Proceedings of the Association of American Physicians最新文献

This article reviews four decades of my professional experience with marijuana, including: 1) my treatment of marijuana-dependent patients, particularly adolescents; 2) my research on the general effects and medical uses of the government-grown marijuana and of oral tetrahydrocannabinol (Marinol); and 3) my social policy experiences, both nationally and internationally, as a member of the National Commission on Marijuana Drug Abuse. The article emphasizes the mythology, morality, and misunderstanding that clouds so much of the thinking about marijuana in general and its medical utility in particular.

The case for marijuana's medical use is primarily from anecdotal clinical reports, human studies of delta-9-tetrahydrocannabinol, and animal studies on constituent compounds. The authors believe that while a key policy issue is to keep marijuana out of the hands of children, its use for medicinal purposes should be resolved by scientific research and Food and Drug Administration (FDA) review. Weighed against possible benefits are increased risks such as cancer, pulmonary problems, damage to the immune system, and unacceptable psychological effects. More study is needed to determine the efficacy of marijuana as an antiemetic for cancer patients, as an appetite stimulant for AIDS and cancer patients, as a treatment for neuropathic pain, and as an antispasmodic for multiple sclerosis patients. If this new research shows marijuana to have important medical uses, FDA approval could be sought. However, the better response is accelerated development of delivery systems other than smoking for key ingredients, as well as the identification of targeted molecules that deliver beneficial effects without intoxicating effects. If the National Institutes of Health conducts research on marijuana, we would propose parallel trials on those indications under careful controls making marijuana available to appropriate patients who fail to benefit from standard existing treatments. This effort would begin after efficacy trials and sunset no later than 5 years. If this open-trial mechanism is adopted, the compassion that Americans feel for seriously ill individuals would have an appropriate medical/scientific outlet and not need to rely on referenda that can confuse adolescents by disseminating misleading information about marijuana effects.

Substance abuse causes illness and disease, results in high use of medical and other services and high productivity losses, and imposes a multibillion-dollar burden on the economy each year. This article presents estimates of the economic burden of alcohol and drug abuse and smoking in 1995. Included are the direct medical care expenditures and indirect costs and the value of lost productivity for people who are ill and disabled and for people who die prematurely due to substance abuse. The methodology for the cost of alcohol and drug abuse is based on a study conducted by the Lewin Group in 1998 and prepared for the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. The smoking-attributable costs are based on a published study conducted by the author and her colleagues at University of California-Berkeley and at University of California-San Francisco for 1993 and updated to 1995. The total economic costs of substance abuse are estimated at $428.1 billion in 1995: alcohol abuse at $175.9 billion, drug abuse at $114.2 billion, and smoking at $138 billion. The distribution by type of cost varies among the three types of disorders, reflecting differences in the prevalence of these disorders, medical care use, morbidity and mortality patterns, and other related costs for each disorder. Effective interventions must be found to prevent and ameliorate the adverse health consequences of substance abuse, thereby reducing the future high costs of alcohol and drug abuse and smoking.

Moderate alcohol consumption (1-2 drinks a day) can be beneficial in reducing the risk of coronary artery disease. This article focuses on cellular and molecular mechanisms underlying the beneficial effect of moderate drinking, including increased plasma high-density lipoprotein levels, changes in cellular signaling, reduction in platelet function, stimulation of fibrinolysis, and reduction in ischemia-reperfusion injury. While moderate drinking may be protective against coronary artery disease for some individuals, populations such as pregnant women and individuals who are about to operate motor vehicles or heavy machinery should not drink alcoholic beverages. People with family histories of alcoholism should exercise extreme caution in their decision to drink.

Drug abuse treatment is a major method for reducing the health and social problems associated with dependence on psychoactive drugs. Drug dependence is very well established in the United States, where cyclical rises and falls in the use of different drugs often occur. Heroin and cocaine use are spreading rapidly throughout the world as a whole, particularly in developing countries. The need for effective treatments for drug dependence is likely to increase in the foreseeable future. Currently three major forms of long-term drug abuse treatment exist: methadone maintenance, in which an agonist medication is used to normalize physiological functioning; residential therapeutic communities, which are based on "resocializing" the drug user; and outpatient drug-free programs, which utilize a wide variety of counseling and psychotherapy approaches. Multiple large treatment outcome studies have been conducted among persons receiving treatment for drug dependence and have shown consistent effects in reducing the use of psychoactive drugs, though complete elimination of drug use is an infrequent outcome. Length of time in drug treatment is the best single predictor of positive post-treatment outcomes. HIV infection has become an extremely important adverse consequence associated with the injection of psychoactive drugs. Multiple studies have shown that drug abuse treatment is an effective method for preventing HIV infection among injecting drug users.

Addiction to tobacco, alcohol, and other drugs inflicts a substantial toll on Americans, measurable in terms of deaths and illnesses, social costs, and economic costs. With approximately 60 million smokers, 14 million dependent on alcohol, and 14 million users of illicit drugs, more than one fourth of Americans over age 15 has a physiological dependence on at least one addictive substance. As a result, nearly 590,000 deaths--about a quarter of all deaths in the United States--are caused by addictive substances: 105,000 from alcohol abuse, 446,000 from tobacco use, and 39,000 from addictive drugs in 1995. The magnitude of addiction's impact on morbidity is also great, causing approximately 40 million illnesses and injuries each year. The economic burden of addiction is estimated at greater than $400 billion every year, including health care costs, lost worker productivity, and crime. Less quantifiable, but equally important, are the social costs to families and communities of addiction. Children of substance-abusing parents are more likely as adults to become plagued by addiction and its related problems. Passive exposure to tobacco smoke affects nonsmokers; drug and alcohol abuse are risk factors for crime and incarceration, family violence, fatal and permanently disabling accidents, birth defects, and divorce. Combined, the effects of tobacco, alcohol, and drugs inflict a greater toll on the health and well-being of Americans than any other single preventable factor.

New insights into our understanding of drug abuse and addiction have revealed that the desire to use drugs and the process of addiction depend on effects on brain function. Drugs of abuse have been hypothesized to produce their rewarding effects by neuropharmacological actions on a common brain reward circuit called the extended amygdala. The extended amygdala involves the mesolimbic dopamine system and specific subregions of the basal forebrain, such as the shell of the nucleus accumbens, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala. The psychomotor stimulants cocaine and amphetamine activate the mesolimbic dopamine system; opiates activate opioid peptide receptors within and independent of the mesolimbic dopamine system. Sedative hypnotics alter multiple neurotransmitter systems in this circuitry, including: 1) gamma aminobutyric acid; 2) dopamine; 3) serotonin; 4) glutamate; and 5) opioid peptides. Nicotine and tetrahydrocannabinol both activate mesolimbic dopamine function and possibly opioid peptide systems in this circuitry. Repeated and prolonged drug abuse leads to compulsive use, and the mechanism for this transition involves, at the behavioral level, a progressive dysregulation of brain reward circuitry and a recruitment of brain stress systems such as corticotropin-releasing factor. The molecular mechanisms of signal transduction in these systems are a likely target for residual changes in that they convey allostatic changes in reward set point, which lead to vulnerability to relapse.

The opium poppy and the coca leaf offer useful perspectives on the current controversies over medical marijuana. In both cases, purified synthetic analogues of biologically active components of ancient folk remedies have become medical mainstays without undermining efforts to reduce nonmedical drug use. A decade ago, a campaign strove to legalize heroin for the compassionate treatment of pain in terminally ill patients. Like the current campaign to legalize medical marijuana, many well-meaning people supported this effort. The campaign for medical heroin was stopped by science when double-blind studies showed that heroin offered no benefits over the standard opioid analgesics in the treatment of severe cancer pain. Scientific medicine requires purified chemicals in carefully controlled doses without contaminating toxic substances. That a doctor would one day write a prescription for leaves to be burned is unimaginable. The Controlled Substances Act and international treaties limit the use of abused drugs or medicines. In contrast to smoked marijuana, specific chemicals in marijuana or, more likely, synthetic analogues, may prove to be of benefit to some patients with specific illnesses. Most opponents of medical use of smoked marijuana are not hostile to the medical use of purified synthetic analogues or even synthetic tetrahydrocannabinol (THC), which has been available in the United States for prescription by any licensed doctor since 1985. In contrast, most supporters of smoked marijuana are hostile to the use of purified chemicals from marijuana, insisting that only smoked marijuana leaves be used as "medicine," revealing clearly that their motivation is not scientific medicine but the back door legalization of marijuana.