Tag Archives: cannabinoid

Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation

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Phytotherapy Research“Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti-inflammatory effects.

We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately.

Colitis was induced in mice by 2,4-dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC-MS-IT-TOF). Endocannabinoids and related mediators were assessed by LC-MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin-1β, and intestinal permeability.

CBG, but not CBD, given by oral gavage, ameliorated DNBS-induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti-inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon.

By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease.”

https://pubmed.ncbi.nlm.nih.gov/32996187/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.6831

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

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ijms-logo“Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats.

PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation.

CBD improved all abovementioned changes induced by PH except right ventricle hypertrophy and lung edema. In addition, CBD increased lung levels of some endocannabinoids (anandamide, N-arachidonoyl glycine, linolenoyl ethanolamide, palmitoleoyl ethanolamide and eicosapentaenoyl ethanolamide but not 2-arachidonoylglycerol). CBD did not affect the cardiopulmonary system of control rats or other parameters of blood morphology in PH.

Our data suggest that CBD ameliorates MCT-induced PH in rats by improving endothelial efficiency and function, normalization of hemostatic alterations and reduction of enhanced leukocyte count determined in PH. In conclusion, CBD may be a safe, promising therapeutic or adjuvant therapy agent for the treatment of human pulmonary artery hypertension.”

https://pubmed.ncbi.nlm.nih.gov/32992900/

https://www.mdpi.com/1422-0067/21/19/7077

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

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cancers-logo“Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors.

Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection.

The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells.

In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel.

Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.”

https://pubmed.ncbi.nlm.nih.gov/32992648/

https://www.mdpi.com/2072-6694/12/10/2774

Development of cannabidiol as a treatment for severe childhood epilepsies

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“In recent years there has been a growing appreciation by regulatory authorities that cannabis-based medicines can play a useful role in disease therapy.

Although often conflagrated by proponents of recreational use, the legislative rescheduling of cannabis-derived compounds, such as cannabidiol (CBD), has been associated with the steady increase in the pursuit of use of medicinal cannabis.

One key driver in this interest has been the scientific demonstration of efficacy and safety of CBD in randomised, placebo-controlled clinical trials in children and young adults with difficult-to-treat epilepsies, which has encouraged increasing numbers of human trials of CBD for other indications and in other populations.

The introduction of CBD as the medicine Epidiolex in the US (in 2018) and as Epidyolex in the EU (in 2019) as the first cannabis-derived therapeutic for the treatment for seizures was underpinned by preclinical research performed at the University of Reading.

This work was awarded the British Pharmacological Society Sir James Black Award for Contributions to Drug Discovery 2019 and is discussed in the following review article.”

https://pubmed.ncbi.nlm.nih.gov/32986848/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15274

CBD Effects on TRPV1 Signaling Pathways in Cultured DRG Neurons

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 “Cannabidiol (CBD) is reported to produce pain relief, but the clinically relevant cellular and molecular mechanisms remain uncertain.

The TRPV1 receptor integrates noxious stimuli and plays a key role in pain signaling. Hence, we conducted in vitro studies, to elucidate the efficacy and mechanisms of CBD for inhibiting neuronal hypersensitivity in cultured rat sensory neurons, following activation of TRPV1.

Results: DRG neurons treated with 10 and 50 µMol/L CBD showed calcium influx, but not at lower doses. Neurons treated with capsaicin demonstrated robust calcium influx, which was dose-dependently reduced in the presence of low dose CBD (IC50 = 100 nMol/L). The inhibition or desensitization by CBD was reversed in the presence of forskolin and cyclosporin. Forskolin-stimulated cAMP levels were significantly reduced in CBD treated neurons.

Conclusion: CBD at low doses corresponding to plasma concentrations observed physiologically inhibits or desensitizes neuronal TRPV1 signalling by inhibiting the adenylyl cyclase – cAMP pathway, which is essential for maintaining TRPV1 phosphorylation and sensitization. CBD also facilitated calcineurin-mediated TRPV1 inhibition. These mechanisms may underlie nociceptor desensitization and the therapeutic effect of CBD in animal models and patients with acute and chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/32982390/

https://www.dovepress.com/cbd-effects-on-trpv1-signaling-pathways-in-cultured-drg-neurons-peer-reviewed-article-JPR

Novel cannabidiol sunscreen protects keratinocytes and melanocytes against ultraviolet B radiation

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“Cannabidiol (CBD), a natural occurring phytocannabinoid, is used extensively in consumer products ranging from foods to shampoos, topical oils and lotions.

Several studies demonstrated the anti-inflammatory and antioxidative properties of cannabidiol. Nevertheless, the role of cannabidiol use in sunscreens is largely unknown as no studies on its effect on keratinocytes or melanocytes exist. As such, we aimed to explore the effect of CBD on keratinocyte and melanocyte viability following ultraviolet B (UVB) irradiation.

CBD exhibited a dose-dependent protective effect on both keratinocytes and melanocyte viability. Further, since CBD does not demonstrate absorption in the UVB spectra, we speculate that the protective effect is due to reduction in reactive oxygen species.

To our knowledge, this is the first study demonstrating the protective effect of CBD on keratinocytes and melanocytes irradiated with UVB.”

https://pubmed.ncbi.nlm.nih.gov/32964699/

https://onlinelibrary.wiley.com/doi/10.1111/jocd.13693

The Impact of Medical Cannabis on Intermittent and Chronic Opioid Users with Back Pain: How Cannabis Diminished Prescription Opioid Usage

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View details for Cannabis and Cannabinoid Research cover image“To determine if cannabis may be used as an alternative or adjunct treatment for intermittent and chronic prescription opioid users.

Results: There were no between-group differences based on demographic, experiential, or attitudinal variables. We found that 50.8% were able to stop all opioid usage, which took a median of 6.4 years (IQR=1.75-11 years) after excluding two patients who transitioned off opioids by utilizing opioid agonists. For those 29 patients (47.5%) who did not stop opioids, 9 (31%) were able to reduce opioid use, 3 (10%) held the same baseline, and 17 (59%) increased their usage. Forty-eight percent of patients subjectively felt like cannabis helped them mitigate their opioid intake but this sentiment did not predict who actually stopped opioid usage. There were no variables that predicted who stopped opioids, except that those who used higher doses of cannabis were more likely to stop, which suggests that some patients might be able to stop opioids by using cannabis, particularly those who are dosed at higher levels.

Conclusions: In this long-term observational study, cannabis use worked as an alternative to prescription opioids in just over half of patients with low back pain and as an adjunct to diminish use in some chronic opioid users.”

https://pubmed.ncbi.nlm.nih.gov/32923663/

“Cannabis has been used for centuries as an analgesic and has been shown to reduce chronic pain. In this long-term observational study of a single-center cannabis medical practice site, the addition of cannabis use worked as an alternative to prescription opioids in 50% of patients with chronic back pain. It worked as an adjunct to diminish use in some chronic opioid users. There was only one variable that predicted those who were able to stop opioids suggesting that some patients might be able to stop opioids by using cannabis and that those who do not stop opioids may not be titrated at doses of cannabis high enough to achieve the desired effect necessary to diminish or stop their opioid usage.”

https://www.liebertpub.com/doi/10.1089/can.2019.0039

Investigating the cumulative effects of Δ9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats

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 Issue Cover“The prevalence of mild traumatic brain injury is highest amongst the adolescent population and can lead to complications including neuroinflammation and excitotoxicity.

Δ9-Tetrahydrocannabinol, the main psychoactive component of cannabis, is known to have anti-inflammatory properties and serves as a neuroprotective agent against excitotoxicity.

Thus, we investigated the effects of Δ9-tetrahydrocannabinol on recovery when administered either prior to or following repeated mild brain injuries.

We hypothesized that, in both experiments, Δ9-tetrahydrocannabinol administration would provide neuroprotection against mild injury outcomes and confer therapeutic benefit.

Δ9-Tetrahydrocannabinol administration following repeated mild traumatic brain injury was beneficial to three of the six behavioural outcomes affected by injury (reducing anxiety and depressive-like behaviours while also mitigating injury-induced deficits in short-term working memory). Δ9-Tetrahydrocannabinol administration following injury also showed beneficial effects on the expression of Cnr1, Comt and Vegf-2R in the hippocampus, nucleus accumbens and prefrontal cortex.

There were no notable benefits of Δ9-tetrahydrocannabinol when administered prior to injury, suggesting that Δ9-tetrahydrocannabinol may have potential therapeutic benefit on post-concussive symptomology when administered post-injury, but not pre-injury.”

https://pubmed.ncbi.nlm.nih.gov/32954298/

 “Overall, this study suggests that THC has potential therapeutic efficacy for the treatment of RmTBI-induced symptomology but requires additional examination.”

https://academic.oup.com/braincomms/article/2/1/fcaa042/5819138

Cannabis Extracts Affected Metabolic Syndrome Parameters in Mice Fed High-Fat/Cholesterol Diet

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View details for Cannabis and Cannabinoid Research cover image“Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD.

While cannabis may potentially be beneficial for treating metabolic disorders such as NAFLD, the effects of cannabis on liver diseases and gut microbiota profile are yet to be addressed. In this study, we evaluated the therapeutic effects of cannabis strains with different cannabinoid profiles on NAFLD progression.

Conclusions: The results of this study indicate that the administration of cannabis containing elevated levels of THC may help ameliorate symptoms of NAFLD, whereas administration of CBD-rich cannabis extracts may cause a proinflammatory effect in the liver, linked with an unfavorable change in the microbiota profile. Our preliminary data suggest that these effects are mediated by mechanisms other than increased expression of the endocannabinoid receptors cannabinoid receptor 1 (CB1) and CB2.”

https://pubmed.ncbi.nlm.nih.gov/32923658/

“The results of this study provide an indication that administration of certain strains of cannabis, preferably with a higher THC level, may be helpful in treating certain symptoms of metabolic syndrome, which include preventing the development and/or ameliorating the symptoms of NAFLD.”

https://www.liebertpub.com/doi/10.1089/can.2020.0013

Daily Cannabis Users with Sickle Cell Disease Show Fewer Admissions than Others with Similar Pain Complaints

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View details for Cannabis and Cannabinoid Research cover image “Previous studies have shown that cannabis use is common in adults with sickle cell disease (SCD), and that many patients report using cannabis to treat pain.

Methods: We performed a cross-sectional study of adults with SCD and compared daily users of cannabis with others using validated patient-reported measures of pain and quality of life as well as opioid and health care utilization.

Results: Daily cannabis users with SCD had worse pain episode severity scores than others (56.7 vs. 48.8, p=0.02) yet had 1.8 fewer annual admissions (p=0.01) and 1.2 fewer annual emergency room (ER) visits (p=0.01), and similar amounts of opioids dispensed to others after matching for age, gender, SCD genotype, hydroxyurea use, and pain impact scores.

Conclusions: We show that people with SCD with more severe pain crisis are more likely to use daily cannabis, yet have lower rates of hospital admission and ER use as compared with others with similar disease severity and pain impact. Randomized controlled trials should be performed.”

https://pubmed.ncbi.nlm.nih.gov/32923662/

“We posit that people with SCD with severe pain are more likely to use daily cannabis due to its analgesic properties. This would explain why daily users reported more severe pain crises yet had fewer admissions and ER visits after propensity matching was performed.”

https://www.liebertpub.com/doi/10.1089/can.2019.0036