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THC and CBD Fingerprinting of an Elite Cannabis Collection from Iran: Quantifying Diversity to Underpin Future Cannabis Breeding.

ABSTRACT: Cannabis (Cannabis sativa L.) has a rich history of human use, and the therapeutic importance of compounds produced by this species is recognized by the medical community. The active constituents of cannabis, collectively called cannabinoids, encompass hundreds of distinct molecules, the most well-characterized of which are tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been used for centuries as recreational drugs and medicinal agents. As a first step to establish a cannabis breeding program, we initiated this study to describe the HPLC-measured quantity of THC and CBD biochemistry profiles of 161 feral pistillate cannabis plants from 20 geographical regions of Iran. Our data showed that Iran can be considered a new region of high potential for distribution of cannabis landraces with diverse THC and CBD content, predominantly falling into three groups, as Type I = THC-predominant, Type II = approximately equal proportions of THC and CBD (both CBD and THC in a ratio close to the unity), and Type III = CBD-predominant. Correlation analysis among two target cannabinoids and environmental and geographical variables indicated that both THC and CBD contents were strongly influenced by several environmental-geographical factors, such that THC and CBD contents were positively correlated with mean, min and max annual temperature and negatively correlated with latitude, elevation, and humidity. Additionally, a negative correlation was observed between THC and CBD concentrations, suggesting that further studies to unravel these genotype × environment interactions (G × E interactions) are warranted. The results of this study provide important pre-breeding information on a collection of cannabis that will underpin future breeding programs.

SUBMITTER: Mostafaei Dehnavi M

PROVIDER: S-EPMC8747537 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundWhile the use of orally consumed Cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC) containing products, i.e. "edibles", has expanded, the health consequences are still largely unknown. This study examines the effects of oral consumption of whole Cannabis and a complex Cannabis extract on neurochemicals, endocannabinoids (eCB), and physiological parameters (body temperature, heart rate) in mice.MethodsIn this pilot study, C57BL/6 J mice were treated with one of the following every other day for 2 weeks: a complex Cannabis extract by gavage, whole Cannabis mixed with nutritional gel through free feeding, or purified THC/CBD by intraperitoneal (i.p.) injection. Treatments were conducted at 4 doses ranging from 0-100 mg/kg/day of CBD with THC levels of ≤ 1.2 mg/kg/day for free feeding and gavage and 10 mg/kg/day for i.p. Body temperature and heart rate were monitored using surgically implanted telemetry devices. Levels of neurochemicals, eCB, THC, CBD, and 11-OH-THC were measured using mass spectrometry 48 h after the final treatment. Statistical comparisons were conducted using ANOVA and t-tests.ResultsDifferences were found between neurochemicals in the brains and plasma of mice treated by i.p. (e.g. dopamine, p < 0.01), gavage (e.g., phenylalanine, p < 0.05) and in mice receiving whole Cannabis (e.g., 3,4-dihydroxyphenylacetic DOPAC p < 0.05). Tryptophan trended downward or was significantly decreased in the brain and/or plasma of all mice receiving Cannabis or purified CBD/THC, regardless of dose, compared to controls. Levels of the eCB, arachidonoyl glycerol (2-AG) were decreased in mice receiving lowest doses of a complex Cannabis extract by gavage, but were higher in mice receiving highest doses compared to controls (p < 0.05). Plasma and brain levels of THC and 11-OH-THC were higher in mice receiving 1:1 THC:CBD by i.p. compared to those receiving 1:5 or 1:10 THC:CBD. Nominal changes in body temperature and heart rate following acute and repeated exposures were seen to some degree in all treatments.ConclusionsChanges to neurochemicals and eCBs were apparent at all doses regardless of treatment type. Levels of neurochemicals seemed to vary based on the presence of a complex Cannabis extract, suggesting a non-linear response between THC and neurochemicals following repeated oral dosing.

Project description:With the recent legalization of inhaled cannabis for medicinal and recreational use, the elderly represents one of the newest, rapidly growing cohorts of cannabis users. To understand the neurobiological effects of cannabis on the aging brain, 19-20 months old mice were divided into three groups exposed to vaporized cannabis containing ~10% Δ9-THC, ~10% CBD, or placebo for 30 min each day. Voxel based morphometry, diffusion weighted imaging, and resting state functional connectivity data were gathered after 28 days of exposure and following a two-week washout period. Tail-flick, open field, and novel object preference tests were conducted to explore analgesic, anxiolytic, and cognitive effects of cannabis, respectively. Vaporized cannabis high in Δ9-THC and CBD achieved blood levels reported in human users. Mice showed antinociceptive effects to chronic Δ9-THC without tolerance while the anxiolytic and cognitive effects of Δ9-THC waned with treatment. CBD had no effect on any of the behavioral measures. Voxel based morphometry showed a decrease in midbrain dopaminergic volume to chronic Δ9-THC followed but an increase after a two-week washout. Fractional anisotropy values were reduced in the same area by chronic Δ9-THC, suggesting a reduction in gray matter volume. Cannabis high in CBD but not THC increased network strength and efficiency, an effect that persisted after washout. These data would indicate chronic use of inhaled cannabis high in Δ9-THC can be an effective analgesic but not for treatment of anxiety or cognitive decline. The dopaminergic midbrain system was sensitive to chronic Δ9-THC but not CBD showing robust plasticity in volume and water diffusivity prior to and following drug cessation an effect possibly related to the abuse liability of Δ9-THC. Chronic inhaled CBD resulted in enhanced global network connectivity that persisted after drug cessation. The behavioral consequences of this sustained change in brain connectivity remain to be determined.

Project description:BACKGROUND: Significant interest has emerged in the therapeutic and interactive effects of different cannabinoids. Cannabidiol (CBD) has been shown to have anxiolytic and antipsychotic effects with high doses administered orally. We report a series of studies conducted to determine the vaporisation efficiency of high doses of CBD, alone and in combination with ?9-tetrahydrocannabinol (THC), to achieve faster onset effects in experimental and clinical trials and emulate smoked cannabis. METHODS: Purified THC and CBD (40 mg/ml and 100 mg/ml respectively) were loaded onto a liquid absorbing pad in a Volcano vaporiser, vaporised and the vapours quantitatively analysed. Preliminary studies determined 200 mg CBD to be the highest dose effectively vaporised at 230 ° C, yielding an availability of approximately 40% in the vapour phase. Six confirmatory studies examined the quantity of each compound delivered when 200 mg or 4 mg CBD was loaded together with 8 mg of THC. RESULTS: THC showed 55% availability when vaporised alone or with low dose CBD, while large variation in the availability of high dose CBD impacted upon the availability of THC when co-administered, with each compound affecting the vaporisation efficiency of the other in a dynamic and dose-dependent manner. We describe optimised protocols that enable delivery of 160 mg CBD through vaporisation. CONCLUSIONS: While THC administration by vaporisation is increasingly adopted in experimental studies, often with oral predosing with CBD to examine interactive effects, no studies to date have reported the administration of CBD by vaporisation. We report the detailed methodology aimed at optimising the efficiency of delivery of therapeutic doses of CBD, alone and in combination with THC, by vaporisation. These protocols provide a technical advance that may inform methodology for clinical trials in humans, especially for examining interactions between THC and CBD and for therapeutic applications of CBD. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24109245.

Project description:Background: The regular use of cannabis by young men has been associated with an increased incidence of testicular germ cell tumors (TGCT). TGCT, the most common cancer in young adults, is believed to arise from an alteration of testicular fetal germ cells differentiation during development, with a possible subsequent environmental trigger (eg drugs or other chemicals) during puberty or adulthood leading to cancer. Cannabis consumption by pregnant women is currently increasing worldwide, and legalization for its recreational and therapeutic purposes is debated in numerous countries. In this context, we aimed to determine whether cannabis exposure can affect development of the fetal testis. Methods: Since phytocannabinoids act on an endogenous system called the endocannabinoid system (ECS), we first investigated these signaling pathways in the human fetal testis, from 6 to 17 developmental weeks. We next investigated the effects of the two main components of cannabis, (−)-Δ9-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD), on the human fetal testis ex vivo. Results: We show the presence of two key endocannabinoids, 2-arachidonylglycerol (2-AG) and anandamide (AEA), albeit with lower levels. The human fetal testis also expressed several enzymes and receptors of this signaling pathway. Human fetal testicular explants collected from first trimester were exposed to CBD, THC or CBD/THC [ratio 1:1] at concentrations ranging from 10-7 to 10-5M during 72h to 14 days. Phytocannabinoids treatments affected fetal testicular cell proliferation and viability, as well as testosterone secretion by Leydig cells and AMH secretion by Sertoli cells. Transcriptomic analysis performed by BRB-seq on exposed versus unexposed fetal testis explants showed 187 differentially expressed genes (DEGs), some of which involved in toxic substances response and steroid synthesis. Conclusions: Our study provides the first evidence of the presence of ECS in human fetal testis and support a potential adverse effect of cannabis consumption in pregnant women on the male reproductive function development.

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THC and CBD Fingerprinting of an Elite Cannabis Collection from Iran: Quantifying Diversity to Underpin Future Cannabis Breeding.

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