CannaSearch Daily on CBD + Hemp

J Pharm Pharmacol. 2023 Mar 22:rgad023. doi: 10.1093/jpp/rgad023. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to investigate the effect of cannabidiol (CBD) on type 4 Toll-like receptors (TLR4), glial cells and pro-inflammatory cytokines during the neuropathic pain induced by the chemotherapy agent paclitaxel (PTX), as well as the involvement of the endocannabinoid system in this process.

METHODS: Male C57BL6 mice were subjected to PTX-induced neuropathic pain. To evaluate the involvement of the TLR4, glial cells and cannabinoid CB2 receptor, specific inhibitors or antagonists were intrathecally administered. The western blotting and immunofluorescence assay was performed to evaluate the spinal expression of TLR4, microglia, astrocytes and cannabinoid CB2 receptor. The levels of spinal pro-inflammatory cytokines and endocannabinoids were determined by enzyme-linked immunosorbent assay and liquid chromatography-mass spectrometry analysis, respectively.

KEY FINDINGS: CBD prevented PTX-induced neuropathic pain, and the cannabinoid CB2 receptor antagonist AM630 reversed this effect. In addition, CBD treatment inhibited the spinal expression of TLR4 and Iba1 in mice with neuropathic pain. CBD also increased spinal levels of endocannabinoids anandamide and 2-arachidonoylglycerol, and reduced levels of cytokines in mice with neuropathic pain.

CONCLUSIONS: CBD was efficient in preventing PTX-induced neuropathic pain, and this effect may involve inhibition of the TLR4 on microglia spinal with activation of the endocannabinoid system.

PMID:36946366 | DOI:10.1093/jpp/rgad023

Curr Neuropharmacol. 2023 Mar 22. doi: 10.2174/1570159X21666230322143401. Online ahead of print.

ABSTRACT

BACKGROUND: Compelling evidence from preclinical and clinical studies supports the therapeutic role of cannabidiol (CBD) in several medical disorders. We reviewed the scientific evidence on CBD-related toxicity and adverse events (AEs) in 2019, at the beginning of the spike in clinical studies involving CBD. However, CBD safety remained uncertain.

OBJECTIVE: With the benefit of hindsight, we aimed to provide an update on CBD-related toxicity and AEs in humans.

METHODS: A systematic literature search was conducted following PRISMA guidelines. PubMed, Cochrane, and Embase were accessed in October 2022 to identify clinical studies mentioning CBD-related toxicity/AEs from February 2019 to September 2022. Study design, population characteristics, CBD doses, treatment duration, co-medications, and AEs were compiled.

RESULTS: A total of 51 reports were included. Most studies investigated CBD efficacy and safety in neurological conditions, such as treatment-resistant epilepsies, although a growing number of studies are focusing on specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Most studies report mild or moderate severity of AEs. The most common AEs are diarrhea, somnolence, sedation, and upper respiratory disturbances. Few serious AEs have been reported, especially when CBD is co-administered with other classes of drugs, such as clobazam and valproate.

CONCLUSIONS: Clinical data suggest that CBD is well tolerated and associated with few serious AEs at therapeutic doses both in children and adults. However, interactions with other medications should be monitored.

PMID:36946485 | DOI:10.2174/1570159X21666230322143401

bioRxiv. 2023 Mar 6:2023.03.03.531053. doi: 10.1101/2023.03.03.531053. Preprint.

ABSTRACT

INTRODUCTION: The endocannabinoids ( eCBs ), 2-arachidonoylglycerol ( 2-AG ) and arachidonoyl ethanolamine ( AEA ), are produced by separate enzymatic pathways, activate cannabinoid receptors with distinct pharmacology, and differentially regulate pathophysiological processes. The genetically encoded sensor, GRAB _eCB2.0 , detects real-time changes in eCB levels in cells in culture and preclinical model systems; however, its activation by eCB analogues produced by cells and by phyto-cannabinoids remains uncharacterized, a current limitation when interpreting changes in its response. This information could provide additional utility for the tool in in vivo pharmacology studies of phyto-cannabinoid action.

METHODS: GRAB _eCB2.0 was expressed in cultured HEK293 cells. Live cell confocal microscopy and high-throughput fluorescent signal measurements.

RESULTS: 2-AG increased GRAB _eCB2.0 fluorescent signal (EC ₅₀ = 85 nM), and the cannabinoid 1 receptor ( CB ₁ R ) antagonist, SR141617, decreased GRAB _eCB2.0 signal ( SR1 , IC ₅₀ = 3.3 nM), responses that mirror their known potencies at cannabinoid 1 receptors ( CB ₁ R ). GRAB _eCB2.0 fluorescent signal also increased in response to AEA (EC ₅₀ = 815 nM), the eCB analogues 2-linoleoylglycerol and 2-oleoylglycerol ( 2-LG and 2-OG , EC ₅₀ s = 1.5 and 1.0 μM, respectively), Δ ⁹ -tetrahydrocannabinol ( Δ ⁹ -THC ) and Δ ⁸ -THC (EC ₅₀ s = 1.6 and 2.0 μM, respectively), and the artificial CB ₁ R agonist, CP55,940 ( CP , EC ₅₀ = 82 nM); however their potencies were less than what has been described at CB ₁ R. Cannabidiol ( CBD ) did not affect basal GRAB _eCB2.0 fluorescent signal and yet reduced the 2-AG stimulated GRAB _eCB2.0 responses (IC ₅₀ = 8.8 nM).

CONCLUSIONS: 2-AG and SR1 modulate the GRAB _eCB2.0 fluorescent signal with EC ₅₀ s that mirror their potencies at CB ₁ R whereas AEA, eCB analogues, THC and CP increase GRAB _eCB2.0 fluorescent signal with EC ₅₀ s significantly lower than their potencies at CB ₁ R. CBD reduces the 2-AG response without affecting basal signal, suggesting that GRAB _eCB2.0 retains the negative allosteric modulator ( NAM ) property of CBD at CB ₁ R. This study describes the pharmacological profile of GRAB _eCB2.0 to improve interpretation of changes in fluorescent signal in response to a series of known eCBs and CB ₁ R ligands.

PMID:36945533 | PMC:PMC10028790 | DOI:10.1101/2023.03.03.531053

Iran J Pharm Res. 2023 Feb 25;21(1):e132647. doi: 10.5812/ijpr-132647. eCollection 2022 Dec.

ABSTRACT

The current study aimed to evaluate the safety profile and efficacy of a cannabis-based sublingual spray, CBDEX10^® (containing 100 µg cannabidiol and 10 µg Δ⁹-tetrahydrocannabinol per puff; CBD/Δ⁹-THC 10:1), in improving lipid profile and glycemic state of the diabetic patients. Fifty diabetic patients were randomly allocated to the treatment (n = 25; receiving two puffs of CBDEX10^® twice daily) or the control groups (n = 25; receiving two puffs of placebo). The primary endpoint of the study was to evaluate the efficacy of the CBDEX10^® adjunctive therapy in improving the lipid profile and glycemic state of diabetic patients; the secondary endpoint was to assess the safety profile and tolerability of the spray. A statistically significant decline in total cholesterol [estimated treatment difference (ETD) = -19.73 mg/dL; P < 0.05], triglyceride (ETD = -27.84 mg/dL; P < 0.01), LDL-C (ETD = -5.37 mg/dL; P < 0.01), FBS (ETD = -12 mg/dL; P < 0.01), Hb A1C (ETD = -0.21 mg/dL; P < 0.01) and insulin secretion (ETD = -5.21 mIU/L; P < 0.01) was observable in the patients treated with CBDEX10^® at the end of the 8-week treatment period. Regarding safety, the mentioned adjunctive regimen was well, and there were no serious or severe adverse effects. Overall, CBDEX1^® sublingual spray could be a new therapeutic agent for lipid and glycemic control in diabetic patients.

PMID:36945340 | PMC:PMC10024807 | DOI:10.5812/ijpr-132647

J Cannabis Res. 2023 Mar 21;5(1):9. doi: 10.1186/s42238-023-00176-x.

ABSTRACT

BACKGROUND: Delta-8 tetrahydrocannabinol (THC) is a psychoactive cannabinoid from the cannabis plant that can be synthetically converted from cannabidiol (CBD). Most states permit the full or restricted sale of hemp and hemp-derived CBD products, and therefore, delta-8 THC products are on the rise. Delta-8 THC consumption can cause intoxication. Products are often sold in edible form and occasionally in packaging that appears similar to candy. Clinical presentations for delta-8 THC ingestions are understudied and may differ from those described for delta-9 THC ingestions.

CASE PRESENTATION: This case report describes unintentional ingestions of putative delta-8 THC by two pediatric patients that results in admission to the pediatric intensive care unit. The ingestions were of putative delta-8 THC infused product that resembled popular candies. Both patients developed periods of bradypnea with continued intermittent periods of agitation. Medical intervention included observation, noninvasive positive pressure ventilation via high flow nasal cannula, and intubation-but was not needed for both patients. Although family noted ongoing irritability for the patients, both were discharged approximately 45 h after ingestion. Delta-8 THC ingestion is reliant on self-report.

CONCLUSIONS: As the availability of delta-8 THC increases, along with associated pediatric exposures, it is imperative for health care providers to quickly recognize and provide adequate treatment. While there is no specific antidote for THC intoxication beyond supportive care, providers can play an important role in prevention by educating parents and guardians on safe cannabis storage and by documenting cases for adverse event monitoring.

PMID:36941718 | DOI:10.1186/s42238-023-00176-x

Cannabis Cannabinoid Res. 2023 Mar 21. doi: 10.1089/can.2022.0344. Online ahead of print.

ABSTRACT

Background: Studies have reported that cannabinoids, in particular Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD), significantly reduce cancer cell viability in vitro. Unfortunately, treatment conditions vary significantly across reports. In particular, a majority of reports utilize conditions with reduced serum concentrations (0-3%) that may compromise the growth of the cells themselves, as well as the observed results. Objectives: This study was designed to test the hypothesis that, based on their known protein binding characteristics, cannabinoids would be less effective in the presence of fetal bovine serum (FBS). Moreover, we wished to determine if the treatments served to be cytotoxic or cytostatic under these conditions. Methods: Six cancer cell lines, representing two independent lines of three different types of cancer (glioblastoma, melanoma, and colorectal cancer [CRC]), were treated with 10 μM pure Δ⁹-THC, CBD, KM-233, and HU-331 for 48 h (in the presence or absence of FBS). Cell viability was measured with the MTT assay. Dose-response curves were then generated comparing the potencies of the four cannabinoids under the same conditions. Results: We found that serum-free medium alone produces cell cycle arrest for CRC cells and slows cell growth for the other cancer types. The antineoplastic effects of three of the four cannabinoids (Δ⁹-THC, CBD, and KM-233) increase when serum is omitted from the media. In addition, dose-response curves for these drugs demonstrated lower IC₅₀ values for serum-free media compared with the media with 10% serum in all cell lines. The fourth compound, HU-331, was equally effective under both conditions. A further confound we observed is that omission of serum produces dramatic binding of Δ⁹-THC and CBD to plastic. Conclusions: Treatment of cancer cells in the absence of FBS appears to enhance the potency of cannabinoids. However, omission of FBS itself compromises cell growth and represents a less physiological condition. Given the knowledge that cannabinoids are 90-95% protein bound and have well-known affinities for plastic, it may be ill-advised to treat cells under conditions where the cells are not growing optimally and where known concentrations cannot be assumed (i.e., FBS-free conditions).

PMID:36944160 | DOI:10.1089/can.2022.0344

Psychopharmacology (Berl). 2023 Mar 20. doi: 10.1007/s00213-023-06349-z. Online ahead of print.

ABSTRACT

RATIONALE: Cannabidiol (CBD) is found in the cannabis plant and has garnered attention as a potential treatment for alcohol use disorder (AUD). CBD reduces alcohol consumption and other markers of alcohol dependence in rodents, but human research on CBD and alcohol is limited. It is unknown whether CBD reduces drinking in humans, and mechanisms through which CBD could impact behavioral AUD phenotypes are unknown.

OBJECTIVES: This study explores effects of oral CBD on breath alcohol level (BrAC), and subjective effects of alcohol in human participants who report heavy drinking.

METHODS: In this placebo-controlled, crossover study, participants consumed 30 mg CBD, 200 mg CBD, or placebo CBD before receiving a standardized alcohol dose. Participants were blind to which CBD dose they received at each session and completed sessions in random order. Thirty-six individuals completed at least one session and were included in analyses.

RESULTS: Differences in outcomes across the three conditions and by sex were explored using multilevel structural equation models. BrAC fell fastest in the placebo condition, followed by 30 mg and 200 mg CBD. Stimulation decreased more slowly in the 200 mg CBD condition than in placebo (b = – 2.38, BCI [- 4.46, – .03]). Sedation decreased more slowly in the 30 mg CBD condition than in placebo (b = – 2.41, BCI [- 4.61, – .09]). However, the magnitude of condition differences in BrAC and subjective effects was trivial.

CONCLUSIONS: CBD has minimal influence on BrAC and subjective effects of alcohol. Further research is needed to test whether CBD impacts alcohol consumption in humans, and if so, what mechanism(s) may explain this effect.

PMID:36939855 | DOI:10.1007/s00213-023-06349-z

Analyst. 2023 Mar 14. doi: 10.1039/d3an00084b. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), the most predominant cannabinoid, may cause addiction and liver damage. In this study, we synthesized a CBD hapten containing the carboxyl group of the spacer arm by derivatizing CBD. A highly specific and sensitive monoclonal antibody (mAb) was prepared with a half-maximal inhibitory concentration of 2.03 ng mL^-1 and a limit of detection of 0.32 ng mL^-1. MAb was highly specific for CBD. We developed an immunochromatographic assay (ICA) for the detection of CBD in functional beverages with a visible limit of detection of 100 ng mL^-1 and a cut-off of 1000 ng mL^-1. Compared with HPLC, ICA is more efficient and accurate and can be used for the rapid on-site detection of CBD in samples.

PMID:36916524 | DOI:10.1039/d3an00084b

Biomed Pharmacother. 2023 Feb;158:114163. doi: 10.1016/j.biopha.2022.114163. Epub 2023 Jan 4.

ABSTRACT

Cannabis has been used for centuries to treat pain. The antinociceptive activity of tetrahydrocannabinol (THC) or cannabidiol (CBD) has been widely studied. However, the antinociceptive effects of other cannabis components, such as cannabichromene (CBC) and cannabigerol (CBG), have rarely been revealed. The antinociceptive mechanism of CBG is not yet clear, so we investigated the antinociceptive effect of CBG on different pain models, and explored the mechanism of action of CBG to exert antinociceptive effects. In the current study, we compared the antinociceptive effects of CBC, CBD, and CBG on the carrageenan-induced inflammatory pain model in mice, and the results showed that CBG had a better antinociceptive effects through intraplantar administration. On this basis, we further investigated the antinociceptive effect of CBG on CIA-induced arthritis pain model and nerve pain model in mice, and found that CBG also relieved on both types of pain. Then, we explored the antinociceptive mechanism of CBG, which revealed that CBG can activate TRPV1 and desensitize it to block the transmission of pain signals. In addition, CBG can further activate CB2R, but not CB1R, to stimulate the release of β-endorphin, which greatly promotes the antinociceptive effect. Finally, the safety test results showed that CBG had no irritating effect on the rabbits’ skin, and it did not induce significant biochemical and hematological changes in mice. Transdermal delivery results also indicated that CBG has certain transdermal properties. Overall, this study indicates that CBG is promising for developing a transdermal dosage for pain management.

PMID:36916438 | DOI:10.1016/j.biopha.2022.114163

Front Vet Sci. 2023 Feb 22;10:1112604. doi: 10.3389/fvets.2023.1112604. eCollection 2023.

ABSTRACT

Many dogs experience stress when separated from their caregivers, as well as when traveling in vehicles. Pet owners employ various approaches to managing these issues, from training, to giving medications and supplements, often with mixed results. Cannabidiol (CBD) can alleviate stress and anxiety in humans but the effect it has on canine stress is less well-documented. The present study aimed to understand the impact of being left alone and traveling in a car on measures of canine stress, and establish whether a single dose of a tetrahydrocannabinol (THC)-free CBD distillate could positively influence any measures of stress. In a blinded, parallel design study, a population of dogs were either left alone in a familiar room (n = 21) or underwent a short car journey (n = 19). A range of physiological and behavioral measures were collected pre, during and post-test. Significant changes in several stress-related measures (serum cortisol, mean ear temperature, heart rate, heart rate variability, whining and a stressed/anxious behavioral factor) were observed from baseline to test, with the car journey test paradigm eliciting a more pronounced stress response overall. The mitigating effect of CBD treatment varied by measure and test, with some indicating a significant reduction in canine stress compared to the placebo group. Additional research is required to fully understand the complex effect of CBD on canine wellbeing.

PMID:36908527 | PMC:PMC9992179 | DOI:10.3389/fvets.2023.1112604

PLoS One. 2023 Mar 13;18(3):e0282920. doi: 10.1371/journal.pone.0282920. eCollection 2023.

ABSTRACT

The most frequently reported use of medical marijuana is for pain relief. However, its psychoactive component Δ9-tetrahydrocannabinol (THC) causes significant side effects. Cannabidiol (CBD) and β-caryophyllene (BCP), two other cannabis constituents, possess more benign side effect profiles and are also reported to reduce neuropathic and inflammatory pain. We evaluated the analgesic potential of CBD and BCP individually and in combination in a rat spinal cord injury (SCI) clip compression chronic pain model. Individually, both phytocannabinoids produced dose-dependent reduction in tactile and cold hypersensitivity in male and female rats with SCI. When co-administered at fixed ratios based on individual A50s, CBD and BCP produced enhanced dose-dependent reduction in allodynic responses with synergistic effects observed for cold hypersensitivity in both sexes and additive effects for tactile hypersensitivity in males. Antinociceptive effects of both individual and combined treatment were generally less robust in females than males. CBD:BCP co-administration also partially reduced morphine-seeking behavior in a conditioned place preference (CPP) test. Minimal cannabinoidergic side effects were observed with high doses of the combination. The antinociceptive effects of the CBD:BCP co-administration were not altered by either CB2 or μ-opioid receptor antagonist pretreatment but, were nearly completely blocked by CB1 antagonist AM251. Since neither CBD or BCP are thought to mediate antinociception via CB1 activity, these findings suggest a novel CB1 interactive mechanism between these two phytocannabinoids in the SCI pain state. Together, these findings suggest that CBD:BCP co-administration may provide a safe and effective treatment option for the management of chronic SCI pain.

PMID:36913400 | DOI:10.1371/journal.pone.0282920

J Intern Med. 2023 Mar 13. doi: 10.1111/joim.13627. Online ahead of print.

ABSTRACT

BACKGROUND: Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI).

METHODS: In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted.

RESULTS: Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84-8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46-9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448-0.1212), and DILI was 0.0296 (95% CI 0.0136-0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported.

CONCLUSIONS: Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.

PMID:36912195 | DOI:10.1111/joim.13627

J Pharm Biomed Anal. 2023 Mar 5;228:115324. doi: 10.1016/j.jpba.2023.115324. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is the most abundant non-psychotropic phytocannabinoid isolated from Cannabis sativa. To support preclinical studies of ocular pharmacology of CBD, a bioanalytical method was developed and validated for quantification of CBD in aqueous humor using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Aqueous humor samples were subjected to protein precipitation by acetonitrile, followed by chromatographic separation using reversed phase LC on a Raptor ARC-18 column with mobile phase A: 0.1 % (v/v) formic acid in water (B) 0.1 % formic acid in acetonitrile (B) as eluents. Detection was carried out with a triple quadrupole mass spectrometer with electrospray ionization operated in positive ion mode. Stable-isotope labeled CBD (CBD-d₃) was used as internal standard. The total run time was 8 min. Quantification was accomplished within the validated concentration range of 0.5-500 ng/mL for CBD using a 5 µL sample. The lower limit of quantitation was 0.5 ng/mL. Inter- and intra-day precision is 4.737-7.620 % and 3.426-5.830 %, respectively. Inter- and intra-day accuracy ranged between 99.01 % and 100.2 % and 99.85-101.4 % respectively. The extraction recoveries were found to be 66.06 ± 5.146 %. The established method was successfully applied to investigate ocular pharmacokinetics of CBD in mice. Following intraperitoneal (i.p.) administration of 50 mg/kg CBD, its concentration reaches a C_max of 71.55 ± 36.64 ng/mL in aqueous humor, with a T_max of 2 h and a half-life of 1.046 h. The AUC was 183.4 ± 49.17 ng * h/mL. The development and validation of this LC-MS/MS method is an important step toward the goal of assessing the aqueous humor concentrations of CBD and correlating the concentrations of this phytocannabinoid with its ocular pharmacologic effects.

PMID:36907022 | DOI:10.1016/j.jpba.2023.115324

Foods. 2023 Feb 24;12(5):958. doi: 10.3390/foods12050958.

ABSTRACT

Hemp press cake flour (HPCF) is a by-product of hemp oil production rich in proteins, carbohydrates, minerals, vitamins, oleochemicals, and phytochemicals. The purpose of this study was to investigate how the addition of HPCF to bovine and ovine plain yoghurts at concentrations of 0%, 2%, 4%, 6%, 8%, and 10% could change the physicochemical, microbiological, and sensory properties of the yoghurts, focusing on the improvement of quality and antioxidant activity, and the issue of food by-products and their utilisation. The results showed that the addition of HPCF to yoghurts significantly affected their properties, including an increase in pH and decrease in titratable acidity, change in colour to darker, reddish or yellowish hue, and a rise in total polyphenols and antioxidant activity during storage. Yoghurts fortified with 4% and 6% HPCF exhibited the best sensory properties, thus maintaining viable starter counts in the yoghurts during the study period. There were no statistically significant differences between the control yoghurts and the samples with 4% added HPCF in terms of overall sensory score while maintaining viable starter counts during the seven-day storage. These results suggest that the addition of HPCF to yoghurts can improve product quality and create functional products and may have potential in sustainable food waste management.

PMID:36900475 | DOI:10.3390/foods12050958

Int J Mol Sci. 2023 Mar 6;24(5):5055. doi: 10.3390/ijms24055055.

ABSTRACT

Several animal studies have described the potential effect of cannabidiol (CBD) in alleviating the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic inflammatory disease of the urinary bladder. However, the effects of CBD, its mechanism of action, and modulation of downstream signaling pathways in urothelial cells, the main effector cells in IC/BPS, have not been fully elucidated yet. Here, we investigated the effect of CBD against inflammation and oxidative stress in an in vitro model of IC/BPS comprised of TNFα-stimulated human urothelial cells SV-HUC1. Our results show that CBD treatment of urothelial cells significantly decreased TNFα-upregulated mRNA and protein expression of IL1α, IL8, CXCL1, and CXCL10, as well as attenuated NFκB phosphorylation. In addition, CBD treatment also diminished TNFα-driven cellular reactive oxygen species generation (ROS), by increasing the expression of the redox-sensitive transcription factor Nrf2, the antioxidant enzymes superoxide dismutase 1 and 2, and hem oxygenase 1. CBD-mediated effects in urothelial cells may occur by the activation of the PPARγ receptor since inhibition of PPARγ resulted in significantly diminished anti-inflammatory and antioxidant effects of CBD. Our observations provide new insights into the therapeutic potential of CBD through modulation of PPARγ/Nrf2/NFκB signaling pathways, which could be further exploited in the treatment of IC/BPS.

PMID:36902479 | DOI:10.3390/ijms24055055

Plants (Basel). 2023 Feb 27;12(5):1061. doi: 10.3390/plants12051061.

ABSTRACT

The standard practice to initiate flowering in medicinal cannabis involves reducing the photoperiod from a long-day period to an equal duration cycle of 12 h light (12L)/12 h dark (12D). This method reflects the short-day flowering dependence of many cannabis varieties but may not be optimal for all. We sought to identify the effect of nine different flowering photoperiod treatments on the biomass yield and cannabinoid concentration of three medicinal cannabis varieties. The first, “Cannatonic”, was a high cannabidiol (CBD)-accumulating line, whereas the other two, “Northern Lights” and “Hindu Kush”, were high Δ9-tetrahydrocannabinol (THC) accumulators. The nine treatments tested, following 18 days under 18 h light/6 h dark following cloning and propagation included a standard 12L:12D period, a shortened period of 10L:14D, and a lengthened period of 14L:10D. The other six treatments started in one of the aforementioned and then 28 days later (mid-way through flowering) were switched to one of the other treatments, thus causing either an increase of 2 or 4 h, or a decrease of 2 or 4 h. Measured parameters included the timing of reproductive development; the dry weight flower yield; and the % dry weight of the main target cannabinoids, CBD and THC, from which the total g cannabinoid per plant was calculated. Flower biomass yields were highest for all lines when treatments started with 14L:10D; however, in the two THC lines, a static 14L:10D photoperiod caused a significant decline in THC concentration. Conversely, in Cannatonic, all treatments starting with 14L:10D led to a significant increase in the CBD concentration, which led to a 50-100% increase in total CBD yield. The results show that the assumption that a 12L:12D photoperiod is optimal for all lines is incorrect as, in some lines, yields can be greatly increased by a lengthened light period during flowering.

PMID:36903921 | DOI:10.3390/plants12051061

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2023 Mar 10:1-14. doi: 10.1080/19440049.2023.2187645. Online ahead of print.

ABSTRACT

Thirty-two crossbred heifers were fed either a control diet or 20% (dry matter basis) hempseed cake in a complete ration for 111 days; of the cattle fed hempseed cake, four each were harvested with 0, 1, 4, and 8-day withdrawal periods. Urine and plasma were collected during the feeding and withdrawal periods and liver, kidney, skeletal muscle, and adipose tissue were collected at harvest. Total cannabinoid (n = 10) concentration of hempseed cake averaged 11.3 ± 11.7 mg kg^-1 across the feeding period with total cannabidiol and tetrahydrocannabinol (CBD/THC) concentrations of 1.3 ± 0.8 mg kg^-1. Neutral cannabinoids (cannabinol [CBN], CBD/THC, and cannabidivarin [CBDV]) were not detected in plasma or urine, but CBD/THC was measured in adipose tissue at all withdrawal periods (6.3 ± 2.1 to 10.1 ± 2.5 ng g^-1). In contrast, cannabinoid acids (cannabinolic acid [CBNA], cannabidiolic acid [CBDA]/tetrahydrocannabinolic acid [THCA], cannabichromenic acid [CBCA], and cannabidivarinic acid [CBDVA]) were sporadically detected (<15 ng mL^-1) in plasma and urine of cattle fed hempseed cake. Cannabinoid acids were depleted from liver by withdrawal day 4, but could still be measured (<1 ng g^-1) in kidney of some animals harvested on withdrawal day 8. Assessment of human exposures to CBD/THC residues through the consumption of beef fat from animals fed hempseed cake suggests that the probability of consuming the equivalent of an acute reference dose (ARfD) is remote, even with the use of a conservative reference dose ARfD (1 μg kg^-1 body weight).

PMID:36897320 | DOI:10.1080/19440049.2023.2187645

Curr Pain Headache Rep. 2023 Mar 10. doi: 10.1007/s11916-023-01101-w. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Cannabis has been used since ancient times for medical and recreational research. This review article will document the validity of how medical cannabis can be utilized for chronic nonmalignant pain management.

RECENT FINDINGS: Current cannabis research has shown that medical cannabis is indicated for symptom management for many conditions not limited to cancer, chronic pain, headaches, migraines, and psychological disorders (anxiety and post-traumatic stress disorder). Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are active ingredients in cannabis that modulate a patient’s symptoms. These compounds work to decrease nociception and symptom frequency via the endocannabinoid system. Research regarding pain management is limited within the USA as the Drug Enforcement Agency (DEA) classifies it as a schedule one drug. Few studies have found a limited relationship between chronic pain and medical cannabis use. A total of 77 articles were selected after a thorough screening process using PubMed and Google Scholar. This paper demonstrates that medical cannabis use provides adequate pain management. Patients suffering from chronic nonmalignant pain may benefit from medical cannabis due to its convenience and efficacy.

PMID:36897501 | DOI:10.1007/s11916-023-01101-w

Front Physiol. 2023 Feb 20;14:1081186. doi: 10.3389/fphys.2023.1081186. eCollection 2023.

ABSTRACT

Introduction: Cannabis contains cannabidiol (CBD), the main non-psychoactive phytocannabinoid, but also many other phytocannabinoids that have therapeutic potential in the treatment of epilepsy. Indeed, the phytocannabinoids cannabigerolic acid (CBGA), cannabidivarinic acid (CBDVA), cannabichromenic acid (CBCA) and cannabichromene (CBC) have recently been shown to have anti-convulsant effects in a mouse model of Dravet syndrome (DS), an intractable form of epilepsy. Recent studies demonstrate that CBD inhibits voltage-gated sodium channel function, however, whether these other anti-convulsant phytocannabinoids affect these classic epilepsy drug-targets is unknown. Voltage-gated sodium (Na_V) channels play a pivotal role in initiation and propagation of the neuronal action potential and Na_V1.1, Na_V1.2, Na_V1.6 and Na_V1.7 are associated with the intractable epilepsies and pain conditions. Methods: In this study, using automated-planar patch-clamp technology, we assessed the profile of the phytocannabinoids CBGA, CBDVA, cannabigerol (CBG), CBCA and CBC against these human voltage-gated sodium channels subtypes expressed in mammalian cells and compared the effects to CBD. Results: CBD and CBGA inhibited peak current amplitude in the low micromolar range in a concentration-dependent manner, while CBG, CBCA and CBC revealed only modest inhibition for this subset of sodium channels. CBDVA inhibited Na_V1.6 peak currents in the low micromolar range in a concentration-dependent fashion, while only exhibiting modest inhibitory effects on Na_V1.1, Na_V1.2, and Na_V1.7 channels. CBD and CBGA non-selectively inhibited all channel subtypes examined, whereas CBDVA was selective for Na_V1.6. In addition, to better understand the mechanism of this inhibition, we examined the biophysical properties of these channels in the presence of each cannabinoid. CBD reduced Na_V1.1 and Na_V1.7 channel availability by modulating the voltage-dependence of steady-state fast inactivation (SSFI, V_0.5 inact), and for Na_V1.7 channel conductance was reduced. CBGA also reduced Na_V1.1 and Na_V1.7 channel availability by shifting the voltage-dependence of activation (V_0.5 act) to a more depolarized potential, and for Na_V1.7 SSFI was shifted to a more hyperpolarized potential. CBDVA reduced channel availability by modifying conductance, SSFI and recovery from SSFI for all four channels, except for Na_V1.2, where V_0.5 inact was unaffected. Discussion: Collectively, these data advance our understanding of the molecular actions of lesser studied phytocannabinoids on voltage-gated sodium channel proteins.

PMID:36891145 | PMC:PMC9986306 | DOI:10.3389/fphys.2023.1081186

Cannabis Cannabinoid Res. 2023 Mar 8. doi: 10.1089/can.2022.0115. Online ahead of print.

ABSTRACT

Background: The aim of this scoping review was to examine the extent that stakeholder’s decisions about and preferences for the provision and use of medicinal cannabis (MC) had been investigated. We sought to identify which populations were examined, the methods used for eliciting preferences and exploring decisions, and the reported outcomes of studies. Methods: Electronic databases (PubMed, CINAHL, Embase, BSC and PsycINFO) and the reference lists of relevant articles were searched for studies published up to March 2022. Studies were included if stakeholder preferences for MC were (1) the primary focus of the research, or (2) an aspect of a larger preference focus. Studies that (3) described the decisions to use MC were also included. Results: Thirteen studies were reviewed. The population focus of these was primarily patient, with seven studies focused on general patient populations and five studies targeting specific patient populations such as cancer survivors, and people experiencing depression. Methods included health economics preference methods, qualitative interviews, and a single multicriteria decision-making study. Four categories of outcomes were defined and included comparisons of MC with a therapeutic alternative (n=5), preferences for MC attributes (n=5), administration preferences (n=4), and the decision process of users (n=2). Motivation differences in preference were found. Purely medicinal users and novice users place more importance on cannabidiol (CBD) than tetrahydrocannabinol. Overall, inhalation methods of administration were preferred due to quick onset of symptom relief. Price was the greatest influence on choice for recreational/medicinal users, whereas purely medicinal users were less price sensitive for products with higher CBD content. Conclusion: Studies examining public preferences for the provision and use of MC were absent. Revealed preference methods are a useful technique for understanding preferences for characteristics that are difficult to visibly assess such as cannabinoid or strain. The outcomes of symptom-specific multicriteria decision method studies that compare the benefit-safety profiles of commonly used treatments and MC may be a useful decision support tool for health practitioners. Studies with representative samples are needed to understand the impact of age, gender, and race on preferences for MC.

PMID:36888538 | DOI:10.1089/can.2022.0115

Sci Rep. 2023 Mar 6;13(1):3694. doi: 10.1038/s41598-023-30872-w.

ABSTRACT

Obesity is one of the principal public health concerns leading to disturbances in glucose and lipid metabolism, which is a risk factor for several chronic diseases, including insulin resistance, type 2 diabetes mellitus, and cardiovascular diseases. In recent years, it turned out that cannabidiol (CBD) is a potential therapeutic agent in the treatment of obesity and its complications. Therefore, in the present study, we used CBD therapy (intraperitoneal injections in a dose of 10 mg/kg of body mass for 14 days) in a rat model of obesity induced by a high-fat diet (HFD). Gas-liquid chromatography and Western blotting were applied in order to determine the intramuscular lipid content and total expression of selected proteins in the white and red gastrocnemius muscle, respectively. Based on fatty acid composition, we calculated de novo lipogenesis ratio (16:0/18:2n-6), desaturation ratio (18:1n-9/18:0), and elongation ratios (18:0/16:0, 20:0/18:0, 22:0/20:0 and 24:0/22:0), in the selected lipid fractions. Two-week CBD administration significantly reduced the intramuscular fatty acids (FAs) accumulation and inhibited de novo lipogenesis in different lipid pools (in the free fatty acid, diacylglycerol, and triacylglycerol fractions) in both muscle types, which coincided with a decrease in the expression of membrane fatty acid transporters (fatty acid translocase, membrane-associated fatty acid binding protein, and fatty acid transport proteins 1 and 4). Moreover, CBD application profoundly improved the elongation and desaturation ratios, which was in line with downregulated expression of enzymes from the family of elongases and desaturases regardless of the metabolism presented by the muscle type. To our knowledge, this study is the first that outlines the novel effects of CBD action on skeletal muscle with different types of metabolism (oxidative vs. glycolytic).

PMID:36879113 | DOI:10.1038/s41598-023-30872-w