Tag: Cannabinoids

Δ8‐Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors

Sándor Bátkai, Partha Mukhopadhyay, Bėla Horváth, Mohanraj Rajesh, Rachel Y Gao, Anu Mahadevan, Mukkanti Amere, Natalia Battista, Aron H Lichtman, Lisa A Gauson, Mauro Maccarrone, Roger G Pertwee, Pál Pacher
British Journal of Pharmacology (2012) 165 2450–2461
DOI: 10.1111/j.1476-5381.2011.01410.x

Activation of cannabinoid CB2 receptors protects against various forms of ischaemia-reperfusion (I/R) injury. D8 -Tetrahydrocannabivarin (D8 -THCV) is a synthetic analogue of the plant cannabinoid D9 -tetrahydrocannabivarin, which exhibits anti-inflammatory effects in rodents involving activation of CB2 receptors. Here, we assessed effects of D8 -THCV and its metabolite 11-OH-D8 -THCV on CB2 receptors and against hepatic I/R injury.

Abstract

Decarboxylation Study of Acidic Cannabinoids: A Novel Approach Using Ultra-High-Performance Supercritical Fluid Chromatography/Photodiode Array-Mass Spectrometry

Mei Wang, Yan-Hong Wang, Bharathi Avula, Mohamed M. Radwan, Amira S. Wanas, John van Antwerp, Jon F. Parcher, Mahmoud A. ElSohly, and Ikhlas A. Khan
Cannabis and Cannabinoid Research
Volume 1.1, 2016 Pg 262-271
DOI: 10.1089/can.2016.0020

Decarboxylation is an important step for efficient production of the major active components in cannabis, for example, D9 -tetrahydrocannabinol (D9-THC), cannabidiol (CBD), and cannabigerol (CBG). These cannabinoids do not occur in significant concentrations in cannabis but can be formed by decarboxylation of their corresponding acids, the predominant cannabinoids in the plant. Study of the kinetics of decarboxylation is of importance for phytocannabinoid isolation and dosage formulation for medical use. Efficient analytical methods are essential for simultaneous detection of both neutral and acidic cannabinoids.

Abstract

Consumer perceptions of strain differences in Cannabis aroma

Gilbert AN, DiVerdi JA (2018)
PLoS ONE 13(2): e0192247.
Doi: 10.1371/journal.pone.0192247

The smell of marijuana (Cannabis sativa L.) is of interest to users, growers, plant breeders, law enforcement and, increasingly, to state-licensed retail businesses. The numerous varieties and strains of Cannabis produce strikingly different scents but to date there have been few, if any, attempts to quantify these olfactory profiles directly. Using standard sensory evaluation techniques with untrained consumers we have validated a preliminary olfactory lexicon for dried cannabis flower, and characterized the aroma profile of eleven strains sold in the legal recreational market in Colorado. We show that consumers perceive differences among strains, that the strains form distinct clusters based on odor similarity, and that strain aroma profiles are linked to perceptions of potency, price, and smoking interest

Abstract

Complete biosynthesis of cannabinoids and their unnatural analogues in yeast

Xiaozhou Luo, Michael A. Reiter, Leo d’Espaux, Jeff Wong, Charles M. Denby, Anna Lechner, Yunfeng Zhang, Adrian T. Grzybowski, Simon Harth, Weiyin Lin, Hyunsu Lee, Changhua Yu, John Shin, Kai Deng, Veronica T. Benites, George Wang, Edward E. K. Baidoo, Yan Chen, Ishaan Dev, Christopher J. Petzold & Jay D. Keasling1
Nature, Letter 2019
DOI: 10.1038/s41586-019-0978-9

Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia1 . Some cannabinoids, the hallmark constituents of Cannabis, and their analogues have been investigated extensively for their potential medical applications. Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a range of human ailments . However, the study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis, the low in plant abundances of nearly all of the dozens of known cannabinoids , and their structural complexity, which limits bulk chemical synthesis. Here we report the complete biosynthesis of the major cannabinoids cannabigerolic acid, Δ9 -tetrahydrocannabinolic acid, cannabidiolic acid, Δ9 – tetrahydrocannabivarinic acid and cannabidivarinic acid in Saccharomyces cerevisiae, from the simple sugar galactose. To accomplish this, we engineered the native mevalonate pathway to provide a high flux of geranyl pyrophosphate and introduced a heterologous, multi-organism-derived hexanoyl-CoA biosynthetic pathway . We also introduced the Cannabis genes that encode the enzymes involved in the biosynthesis of olivetolic acid , as well as the gene for a previously undiscovered enzyme with geranylpyrophosphate:olivetolate geranyltransferase activity and the genes for corresponding cannabinoid synthases. Furthermore, we established a biosynthetic approach that harnessed the promiscuity of several pathway genes to produce cannabinoid analogues. Feeding different fatty acids to our engineered strains yielded cannabinoid analogues with modifications in the part of the molecule that is known to alter receptor binding affinity and potency . We also demonstrated that our biological system could be complemented by simple synthetic chemistry to further expand the accessible chemical space. Our work presents a platform for the production of natural and unnatural cannabinoids that will allow for more rigorous study of these compounds and could be used in the development of treatments for a variety of human health problems.

Abstract

Combined effects of THC and caffeine on working memory in rats

Leigh V Panlilio1 , Sergi Ferré1 , Sevil Yasar2 , Eric B Thorndike1 , Charles W Schindler1 and Steven R Goldberg1
British Journal of Pharmacology (2012) 165 2529–2538
DOI: 10.1111/j.1476-5381.2011.01554.x

Cannabis and caffeine are two of the most widely used psychoactive substances. D9 -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory.

Abstract

Chemotaxonomy Of Cannabis I. Crossbreeding Between Cannabis Sativa And C. Ruderalis, With Analysis Of Cannabinoid Content

JOHN A. BEUTLER, ARA H. DER MARDEROSIAN
Economic Botany, 1978; 32(4) 387-394
DOI: 10.1007/BF02907934

A controlled cross between Cannabis sativa L. and C. ruderalis Janisch. gave progeny intermediate in both cannabinoid content and morphology. The progeny fell into two distinct populations, those whose tetrahydrocannabinol (THC) content was closer to the C. sativa parent (greater than 60% of total cannabinoids) and those whose THC content was closer to the C. ruderalis parent (less than 40% of total cannabinoids). The lower THC group was twice as frequent as the other group. Earliness of flowering, number of flowers, and height characteristics were intermediate between the parents.

Abstract

Chemometric Analysis of Cannabinoids: Chemotaxonomy and Domestication Syndrome

E. M. Mudge, S. J. Murch & P. N. Brown
Nature Scientific Reports | (2018) 8:13090 
DOI: 10.1038/s41598-018-31120-2

Cannabis is an interesting domesticated crop with a long history of cultivation and use. Strains have been selected through informal breeding programs with undisclosed parentage and criteria. The term “strain” refers to minor morphological differences and grower branding rather than distinct cultivated varieties. We hypothesized that strains sold by different licensed producers are chemotaxonomically indistinguishable and that the commercial practice of identifying strains by the ratio of total THC and CBD is insufficient to account for the reported human health outcomes. We used targeted metabolomics to analyze 11 known cannabinoids and an untargeted metabolomics approach to identify 21 unknown cannabinoids. Five clusters of chemotaxonomically indistinguishable strains were identified from the 33 commercial products. Only 3 of the clusters produce CBDA in significant quantities while the other 2 clusters redirect metabolic resources toward the THCA production pathways. Six unknown metabolites were unique to CBD-rich strains and/or correlated to CBDA and 3 unknowns were found only in THCrich strains. Together, these data indicate the domestication of the cannabis germplasm has resulted in a loss of the CBDA pathway in some strains and reallocation of resources between CBDA and THCA pathways in others. The impact of domestication is a lack of chemical diversity and loss of biodiversity in modern cannabis strains.

Abstract

Characterisation of cannabinoid composition in a diverse Cannabis sativa L. germplasm collection

Matthew T. Welling, Lei Liu, Tim Shapter, Carolyn A. Raymond, Graham J. King
Euphytica (2016) 208:463–475
DOI: 10.1007/s10681-015-1585-y

The ability to characterise cannabinoid chemical phenotype (chemotype) accurately is important for the development of Cannabis sativa L. cultivars specific for pharmacological, hemp fibre, or seed end use. Although a number of chemotyping and genotyping methods have previously been developed to predict and characterise cannabinoid composition, only a subset of the gene pool has been examined. A representative survey from a wide range of geographically and genetically diverse C. sativa accessions using liquid chromatography–mass spectrometry (LC–MS) cannabinoid profiling together with dominant and co-dominant DNA marker assays was performed. Overall variability of chemotype across the gene pool was found to be three-fold greater within heterozygote genotypes than previously reported. Interestingly, an individual plant of East Asian origin was found to exhibit a rare propyl alkyl cannabinoid homologue and a chemotype inconsistent with the predicted genotype. We propose that in order to carry out comprehensive screening of genetic resource collections and to identify chemotypic variants specific for end-use pharmacological applications, a strategy which adopts both cannabinoid profiling and the co-dominant DNA marker assay is required. Further research with consideration of propyl-alkyl-cannabinoid homologues should explore the relationship between chemotype and genotype in greater detail.

Abstract

Characteristics of cannabinoids composition of Cannabis plants grown in Northern Thailand and its forensic application

Prapatsorn Tipparat, Surapol Natakankitkul, Pipop Chamnivikaipong, Sirot Chutiwat
Forensic science international 215(1-3):164-70 May 2011
DOI: 10.1016/j.forsciint.2011.05.006

The Thai government has recognized the possibility for legitimate cultivation of hemp. Further study of certain cannabinoid characteristics is necessary in establishing criteria for regulation of cannabis cultivation in Thailand. For this purpose, factors affecting characteristics of cannabinoids composition of Thai-grown cannabis were investigated. Plants were cultivated from seeds derived from the previous studies under the same conditions. 372 cannabis samples from landraces, three different trial fields and seized marijuana were collected. 100g of each sample was dried, ground and quantitatively analyzed for THC, CBD and CBN contents by GC-FID. The results showed that cannabis grown during March-June which had longer vegetative stages and longer photoperiod exposure, had higher cannabinoids contents than those grown in August. The male plants grown in trial fields had the range of THC contents from 0.722% to 0.848% d.w. and average THC/CBD ratio of 1.9. Cannabis in landraces at traditional harvest time of 75 days had a range of THC contents from 0.874% to 1.480% d.w. and an average THC/CBD ratio of 2.6. The THC contents and THC/CBD ratios of cannabis in second generation crops grown in the same growing season were found to be lower than those grown in the first generation, unless fairly high temperatures and a lesser amount of rainfall were present. The average THC content in seized fresh marijuana was 2.068% d.w. while THC/CBD ratios were between 12.6 and 84.09, which is 10-45 times greater than those of similar studied cannabis samples from the previous study. However, most Thai cannabis in landraces and in trial fields giving a low log(10) value of THC/CBD ratio at below 1 may be classified as intermediate type, whereas seized marijuana giving a higher log(10) value at above 1 could be classified as drug type. Therefore, the expanded information provided by the current study will assist in the development of criteria for regulation of hemp cultivation in Thailand.

Abstract

Effects of Cannabis and Cannabinoids in the Human Nervous System


Harold Kalant 2014
The Effects of Drug Abuse on the Human Nervous System
Doi: 10.1016/B978-0-12-418679-8.00013-7

Although the actions of phytocannabinoids are exerted through the endocannabinoid system, the pattern of effects of cannabis as usually used, though similar to that of the endocannabinoids, is not identical and in some particulars even appears to be opposite. The possible reasons for the differences will be discussed in the course of this review. The shared basic mechanisms of action, as well as the differences, also underlie the actual and proposed therapeutic uses of cannabis and cannabinoids (Pertwee, 2009, 2012a), and the adverse effects that are commonly encountered in both medical and nonmedical use.

Introduction