Biology 202, Spring 2005
Third Web Papers
On Serendip

There are many different ways to define addiction. In the past, it has been defined as tolerance to and physical dependence on a drug of abuse, where tolerance represents an adaptation to repeated exposure to a drug so that the normal pharmacological response generated is lessened. Recently, however, a new definition has emerged due to further research. A more modern viewpoint of addiction has led to the understanding that tolerance and dependence can be major factors associated with addiction but is not essential; it is possible for tolerance and withdrawal symptoms to resolve within weeks but addiction can persist. This is evident in addicts who have gone years without using but then relapse. Currently, the definition has evolved to be described as an overwhelming involvement with the use of a drug (compulsive use) and a number of symptoms or criteria that reflect a loss of control over drug intake and a high tendency toward drug-seeking (1). Because of the different perspective of what makes someone an "addict", the debate on whether marijuana has the characteristic of being addictive has come into hot topic. In order to look at this question, one must understand the history of marijuana and previous addiction studies.

In the 1930's, marijuana was portrayed by the Commissioner of Narcotics, Harry Anslinger, as "a social menace capable of destroying the youth of America." During this time, it was believed that marijuana use not only triggered mental deterioration in the users but also provoked abusers to commit violent crimes. In 1937, the Marijuana Tax Act was passed in hopes of thwarting marijuana abuse. However, in 1969 the law was deemed unconstitutional. Currently, cannabis is regulated and regarded as illegal according to the Controlled Substances Act of 1970. However, this has not prevented many people from fiercely debating the dangers of cannabis as well as discussing its questionable abilities to turn someone into an addict. As Earl Thomas, a professor at Bryn Mawr College, said, "You don't see marijuana users pushing their drug dealers for another hit on the street corner." Whether or not cannabis should indeed be regarded as an addictive drug and whether this addiction is a physical one or an emotional one is a topic that has spurred a great deal of research. Therefore, it is essential to learn about the very nature of the drug and of addiction (2).

The main psychoactive ingredient in cannabis is a cannabinoid called tetrahydrocannibinol (THC). The active ingredient, THC has been known to induce mild relaxation, euphoria, analgesia, and hunger. THC usually consists of approximately 4% of the cannabis. Therefore, if there is a 1 gram "joint", 40 mg will be THC. When smoked, 20% of the THC gets absorbed by the lungs. This percent, however, can be influenced by the many factors involved with smoking (3).

Recent research has found two receptors of THC. They are called, respectively, CB1 and CB2. These receptors are located in the basal ganglia, cerebellum, hippocampus, and cerebral cortex. More importantly, they are concentrated in the substantia nigra and the caudate putamen, which are areas of the brain that are often associated with drug abuse. When these two receptors were found in the brain, researchers were encouraged to find the endogenous cannaboid compounds that these receptors accommodated. An endocannabinoid is a family of chemical signals composed of unsaturated fatty acids with polar head groups. They are produced by enzymatic degradation of membrane lipids. Although there are many endocannabinoids that are yet to be determined, Anandamide and 2-Arachidonylglycerol (2-AG) are two endocannabinoids that have been discovered.

Marijuana has been shown to have many immediate effects which last 1 to 3 hours. These effects can include: bloodshot eyes, faster heartbeat, hunger, intense sensations, dry mouth, fear, loss of memory and coordination, slowed reaction time, etc. There are also long term effects that can occur if marijuana smoking occurs over a long period of time. It can damage the reproductive system, increase the risk of lung infection, heart disease, and the more controversial "amotivational syndrome", which is lack of motivation to do activities related to school, work, or even previous friendships and interests. It is evident that marijuana has many positive and negative effects and thus it is important to understand whether this drug is addictive.

The mesolimbic dopamine system is one of the major neural substrates of reinforcement. It consists of dopaminergic neurons that start in the ventral tegmental area and end in the limbic forebrain. Cannabinoids can produce dopamine in this system. However, does this mean that cannabis is addictive? (4). As mentioned previously, it is difficult to pin down what addiction is and how it differs from habit. The central process of forming habits is through reinforcement. In order to understand the addiction process, a drug self-administration paradigm is often used with animals. This paradigm allows for the animal to supply itself with reinforcement (via the dopaminergic system). Although most studies have not been able to show self-administration of cannabis or THC, there have been studies which showed decreased reward thresholds and conditioned place preference in rats. This means that if rats were placed in the same environment, they would have a higher tolerance for the drug than if they were in a different environment. Further support for marijuana being addictive is found in studies using cannabinoid receptor antagonists, which can block the effects of marijuana. These antagonists were shown to induce withdrawal symptoms in rats such as shaking, tremors, tongue rolling, biting, etc. Furthermore, it was found that heavy marijuana users need 8 times the dose in order to get the same effects as infrequent users. This shows that tolerance definitely occurs, as well. Since tolerance and withdrawal symptoms are part of the definition for addiction, this leads one to believe that marijuana may be addictive after all (5)

Due to research, it is obvious that the drug causes cravings and changes in the dopamine system (6). It is true that many people go into therapy for cannabis addiction but there are also a number of people who try marijuana and do not become addicted. Nearly 40% the population over the age of 12 has tried pot at least once in their lives but not all have become addicted (7).). What is the difference between those that become addicted and those that do not? It is obvious from past studies that the dopamine system is involved in the addiction process to marijuana; however it does not completely explain it. What initiates the drug use?

It has been postulated that the initial drug use is a result of personality traits, peer pressure, or other stress. It is possible that after many times, the normal homeostatic environment of your brain is disrupted. Possibly, the reward system is being over activated during drug use. A compensatory response due to the excessive flood of drug-induced neurotransmitters results, dampening the drug's effect. This leads to tolerance. Another theory is that the withdrawal symptoms could cause someone to use again. A final theory is that the drug becomes context dependent. This could mean that any environment that surrounds the user when they smoke will become a potential incentive to use the drug the next time they are around that person, place, or thing. This ties into the fact that social factors and personality factors have also been suggested to spur marijuana use (1).

The criteria for addiction has been looked at and revised quite a bit over the past decade. Originally, it was thought that dependence, tolerance, and withdrawal all have to occur in order to call someone addicted. However, a different point of view has put attention on drugs that now have the possibility of being addictive. Through excessive animal models and correlational studies, it has been found that marijuana does indeed show evidence for being both emotionally and physically addictive. Based on the fact that the dopamine system is being stimulated and thus, the reward system is being activated, one could conclude that almost anything can be addictive, if it creates euphoria. Cannabis is certainly something that brings about pleasure. As we discussed in the beginning of class, doing anything will have an effect on the brain. When you are putting a chemical like THC into your body, which changes the way you act and think, it is only common sense that constant use of it can cause permanent changes. Therefore, I think it is not very far off to conclude that it is possible to create a new "constant state" of your dopamine system. Future research is definitely needed to further validate the point that marijuana is physically addictive. Particularly, it would be beneficial to understand what initiates the addictive process. However, science has taken leaps in its effort to understand what once looked like a harmless drug.

References

1) Kopnisky & Hyman. "Molecular and Cellular Biology of Addiction": National Institutes of Health, MD.

2) Meyer & Quenzer. Psychopharmacology. Sinauer Associates, Inc.: MA, 2005.

3) , an interesting journal websource

4) Nestler . "Cellular and molecular mechanisms of drug addiction" Substance Abuse Disorders 45 (698).

5)Health Education>, a health resource on marijuana

6)About Addiction, a useful addiction site

7) Marijuana Addiction, a useful addiction site


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