Introduction: DEA's List of Pharmacological Ignorance

The DEA maintains that the chemistry, toxicology, and pharmacology of marijuana are not established. They assert that because marijuana is made up of over 400 chemicals, and that only a few of them have been individually tested, that existing studies are inadequate to explain the pharmacology of the substance. For example:

"Because of the complex composition of marijuana, containing over 400 separate constituents (many of which have not been tested) varying from plant to plant, the chemistry, toxicology, and pharmacology of marijuana is not established."(1)

These studies are inadequate, according to DEA, because of differences between the studies and actual marijuana use, in that the studies tend to be with oral and intravenous THC, not with smoked marijuana plant material used by the public. For example:

"Most pharmacological research with cannabis or its constituents has actually been conducted with orally ingested THC, rather than smoked marijuana. Although the pharmacologic effects are presumed to be similar, the studies with oral THC do not provide a complete picture of marijuana's effects. Few of the other cannabinoids have been pharmacologically evaluated. The health consequences from smoking marijuana are likely to be quite different than those of orally ingested THC. Yet most of the chronic animal studies have been conducted with oral or intravenous THC."(2)

According to DEA, this lack of knowledge produces a lack of standardization of the drug which creates problems measuring the bio-availability, metabolic pathways, and pharmacokinetics of marijuana. Botanical variation in the relative amounts of the constituent chemicals in marijuana compounds the problem. DEA continually asserts that marijuana is just far too complicated for scientists to understand. For example:

"[M]arijuana's chemistry is neither fully known, nor reproducible. Thus far, over 400 different chemicals have been identified in the plant. The proportions and concentrations differ from plant to plant, depending on growing conditions, age of the plant, harvesting and storage factors. THC levels can vary from less than 0.2% to over 10%. It is not known how smoking or burning the plant material affects the composition of all these chemicals. It is not possible to reproduce the drug in dosages which can be considered standardized by any currently accepted scientific criteria."(3)

Regardless of this lack of knowledge, DEA asserts that marijuana use has acute and chronic side effects which render the substance dangerous for public use regardless of abuse potential. For example:

"There is a need for more information about the metabolism of the various marijuana constituents and their biologic effects. This requires many more animal studies. Then the pharmacologic information obtained from the animal studies must be tested in clinical studies involving humans. The pharmacologic testing of cannabinoids in animals thus far has shown that while they do not appear to be highly toxic, they exert some alteration in almost every biological system that has been studied."(4) (emphasis added)

This last assertion will be addressed near the end of this section.

All of these assertions by DEA were made as part of an administrative rule-making process, and serve as findings of fact that are part of the scientific justification for retaining marijuana in schedule I. These assertions of DEA rest on an evidentiary record that was closed in 1988. Perhaps in 1988 they were valid statements, perhaps they were not. That is beyond the scope of this review, which primarily concerns scientific findings published after this prior record was closed. These claims of DEA's are presented both as an indication of the agency's own apprehension of scientific research, and as a baseline from which to understand the progress that has occurred in pharmacological research since the late 1980's.

The chemicals in marijuana can be divided into two categories, the unique family of chemicals named cannabinoids, and other chemicals commonly occurring in nature.