Mary Lynn Mathre, R.N., M.S.N., C.A.R.N., is an addictions specialist at the University of Virginia Medical Center in Charlottesville.

 

Prejudice Against 'Medical" Marijuana

 

When the subject of marijuana is brought up, the context is almost always that of substance abuse. An examination of pharmacology text books would show that marijuana is listed only under the chapters addressing substance abuse. In textbooks designed for healthcare professionals, marijuana is discussed under the health or medical problem of substance abuse. It may be discussed in detail including information regarding the number of "abusers," its intoxicating effects, dangerous health risks, and its addiction potential. And finally, in books on the topic of substance abuse or chemical dependency, a chapter is usually devoted to marijuana.

 

On the other hand, in trying to learn more about the treatment for spasticity, increased intraocular pressure, severe nausea and vomiting, and other such disorders discussed in the preceding chapters, one would be hard pressed to find marijuana or cannabis mentioned as a therapeutic remedy. Because of the governmental and political marijuana prohibition, a discussion of its merits has become taboo. Generations of American citizens have been raised under this information censorship and consequently their thinking about the drug is biased.

 

A New Paradigm for Substance Abuse

 

The prevailing black-and-white thinking about substance abuse in general is misleading and dangerous. Drugs are labeled according to their "abuse [or addictive] potential" and specific drugs are believed to "cause" an addiction. Illogical thinking such as the following develops: "I would not have been an addict if I never had the opportunity to use this drug. ... It's not my fault, it's the drug's fault ... therefore this drug is bad and should not be available for use." This perpetuates the war on drugs propaganda that certain drugs are inherently bad and therefore should be banned and drug users are criminals who should be punished. The awareness that not all drug users are addicts (e.g., the moderate and responsible alcohol consumer) and that only a minority of drug users (7 to 20 percent) develop an addiction problem is soon forgotten. This zero tolerance approach limits the responsible behavior of the majority because of problems that occur among the minority.

 

More importantly, this zero tolerance approach fosters the unsafe and irrational belief that there are in fact "good drugs" and "bad drugs." The public is wrongly encouraged to believe that if a drug is sold over the counter, "it must be safe," and if a physician prescribes a controlled drug, "it must be good for me." This lack of personal responsibility regarding drug consumption often results in medical complications, drug dependence, or overdose because of the unsafe manner in which a "good" drug was used. A zero tolerance policy on illegal drugs deters rational dialogue regarding the benefits and risks of these substances, and so creates a shortage of reliable information for responsible citizens who need accurate information to make informed decisions about using drugs.

 

Drug addiction does not simply mean that the use of certain drugs makes people addicted. The problem is more complex. Drug addiction is about an unhealthy relationship with a drug or drugs and continued use despite the subsequent health and life problems. This can apply to OTC or prescription drugs as well as to alcohol or caffeine. Substance abuse and addiction indicate problems associated with the pattern of use of a drug. Why is the person using the drug? Is there a feeling of loss of control regarding the use of the drug? Is the pattern of use of this drug dangerous to the user? When under the influence of the drug, does the user find himself or herself doing things he or she would not normally do (and does not want to do)? These are the important questions to pursue instead of simply assuming that because a specific drug is consumed, the user has a substance abuse or addiction problem.

 

Drug abuse may be a symptom of a larger problem. Barry Beyerstein, a psychopharmacologist from Canada, did not simply believe that certain drugs will cause addiction, as was scientifically believed according to numerous animal studies. He believed that there may be factors other than simply a drug's inherent addictive potential that determined whether or not an animal became addicted. Most animal studies involve a caged animal with the opportunity to ingest a psychoactive drug. The drug's addictive potential is rated according to how eager the animal is to obtain and consume the drug. Beyerstein designed a study involving rats and morphine. The control rats were typically alone and caged, were given a sufficient supply of food and water, and had access to the morphine. The rats preferred the morphine over the water.

For the experimental rats, his students built a large cage, filled it with wood shavings and objects, and allowed both sexes to cohabitate. They called it "Rat Park." These rats were also provided with adequate food, water, and a morphine solution. His students closely observed these rats and the morphine supply and soon noted that the rats avoided the morphine. A sweetener was added to the morphine to entice the rats but to no avail. As a last resort, the water was removed. As the rats became thirsty, they soon began to drink the morphine, and Beyerstein's students kept careful records of the amounts consumed by each rat. They continued with this protocol for 57 days and then reintroduced the water. All of the rats abandoned the morphine in preference to the water. All of the rats experienced withdrawal symptoms from their abrupt cessation of morphine intake.

 

This study may not have been large enough to justify any broad conclusions, but it seems to indicate that caged rats given no quality of life may choose to escape this abnormal existence through the use of a psychoactive drug such as morphine. On the other hand, rats in a more normal and healthy environment had no urge to alter their mental status. They did consume the morphine only out of necessity when their water supply was withdrawn, yet all rejected the morphine when their water supply was returned. Certainly humans are more complex, but as with the rats, it is not simply the drug that determines whether or not addiction will develop. When discussing the addictive potential of drugs it is also important to note that animals do not self-administer cannabis or THC as they do with amphetamines, cocaine, nicotine, depressants, and opioids.

 

Stages of Drug Use

 

It has long been understood that there are different patterns of drug use. One way of describing these behaviors was to divide these patterns into stages or levels of use. The government described five stages of drug use (experimental, social or recreational, situational or circumstantial, intensified, and compulsive) to differentiate drug using behavior (National Commission on Marihuana and Drug Abuse 1973). Definitions of these stages are as follows:

 

Experimental use is short term use, a non-patterned trial of one or more drugs either concurrently or consecutively with variable intensity but maximum frequency of ten times per drug. Experimental use is primarily motivated by curiosity and usually takes place with others.

 

Social or recreational use occurs in social settings among friends or acquaintances who desire to share an experience perceived by them as both acceptable and pleasurable. This use is a voluntary act that tends not to escalate either in frequency or intensity to patterns of uncontrolled or uncontrollable use.' Also under the social use stage is the use of psychoactive drugs by various cultures for religious or sacred purposes.

Circumstantial or situational use is generally task-specific and self-limited. The level of drug use is motivated by a perceived need or desire to achieve a known and anticipated effect deemed desirable to cope with a specific, sometimes recurrent, situation or condition of a personal or vocational nature.

 

Intensified use occurs at least daily and is motivated by the user's perceived need to achieve relief from a persistent problem or stressful situation, or his or her desire to maintain a certain self-prescribed level of performance. Drug use becomes a normal and customary activity of daily life. However, the individual generally remains both socially and economically integrated in community life.

 

Finally, compulsive use includes a pattern of both high frequency and high intensity of relatively long duration, producing physiological or psychological dependence. The drug use is motivated by a need to elicit a sense of security, comfort or relief. At this stage drug use dominates the individual's existence and preoccupation with procuring and taking the drug precludes other social functioning.

 

These stages offer a framework for understanding that a person's use of a drug (or medicine) may range from a low risk activity to a major health problem. Currently healthcare professionals discuss drug use in terms of use, abuse, dependence, and addiction. The similarities between these terms and the stages of drug use are fairly clear.

 

Defining the Terms and Their Relevance to Cannabis

 

Before specifically addressing the dependence and addiction potential of cannabis, the relevant terms should be defined. The terms drug use, abuse, dependence, and addiction are often used interchangeably, and this accounts for much of the confusion surrounding "drug abuse" problems.

 

A drug is any substance other than food that by its chemical nature affects the structure or functioning of the living organism. Drugs do not always act in the same way for everyone. Body chemistry is different in different people, and this will be a factor in how the drug acts on each individual. The body chemistry of an individual also varies from day to day, and this will be a factor in how the drug works.

 

Wore recently the federal government's Center for Substance Abuse Prevention in its 1982 and 1983 Prevention Pipeline publications has instructed all readers no longer to use the phrase "recreational use of drugs" and instead simply refer to drug "use" "since no drug use is recreational." This new-speak by the government does not alter the reality that most people do use drugs in a social or recreational manner.

 

In the context of substance abuse, the primary group of drugs considered are the "psychoactive drugs." These are drugs that change the way a person feels (e.g., happy, relaxed, energized, etc.) or that alter the senses (e.g., cause hallucinations or change perceptions of time or sound). Two factors important to consider when a person uses a psychoactive drug are the set and setting. Set refers to the mood and expectations of the user, and setting refers to the environment in which the drug is used. The intoxicating or "high" mental experience of a psychoactive drug is often influenced by these two factors.

 

Drug abuse is a very ambiguous and value-laden term, and therefore its usefulness is questionable. Drug abuse has been defined as use of a drug without a prescription. This narrow definition is not helpful for those persons and cultures that do not automatically accept the paternalistic notion that only a physician can decide whether or not a person should use a drug, when to use it, and how often to use it. This definition is also too narrow because it does not address the use of OTC drugs or other substances such as caffeine, chocolate, or alcohol that people may use without a prescription though their patterns of use could be harmful.

 

Another definition of drug abuse has been the use of a drug that is not socially approved. This definition is also limited because what constitutes drug abuse in one culture may be appropriate use in another culture, and therefore to determine the presence of drug abuse implies acceptance of a specific culture's values. Drug abuse is more usefully defined as the use of a drug in a manner that negatively affects the user's health or his or her social or economical functioning. This definition assumes the understanding that any drug can be abused and that drugs have different effects on different people; thus a drug that may be pleasant and therapeutic for one person may be unpleasant and detrimental for another.

 

Abuse of marijuana may be identified when a person with heart problems such as angina, uses cannabis and the subsequent increase in the heart rate from the cannabis causes harm to that person (health problem). Abuse of marijuana may be identified when a person uses cannabis to relax but continually smokes too much and falls asleep when socializing with friends and never seems to have the energy for social activities (social problem). Abuse of a drug may occur because the user lacks information about how the drug works or how it should be administered. It may also occur because the user is experiencing other problems and wants to escape from them. Despite many subjective judgments of healthcare professionals regarding drug abuse, abuse should be determined with agreement from the user. Is the person experiencing health problems because of the cannabis use and is that person aware of the connection? Is the person experiencing severe stress and using cannabis to medicate the stress to avoid dealing with the stressor? Are the results of the drug use other than what the user intended?

 

Tolerance is defined as the need for increased amounts of a drug to produce the desired effect. It is important to understand that while tolerance to one effect of a drug may develop, there may not be a tolerance to other effects of the drug, and at the same time the user may become more sensitive to other effects (reverse tolerance). As tolerance to the desired effects develops and the dose must be increased, the side effects of a drug may become more severe because the dosage is increased.

 

To develop tolerance, the user usually must consume enough of the drug with sufficient frequency for a long enough period of time. Studies have found that users can develop a tolerance to the "high" from cannabis, but only when the user consumes large amounts of cannabis (Wikler 1976). Robert Randall, the first legal medical marijuana patient in the Investigational New Drug Program has been smoking ten low-grade marijuana cigarettes per day since 1976 to control his glaucoma. He does not report experiencing a high from the cannabis, but he has consistently maintained his intraocular pressure with this same dose, thus he has experienced tolerance to the "high" but has not experienced tolerance to the desired medical benefits.

 

"Less is more" was a phrase used to deter recreational cannabis users from overusing cannabis, and in effect, it exemplifies the concept of tolerance with cannabis. The less frequently a person uses cannabis, the less likely is that person to develop tolerance to the original dose, thus the less likely would that person require higher doses (develop tolerance) to achieve the same effect. Hollister summarized tolerance to cannabis in his conclusions that relatively little tolerance develops when the doses are small or infrequent and the drug exposure is of limited duration. Tolerance clearly develops when persons consume high doses for a sustained period of time (1986).

 

Dependence is a term often misused as it is considered a synonym for addiction, or the term is separated into physical dependence and psychological dependence. For the purposes of this book, we will simplify the concept of dependence to what others sometimes more specifically refer to as physical dependence. Dependence is the result of continued regular use of a drug that produces a physiological change in the central nervous system to the extent that abrupt cessation of the drug causes withdrawal symptoms. The seriousness of the withdrawal symptoms depends on the particular drug used and the extent of its use (i.e., the amount used, the frequency, and duration of use). In order for a person to experience withdrawal symptoms the dose must be relatively high. However, the high dose is not enough, the drug must also have been consumed for a sufficiently long time period (days to months depending on the drug) on a frequency schedule that provides for a "continual neuronal exposure" to the drug. The frequency of use required for dependence to develop depends on the drug and its duration of action. For those drugs that can produce physical dependence, there is an expected physiological response that would occur in anyone who used the drug on a regular basis, but this is not by itself indicative of addiction. For example, it is expected that if a person was put on morphine on a regular basis (at least every four hours) for several days because of severe pain, that person would experience withdrawal symptoms if the morphine was suddenly taken away—similar to what happened to the rats in "Rat Park." To avoid this, the morphine dose is usually decreased gradually as the pain decreases, and thus the person does not experience withdrawal symptoms.

 

Chronic, heavy cannabis use (smoked every four hours) may produce a mild dependence with relatively benign withdrawal symptoms. Cannabis withdrawal symptoms may include irritability, restlessness, difficulty sleeping, nausea, and decreased appetite, and less frequently sweating and tremors. (Adams and Martin 1996, Jones et al. 1981, Wiesbeck et al. 1996). These symptoms generally peak in a few days then subside. There is no life-threatening withdrawal syndrome associated with cannabis dependence as seen in withdrawal from alcohol, barbiturates or benzodiazepines.

 

Patients requiring long-term high doses of cannabis may become mildly dependent upon it, but that is not necessarily a problem. The therapeutic benefit of the drug may well be worth the small risk of physical dependence. As mentioned earlier in this book, Corinne Millet, a patient suffering from glaucoma and receiving marijuana legally as a medicine, had her government supply arbitrarily stopped and was unable to get her medicine for six weeks. She experienced minor withdrawal symptoms, but of greater significance was that she lost 80 percent of her peripheral vision while she was without her medicine. Addiction (also called psychological dependence) is defined as a pattern of drug abuse characterized by an overwhelming preoccupation with the compulsive use of a drug, securing its supply, and a high tendency to relapse if the drug is taken away. When a drug is described in terms of its "addictive potential," the intensity of the "high" is considered as well as the possibility of withdrawal symptoms. Tolerance and dependence (physical) are common results of addiction, but are not necessary components of addiction.

 

For patients receiving cannabis for medical reasons, the "high" effect is one of the first effects they lose as they develop a tolerance to this. Studies have shown that patients smoking cannabis titrate to the dose required to relieve symptoms and that once the dose is determined, they can be maintained on that dose for long periods of time. Examples of this have already been discussed in reference to glaucoma patients using cannabis to control their intraocular pressure and cancer patients receiving cannabis to combat the nausea and vomiting induced by chemotherapy.

 

Addiction to cannabis rarely occurs because in general, persons who have problems with drug addiction usually prefer more potent psychoactive drugs. Nicotine, alcohol, tranquilizers, cocaine, and opioids (narcotics) have a stronger effect on how a person feels, and therefore these are the drugs more commonly associated with addiction. Since the synthetic THC pill (the primary psychoactive cannabinoid in cannabis), Marinol, has been available, there has been little evidence of illicit marketing of this drug to drug addicts.

 

Schedule I Status of Cannabis Is Unjustified

 

As previously explained, marijuana is classified as a Schedule I drug and synthetic THC as a Schedule II drug. The three criteria for Schedule I classification are: (1) high potential for abuse, (2) has no therapeutic value, and (3) is not safe for medical use. Preceding chapters have discussed the remarkably wide margin of safety and the therapeutic value of cannabis.

 

According to the Controlled Substances Act of 1970, "a key criterion for controlling a substance, and the one which will be used most often, is the substance's potential for abuse." In reading about the determination of the potential for abuse (dependence liability) for all drugs, it must be noted that the dependence liability criteria are similar to the defining characteristics of addiction.

 

The Committee on Problems of Drug Dependence (CPDD) is responsible for applying standardized tests to evaluate the abuse liability and dependence potential of drugs for the National Institute on Drug Abuse (NIDA) to determine the level of regulation for the drug under the provisions of the Controlled Substances Act. Thomas Cicero, chairman of the Drug Evaluation Committee of the CPDD, identified five criteria to evaluate the degree to which a drug has dependence liability: (1) harmful, compulsive drug self-administration, (2) a preoccupation with drug-seeking behavior to the exclusion of all other activities, (3) craving for the drug, (4) tolerance, and (5) withdrawal symptoms (Cicero 1992). Cicero further states:

 

Thus, it is essential that one look at the full spectrum of the drug's effects and the degree to which it satisfies the foregoing criteria before any conclusions regarding its dependence potential are drawn. However, it should be clear that the first three criteria mentioned above (harmful self-administration, compulsive drug-seeking behavior, and craving) must be satisfied in all cases to classify a drug as having significant dependence liability [p. 4].

 

Cicero elaborates on the self-administration criterion by explaining that people self-administer many substances because of the perceived beneficial effects. However, it is when this behavior results in adverse consequences that self-administration becomes an indication of drug dependence: "To summarize, self-administration of a drug to the point where the behavior becomes obsessive and detrimental to the individual is the primary criterion which must be met to classify a drug with significant potential for dependence" (p. 6).

 

Initially, animal studies are used to evaluate the abuse potential with the understanding that these do not necessarily reflect similar outcomes in humans. It is important to note that numerous studies conclude that while cannabis may produce a feeling of euphoria in humans, in general, animals will not self-administer THC (Office of Technological Assessment 1993; Abood and Martin 1992; Herkenham 1992). Unfortunately, rather than relying on scientific evidence to evaluate abuse potential, the DEA uses its rigid view of drug abuse according to which use of any illicit drug, regardless of its consequences or frequency of use (Cicero 1992) constitutes abuse.

 

In 1994 Dr. Jack E. Henningfield of the National Institute on Drug Abuse (NIDA) and Dr. Neal L. Benowitz of the University of California at San Francisco (ucsF) ranked six commonly used drugs by five criteria: withdrawal symptoms, reinforcement (craving), tolerance, dependence (addiction potential), and intoxication (Table 1). They ranked these drugs from 1 as most serious to 6 as least serious. Marijuana was ranked lowest for withdrawal symptoms, tolerance, and dependence (addiction) potential; it ranked close to caffeine in the degree of reinforcement and higher than caffeine and nicotine only in the degree of intoxication.

 

Conclusions

When used as a medicine, cannabis has a wide margin of safety due to its low toxicity. If taken in large amounts on a regular basis, patients often develop a tolerance to its psychoactive effects but not to its therapeutic effects. A mild physical dependence on cannabis might possibly occur for patients using cannabis in high doses, on a regular basis, over a long period of time. However, acute withdrawal from cannabis produces only mild discomfort (less problematic than caffeine withdrawal) rather than life-threatening symptoms as seen with many other medicines. Addiction to cannabis is not common, but if a person becomes addicted to cannabis, treatment is available.

References

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Adams, I.B. and B.R. Martin, 1996. Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-1614.

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Compton, D.R., W.L. Dewey, and B.R. Martin. 1990. Cannabis dependence and tolerance production. Advances in Alcohol and Substance Abuse 9 (1-2): 129-147.

Herkenham, M. 1992. Cannabinoid receptor localization in the brain: Relationship to motor and reward systems. Annals of the American Academy of Sciences 654: 19-32.

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Jones, R.T., N. Benowitz, and J. Bachman. 1976. Clinical studies of cannabis tolerance and dependence. Annals of New York Academy of Sciences 282: 221-239.

National Commission on Marihuana and Drug Abuse. 1973. Drug Use in America: Problem in Perspective. Washington D.C.: U.S. Government Printing Office.

Office of Technology Assessment, U.S. Congress. 1993. Biological Components of Substance Abuse and Addiction. Washington, D.C.: U.S. Government Printing Office (OTA-BP-BBS-117).

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Wikler, A. 1976. Aspects of tolerance and dependence on cannabis. Annals of NewYork Academy of Sciences 282: 126-147.