were used to identify their structures (Fig.7.1) as mono- or sesquiterpenoid esters
ofD^9 -tetrahydrocannabinolic acid A, the precursor ofD^9 -THC (Ahmed et al. 2008 ).
A dimeric cannabinoid (cannabisol, 18 ) was isolated by Zulfiqar et al. from the
extract of high CBG Cannabis plants. The extract was subjected to Si gel vacuum
liquid chromatography followed byflash silica gel column chromatography to give
cannabisol. Cannabisol displayed two molecular ion peaks in the GC-MS atm/z
314 and m/z 328, corresponding toD^9 -THC and 2-methyl-D^9 -THC respectively
(Zulfiqar et al. 2012 ).
In 2015, Radwan et al. isolated and identified 8a-hydroxy-D^9 -tetra-
hydrocannabinol ( 19 ), 8b-hydroxy-D^9 -tetrahydrocannabinol ( 20 ) and 11-acetoxy-
D^9 -tetrahydrocannabinolic acid A ( 21 ) from a high potencyC. sativa.D^9 -THC
aldehyde ( 22 ) and 8-oxo-D^9 -THC ( 23 ) were also isolated from the same variety
(Fig.7.1). The hexane extract was subjected to silica gel VLC, eluting with EtOAc–
n-hexane with gradient elution. The collected fractions were purified using different
types of chromatography including Si gel column, C18flash column, C18-SPE
column, Si gel HPLC, Sephadex LH-20 andfinally reversed-phase HPLC (Ahmed
et al. 2015 ; Radwan et al. 2015 ).
7.3 D
9
-THC Pharmaceutical Preparation
As of today only one pharmaceutical product is on the market (mainly in Europe
and Canada) that containsD^9 -THC, Sativex®. Sativex®is a mixture of two cannabis
extracts: a high THC variety extract and a high CBD variety extract in a proportion
to produce equal amounts of THC and CBD. It is indicated for the treatment of
neuropathic pain and spasticity in patients with Multiple Sclerosis (MS). It is
currently under clinical trials in USA for the treatment of cancer pain.
Marinol®/Dronabinol is a syntheticD^9 -THC, FDA approved in United States as
Schedule II drug for the treatment of nausea and vomiting for patients in cancer
treatment in 1985, and appetite stimulant for AIDS patients in 1992. In July 1999,
Marinol®was moved to Schedule III.
7.4 Stability ofD^9 -THC
The stability of cannabis oil during its long term storage in different conditions is
very crucial point to be studied. Trofin et al. ( 2012 ) studied the content of major
cannabinoids, namely tetrahydrocannabinol (D^9 -THC), cannabinol (CBN), and
cannabidiol (CBD) contained in two batch samples of cannabis oil. The samples
stored over a period of four years in darkness at 4 °C and in laboratory light at 22 °
C. The analysis showed a stead decay ofD^9 -THC over the entire storage period
from a very high initial content up to a relatively lowfinal content. A slight dif-
ference regarding the degree of decay of D^9 -THC between the two storage
174 M.M. Radwan et al.