsonian Associate Lecture, “Storm Center: The Brain on Drugs.” I have also observed the difference between self-administration and physician-guided administration in evaluating the histories of patients monitored by the Physician Health Committee. That patients with a history of addiction can safely receive addicting drugs under medical supervision is generally accepted by treating physicians.Google Scholar
See note 46, supra.Google Scholar
National Institute on Drug Abuse, Intramural Research Program, Policies and Procedures, Recruitment of IRP Research Participants, I(A)(4)(a) (internal memorandum) (Baltimore, 2000) (“Participants who were enrolled in a treatment program or treatment study in the preceding 90 days or seeking … treatment are excluded from all non-therapeutic research studies.”).Google Scholar
National Advisory Council on Alcohol Abuse and Alcoholism, Recommended Council Guidelines on Ethyl Alcohol Administration in Human Experimentation (Rockville, Maryland: National Institute on Alcohol Abuse and Alcoholism, 1989).Google Scholar
Adler, , supra note 4, at 172.Google Scholar
Capron, A.M., “Ethical and Human Rights Issues in Research on Mental Disorders That May Affect Decision-Making Capacity,” N. Engl. J. Med., 340 (1999): 1430–34.CrossRefGoogle Scholar