PubMed: In vitro Effect of Cannabidiol on Red Blood Cells: Implication in Long-Lasting Pathology Treatment

PubMed: In vitro Effect of Cannabidiol on Red Blood Cells: Implication in Long-Lasting Pathology Treatment

Curr Pharm Des. 2024 Jun 13. doi: 10.2174/0113816128287272240529072040. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) is the principal non-hallucinogenic compound of Cannabis plants with high clinical interest because CBD has been described as having anti-inflammatory, analgesic and anticonvulsant properties. CBD is considered a multitarget compound as it can interact with a wide range of targets, explaining their multiplicity of effects. Some clinical studies have indicated certain side effects of CBD, including somnolence, anemia and diarrhea, while the elevation of transaminases is considered as an exclusion criterion from the trial. Since the red blood cells (RBCs) are a source of transaminase, we assayed in vitro effect on RBCs stability.

METHODS: We performed in vitro experiments with RBCs obtained from human peripheral blood with normal hematological parameters exposed to CBD in the range of therapeutic uses. We evaluated RBCs morphological changes, membrane fragility and hemoglobin release as a reflection of hemolysis.

RESULTS: CBD induced an increase in the hemoglobin release (3.27 μg/106 RBC), without altered RBC osmotic fragility. When RBCs suspensions were incubated with CBD the initial number of elements (RBCs + vesicles) was increased up to 65% after 20 min and returned to basal level after 40 min of incubation. In the first 20 min, the accounts of elements were enriched in the smaller vesicles that disappeared after the remaining 20 minutes.

CONCLUSION: These results suggest that CBD affects the indemnity of erythrocytes in vitro, inducing the formation of hemolytic vesicles that can provide the basis for the development of anemia, transaminase elevation and underlying tissular iron overload in patients chronically treated with CBD.

PMID:38874045 | DOI:10.2174/0113816128287272240529072040

https://pubmed.ncbi.nlm.nih.gov/38874045/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240614132139&v=2.18.0.post9+e462414 June 14, 2024 10:00 am

PubMed: Systematic review of drug-drug interactions of delta-9-tetrahydrocannabinol, cannabidiol, and Cannabis

PubMed: Systematic review of drug-drug interactions of delta-9-tetrahydrocannabinol, cannabidiol, and Cannabis

Front Pharmacol. 2024 May 22;15:1282831. doi: 10.3389/fphar.2024.1282831. eCollection 2024.

ABSTRACT

BACKGROUND: The recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter products (e.g., cannabidiol (CBD) oil, and delta-8-tetrahydrocannabinol (delta-8-THC)), has the potential to create unintended health consequences. The major cannabinoids (delta-9-tetrahydrocannabinol and cannabidiol) are metabolized by the same cytochrome P450 (CYP) enzymes that metabolize most prescription medications and xenobiotics (CYP3A4, CYP2C9, CYP2C19). As a result, we predict that there will be instances of drug-drug interactions and the potential for adverse outcomes, especially for prescription medications with a narrow therapeutic index.

METHODS: We conducted a systematic review of all years to 2023 to identify real world reports of documented cannabinoid interactions with prescription medications. We limited our search to a set list of medications with predicted narrow therapeutic indices that may produce unintended adverse drug reactions (ADRs). Our team screened 4,600 reports and selected 151 full-text articles to assess for inclusion and exclusion criteria.

RESULTS: Our investigation revealed 31 reports for which cannabinoids altered pharmacokinetics and/or produced adverse events. These reports involved 16 different Narrow Therapeutic Index (NTI) medications, under six drug classes, 889 individual subjects and 603 cannabis/cannabinoid users. Interactions between cannabis/cannabinoids and warfarin, valproate, tacrolimus, and sirolimus were the most widely reported and may pose the greatest risk to patients. Common ADRs included bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal distress. Additionally, we identified 18 instances (58%) in which clinicians uncovered an unexpected serum level of the prescribed drug. The quality of pharmacokinetic evidence for each report was assessed using an internally developed ten-point scale.

CONCLUSION: Drug-drug interactions with cannabinoids are likely amongst prescription medications that use common CYP450 systems. Our findings highlight the need for healthcare providers and patients/care-givers to openly communicate about cannabis/cannabinoid use to prevent unintended adverse events. To that end, we have developed a free online tool (www.CANN-DIR.psu.edu) to help identify potential cannabinoid drug-drug interactions with prescription medications.

PMID:38868665 | PMC:PMC11167383 | DOI:10.3389/fphar.2024.1282831

https://pubmed.ncbi.nlm.nih.gov/38868665/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240613072110&v=2.18.0.post9+e462414 June 13, 2024 10:00 am

Licensed hemp fields double in Idaho, where farmers are focused on fiber production

HempToday®: Licensed hemp fields double in Idaho, where farmers are focused on fiber production
Late-comer Idaho has joined the ranks of leading hemp states in the U.S., with more than 2,440 acres licensed this year, according to the state’s agriculture department. Compared to last […]

#CBD #Hemp
https://hemptoday.net/licensed-hemp-fields-double-in-idaho-where-farmers-are-focused-on-fiber-production/
June 13, 2024 8:12 am

Hemp provisions in U.S. spending bill could speed up crackdown on synthetic intoxicants

HempToday®: Hemp provisions in U.S. spending bill could speed up crackdown on synthetic intoxicants
A U.S. Congressional spending bill released this week includes language that would likely shut down widespread distribution of unregulated intoxicating hemp products – perhaps before the end of the year. […]

#CBD #Hemp
https://hemptoday.net/hemp-provisions-in-u-s-spending-bill-could-speed-up-crackdown-on-hemp-intoxicants/
June 12, 2024 10:21 am

Draft remarks for NC Hearing June 12

CNR: Draft remarks for NC Hearing June 12

Hemp drugs: Hearing Wednesday 2 EDT in North Carolina, streamed at https://ncleg.gov/LegislativeCalendarEvent/132863#videoHeader

Constructive comments welcomed. Sometimes they let the public speak.

Mr. Chairman, Thank you.  

My name is Pat Oglesby.  I’m a lawyer with the Center for New Revenue in Chapel Hill. Some of you all are old enough to remember Bob Dole and Lloyd Bentsen.  I was a staffer for the nonpartisan Joint Committee on Taxation when they chaired it.     I’ve been a paid advisor to several states on cannabis tax policy.  

As you’re discovering, hemp-derived cannabinoids create both costs and externalities.  That’s why North Carolina should tax these substances – ideally by THC content – as part of a comprehensive cannabis strategy. 

Louisiana, Minnesota, Tennessee, and West Virginia are four states that already collect extra excise taxes on these substances.  Taxes that range from 3 percent to 11 percent of retail price.

But that’s just one approach. An alternative and more effective tax is one being used in Connecticut, Illinois, and all Canadian provinces. They tax legalized cannabis products by the volume of THC they contain. This THC tax aims straight at the target you want to hit.

Whichever taxes you choose — taxes based on price or taxes based on THC levels – there’s a risk of overdoing it.  If you tax too heavily, illicit sellers will bypass the tax and you won’t get the revenue you hope for.  I don’t work for industry, but I do know that other states have learned this lesson the hard way: Overtaxing backfires.  

The journey you’re on won’t be easy. But please know that I will do what I can to help. 


#CBD #Hemp

Draft remarks for NC Hearing June 12


June 11, 2024 11:10 pm

PubMed: The Effects of Nicotine and Cannabinoids on Cytokines

PubMed: The Effects of Nicotine and Cannabinoids on Cytokines

Curr Pharm Des. 2024 Jun 7. doi: 10.2174/0113816128293077240529111824. Online ahead of print.

ABSTRACT

BACKGROUND: The usage of nicotine and cannabinoids has rapidly grown in popularity, leading to increased research into how they can affect people’s health, both positively and negatively. Nicotine, Cannabidiol (CBD), and Tetrahydrocannabidiol (THC) have been shown to have significant effects on cytokine function and inflammatory response.

OBJECTIVE: This study aimed to review and summarize the current literature on the effects of nicotine and cannabinoids on cytokines, including interleukins, TNF, IFN, and TGF-β.

METHODS: Literature search was conducted on Medline/PubMed electronic databases utilizing the search terms “nicotine” OR “cannabis” OR “cannabinoids” AND “cytokine” AND “inflammation” AND “stress” AND “immune” from 11/1973 to 02/2024.

RESULTS: THC and CBD usage have been associated with conflicting impacts on immune response, and observed to both exacerbate and inhibit inflammation. Nicotine has been shown to be generally proinflammatory with regards to cytokines. These responses have been reported to have significant effects on bodily response to inflammation-related diseases. Nicotine usage is associated with worsened outcomes for some conditions, like chronic pain, but improved outcomes for others, like arthritis. The impacts of cannabinoid usage tend to be more positive, exerting anti-inflammatory effects across a wide range of diseases. Given the widespread usage of these substances, it is important to understand the nature of their consequences on immune functions and the underlying mechanisms by which they act.

CONCLUSION: This review has covered how cannabinoids and nicotine affect inflammation directly and how these effects can be attributed to the treatment of inflammatory diseases. In summary, the existing research studying the effects of cannabinoids and nicotine supports the major relationship between nicotine and cannabis use and inflammatory diseases.

PMID:38859790 | DOI:10.2174/0113816128293077240529111824

https://pubmed.ncbi.nlm.nih.gov/38859790/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240611072146&v=2.18.0.post9+e462414 June 11, 2024 10:00 am

PubMed: Ultrafast, Selective, and Highly Sensitive Nonchromatographic Analysis of Fourteen Cannabinoids in Cannabis Extracts, delta8-Tetrahydrocannabinol Synthetic Mixtures, and Edibles by Cyclic Ion Mobility Spectrometry-Mass Spectrometry

PubMed: Ultrafast, Selective, and Highly Sensitive Nonchromatographic Analysis of Fourteen Cannabinoids in Cannabis Extracts, delta8-Tetrahydrocannabinol Synthetic Mixtures, and Edibles by Cyclic Ion Mobility Spectrometry-Mass Spectrometry

Anal Chem. 2024 Jun 11. doi: 10.1021/acs.analchem.3c05879. Online ahead of print.

ABSTRACT

The diversity of cannabinoid isomers and complexity of Cannabis products pose significant challenges for analytical methodologies. In this study, we developed a method to analyze 14 different cannabinoid isomers in diverse samples within milliseconds by leveraging the unique adduct-forming behavior of silver ions in advanced cyclic ion mobility spectrometry-mass spectrometry. The developed method achieved the separation of isomers from four groups of cannabinoids: Δ3-tetrahydrocannabinol (THC) (1), Δ8-THC (2), Δ9-THC (3), cannabidiol (CBD) (4), Δ8-iso-THC (5), and Δ(4)8-iso-THC (6) (all MW = 314); 9α-hydroxyhexahydrocannabinol (7), 9β-hydroxyhexahydrocannabinol (8), and 8-hydroxy-iso-THC (9) (all MW = 332); tetrahydrocannabinolic acid (THCA) (10) and cannabidiolic acid (CBDA) (11) (both MW = 358); Δ8-tetrahydrocannabivarin (THCV) (12), Δ8-iso-THCV (13), and Δ9-THCV (14) (all MW = 286). Moreover, experimental and theoretical traveling wave collision cross section values in nitrogen (TWCCSN2) of cannabinoid-Ag(I) species were obtained for the first time with an average error between experimental and theoretical values of 2.6%. Furthermore, a workflow for the identification of cannabinoid isomers in Cannabis and Cannabis-derived samples was established based on three identification steps (m/z and isotope pattern of Ag(I) adducts, TWCCSN2, and MS/MS fragments). Afterward, calibration curves of three major cannabinoids were established with a linear range of 1-250 ng·ml-1 for Δ8-THC (2) (R2 = 0.9999), 0.1-25 ng·ml-1 for Δ9-THC (3) (R2 = 0.9987), and 0.04-10 ng·ml-1 for CBD (4) (R2 = 0.9986) as well as very low limits of detection (0.008-0.2 ng·ml-1). Finally, relative quantification of Δ8-THC (2), Δ9-THC (3), and CBD (4) in eight complex acid-treated CBD mixtures was achieved without chromatographic separation. The results showed good correspondence (R2 = 0.999) with those obtained by gas chromatography-flame ionization detection/mass spectrometry.

PMID:38862388 | DOI:10.1021/acs.analchem.3c05879

https://pubmed.ncbi.nlm.nih.gov/38862388/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240612012340&v=2.18.0.post9+e462414 June 11, 2024 10:00 am

PubMed: Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications

PubMed: Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications

AAPS PharmSciTech. 2024 Jun 11;25(5):136. doi: 10.1208/s12249-024-02857-z.

ABSTRACT

Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire®59/14, PEO N80 and Soluplus®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.

PMID:38862810 | DOI:10.1208/s12249-024-02857-z

https://pubmed.ncbi.nlm.nih.gov/38862810/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240612012340&v=2.18.0.post9+e462414 June 11, 2024 10:00 am

For Florida Gov. Ron DeSantis, intoxicating hemp is OK, but marijuana isn’t

HempToday®: For Florida Gov. Ron DeSantis, intoxicating hemp is OK, but marijuana isn’t
Intoxicating hemp substances will remain on the market in Florida after Gov. Ron DeSantis nixed a proposed law that would have banned products containing them. DeSantis on Friday vetoed Senate […]

#CBD #Hemp
https://hemptoday.net/for-florida-gov-ron-desantis-intoxicating-hemp-is-ok-but-marijuana-isnt/
June 10, 2024 11:07 am

PubMed: Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis

PubMed: Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun 8. doi: 10.1007/s00210-024-03185-6. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is a non-psychoactive substance that exerts numerous pharmacological benefits, including anti-inflammatory and antioxidant properties. It has received attention as a useful substance for the treatment of intractable pain, seizures, and anxiety, and related clinical trials have continued. However, the CBD pharmacokinetic results between reports are highly variable, making it difficult to clearly identify the pharmacokinetic properties of CBD. The main purpose of this study was to identify CBD clinical pharmacokinetic properties through meta-analysis. In particular, we sought to derive valid, interpretable independent variables and interpret their pharmacokinetic parameter correlations in relation to the large inter-individual and inter-study variability in CBD pharmacokinetics. For this study, CBD-related clinical trial reports were extensively screened and intercomparisons were performed between internal data sets through systematic classification and extraction of pharmacokinetic parameter values. The candidate independent variables associated with interpretation of CBD pharmacokinetic diversity established and explored in this study were as follows: diet, tetrahydrocannabinol (THC) combination, sample matrix type, liver and renal function, exposure route, dosage form, CBD exposure dose, cannabis smoking frequency, multiple exposure. The results of this study showed that CBD pharmacokinetics were influenced (increased plasma exposure by approximately 2-5 times) by diet immediately before or during CBD exposure, and that THC was not expected to have an antagonistic effect on the CBD absorption. The influence of changes in liver function would be significant in CBD pharmacokinetic diversity. Due to decreased liver function, the plasma exposure of CBD increased 2.57-5.15 times compared to healthy adults, and the half-life and clearance showed a 2.58-fold increase and a 5.15-fold decrease, respectively. CBD can be rapidly absorbed into the body (time to reach maximum concentration within 3.18 h) by oral, transdermal, and inhalation exposures, and lipid emulsification and nanoformulation of CBD will greatly improve CBD bioavailability (up to approximately 2 times). The pharmacokinetics of CBD generally follow linear kinetic characteristics. The importance of this study is that it suggests key factors that should be considered in terms of pharmacokinetics in further clinical trials and formulations of CBD in the future.

PMID:38850302 | DOI:10.1007/s00210-024-03185-6

https://pubmed.ncbi.nlm.nih.gov/38850302/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240608202235&v=2.18.0.post9+e462414 June 8, 2024 10:00 am

PubMed: Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells

PubMed: Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells

Int Immunopharmacol. 2024 Jun 7;137:112429. doi: 10.1016/j.intimp.2024.112429. Online ahead of print.

ABSTRACT

BACKGROUND: Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action.

METHOD: An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action.

RESULTS: Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD.

CONCLUSION: This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.

PMID:38851157 | DOI:10.1016/j.intimp.2024.112429

https://pubmed.ncbi.nlm.nih.gov/38851157/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240609102250&v=2.18.0.post9+e462414 June 8, 2024 10:00 am

PubMed: Understanding the Potential of CBD for Health Benefits: an Overview

PubMed: Understanding the Potential of CBD for Health Benefits: an Overview

Curr Drug Discov Technol. 2024 Jun 6. doi: 10.2174/0115701638305553240529103622. Online ahead of print.

ABSTRACT

Cannabinoids are compounds with increasing scientific interest, particularly due to their interaction with the endocannabinoid system via CBR1 and CBR2 receptors. They can interfere with appetite, pain, and sleep or develop mood changes of the individual. Cannabidiol (CBD) is a well-known cannabinoid with potential benefits, including reducing epilepsy seizures, alleviating anxiety, and obsessive-compulsive disorder (OCD) symptoms, aiding in Tourette Syndrome (a neurodevelopmental disorder), depression, sleep disorders, and promising in the treatment of cancer, pain relief, and heart health. Although generally safe, CBD can have side effects, including drug metabolism interference, fertility, and liver function. In addition, it can be administered by oral, sublingual, transdermal or inhalation via, each one with different bioavailability. The application of nanotechnology, specifically through colloidal carrier systems, holds promising potential for maximizing CBD’s efficacy and pharmacological profile. There are reported CBD extraction methods using ethanol, carbon dioxide, deionised water, and non-polar oils like olive or coconut oil. The green extraction methods have gained popularity for their higher yields, shorter extraction time, and reduced costs. A specific dose with the desired effects is challenging due to individual factors, with most studies suggesting a range between less than 1 and 50 mg/kg/d. This review aims to explore the principles of CBD-based products development, focusing on extraction methods and purification processes of this cannabinoid for tinctures, topicals, and other pharmaceutical forms, as well as further research to attain the objectives.

PMID:38847170 | DOI:10.2174/0115701638305553240529103622

https://pubmed.ncbi.nlm.nih.gov/38847170/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240607072225&v=2.18.0.post9+e462414 June 7, 2024 10:00 am

Florida university now suspects $238 million gift from hemp entrepreneur is bogus

HempToday®: Florida university now suspects $238 million gift from hemp entrepreneur is bogus
A Florida university that received a $238 million “gift” from a Texas hemp entrepreneur likely won’t cash in on the pledge, school officials have indicated. The donation to Florida Agricultural […]

#CBD #Hemp
https://hemptoday.net/florida-university-now-suspects-238-million-gift-from-hemp-entrepreneur-is-bogus/
June 6, 2024 9:19 am

Investors will lose millions if Thailand backtracks on hemp, marijuana, trade group says

HempToday®: Investors will lose millions if Thailand backtracks on hemp, marijuana, trade group says
A plan to re-criminalize cannabis in Thailand could cost CBD stakeholders millions of dollars in lost investments, a key trade group has warned. The Thai Hemp and Cannabis Industry Association […]

#CBD #Hemp
https://hemptoday.net/investors-will-lose-millions-if-thailand-backtracks-on-hemp-marijuana-trade-group-says/
June 5, 2024 5:25 am

PubMed: Select Minor Cannabinoids from Cannabis sativa are Cannabimimetic and Antinociceptive in a Mouse Model of Chronic Neuropathic Pain

PubMed: Select Minor Cannabinoids from Cannabis sativa are Cannabimimetic and Antinociceptive in a Mouse Model of Chronic Neuropathic Pain

J Pharmacol Exp Ther. 2024 Jun 4:JPET-AR-2024-002212. doi: 10.1124/jpet.124.002212. Online ahead of print.

ABSTRACT

Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between labs or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), Δ8-tetrahydrocannabinol (Δ8-THC), and Δ9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high dose Δ8-THC evoked some tetrad behaviors in both sexes, while THCV and low dose Δ8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential. Significance Statement Minor cannabinoids are poorly studied ligands present in lower levels in Cannabis than cannabinoids like THC. In this study we evaluated 5 minor cannabinoids (CBN, CBDV, CBG, THCV, and Δ8-THC) for their cannabimimetic and analgesic effects in mice. We found that 4 of the 5 minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization.

PMID:38834356 | DOI:10.1124/jpet.124.002212

https://pubmed.ncbi.nlm.nih.gov/38834356/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240605022110&v=2.18.0.post9+e462414 June 4, 2024 10:00 am

Debate over intoxicating hemp rages in southern states, but it’s mostly talk

HempToday®: Debate over intoxicating hemp rages in southern states, but it’s mostly talk
Southern states are coming down on both sides of the intoxicating hemp debate, with Texas being urged to enact strict rules for the synthetic compounds while Louisiana lawmakers have sidelined […]

#CBD #Hemp
https://hemptoday.net/debate-over-intoxicating-hemp-rages-in-southern-states-but-its-all-talk/
June 4, 2024 9:02 am

PubMed: Safety of cannabidiol products as a social issue: A case series

PubMed: Safety of cannabidiol products as a social issue: A case series

Acute Med Surg. 2024 May 31;11(1):e965. doi: 10.1002/ams2.965. eCollection 2024 Jan-Dec.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) products have increased in popularity in Japan in recent years, particularly among young people. Some CBD products contain tetrahydrocannabinol (THC), the main ingredient of cannabis, and its analogs, which are illegal in Japan and have become a social issue. This report discusses the safety of CBD products.

CASE PRESENTATION: Five patients with symptoms of CBD ingestion, including nausea, presented to our hospital. Three of the products these patients ingested contained THC. Metabolites of THC were detected in the blood and urine of all three patients, although there were some discrepancies in the urine drug screening test (DS10®). These examination results differed even when the same product was consumed.

CONCLUSION: CBD products are unsafe and may unintentionally contain THC. It is also important to understand that CBD can turn into THC, and the effective time needed to conduct urine drug screening.

PMID:38828078 | PMC:PMC11142928 | DOI:10.1002/ams2.965

https://pubmed.ncbi.nlm.nih.gov/38828078/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240603072126&v=2.18.0.post9+e462414 June 3, 2024 10:00 am

PubMed: Unraveling the Mechanisms of Cannabidiol's Pharmacological Actions: A Comprehensive Research Overview

PubMed: Unraveling the Mechanisms of Cannabidiol's Pharmacological Actions: A Comprehensive Research Overview

Top Curr Chem (Cham). 2024 Jun 3;382(2):20. doi: 10.1007/s41061-024-00465-w.

ABSTRACT

Cannabis sativa has long been used for neurological and psychological healing. Recently, cannabidiol (CBD) extracted from cannabis sativa has gained prominence in the medical field due to its non-psychotropic therapeutic effects on the central and peripheral nervous systems. CBD, also acting as a potent antioxidant, displays diverse clinical properties such as anticancer, antiinflammatory, antidepressant, antioxidant, antiemetic, anxiolytic, antiepileptic, and antipsychotic effects. In this review, we summarized the structural activity relationship of CBD with different receptors by both experimental and computational techniques and investigated the mechanism of interaction between related receptors and CBD. The discovery of structural activity relationship between CBD and target receptors would provide a direction to optimize the scaffold of CBD and its derivatives, which would give potential medical applications on CBD-based therapies in various illnesses.

PMID:38829467 | DOI:10.1007/s41061-024-00465-w

https://pubmed.ncbi.nlm.nih.gov/38829467/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240603132300&v=2.18.0.post9+e462414 June 3, 2024 10:00 am

PubMed: Cannabidiol mitigates radiation-induced intestine ferroptosis via facilitating the heterodimerization of RUNX3 with CBFbeta thereby promoting transactivation of GPX4

PubMed: Cannabidiol mitigates radiation-induced intestine ferroptosis via facilitating the heterodimerization of RUNX3 with CBFbeta thereby promoting transactivation of GPX4

Free Radic Biol Med. 2024 Jun 1:S0891-5849(24)00506-9. doi: 10.1016/j.freeradbiomed.2024.05.047. Online ahead of print.

ABSTRACT

Radiation enteritis remains a major challenge for radiotherapy against abdominal and pelvic malignancies. Nevertheless, there is no approved effective therapy to alleviate irradiation (IR)-induced gastrointestinal (GI) toxicity. In the current study, Cannabidiol (CBD) was found to mitigate intestinal injury by GPX4-mediated ferroptosis resistance upon IR exposure. RNA-sequencing was employed to investigate the underlying mechanism involved in the radio-protective effect of CBD, wherein runt-related transcription factor 3 (RUNX3) and its target genes were changed significantly. Further experiment showed that the transactivation of GPX4 triggered by the direct binding of RUNX3 to its promoter region, or by stimulating the transcriptional activity of NF-κB via RUNX3-mediated LILRB3 upregulation was critical for the anti-ferroptotic effect of CBD upon IR injury. Specially, CBD was demonstrated to be a molecular glue skeleton facilitating the heterodimerization of RUNX3 with its transcriptional chaperone core-biding factor β (CBFβ) thereby promoting their nuclear localization and the subsequent transactivation of GPX4 and LILRB3. In short, our study provides an alternative strategy to counteract IR-induced enteritis during the radiotherapy on abdominal/pelvic neoplasms.

PMID:38830513 | DOI:10.1016/j.freeradbiomed.2024.05.047

https://pubmed.ncbi.nlm.nih.gov/38830513/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240604012133&v=2.18.0.post9+e462414 June 3, 2024 10:00 am

Intoxicating hemp products are ‘public menace,’ says Massachusetts regulator

HempToday®: Intoxicating hemp products are ‘public menace,’ says Massachusetts regulator
Massachusetts cannabis regulators say intoxicating hemp products constitute a “public menace” to the health of the state’s citizens, and are harming regulated marijuana dispensaries that operate under strict rules. The […]

#CBD #Hemp
https://hemptoday.net/intoxicating-hemp-products-are-public-menace-says-massachusetts-regulator/
June 3, 2024 7:37 am

PubMed: Cannabidiol reverts the malignant phenotype of hepatocellular carcinoma cells via the GPR55/TP53/MAPK axis

PubMed: Cannabidiol reverts the malignant phenotype of hepatocellular carcinoma cells via the GPR55/TP53/MAPK axis

Biochim Biophys Acta Gen Subj. 2024 May 31:130651. doi: 10.1016/j.bbagen.2024.130651. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) has antioxidant and anti-inflammatory activities. However, the anti-tumor effect of CBD on hepatocellular carcinoma (HCC) remains unclear. Here, we investigated whether CBD displays anti-tumorigenic effects in HCC cells and whether it could reduce tumorigenesis and metastases in vivo. First, this study treated HCC cells with different concentrations of CBD, followed by analyzing the changes in the proliferative, apoptotic, migratory and invasive abilities. The effects of CBD on the growth and metastasis of HCC cells in vivo were verified by tumorigenesis and metastasis assays. Subsequently, the target genes of CBD were predicted through the SwissTarget website and the genes differentially expressed in cells after CBD treatment were analyzed by microarray for intersection. The enrichment of the pathways after CBD treatment was analyzed by KEGG enrichment analysis, followed by western blot validation. Finally, rescue assays were used to validate the functions of genes as well as pathways in the growth and metastasis of HCC cells. A significant weakening of the ability of HCC cells to grow and metastasize in vitro and in vivo was observed upon CBD treatment. Mechanistically, CBD reduced GRP55 expression in HCC cells, along with increased TP53 expression and blocked MAPK signaling activation. In CBD-treated cells, the anti-tumor of HCC cells was restored after overexpression of GRP55 or deletion of TP53. CBD inhibits the MAPK signaling activation and increases the TP53 expression by downregulating GRP55 in HCC cells, thereby suppressing the growth and metastasis of HCC cells.

PMID:38825256 | DOI:10.1016/j.bbagen.2024.130651

https://pubmed.ncbi.nlm.nih.gov/38825256/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240603013152&v=2.18.0.post9+e462414 June 2, 2024 10:00 am

PubMed: The effect of cannabis edibles on driving and blood THC

PubMed: The effect of cannabis edibles on driving and blood THC

J Cannabis Res. 2024 May 31;6(1):26. doi: 10.1186/s42238-024-00234-y.

ABSTRACT

BACKGROUND: Cannabis has been shown to impact driving due to changes produced by delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis. Current legal thresholds for blood THC while driving are based predominantly on evidence utilizing smoked cannabis. It is known that levels of THC in blood are lower after eating cannabis as compared to smoking yet the impact of edibles on driving and associated blood THC has never been studied.

METHODS: Participants drove a driving simulator before and after ingesting their preferred legally purchased cannabis edible. In a counterbalanced control session, participants did not consume any THC or cannabidiol (CBD). Blood was collected for measurement of THC and metabolites as well as CBD. Subjective experience was also assessed.

RESULTS: Participants consumed edibles with, on average, 7.3 mg of THC, which is less than the maximum amount available in a single retail package in Ontario, providing an ecologically valid test of cannabis edibles. Compared to control, cannabis edibles produced a decrease in mean speed 2 h after consumption but not at 4 and 6 h. Under dual task conditions in which participants completed a secondary task while driving, changes in speed were not significant after the correction for multiple comparison. No changes in standard deviation of lateral position (SDLP; ‘weaving’), maximum speed, standard deviation of speed or reaction time were found at any time point or under either standard or dual task conditions. Mean THC levels were significantly increased, relative to control, after consuming the edible but remained relatively low at approximately 2.8 ng/mL 2 h after consumption. Driving impairment was not correlated with blood THC. Subjective experience was altered for 7 h and participants were less willing/able to drive for up to 6 h, suggesting that the edible was intoxicating.

INTERPRETATION: This is the first study of the impact of cannabis edibles on simulated driving. Edibles were intoxicating as revealed by the results of subjective assessments (VAS), and there was some impact on driving. Detection of driving impairment after the use of cannabis edibles may be difficult.

PMID:38822413 | DOI:10.1186/s42238-024-00234-y

https://pubmed.ncbi.nlm.nih.gov/38822413/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240601212431&v=2.18.0.post9+e462414 June 1, 2024 10:00 am

Region in southern Uruguay forging a model supply chain for hemp food products

HempToday®: Region in southern Uruguay forging a model supply chain for hemp food products
An administrative region in Uruguay is setting a model for a hemp food production supply chain, and continues to expand exports to the USA, Europe and other South American countries. […]

#CBD #Hemp
https://hemptoday.net/region-in-southern-uruguay-forging-a-model-supply-chain-for-hemp-food-products/
May 31, 2024 10:27 am

PubMed: Physiological profiling of cannabidiol reveals profound inhibition of sensory neurons

PubMed: Physiological profiling of cannabidiol reveals profound inhibition of sensory neurons

Pain. 2024 May 29. doi: 10.1097/j.pain.0000000000003273. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), the main nonpsychoactive cannabinoid of cannabis, holds promise for nonaddictive treatment of pain. Although preclinical studies have been encouraging, well-controlled human trials have been largely unsuccessful. To investigate this dichotomy and better understand the actions of CBD, we used high-content calcium imaging with automated liquid handling and observed broad inhibition of neuronal activation by a host of ionotropic and metabotropic receptors, including transient receptor potential (Trp) and purinergic receptors, as well as mediators of intracellular calcium cycling. To assess the effect of CBD on overall nociceptor electrical activity, we combined the light-activated ion channel channelrhodposin in TRPV1-positive nociceptors and a red-shifted calcium indicator and found that 1 µM CBD profoundly increased the optical threshold for calcium flux activation. Experiments using traditional whole-cell patch-clamp showed increase of nociceptor activation threshold at submicromolar concentrations, but with unusually slow kinetics, as well as block of voltage-activated currents. To address a more integrated capacity of CBD to influence nociceptor sensitization, a process implicated in multiple pain states, we found that submicromolar concentrations of CBD inhibited sensitization by the chemotherapeutic drug vincristine. Taken together, these results demonstrate that CBD can reduce neuronal activity evoked by a strikingly wide range of stimuli implicated in pain signaling. The extensive effects underscore the need for further studies at substantially lower drug concentrations, which are more likely to reflect physiologically relevant mechanisms. The slow kinetics and block raise biophysical questions regarding the lipophilic properties of CBD and its action on channels and receptors within membranes.

PMID:38815194 | DOI:10.1097/j.pain.0000000000003273

https://pubmed.ncbi.nlm.nih.gov/38815194/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240530192122&v=2.18.0.post9+e462414 May 30, 2024 10:00 am

PubMed: Development, Characterization and In Vitro Gastrointestinal Release of PLGA Nanoparticles Loaded with Full-Spectrum Cannabis Extracts

PubMed: Development, Characterization and In Vitro Gastrointestinal Release of PLGA Nanoparticles Loaded with Full-Spectrum Cannabis Extracts

AAPS PharmSciTech. 2024 May 30;25(5):120. doi: 10.1208/s12249-024-02836-4.

ABSTRACT

Cannabinoids, such as ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective bioactive compounds that improve the quality of life of patients with certain chronic conditions. The copolymer poly(lactic-co-glycolic acid) (PLGA) has been used to encapsulate such compounds separately, providing pharmaceutical grade edible products with unique features. In this work, a variety of PLGA based nanoformulations that maintain the natural cannabinoid profile found in the plant (known as full-spectrum) are proposed and evaluated. Three different cannabis sources were used, representing the three most relevant cannabis chemotypes. PLGA nanocapsules loaded with different amounts of cannabinoids were prepared by nanoemulsion, and were then functionalized with three of the most common coating polymers: pectin, alginate and chitosan. In order to evaluate the suitability of the proposed formulations, all the synthesized nanocapsules were characterized, and their cannabinoid content, size, zeta-potential, morphology and in vitro bioaccessibility was determined. Regardless of the employed cannabis source, its load and the functionalization, high cannabinoid content PLGA nanocapsules with suitable particle size and zeta-potential were obtained. Study of nanocapsules’ morphology and in vitro release assays in gastro-intestinal media suggested that high cannabis source load may compromise the structure of nanocapsules and their release properties, and hence, the use of lower content of cannabis source is recommended.

PMID:38816596 | DOI:10.1208/s12249-024-02836-4

https://pubmed.ncbi.nlm.nih.gov/38816596/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240531013201&v=2.18.0.post9+e462414 May 30, 2024 10:00 am

New Jersey law would ban delta-8, other hemp intoxicants, limit CBD to pot shops

HempToday®: New Jersey law would ban delta-8, other hemp intoxicants, limit CBD to pot shops
A proposed law in New Jersey would essentially wipe out delta-8 THC and other intoxicating hemp substances and restrict the sale of CBD to the state’s licensed pot dispensaries. Under […]

#CBD #Hemp
https://hemptoday.net/new-jersey-law-would-ban-delta-8-other-hemp-intoxicants-limit-cbd-to-pot-shops/
May 30, 2024 7:55 am

PubMed: Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study

PubMed: Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study

Epilepsia. 2024 May 29. doi: 10.1111/epi.18025. Online ahead of print.

ABSTRACT

OBJECTIVE: Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO.

METHODS: We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking.

RESULTS: Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068).

SIGNIFICANCE: CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment.

PMID:38808601 | DOI:10.1111/epi.18025

https://pubmed.ncbi.nlm.nih.gov/38808601/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240529132134&v=2.18.0.post9+e462414 May 29, 2024 10:00 am

PubMed: Identification of Genes Hub Associated with Triple-Negative Breast Cancer and Cannabidiol Analogs Potential Inhibitory Agents: An In-silico Study

PubMed: Identification of Genes Hub Associated with Triple-Negative Breast Cancer and Cannabidiol Analogs Potential Inhibitory Agents: An In-silico Study

Asian Pac J Cancer Prev. 2024 May 1;25(5):1649-1661. doi: 10.31557/APJCP.2024.25.5.1649.

ABSTRACT

OBJECTIVE: Triple-negative breast cancer presents a significant challenge in oncology due to its complex treatment and aggressive nature. This subtype lacks common cancer cell receptors like estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. This study aimed to identify, through bioinformatic analysis, the key genes associated with triple-negative breast cancer. In addition, CBD analogs with potential inhibitory effects on these genes were evaluated through docking and molecular dynamics.

METHODS: Gene expression profiles from the GSE178748 dataset were analyzed, focusing on MDA-MB-231 breast cancer cell lines. Differentially expressed genes were determined through protein-protein interaction networks and subsequently validated. Additionally, the inhibitory effects of cannabidiol analogs on these hub genes were assessed using molecular docking and dynamics.

RESULTS: Analysis of the hub highlighted RPL7A, NHP2L1, and PSMD11 as significant players in TNBC regulation. Ligand 44409296 showed the best affinity energy with RPL7A, while 166505341 exhibited the highest affinity with NHP2L1 and PSMD11, surpassing CBD. Analyses of RMSD, RMSF, SASA, and Gyration Radius indicated structural stability and interactions of the proteins with ligands over time. MMGBSA calculations showed favorable binding energies for the ligands with the target proteins.

CONCLUSION: In conclusion, this study identified key genes, namely RPL7A, NHP2L1, and PSMD11, associated with triple-negative breast cancer and demonstrated promising interactions with cannabidiol analogs, particularly 44409296 and 166505341. These findings suggest potential therapeutic targets and highlight the relevance of further clinical investigations. Additionally, the ligands exhibited favorable ADME properties and low toxicity, underscoring their potential in future drug development for TNBC treatment.

PMID:38809637 | DOI:10.31557/APJCP.2024.25.5.1649

https://pubmed.ncbi.nlm.nih.gov/38809637/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240529192251&v=2.18.0.post9+e462414 May 29, 2024 10:00 am

Clarification by DEA expands definition of THC in hemp to include THCA

HempToday®: Clarification by DEA expands definition of THC in hemp to include THCA
The U.S. Drug Enforcement Administration (DEA) has clarified the definition of THC in the context of industrial hemp, potentially placing greater restrictions on intoxicating products derived from hemp compounds, according […]

#CBD #Hemp
https://hemptoday.net/clarification-by-dea-expands-definition-of-thc-in-hemp-to-include-thca/
May 29, 2024 8:06 am

PubMed: Differentiation of Δ<sup>9</sup>-THC and CBD Using Silver-Ligand Ion Complexation and Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS)

PubMed: Differentiation of Δ<sup>9</sup>-THC and CBD Using Silver-Ligand Ion Complexation and Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS)

J Am Soc Mass Spectrom. 2024 May 28. doi: 10.1021/jasms.3c00452. Online ahead of print.

ABSTRACT

The 2018 Farm Bill defines marijuana as Cannabis sativa L. or any derivative thereof that contains greater than 0.3% Δ9-tetrahydrocannabinol (Δ9-THC) on a dry weight basis. The main cannabinoids present in Cannabis sativa L., Δ9-THC and cannabidiol (CBD), are structural isomers that cannot be differentiated using direct mass spectrometry with soft ionization techniques alone. Due to the classification of marijuana as a Schedule I controlled substance, the differentiation of Δ9-THC and CBD is crucial within the seized drug community. This study explores the use of Ag-ligand ion complexation and electrospray ionization tandem mass spectrometry (ESI-MS/MS) for the differentiation of Δ9-THC and CBD using six different Ag complexes. Differences between the binding affinities of Δ9-THC and CBD for [Ag(PPh3)(OTf)]2 lead to the formation of unique product ions at m/z 421/423, m/z 353/355, and m/z 231 for CBD, enabling the differentiation of CBD from Δ9-THC. When applied to the analysis of known Δ9-THC:CBD mixture ratios, the developed [Ag(PPh3)(OTf)]2 ion complexation method was able to differentiate Δ9-THC-rich and CBD-rich samples based on the average abundance of the product ions at m/z 421/423. The developed approach was then applied to methanolic extracts of 20 authentic cannabis samples with known Δ9-THC and CBD compositions, resulting in a 95% correct classification rate. Even though the developed Ag-ligand ion complexation method was only demonstrated for the qualitative differentiation of Δ9-THC-rich and CBD-rich cannabis, this study establishes a foundation for the use of Ag-ligand ion complexation that is essential for future quantitative approaches.

PMID:38804709 | DOI:10.1021/jasms.3c00452

https://pubmed.ncbi.nlm.nih.gov/38804709/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240528132217&v=2.18.0.post9+e462414 May 28, 2024 10:00 am

PubMed: Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks

PubMed: Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks

Neuropsychopharmacology. 2024 May 28. doi: 10.1038/s41386-024-01891-6. Online ahead of print.

ABSTRACT

Adolescence is a time of rapid neurodevelopment and the endocannabinoid system is particularly prone to change during this time. Cannabis is a commonly used drug with a particularly high prevalence of use among adolescents. The two predominant phytocannabinoids are Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which affect the endocannabinoid system. It is unknown whether this period of rapid development makes adolescents more or less vulnerable to the effects of cannabis on brain-network connectivity, and whether CBD may attenuate the effects of THC. Using fMRI, we explored the impact of vaporized cannabis (placebo, THC: 8 mg/75 kg, THC + CBD: 8 mg/75 kg THC & 24 mg/75 kg CBD) on resting-state networks in groups of semi-regular cannabis users (usage frequency between 0.5 and 3 days/week), consisting of 22 adolescents (16-17 years) and 24 young adults (26-29 years) matched for cannabis use frequency. Cannabis caused reductions in within-network connectivity in the default mode (F[2,88] = 3.97, P = 0.022, η² = 0.018), executive control (F[2,88] = 18.62, P < 0.001, η² = 0.123), salience (F[2,88] = 12.12, P < 0.001, η² = 0.076), hippocampal (F[2,88] = 14.65, P < 0.001, η² = 0.087), and limbic striatal (F[2,88] = 16.19, P < 0.001, η² = 0.102) networks compared to placebo. Whole-brain analysis showed cannabis significantly disrupted functional connectivity with cortical regions and the executive control, salience, hippocampal, and limbic striatal networks compared to placebo. CBD did not counteract THC's effects and further reduced connectivity both within networks and the whole brain. While age-related differences were observed, there were no interactions between age group and cannabis treatment in any brain network. Overall, these results challenge the assumption that CBD can make cannabis safer, as CBD did not attenuate THC effects (and in some cases potentiated them); furthermore, they show that cannabis causes similar disruption to resting-state connectivity in the adolescent and adult brain.

PMID:38806583 | DOI:10.1038/s41386-024-01891-6

https://pubmed.ncbi.nlm.nih.gov/38806583/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240529012248&v=2.18.0.post9+e462414 May 28, 2024 10:00 am

Italian government in ‘grotesque crackdown’ on CBD, other flower-based products

HempToday®: Italian government in ‘grotesque crackdown’ on CBD, other flower-based products
The Italian government of Prime Minister Giorgia Meloni has taken aim at industrial hemp in legislation that would wipe out CBD and all other products derived from the plant’s flowers. […]

#CBD #Hemp
https://hemptoday.net/italian-government-in-grotesque-crackdown-on-cbd-other-flower-based-products/
May 28, 2024 8:26 am

Top hemp ‘dual-cropping’ varieties are identified, but practice involves tradeoffs

HempToday®: Top hemp ‘dual-cropping’ varieties are identified, but practice involves tradeoffs
Canadian and French hemp varieties offer the most potential yields of grain and straw from a single crop, according to ongoing trials in four Midwestern U.S. states. Researchers also found […]

#CBD #Hemp
https://hemptoday.net/top-hemp-dual-cropping-varieties-are-identified-but-practice-involves-tradeoffs/
May 27, 2024 7:15 am

PubMed: Harnessing therapeutic deep eutectic solvents in self-emulsifying systems to improve CBD delivery

PubMed: Harnessing therapeutic deep eutectic solvents in self-emulsifying systems to improve CBD delivery

Int J Pharm. 2024 May 24:124267. doi: 10.1016/j.ijpharm.2024.124267. Online ahead of print.

ABSTRACT

In this study, Cannabidiol crystals (CBD) were used as a BCS class II model drug to generate a novel therapeutic deep eutectic solvent (THEDES) with easy preparation using caprylic acid (CA). The hydrogen bonding interaction was confirmed by different techniques such as FT-IR and NMR, resulting in a hydrophobic system suitable for liquid formulations. The CBD-based THEDES, combined with a specific mixture of surfactants and co-surfactants, successfully formed a self-emulsifying drug delivery system (SEDDS) that generated uniform nano-sized droplets once dispersed in water. Hence, the THEDES showed compatibility with the self-emulsifying approach, offering an alternative method to load drugs at their therapeutic dosage. Physical stability concerns regarding the unconventional oily phase were addressed through stress tests using multiple and dynamic light scattering, demonstrating the robustness of the system. In addition, the formulated SEDDS proved effective in protecting CBD from the harsh acidic gastric environment for up to 2 h at pH 1.2. Furthermore, in vitro studies have confirmed the safety of the formulation and the ability of CBD to permeate Caco-2 cells when formulated. This investigation highlights the potential incorporation of THEDES in lipid-based formulations like SEDDS, expanding the avenues for innovative oral drug delivery approaches.

PMID:38797251 | DOI:10.1016/j.ijpharm.2024.124267

https://pubmed.ncbi.nlm.nih.gov/38797251/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240527012520&v=2.18.0.post9+e462414 May 26, 2024 10:00 am

PubMed: Cannabidiol in the dorsal hippocampus attenuates emotional and cognitive impairments related to neuropathic pain: Role of prelimbic neocortex-hippocampal connections

PubMed: Cannabidiol in the dorsal hippocampus attenuates emotional and cognitive impairments related to neuropathic pain: Role of prelimbic neocortex-hippocampal connections

Prog Neuropsychopharmacol Biol Psychiatry. 2024 May 24:111039. doi: 10.1016/j.pnpbp.2024.111039. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Chronic neuropathic pain (NP) is commonly associated with cognitive and emotional impairments. Cannabidiol (CBD) presents a broad spectrum of action with a potential analgesic effect. This work investigates the CBD effect on comorbidity between chronic NP, depression, and memory impairment.

EXPERIMENTAL APPROACH: The connection between the neocortex and the hippocampus was investigated with biotinylated dextran amine (BDA) deposits in the prelimbic cortex (PrL). Wistar rats were submitted to chronic constriction injury (CCI) of the sciatic nerve and CA1 treatment with CBD (15, 30, 60 nmol).

KEY RESULTS: BDA-labeled were found in CA1 and dentate gyrus. CCI-induced mechanical and cold allodynia increased c-Fos protein expression in the PrL and CA1. The number of astrocytes in PrL and CA1 increased, and the number of neuroblasts decreased in CA1. The CCI animals showed increasing depressive-like behaviors, such as memory impairment. CBD (60 nmol) treatment decreased mechanical and cold allodynia, attenuated depressive-associated behaviors, and improved memory performance. Cobalt chloride (CoCl2: 1 nM), WAY-100635 (0.37 nmol), and AM251 (100 nmol) intra-PrL reversed the CBD (60 nmol) effect intra-CA1, both in nociceptive, cognitive, and depressive behaviors.

CONCLUSION: CBD represents a promising therapeutic perspective in the pharmacological treatment of chronic NP and associated comorbidities such as depression and memory impairments. The CBD effects possibly recruit the CA1-PrL pathway, inducing neuroplasticity. CBD acute treatment into the CA1 produces functional and molecular morphological improvements.

PMID:38797491 | DOI:10.1016/j.pnpbp.2024.111039

https://pubmed.ncbi.nlm.nih.gov/38797491/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240527012520&v=2.18.0.post9+e462414 May 26, 2024 10:00 am

PubMed: Opportunities, Challenges, and Scientific Progress in Hemp Crops

PubMed: Opportunities, Challenges, and Scientific Progress in Hemp Crops

Molecules. 2024 May 20;29(10):2397. doi: 10.3390/molecules29102397.

ABSTRACT

The resurgence of cannabis (Cannabis sativa L.) has been propelled by changes in the legal framework governing its cultivation and use, increased demand for hemp-derived products, and studies recognizing the industrial and health benefits of hemp. This has led to the creation of novel high-cannabidiol, low-Δ9-tetrahydrocannabinol varieties, enabling hemp crop expansion worldwide. This review elucidates the recent implications for hemp cultivation in Europe, with a focus on the legislative impacts on the cultivation practices, prospective breeding efforts, and dynamic scientific landscape surrounding this crop. We also review the current cultivars’ cannabinoid composition of the European hemp market and its major differences with that of the United States.

PMID:38792258 | DOI:10.3390/molecules29102397

https://pubmed.ncbi.nlm.nih.gov/38792258/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240525112158&v=2.18.0.post9+e462414 May 25, 2024 10:00 am

PubMed: Drug-Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain

PubMed: Drug-Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain

Pharmaceuticals (Basel). 2024 May 10;17(5):613. doi: 10.3390/ph17050613.

ABSTRACT

Clinical practice entails a translation of research that assists in the use of scientific data and therapeutic evidence for the benefit of the patient. This review critically summarizes the potential impact of cannabinoids in conjunction with other drugs when associated with treatments for epilepsy, autism spectrum disorder, cancer, multiple sclerosis, and chronic pain. In these associations, potential drug interactions may occur and alter the predicted clinical results. Therefore, the potential for drug interactions must always be assessed to avoid therapeutic failures and/or increased side effects. Some effects may be additive, synergistic, or antagonistic, but changes in absorption, distribution, metabolism, particularly through cytochrome P450 (CYP) isoenzymes (e.g., CYP2C9 and CYP3A4), and excretion may also occur. For example, the combination of cannabis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases the plasma concentration of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In contrast, rifampicin, a CYP3A4 inducer, stands out for reducing plasma THC levels by approximately 20-40% and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Pharmacokinetic interactions with anticonvulsant medications have also been reported, as have pharmacodynamic interactions between cannabinoids and medications with sympathomimetic effects (e.g., tachycardia, hypertension), central nervous system depressants (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia and somnolence). Although further studies are still pending, there is currently clinical evidence supporting drug interactions with cannabinoids, requiring doctors to evaluate the risk of drug combinations with cannabinoids and vice versa. The tables provided here were designed to facilitate the identification of biorelevant interactions that may compromise therapeutic efficacy and toxicity.

PMID:38794183 | DOI:10.3390/ph17050613

https://pubmed.ncbi.nlm.nih.gov/38794183/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240525112158&v=2.18.0.post9+e462414 May 25, 2024 10:00 am

PubMed: Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism

PubMed: Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism

Front Neurosci. 2024 May 9;18:1359810. doi: 10.3389/fnins.2024.1359810. eCollection 2024.

ABSTRACT

INTRODUCTION: The prevalence of Autism Spectrum Disorder (ASD) has drastically risen over the last two decades and is currently estimated to affect 1 in 36 children in the U.S., according to the center for disease control (CDC). This heterogenous neurodevelopmental disorder is characterized by impaired social interactions, communication deficits, and repetitive behaviors plus restricted interest. Autistic individuals also commonly present with a myriad of comorbidities, such as attention deficit hyperactivity disorder, anxiety, and seizures. To date, a pharmacological intervention for the treatment of core autistic symptoms has not been identified. Cannabidiol (CBD), the major nonpsychoactive constituent of Cannabis sativa, is suggested to have multiple therapeutic applications, but its effect(s) on idiopathic autism is unknown. We hypothesized that CBD will effectively attenuate the autism-like behaviors and autism-associated comorbid behaviors in BTBR T+Itpr3tf/J (BTBR) mice, an established mouse model of idiopathic ASD.

METHODS: Male BTBR mice were injected intraperitoneally with either vehicle, 20 mg/kg CBD or 50 mg/kg CBD daily for two weeks beginning at postnatal day 21 ± 3. On the final treatment day, a battery of behavioral assays were used to evaluate the effects of CBD on the BTBR mice, as compared to age-matched, vehicle-treated C57BL/6 J mice.

RESULTS: High dose (50 mg/kg) CBD treatment attenuated the elevated repetitive self-grooming behavior and hyperlocomotion in BTBR mice. The social deficits exhibited by the control BTBR mice were rescued by the 20 mg/kg CBD treatment.

DISCUSSION: Our data indicate that different doses for CBD are needed for treating specific ASD-like behaviors. Together, our results suggest that CBD may be an effective drug to ameliorate repetitive/restricted behaviors, social deficits, and autism-associated hyperactivity.

PMID:38784096 | PMC:PMC11112039 | DOI:10.3389/fnins.2024.1359810

https://pubmed.ncbi.nlm.nih.gov/38784096/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240524073521&v=2.18.0.post9+e462414 May 24, 2024 10:00 am

PubMed: Modulation of Oxidative Stress and Neuroinflammation by Cannabidiol (CBD): Promising Targets for the Treatment of Alzheimer's Disease

PubMed: Modulation of Oxidative Stress and Neuroinflammation by Cannabidiol (CBD): Promising Targets for the Treatment of Alzheimer's Disease

Curr Issues Mol Biol. 2024 May 6;46(5):4379-4402. doi: 10.3390/cimb46050266.

ABSTRACT

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common form of dementia globally. Although the direct cause of AD remains under debate, neuroinflammation and oxidative stress are critical components in its pathogenesis and progression. As a result, compounds like cannabidiol (CBD) are being increasingly investigated for their ability to provide antioxidant and anti-inflammatory neuroprotection. CBD is the primary non-psychotropic phytocannabinoid derived from Cannabis sativa. It has been found to provide beneficial outcomes in a variety of medical conditions and is gaining increasing attention for its potential therapeutic application in AD. CBD is not psychoactive and its lipophilic nature allows its rapid distribution throughout the body, including across the blood-brain barrier (BBB). CBD also possesses anti-inflammatory, antioxidant, and neuroprotective properties, making it a viable candidate for AD treatment. This review outlines CBD’s mechanism of action, the role of oxidative stress and neuroinflammation in AD, and the effectiveness and limitations of CBD in preclinical models of AD.

PMID:38785534 | DOI:10.3390/cimb46050266

https://pubmed.ncbi.nlm.nih.gov/38785534/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240524132106&v=2.18.0.post9+e462414 May 24, 2024 10:00 am

PubMed: Protective Effects of Cannabidiol (CBD) against Qxidative Stress, but Not Excitotoxic-Related Neuronal Cell Damage-An In Vitro Study

PubMed: Protective Effects of Cannabidiol (CBD) against Qxidative Stress, but Not Excitotoxic-Related Neuronal Cell Damage-An In Vitro Study

Biomolecules. 2024 May 9;14(5):564. doi: 10.3390/biom14050564.

ABSTRACT

Cannabidiol (CBD) appears to possess some neuroprotective properties, but experimental data are still inconsistent. Therefore, this in vitro study aimed to compare the effects of CBD in a wide range of concentrations on oxidative stress and excitotoxic-related cell damage. Results showed that low concentrations of CBD ameliorated the H2O2-evoked cell damage of primary cortical neuronal cell culture. However, higher concentrations of CBD alone (5-25 μM) decreased the viability of cortical neurons in a concentration-dependent manner and aggravated the toxic effects of hydrogen peroxide (H2O2). Neuroprotection mediated by CBD in primary neurons against H2O2 was not associated with a direct influence on ROS production nor inhibition of caspase-3, but we found protective effects of CBD at the level of mitochondrial membrane potential and DNA fragmentation. However, CBD had no protective effect on the glutamate-induced cell damage of cortical neurons, and in higher concentrations, it enhanced the toxic effects of this cell-damaging factor. Likewise, CBD, depending on its concentration, at least did not affect or even enhance cortical cellular damage exposed to oxygen-glucose deprivation (OGD). Finally, we showed that CBD in submicromolar or low micromolar concentrations significantly protected human neuronal-like SH-SY5Y cells against H2O2– and 6-hydroxydopamine (6-OHDA)-induced cell damage. Our data indicate that CBD has a dual effect on oxidative stress-induced neuronal death-in low concentrations, it is neuroprotective, but in higher ones, it may display neurotoxic activity. On the other hand, in excitotoxic-related models, CBD was ineffective or enhanced cell damage. Our data support the notion that the neuroprotective effects of CBD strongly depend on its concentration and experimental model of neuronal death.

PMID:38785971 | DOI:10.3390/biom14050564

https://pubmed.ncbi.nlm.nih.gov/38785971/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240524132106&v=2.18.0.post9+e462414 May 24, 2024 10:00 am

PubMed: Cannabidiol and its application in the treatment of oral diseases: therapeutic potentials, routes of administration and prospects

PubMed: Cannabidiol and its application in the treatment of oral diseases: therapeutic potentials, routes of administration and prospects

Biomed Pharmacother. 2024 May 23;176:116271. doi: 10.1016/j.biopha.2024.116271. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), one of the most important active ingredients in cannabis, has been reported to have some pharmacological effects such as antibacterial and analgesic effects, and to have therapeutic potential in the treatment of oral diseases such as oral cancer, gingivitis and periodontal diseases. However, there is a lack of relevant systematic research and reviews. Therefore, based on the etiology and clinical symptoms of several common oral diseases, this paper focuses on the therapeutic potential of CBD in periodontal diseases, pulp diseases, oral mucosal diseases, oral cancer and temporomandibular joint diseases. The pharmacological effects of CBD and the distribution and function of its receptors in the oral cavity are also summarized. In order to provide reference for future research and further clinical application of CBD, we also summarize several possible routes of administration and corresponding characteristics. Finally, the challenges faced while applying CBD clinically and possible solutions are discussed, and we also look to the future.

PMID:38788594 | DOI:10.1016/j.biopha.2024.116271

https://pubmed.ncbi.nlm.nih.gov/38788594/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240525062209&v=2.18.0.post9+e462414 May 24, 2024 10:00 am

Language floated for Farm Bill would wipe out delta-8, other hemp intoxicants

HempToday®: Language floated for Farm Bill would wipe out delta-8, other hemp intoxicants
Proposed new provisions for the next U.S. Farm Bill are bearing down on delta-8 THC and other intoxicating hemp-derived substances as lawmakers begin to look at serious language that would […]

#CBD #Hemp
https://hemptoday.net/language-floated-for-farm-bill-would-wipe-out-delta-8-other-hemp-intoxicants/
May 23, 2024 6:12 pm

PubMed: Cannabis sativa (Hemp) seed-derived peptides WVYY and PSLPA modulate the Nrf2 signaling pathway in human keratinocytes

PubMed: Cannabis sativa (Hemp) seed-derived peptides WVYY and PSLPA modulate the Nrf2 signaling pathway in human keratinocytes

PLoS One. 2024 May 23;19(5):e0298487. doi: 10.1371/journal.pone.0298487. eCollection 2024.

ABSTRACT

Cannabis sativa (Hemp) seeds are used widely for cosmetic and therapeutic applications, and contain peptides with substantial therapeutic potential. Two key peptides, WVYY and PSLPA, extracted from hemp seed proteins were the focal points of this study. These peptides have emerged as pivotal contributors to the various biological effects of hemp seed extracts. Consistently, in the present study, the biological effects of WVYY and PSLPA were explored. We confirmed that both WVYY and PSLPA exert antioxidant and antibacterial effects and promote wound healing. We hypothesized the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in these observed effects, given that Nrf2 is reported to be a central player in the regulation of these observed effects. Molecular-level investigations unequivocally confirmed the role of the Nrf2 signaling pathway in the observed effects of WVYY and PSLPA, specifically their antioxidant effects. Our study highlights the therapeutic potential of hemp seed-derived peptides WVYY and PSLPA, particularly with respect to their antioxidant effects, and provides a nuanced understanding of their effects. Further, our findings can facilitate the investigation of targeted therapeutic applications and also underscore the broader significance of hemp extracts in biological contexts.

PMID:38781174 | DOI:10.1371/journal.pone.0298487

https://pubmed.ncbi.nlm.nih.gov/38781174/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240523192314&v=2.18.0.post9+e462414 May 23, 2024 10:00 am

PubMed: The Effect of Cannabidiol on Subjective Responses to Endurance Exercise: A Randomised Controlled Trial

PubMed: The Effect of Cannabidiol on Subjective Responses to Endurance Exercise: A Randomised Controlled Trial

Sports Med Open. 2024 May 23;10(1):61. doi: 10.1186/s40798-024-00727-3.

ABSTRACT

BACKGROUND: Exercise is known to improve health. However, it can be unpleasant, often inducing negative feelings, or ‘affect’. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has been reported to enhance the subjective experience of exercise; specifically, in trained individuals performing fixed-intensity endurance activity. Here, we investigated the effects of CBD on subjective responses to exercise under more ecologically valid conditions; namely, in recreationally active individuals performing self-paced endurance activity.

METHODS: A randomised, double-blind, placebo-controlled, crossover trial was conducted at Griffith University between July 17 and August 28, 2023. Griffith University students studying sports nutrition were invited to take part, with eligible volunteers ≥ 18 years of age and able to perform endurance exercise. Participants ingested placebo or 150 mg CBD in two soft-gel capsules 90 min before completing a self-paced 25-lap (10 km) run around an outdoor athletics track (400 m, synthetic). The primary outcomes were affective valence during exercise, assessed on completion of laps 6, 12, 18 and 24 using the ‘Feelings Scale’, and positive and negative affect, assessed at baseline, pre-run and post-run using the ‘Positive and Negative Affect Schedule’. Exercise enjoyment, motivation and self-efficacy, the core features of the ‘runner’s high’ (i.e., euphoria, pain, anxiety, sedation), perceived exertion and run time were also assessed.

RESULTS: Fifty-two participants were randomised and 51 were included in the final sample (n = 22 female; 22 [21-25] years). Exercise induced negative affect (i.e., at the time of undertaking) and increased pain. CBD did not counteract either response. In fact, CBD had no significant effects on any of the outcomes measured. In contrast, exercise, once completed, increased positive affect, and decreased negative affect and anxiety.

CONCLUSIONS: CBD (150 mg, oral) does not appear to enhance the subjective experience of self-paced endurance exercise in recreationally active individuals. Nor, however, does it appear to compromise it. These findings suggest that CBD use is safe under exercise conditions and unlikely to impede physical activity participation. Our study also reaffirms the powerful mood-enhancing effects of exercise.

TRIAL REGISTRATION: Registered with the Australian New Zealand Clinical Trials Registry ( www.anzctr.org.au ) on May 31, 2023 (Trial ID: ACTRN12623000593639).

PMID:38782848 | DOI:10.1186/s40798-024-00727-3

https://pubmed.ncbi.nlm.nih.gov/38782848/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240524012314&v=2.18.0.post9+e462414 May 23, 2024 10:00 am

PubMed: An open-label feasibility trial of transdermal cannabidiol for hand osteoarthritis

PubMed: An open-label feasibility trial of transdermal cannabidiol for hand osteoarthritis

Sci Rep. 2024 May 23;14(1):11792. doi: 10.1038/s41598-024-62428-x.

ABSTRACT

Hand osteoarthritis (OA) is an irreversible degenerative condition causing chronic pain and impaired functionality. Existing treatment options are often inadequate. Cannabidiol (CBD) has demonstrated analgesic and anti-inflammatory effects in preclinical models of arthritis. In this open-label feasibility trial, participants with symptomatically active hand OA applied a novel transdermal CBD gel (4% w/w) three times a day for four weeks to their most painful hand. Changes in daily self-reported pain scores were measured on a 0-10 Numeric Pain Rating Scale (NPRS). Hand functionality was determined via daily grip strength measures using a Bluetooth equipped squeeze ball and self-report questionnaire. Quality of life (QoL) ratings around sleep, anxiety, stiffness and fatigue were also measured. All self-report measures and grip strength data were gathered via smartphone application. Urinalysis was conducted at trial end to determine systemic absorption of CBD. Eighteen participants were consented and 15 completed the trial. Pain ratings were significantly reduced over time from pre-treatment baseline including current pain (- 1.91 ± 0.35, p < 0.0001), average pain (- 1.92 ± 0.35, p < 0.0001) and maximum pain (- 1.97 ± 0.34, p < 0.0001) (data represent mean reduction on a 0-10 NPRS scale ± standard error of the mean (SEM)). A significant increase in grip strength in the treated hand (p < 0.0001) was observed although self-reported functionality did not improve. There were significant (p < 0.005) improvements in three QoL measures: fatigue, stiffness and anxiety. CBD and its metabolites were detected at low concentrations in all urine samples. Measured reductions in pain and increases in grip strength seen during treatment reverted back towards baseline during the washout phase. In summary, pain, grip strength and QoL measures, using smartphone technology, was shown to improve over time following transdermal CBD application suggesting feasibility of this intervention in relieving osteoarthritic hand pain. Proof of efficacy, however, requires further confirmation in a placebo-controlled randomised trial.Trial registration: ANZCTR public trials registry (ACTRN12621001512819, 05/11/2021).

PMID:38783008 | DOI:10.1038/s41598-024-62428-x

https://pubmed.ncbi.nlm.nih.gov/38783008/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240524012314&v=2.18.0.post9+e462414 May 23, 2024 10:00 am

Fiber comes on strong as Australian hemp fields double, stemming 3-year slide

HempToday®: Fiber comes on strong as Australian hemp fields double, stemming 3-year slide
While Australia’s hemp industry faces significant challenges to development, political momentum is growing in some states and healthy investment levels are projected over the next two years in the fiber […]

#CBD #Hemp
https://hemptoday.net/fiber-comes-on-strong-as-australian-hemp-fields-double-stemming-3-year-slide/
May 23, 2024 7:41 am

PubMed: Commercial Cannabidiol for Community-Based Young Adolescents: Predicting Medicinal Use

PubMed: Commercial Cannabidiol for Community-Based Young Adolescents: Predicting Medicinal Use

Cannabis Cannabinoid Res. 2024 May 7. doi: 10.1089/can.2024.0015. Online ahead of print.

ABSTRACT

Objectives: Cannabidiol (CBD) is rising in popularity, including as a potential medicinal product. Yet data on use of commercial CBD for medicinal or health reasons in adolescents are lacking. In this study we aim to detail characteristics of adolescents given commercial CBD for health reasons (health CBD [hCBD]) and to investigate predictors of use. Materials and Methods: The Adolescent Brain Cognitive Development (ABCD) Study is a population-based cohort study following U.S. healthy, community-based adolescents annually, with data from 2018 to 2022 (11- to 15-year-olds; N=11,189). Participants and caregivers completed questionnaires, including whether adolescents were given CBD with parent or doctor’s permission. Participants reported past-month pain, attention problems, externalizing symptoms, internalizing symptoms, and total mental health problems. Caregivers reported youth sociodemographics, sleep problems, whether the youth had mental health treatment or sought medical treatment, and rules about recreational cannabis use. We describe youth given hCBD, and run generalized estimating equations predicting odd ratios (ORs) and 95% confidence intervals of adolescents given hCBD by mental health, physical health, or sociodemographics of factors. Results: Of the 11,189 participants across up to three waves of data, 48% were female. Mean age across waves was 12.8 years old (SD=1). In total, 307 (2.8%) were given hCBD. Common administration methods were oil (42%), topical (31%), and edibles (29%). Increased hCBD odds were associated with being older (OR=1.32 [1.17-1.49]), White (relative to Black, OR=05.97 [2.81-12.65] or Hispanic, OR=1.82 [1.17-2.82]), parents with some college (relative to no high school diploma, OR=3.55 [1.09-11.6]), internalizing symptoms (OR=1.81 [1.13-2.91]), mental health treatment (OR=1.76 [1.3-2.38]), pain (OR=1.38 [1.09-1.76]), medical treatment (OR=1.39 [1.08-1.79]), and sleep problems (OR=1.69 [1.27-2.25]). Rules against recreational cannabis decreased odds of hCBD (OR=1.75 [1.30-2.36]). Conclusions: Findings indicate some healthy adolescents are given hCBD, and predictors of use include mental and physical health concerns, being White, older, and parents with some college education. Providers should ask if their youth patients are being given CBD medicinally, and transparently discuss potential benefits, consequences, and unknowns of CBD.

PMID:38775636 | DOI:10.1089/can.2024.0015

https://pubmed.ncbi.nlm.nih.gov/38775636/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240522132251&v=2.18.0.post9+e462414 May 22, 2024 10:00 am

PubMed: Cannabidiol and Aza-BODIPY Coencapsulation for Photodynamic Therapy Enhancement in Liver Cancer Cells

PubMed: Cannabidiol and Aza-BODIPY Coencapsulation for Photodynamic Therapy Enhancement in Liver Cancer Cells

ACS Appl Bio Mater. 2024 May 22. doi: 10.1021/acsabm.4c00239. Online ahead of print.

ABSTRACT

Photodynamic therapy (PDT) and cannabidiol (CBD) have been explored for their potential in synergistic cancer treatment. In this study, we employed CBD oil as a lipid phase, encapsulated within AZB-I@Lec-T to create lipid-based nanoparticles. Here, CBD oil does two tasks: it acts as a pyroptosis agent to destroy liver cancer cells and as a lipid phase to dissolve the photosensitizer. It was expected that this system would offer synergistic therapy between CBD and PDT better than a single use of each treatment. With a series of in vitro experiments, the nanoparticles exhibited induced apoptosis in 68% of HepG2 cells treated with AZB-I@Lec-T@CBD and near-infrared (NIR)-light irradiation, reducing expression levels of antioxidant defense system genes. Furthermore, both components worked well in a submicromolar range when combined in our formulation. These results highlight the potential for amplifying primary cellular damage with the combination of PDT and CBD encapsulation, providing a promising therapeutic approach for liver cancer treatment guidelines.

PMID:38776245 | DOI:10.1021/acsabm.4c00239

https://pubmed.ncbi.nlm.nih.gov/38776245/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240522193331&v=2.18.0.post9+e462414 May 22, 2024 10:00 am

PubMed: Selected cannabis cultivars modulate glial activation: in vitro and in vivo studies

PubMed: Selected cannabis cultivars modulate glial activation: in vitro and in vivo studies

J Cannabis Res. 2024 May 22;6(1):25. doi: 10.1186/s42238-024-00232-0.

ABSTRACT

INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination and axonal loss. Cannabis, an immunomodulating agent, is known for its ability to treat MS effectively. However, due to variations in the profile of secondary metabolites, especially cannabinoids, among cannabis cultivars, the effectiveness of cannabis treatment can vary, with significant variability in the effects on different biological parameters. For screening available cultivars, cellular in vitro as well as pre-clinical in vivo assays, are required to evaluate the effectiveness of the wide range of chemical variability that exists in cannabis cultivars. This study evaluated comparatively three chemically diverse cannabis cultivars, CN2, CN4 and CN6, containing different ratios of phytocannabinoids, for their neuroinflammatory activity in MS model.

MATERIALS AND METHODS: In vitro experiments were performed with lipopolysaccharide (LPS)-activated BV-2 microglia and primary glial cells to evaluate the effect of different cannabis cultivars on nitric oxide (NO) and inflammatory cytokines, as well as inducible nitric oxide synthase (iNOS) protein expression. An in vivo experiment using the experimental autoimmune encephalomyelitis (EAE) MS model was conducted using Myelin oligodendrocyte glycoprotein (MOG) as the activating peptide. The cannabis extracts of the cultivars CN2, CN4, CN6 or vehicle, were intraperitoneally injected with clinical scores given based on observed symptoms over the course of study. At the end of the experiment, the mice were sacrificed, and splenocyte cytokine secretion was measured using ELISA. Lumbar sections from the spinal cord of treated MS mice were evaluated for microglia, astrocytes and CD4+ cells.

RESULTS: Extracts of the CN2 cultivar contained tetrahydrocannabinolic acid (THCA) and tetrahydrocannabinol (THC) without cannabidiol (CBD), and a number of monoterpenes. CN4 contained cannabidiolic acid (CBDA) and tetrahydrocannabidiolic acid (THCA), with significant amounts of THC: CBD in a 1:1 ratio, as well as sesquiterpenes and some monoterpenes; and CN6 contained primarily CBDA and THCA, as well as THC and CBD in a 2:1 ratio, with some sesquiterpenes and no monoterpenes. All extracts were not cytotoxic in glial cells up to 50 µg/ml. Dose dependent inhibition of LPS-induced BV2 as well as primary microglial NO secretion confirmed the anti-inflammatory and anti-oxidative activity of the three cannabis cultivars. CN2 but not CN4 reduced both astrocytosis and microglial activation in lumbar sections of EAE mice. In contrast, CN4 but not CN2 significantly decreased the secretion of TNFα and Interferon γ (IFNγ) in primary splenocytes extracted from EAE mice.

CONCLUSIONS: While both cannabis cultivars, CN2 and CN4, significantly reduced the severity of the clinical signs throughout the course of the study, they modulated different inflammatory mediators and pathways, probably due to differences in their phytocannabinoid composition. This demonstrates the differential potential of cannabis cultivars differing in chemotype to regulate neuroinflammation and their potential to treat MS.

PMID:38778343 | DOI:10.1186/s42238-024-00232-0

https://pubmed.ncbi.nlm.nih.gov/38778343/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240523012639&v=2.18.0.post9+e462414 May 22, 2024 10:00 am

PubMed: The Potential of Cannabichromene (CBC) as a Therapeutic Agent

PubMed: The Potential of Cannabichromene (CBC) as a Therapeutic Agent

J Pharmacol Exp Ther. 2024 May 22:JPET-MR-2024-002166. doi: 10.1124/jpet.124.002166. Online ahead of print.

ABSTRACT

There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa The two most abundant cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). While the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials. In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC. Significance Statement Cannabichromene (CBC) has been suggested to have disparate therapeutic benefits such as anti-inflammatory, anticonvulsant, antibacterial, and antinociceptive effects. Most of the focus on the medical benefits of cannabinoids has been focused on THC and CBD. The preliminary studies on CBC indicate that this phytocannabinoid may have unique therapeutic potential that warrants further investigation. Following easier access to hemp, CBC products are commercially available over-the-counter and are being widely utilized with little or no evidence of their safety or efficacy.

PMID:38777605 | DOI:10.1124/jpet.124.002166

https://pubmed.ncbi.nlm.nih.gov/38777605/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240523012639&v=2.18.0.post9+e462414 May 22, 2024 10:00 am

SEC lawsuit claims CBD exec spent most of investor funds on gambling, luxury goods

HempToday®: SEC lawsuit claims CBD exec spent most of investor funds on gambling, luxury goods
The U.S. Securities and Exchange Commission (SEC) has filed suit against a Texas man the agency said collected $1.2 million from investors for a hemp business and then spent more than $755,000 […]

#CBD #Hemp
https://hemptoday.net/sec-suit-claims-cbd-exec-spent-most-of-investor-funds-on-gambling-luxury-goods/
May 22, 2024 9:23 am

Germany nixes troublesome hemp ‘intoxication clause’ and revises other rules

HempToday®: Germany nixes troublesome hemp ‘intoxication clause’ and revises other rules
A controversial clause on THC will be removed from German regulations on industrial hemp, and other rules are being adjusted to ease the path for producers, according to the country’s […]

#CBD #Hemp
https://hemptoday.net/germany-nixes-troublesome-hemp-intoxication-clause-and-revises-other-rules/
May 21, 2024 10:50 am

PubMed: Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo

PubMed: Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo

Int J Nanomedicine. 2024 May 16;19:4321-4337. doi: 10.2147/IJN.S455032. eCollection 2024.

ABSTRACT

PURPOSE: Cannabidiol (CBD) is a promising therapeutic drug with low addictive potential and a favorable safety profile. However, CBD did face certain challenges, including poor solubility in water and low oral bioavailability. To harness the potential of CBD by combining it with a transdermal drug delivery system (TDDS). This innovative approach sought to develop a transdermal patch dosage form with micellar vesicular nanocarriers to enhance the bioavailability of CBD, leading to improved therapeutic outcomes.

METHODS: A skin-penetrating micellar vesicular nanocarriers, prepared using nano emulsion method, cannabidiol loaded transdermal nanocarriers-12 (CTD-12) was presented with a small particle size, high encapsulation efficiency, and a drug-loaded ratio for CBD. The skin permeation ability used Strat-M™ membrane with a transdermal diffusion system to evaluate the CTD and patch of CTD-12 (PCTD-12) within 24 hrs. PCTD-12 was used in a preliminary pharmacokinetic study in rats to demonstrate the potential of the developed transdermal nanocarrier drug patch for future applications.

RESULTS: In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application. Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation. Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application.

CONCLUSION: CTD-12, a transdermal nanocarrier, represents a promising approach for CBD delivery, suggesting its potential as an effective transdermal dosage form.

PMID:38770103 | PMC:PMC11104392 | DOI:10.2147/IJN.S455032

https://pubmed.ncbi.nlm.nih.gov/38770103/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240521072315&v=2.18.0.post9+e462414 May 21, 2024 10:00 am

PubMed: Cannabidiol improves nonmotor symptoms, attenuates neuroinflammation and favors hippocampal newborn neuronal maturation in a rat model of Parkinsonism

PubMed: Cannabidiol improves nonmotor symptoms, attenuates neuroinflammation and favors hippocampal newborn neuronal maturation in a rat model of Parkinsonism

Acta Neuropsychiatr. 2024 May 21:1-30. doi: 10.1017/neu.2024.15. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effects of cannabidiol (CBD) on emotional and cognitive symptoms in rats with intra-nigral 6-hydroxydopamine (6-OHDA) lesions.

METHODS: Adult male Wistar rats received bilateral intranigral 6-OHDA infusions and were tested in a battery of behavioral paradigms to evaluate nonmotor symptoms. The brains were obtained to evaluate the effects of CBD on hippocampal neurogenesis.

RESULTS: 6-hydroxydopamine-lesioned rats exhibited memory impairments and despair-like behavior in the novelty-suppressed feeding test and forced swim test, respectively. The animals also exhibited dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), striatum, and ventral tegmental area and a reduction of hippocampal neurogenesis. Cannabidiol decreased dopaminergic neuronal loss in the SNpc, reduced the mortality rate and decreased neuroinflammation in 6-OHDA-lesioned rats. In parallel, CBD prevented memory impairments and attenuated despair-like behavior that were induced by bilateral intranigral 6-OHDA lesions. Repeated treatment with CBD favored the neuronal maturation of newborn neurons in the hippocampus in Parkinsonian rats.

CONCLUSION: The present findings suggest a potential beneficial effect of CBD on nonmotor symptoms induced by intra-nigral 6-OHDA infusion in rats.

PMID:38770713 | DOI:10.1017/neu.2024.15

https://pubmed.ncbi.nlm.nih.gov/38770713/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240521072315&v=2.18.0.post9+e462414 May 21, 2024 10:00 am

PubMed: Absence of Evidence for Sustained Effects of Daily Cannabidiol Administration on Anandamide Plasma Concentration in Individuals with Cocaine Use Disorder: Exploratory Findings from a Randomized Controlled Trial

PubMed: Absence of Evidence for Sustained Effects of Daily Cannabidiol Administration on Anandamide Plasma Concentration in Individuals with Cocaine Use Disorder: Exploratory Findings from a Randomized Controlled Trial

Cannabis Cannabinoid Res. 2024 May 21. doi: 10.1089/can.2023.0273. Online ahead of print.

ABSTRACT

Background: Cannabidiol (CBD) has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders, including substance use disorders. Pre-clinical evidence suggests that CBD can increase anandamide (AEA) plasma concentration, possibly mediating some of its therapeutic properties. Whether CBD exerts such an effect on AEA in individuals with cocaine use disorder (CUD) remains unknown. Aims: To explore the sustained effects of daily CBD administration on AEA plasma concentrations compared with placebo in CUD. Methods: We used data from a randomized, double-blind, placebo-controlled trial evaluating CBD’s efficacy in CUD. Seventy-eight individuals were randomized to receive a daily oral dose of 800 mg CBD (n = 40) or a placebo (n = 38). Participants stayed in an inpatient detoxification setting for 10 days, after which they were followed in an outpatient setting for 12 weeks. AEA plasma concentration was measured at baseline and at 23-h post CBD ingestion on day 8 and week 4. A generalized estimating equation model was used to assess CBD’s effects on AEA, and sensitivity analyses were computed using Bayesian linear regressions. Results: Sixty-four participants were included in the analysis. Similar mean AEA plasma concentrations in both treatment groups (p = 0.357) were observed. At day 8, mean AEA plasma concentrations (± standard deviation) were 0.26 (± 0.07) ng/mL in the CBD group and 0.29 (± 0.08) ng/mL in the placebo group (p = 0.832; Bayes factor [BF] = 0.190). At week 4, they were 0.27 (± 0.09) ng/mL in the CBD group and 0.30 (± 0.09) ng/mL in the placebo group (p = 0.181; BF = 0.194). Conclusion: While not excluding any potential acute and short-term effect, daily CBD administration did not exert a sustained impact on AEA plasma concentrations in individuals with CUD compared with placebo. Registration: clinicaltrials.gov (NCT02559167).

PMID:38770686 | DOI:10.1089/can.2023.0273

https://pubmed.ncbi.nlm.nih.gov/38770686/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240521072315&v=2.18.0.post9+e462414 May 21, 2024 10:00 am

PubMed: Applying machine learning to international drug monitoring: classifying cannabis resin collected in Europe using cannabinoid concentrations

PubMed: Applying machine learning to international drug monitoring: classifying cannabis resin collected in Europe using cannabinoid concentrations

Eur Arch Psychiatry Clin Neurosci. 2024 May 21. doi: 10.1007/s00406-024-01816-w. Online ahead of print.

ABSTRACT

In Europe, concentrations of ∆9-tetrahydrocannabinol (THC) in cannabis resin (also known as hash) have risen markedly in the past decade, potentially increasing risks of mental health disorders. Current approaches to international drug monitoring cannot distinguish between different types of cannabis resin which may have contrasting health effects due to THC and cannabidiol (CBD) content. Here, we compared concentrations of THC and CBD in different types of cannabis resin collected in Europe (either Moroccan-type, or Dutch-type). We then tested the ability of machine learning algorithms to classify the type of cannabis resin (either Moroccan-type, or Dutch-type) using routinely collected monitoring data on THC and CBD. Finally, we applied the optimal algorithm to new samples collected in countries where the type of cannabis resin was unknown, the UK and Denmark. Results showed that overall, Dutch-type samples had higher THC (Hedges’ g = 2.39) and lower CBD (Hedges’ g = 0.81) than Moroccan-type samples. A Support Vector Machine algorithm achieved classification accuracy exceeding 95%, with little variation in this estimate, good interpretability, and plausibility. It made contrasting predictions about the type of cannabis resin collected in the UK (94% Moroccan-type; 6% Dutch-type) and Denmark (36% Moroccan-type; 64% Dutch-type). In conclusion, we provide proof-of-concept evidence for the potential of machine learning to inform international drug monitoring. Our findings should not be interpreted as objective confirmatory evidence but suggest that Dutch-type cannabis resin has higher THC concentrations than Moroccan-type cannabis resin, which may contribute to variation in drug markets and health outcomes for people who use cannabis in Europe.

PMID:38771330 | DOI:10.1007/s00406-024-01816-w

https://pubmed.ncbi.nlm.nih.gov/38771330/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240521132305&v=2.18.0.post9+e462414 May 21, 2024 10:00 am