Samir A. Ross

Potency Trends of Δ9‐THC and Other Cannabinoids in Confiscated Cannabis Preparations from 1993 to 2008*

Abstract:  The University of Mississippi has a contract with the National Institute on Drug Abuse (NIDA) to carry out a variety of research activities dealing with cannabis, including the Potency Monitoring (PM) program, which provides analytical potency data on cannabis preparations confiscated in the United States. This report provides data on 46,211 samples seized and analyzed by gas chromatography‐flame ionization detection (GC‐FID) during 1993–2008. The data showed an upward trend in the mean Δ9‐tetrahydrocannabinol (Δ9‐THC) content of all confiscated cannabis preparations, which increased from 3.4% in 1993 to 8.8% in 2008. Hashish potencies did not increase consistently during this period; however, the mean yearly potency varied from 2.5–9.2% (1993–2003) to 12.0–29.3% (2004–2008). Hash oil potencies also varied considerably during this period (16.8 ± 16.3%). The increase in cannabis preparation potency is mainly due to the increase in the potency of nondomestic versus domestic samples.

Potency Trends of Δ9-THC and Other Cannabinoids in Confiscated Marijuana from 1980–1997

The analysis of 35,312 cannabis preparations confiscated in the USA over a period of 18 years for delta-9-tetrahydrocannabinol (delta9-THC) and other major cannabinoids is reported. Samples were identified as cannabis, hashish, or hash oil. Cannabis samples were further subdivided into marijuana (loose material, kilobricks and buds), sinsemilla, Thai sticks and ditchweed. The data showed that more than 82% of all confiscated samples were in the marijuana category for every year except 1980 (61%) and 1981 (75%). The potency (concentration of delta9-THC) of marijuana samples rose from less than 1.5% in 1980 to approximately 3.3% in 1983 and 1984, then fluctuated around 3% till 1992. Since 1992, the potency of confiscated marijuana samples has continuously risen, going from 3.1% in 1992 to 4.2% in 1997. The average concentration of delta9-THC in all cannabis samples showed a gradual rise from 3% in 1991 to 4.47% in 1997. Hashish and hash oil, on the other hand, showed no specific potency trends. Other major cannabinoids [cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC)] showed no significant change in their concentration over the years.

Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.

The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Delta(9)-THC and Delta(8)-THC showed a U-shaped dose response with only Delta(9)-THC showing significant antidepressant-like effects at 2.5 mg/kg (p<0.05) in the FST. The cannabinoids cannabigerol (CBG) and cannabinol (CBN) did not produce antidepressant-like actions up to 80 mg/kg in the mouse FST, while cannabichromene (CBC) and cannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of Delta(9)-THC and CBC was further confirmed in the TST. Delta(9)-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80 mg/kg doses (p<0.01). Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.

Variance of common flavonoids by brand of grapefruit juice

Nine commercial brands of grapefruit juice were analyzed for their flavonoid content by HPLC to determine if significant brand-to-brand variance in grapefruit juice flavonoid content exists. Flavonoid glycosides narirutin, naringin, hesperidin, neohesperidin, didymin, and poncirin have been identified in all the grapefruit juices examined. The aglycone quercetin was detected in only two brands. All the juices were free from methoxylated flavonoid aglycones. There was a significant difference in the amounts of total flavonoids and individual flavonoids in the nine brands. The concentration of total flavonoids ranged between 19.44 and 84.28 mg/100 ml juice. Naringin was found to be the major flavonoid followed by narirutin and hesperidin. Their concentrations ranged from 14.56 to 63.8; 2.25 to 12.20; and 0.24 to 3.12 mg/100 ml juice, respectively.

Cannabinoid ester constituents from high-potency Cannabis sativa.

Eleven new cannabinoid esters, together with three known cannabinoid acids and Delta9-tetrahydrocannabinol ( Delta9-THC ), were isolated from a high-potency variety of Cannabis sativa. The structures were determined by extensive spectroscopic analyses to be beta-fenchyl Delta9-tetrahydrocannabinolate ( 1), epi-bornyl Delta9-tetrahydrocannabinolate ( 2), alpha-terpenyl Delta9-tetrahydrocannabinolate ( 3), 4-terpenyl Delta 9-tetrahydrocannabinolate ( 4), alpha-cadinyl Delta9-tetrahydrocannabinolate ( 5), gamma-eudesmyl Delta9-tetrahydrocannabinolate ( 6), gamma-eudesmyl cannabigerolate ( 7), 4-terpenyl cannabinolate ( 8), bornyl Delta9-tetrahydrocannabinolate ( 9), alpha-fenchyl Delta9-tetrahydrocannabinolate ( 10), alpha-cadinyl cannabigerolate ( 11), Delta9-tetrahydrocannabinol ( Delta9-THC ), Delta9-tetrahydrocannabinolic acid A ( Delta9-THCA ), cannabinolic acid A ( CBNA), and cannabigerolic acid ( CBGA). Compound 8 showed moderate antimicrobial activity against Candida albicans ATCC 90028 with an IC 50 value of 8.5 microg/mL. The isolated acids and the ester-containing fractions showed low affinity to the CB-1 receptor. [corrected]

Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity.

Twelve artemisinin acetal dimers were synthesized and tested for antitumor activity in the National Cancer Institute (NCI) in vitro human tumor 60 cell line assay, producing a mean GI(50) concentration between 8.7 (least active) and 0.019 microM (most active). The significant activity of the compounds in this preliminary screen led to additional in vitro antitumor and antiangiogenesis studies. Several active dimers were also evaluated in the in vivo NCI hollow fiber assay followed by a preliminary xenograft study. The title compounds were found to be active against solid tumor-derived cell lines and showed good correlation with other artemisinin-based molecules in the NCI database. The dimers were also evaluated for their antimalarial and antileishmanial activities. The antimalarial activity ranged from 0.3 to 32 nM (IC(50)), compared to 9.9 nM for artemisinin.

Mangostanaxanthones I and II, new xanthones from the pericarp of Garcinia mangostana.

Two new xanthones: mangostanaxanthones I (3) and II (5) were isolated from the pericarp of Garcinia mangostana, along with four known xanthones: 9-hydroxycalabaxanthone (1), parvifolixanthone C (2), α-mangostin (4), and rubraxanthone (6). Their structures were elucidated on the basis of IR, UV, 1D, 2D NMR, and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their antioxidant, antimicrobial, and quorum-sensing inhibitory activities. Compounds 3 and 5 displayed promising antioxidant activity with IC50 12.07 and 14.12 μM, respectively using DPPH assay. Compounds 4-6 had weak to moderate activity against Escherichia coli and Staphylococcus aureus, while demonstrated promising action against Bacillus cereus with MICs 0.25, 1.0, and 1.0mg/mL, respectively. The tested compounds were inactive against Candida albicans. However, they showed selective antifungal potential toward Aspergillus fumigatus. Compounds 3 and 4 possessed quorum-sensing inhibitory activity against Chromobacterium violaceum ATCC 12472.

Antiparasitic, nematicidal and antifouling constituents from Juniperus berries

A bioassay‐guided fractionation of Juniperus procera berries yielded antiparasitic, nematicidal and antifouling constituents, including a wide range of known abietane, pimarane and labdane diterpenes. Among these, abieta‐7,13‐diene (1) demonstrated in vitro antimalarial activity against Plasmodium falciparum D6 and W2 strains (IC50 = 1.9 and 2.0 µg/mL, respectively), while totarol (6), ferruginol (7) and 7β‐hydroxyabieta‐8,13‐diene‐11,12‐dione (8) inhibited Leishmania donovani promastigotes with IC50 values of 3.5–4.6 µg/mL. In addition, totarol demonstrated nematicidal and antifouling activities against Caenorhabditis elegans and Artemia salina at a concentration of 80 µg/mL and 1 µg/mL, respectively. The resinous exudate of J. virginiana afforded known antibacterial E‐communic acid (4) and 4‐epi‐abietic acid (5), while the volatile oil from its trunk wood revealed large quantities of cedrol (9). Using GC/MS, the two known abietanes totarol (6) and ferruginol (7) were identified from the berries of J. procera, J. excelsa and J. phoenicea. Copyright

Cyclooxygenase‐2 inhibitory and antioxidant compounds from the truffle Elaphomyces granulatus

The ethanol extract of fruiting bodies of Elaphomyces granulatus, a truffle‐like fungus, was evaluated for cyclooxygenase‐2 (COX‐2) enzyme inhibitory and antioxidant activities. Inhibition of COX‐2 activity was evaluated in mouse macrophages (RAW 264.7). The extract of E. granulatus caused a 68% inhibition of COX‐2 activity at 50 µg/mL. Bioassay‐guided investigation led to the isolation and identification of two active compounds, syringaldehyde and syringic acid. Syringaldehyde moderately inhibited COX‐2 activity with an IC50 of 3.5 µg/mL, while syringic acid strongly inhibited COX‐2 activity with an IC50 of 0.4 µg/mL. The antioxidant activity of the extract and isolated compounds was evaluated in HL‐60 cells by the DCFH‐DA method. The extract of E. granulatus showed a potent antioxidant effect, with an IC50 of 41 µg/mL. Of the pure compounds, syringic acid displayed a strong antioxidant activity, with an IC50 of 0.7 µg/mL, while syringaldehyde showed no activity in the assay. Copyright

Brevione A. The first member of a novel family of bioactive spiroditerpenoids isolated from Penicillium brevicompactum Dierckx

Abstract (+)-Brevione A, the first member of a novel family of bioactive spiroditerpenoids, a potential allelopathic agent, has been isolated from the ethyl acetate active fractions of the aqueous acetone extracts of semi-solid fermented Penicillium brevicompactum Dierckx. The structure displays the novel spiroditerpenoid skeleton of breviane. The structure elucidation of brevione A was performed by homo- and hetero-nuclear 2D NMR spectral data. On the basis of combined studies of the theoretical conformations and NOEDIFF data, its relative stereochemistry is proposed.