https://link.springer.com/article/10.1007/s10722-015-0254-2
I CAN'T POST THE FULL LINK, TRY ADDING THE SECOND ONE BELOW TO THE END OF THE FIRST BELOW. THAT WORKS.
https://link.springer.com/article/
10.1007%2Fs10722-015-0254-2
Size matters: evolution of large drug-secreting resin glands
in elite pharmaceutical strains of Cannabis sativa (marijuana)
Ernest Small . Steve G. U. Naraine
Genet Resour Crop Evol
doi: 10.1016/j.phytochem.2012.11.001
----------------------------------------------
https://link.springer.com/article/10....722-015-0253-3
https://link.springer.com/article/
10.1007%2Fs10722-015-0253-3
OR
https://link.springer.com/article/
10.1007/s10722-015-0253-3#page-1
Expansion of female sex organs in response to prolonged
virginity in Cannabis sativa (marijuana)
Ernest Small . Steve G. U. Naraine
Genet Resour Crop Evol
Abstract
Female flowers of Cannabis sativa in wild-growing populations and in hemp plantations are almost always well supplied with pollen. The style-stigma portion of the pistils of such plants was found to average only about 3 mm in length and to invariably be two-branched. By contrast, “buds” (congested female inflorescences), the standard form of marijuana now produced in the illicit and medicinal marijuana sectors, are protected against pollen. This report documents that in the absence of pollen, the style-stigma parts of virgin pistils expand notably, average over 8 mm in length, and tend to develop more than two branches and to increase in girth. From an evolutionary viewpoint, this expansion of pollen-receptive tissue is an apparent adaptation for increasing the probability of fertilizing the females when males are extremely scarce. From a practical viewpoint, the expanded presence of stigma tissues may be both advantageous and disadvantageous. The high-THC secretory gland heads of Cannabis tend to fall away from marijuana buds, significantly decreasing pharmacological potency, but many gland heads become stuck to the receptive papillae of the stigmas, reducing the loss. Although stigmas constitute a small proportion of marijuana, their distinctive chemistry could have health effects.
-------------------------------------------------
https://www.sciencedirect.com/science/article/pii/S0031942215001181
Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase in Cannabis sativa L. and its relationship with chemical phenotype
Chiara Onofri a, Etienne P.M. de Meijer b, Giuseppe Mandolino a,
a Consiglio per la ricerca in agricoltura e l’analisi dell’economia agraria, Centro di Ricerca per le Colture Industriali, via di Corticella 133, 40128 Bologna, Italy
b GW Pharmaceuticals PLC, Ground Floor South Wing, Kingsgate House, Newbury Road, Andover SP10 4DU, United Kingdom
Received 2 October 2014, Revised 21 March 2015, Available online 9 April 2015
Abstract
Sequence variants of THCA- and CBDA-synthases were isolated from different Cannabis sativa L. strains expressing various wild-type and mutant chemical phenotypes (chemotypes). Expressed and complete sequences were obtained from mature inflorescences. Each strain was shown to have a different specificity and/or ability to convert the precursor CBGA into CBDA and/or THCA type products. The comparison of the expressed sequences led to the identification of different mutations, all of them due to SNPs. These SNPs were found to relate to the cannabinoid composition of the inflorescence at maturity and are therefore proposed to have a functional significance. The amount of variation was found to be higher within the CBDAS sequence family than in the THCAS family, suggesting a more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore consider CBDAS as the ancestral type of these synthases.
-----------
Does this mean THC synthase evolved or mutated from CBD synthase? Maybe man helped select the few that were THC synthase however they came to be, and spread them worldwide? I would not be surprised......
Man selects for THC and against CBD, in the case of Ganja, he selects for high resin contents regardless of Cannabinoid for Hashish, for hemp until recently there was little selections for Cannabinoids until after Cannabis became illegal less then 100 years ago, and very recently for CBD for mediacal varieties.
-SamS
------------------
https://onlinelibrary.wiley.com/doi/10.1111/bph.12944/full
Are cannabidiol and Δ9-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review
John M McPartland1, Marnie Duncan, Vincenzo Di Marzo and Roger G Pertwee
Article first published online: 8 JAN 2015
© 2014 The British Pharmacological Society
Issue
British Journal of Pharmacology
Volume 172, Issue 3, pages 737–753, February 2015
Abstract
Based upon evidence that the therapeutic properties of Cannabis preparations are not solely dependent upon the presence of Δ9-tetrahydrocannabinol (THC), pharmacological studies have been recently carried out with other plant cannabinoids (phytocannabinoids), particularly cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV). Results from some of these studies have fostered the view that CBD and THCV modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. Here, we review in vitro and ex vivo mechanistic studies of CBD and THCV, and synthesize data from these studies in a meta-analysis. Synthesized data regarding mechanisms are then used to interpret results from recent pre-clinical animal studies and clinical trials. The evidence indicates that CBD and THCV are not rimonabant-like in their action and thus appear very unlikely to produce unwanted CNS effects. They exhibit markedly disparate pharmacological profiles particularly at CB1 receptors: CBD is a very low-affinity CB1 ligand that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant. These cannabinoids illustrate how in vitro mechanistic studies do not always predict in vivo pharmacology and underlie the necessity of testing compounds in vivo before drawing any conclusion on their functional activity at a given target.
-------------------------------
https://www.sciencedirect.com/science...3194221200475X
Try this , to correct it remove the empty space between the last w and the . in the http below
https://www .sciencedirect.com/science/article/pii/S003194221200475X
Phytochemistry
Volume 87, March 2013, Pages 51–59
Analysis of cannabinoids in laser-microdissected trichomes of medicinal Cannabis sativa using LCMS and cryogenic NMR
Nizar Happyanaa, b, Sara Agnoletc, Remco Muntendamd, Annie Van Dame, Bernd Schneiderc, Oliver Kaysera, ,
a Department of Technical Biochemistry, Technical University of Dortmund, Technische Biochemie, Emil-Figge-Strasse 66, D-44227 Dortmund, Germany
b Department of Chemistry, Bandung Institute of Technology, Jl. Ganesha 10, Bandung 40132, Indonesia
c Research Group Biosynthesis/NMR, Max Planck Institute for Chemical Ecology, Hans-Knöll-Straße 8, 07745 Jena, Germany
d Department of Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands
e Mass Spectrometry Core Facility, Center for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands
Abstract
Trichomes, especially the capitate-stalked glandular hairs, are well known as the main sites of cannabinoid and essential oil production of Cannabis sativa. In this study the distribution and density of various types of Cannabis sativa L. trichomes, have been investigated by scanning electron microscopy (SEM). Furthermore, glandular trichomes were isolated over the flowering period (8 weeks) by laser microdissection (LMD) and the cannabinoid profile analyzed by LCMS. Cannabinoids were detected in extracts of 25–143 collected cells of capitate-sessile and capitate stalked trichomes and separately in the gland (head) and the stem of the latter. Δ9-Tetrahydrocannabinolic acid [THCA (1)], cannabidiolic acid [CBDA (2)], and cannabigerolic acid [CBGA (3)] were identified as most-abundant compounds in all analyzed samples while their decarboxylated derivatives, Δ9-tetrahydrocannabinol [THC (4)], cannabidiol [CBD (5)], and cannabigerol [CBG (6)], co-detected in all samples, were present at significantly lower levels. Cannabichromene [CBC (8)] along with cannabinol (CBN (9)) were identified as minor compounds only in the samples of intact capitate-stalked trichomes and their heads harvested from 8-week old plants. Cryogenic nuclear magnetic resonance spectroscopy (NMR) was used to confirm the occurrence of major cannabinoids, THCA (1) and CBDA (2), in capitate-stalked and capitate-sessile trichomes. Cryogenic NMR enabled the additional identification of cannabichromenic acid [CBCA (7)] in the dissected trichomes, which was not possible by LCMS as standard was not available. The hereby documented detection of metabolites in the stems of capitate-stalked trichomes indicates a complex biosynthesis and localization over the trichome cells forming the glandular secretion unit.
-----------------------------------------
https://www.sciencedirect.com/science/article/pii/S0926669013000526
Industrial Crops and Products
Volume 46, April 2013, Pages 269–273
Ethephon application stimulats cannabinoids and plastidic terpenoids production in Cannabis sativa at flowering stage
Hakimeh Mansouri, , Fatemeh Salari, Zahra Asrar
Received 27 November 2012, Accepted 4 January 2013, Available online 1 March 2013
Abstract
We studied the effect of ethephon on levels of the major cannabinoids (tetrahydrocannabinol and cannabidiol) and chlorophyll, carotenoids and α-tocopherol in Cannabis sativa at productive stage. Results revealed that ethephon increased THC content of leaf in male and female plants and of male flowers. However, ethephon unable to enhancing THC content in female flowers. Treatment with etheohon increased CBD content in male and female leaf and female flowers. The treatment of male flowers with low ethephon concentration caused an increase, and those treated with high ethephon concentration resulted in a decrease in CBD content. The lowest level of ethephon (1 μM) enhanced chlorophyll a, b and total chlorophyll in male and female plants. Both sexes treated with ethephon showed an increase in carotenoids content, but 1 μM ethephon had the stronger effect in this regards. Male and female plants had a higher content of α-tocopherol when treated with ethephon. These results showed ethephon is a suitable treatment for increasing cannabinoids and α-tocopherol in productive stage of cannabis and there was not a relation between primary and secondary terpenoids.
Highlights
► Ethephon treatment has considerable effects on increasing of cannabinoids in male and female cannabis. ► There is no correlation between cannabinoids and other plastidial terpenoids. ► Using of ethephon treatment in flowering stage do not adverse effect on plant growth.
https://www.ncbi.nlm.nih.gov/pubmed/26000707
J Nat Prod. 2015 May 22. [Epub ahead of print]
Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa.
Radwan MM1, ElSohly MA1, El-Alfy AT1, Ahmed SA1, Slade D1, Husni AS1, Manly SP1, Wilson L1, Seale S1, Cutler SJ1, Ross SA1.
Abstract
Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ9-tetrahydrocannabinol (1), 8β-hydroxy-Δ9-tetrahydrocannabinol (2), 10α-hydroxy-Δ8-tetrahydrocannabinol (3), 10β-hydroxy-Δ8-tetrahydrocannabinol (4), 10α-hydroxy-Δ9,11-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ9-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ9-tetrahydrocannabinol, and Δ8-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied. The results indicated that compound 3, with the highest affinity to the CB1 receptors, exerted the most potent cannabimimetic-like actions in the tetrad assay, while compound 4 showed partial cannabimimetic actions. Compound 2, on the other hand, displayed a dose-dependent hypolocomotive effect only.
I CAN'T POST THE FULL LINK, TRY ADDING THE SECOND ONE BELOW TO THE END OF THE FIRST BELOW. THAT WORKS.
https://link.springer.com/article/
10.1007%2Fs10722-015-0254-2
Size matters: evolution of large drug-secreting resin glands
in elite pharmaceutical strains of Cannabis sativa (marijuana)
Ernest Small . Steve G. U. Naraine
Genet Resour Crop Evol
doi: 10.1016/j.phytochem.2012.11.001
----------------------------------------------
https://link.springer.com/article/10....722-015-0253-3
https://link.springer.com/article/
10.1007%2Fs10722-015-0253-3
OR
https://link.springer.com/article/
10.1007/s10722-015-0253-3#page-1
Expansion of female sex organs in response to prolonged
virginity in Cannabis sativa (marijuana)
Ernest Small . Steve G. U. Naraine
Genet Resour Crop Evol
Abstract
Female flowers of Cannabis sativa in wild-growing populations and in hemp plantations are almost always well supplied with pollen. The style-stigma portion of the pistils of such plants was found to average only about 3 mm in length and to invariably be two-branched. By contrast, “buds” (congested female inflorescences), the standard form of marijuana now produced in the illicit and medicinal marijuana sectors, are protected against pollen. This report documents that in the absence of pollen, the style-stigma parts of virgin pistils expand notably, average over 8 mm in length, and tend to develop more than two branches and to increase in girth. From an evolutionary viewpoint, this expansion of pollen-receptive tissue is an apparent adaptation for increasing the probability of fertilizing the females when males are extremely scarce. From a practical viewpoint, the expanded presence of stigma tissues may be both advantageous and disadvantageous. The high-THC secretory gland heads of Cannabis tend to fall away from marijuana buds, significantly decreasing pharmacological potency, but many gland heads become stuck to the receptive papillae of the stigmas, reducing the loss. Although stigmas constitute a small proportion of marijuana, their distinctive chemistry could have health effects.
-------------------------------------------------
https://www.sciencedirect.com/science/article/pii/S0031942215001181
Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase in Cannabis sativa L. and its relationship with chemical phenotype
Chiara Onofri a, Etienne P.M. de Meijer b, Giuseppe Mandolino a,
a Consiglio per la ricerca in agricoltura e l’analisi dell’economia agraria, Centro di Ricerca per le Colture Industriali, via di Corticella 133, 40128 Bologna, Italy
b GW Pharmaceuticals PLC, Ground Floor South Wing, Kingsgate House, Newbury Road, Andover SP10 4DU, United Kingdom
Received 2 October 2014, Revised 21 March 2015, Available online 9 April 2015
Abstract
Sequence variants of THCA- and CBDA-synthases were isolated from different Cannabis sativa L. strains expressing various wild-type and mutant chemical phenotypes (chemotypes). Expressed and complete sequences were obtained from mature inflorescences. Each strain was shown to have a different specificity and/or ability to convert the precursor CBGA into CBDA and/or THCA type products. The comparison of the expressed sequences led to the identification of different mutations, all of them due to SNPs. These SNPs were found to relate to the cannabinoid composition of the inflorescence at maturity and are therefore proposed to have a functional significance. The amount of variation was found to be higher within the CBDAS sequence family than in the THCAS family, suggesting a more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore consider CBDAS as the ancestral type of these synthases.
-----------
Does this mean THC synthase evolved or mutated from CBD synthase? Maybe man helped select the few that were THC synthase however they came to be, and spread them worldwide? I would not be surprised......
Man selects for THC and against CBD, in the case of Ganja, he selects for high resin contents regardless of Cannabinoid for Hashish, for hemp until recently there was little selections for Cannabinoids until after Cannabis became illegal less then 100 years ago, and very recently for CBD for mediacal varieties.
-SamS
------------------
https://onlinelibrary.wiley.com/doi/10.1111/bph.12944/full
Are cannabidiol and Δ9-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review
John M McPartland1, Marnie Duncan, Vincenzo Di Marzo and Roger G Pertwee
Article first published online: 8 JAN 2015
© 2014 The British Pharmacological Society
Issue
British Journal of Pharmacology
Volume 172, Issue 3, pages 737–753, February 2015
Abstract
Based upon evidence that the therapeutic properties of Cannabis preparations are not solely dependent upon the presence of Δ9-tetrahydrocannabinol (THC), pharmacological studies have been recently carried out with other plant cannabinoids (phytocannabinoids), particularly cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV). Results from some of these studies have fostered the view that CBD and THCV modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. Here, we review in vitro and ex vivo mechanistic studies of CBD and THCV, and synthesize data from these studies in a meta-analysis. Synthesized data regarding mechanisms are then used to interpret results from recent pre-clinical animal studies and clinical trials. The evidence indicates that CBD and THCV are not rimonabant-like in their action and thus appear very unlikely to produce unwanted CNS effects. They exhibit markedly disparate pharmacological profiles particularly at CB1 receptors: CBD is a very low-affinity CB1 ligand that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant. These cannabinoids illustrate how in vitro mechanistic studies do not always predict in vivo pharmacology and underlie the necessity of testing compounds in vivo before drawing any conclusion on their functional activity at a given target.
-------------------------------
https://www.sciencedirect.com/science...3194221200475X
Try this , to correct it remove the empty space between the last w and the . in the http below
https://www .sciencedirect.com/science/article/pii/S003194221200475X
Phytochemistry
Volume 87, March 2013, Pages 51–59
Analysis of cannabinoids in laser-microdissected trichomes of medicinal Cannabis sativa using LCMS and cryogenic NMR
Nizar Happyanaa, b, Sara Agnoletc, Remco Muntendamd, Annie Van Dame, Bernd Schneiderc, Oliver Kaysera, ,
a Department of Technical Biochemistry, Technical University of Dortmund, Technische Biochemie, Emil-Figge-Strasse 66, D-44227 Dortmund, Germany
b Department of Chemistry, Bandung Institute of Technology, Jl. Ganesha 10, Bandung 40132, Indonesia
c Research Group Biosynthesis/NMR, Max Planck Institute for Chemical Ecology, Hans-Knöll-Straße 8, 07745 Jena, Germany
d Department of Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands
e Mass Spectrometry Core Facility, Center for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands
Abstract
Trichomes, especially the capitate-stalked glandular hairs, are well known as the main sites of cannabinoid and essential oil production of Cannabis sativa. In this study the distribution and density of various types of Cannabis sativa L. trichomes, have been investigated by scanning electron microscopy (SEM). Furthermore, glandular trichomes were isolated over the flowering period (8 weeks) by laser microdissection (LMD) and the cannabinoid profile analyzed by LCMS. Cannabinoids were detected in extracts of 25–143 collected cells of capitate-sessile and capitate stalked trichomes and separately in the gland (head) and the stem of the latter. Δ9-Tetrahydrocannabinolic acid [THCA (1)], cannabidiolic acid [CBDA (2)], and cannabigerolic acid [CBGA (3)] were identified as most-abundant compounds in all analyzed samples while their decarboxylated derivatives, Δ9-tetrahydrocannabinol [THC (4)], cannabidiol [CBD (5)], and cannabigerol [CBG (6)], co-detected in all samples, were present at significantly lower levels. Cannabichromene [CBC (8)] along with cannabinol (CBN (9)) were identified as minor compounds only in the samples of intact capitate-stalked trichomes and their heads harvested from 8-week old plants. Cryogenic nuclear magnetic resonance spectroscopy (NMR) was used to confirm the occurrence of major cannabinoids, THCA (1) and CBDA (2), in capitate-stalked and capitate-sessile trichomes. Cryogenic NMR enabled the additional identification of cannabichromenic acid [CBCA (7)] in the dissected trichomes, which was not possible by LCMS as standard was not available. The hereby documented detection of metabolites in the stems of capitate-stalked trichomes indicates a complex biosynthesis and localization over the trichome cells forming the glandular secretion unit.
-----------------------------------------
https://www.sciencedirect.com/science/article/pii/S0926669013000526
Industrial Crops and Products
Volume 46, April 2013, Pages 269–273
Ethephon application stimulats cannabinoids and plastidic terpenoids production in Cannabis sativa at flowering stage
Hakimeh Mansouri, , Fatemeh Salari, Zahra Asrar
Received 27 November 2012, Accepted 4 January 2013, Available online 1 March 2013
Abstract
We studied the effect of ethephon on levels of the major cannabinoids (tetrahydrocannabinol and cannabidiol) and chlorophyll, carotenoids and α-tocopherol in Cannabis sativa at productive stage. Results revealed that ethephon increased THC content of leaf in male and female plants and of male flowers. However, ethephon unable to enhancing THC content in female flowers. Treatment with etheohon increased CBD content in male and female leaf and female flowers. The treatment of male flowers with low ethephon concentration caused an increase, and those treated with high ethephon concentration resulted in a decrease in CBD content. The lowest level of ethephon (1 μM) enhanced chlorophyll a, b and total chlorophyll in male and female plants. Both sexes treated with ethephon showed an increase in carotenoids content, but 1 μM ethephon had the stronger effect in this regards. Male and female plants had a higher content of α-tocopherol when treated with ethephon. These results showed ethephon is a suitable treatment for increasing cannabinoids and α-tocopherol in productive stage of cannabis and there was not a relation between primary and secondary terpenoids.
Highlights
► Ethephon treatment has considerable effects on increasing of cannabinoids in male and female cannabis. ► There is no correlation between cannabinoids and other plastidial terpenoids. ► Using of ethephon treatment in flowering stage do not adverse effect on plant growth.
https://www.ncbi.nlm.nih.gov/pubmed/26000707
J Nat Prod. 2015 May 22. [Epub ahead of print]
Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa.
Radwan MM1, ElSohly MA1, El-Alfy AT1, Ahmed SA1, Slade D1, Husni AS1, Manly SP1, Wilson L1, Seale S1, Cutler SJ1, Ross SA1.
Abstract
Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ9-tetrahydrocannabinol (1), 8β-hydroxy-Δ9-tetrahydrocannabinol (2), 10α-hydroxy-Δ8-tetrahydrocannabinol (3), 10β-hydroxy-Δ8-tetrahydrocannabinol (4), 10α-hydroxy-Δ9,11-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ9-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ9-tetrahydrocannabinol, and Δ8-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied. The results indicated that compound 3, with the highest affinity to the CB1 receptors, exerted the most potent cannabimimetic-like actions in the tetrad assay, while compound 4 showed partial cannabimimetic actions. Compound 2, on the other hand, displayed a dose-dependent hypolocomotive effect only.
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