Notices - 2001
Medical Uses for Marijuana
FDA has not approved a new drug application for marijuana, although there are several INDs currently active. There is suggestive evidence that
marijuana may have beneficial therapeutic effects in relieving spasticity associated with multiple sclerosis, as an analgesic, as an antiemetic, as an appetite stimulant and as a bronchodilator, but there is no data from controlled clinical trials to support a new drug application for any of these indications. Data of the risks and potential benefits of using marijuana for these various indications must be developed to determine whether botanical marijuana, or any cannabinoid in particular, has a therapeutic role.
In February 1997, a NIH-sponsored workshop analyzed available scientific information and concluded that "in order to evaluate various hypotheses concerning the potential utility of marijuana in various therapeutic areas, more and better studies would be needed" (NIH, 1997). In addition, in March 1999, the Institute of Medicine (IOM) issued a detailed report that supports the absolute need for evidence-based research into the effects of marijuana and cannabinoid components of marijuana, for patients with specific disease conditions. The IOM report also emphasized that smoked marijuana is a crude drug delivery system that exposes patients to a significant number of harmful substances and that "if there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and
their synthetic derivatives." As such, the IOM recommended that clinical trials should be conducted with the goal of developing safe delivery systems (Institute of Medicine, 1999). Additionally, State-level public initiatives, including referenda in support of the medical use of marijuana have generated interest in the medical community for high quality clinical investigation and comprehensive safety and effectiveness data.
The Department of Health and Human Services (DHHS) is committed to providing "research-grade marijuana for studies that are the most likely to yield usable, essential data" (DHHS, 1999). The opportunity for scientists to conduct clinical research with botanical marijuana has increased due to changes in the process for obtaining botanical marijuana from the National Institute on Drug Abuse, the only legal source of the drug for research. Studies published in the current medical literature demonstrate that clinical research with marijuana is being conducted in the US under FDA-authorized Investigational New Drug applications. In May 1999, DHHS provided guidance on the procedures for providing research-grade marijuana to scientists who intend to study marijuana in scientifically valid investigations and well-controlled clinical trials (DHHS, 1999). This action was prompted by the increasing interest in determining through scientifically valid investigations whether cannabinoids have medical use.
4. Its History and Current Pattern of Abuse
To assess drug abuse patterns and trends, data from different sources such as National Household Survey on Drug Abuse (NHSDA), Monitoring the Future (MTF), Drug Abuse Warning Network (DAWN), and Treatment Episode Data Set (TEDS) have been analyzed. These indicators of marijuana use in the United States are described below:
National Household Survey on Drug Abuse
The National Household Survey on Drug Abuse (NHSDA, 1999) is conducted by the Department of Health and Human Service's Substance Abuse and Mental Health Services Administration (SAMHSA) annually. This survey has been the primary source of estimates of the prevalence and incidence of alcohol, tobacco and illicit drug use in the US. It is important to note that this survey identifies whether an individual used a drug during a certain period, but not the amount of the drug used on each occasion. The survey is based on a nationally representative sample of the civilian, non-institutionalized population 12 years of age and older. Persons excluded from the survey include homeless people who do not use shelters, active military personnel, and residents of institutional group quarters, such as jails and hospitals. In 1999, 66,706 individuals were interviewed.
According to the 1999 NHSDA, illicit drug use involved approximately 14.8 million Americans (6.7% of the US population) on a monthly basis. The most frequently used illicit drug was marijuana, with 11.2 million Americans (5.1% of the US population) using it monthly. The 1999 NHSDA no longer provides data on the weekly or daily use of any drug, so these statistics are unavailable for marijuana. The NHSDA estimated that 76.4 million Americans (34.6% of the population) have tried marijuana at least once during their lifetime. Thus, 14.7% of those who try marijuana go on to use it monthly. NHSDA data from
1999 show that 57% of illicit drug users only use marijuana on a monthly basis, which corresponds to 8.44 million persons (3.8% of the US population). However, there are no data available on marijuana-only use as a percent of use of any drug.
An estimated 2.3 million persons of all ages used marijuana for the first time in 1998, of whom 1.6 million were between the ages of 12-17. (Information on when people first used a substance is collected on a retrospective basis, so this information is always one year behind information on current use.) This represents a slight reduction in new marijuana users from 1997, when the rate was 2.6 million people of all ages and 1.8 million for those 12-17 years old. Trends for marijuana use were similar to the trends for any illicit use. There were no significant changes between 1998 and 1999 for any of the four age groups, but an increasing trend since 1997 among young adults age 18-25 years (12.8 % in 1997, 13.8 % in 1998, and 16.4 % in 1999) and a decreasing trend since 1997 for youths age 12-17 years (9.4 % in 1997, 8.3 % in 1998, and 7.0 % in 1999).
Monitoring the Future
Monitoring the Future (MTF, 1999) is a national survey that tracks drug use trends among American adolescents. The MTF has surveyed 8th, 10th and 12th graders every spring in randomly selected U.S. schools since 1975 for 12th graders and since 1991 for 8th and 10th graders. This survey is conducted by the Institute for Social Research at the University of Michigan under a grant from NIDA. The 1999 sample sizes were 17,300, 13,900, and 14,100 in 8th, 10th, and 12th grades, respectively. In all, about 45,000 students in 433 schools participated. Because multiple questionnaire forms are administered at each grade level, and because not all questions are contained in all forms, the numbers of cases upon which a particular statistic are based can be less than the total sample.
Comparisons between the MTF and students sampled in the NHSDA (described above) have generally shown NHSDA prevalence to be lower than MFT estimates, in which the largest difference occurred with 8th graders. The MTF survey showed the use of illegal drugs by adolescents leveled off in 1997 and then declined somewhat for most drugs in 1998. Also, the 1998-year survey showed that for the first time since 1991 an increase in the percentage of 8th graders who said marijuana is a risk to their health.
Illicit drug use among teens remained steady in 1999 in all three grades, as did the use of a number of important specific drugs such as marijuana, amphetamines, hallucinogens taken as a class, tranquilizers, heroin, and alcohol. Marijuana is the most widely used illicit drug. For 1999, the annual prevalence rates in grades 8, 10, and 12,
respectively, are 17%, 32%, and 38%. Current monthly prevalence rates are 9.7%, 19.4% and 23.1%. (See Table 1), whereas current daily prevalence rates (defined as the proportion using it on 20 or more occasions in the prior thirty days) are 1.4%, 3.8%, and 6.0%.
Table 1.--Trends in Annual and Monthly Prevalence of Use of Various Drugs for Eighth, Tenth, and Twelfth Graders
[Entries are precentages]
|Any illicit drug (a)|
|hAny illicit drug other than cannabis (a)h|
Source. The Monitoring the Future Study, the University of Michigan.
- For 12th graders only: Use of "any illicit drug" includes any use of marijuana, LSD, other hallucinogens, crack, other cocaine, or heroin, or any use of other opiates, stimulants, barbiturates, or tranquilizers not under a doctor's orders. For 8th and 10th graders: The use of other opiates and barbiturates has been excluded, because these younger respondents appear to over-report use (perhaps because they include the use of nonprescription drugs in their answers).
- In 1995, the heroin question was changed in three of six forms for 12th graders and in two forms for 8th and 10th graders. Separate questions were asked for use with injection and without injection. Data presented here represents the combined data from all forms. In 1996, the heroin question was changed in the remaining 8th and 10th grade forms.
Drug Abuse Warning Network (DAWN)
The Drug Abuse Warning Network (DAWN, 1998) is a national probability survey of hospitals with emergency departments (EDs) designed to obtain information on ED episodes that are induced by or related to the use of an illegal drug or the non-medical use of a legal drug. The DAWN system provides information on the health consequences of drug use in the United States as manifested by drug-related visits to emergency departments (ED episodes). DAWN captures the non-medical use of a substance either for psychological effects, dependence, or suicide attempt. The ED data come from a representative sample of hospital emergency department's which are weighted to produce national estimates. As stated in DAWN methodology, "the terms 'ED drug abuse episode' or 'ED episode' refer to any ED visit that was induced by or related to drug abuse. Similarly, the terms 'ED drug mention' or 'ED mention' refer to a substance that was mentioned in a drug abuse episode. Up to 4 substances can be reported for each ED episode. Thus, the number of ED mentions will always equal or exceed the number of ED episodes."
Many factors can influence the estimates of ED visits, including trends in the ED usage in general. Some drug users may have visited EDs for a variety of reasons, some of which may have been life threatening, whereas others may have sought care at the ED for detoxification because they needed certification before entering treatment. It is important to note that the variable "Motive" applies to the entire episode and since more than one drug can be mentioned per episode, it may not apply to the specific drug for which the tables have been created. DAWN data do not distinguish the drug responsible for the ED visit from others used concomitantly. The DAWN report itself states, "Since marijuana/hashish is frequently present in combination with other drugs, the reason for the ED contact may be more relevant to the other drug(s) involved in the episode."
In 1999, there were an estimated 554,932 drug-related ED episodes and 1,015,206 ED drug mentions from these drug-related episodes. Nationally, the number of ED episodes and mentions remained relatively stable from 1998 to 1999. The 4 drugs mentioned most frequently in ED reports--alcohol-in-combination (196,277 mentions), cocaine (168,763), marijuana/hashish (87,150), and heroin/morphine (84,409)--were statistically unchanged from 1998 to 1999. Marijuana/hashish mentions represented 16% of all drug-related episodes in 1999. For adolescent patients age 12-17, there was no statistical change from 1998 to 1999 in drug use for any drug category (Table 2). There was no a statistically significant change in the number of marijuana/hashish mentions, heroin/morphine of cocaine from 1998 to 1999.
Table 2.--Estimated Number of Emergency Department Drug Episodes, Drug Mentions and Mentions for Selected Drugs for Total Coterminous US by year for 1997-1999
Source: Office of applied studies, SAMHSA, Drug Abuse Warning Network, 1999 (03/2000 update). Note: These estimates are based on a representative sample of non-federal, short-stay hospitals with 24-hour emergency departments in the U.S.
There were no statistically significant increases in marijuana/hashish mentions on the basis of age, gender, or race/ethnicity subgroups between 1998 and 1999, although a 19% increase in marijuana/hashish mentions (from 22,907 to 27,272) among young adults age 18 to 25 was observed.
Approximately 15 percent of the emergency department marijuana/hashish mentions involved patients in the 6-17 years of age, whereasthis age group only accounts for less than 1 percent of the emergencydepartment heroin/morphine and approximately 2 percent of the cocaineemergency department mentions. Most of the emergency department heroin/morphine and cocaine mentions involved subjects in the 26-44 years of age range.
Marijuana/hashish is likely to be mentioned in combination with other substances, particularly with alcohol and cocaine. Marijuana use as a single drug accounted for approximately 22% of the marijuana episodes. Single use of cocaine and heroin accounted for 29% and 47% of the cocaine and heroine episodes respectively.
The petitioner asserts that "common household painkillers" and benzodiazepines produce more ED visits than marijuana and that marijuana users are no more likely to be seen in EDs
than other chronic drug users. DAWN data do not confirm the petitioner's assertions. For 1999, the estimated rate of mentions of selected drugs per 100,000 population is 69.4 for cocaine, 35.8 for marijuana/hashish, 34.7 for heroin/morphine, 17.5 for alprazolam/diazepam/lorazepam, and 16.9 for aspirin/acetaminophen. The estimated rate of mentions of marijuana/hashish per 100,000 population is similar to that of heroin/morphine, but approximately twice that of aspirin/acetaminophen and that of alprazolam/diazepam/ lorazepam. However,marijuana estimated rate of mentions/100,000 population is approximately half that of cocaine.
These drugs are easily distinguished by the motivation for their use. In 1999, marijuana/hashish mentions were related to episodes in which the motive for drug intake was primarily dependence (34.2%) followed by recreational use (28%), suicide (11.5%) and other psychic effects (8.1%). DAWN defines "psychic effects" as a conscious action to use a drug to improve or enhance any physical, emotional, or social situation or condition. The use of a drug for experimentation or to enhance a social situation, as well as the use of drugs to enhance or improve any mental, emotional, or physical state, is reported to DAWN under this category. Examples of the latter include anxiety, stay awake, help to study, weight control, reduce pain and to induce sleep. A different pattern is observed for tranquilizers (alprazolam/diazepam/lorazepam) and aspirin/acetamipnophen. Alprazolam/diazepam/lorazepam mentions were primarily related to episodes where the motive for drug intake was primarily suicide (approximately 58%), followed by dependence (approximately 17%), other psychic effects (approximately 11%), and recreational use (approximately 5%). For the use of aspirin/acetaminophen the primary motive of the episode was suicide (80%), other psychic effects (9%) and recreational use (2%).
DAWN also collects information on drug-related deaths from selected medical examiner offices from more than 40 metropolitan areas. In 1997 and 1998, there were 678 and 595 marijuana-related death mentions, representing 7.1 and 5.9 percent of the total drug abuse deaths for each year respectively. Medical examiner data also showed that in the majority of the mentions, marijuana was used concomitantly with cocaine, heroin and alcohol.
Treatment Episode Data Set
The Treatment Episode Data Set (TEDS, 1998) system is part of SAMHSA's Drug and Alcohol Services Information System (Office of Applied Science, SAMHSA). TEDS comprises data on treatment admissions that are routinely collected by States in monitoring their substance abuse treatment systems. The TEDS report provides information on the demographic and substance use characteristics of the 1.5 million annual admissions to treatment for abuse of alcohol and drugs in facilities that report to individual State administrative data systems. It is important to note that TEDS is an admission-based system, and TEDS admissions do not represent individuals, because a given individual admitted to treatment twice within a given year would be counted as two admissions. TEDS includes facilities that are licensed or certified by the State substance abuse agency to provide substance abuse treatment and that are required by the States to provide TEDS client-level data. Facilities that report TEDS data are those that receive State alcohol and/or drug agency funds for the provision of alcohol and/or drug treatment services. The primary goal for TEDS is to monitor the characteristics of treatment episodes for substance abusers.
Primary marijuana abuse accounted for 13% of TEDS admissions in 1998, the latest year for which data are available. In general, most of the individuals admitted for marijuana were white young males. Marijuana use began at an early age among primary marijuana admissions and more than half of the admitted patients had first used marijuana by the age of 14 and 92% by the age of 18. More than half of marijuana treatment admissions were referred through the criminal justice system.
Approximately one-third of those who were admitted for primary marijuana abuse use the drug daily. Between 1992 and 1998, the proportion of admissions for primary marijuana use increased from 6% to 13%, whereas the proportion of admissions for primary cocaine use declined from 18% in 1992 to 15% in 1998. The proportion of opiate admissions increased from 12% in 1992 to 15% in 1998 and alcohol accounted for about half (47%) of all TEDS admissions in 1998. Marijuana has not been associated with other drugs in 30.8% of the primary marijuana admissions that corresponds to 4.1% of all admissions. Secondary use of alcohol was reported by 38.2% of the marijuana admissions and secondary cocaine use was reported by 4% of admissions for primary marijuana abuse. The combination marijuana/alcohol/cocaine accounts for 8.5% of marijuana primary admissions and 1.1% of all admissions.
The TEDS Report concludes that, "Overall, TEDS admissions data confirm that those admitted to substance abuse treatment have problems beyond their dependence on drugs and alcohol, being disadvantaged in education and employment when compared to the general population after adjusting for age, gender, and race/ethnicity distribution differences between the general population and the TEDS. It is not possible to conclude cause and effect from TEDS data--whether substance abuse precedes or follows the appearance of other life problems--but the association between problems seems clear."
NIDA's Community Epidemiology Work Group (CEWG, 1999)
The CEWG is a network composed of epidemiologic and ethnographic researchers from major metropolitan areas of the United States and selected countries from abroad that meets semiannually to discuss the current epidemiology of drug abuse. Large-scale databases used in analyses include TEDS; DAWN; the Arrestee Drug Abuse Monitoring (ADAM) program funded by the National Institute of Justice; information on drug seizures, price, and purity from the Drug Enforcement Administration; Uniform Crime Reports maintained by the Federal Bureau of Investigation and Poison Control Centers. These data are enhanced with qualitative information obtained from ethnographic research, focus groups, and other community-based sources. Although data from TEDS and DAWN have been previously discussed this document, the analysis offered by the CEWG gives a more descriptive overview of individual geographical areas. In 1999, marijuana indicators were stable in 17 of the 21 CEWG areas. Indicators were mixed in two areas (Atlanta and Baltimore) and increased in two (Los Angeles and St. Louis). Despite the stability of certain indicators, marijuana abuse remains a serious problem in CEWG areas. In Atlanta, marijuana is the second most prevalent drug on the market and is increasingly used by a wide variety of people mostly white males and young adolescents. In St. Louis, marijuana indicators are increasing and DAWN marijuana ED mentions rose 33.3% from the last half of 1998 to the first half of 1999. Treatment admissions rose 40.1% from the second half of 1998 to the first
half of 1999, and another 9.6% in the second half of 1999.
In recent years, the proportion of primary marijuana abusers entering drug abuse treatment programs has been increasing in many CEWG cities. For example, between 1998 and the first semester of 1999, drug treatment admissions for primary marijuana abuse increased from 15.2% to 20.3% in Atlanta. In the first half of 1999, primary marijuana abusers represented 18.8% of drug treatment admissions in New York City compared with 16.6% in the first half of 1998. In the first half of 1999, primary marijuana abuse represented 41.2% of all drug treatment admissions in Denver and totaled 3,179. The number of primary marijuana admissions in St. Louis increased dramatically in the first half of 1999, representing 40.8% of treatment admissions.
The CEWG reports an increase in problems associated with marijuana that they attribute to the drug's greater availability/potency, its relative low cost, and a public attitude that use of marijuana is less risky than use of other drugs.
5. The Scope, Duration, and Significance of Abuse
According to the National Household Survey on Drug Abuse and the Monitoring the Future study, marijuana remains the most extensively used illegal drug in the US, with 34.6% of individuals over age 12 (76.4 million) and 49.7% of 12th graders having tried it at least once in their lifetime. While the majority of individuals (85.3%) who have tried marijuana do not use the drug monthly, 11.2 million individuals (14.7%) report that they used marijuana within the past 30 days. An examination of use among various age cohorts demonstrates that monthly use occurs primarily among college age individuals, with use dropping off sharply after age 25.
The Drug Abuse Warning Network data show that among 18-25 year olds, there was a 19% increase in 1999 for marijuana emergency department mentions. The fact that this age cohort had the greatest degree of acute adverse reactions to marijuana might be expected given that this group has the largest prevalence of marijuana use. Marijuana was commonly associated with alcohol and cocaine.
According to 1999 DAWN data, there were 187 deaths mentions where marijuana was the only drug reported, out of the total 664 medical examiners episodes involving marijuana in 1999. In the majority of the medical examiners episodes marijuana was associated with alcohol, cocaine, and morphine.
Data from the Treatment Episode Data Set confirm that 69% of admissions to drug treatment programs for primary marijuana abuse also had concurrent use of alcohol and other drugs. The TEDS report also emphasizes that individuals who are admitted for drug treatment have multiple disadvantages in education and employment compared to the general population. Individuals most likely to develop dependence on marijuana have a higher rate of associated psychiatric disorders or are socializing with a delinquent crowd.
6. What, if Any, Risk There is to the Public Health
The risk to the public health as measured by quantifiers such as emergency room episodes, marijuana-related deaths, and drug treatment admissions is discussed in full in sections 1, 4, and 5 above. Accordingly, this section focuses on the health risks to the individual user. All drugs, both medicinal and illicit, have a broad range of effects on the individual user that are dependent on dose and duration of usage. It is not uncommon for a FDA approved drug product to produce adverse effects even at doses in the therapeutic range. Such adverse responses are known as "side effects". When determining whether a drug product is safe and effective for any indication, FDA performs a thorough risk-benefit analysis to determine whether the risks posed by the drug product's potential or actual side effects are outweighed by the drug product's potential benefits. As marijuana is not approved for any use, any potential benefits attributed to marijuana use have not been found to be outweighed by the risks. However, cannabinoids have a remarkably low acute lethal toxicity despite potent psychoactivity and pharmacologic actions on multiple organ systems.
The consequences of marijuana use and abuse are discussed below in terms of the risk from acute and chronic use of the drug to the individual user (IOM, 1999) (see also the discussion of the central nervous system effects, cognitive effects, cardiovascular and autonomic effects, respiratory effects, and the effect on the immune system in Section 2):
Risks from acute use of marijuana:
Acute use of marijuana causes an impairment of psychomotor performance, including performance of complex tasks, which makes it inadvisable to operate motor vehicles or heavy equipment after using marijuana. People who have or are at risk of developing psychiatric disorders may be the most vulnerable to developing dependence on marijuana. Dysphoria is a potential response in a minority of individuals who use marijuana.
Risks from chronic use of marijuana:
Marijuana smoke is considered to be comparable to tobacco smoke in respect to increased risk of cancer, lung damage, and poor pregnancy outcome. An additional concern includes the potential for dependence on marijuana, which has been assessed to be rare among the general population but more common among adolescents with conduct disorder and individuals with psychiatric disorders. Although a distinctive marijuana withdrawal syndrome has been identified, it is mild and short-lived.
The Diagnostic and Statistical Manual (DSM-IV-SR, 2000) of American Psychiatric Association states that the consequences of cannabis abuse are as follows:
[P]eriodic cannabis use and intoxication can interfere with performance at work or school and may be physically hazardous in situations such as driving a car. Legal problems may occur as a consequence of arrests for cannabis possession. There may be arguments with spouses or parents over the possession of cannabis in the home or its use in the presence of children. When psychological or physical problems are associated with cannabis in the context of compulsive use, a diagnosis of Cannabis Dependence, rather than Cannabis Abuse, should be considered.
Individuals with Cannabis Dependence have compulsive use and associated problems. Tolerance to most of the effects of cannabis has been reported in individuals who use cannabis chronically. There have also been some reports of withdrawal symptoms, but their clinical significance is uncertain. There is some evidence that a majority of chronic users of cannabinoids report histories of tolerance or withdrawal and that these individuals evidence more severe drug-related problems overall. Individuals with Cannabis Dependence may use very potent cannabis throughout the day over a period of months or years, and they may spend several hours a day acquiring and using the substance. This often interferes with family, school, work, or recreational activities. Individuals with Cannabis Dependence may also persist in their use despite knowledge of physical problems (e.g., chronic cough related to smoking) or psychological problems (e.g., excessive sedation and a decrease in goal-oriented activities resulting from repeated use of high doses).
7. Its Psychic or Physiologic Dependence Liability
Tolerance can develop to marijuana-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes (Jones et al., 1981). Down-regulation of cannabinoid receptors has been suggested as the mechanism underlying tolerance to the effects of marijuana (Rodriguez de Fonseca et al., 1994). Pharmacological tolerance does not indicate the physical dependence liability of a drug.
In order for physical dependence to exist, there must be evidence for a withdrawal syndrome. Although pronounced withdrawal symptoms can be provoked from the administration of a cannabinoid antagonist in animals who had received chronic THC administration, there is no overt withdrawal syndrome behaviorally in animals under conditions of natural discontinuation following chronic THC administration. The marijuana withdrawal syndrome is distinct but mild compared to the withdrawal syndromes associated with alcohol and heroin use, consisting of symptoms such as restlessness, mild agitation, insomnia, nausea and cramping that resolve after 4 days (Budney et al., 1999; Haney et al., 1999). These symptoms are comparable to the decreased vigor, increased fatigue, sleepiness, headache, and reduced ability to work seen with caffeine withdrawal (Lane et al., 1998). However, marijuana withdrawal syndrome has only been reported in adolescents who were inpatients for substance abuse treatment or in individuals who had been given marijuana on a daily basis during research conditions. Physical dependence on marijuana is a rare phenomenon compared to other psychoactive drugs and if it develops, it is milder when marijuana is the only drug instead of being used in combination with other drugs.
TEDS data for 1998 show that 37.9% of admissions for treatment for primary marijuana use met DSM IV criteria for cannabis dependence, whereas 27.7% met DSM IV criteria for cannabis abuse. Taken in the context of the total number of admissions, a DSM IV diagnosis for cannabis dependence represented 6.6%, and a diagnosis for cannabis abuse represented 4.9%, of all subjects admitted to treatment. In contrast, opioid and cocaine dependence was the DSM diagnosis of 12.2% and 12.6% of all admissions, respectively. (See Section 6 regarding marijuana abuse and dependence).
According to the NHSDA, data discussed above in Section 1, 6.8 million Americans used marijuana weekly in 1998. In addition, the DAWN data discussed in Section 4 indicates that 34.2% of the 87,150 ED marijuana mentions in 1999 were related to episodes in which the motive for drug intake was primarily dependence. It should be emphasized that the patient-reported "motive" for the drug intake applies to the entire episode and since more than one drug can be mentioned per episode, it may not apply to one specific drug. DAWN data do not distinguish the drug responsible for the ED visit from others used concomitantly. Finally, the CEWG data discussed in Section 4 above reports an increase in the proportion of primary marijuana users entering drug abuse treatment programs. Thus, there is evidence among a certain proportion of marijuana users for a true psychological dependence syndrome.
8. Whether the Substance is an Immediate Precursor of a Substance Already Controlled Under This Article
Marijuana is not an immediate precursor of another controlled substance.
C. Findings and Recommendation
After considering the scientific and medical evidence presented under the eight factors above, FDA finds that marijuana meets the three criteria for placing a substance in Schedule I of the CSA under 21 U.S.C. 812(b)(1). Specifically:
1. Marijuana Has a High Potential for Abuse
11.2 million Americans used marijuana monthly in 1999 and 1998 data indicate that 6.8 million Americans used marijuana weekly. A 1999 study indicates that by 12th grade, 37.8% of students report having used marijuana in the past year, and 23.1 % report using it monthly. In 1999, 87,150 emergency department episodes were induced by or related to the use of marijuana/hashish, representing 16% of all drug-related episodes. The primary motive for drug intake in 34.2 % of those episodes was reported to be dependence. DAWN data from that same year show that out of 664 medical examiner episodes involving marijuana, marijuana was the only drug reported in 187 deaths. In recent years, the proportion of primary marijuana abusers entering drug abuse treatment programs has been increasing in major U.S. cities, ranging from 19% in New York City to 41% in St. Louis and Denver.
Data show that humans prefer higher doses of marijuana to lower doses, demonstrating that marijuana has dose-dependent reinforcing effects. Marijuana has relatively low levels of toxicity and physical dependence as compared to other illicit drugs. However, as discussed above, physical dependence and toxicity are not the only factors to consider in determining a substance's abuse potential. The large number of individuals using marijuana on a regular basis and the vast amount of marijuana that is available for illicit use are indicative of widespread use. In addition, there is evidence that marijuana use can
result in psychological dependence in a certain proportion of the population.
2. Marijuana Has No Currently Accepted Medical Use in Treatment in the United States
The FDA has not approved a new drug application for marijuana. The opportunity for scientists to conduct clinical research with marijuana has increased recently due to the implementation of DHHS policy supporting clinical research with botanical marijuana. While there are INDs for marijuana active at the FDA, marijuana does not have a currently accepted medical use for treatment in the United States nor does it have an accepted medical use with severe restrictions.
A drug has a "currently accepted medical use" if all of the following five elements have been satisfied:
- The drug's chemistry is known and reproducible;
- There are adequate safety studies;
- There are adequate and well-controlled studies proving efficacy;
- The drug is accepted by qualified experts; and
- The scientific evidence is widely available.
Alliance for Cannabis Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).
Although the chemistry of many cannabinoids found in marijuana have been characterized, a complete scientific analysis of all the chemical components found in marijuana has not been conducted. Safety studies for acute or subchronic administration of marijuana have been carried out through a limited number of Phase 1 clinical investigations approved by the FDA, but there have been no studies that have scientifically assessed the efficacy of marijuana for any medical condition. A material conflict of opinion among experts precludes a finding that marijuana has been accepted by qualified experts. At this time, it is clear
that there is not a consensus of medical opinion concerning medical applications of marijuana.
Alternately, a drug can be considered to have "a currently accepted medical use with severe restrictions" (21 U.S.C. 812(b)(2)(B)). Although some evidence exists that some form of marijuana may prove to be effective in treating a number of conditions, research on the medical use of marijuana has not progressed to the point that marijuana can be considered to have a "currently accepted medical use with severe restrictions."
3. There Is a Lack of Accepted Safety for Use of Marijuana Under Medical Supervision
There are no FDA-approved marijuana products. Marijuana does not have a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. As discussed earlier, the known risks of marijuana use are not outweighed by any potential benefits. In addition, the agency cannot conclude that marijuana has an acceptable level of safety without assurance of a consistent and predictable potency and without proof that the substance is free of contamination. If marijuana is to be investigated more widely for medical use, information and data regarding the chemistry, manufacturing and specifications of marijuana must be developed. Therefore, FDA concludes that, even under medical supervision, marijuana has not been shown to have an acceptable level of safety.
FDA therefore recommends that marijuana be maintained in Schedule I of the CSA.
NOTICE: This is an unofficial version. An official version of this publication may be obtained directly from the Government Publishing Office (GPO).