Monthly Archives: February 2014

Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes.

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“The inhibition of adenylate cyclase activity by cannabimimetic compounds in a membrane fraction from cultured neuroblastoma cells has been examined. The inhibition was shown to be concentration-dependent over a nanomolar range for both delta 9-tetrahydrocannabinol and its synthetic analog…

This study points to the similarities between the enzyme inhibition by cannabimimetic compounds and by muscarinic cholinergic compounds. It is inferred that the cannabimimetic compounds must act via regulatory mechanisms similar to those operating for receptor-mediated inhibition of adenylate cyclase.”

http://www.ncbi.nlm.nih.gov/pubmed/2984538

Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes.

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“Adenylate cyclase in plasma membranes was inhibited by micromolar concentrations of delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol…

The inhibition of adenylate cyclase was specific for psychoactive cannabinoids, since cannabinol and cannabidiol produced minimal or no response…

Possible mechanisms for the effects of cannabinoid drugs on adenylate cyclase activity…”

http://www.ncbi.nlm.nih.gov/pubmed/6092901

Cannabinoid inhibition of adenylate cyclase: relative activity of constituents and metabolites of marihuana.

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“delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.”

http://www.ncbi.nlm.nih.gov/pubmed/3601007

Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L.

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“Chemical investigation of the pollen grain collected from male plants of Cannabis sativa L. resulted in the isolation for the first time of two flavonol glycosides from the methanol extract, and the identification of 16 cannabinoids in the hexane extract. The two glycosides were identified as kaempferol 3-O-sophoroside and quercetin 3-O-sophoroside by spectroscopic methods including high-field two-dimensional NMR experiments. The characterisation of each cannabinoid was performed by GC-FID and GC-MS analyses and by comparison with both available reference cannabinoids and reported data. The identified cannabinoids were delta9-tetrahydrocannabiorcol, cannabidivarin, cannabicitran, delta9-tetrahydrocannabivarin, cannabicyclol, cannabidiol, cannabichromene, delta9-tetrahydrocannabinol, cannabigerol, cannabinol, dihydrocannabinol, cannabielsoin, 6a, 7, 10a-trihydroxytetrahydrocannabinol, 9, 10-epoxycannabitriol, 10-O-ethylcannabitriol, and 7, 8-dehydro-10-O-ethylcannabitriol.”

http://www.ncbi.nlm.nih.gov/pubmed/15688956

Recent advances in Cannabis sativa research: biosynthetic studies and its potential in biotechnology.

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“Cannabinoids, consisting of alkylresorcinol and monoterpene groups, are the unique secondary metabolites that are found only in Cannabis sativa. Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabichromene (CBC) are well known cannabinoids and their pharmacological properties have been extensively studied. Recently, biosynthetic pathways of these cannabinoids have been successfully established. Several biosynthetic enzymes including geranylpyrophosphate:olivetolate geranyltransferase, tetrahydrocannabinolic acid (THCA) synthase, cannabidiolic acid (CBDA) synthase and cannabichromenic acid (CBCA) synthase have been purified from young rapidly expanding leaves of C. sativa. In addition, molecular cloning, characterization and localization of THCA synthase have been recently reported. THCA and cannabigerolic acid (CBGA), its substrate, were shown to be apoptosis-inducing agents that might play a role in plant defense. Transgenic tobacco hairy roots expressing THCA synthase can produce THCA upon feeding of CBGA. These results open the way for biotechnological production of cannabinoids in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/17691992

Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

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“… we have reported here for the first time the potent and efficacious modulatory effects by some phytocannabinoids on TRPA1- and TRPM8-mediated [Ca2+]ielevation…

Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.”

http://jpet.aspetjournals.org/content/325/3/1007.long

Thermal isomerization of cannabinoid analogues.

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“Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabichromene (CBC) and Delta(1)-tetrahydrocannabinol (THC), respectively] is predicted in silico and demonstrated experimentally. Density functional theory calculations support a similar isomerization mechanism for the corresponding plant cannabinoids. Docking studies suggest that THC(an), although nonaromatic, has a CB(1) receptor binding affinity similar to that of natural THC.”

http://www.ncbi.nlm.nih.gov/pubmed/19919138

Cannabichromene and tetrahydrocannabinol determination in mouse blood and brain by gas chromatography-mass spectrometry.

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“Cannabichromene (CBC) is a phytocannabinoid, the second most abundant cannabinoid quantitatively in marijuana. CBC has been shown to produce antinociception and anti-inflammatory effects…”

 http://www.ncbi.nlm.nih.gov/pubmed/21871159

The effect of cannabichromene on adult neural stem/progenitor cells.

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“Apart from the psychotropic compound Δ(9)-tetrahydrocannabinol (THC), evidence suggests that other non-psychotropic phytocannabinoids are also of potential clinical use.

This study aimed at elucidating the effect of major non-THC phytocannabinoids on the fate of adult neural stem progenitor cells (NSPCs), which are an essential component of brain function in health as well as in pathology.

We tested three compounds: cannabidiol, cannabigerol, and cannabichromene (CBC), and found that CBC has a positive effect on the viability of mouse NSPCs during differentiation in vitro.

Taken together, our results suggest that CBC raises the viability of NSPCs while inhibiting their differentiation into astroglia, possibly through up-regulation of ATP and adenosine signalling.”

http://www.ncbi.nlm.nih.gov/pubmed/23941747

Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.

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“Plant cannabinoids, like Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other ‘thermo-TRP’s’, the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract…

CONCLUSIONS:

Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract.”

http://www.ncbi.nlm.nih.gov/pubmed/21726418