Tag Archives: cannabis

Monocyclic Quinone Structure-Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Antiproliferative Activity.

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Publication cover image“The monocyclic 1,4-benzoquinone, HU-331, the direct oxidation product of cannabidiol, inhibits the catalytic activity of topoisomerase II but without inducing DNA strand breaks or generating free radicals, and unlike many fused-ring quinones exhibits minimal cardiotoxicity. Thus, monocyclic quinones have potential as anticancer agents, and investigation of the structural origins of their biological activity is warranted. New syntheses of cannabidiol and (±)-HU-331 are here reported. Integrated synthetic protocols afforded a wide range of polysubstituted resorcinol derivatives; many of the corresponding novel 2-hydroxy-1,4-benzoquinone derivatives are potent inhibitors of the catalytic activity of topoisomerase II, some more so than HU-331, whose monoterpene unit replaced by a 3-cycloalkyl unit conferred increased antiproliferative properties in cell lines with IC50 values extending below 1 mM, and greater stability in solution than HU-331. The principal pharmacophore of quinones related to HU-331 was identified. Selected monocyclic quinones show potential for the development of new anticancer agents.”

https://www.ncbi.nlm.nih.gov/pubmed/31778038

https://onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201900548

Cannabinoids for drug-resistant seizures in a critically ill patient-Case report and literature review.

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Publication cover image“Drug-resistant seizures are life-threatening and contribute to sustained hospitalization.

We present the case of a critically ill 28-year-old male with Lennox-Gastaut syndrome who had approximately 30 seizures/day in the intensive care unit.

CASE DESCRIPTION:

Patient required mechanical ventilation and pharmacologically induced thiopentone coma.

He was commenced on cannabidiol and subsequently extubated.

He remained seizure-free thereafter on a combination of cannabidiol and anti-epileptic medication that predated his critical illness.

WHAT IS NEW AND CONCLUSION:

Our case report provides a unique perspective on the role of cannabidiol in achieving remission from drug-resistant seizures in critically ill patients.”

https://www.ncbi.nlm.nih.gov/pubmed/31770462

https://onlinelibrary.wiley.com/doi/abs/10.1111/jcpt.13082

Experimental Cannabinoid 2 Receptor Activation by Phyto-Derived and Synthetic Cannabinoid Ligands in LPS-Induced Interstitial Cystitis in Mice.

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molecules-logo“Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology.

The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation.

This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R).

BCP’s anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion.

The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC.

Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.”

https://www.ncbi.nlm.nih.gov/pubmed/31766439

https://www.mdpi.com/1420-3049/24/23/4239

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Does Integrative Medicine Reduce Prescribed Opioid Use for Chronic Pain? A Systematic Literature Review.

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Image result for pain medicine journal“Chronic pain (CP) is a major public health problem. Many patients with CP are increasingly prescribed opioids, which has led to an opioid crisis.

Integrative medicine (IM), which combines pharmacological and complementary and alternative medicine (CAM), has been proposed as an opioid alternative for CP treatment.

The majority of the studies showed that opioid use was reduced significantly after using IM. Cannabinoids were among the most commonly investigated approaches in reducing opioid use, followed by multidisciplinary approaches, cognitive-behavioral therapy, and acupuncture. The majority of the studies had limitations related to sample size, duration, and study design.

CONCLUSIONS:

There is a small but defined body of literature demonstrating positive preliminary evidence that the IM approach including CAM therapies can help in reducing opioid use. As the opioid crisis continues to grow, it is vital that clinicians and patients be adequately informed regarding the evidence and opportunities for IM/CAM therapies for CP.”

https://www.ncbi.nlm.nih.gov/pubmed/31755962

https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pnz291/5637803?redirectedFrom=fulltext

Marijuana Use in Patients with Symptoms of Gastroparesis: Prevalence, Patient Characteristics, and Perceived Benefit.

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“Marijuana may be used by some patients with gastroparesis (Gp) for its potential antiemetic, orexigenic, and pain-relieving effects.

The aim of this study was to describe the use of marijuana by patients for symptoms of Gp, assessing prevalence of use, patient characteristics, and patients’ perceived benefit on their symptoms of Gp.

RESULTS:

Fifty-nine of 506 (11.7%) patients with symptoms of Gp reported current marijuana use, being similar among patients with delayed and normal gastric emptying and similar in idiopathic and diabetic patients. Patients using marijuana were younger, more often current tobacco smokers, less likely to be a college graduate, married or have income > $50,000. Patients using marijuana had higher nausea/vomiting subscore (2.7 vs 2.1; p = 0.002), higher upper abdominal pain subscore (3.5 vs 2.9; p = 0.003), more likely to be using promethazine (37 vs 25%; p = 0.05) and dronabinol (17 vs 3%; p < 0.0001). Of patients using marijuana, 51% had been using it for more than 2 years, 47% were using this once or more per day, and 81% of marijuana users rated their benefit from marijuana as better or much better.

CONCLUSIONS:

A subset of patients (12%) with symptoms of Gp use marijuana. Patients with severe nausea and abdominal pain were more likely to use marijuana and perceive it to be beneficial for their symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/31758430

https://link.springer.com/article/10.1007%2Fs10620-019-05963-2

“Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea”

https://pubmed.ncbi.nlm.nih.gov/32185665/

Cannabis Influences the Putative Cytokines-Related Pathway of Epilepsy among Egyptian Epileptic Patients.

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brainsci-logo“The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels in epilepsy patients, triggering its future use in treatment.

We recruited 440 epilepsy patients and 200 controls matched for age, gender, and ethnicity. Of the epileptic patients, 37.5% demonstrated lifetime cannabis use with a mean duration of 15 ± 73 years. Serum levels of interleukin IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were analyzed and gene expression analysis was conducted only for those cytokines that were different between groups in the serum analysis.

The “Epilepsy-only” patients had significantly higher serum and mRNA levels of IL-1α, β, IL-2,6,8, and TNF-α compared to the controls and the “Cannabis+Epilepsy” group (p = 0.0001). IL-10 showed significantly lower levels in the “Epilepsy-only” patients compared to the controls and “Cannabis+Epilepsy” (p = 0.0001). Cannabis use is prevalent among epilepsy patients.

Epilepsy is characterized by a pro-inflammatory state supported by high serum and gene expression levels.

Cannabis users demonstrated significantly lower levels of inflammatory cytokines compared to epilepsy non-cannabis users which might contribute to its use in the treatment of resistant epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31757102

https://www.mdpi.com/2076-3425/9/12/332

Investigating the causal effect of cannabis use on cognitive function with a quasi-experimental co-twin design.

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Drug and Alcohol Dependence“It is unclear whether cannabis use causes cognitive decline; several studies show an association between cannabis use and cognitive decline, but quasi-experimental twin studies have found little support for a causal effect.

Here, we evaluate the association of cannabis use with general cognitive ability and executive functions (EFs) while controlling for genetic and shared environmental confounds in a longitudinal twin study.

CONCLUSIONS:

We found little support for a potential causal effect of cannabis use on cognition, consistent with previous twin studies. Results suggest that cannabis use may not cause decline in cognitive ability among a normative sample of cannabis users.”

https://www.ncbi.nlm.nih.gov/pubmed/31753729

“Overall, there was little evidence for causal effect of cannabis on cognition.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871619304892?via%3Dihub

Association between cannabis and the eyelids: A comprehensive review.

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Publication cover image“Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients.

There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug.

These include: ptosis induction, an “eyelid tremor” appearance and blepharospasm attenuation.

Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors.

The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear.

Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/31747112

https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.13687

Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy.

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Image result for translational psychiatry“Autism spectrum disorder (ASD) is a high cost neurodevelopmental condition; and there are currently no effective pharmacological treatments for its core symptoms. This has led some families and researchers to trial alternative remedies – including the non-intoxicating Cannabis sativa-derived compound cannabidivarin (CBDV). However, how CBDV affects the human brain is unknown.

Previous (pre)clinical evidence suggests that CBDV may modulate brain excitatory-inhibitory systems, which are implicated in ASD. Hence, our main aim was to test, for the first time, if CBDV shifts glutamate and/or GABA metabolites – markers of the brain’s primary excitatory and inhibitory system – in both the ‘typical’ and autistic brain.

Our subsidiary aim was to determine whether, within ASD, brain responsivity to CBDV challenge is related to baseline biological phenotype. We tested this using a repeated-measures, double-blind, randomized-order, cross-over design.

We used magnetic resonance spectroscopy (MRS) to compare glutamate (Glx = glutamate + glutamine) and GABA + (GABA + macromolecules) levels following placebo (baseline) and 600 mg CBDV in 34 healthy men with (n = 17) and without (n = 17) ASD. Data acquisition from regions previously reliably linked to ASD (dorsomedial prefrontal cortex, DMPFC; left basal ganglia, BG) commenced 2 h (peak plasma levels) after placebo/CBDV administration. Where CBDV significantly shifted metabolite levels, we examined the relationship of this change with baseline metabolite levels. Test sessions were at least 13 days apart to ensure CBDV wash-out. CBDV significantly increased Glx in the BG of both groups. However, this impact was not uniform across individuals. In the ASD group, and not in the typically developing controls, the ‘shift’ in Glx correlated negatively with baseline Glx concentration. In contrast, CBDV had no significant impact on Glx in the DMPFC, or on GABA+ in either voxel in either group.

Our findings suggest that, as measured by MRS, CBDV modulates the glutamate-GABA system in the BG but not in frontal regions. Moreover, there is individual variation in response depending on baseline biochemistry. Future studies should examine the effect of CBDV on behaviour and if the response to an acute dose of CBDV could predict a potential clinical treatment response in ASD.”

https://www.ncbi.nlm.nih.gov/pubmed/31748505

“Here we report that CBDV can ‘shift’ subcortical levels of the brain’s primary excitatory metabolite glutamate (measured as Glx) both in the neurotypical and autistic brain; but that there may be significant response variability in ASD. These findings add to our understanding of the effects of CBDV in the adult human brain. Nonetheless, future studies will need to explore (i) the mechanisms of action of CBDV; (ii) the impact of CBDV on (ASD-related) cognition and behaviour; (iii) if single-dose responsivity could facilitate the identification of pharmacologically homogeneous sub-groups; and (iv) if acute CBDV effects are indicative of the impact of long-term treatment in ASD.”

https://www.nature.com/articles/s41398-019-0654-8

Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol.

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medicina-logo“Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD).

Results: Pre-treatment with CBG (at 2.5 and 5 µM doses) alone and in combination with CBD (at 2.5 and 5 µM doses) was able to reduce neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In particular, the pre-treatment with CBD at a 5 µM dose decreased TNF-α levels and increased IL10 and IL-37 expression. CBG-CBD association at a 5 µM dose also reduced NF-kB nuclear factor activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a 5 µM dose decreased iNOS expression and increased Nrf2 levels. Furthermore, the pre-treatment with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-2 expression. Our data show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated.

Conclusions: Our results provide preliminary support on the potential therapeutic application of a CBG-CBD combination for further preclinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31752240

https://www.mdpi.com/1010-660X/55/11/747