The use of highly potent, stereoselective synthetic cannabinoid
analogs made the discovery and characterization of the endogenous
cannabinoid receptor system between 1988 and 1993 possible.
As discussed throughout the petition above, all recent advances
in understanding about the effects of marijuana have been
based on the discovery of the common mechanism of action for
cannabinoids, including D9-THC,
which provide the pharmacological basis for the effects of
A review of the conclusions of Herkenham's team's findings
on tolerance reiterates this important point:
"The magnitude of the present effect, like the striking
behavioral tolerance, may stem in part that, unlike other
psychoactive agonist drugs, cannabinoids can be administered
in very high doses. It is ironic that the magnitude of both
tolerance (complete disappearance of the inhibitory motor
effect) and receptor down-regulation (78)% loss . . .) is
so large, whereas cannabinoid dependence and withdrawal phenomena
are minimal. This supports the claim(35) that tolerance and
dependence are independently mediated in the brain."(36)
WIN 55,212 is another experimental cannabinoid which
produces the same effects as D9-THC
and CP-55,940, however there are some differences in the effects
of each of the three. A 1994 study demonstrated cross-tolerance
between these three cannabinoids.(37) The authors hypothesize
that D9-THC and WIN-55,212 are
partial agonists whereas CP 55,940 is a complete agonist,
explaining some of the minor differences between these cannabinoids.
Cross tolerance among certain psychoactive cannabinoids has
been well documented.(38)
Valid assertions about the relative abuse potential and
relative dependence liability of marijuana can now be made
by scientists on the basis of the known existence of a cannabinoid
receptor system in the human body. Valid assertions about
the relative abuse potential and relative dependence liability
of all cannabinoids can be made on the same scientific basis.
The psychoactive qualities of marijuana are produced
by one constituent chemical, D9-THC.
Conclusive evidence exists that marijuana does not have a
dependence liability greater than that of D9-THC
alone, and that no other cannabinoid has psychoactive properties.
Conclusive evidence exists that the pharmacological properties
of individual natural cannabinoids have less pharmacological
action than either marijuana or D9-THC
alone, and that their dependence liabilities (if any) and
potential for abuse is less than that of marijuana and D9-THC.
Experimental cannabinoids may have greater potencies,
and may present qualities which warrant stricter controls
than necessary for natural cannabinoids or synthetic copies
of naturally occurring cannabinoids, such as synthetic THC.
There is no scientific basis for an assertion that marijuana
had a greater dependence liability than D9-THC.
There is no scientific basis for an assertion that any cannabinoid
compound has a greater dependence liability than D9-THC. Consequently,
there is no basis for distinguishing between the scheduling
of marijuana, cannabinoids, and D9-THC
on the basis of dependence liability or potential for abuse.
As discussed in sections 1 and 7 above, neither marijuana,
cannabinoids, or D9-THC have sufficient
potential for abuse for inclusion in schedule I or II of the
Controlled Substances Act.
On the basis of the chemical similarities between marijuana,
cannabinoids, and specifically D9-THC,
their common endogenous receptor system, the lack of self-administration
of cannabinoids in animals, the lack of cannabinoid receptor
activity in dopamine producing areas of the brain, and the
additional scientific and medical evidence discussed above,
this petition calls for the repeal of the administrative rules
placing marijuana and cannabinoids in schedule I and placing
D9-THC in schedule II.