The State of Synthetic Cannabinoid Medications for the Treatment of Pain.

Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of other clinical conditions, including neuropathic pain, spasticity-related pain, and nociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.

Cannabinoids detected in exhaled breath condensate after cannabis use.

Cannabinoids can be detected in breath after cannabis use, but different breath matrices need to be explored as studies to date with filter-based devices that collect breath aerosols have not demonstrated that breath-based measurements can reliably identify recent cannabis use. Exhaled breath condensate (EBC) is an unexplored aqueous breath matrix that contains condensed volatile compounds and water vapor in addition to aerosols. EBC was collected from participants both before and at two time points (0.7 ± 0.2 h and 1.7 ± 0.3 h) after observed cannabis use. Eleven different cannabinoids were monitored with liquid chromatography tandem mass spectrometry. Five different cannabinoids, including Δ9-tetrahydrocannabinol (THC), were detected in EBC collected from cannabis users. THC was detected in some EBC samples before cannabis use, despite the requested abstinence period. THC was detected in all EBC samples collected at 0.7 h post use and decreased for all participants at 1.7 h. Non-THC cannabinoids were only detected after cannabis use. THC concentrations in EBC samples collected at 0.7 h showed no trend with sample metrics like mass or number of breaths. EBC sampling devices deserve further investigation with respect to modes of cannabis use (e.g, edibles), post use time points, and optimization of cannabinoid recovery.

Association between cannabis potency and mental health in adolescence.

INTRODUCTION: In legal and illegal markets, high-potency cannabis (>10 % delta-9-tetrahydrocannabinol (THC)) is increasingly available. In adult samples higher-potency cannabis has been associated with mental health disorder but no studies have considered associations in adolescence. METHODS: A population-wide study compared no, low and high potency cannabis using adolescents (aged 13-14 years) self-reported symptoms of probable depression, anxiety, and auditory hallucinations. RESULTS: Of the 6672 participants, high-potency cannabis was used by 2.6 % (n=171) and low-potency by 0.6 % (n=38). After adjustment for sociodemographic factors, tobacco and alcohol use, in comparison to participants who had never used cannabis, people who had used high-potency but not low-potency cannabis were more likely to report symptoms of depression (odds ratio 1.59 [95 % confidence interval 1.06, 2.39), anxiety (OR 1.45, 95 % CI 0.96, 2.20), and auditory hallucinations (OR 1.56, 95 % CI 0.98, 2.47). CONCLUSIONS: High-potency cannabis use is associated with an increased risk of probable mental health disorders. Services and programming to minimise drug harms may need to be adapted to pay more attention to cannabis potency.

Potent, Selective Agonists for the Cannabinoid-like Orphan G Protein-Coupled Receptor GPR18: A Promising Drug Target for Cancer and Immunity.

The human orphan G protein-coupled receptor GPR18, activated by Δ9-tetrahydrocannabinol (THC), constitutes a promising drug target in immunology and cancer. However, studies on GPR18 are hampered by the lack of suitable tool compounds. In the present study, potent and selective GPR18 agonists were developed showing low nanomolar potency at human and mouse GPR18, determined in ß-arrestin recruitment assays. Structure-activity relationships were analyzed, and selectivity versus cannabinoid (CB) and CB-like receptors was assessed. Compound 51 (PSB-KK1415, EC50 19.1 nM) was the most potent GPR18 agonist showing at least 25-fold selectivity versus CB receptors. The most selective GPR18 agonist 50 (PSB-KK1445, EC50 45.4 nM) displayed >200-fold selectivity versus both CB receptor subtypes, GPR55, and GPR183. The new GPR18 agonists showed minimal species differences, while THC acted as a weak partial agonist at the mouse receptor. The newly discovered compounds represent the most potent and selective GPR18 agonists reported to date.

Medicinal Cannabis (MedCan 3): a randomised, multicentre, double-blind, placebo-controlled trial to assess THC/CBD (1:20) to relieve symptom burden in patients with cancer-a study protocol for a randomised controlled trial.

BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.

Profiling of seized Cannabis sativa L. flowering tops by means of microwave-assisted hydro distillation and gas chromatography analyses.

This research aimed to support police forces in their battle against illicit drug trafficking by means of a multi-technique approach, based on gas chromatography. In detail, this study was focused on the profiling of volatile substances in narcotic Cannabis sativa L. flowering tops. For this purpose, the Scientific Investigation Department, RIS Carabinieri of Messina, provided 25 seized samples of Cannabis sativa L. The content of Δ9-tetrahydrocannabinol (THC), useful to classify cannabis plant as hemp (≤ 0.2 %) or as marijuana (> 0.2 %), was investigated. Essential oils of illicit drug samples were extracted using a microwave-assisted hydro-distillation (MAHD) system; GC-MS and GC-FID analytical techniques were used for the characterization of the terpenes and terpenoids fingerprint. Furthermore, the enantiomeric and carbon isotopic ratios of selected chiral compounds were investigated using a heart-cutting multidimensional GC (MDGC) approach. The latter exploited a combination of an apolar column in the first dimension, and a chiral cyclodextrin-based column in the second one, prior to parallel isotope-ratio mass spectrometry (C-IRMS) and MS detection. Finally, all the data were gathered into a statistical model, to demonstrate the existence of useful parameters to be used for the classification of seized samples.

Sensor for Rapid In-Field Classification of Cannabis Samples Based on Near-Infrared Spectroscopy.

A rugged handheld sensor for rapid in-field classification of cannabis samples based on their THC content using ultra-compact near-infrared spectrometer technology is presented. The device is designed for use by the Austrian authorities to discriminate between legal and illegal cannabis samples directly at the place of intervention. Hence, the sensor allows direct measurement through commonly encountered transparent plastic packaging made from polypropylene or polyethylene without any sample preparation. The measurement time is below 20 s. Measured spectral data are evaluated using partial least squares discriminant analysis directly on the device's hardware, eliminating the need for internet connectivity for cloud computing. The classification result is visually indicated directly on the sensor via a colored LED. Validation of the sensor is performed on an independent data set acquired by non-expert users after a short introduction. Despite the challenging setting, the achieved classification accuracy is higher than 80%. Therefore, the handheld sensor has the potential to reduce the number of unnecessarily confiscated legal cannabis samples, which would lead to significant monetary savings for the authorities.

Effects of Cannabidiol, ∆9-Tetrahydrocannabinol, and WIN 55-212-22 on the Viability of Canine and Human Non-Hodgkin Lymphoma Cell Lines.

In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines' viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 µM to 50 µM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.

Targeting Colorectal Cancer: Unravelling the Transcriptomic Impact of Cisplatin and High-THC Cannabis Extract.

Cisplatin and other platinum-derived chemotherapy drugs have been used for the treatment of cancer for a long time and are often combined with other medications. Unfortunately, tumours often develop resistance to cisplatin, forcing scientists to look for alternatives or synergistic combinations with other drugs. In this work, we attempted to find a potential synergistic effect between cisplatin and cannabinoid delta-9-THC, as well as the high-THC Cannabis sativa extract, for the treatment of HT-29, HCT-116, and LS-174T colorectal cancer cell lines. However, we found that combinations of the high-THC cannabis extract with cisplatin worked antagonistically on the tested colorectal cancer cell lines. To elucidate the mechanisms of drug interactions and the distinct impacts of individual treatments, we conducted a comprehensive transcriptomic analysis of affected pathways within the colorectal cancer cell line HT-29. Our primary objective was to gain a deeper understanding of the underlying molecular mechanisms associated with each treatment modality and their potential interactions. Our findings revealed an antagonistic interaction between cisplatin and high-THC cannabis extract, which could be linked to alterations in gene transcription associated with cell death (BCL2, BAD, caspase 10), DNA repair pathways (Rad52), and cancer pathways related to drug resistance.

Determination of Δ9-tetrahydrocannabinol, 11-nor-carboxy-Δ9-tetrahydrocannabinol and cannabidiol in human plasma and urine after a commercial cannabidiol oil product intake.

PURPOSE: Cannabidiol (CBD) products are widely used for pain relief, sleep improvement, management of seizures etc. Although the concentrations of Δ9-tetrahydrocannabinol (Δ9-THC) in these products are low (≤0.3% w/w), it is important to investigate if its presence and/or that of its metabolite 11-nor-carboxy-Δ9-THC, is traceable in plasma and urine samples of individuals who take CBD oil products. METHODS: A sensitive GC/MS method for the determination of Δ9-THC, 11-nor-carboxy-Δ9-THC and CBD in plasma and urine samples was developed and validated. The sample preparation procedure included protein precipitation for plasma samples and hydrolysis for urine samples, solid-phase extraction and finally derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide) with 1% trimethylchlorosilane. RESULTS: For all analytes, the LOD and LOQ were 0.06 and 0.20 ng/mL, respectively. The calibration curves were linear (R2 ≥ 0.992), and absolute recoveries were ≥91.7%. Accuracy and precision were within the accepted range. From the analysis of biologic samples of 10 human participants who were taking CBD oil, it was realized that Δ9-THC was not detected in urine, while 11-nor-carboxy-Δ9-THC (0.69-23.06 ng/mL) and CBD (0.29-96.78 ng/mL) were found in all urine samples. Regarding plasma samples, Δ9-THC (0.21-0.62 ng/mL) was detected in 10, 11-nor-carboxy-Δ9-THC (0.20-2.44 ng/mL) in 35, while CBD (0.20-1.58 ng/mL) in 25 out of 38 samples, respectively. CONCLUSION: The results showed that Δ9-THC is likely to be found in plasma although at low concentrations. In addition, the detection of 11-nor-carboxy-Δ9-THC in both urine and plasma samples raises questions and concerns for the proper interpretation of toxicological results, especially considering Greece's zero tolerance law applied in DUID and workplace cases.

Low UV radiation influenced DNA methylation, gene regulation, cell proliferation, viability, and biochemical differentiation in the cell suspension cultures of Cannabis indica.

The effect of low artificial Ultraviolet (UV) on the DNA methylation remains controversial. This study addresses how differential photoperiods of UV radiation affect the biochemical and molecular behaviors of Cannabis indica cell suspension cultures. The cell suspensions were illuminated with the compact fluorescent lamps (CFL), emitting a combination of 10% UVB, 30% UVA, and the rest visible wavelengths for 0, 4, 8, and 16 h. The applied photoperiods influenced cell morphological characteristics. The 4 h photoperiod was the most effective treatment for improving biomass, growth index and cell viability percentage while these indices remained non-significant in the 16 h treatment. The methylation-sensitive amplified polymorphism (MASP) assay revealed that the UV radiation was epigenetically accompanied by DNA hypermethylation. The light-treated cells significantly displayed higher relative expression of the cannabidiolic| acid synthase (CBDAS) and delta9-tetrahydrocannabinolic acid synthase (THCAS) genes about 4-fold. The expression of the olivetolic acid cyclase (OAC) and olivetol synthase (OLS) genes exhibited an upward trend in response to the UV radiation. The light treatments also enhanced the proline content and protein concentration. The 4 h illumination was significantly capable of improving the cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) concentrations, in contrast with 16 h. By increasing the illumination exposure time, the activity of the phenylalanine ammonia-lyase (PAL) enzyme linearly upregulated. The highest amounts of the phenylpropanoid derivatives were observed in the cells cultured under the radiation for 4 h. Taken collective, artificial UV radiation can induce DNA methylation modifications and impact biochemical and molecular differentiation in the cell suspensions in a photoperiod-dependent manner.

Patterns of delta 8 THC and cannabis uptake in Nebraska: A cannabis prohibition state.

BACKGROUND: Following the passage of the 2018 Farm Bill, derived psychoactive cannabis products containing delta 8 tetrahydrocannabinol (THC) have become increasingly popular across the US, particularly in states that lack medical or recreational cannabis programs. Despite this, little is known about patterns of delta 8 THC use. METHODS: A sample of Nebraska residents (a state without legal medical or recreational cannabis) were surveyed to gather data on substance use, including delta 8 THC and cannabis, across the state. Then, logistic regressions were used to calculate relative odds ratios to understand the factors that increased the likelihood at which Nebraska residents use delta 8 THC or cannabis products. RESULTS: Analysis revealed that younger adults have higher odds of delta 8 THC use but not cannabis and that non-white participants had higher odds of delta 8 use than white non-Hispanic groups but there was no difference for cannabis use. Political affiliation, sexual orientation, access, and knowledge of friends who used cannabis were also associated with cannabis use but not delta 8 THC use. Past substance use and personal opinion regarding cannabis use increased likelihood for both delta 8 THC and cannabis use. CONCLUSION: These results illuminate several factors which affect cannabis and delta 8 THC use while providing insight on the people that are most likely to be impacted by the potential consequences of substance use, especially when considering the inconsistent laws governing cannabis and delta 8 THC use across the US.

Does medicinal cannabis affect depression, anxiety, and stress in people with cancer? A systematic review and meta-analysis of intervention studies.

INTRODUCTION: Medicinal cannabis might have a role in supporting the mental health of people with cancer. This systematic review and meta-analysis examined the efficacy and safety of medicinal cannabis, compared with any control, as an intervention for depression, anxiety, and stress symptoms in people living with cancer. A secondary aim was to examine the effect of low versus high Δ9-tetrahydrocannabinol (THC) dose on these outcomes. METHODS: Five databases were systematically searched, and complemented with a snowball search from inception to May 2023, for any type of interventional study that included humans of any age with any cancer type. Primary outcomes were incidence and severity of depression, anxiety, and stress symptoms. Secondary outcomes were mood, cognition, quality of life, appetite, nutrition status, gastrointestinal symptoms, and adverse events. Data were pooled using Review Manager. Evidence was appraised using Cochrane risk of bias tools. Confidence in the estimated effect of pooled outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Fifteen studies (n = 11 randomized trials, n = 4 non-randomized trials) of 18 interventions (N = 1898 total participants; 100 % ≥18 years of age) were included. Ten studies examined THC (70 % synthetic), two synthetic cannabidiol with or without THC, and six whole-plant extracts. No clinically significant effects of medicinal cannabis were found on primary outcomes. The likelihood of anxiety events increased with higher-dose synthetic THC compared with a lower dose (OR: 2.0; 95 % CI: 1.4, 2.9; p < 0.001; Confidence: very low). Medicinal cannabis (THC, cannabidiol, and whole-plant extract) increased the likelihood of improved appetite (OR: 12.3; 95 % CI: 3.5, 45.5; p < 0.001; n = 3 interventions; Confidence: moderate) and reduced severity of appetite loss (SMD: -0.4; 95 % CI: -0.8, -0.1; p = 0.009; Confidence: very low). There was very low confidence that higher doses of synthetic THC increased the likelihood of any adverse event (OR: 0.5; 95 % CI: 0.3, 0.7; p < 0.001). Medicinal cannabis had no effect on emotional functioning, mood changes, confusion, disorientation, quality of life, and gastrointestinal symptoms. Confidence in findings was limited by some studies having high or unclear risk of bias and imprecise pooled estimates. CONCLUSIONS: There was insufficient evidence to determine the efficacy and safety of medicinal cannabis as a therapeutic intervention for depression, anxiety, or stress in people with active cancer. Further research should explore whether medicinal cannabis might improve and maintain appetite and if high-dose synthetic THC might increase the incidence of side-effects, including anxiety. To inform clinical practice, well-powered and rigorously designed trials are warranted that evaluate the effects of medicinal cannabis prescribed to target anxiety, depression, and stress.

Δ(9)-tetrahydrocannabinol protects cardiac tissue against endoplasmic reticulum and oxidative stresses, apoptosis, and inflammation in rats with hyperinsulinemia.

OBJECTIVES: In our study, we aimed to examine how δ(9)-tetrahydrocannabinol (THC) administration to hyperinsulinemia (HI) model rats would change endoplasmic reticulum stress (ERS), apoptosis, inflammation, and oxidative stress in cardiac tissue. METHODS: Rats were divided into four groups (n = 32): Control (C), THC, HI, and Treatment (Tre). Fructose (10%) in the drinking water was given to HI and Tre rats for 12 weeks. 1.5 mg/kg/d THC was given intraperitoneally to THC and Tre rats in the last 4 weeks of the experiment. The mRNA expressions of ERS and apoptosis markers in the cardiac tissue were detected. TNF-α concentration and oxidative stress were also analyzed. KEY FINDINGS: THC treatment in rats with HI ameliorated the overexpression of GRP-78, IRE1α, ATF6, ATF4, CHOP, Cas-12, Cas-8, Cas-9, and Cas-3 mRNAs, markers of ERS and apoptosis (P < .0001 for all). In addition, THC has been shown to reduce inflammation in the Tre group by causing a decrease in increased cardiac TNF-α levels (P < .01). Moreover, THC prevented cardiac tissue damage by regulating the degraded oxidative stress marker levels and antioxidant enzyme activities in HI. CONCLUSIONS: Our findings suggest that THC treatment in rats with HI exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.

Adolescent Δ8-THC and Marijuana Use in the US.

Importance: Gummies, flavored vaping devices, and other cannabis products containing psychoactive hemp-derived Δ8-tetrahydrocannabinol (THC) are increasingly marketed in the US with claims of being federally legal and comparable to marijuana. National data on prevalence and correlates of Δ8-THC use and comparisons to marijuana use among adolescents in the US are lacking. Objective: To estimate the self-reported prevalence of and sociodemographic and policy factors associated with Δ8-THC and marijuana use among US adolescents in the past 12 months. Design, Setting, and Participants: This nationally representative cross-sectional analysis included a randomly selected subset of 12th-grade students in 27 US states who participated in the Monitoring the Future Study in-school survey during February to June 2023. Exposures: Self-reported sex, race, ethnicity, and parental education; census region; state-level adult-use (ie, recreational) marijuana legalization (yes vs no); and state-level Δ8-THC policies (regulated vs not regulated). Main Outcomes and Measures: The primary outcome was self-reported Δ8-THC and marijuana use in the past 12 months (any vs no use and number of occasions used). Results: In the sample of 2186 12th-grade students (mean age, 17.7 years; 1054 [48.9% weighted] were female; 232 [11.1%] were Black, 411 [23.5%] were Hispanic, 1113 [46.1%] were White, and 328 [14.2%] were multiracial), prevalence of self-reported use in the past 12 months was 11.4% (95% CI, 8.6%-14.2%) for Δ8-THC and 30.4% (95% CI, 26.5%-34.4%) for marijuana. Of those 295 participants reporting Δ8-THC use, 35.4% used it at least 10 times in the past 12 months. Prevalence of Δ8-THC use was lower in Western vs Southern census regions (5.0% vs 14.3%; risk difference [RD], -9.4% [95% CI, -15.2% to -3.5%]; adjusted risk ratio [aRR], 0.35 [95% CI, 0.16-0.77]), states in which Δ8-THC was regulated vs not regulated (5.7% vs 14.4%; RD, -8.6% [95% CI, -12.9% to -4.4%]; aRR, 0.42 [95% CI, 0.23-0.74]), and states with vs without legal adult-use marijuana (8.0% vs 14.0%; RD, -6.0% [95% CI, -10.8% to -1.2%]; aRR, 0.56 [95% CI, 0.35-0.91]). Use in the past 12 months was lower among Hispanic than White participants for Δ8-THC (7.3% vs 14.4%; RD, -7.2% [95% CI, -12.2% to -2.1%]; aRR, 0.54 [95% CI, 0.34-0.87]) and marijuana (24.5% vs 33.0%; RD, -8.5% [95% CI, -14.9% to -2.1%]; aRR, 0.74 [95% CI, 0.59-0.94]). Δ8-THC and marijuana use prevalence did not differ by sex or parental education. Conclusions and Relevance: Δ8-THC use prevalence is appreciable among US adolescents and is higher in states without marijuana legalization or existing Δ8-THC regulations. Prioritizing surveillance, policy, and public health efforts addressing adolescent Δ8-THC use may be warranted.

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

PURPOSE: Cannabis 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. METHODS: People 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. RESULTS: Less 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. CONCLUSION: Self-reported knowledge of THC and CBD concentration statistically differed according to MOD, source of acquisition, source of instruction, and current cannabis use.

Hexahydrocannabinol poisoning reported to French poison centres.

INTRODUCTION: Hexahydrocannabinol is a hexahydro derivative of cannabinol. Poisoning with hexahydrocannabinol was first observed in Europe in May 2022. METHOD: This is a retrospective observational study of cases of self-reported hexahydrocannabinol exposure reported to French poison centres between 1 January 2022 and 31 May 2023. RESULTS: There were 37 cases, including 19 in May 2023. The median age of the patients was 36 (interquartile range 28-43) years, and most were men. Eight patients had a history of substance use disorder. The route of exposure was ingestion in 24, inhalation (smoking or vaping) in 10, inhalation and ingestion in two and sublingual in one. Clinical features were neurological (85 per cent), cardiovascular (61 per cent), gastrointestinal (33 per cent), psychiatric (27 per cent) and ocular (21 per cent). Fifty-nine per cent of the patients were hospitalized. In four patients, the Poisoning Severity Score was 0 (asymptomatic); in 15 patients, the Score was 1 (minor); in 16, the Score was 2 (moderate); and in two cases, the Score was 3 (severe). In 70 per cent of patients, the outcome was known, and all recovered. Testing of biological samples was only undertaken in six cases. Five patients had positive blood or urine tests for hexahydrocannabinol; in two patients, tetrahydrocannabinol and metabolites were also detected. In addition, there was an additional patient in whom Δ8- and Δ9-tetrahydrocannabinol was detected in the substances used. DISCUSSION: Clinical effects reported in this series included neuropsychiatric and somatic effects. Whilst these cases related to self-reported hexahydrocannabinol use, it is likely that tetrahydrocannabinol use also contributed to the effects in a substantial proportion of cases. This study has some limitations, such as the lack of available information due to the retrospective nature of the study. As a result, it probably overestimates the number of moderate and severe cases due to under-reporting of cases of little or no severity. Analysis of the patient's blood and urine was performed only in six patients, so we cannot be certain that the products consumed by the other patients were hexahydrocannabinol. CONCLUSION: The clinical effects attributed to hexahydrocannabinol were neurological, cardiovascular, gastrointestinal, psychiatric and ocular predominantly and were sometimes serious.

A Comparative Analysis on the Potential Anticancer Properties of Tetrahydrocannabinol, Cannabidiol, and Tetrahydrocannabivarin Compounds Through In Silico Approach.

OBJECTIVE: The purpose of this study is to comparatively analyze the anticancer properties of Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Tetrahydrocannabivarin (THCV) using In silico tools. METHODS: Using SwissADME and pkCSM, the physicochemical and pharmacokinetics properties of the cannabinoids were evaluated. Protox-II was utilized for the assessment of their cytotoxicity. The chemical-biological interactions of the cannabinoids were also predicted using the Way2Drug Predictive Server which comprises Acute Rat Toxicity, Adver-Pred, CLC-Pred, and Pass Target Prediction. RESULTS: Both physicochemical and drug-likeness analysis using SwissADME favored THCV due to high water solubility and lower MLOGP value. On the other hand, ADMET assessment demonstrated that THC and CBD have good skin permeability while both THC and THCV exhibited better BBB permeability and have low inhibitory activity on the CYP1A2 enzyme. Furthermore, toxicity predictions by Protox-II revealed that CBD has the lowest probability of hepatotoxicity, carcinogenicity, and immunotoxicity. Contrarily, it has the highest probability of being inactive in mutagenicity and cytotoxicity. Additionally, CLC results revealed that CBD has the highest probability against lung carcinoma. The rat toxicity prediction showed that among the cannabinoids, THCV had the lowest LD50 concentration in rat oral and IV. CONCLUSION: Overall, in silico predictions of the three cannabinoid compounds revealed that they are good candidates for oral drug formulation. Among the three cannabinoids, THCV is an excellent anticancer aspirant for future chemotherapy with the most favorable results in drug-likeness and ADMET analysis, pharmacological properties evaluation, and cytotoxicity assessment results. Further study on bioevaluation of compounds is needed to elucidate their potential pharmacological activities.

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® - A Cannabis-derived Spray.

Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.