These are Hollister's conclusions on marijuana dependency in 1986:

"Brain damage has not been proven. Physical dependence is rarely encountered in the usual pattern of social use, despite some degree of tolerance that may develop."(10)

These are Abood and Martin's comments on dependence in 1992:

"It is well established that chronic heavy use of cannabis does not result in a withdrawal syndrome with severe symptomatology. However, the occurrence of some form of psychological dependency or craving is more probable than physical dependence . . .There are few reports in which an abrupt interruption in marijuana use has led to incapacitation of the individual using the substance. The number of people who have difficulty in controlling their abuse of cannabis to the extent that they require professional treatment is relatively small."(11)

The only rationale defense for basing marijuana's scheduling on a presumptive finding is that at the time no scientific knowledge was available regarding marijuana's mechanism of action in the brain that allowed a comparative assessment of the abuse potential of marijuana and other drugs. The discovery of the cannabinoid receptor system has finally provided the means to mark the "extent' to which marijuana has a dependence liability.

Early research into brain functions centered on the role of electrical impulses in creating pleasure and pain. Dr. Gabriel Nahas praises Robert Heath's work in this field, and includes a commentary by Heath on the relationship between his work and public policy in a 1981 text on Drug Abuse in the Modern World.(12)

Dr. Heath's research also suggested that marijuana use caused irreversible brain damage, however this conclusion has rejected by reviewers for various reasons including excessive doses and lack of replication.(13) Given his own conclusions about marijuana, Heath eloquently describes what he believes to be the problem at hand:

"In short, the initial use of marihuana produces a provocative phenomenon: the person smoking the joint can, at will, activate his brain's pleasure system . . . What is wrong with this? . . . The deleterious effects to both the individual and society have been repeatedly and consistently demonstrated. . .The fate of cultures in which drug use has been extensive serves to substantiate the consequences of inducing pleasure dissociated from utility and survival. In our own culture . . when the pleasure a person gains from taking a drug replaces reward for a job well done, we have shoddy workmanship. When puffs from a joint replace the pleasure of a good golf game or a swim on a warm afternoon, we have apathy and physical deterioration. When the anxiety before an examination is eliminated by the instant pleasure of a drug, the student does not prepare and fails the examination. When ingestion of a chemical substitute replaces the pleasant arousal of solving a problem or designing a new engine, what are the implications for the future of our society -- or even our survival as a nation?"(14)

More recent research also associates addiction with the pleasure/reward system in the brain. Unlike Heath, who associated activity in various regions of the brain as pleasure-oriented, modern theory is based on activation of the pleasure/reward system by the neurotransmitter dopamine. Izenwasser and Kornetsky discuss the discovery by Olds and Milner in 1954 that animals would work to receive electrical stimulation to brain regions, and the modern "evidence about the neurochemical bases underlying drug reinforcement [that] suggests that dopamine plays a major role."(15) The role of dopamine in the brain pleasure/reward system is now well established in the pharmacological literature.(16)

According to Izenwasser and Kornetsky:

"Using in vivo microdialysis, Di Chiara and Imperto(17) (in 1988) showed that many drugs abused by humans (opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine in the nucleus accumbrens, whereas drugs that are dysphoric . . . reduce dopamine release. Drugs such as diphenhydramine (an antihistamine), imipramine (an antidepressant), and atropine (a muscarinic cholinergic agonist), which are not abused by humans, have no effect on the concentration of synaptic dopamine in the nucleus accumbrens."(18)

Microdialysis in freely moving rats is a new technology that allows researchers to implant measuring devices in the rat brain. The device extrudes from the live rat's skull. When the rat recovers from the surgery, researchers are able to use the microdialysis device to measure changes in dopamine levels in a living, "freely moving" specimen. Izenwasser and Kornetsky have used these and other experimental data to correlate brain wave data with neurobiological processes, as have others. Technological innovation allows modern researchers access to more accurate data than was available to their predecessors.

In 1992 the National Institute on Drug Abuse published a monograph on Neurobiological Approaches to Brain-Behavior Interaction.(19) This monograph presents several papers on the various technologies being applied to brain-behavior research. A paper on microdialysis provides extensive citations on the role of dopamine in reinforcement. These citations will not be repeated in the excerpt below, but are available in the NIDA monograph.

"The mesolimbic DA [Dopamine] system has attracted the most attention in the study of the neural circuitry underlying drug abuse. Its importance is undeniable. If the mesolimbic system is blocked or almost completely depleted of DA, animals refuse to work for food, self stimulation, or self-injection. . . . Not only is the DA system necessary, its functions are sufficient to motivate and reward behavior. Rats will work to stimulate certain DA cell regions electrically or chemically. For example, they will electrically self-stimulate the mesolimbic DA cell body region in the ventral tegmental area (VTA)."(20)

"Many drugs of abuse given systematically increase extracellualr DA. Similarly, when AMPH, cocaine, PCP, or nicotine was injected locally into the nucleus accumbens or infused through the microdialysis probe itself, this local treatment increased levels of extracellular DA in a manner similar to an intraperitoneal injection."(21)

The Office of Technology Assessment cites several pharmacological studies in support of the following summary.

"A key part of this drug reward pathway appears to be the mesocorticolimbic pathway (MCLP) . . .

"These structures and pathways are thought to play a role in the reinforcing properties of many drugs of abuse, although the precise mechanisms involved in all drugs of abuse lack a thorough description. The mesocorticolimbic dopamine pathway appears to be critical in the rewarding properties of stimulant drugs such as cocaine and amphetamines. Also, both the ventral tegmental area and the nucleus accumbens appear to be important for opiate reward, while these same structures and their connections to other limbic areas, like the amygdala, may play a role in the rewarding properties of barbiturates and alcohol."(22)

As recent as 1992 many believed marijuana had an effect on dopamine levels in the brain. Izenwasser and Kornetsky cite research on self-stimulation by Lewis rats in support of the notion that marijuana shares this quality with other drugs.(23) They also note that this quality is only observable in the Lewis Rat strain. Martin also notes that this finding is confined to "one strain of rat" and its application "to human abuse is tentative at best."(24) This conclusion is also reported by the Office of Technology Assessment, which attributes the finding to an in-bred quality specific to Lewis Rats.(25)

In 1992 Herkenham, using a lesion-technique, established that there are no cannabinoid receptors in the dopamine producing areas of the human brain.(26) This confirms a 1991 microdialysis study indicating that THC does not affect striatal dopamine release in freely moving rats.(27)

Dopaminergic qualities are now a widely acknowledged biological marker of a drug's dependence producing qualities. The brain is evolutionarily conditioned to adjust behavior to increase dopamine production. Usually, this neurotransmitter activity rewards essential activities related to eating, reproduction, and physical fitness that contribute to the perpetuation of the species. Dopamine release provides a reinforcing effect that encourages repetition of the source activity.

Addressing interest in dopamine release in the brain, Herkenham and his colleagues noted in his breakthrough 1990 report that:

"The presence of cannabinoid receptors in the ventromedial striatum suggests an association with dopamine circuits thought to mediate reward. However, reinforcing properties of cannabinoids have been difficult to demonstrate in animals. Moreover, cannabinoid receptors in the basal ganglia are not localized on dopamine neurons."(28)

Herkenham's 1992 review of the literature concludes that:

"The effects of cannabinoids on dopamine circuits thought to be common mediators of reward are indirect and different from those drugs such as cocaine and morphine which directly affect extracellular dopamine levels and produce craving and powerful drug-seeking behavior."(29)

Marijuana does not stimulate the pleasure/reward center of the brain and is categorically different from popular drugs of abuse.

This information explains why marijuana does not produce self-administration in animals, and why evidence of a damaging dependence liability in humans has not emerged in the 25 years since the creation of the Controlled Substances Act.

Popular drugs of abuse, such as heroin, cocaine, and amphetamines, produce reinforcing self-administration in animal models, and all have effects on the production of the neurotransmitter dopamine, explaining the biological basis for their respective dependence liabilities. Marijuana does not produce reinforcing self-administration in animal models, and does not have an effect on the production of dopamine, explaining the biological basis for its lack of a significant dependence liability.

Consequently, marijuana does not have a sufficient dependence liability for schedule I or II status.