Cannabis Research Articles

Nanocarriers for Cannabinoid Delivery: Enhancing Therapeutic Potential.

Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine.

F1 Hybrid Seed Can Enhance Cannabis Crop Uniformity and Yield

Cannabis (Cannabis sativa) growers seek greater crop uniformity and yield; however, use of vegetatively propagated plants has several drawbacks. There is increased interest in F1 hybrid seed, especially for flower production. Plant growth and performance of inbred lines of the cultivars Wife (WF) and Wilhelmina (WH), produced from one to four rounds of selfing (S1 to S4), and three F1 hybrid lines (WF S1 × WH S1, WF S2 × WH S2, and WF S3 × WH S3) were evaluated. As selfing increased from S1 to S4, within line plant variation did not change substantially for most measures for WF, but variation progressively decreased for plant height, total shoot length and plant dry weight for WH. S4 plants of WH were uniformly diminutive and likely exhibited inbreeding depression. F1 hybrids between WF and WH were larger than WH plants for all measures because WH is photoperiod insensitive (autoflowering) and dwarf. Compared with WF self-lines, F1 WF × WH hybrid lines exhibited greater uniformity, plant dry weight, flower dry weight, and percent cannabidiol and tetrahydrocannabinol. F1 WF × WH hybrid plants were able to achieve similar height and shoot growth to WF self-lines, even though they had a dwarf parent in WH. It is likely that heterosis is responsible for the growth enhancements observed in the F1 WF × WH hybrids. These findings indicate that F1 hybridization can produce uniform, stable, and high-yielding cannabis plants from seed.

Identification of Marijuana Using Silver-Phosphine Ion Complexation and a Semi-Quantitative 1% Decision-Point Assay

Due to the strict federal regulations concerning ∆9-tetrahydrocannabinol (∆9-THC) content for the differentiation of hemp and marijuana outlined in the 2018 Farm Bill, the ability to quickly and reliably differentiate cannabis as marijuana or hemp is crucial within both the seized drug community and hemp industry. This study provides a novel direct mass spectrometry approach for the identification of marijuana using Ag-phosphine ion complexation and a semi-quantitative 1% decision-point assay. The main constituents of hemp and marijuana, cannabidiol (CBD) and ∆9-THC, are isomeric and cannot be differentiated using soft ionization mass spectrometry techniques alone. However, the incorporation of [Ag(PPh3)(OTf)]2 enables the formation of unique MS/MS product ions at m/z 421/423, m/z 353/355, and m/z 231 for CBD due to differences in binding affinity, allowing CBD to be differentiated from ∆9-THC. Likewise, the isomeric cannabinoid precursors ∆9-tetrahydrocannabinolic acid (∆9-THCA) and cannabidiolic acid (CBDA) can be differentiated due to the formation of unique MS/MS product ions at m/z 465/467 and m/z 379/381, which are specific to CBDA. Eight additional cannabinoids were also characterized utilizing the proposed Ag-phosphine ion complexation approach. To reduce the potential for false positives, a more conservative 1% decision-point assay was developed by fortifying 1% weight-by-volume ∆9-THC-d9 into methanolic extracts of authentic cannabis plant material, followed by assessing if the total ∆9-THC content (containing ∆9-THC and ∆9-THCA) was greater than or less than the intensity of the spiked internal standard. When the developed approach was applied to 20 methanolic extracts of authentic cannabis samples with known cannabinoid compositions, 90% of the samples were correctly identified as marijuana or not marijuana based on the 1% administrative threshold for the total ∆9-THC content. The two lone misidentifications were due to the presence of elevated ∆8-THC, which highlights the necessity to explore more selective ligands in the future. This study provides the first application of Ag-ligand ion complexation for the identification of marijuana based on a semi-quantitative 1% decision-point assay, which shows great promise as an alternative method for the rapid identification of marijuana.

The role of cannabis on total hip and knee surgeries outcomes: a systematic review and meta-analysis.

Cannabis refers to medications derived from the Cannabis plant. Cannabis has long been used to treat a wide range of conditions. The widespread legalization of cannabis has increased its use. This meta-analysis evaluates the effects of preoperative cannabis usage on TKA and THA outcomes and complications. This review follows CRD Guidance for Undertaking Reviews in Healthcare and PRISMA 2020 guidelines. On October 12, 2023, we extensively searched MEDLINE (PubMed), Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. There were no time, place, or language restrictions. We also examined the references and citations in the included publications to find relevant research. We found 208 references in PubMed/Medline, Scopus, Web of Science, and other databases. After reviewing all publications, we identified 18 references that match the requirements for further assessment. The odds ratios (ORs) for reoperation and readmission are 1.35 (95% CI: 0.69, 2.66, and p-value = 0.38), and 0.89 (95% CI: 0.41, 1.92, and p-value = 0.76). Inpatient morphine milligram equivalent (MME) and length of stay (LOS) have a mean difference (MD) of -1.71 (95% CI: -13.46, 10.05, and p-value = 0.78), and - 0.13 (95% CI: -0.33, 0.08, and p-value = 0.23). The MD of the VAS pain score 24-72h after surgery is 0.40 (95% CI: -0.07, 0.87, and p-value = 0.10). The odds ratio for PTE and DVT is 1.54 (95% CI: 0.1, 23.24, and p-value = 0.75), and 1.38 (95% CI: 1.08, 1.77, and p-value = 0.01), respectively. Cannabis users experienced significantly higher rates of DVT following THA and TKA. Our subgroup analysis found that cannabis users who underwent TKA had considerably higher rates of reoperation (p-value = 0.10) and readmission (p-value ≤ 0.01), while those who underwent THA had significantly lower rates of PTE. These findings highlight the need to include cannabis use as a risk factor in surgical planning and patient care protocols, and further studies are warranted. This study design and protocol were performed in accordance with the PRISMA Statement. The protocol was registered previously on PROSPERO CRD42024551078.

Cannabidiol Plays a Modulatory Function on the Methamphetamine-Induced Reward Through Hippocampal D2-Like Dopamine Receptors.

Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH's abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH's rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10μg/5 μL for CPP acquisition and 50μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG.

Evaluation of the Efficacy of a Full-Spectrum Low-THC Cannabis Plant Extract Using In Vitro Models of Inflammation and Excitotoxicity.

Evidence has accumulated that Cannabis-derived compounds have the potential to treat neuroinflammatory changes present in neurodevelopmental conditions such as autism spectrum disorder. However, research is needed on the specific brain health benefits of strains of whole Cannabis extract that are ready for commercial production. Here, we explore the anti-inflammatory and neuroprotective effects of NTI-164, a genetically unique high-cannabidiol (CBD), low-Δ9-tetrahydrocannabinol extract, and also CBD alone on BV-2 microglia and SHSY-5Y neurons. Inflammation-induced up-regulation of microglial inflammatory markers was significantly attenuated by NTI-164, but not by CBD. NTI-164 promoted undifferentiated neuron proliferation and differentiated neuron survival under excitotoxic conditions. These effects suggest the potential for NTI-164 as a treatment for neuropathologies.

Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Analysis of Δ9-Tetrahydrocannabinol and Cannabidiol in Commercial Suk-Saiyasna Herbal Remedy: Applying Hansen Solubility Parameters for Sample Extraction to Ensure Regulatory Compliance.

Suk-Saiyasna is a traditional Thai herbal remedy that comprises 12 distinct herbs. Among these, cannabis leaves constitute 12 of the total 78 components in this formulation. This study specifically examines the portion of the cannabis plant, which accounts for approximately 15.8% of the overall herbal composition used in the entire remedy. According to the Thailand Narcotics Act of 2022, the Δ9-tetrahydrocannabinol (Δ9-THC) concentration in herbal extracts must not exceed 0.2% by weight. This study aims to quantify the levels of Δ9-THC and cannabidiol (CBD) in commercial Suk-Saiyasna products. This research utilizes Hansen Solubility Parameters (HSPs) to identify the optimal solvent for ultrasonic extraction, thereby maximizing cannabinoid yield. An advanced method was developed employing ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), compliant with AOAC standards to meet regulatory guidelines. The method validation emphasized specificity, linearity, sensitivity, accuracy, and precision. Dichloromethane was chosen due to its favorable HSP values, enabling highly efficient extraction of Δ9-THC and CBD, achieving recovery rates of over 99.9% after the second extraction. This investigation benefits from the accuracy of the UHPLC-MS/MS technique in quantifying cannabinoids in commercial products, with Δ9-THC concentrations observed between 0.00231% and 0.14218%, and CBD concentrations ranging from 0.00002% to 0.01541%, all remaining below the legal limit. The variability in cannabinoid concentrations among various commercial products highlights the need for standardization in the herbal industry. This finding underscores the critical role of rigorous quality control measures in ensuring the safety and efficacy of cannabis-derived products.

Leveraging genetics to support forensic toxicology analysis: Demonstrating concordance among marijuana samples

Cannabis sativa is an important plant for industrial purposes. Indeed, it is legal to cultivate and supply authorized low level Δ9-tetrahydrocannabinol (THC) cannabis plants for fiber and seeds (i.e., 0.2 % according to the European Union regulation on drugs). Today, chromatography/mass spectrometry-based procedures are successfully applied to determine THC concentration. Unfortunately, when cannabis samples have been degraded because wrongfully stored, toxicological results were affected, altering the final status of legal sample or illegal sample. Rather, genetic identification could give more information about the identity of these plants. For this reason, a degradation study was run to support how genetics can help to detect concordance in cannabis highly-degraded samples. Forty cannabis sub-samples were stored (for one week, two weeks, one month and two months) in auto-sealing bag to assess the effects of a wrong cannabis storage on weight reduction, genomic DNA changes, and corresponding STR profiles. Once respective time-period elapsed, each sub-sample’s weight was measured, the percentage weight loss calculated, and the genomic DNA was extracted and quantified, obtaining a complete STR profile for all samples. Furthermore, the aim of this study was to assess the same 13-loci short tandem repeat (STR) multiplex system used for the degradation experiment and evaluate the power of such markers in the identification and discrimination of highly degraded cannabis samples coming from real cases. The results of this study demonstrated that the 13-loci STR multiplex system successfully achieved the objective both for industry and forensic purposes. For each sample, all 13 loci were amplified, and degraded samples were correctly identified, suggesting that genetic typification could be a useful tool. The proposed procedure could be parallelly applied to toxicology analysis to detect if vegetable sample become from authorized plant, to help courts track back illegal samples or to achieve illegal cannabis genetic profiles for further comparison.

The molecular anti-metastatic potential of CBD and THC from Lebanese Cannabis via apoptosis induction and alterations in autophagy

The medicinal plant Cannabis sativa L. (C. sativa) is currently being extensively studied to determine the full extent of its therapeutic pharmacological potential. Δ9-tetrahydocannabinol (THC) and cannabidiol (CBD) are the most thoroughly investigated compounds. We aimed to explore the anticancer activity of cannabinoids mixture isolated from the Lebanese C. sativa plant in ratios comparable to the local medicinal plant, to elucidate its mechanism of action in breast cancer cells in vitro. Cells were subjected to cytotoxicity assay, cell cycle analysis, Annexin V/PI dual staining, cell death ELISA, immunofluorescence, in addition to western blot analysis of apoptotic and autophagy markers. We further evaluated the anti-metastatic effect of cannabinoids on MDA-MB-231 using the scratch wound-healing, trans-well migration and invasion assays. Our results revealed the promising therapeutic benefits of CBD/THC on inhibiting the growth of breast cancer cells by promoting cellular fragmentation, phosphatidylserine translocation to the outer membrane leaflet and DNA fragmentation in both cell lines while inhibiting the motility of the triple negative breast cancer cells. In our study, CBD/THC mixture was found to exhibit a pro-apoptotic activity via the activation of the mitochondrial apoptotic pathway, independent from ROS production while also suggesting the activation of a caspase-dependent apoptotic pathway. Even though autophagy was altered upon exposure to the cannabinoid mixture, our data suggested that it is not the mechanism responsible of inducing cell death. In conclusion, our study demonstrates the promising therapeutic benefits of CBD and THC isolated from the Lebanese C. sativa plant on breast cancer cells in vitro.

The effects of cannabinoids on the kidney.

Cannabinoids are a class of drugs derived from the Cannabis plant that are widely used for the treatment of various medical conditions and recreational use. Common examples include Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), spice, and 2-arachidonoylglycerol (2-AG). With more than 100 cannabinoids identified, their influence on the nervous system, role in pain management, and effects due to illicit use have been extensively studied. However, their effects on peripheral organs, such as the kidneys, require further examination. With dramatic rises in use, production, and legalization, it is essential to understand the impact and mechanistic properties of these drugs as they pertain to renal and cardiovascular physiology. The goal of this review is to summarize prior literature on the expression of cannabinoid receptors and how cannabinoids influence renal function. This review first discusses the interaction of the endocannabinoid system (ECS) and renal physiology and pathophysiology. Following, we briefly discuss the role of the ECS in various kidney diseases and the potential therapeutic applications of drugs targeting the cannabinoid system. Lastly, recent studies have identified several detrimental effects of cannabinoids, not only on the kidney but also in contributing to adverse cardiovascular outcomes. Thus, the negative impact of cannabinoids on renal function and the development of various cardiovascular diseases is also discussed.

Effects of cannabidiol on AMPKα2 /HIF-1α/BNIP3/NIX signaling pathway in skeletal muscle injury.

Cannabidiol: (CBD) is a non-psychoactive natural active ingredient from cannabis plant, which has many pharmacological effects, including neuroprotection, antiemetic, anti-inflammatory and anti-skeletal muscle injury. However, the mechanism of its effect on skeletal muscle injury still needs further research. In order to seek a scientifically effective way to combat skeletal muscle injury during exercise, we used healthy SD rats to establish an exercise-induced skeletal muscle injury model by treadmill training, and systematically investigated the effects and mechanisms of CBD, a natural compound in the traditional Chinese medicine Cannabis sativa L., on combating skeletal muscle injury during exercise. CBD effectively improved the fracture of skeletal muscle tissue and reduced the degree of inflammatory cell infiltration. Biochemical indexes such as CK, T, Cor, LDH, SOD, MDA, and GSH-Px in serum of rats returned to normal. Combining transcriptome and network analysis results, CBD may play a protective role in exercise-induced skeletal muscle injury through HIF-1 signaling pathway. The experimental results implied that CBD could down-regulate the expression of IL-6, NF-κB, TNF-α, Keap1, AMPKα2, HIF-1α, BNIP3 and NIX, and raised the protein expression of IL-10, Nrf2 and HO-1. These results indicate that the protective effect of CBD on exercise-induced skeletal muscle injury may be related to the inhibition of oxidative stress and inflammation, thus inhibiting skeletal muscle injury through AMPKα2/HIF-1α/BNIP3/NIX signal pathways.

Development of efficient and scalable regeneration tissue culture method for Cannabis sativa

Large scale production of uniform disease-free plants is crucial for Cannabis sativa biotechnology. Existing micropropagation protocols rely heavily on shoot multiplication from existing meristems via direct organogenesis. Such protocols do not allow multiplication of plant material through continuous sub-culturing. Protocols that use indirect regeneration are usually not efficient enough and have very low multiplication rates. In the present study, an efficient protocol that uses a combination of direct organogenesis and callogenesis to induce multiple shoot development cultures is developed. Callogenesis was induced from various explants cultured on the media having various combinations of thidiazuron (TDZ) and naphthaleneacetic acid (NAA); best callogenesis and shoot regeneration was achieved from hypocotyl explants cultured on TDZ 0.4 mg l−1 NAA 0.2 mg l−1. Hypocotyls with cotyledonary node and shoot apical meristem were significantly better for shoot regeneration than explants without it. Shoots obtained from multiple shoot cultures were successfully rooted and then acclimatized under greenhouse conditions to develop into adult cannabis plants.

Effect of Cannabidiol (CBD), a cannabis plant derivative, against Candida albicans growth and biofilm formation.

This study aimed to evaluate the antifungal activities of cannabidiol (CBD) against C. albicans. Yeast cells were treated once or twice with different concentrations (from 0 to 20 mg/ml) of CBD, showing a significant (p < 0.05) decreased the growth of C. albicans, with cell concentrations ranging from 5.1 × 106 cell/mL in the control to 1.8 × 106 cell/mL after one exposure to 20 µg/mL CBD. This growth reduction was greater after two exposures to CBD. After two exposures to 20 µg/mL CBD, the cell concentration was only 1.1 × 106 cell/mL. Such a growth decrease in C. albicans was confirmed by a reduced number of CFUs and a lower MTT value compared to the control. The growth inhibition was supported by a significant (p < 0.001) decrease in the yeast-to-hyphae transition, ranging from 20 ± 0.2% in the control to 2 ± 0.5% after exposure to 20 µg/mL CBD. Biofilm formation was also significantly reduced following CBD exposure. CBD at 10 and 20 µg/mL promoted the death of C. albicans through an apoptosis/necrotic pathway. Altogether, our results suggest the possible use of CBD, a cannabis derivative, to control C. albicans infection, including oral candidiasis.

Updated Risk Assessment of Cannabidiol in Foods Based on Benchmark Dose–Response Modeling

Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, has been approved as a drug in the European Union (EU) under the name “Epidyolex”. However, its approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating the benchmark dose were identified from the available data. Animal studies yielded a benchmark dose lower confidence limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only the Lowest-Observed-Adverse-Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed a health-based guidance value (HBGV) of 10 mg/day based on human LOAEL. Despite the existing data gaps, preliminary regulation appears advisable because the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

High-throughput LC-PDA method for determination of Δ9-THC and related cannabinoids in Cannabis sativa

Before the passage of the Agriculture Improvement Act of 2018, more commonly referred to as the 2018 Farm Bill, forensic laboratories were only required to perform qualitative measurements to confirm the identity of seized plant samples as Cannabis sativa (hemp or marijuana). The new law defines hemp at a federal level as Cannabis sativa containing 0.3 % or less Δ9-THC. Because forensic laboratories were not adequately equipped with the proper methods or training to meet these requirements, significant backlogs in casework resulted. The National Institute of Standards and Technology (NIST) responded by providing analytical tools to the forensic community. An accurate and precise method was previously developed to determine Δ9-THC, Δ9-THCA, and total Δ9-THC in botanical samples based on liquid chromatography with photodiode array detection (LC-PDA). Cannabis plant samples were ground and extracted with methanol using routine laboratory equipment. The original sample preparation procedure was time-consuming, taking over 70 min. The method described here has been optimized with the time required for sample preparation and LC-PDA analysis has been reduced to less than 30 min.

Real world clinical outcomes of treatment of cannabis-induced psychosis and prevalence of cannabis-related primary psychosis: a retrospective study

BackgroundCurrent treatment of cannabis-induced psychosis (CIP) focus on the presenting symptoms of individual patient. Therefore, the objective of this study was to investigate the efficacy of pharmacological treatment for CIP in a retrospective manner.MethodsA retrospective chart review study was conducted at the Princess Mother National Institute on Drug Abuse Treatment (PMNIDAT), Thailand. Patients aged more than 12 years who met the International Classification of Disease-10 (ICD-10) criteria of CIP, had recorded of cannabis use in medical chart, and had positive urine test of cannabis on the first day of admission from October 2013 to September 2019 were enrolled. The primary outcome was the efficacy of pharmacological treatment of CIP. Brief Psychotic Rating Scale (BPRS) on the first day and weekly after receiving treatment were used to assess the primary outcome.ResultsFour hundred and three medical charts with diagnosis of CIP were enrolled into the study and only 317 charts were analyzed. Most of them were male with an average aged of 21.0 (19.0–24.0) years old. All of them used smoked cannabis from dried leaves and flowers of cannabis plant. The presented symptoms on admission were psychosis, mood symptoms, sleep problems, weight loss, and cognitive problems (100%, 64%, 61%, 11%, and 7%, respectively). Baseline BPRS score of the first day of admission was 55.2 ± 9.6. Majority of patients received antipsychotic (98.7%) followed by the combination of antipsychotics with benzodiazepines (34.5.%), antipsychotics with antidepressants (14.4%) and antipsychotics treatment with antidepressants and benzodiazepines (25.9%). Only few patients received antipsychotic monotherapy (17.9%). Risperidone was the most frequently prescribed antipsychotics (83.6%). Mean equivalence dose of risperidone was 8.0 ± 5.9 mg/day. The average hospital length of stay was 28 days (range 22-31). BPRS at 22 days significantly improved compared to the first day of admission (p < 0.001). Schizophrenia was diagnosed in 7% at 1.3 years of follow up.ConclusionAntipsychotics was still a key psychotropic drug for treatment of CIP. The symptoms were decreased rapidly and sustained among the treatment period. However, antidepressants and benzodiazepines were commonly used for treatment of other symptoms beyond psychosis.Trial registrationClinicalTrials.gov ID: NCT04945031 (Registration Date: 30 June, 2021).

Cannabinoids and the heart-apsychiatrist's perspective.

The partial legalization of cannabis in Germany in 2024 will affect both medical and recreational use of cannabis. Tetrahydrocannabinol (THC), the main psychoactive component of the cannabis plant, influences heart rate and blood pressure through the endocannabinoid system. Acute and chronic use can pose cardiovascular risks. There is evidence of alink between cannabis use and cardiovascular events such as stroke and myocardial infarction, although studies show conflicting results. The non-psychoactive cannabidiol (CBD) could have anti-inflammatory and antioxidant effects. Smoking cannabis poses additional cardiovascular risks similar to tobacco. Given these risks, cardiologists should routinely ask their patients about possible cannabis use and inform them about the potential cardiovascular dangers. The article also highlights the psychiatric risks of cannabis use, including dependence and psychosis, and emphasizes the need for interdisciplinary collaboration between cardiologists and psychiatrists to effectively manage cannabis-related health problems.

Total Synthesis of the Dimeric Phytocannabinoid Cannabitwinol (CBD Dimer) and Its Analogues.

A new synthetic route to access the natural product phytocannabinoid cannabitwinol (1) starting from commercially available raw materials is disclosed. We have also demonstrated the synthesis of other related dimers, including their enantiomers, using the present sequence. This route avoids the legal constraints concerning the acquisition of cannabis plant material or CBD.

A Statewide Examination of Medical Cannabis Purchasing Patterns in Arkansas Over the Three Years Immediately Following Legalization.

Introduction: The use of medical cannabis (MC) to treat a host of conditions has expanded considerably in the United States; however, precise quantitative assessments of purchasing characteristics are unknown. This study sought to characterize the trends in MC purchases, US dollars spent, and type and amount purchased by demographic and clinical characteristics. Materials and Methods: This descriptive exploratory association study examined statewide MC registry data in Arkansas linked at the person level with statewide transaction data documenting each MC purchase. MC transaction data (May 11, 2019-August 31, 2022) were assessed to identify persons who could be linked to the registry data and made at least one purchase. Individual demographic characteristics and MC qualifying conditions (QCs) were ascertained. Product types were classified into plant cannabis, cannabis extract for inhalation (vape), edibles, and others. The average daily total delta-9-tetrahydrocannabinol (THC) purchased was calculated based on the concentration and quantity purchased. Purchasing characteristics are described and demographic and clinical factors associated with THC purchased per day and dollars spent per year were estimated by ordinary least square regression and general linear models with a gamma distribution. Results: On average, 89,057 MC purchasers spent $3343 (interquartile range [IQR], $907-$4802), had 33.34 (IQR, 8.32-46.03) transaction days per year, and purchased 162.32 mg (IQR, 30.51-237.69) of THC per day. Most persons predominantly purchased plant cannabis (68.27%), followed by edibles (14.92%) and vape (11.96%). Individuals younger than 18 years of age (β=-78.23; 95% confidence interval [CI], -116.599 to -39.863), persons 70 and older (β = -122.30; 95% CI, -128.18 to -116.422), and women (β=-33.70; 95% CI, -35.95 to -31.446) purchased less THC per day than their counterparts after multivariate adjustment. The most common QCs were pain and post-traumatic stress disorder (PTSD), and compared to those with cancer, persons with pain (β = 26.30; 95% CI, 18.636-33.96) and PTSD (β = 38.34; 95% CI, 30.467-46.222) purchased more THC per day. Conclusion: The average THC purchased per person per day exceeds typically recommended daily doses for therapeutic uses, and further research is warranted to assess the safety and benefits of MC across these conditions.

Transcriptomic analysis reveals differential gene expression patterns during cannabis leaf morphogenesis and phase transition

ABSTRACT Understanding the molecular mechanisms governing leaf morphogenesis and phase transition in Cannabis sativa is critical for optimizing its growth, development and yield. In this study, we conducted a comparative transcriptomic analysis to investigate the gene expression patterns associated with leaf development and the transition from vegetative to reproductive phases in cannabis plants. Following germination, cannabis plants display a distinct leaf developmental pattern. While the specific number of leaflets varies among cultivars, here we focused on the White Widow cultivar as a model. It showed an increase in the number of serrated leaflets from one (L1) to nine (L5) in a node-specific manner. Subsequently, the number of leaflets decreased from eight (L6) to three (L9). The transition from vegetative to reproductive phases, marked by the appearance of solitary flowers and a shift from opposite to alternate leaf phyllotaxy, occurred at node 7 and node 12, respectively. Analysis of gene expression revealed 1358 differentially expressed genes, with 1,182 genes showing differential expression across all leaves. Notably, several genes involved in leaf morphogenesis (e.g. YAB, AGO5, and TCP4) were found to be upregulated in compound leaves (L2) compared to simple leaves (L1), implying a role in leaflet formation and overall leaf morphology. Furthermore, several genes associated with phase transition and flowering (e.g. SPLs, ELFs, SOC1, and CEN-Like) exhibited specific expression patterns during the transition from vegetative to reproductive phases. These findings provide valuable insights into the genetic regulation of leaf morphogenesis and phase transition in cannabis.