Tetrahydrocannabinol Concentrations Research Articles

Rendimiento y contenido de cannabidiol (CBD) y tetrahidrocannabinol (THC) en cannabis medicinal (Cannabis sativa) cultivado en la Sierra ecuatoriana

Cannabis is an herbaceous species of the Cannabaceae family and is native to the Himalayas. It contains hundreds of metabolites with potential bioactivity, including cannabinoids, terpenes, and flavonoids. The objective of this experiment was to evaluate the yield and the cannabidiol (CBD) and tetrahydrocannabinol (THC) content of medicinal cannabis (variety Cherry Oregon) in two localities of the Ecuadorian highlands. A Randomized Complete Block Design with four treatments and four replications was carried out. Treatment 1 was maintained with natural light, treatment 2 received 16/8 photoperiod (16 hours light, 8 hours dark) for one week, treatment 3 received 16/8 photoperiod for two weeks, and treatment 4 received 16/8 photoperiod for 3 weeks. In the locality 1, treatment 4 showed better values of plant height, dry biomass, biomass yield per plant and greater biomass yield per m2, in both cycles. In the locality 2, the treatments were statistically similar in all variables in both cycles, but a trend where treatment 4 presented higher values compared to the rest of the treatments was observed. The THC and CBD contents for the treatments and cycles ranged between 0.06% and 0.51%, and between 13.76% and 15.29% respectively in both localities. Finally, the results obtained agree with what is reported in the variety's technical sheet, and the THC content does not exceed the maximum value allowed by Ecuadorian regulations.

Self-reported knowledge of tetrahydrocannabinol and cannabidiol concentration in cannabis products among cancer patients and survivors

PurposeCannabis use may introduce risks and/or benefits among people living with cancer, depending on product type, composition, and nature of its use. Patient knowledge of tetrahydrocannabinol (THC) or cannabidiol (CBD) concentration could provide information for providers about cannabis use during and after treatment that may aide in risk and benefit assessments. This study aimed to examine knowledge of THC or CBD concentration among patients living with cancer who consume cannabis, and factors associated with knowledge of cannabinoid concentrations.MethodsPeople living with cancer who consumed cannabis since their diagnosis (n = 343) completed an anonymous, mixed-mode survey. Questions assessed usual mode of delivery (MOD), knowledge of THC/CBD concentration, and how source of acquisition, current cannabis use, and source of instruction are associated with knowledge of THC/CBD concentration. Chi-square and separate binary logistic regression analyses were examined and weighted to reflect the Roswell Park patient population.ResultsLess than 20% of people living with cancer had knowledge of THC and CBD concentration for the cannabis products they consumed across all MOD (smoking- combustible products, vaping- vaporized products (e-cigarettes), edibles-eating or drinking it, and oral- taking by mouth (pills)). Source of acquisition (smoking-AOR:4.6, p < 0.01, vaping-AOR:5.8, p < 0.00, edibles-AOR:2.6, p < 0.04), current cannabis use (edibles-AOR:5.4, p < 0.01, vaping-AOR: 11.2, p < 0.00, and oral-AOR:9.3, p < 0.00), and source of instruction (vaping only AOR:4.2, p < 0.05) were found to be variables associated with higher knowledge of THC concentration.ConclusionSelf-reported knowledge of THC and CBD concentration statistically differed according to MOD, source of acquisition, source of instruction, and current cannabis use.

Detection of Δ9 -tetrahydrocannabinol (THC) in oral fluid using two point-of-collection testing devices following oral administration of a THC and cannabidiolcontaining oil.

Point-of-collection testing (POCT) devices are widely used in roadside and workplace drug testing to identify recent cannabis use by measuring the presence of Δ9 -tetrahydrocannabinol (THC) in oral fluid (OF). However, the performance of POCT devices with oral medicinal cannabis products remains poorly described. In a randomised, double-blinded, crossover trial, adults with insomnia disorder (n= 20) received a single (2mL) oral dose of oil containing 10mg THC + 200 mg cannabidiol, or placebo, prior to sleep. Participants were tested with the Securetec DrugWipe® 5S (10ng/mL THC cut-off) and Dräger DrugTest® 5000 (25 ng/mL THC cut-off) POCT devices at baseline (pre-treatment) and then at 0.5, 10, and 18 h post-treatment. An OF sample, taken at each time point, was also analysed using liquid chromatography-tandem mass spectrometry. Large individual variability in OF THC concentrations was observed 0.5h post-treatment (range: 0-425 ng/mL; mean (SD) 48.7(107.5)ng/mL). Both the Securetec DrugWipe® 5S and DrugTest® 5000 demonstrated poor sensitivity to THC at 0.5h post-treatment (25% and 50%, respectively). At 10 and 18 h post-treatment, all participant OF THC concentrations were below screening cut-offs, and all test results were negative. These findings highlight the relatively poor sensitivity of both devices in detecting recent use of an oral medicinal cannabis product. They also suggest a low probability of obtaining a positive THC result the morning after ('one-off') use. Further research is required to establish the probability of obtaining a positive THC result with regular medicinal cannabis use.

Evaluation of the Canadian approved drug screening equipment cut-off levels for tetrahydrocannabinol (THC).

In 2018, Canada introduced roadside oral fluid (OF) screening devices, called Approved Drug Screening Equipment (ADSE), as an investigative tool in impaired driving investigations to detect tetrahydrocannabinol (THC), cocaine and/or methamphetamine in drivers. In this work, we compare the detection and concentration of THC in blood samples collected from suspected impaired drivers that tested positive at the roadside for THC on an ADSE. The two ADSEs that were utilized were the Dräger DrugTest® 5000 (DDT) and the Abbott SoToxa™ (SoToxa), both configured with a THC OF concentration cut-off concentration of 25 ng/mL. Blood samples were screened for cannabinoids using immunoassay and positive results were followed up by confirmation/quantitation of THC by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS-MS). A total of 230 cases were available where a blood sample was collected from a suspected impaired driver subsequent to a positive THC screen result on an ADSE. The blood samples were taken an average of 1.4 hours (range = 9 minutes to 3.2 hours) after the ADSE test. THC was confirmed in 98% of blood samples with concentrations across all samples ranging from not detected (cut = off 0.5 ng/mL) to greater than 20 ng/mL. Further, 90% of the blood samples had a THC concentration of 2.0 ng/mL (the lower per se limit in Canada) or greater. A positive ADSE test of a suspected impaired driver may predict that the driver has a detectable level of THC in their blood, and there is a high likelihood that the THC blood concentration is 2.0 ng/mL or higher. Hence, ADSE may be a useful tool for law enforcement and aid in the development of grounds to believe that a driver is operating a conveyance with a THC concentration exceeding Canadian per se limits.

How much THC is in that joint? A daily diary study of young adults' knowledge of the cannabinoid content of cannabis products.

Many young adults report frequent cannabis use and are at risk for cannabis harms. Knowledge of the tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations of cannabis products may promote harm reduction, but few studies have characterized cannabinoid concentration knowledge in this population. This study used day-level data to examine predictors of cannabinoid concentration knowledge and associations of cannabinoid concentration knowledge with substance-related consequences among young adults. Participants (N=131; mean age 22.11 years, 64.12% female) from a larger study of cannabis and alcohol co-use completed daily surveys over 21 days assessing knowledge of the cannabinoid concentrations of cannabis used, forms of cannabis used, motives for cannabis use (medicinal, nonmedicinal, both), and substance-related consequences. On average, participants reported at least some knowledge of the THC and CBD concentrations of their cannabis on a respective 48% and 32% of their cannabis days. Generalized linear mixed models revealed that participants with a greater propensity to use non-flower (relative to flower) cannabis products and to report medicinal (relative to exclusively non-medicinal) motives for cannabis use reported greater cannabinoid concentration knowledge overall across days, controlling for sociodemographic factors and level of cannabis involvement. Participants with greater overall cannabinoid concentration knowledge reported positive substance-related consequences more often. In addition, participants were more likely to report negative substance-related consequences on days during which cannabinoid concentrations were known versus unknown. Findings suggest that cannabinoid concentration knowledge may be higher among young adults who report primarily non-flower and medicinally-motivated cannabis use, although cannabinoid concentration knowledge, alone, may not protect against negative substance-related consequences at the day level.

CFPD-PK simulation of inhaled Delta-9-tetrahydrocannabinol aerosol dynamics: Transport, deposition, and translocation in a mouth-to-G10 subject-specific human airway

Medical cannabis is increasingly used as an alternative therapy for various conditions, including chronic pain, multiple sclerosis, epilepsy, and cancer-related symptoms. However, it is crucial to ensure that patients receive the intended dose of tetrahydrocannabinol (THC) from inhaled cannabis for optimal therapeutic effect without overdose risk. This requires a comprehensive understanding of the factors that influence the pharmacokinetics (PKs) of THC in the respiratory system. However, accurate estimation of lung dosimetry and blood concentration of inhaled THC remains challenging partially because the influence of diversified patient-specific puff patterns on inhaled THC transport, deposition, and translocation is still not well quantified. To address the knowledge gap mentioned above, this study employed a hybrid computational fluid-particle dynamics (CFPD) and PK model to evaluate factors that influence delivered doses of THC to the human respiratory system and the resultant THC-plasma concentration-time profile. Specifically, this study compared multiple puff waveforms for inhalation-holding-exhalation (IHE) with total puff volumes from 55 to 82 ml for 2 or 3 s, hold durations from 0 to 5 s, and three puff waveforms (i.e., square, sinusoidal, and realistic). THC deposition in the airways was recorded during all phases for each case using either 452,849 particles per second for the 1.128-μm monodisperse cases or 399,866 particles per second for the polydisperse cases, with the mass median aerodynamic diameter (MMAD) of 1.128 μm. Pulmonary air-THC particle flow transport dynamics, THC particle deposition data, and THC vapor absorption were predicted using CFPD for four airway regions, then scaled by region-specific bioavailability factors. The deposited THC mass in airway regions represents the initial mass entering a 3-compartment PK model, to predict the THC-plasma concentration-time profiles. The CFPD-PK results revealed significant variability in THC transport, deposition, and plasma concentration based on IHE factors. Specifically, larger puff volumes and longer holding times enhanced THC deposition in deeper airways and increased THC-plasma concentrations. Realistic transient puff waveforms predicted higher particle deposition and THC-plasma concentrations than simplified square waveforms. Polydisperse particle distributions show more realistic deposition patterns than monodisperse particle simulations. This study provides insights into the complexity of THC inhalation therapy, emphasizing the importance of considering individualized puff patterns and realistic particle size distributions in accurately predicting therapeutic outcomes, which is highly related to THC deposition in the lung and THC plasma concentration. These findings and the CFPD-PK modeling framework offer guidance for clinicians in prescribing personalized THC dosages, support regulatory science in evaluating inhalation devices, and contribute to ongoing research aimed at optimizing THC delivery for maximum therapeutic effectiveness while minimizing potential overdose risks.

Therapeutic uses of Cannabis in Indian Traditional medicine with attention on Gastrointestinal disorders

Ayurveda is the world's oldest and most complete spiritual teachings, as well as the "oldest medicinal system" known to man. Ayurvedic treatments along with natural substances do not have any usual side effects as contemporary drugs. The cannabis plant has been used as a medicine for thousands of years to treat various illnesses including gastrointestinal disorders. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well-known and researched phyto cannabinoids, with impressive therapeutic properties for a variety of neurological, gastrointestinal, ophthalmic, and skin problems. Cannabis and cannabinoids are beneficial in healing the sign and symptoms of several gastrointestinal diseases, according to research, in part because they interact with the digestive tracts endogenous cannabinoid receptors. This could help in relaxing pain and cramps, reducing discomfort, and improving motility. Many Indian classical formulations were found cannabis is used processing agent in pharmaceuticals. For the treatment of GI issues, there are some popular cannabis-based ayurveda or herbal formulations on the market. CBD levels are frequently higher in medical marijuana, while THC levels are lower. For certain people, the therapeutic CBD is desirable for medicinal purposes, but the psychoactive THC may be needless and undesired. There are numbers of traditional cannabis formulations on the market that lack standardised quality control parameters and methods of evaluation.So, there is a need to develop a standardization technique with special reference to CBD and THC content to include this system of medicine in the main stream of health science. Standardization of popular Ayurvedic or herbal formulations is essential in order to assess the quality, safety, efficacy of that.

Severe drought significantly reduces floral hemp (Cannabis sativa L.) yield and cannabinoid content but moderate drought does not

Floral Hemp (Cannabis sativa L.) is a new crop of interest due to its capacity of producing medicinally active substances such as cannabidiol (CBD) and other cannabinoids and low tetrahydrocannabinol (THC). Preliminary experiments performed in high-THC cannabis have found that light drought stress close to inflorescence maturity can increase THC levels raising concerns about the negative effects that drought can have on floral hemp production. Therefore, the objective of this study was to examine the effects of various timings and levels of drought on floral hemp yield, CBD and THC content. The hemp cultivars ‘BaOx’ and ‘Cherry Mom’ were planted in a commercial greenhouse setting in 2021 and 2022 and grown under well-watered conditions until flowering, at which drought treatments started. Moderate drought intensities (30–50 % field capacity) did not modify yield or THC and cannabidiol (CBD) levels. However, intense drought treatments led to significantly decreased yield and THC and CBD concentrations. Overall, drought stress reduced the THC percentage less than CBD, therefore decreasing the CBD:THC ratio. This research also demonstrates that intense drought decreases THC and CBD content instead of increasing it.

Exploring consumer preferences for cannabis edible products to support public health policy: A discrete choice experiment.

In October 2019, cannabis edibles were legalized for sale in Canada for non-medical use. This move was intended to improve public safety by regulating contents (including a maximum 10 mg tetrahydrocannabinol (THC) per package) and packaging to prevent accidental ingestion or over consumption. This study aimed to explore consumer preferences for cannabis edibles to inform cannabis policy. We explored the relative importance and trade-offs consumers make for attributes of cannabis edibles using a discrete choice experiment. Attributes included type of edible, price, THC content, cannabis taste, package information, product consistency, product recommendations, and Health Canada regulation. Participants lived in Canada, were 19 years of age or older, and purchased a cannabis edible in the last 12 months. A multinomial logit (MNL) model was used for the base model, and latent class analysis to assess preference sub-groups. This study was approved by the institutional ethics committee. Among 684 participants, the MNL model showed that potency was the most relevant attribute, followed by edible type. A two-group latent class model revealed two very distinct preference patterns. Preferences for group 1 (~65% of sample) were driven primarily by edible type, while for group 2 (~35% of sample) were driven almost entirely by THC potency. This study found that consumer preferences for ~65% of consumers of cannabis edibles are being met through regulated channels. The remaining ~35% are driven by THC potency at levels that are not currently available on the licensed market. Attracting this market segment will require reviewing the risks and benefits of restricting THC package content.

Enhanced cannabis timeline followback (EC-TLFB): Comprehensive assessment of cannabis use including standard THC units and validation through biological measures.

The aims of this study were to present an enhanced cannabis timeline followback (EC-TLFB) enabling comprehensive assessment of cannabis use measures, including standard tetrahydrocannabinol (THC) units, and to validate these against objectively indexed urinary 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) concentrations. We used cross-sectional baseline data from the 'CannTeen' observational longitudinal study. The study was conducted in London, UK. A total of 147 participants who used cannabis regularly took part in the study (n = 71 female, n = 76 male; mean age = 21.90, standard deviation = 5.32). The EC-TLFB was used to calculate frequency of cannabis use, method of administration, including co-administration with tobacco, amount of cannabis used (measured with unaided self-report and also using pictorial aided self-report) and type of cannabis product (flower, hash) which was used to estimate THC concentration (both from published data on THC concentration of products and analysis of cannabis samples donated by participants in this study). We calculated total weekly standard THC units (i.e. 5 mg THC for all cannabis products and methods of administration) using the EC-TLFB. The outcome variable for validation of past week EC-TLFB assessments was creatinine-normalized carboxy-tetrahydrocannabinol (THC-COOH) in urine. All measures of cannabis exposure included in this analysis were positively correlated with levels of THC-COOH in urine (r = 0.41-0.52). Standard THC units, calculated with average concentrations of THC in cannabis in the UK and unaided self-report measures of amount of cannabis used in grams showed the strongest correlation with THC-COOH in urine (r = 0.52, 95% bias-corrected and accelerated = 0.26-0.70). The enhanced cannabis timeline followback (EC-TLFB) can provide a valid assessment of a comprehensive set of cannabis use measures including standard tetrahydrocannabinol units as well as and traditional TLFB assessments (e.g. frequency of use and grams of cannabis use).

Drug Interactions of Tetrahydrocannabinol and Cannabidiol in Cannabinoid Drugs.

Cannabinoid drugs containing tetrahydrocannabinol (THC), or its structural analogues, as monotherapeutic agents or as extracts or botanical preparations with or without cannabidiol (CBD) are often prescribed to multimorbid patients who are taking multiple drugs. This raises the question of the risk of drug interactions. This review of the pharmacokinetics and pharmacodynamics of interactions with cannabinoid drugs and their potential effects is based on pertinent publications retrieved by a selective literature search. As THC and CBD are largely metabolized in the liver, their bioavailability after oral or oral-mucosal administration is low (6-8% and 11-13%, respectively). The plasma concentrations of THC and its active metabolite 11-OH-THC can be increased by strong CYP3A4 inhibitors (verapamil, clarithromycin) and decreased by strong CYP3A4 inductors (rifampicin, carbamazepine). The clinical significance of these effects is unclear because of the variable plasma level and therapeutic spectrum of THC. The metabolism of CBD is less dependent on cytochrome P450 enzymes than that of THC. THC and CBD inhibit CYP2C and CYP3A4; the corresponding clinically relevant drug interactions probably are likely to arise only with THC doses above 30 mg/day and CBD doses above 300 mg/day. Potential drug interactions with THC and CBD are probably of little importance at low or moderate doses. Strong CYP inhibitors or inductors can intensify or weaken their effect. Slowly ramping up the dose of oral cannabinoid drugs can lessen their pharmacodynamic interactions, which can generally be well controlled. Administration by inhalation can worsen the interactions.

Transcriptomic and metabolomic analyses reveal the differential accumulation of phenylpropanoids and terpenoids in hemp autotetraploid and its diploid progenitor

BackgroundCannabis sativa, a dioecious plant that has been cultivated worldwide for thousands of years, is known for its secondary metabolites, especially cannabinoids, which possess several medicinal effects. In this study, we investigated the autopolyploidization effects on the biosynthesis and accumulation of these metabolites, transcriptomic and metabolomic analyses were performed to explore the gene expression and metabolic variations in industrial hemp autotetraploids and their diploid progenitors.ResultsThrough these analyses, we obtained 1,663 differentially expressed metabolites and 1,103 differentially expressed genes. Integrative analysis revealed that phenylpropanoid and terpenoid biosynthesis were regulated by polyploidization. No substantial differences were found in the cannabidiol or tetrahydrocannabinol content between tetraploids and diploids. Following polyploidization, some transcription factors, including nine bHLH and eight MYB transcription factors, affected the metabolic biosynthesis as regulators. Additionally, several pivotal catalytic genes, such as flavonol synthase/flavanone 3-hydroxylase, related to the phenylpropanoid metabolic pathway, were identified as being modulated by polyploidization.ConclusionsThis study enhances the overall understanding of the impact of autopolyploidization in C. sativa and the findings may encourage the application of polyploid breeding for increasing the content of important secondary metabolites in industrial hemp.

Identifying policy options to regulate high potency cannabis: A multiple stakeholder concept mapping study in Washington State, USA

BackgroundCannabis legalization in some U.S.A. states has catapulted the mass production of concentrates, with tetrahydrocannabinol (THC) concentrations ranging from 50-90%. A major public health concern is that these products will increase cannabis-related harms such as use disorders, psychotic symptoms, and accidental poisonings. This paper describes and contextualizes the results of a study requested by the WA State Legislature to understand perspectives of WA stakeholders on the topic. MethodsConcept Mapping (CM), a mixed-methods research approach that supports people-centered policy decisions was utilized. The goal of the study was to explore stakeholders’ concern levels and support of policies to address the availability of high THC cannabis products. For analysis purposes, stakeholders were categorized into three groups: community, professionals, and cannabis advocates. ResultsCM generated an inventory of policy ideas for regulating high-potency cannabis from a variety of stakeholders. Notably, stakeholders from community and professional groups supported environmental policy changes such as such as taxation, increasing minimum age for high concentration cannabis products, and advertising prohibition. Meanwhile, cannabis advocates (mostly industry actors) opposed taxation per THC content, proposed lowering taxes, and supported policies with low population impact such as educating parents, teachers, and youth. ConclusionSupport for regulating high concentration THC products varied by stakeholder group. Consistent with how other health compromising industries have historically acted, cannabis industry stakeholders rejected regulation of their products. Future studies should explore non-cannabis industry stakeholders’ willingness to work towards minimizing the influence of the cannabis industry in policy development processes to assure public health regulations prevail.

Driving under the influence of cannabis: A 5-year retrospective Italian study

IntroductionCannabis consumption is associated with driving impairment and increased crash risk, endangering road safety. Toxicological analyses play a fundamental role in detecting a recent consumption of psychoactive substances. The aim of this study was to examine the concentration of cannabinoids in blood samples of driving-under-the-influence (DUI) offenders in order to investigate whether delayed sample collection affects the toxicological assessment of the offenders. Materials and MethodsAn observational retrospective study was performed using anonymized toxicological data referring to cannabis-related DUI offenders involved in road traffic accidents (RTA) or apprehended by the police from 1 January 2017–31 December 2021 archived at Legal Medicine and Toxicology Department of the University Hospital of Padova, Italy. ResultsIn a total sample of 318 drivers, 143 blood samples tested positive for tetrahydrocannabinol (THC) and metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), and 173 blood samples were positive for THC-COOH with THC negative. In the first group, the mean concentrations of THC and THC-COOH were 4.05 ng/mL and 28.29 ng/mL, respectively. In THC-negative cases, the mean THC-COOH concentration was 7.3 ng/mL. The time elapsed between the event and sample collection varied from 15 min to 7 h (mean 2 h 29 min). The average estimated time elapsed after consumption of cannabinoids was 3 h 7 min (Model I) and 2 h 36 min (Model II). ConclusionsThe present research discussed the main difficulties in the toxicological evaluation of drivers under the influence of Cannabis. Issues related to the time between RTA and sample collection, the laws and legal limits in force in various Countries were presented

How much cannabis is used in a joint in Australia? An experimental investigation into use by potency and frequency.

Cannabis use is highly prevalent in Australia, yet current survey metrics measure tetrahydrocannabinol (THC) exposure with limited accuracy. Often survey items measure cannabis quantity by assuming specific modes of use (i.e., 'how many joints do you use?'), which fail to capture variations in cannabis use and the diverse modes of use (e.g., joints, cones, spliffs). This study investigated how much cannabis is used in these modes of administration in an Australian sample. Participants (N = 31, Mage = 25.77; 51% university students) completed the Roll a Joint Paradigm in which they rolled joints, spliffs and packed cones as they would typically, using oregano as 'cannabis.' Participants then prepared each again but with cannabis of higher or lower potency. The amount of cannabis used across different modes of administration was variable: joints (range 0.10-1.25 g), spliffs (range 0.12-1.21 g) and cones (range 0.03-0.41 g). Participants who used cannabis daily rolled three times the amount of cannabis into a joint. The amount of cannabis used in common modes of administration may be highly variable. Daily use may be associated using larger quantities of cannabis. Titration attempts based on potency were not proportional or consistent across modes of administration. The results indicate people may adjust the quantity of cannabis based on perceived potency, however, not proportional to THC concentration. Inconsistency in the amount of cannabis used based on potency and within different modes of administration may represent a problem for self-report metrics which ask participants to report cannabis use in joints.

Features of populations of hemp varieties with different composition of cannabinoid compounds

Aim. To study the biological features of populations of hemp varieties with the absence of narcotic activity – tetrahydrocannabinol (THC) not higher than 0.08 %, but with the presence of non-psychoactive components of cannabinoids: cannabidiol (CBD) and cannabichromene (CBC); cannabigerol (CBG); CBG and CBD. To identify breeding prospects for increasing the content of cannabinoids that have therapeutic properties. Methods. Samples of elite plants were analyzed for cannabinoid content by gas-liquid chromatography (GC Agilent Technologies HP 6890, Series Hewlett Packard). Results. The limits of variation of the population variability of the sign of CBD content of the Medana variety are from 0.0253 to 3.3469 %, 75 % of the plants of which contain CBD in the range of 1.0-2.2 %. Studies of the Vik 2020 hybrid population confirmed a high correlation between CBD and THC and the absence of a relationship between CBD and CBG, THC and CBG. More than 11 % of plants in the population contain CBG from 3.5849 to 4.6207 %. There are no correlations between CBD and CBG, CBD and THC in these plants. The presence of such plants indicates the possibility of further increasing the content of СBG to 8 % and above, without exceeding the THC limit in our country (0.08 %). Conclusions. Conducted research has proven that with the current permissible level of THC, the content of CBD can be increased only to 2.5-3.0 % (Medana variety) through purposeful selection. The hybrid Vik 2020 is especially valuable, because in its population unique plants with the presence of several cannabinoid compounds with a THC content of no more than 0.08 % were found. The obtained valuable breeding material of the Medana variety and the Vik 2020 hybrid is a donor for its inclusion in hybridization and further multi-vector selection in the direction of increasing of the content of CBD, CBC and CBG with the absence of THC.

In Vivo and In Vitro Chromosome Doubling of ‘I3’ Hemp

Cannabis sativa L. is a diploid (2x) herbaceous plant that provides a wide variety of products such as essential oils, fiber, and medicine. Hemp was defined in the 2018 Farm Bill as a Cannabis plant with a delta-9 tetrahydrocannabinol concentration of not more than 0.3% on a dry-weight basis. Polyploidy is frequently used in plant breeding to manipulate vigor, reproductive fertility, and biochemistry. By inducing polyploidy/chromosome doubling, we may increase the compounds of interest, principally CBD (cannabidiol), produced by hemp. The purpose of this experiment was to evaluate the efficacy of different treatments of colchicine and oryzalin applied in vivo and in vitro to induce polyploidy in ‘I3’ hemp. After treating vegetative cuttings with colchicine or oryzalin, we had a 31% survival rate. Of the 85 survivors, we recovered two tetraploids: one from the 12-h 0.05% colchicine treatment group and the other from the 12-h 0.2% colchicine treatment group. For the in vitro portion of the experiment, the 12-h 50-µM oryzalin treatment yielded one tetraploid and the 36 h 50 µM oryzalin treatment yielded one cytochimera (mixoploid). The relative efficiency of some treatments showed potential for a simple method to induce tetraploids in clonal hemp for breeding.

Medical Cannabis Alleviates Chronic Neuropathic Pain Effectively and Sustainably without Severe Adverse Effect: A Retrospective Study on 99 Cases.

Medical cannabis may provide a treatment option for chronic neuropathic pain. However, empirical disease-specific data are scarce. This is a retrospective observational study including 99 patients with chronic neuropathic pain. These patients received medical cannabis by means of inhaling dried flowers with tetrahydrocannabinol content of <12-22% at a maximal daily dose of 0.15-1 g. Up to six follow-ups were carried out at intervals of 4-6 weeks. Pain severity, sleep disturbance, general improvement, side effects, and therapy tolerance at the follow-up consultations were assessed in interviews and compared with the baseline data using non-parametric Wilcoxon signed-rank test. Within 6 weeks on the therapy, median of the pain scores decreased significantly from 7.5 to 4.0 (p < 0.001). The proportion of patients with severe pain (score >6) decreased from 96% to 16% (p < 0.001). Sleep disturbance was significantly improved with the median of the scores decreased from 8.0 to 2.0 (p < 0.001). These improvements were sustained over a period of up to 6 months. There were no severe adverse events reported. Mild side effects reported were dryness in mucous tissue (5.4%), fatigue (4.8%), and increased appetite (2.7%). Therapy tolerance was reported in 91% of the interviews. Medical cannabis is safe and highly effective for treating neuropathic pain and concomitant sleep disturbance.

Understanding the Mechanism and Extent of Transplacental Transfer of (-)-∆9 -Tetrahydrocannabinol (THC) in the Perfused Human Placenta to Predict In Vivo Fetal THC Exposure.

Cannabis use during pregnancy may cause fetal toxicity driven by in utero exposure to (-)-∆9 -tetrahydrocannabinol (THC) and its psychoactive metabolite, (±)-11-hydroxy-∆9 -THC (11-OH-THC). THC concentrations in the human term fetal plasma appear to be lower than the corresponding maternal concentrations. Therefore, we investigated whether THC and its metabolites are effluxed by placental transporters using the dual cotyledon, dual perfusion, term human placenta. The perfusates contained THC alone (5 μM) or in combination (100-250 nM) with its metabolites (100 nM or 250 nM 11-OH-THC, 100 nM COOH-THC), plus a marker of P-glycoprotein (P-gp) efflux (1 or 10 μM saquinavir), and a passive diffusion marker (106 μM antipyrine). All perfusions were conducted with (n = 7) or without (n = 16) a P-gp/BCRP (breast-cancer resistance protein) inhibitor, 4 μM valspodar. The maternal-fetal and fetal-maternal unbound cotyledon clearance indexes (m-f-CLu,c,i and f-m-CLu,c,i ) were normalized for transplacental antipyrine clearance. At 5 μM THC, the m-f-CLu,c,i , 5.1 ± 2.1, was significantly lower than the f-m-CLu,c,i , 13 ± 6.1 (P = 0.004). This difference remained in the presence of valspodar or when the lower THC concentrations were perfused. In contrast, neither metabolite, 11-OH-THC/COOH-THC, had significantly different m-f-CLu,c,i vs. f-m-CLu,c,i . Therefore, THC appears to be effluxed by placental transporter(s) not inhibitable by the P-gp/BCRP antagonist, valspodar, while 11-OH-THC and COOH-THC appear to passively diffuse across the placenta. These findings plus our previously quantified human fetal liver clearance, extrapolated to in vivo, yielded a THC fetal/maternal steady-state plasma concentration ratio of 0.28 ± 0.09, comparable to that observed in vivo, 0.26 ± 0.10.

Antifungal and antibacterial activities of Cannabis sativa L. resins.

Ethnopharmacological relevanceCannabis sativa L. (Cannabaceae) is a plant native to Eastern Asia spread throughout the world because of its medicinal properties. Despite being used for thousands of years as a palliative therapeutic agent for many pathologies, in many countries research on its effects and properties could only be carried out in recent years, after its legalization. Aims of the studyIncreasing resistance to traditional antimicrobial agents demands finding new strategies to fight against microbial infections in medical therapy and agricultural activities. Upon legalization in many countries, Cannabis sativa is gaining attention as a new source of active components, and the evidence for new applications of these compounds is constantly increasing. MethodsExtracts from five different varieties ofCannabis sativa were performed and their cannabinoids and terpenes profiles were determined by liquid and gas chromatography. Antimicrobial and antifungal activities against Gram (+) and Gram (−) bacteria, yeast and phytopathogen fungus were measured. To analyze a possible action mechanism, cell viability of bacteria and yeast was assessed by propidium iodide stain. ResultsCannabis varieties were grouped into chemotype I and II as a consequence of their cannabidiol (CBD) or tetrahydrocannabinol (THC) content. The terpenes profile was different in quantity and quality among varieties, with (−)b-pinene, b-myrcene, p-cymene and b-caryophyllene being present in all plants. All cannabis varieties were effective to different degree against Gram (+) and Gram (−) bacteria as well as on spore germination and vegetative development of phytopathogenic fungi. These effects were not correlated to the content of major cannabinoids such as CBD or THC, but with the presence of a complex terpenes profile. The effectiveness of the extracts allowed to reduce the necessary doses of a widely used commercial antifungal to prevent the development of fungal spores. ConclusionAll the extracts of the analysed cannabis varieties showed antibacterial and antifungal activities. In addition, plants belonging to the same chemotype showed different antimicrobial activity, demonstrating that the classification of cannabis strains based solely on THC and CBD content is not sufficient to justify their biological activities and that other compounds present in the extracts are involved in their action against pathogens. Cannabis extracts act in synergy with chemical fungicides, allowing to reduce its doses.