----------------------------------------------------
        Why you should isomerize !
----------------------------------------------------


        Raw Cannabis contains numerous species of
cannabinoids. The ones of principal interest to
students of neuropharmacology (i.e. stoners) are:

        CBN     Cannabinol
        CBD     Cannabidiol
        THC     d^1-Tetrahydrocannabinol
                d^1(6)-Teterahydrocannabinol

        As well, the latter two (CBD & THC) are
very often found in their corresponding
carboxylic acid form [see figure ?] especially
in the fresh plant material.

----------------------------------------------------

"Accelerated aging tests were carried out by heating
samples on filter paper in an oven at controlles
temperatures. . . . d^1(6)-THC showed no
change in composition after 7 days at 80 degrees
Celsius, whereas under the same conditions d1-THC
disappeared completely with the concomitant
appearance of cannabinol."

"One half of d1-THC had disappeared after 4 days'
exposure to air at 80 deg. C, whereas it took 7
days under nitrogen atmosphere to produce a similar
change in composition."

"The addition of antioxidants . . . did not improve
the stability of d^1-THC when examined in
accelerated filter paper tests at 80 deg. C.
However, in a comparative study of the stability
of d^1-THC as a 5% solution in ethanol, hexane and
CCl4 at room temperature, we found that ethanol
prevented apparent decomposition. After 75
days there was no deterioration . . ."


 d1-THC : Tetra-hydro-cannabinol ==> Our friend!

                H
               HCH       *  OH
                 \     H     \     H     H H H H
                  C===C       C---C       C   C
               H /     \     //   \\     / \ / \
                C      HC---C       C---C   C  HCH
               H \     /     \     /   H H H H  H
                 HC---CH      C===C
                  H    \     /     H
                        C---O
                       / \            C  H  O
                     HCH HCH           21 30 2
                      H   H


Note (*) indicates steric interference. The hydrogen
and hydroxyl groups present are close enough to each other
that a certain amount of strain exists to "bend"
them out of the way of each other.

        This is why boiling d^1-THC or THC containing material
in an appropriate (see below) solvent with catalytic
amounts of an appropriate (see below) acid, will
bring about isomerization to d^1(6)-THC :

                      *
                Me  H   H   OH
                 \   \ /     \
                  C---C       C---C
                 //    \     //   \\
                C       C---C       C---Pentyl
                 \     /     \     /
                  C---C       C===C
                       \     /
                        C---O
                       / \            C  H  O
                      Me  Me           21 30 2

 d1(6)-THC : an isomer with significantly more heat stability,
             and approximately equivalent biological activity.

Note (*) the hydrogens marked by the asterisk now have much
less steric hindrance with the hydroxyl group than
the single hydrogen in d^1-THC, even though there are two of them.
The reason is that in d^1-THC the hydrogen and hydroxyl
are forced by the ring structure of the molecule to coexist
in the same plane. With d^1(6)-THC, the groups interact in a
staggered conformation.
Something like this:           H
                            H  O  H
                             \ | /

----------------------------------------------------

                Me          OH
                 \           \
                  C===C       C---C
                 /     \     //   \\
                C       C---C       C---Pentyl
                 \     /     \     /
                  C---C       C===C
                       \     /
                        C  HO
                      // \            C  H  O
                    H C   Me           21 30 2
                      H

 Cannabidiol: inactive isomer of THC often present in equivalent or
              greater concentrations than THC itself. Can be easilly
              isomerized into d1(6)-THC.

-----------------------------------------------------

                Me          OH
                 \           \
                  C---C       C---C
                 //   \\     //   \\
                C       C---C       C---Pentyl
                 \     /     \     /
                  C===C       C===C
                       \     /
                        C---O
                       / \            C  H  O
                      Me  Me           21 30 2

Cannabinol : oxidation product of THC, inactive.
-----------------------------------------------------




                Watch this space for more;

                Peter Jordan
                (pjordan@amisk.cs.ualberta.ca)