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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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