The 1995 Marijuana Rescheduling Petition

Institute of Medicine Report: Cannabinoid Pharmacology


A 1982 report from the Institute of Medicine provides a benchmark and context for understanding the nature of modern understanding of the chemistry and pharmacology of marijuana.

"Although the behavioral and psychological effects were well described in literature of the nineteenth century, the complex chemistry and pharmacology of the cannabis plant discouraged extensive investigation until 15 years ago.

"The most prominent effects of cannabis are on psychological phenomena and behavior. Psychopharmacology and behavioral pharmacology have developed as divisions of scientific inquiry only over the past 25 years; therefore, the older cannabis literature, no matter how valuable for observations on other matters, does not provide a basis for quantitative pharmacological analysis and evaluation.

"Early pharmacologists could work only with crude extracts of the plant. Although the general structure of the cannabinoids was known by the turn of the century, the particular cannabinoids that were identified early and were available as pure substances were largely devoid of the characteristic psychoactive effects of cannabis. Synthetic cannabinoids with cannabis-like activity became available in the 1930's. It was not until 1964 that an active ingredient of cannabis was identified as D-9-tetrahydrocannabinol (THC) and synthesized. In the 1960's, the isolation and synthesis of the main psychoactive component of cannabis and related cannabinoids, together with a rapid increase in the use of marijuana by middle class North American students, stimulated scientific activity . .

"Cannabis, the crude material from the plant Cannabis sativa, contains hundreds of chemicals. Most of these are found in other plants, but 61, termed cannabinoids, are unique to the cannabis plant . . .A single cannabinoid, D9-THC, produces almost all the characteristic specific pharmacological effects of the complex, crude cannabis mixtures. A number of synthetic cannabinoids have pharmacological effects similar to D9-THC. Other cannabinoids in the plant, for example, cannabinol, are almost inactive pharmacologically or may interact with D9-THC to modify its actions. One cannabinoid, cannabidiol (CBD), can influence the metabolism of another, D9-THC. A few cannabinoids have effects quite different from D9-THC. For example, cannabidiol has relatively little psychoactive and cardiovascular effect but is an active anticonvulsant.

"Investigators have chemically altered the D9-THC molecule in an attempt to determine which of its structural elements are required to produce behavioral and other effects. Studies of the structure-activity relationships indicate that, to produce effects on behavior, a pyran ring must be part of the three-ring system, a free phenolic hydroxyl on the aromatic ring at C-1, and a lipophilic side chain (C5H11) at C-3. Understanding chemical structure-effect relationships is important to guide the synthesis of cannabinoids with differing pharmacological effects. Different effects of D9-THC activity by chemical design will require further syntheses and pharmacological study of a large number of cannabinoids."(17)

Even at this relatively early date (1982) scientists have established that the key to unlocking the pharmacological secrets of the marijuana plant lies in an understanding of the active ingredients as a chemically distinct family of interrelated molecules.

There are 61 known cannabinoids, however they can be further subdivided into 12 categorical types.

" 1. Cannabigerol (CBG) type: 6 known

2. Cannabichomene (CBC) type: 4 known

3. Cannabidiol (CBD) type: 7 known

4. D9-Tetrahydrocannabinol (D9-THC) type: 9 known

5. D8-Tetrahydrocannabinol (D8-THC) type: 2 known

6. Cannabicycol (CBL) type: 3 known

7. Cannabielsoin (CBE) type: 3 known

8. Cannabinol (CBN) type: 2 known

9. Cannabinodiol (CBND) type: 2 known

10. Cannabitriol (CBT) type: 6 known

11. Miscellaneous types: 9 known

12. Other cannabinoids: 4 known" (18)

 

 
 
 
  
 
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