The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease

ijms-logo“Cannabidiol (CBD) is a non-intoxicating and generally well-tolerated constituent of cannabis which exhibits potential beneficial properties in a wide range of diseases, including cardiovascular disorders.

Due to its complex mechanism of action, CBD may affect the cardiovascular system in different ways. Thus, we reviewed the influence of CBD on this system in health and disease to determine the potential risk of cardiovascular side effects during CBD use for medical and wellness purposes and to elucidate its therapeutic potential in cardiovascular diseases.

Administration of CBD to healthy volunteers or animals usually does not markedly affect hemodynamic parameters. Although CBD has been found to exhibit vasodilatory and antioxidant properties in hypertension, it has not affected blood pressure in hypertensive animals. Hypotensive action of CBD has been mainly revealed under stress conditions.

Many positive effects of CBD have been observed in experimental models of heart diseases (myocardial infarction, cardiomyopathy, myocarditis), stroke, neonatal hypoxic ischemic encephalopathy, sepsis-related encephalitis, cardiovascular complications of diabetes, and ischemia/reperfusion injures of liver and kidneys.

In these pathological conditions CBD decreased organ damage and dysfunction, oxidative and nitrative stress, inflammatory processes and apoptosis, among others. Nevertheless, further clinical research is needed to recommend the use of CBD in the treatment of cardiovascular diseases.”

https://pubmed.ncbi.nlm.nih.gov/32937917/

https://www.mdpi.com/1422-0067/21/18/6740

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Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence

View details for Cannabis and Cannabinoid Research cover image“Anxiety disorders have the highest lifetime prevalence of any mental illness worldwide, leading to high societal costs and economic burden. Current pharmacotherapies for anxiety disorders are associated with adverse effects and low efficacy.

Cannabidiol (CBD) is a constituent of the Cannabis plant, which has potential therapeutic properties for various indications. After the recent legalization of cannabis, CBD has drawn increased attention as a potential treatment, as the majority of existing data suggest it is safe, well tolerated, has few adverse effects, and demonstrates no potential for abuse or dependence in humans.

Pre-clinical research using animal models of innate fear and anxiety-like behaviors have found anxiolytic, antistress, anticompulsive, and panicolytic-like effects of CBD. Preliminary evidence from human trials using both healthy volunteers and individuals with social anxiety disorder, suggests that CBD may have anxiolytic effects.

Although these findings are promising, future research is warranted to determine the efficacy of CBD in other anxiety disorders, establish appropriate doses, and determine its long-term efficacy. The majority of pre-clinical and clinical research has been conducted using males only. Among individuals with anxiety disorders, the prevalence rates, symptomology, and treatment response differ between males and females. Thus, future research should focus on this area due to the lack of research in females and the knowledge gap on sex and gender differences in the effectiveness of CBD as a potential treatment for anxiety.”

https://pubmed.ncbi.nlm.nih.gov/32923656/

“Cannabidiol (CBD) is a constituent of the Cannabis plant, which has potential therapeutic properties across many neuropsychiatric disorders. Overall, existing pre-clinical and clinical evidence supports a possible role for CBD as a novel treatment for anxiety disorders.”

https://www.liebertpub.com/doi/10.1089/can.2019.0052

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A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis

 Translational Psychiatry“Emotional dysregulation and anxiety are common in people at clinical high risk for psychosis (CHR) and are associated with altered neural responses to emotional stimuli in the striatum and medial temporal lobe.

Using a randomised, double-blind, parallel-group design, 33 CHR patients were randomised to a single oral dose of CBD (600 mg) or placebo. Healthy controls (n = 19) were studied under identical conditions but did not receive any drug. Participants were scanned with functional magnetic resonance imaging (fMRI) during a fearful face-processing paradigm. Activation related to the CHR state and to the effects of CBD was examined using a region-of-interest approach.

During fear processing, CHR participants receiving placebo (n = 15) showed greater activation than controls (n = 19) in the parahippocampal gyrus but less activation in the striatum. Within these regions, activation in the CHR group that received CBD (n = 15) was intermediate between that of the CHR placebo and control groups.

These findings suggest that in CHR patients, CBD modulates brain function in regions implicated in psychosis risk and emotion processing. These findings are similar to those previously evident using a memory paradigm, suggesting that the effects of CBD on medial temporal and striatal function may be task independent.”

https://pubmed.ncbi.nlm.nih.gov/32921794/

“This study is the first to demonstrate that a single dose of CBD modulates activation of the medial temporal cortex and striatum during fear processing in CHR patients. In showing that CBD modulates function of the neural circuitry directly implicated in psychosis onset, these results add to previous evidence that CBD may be a promising novel therapeutic for patients at CHR. Our results also support further investigation of the potential utility of CBD outside of the CHR field in other populations, such as in those with anxiety.”

https://www.nature.com/articles/s41398-020-0862-2

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Cannabidiol-Mediated Changes to the Phospholipid Profile of UVB-Irradiated Keratinocytes from Psoriatic Patients

ijms-logo“UVB phototherapy is treatment for psoriasis, which increases phospholipid oxidative modifications in the cell membrane of the skin. Therefore, we carried out lipidomic analysis on the keratinocytes of healthy individuals and patients with psoriasis irradiated with UVB and treated with cannabidiol (CBD), phytocannabinoid with antioxidant and anti-inflammatory properties.

Our results showed that, in psoriatic keratinocytes phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), and ether-linked phosphoethanolamine (PEo), were downregulated, while SM (d41:2) was upregulated. These changes were accompanied by an increase in negative zeta potential, which indicates translocation of PS to the outer layer of the membrane.

CBD treatment of psoriatic keratinocytes led to downregulation of PC, PS, and upregulation of certain PEo and an SM species, SM (d42:2), and the zeta potential. However, UVB irradiation of psoriatic keratinocytes resulted in upregulation of PC, PC plasmalogens (PCp), PEo, and a decrease in the negative zeta potential. The exposure of UVB-irradiated cells to CBD led to a decrease in the level of SM (d42:2).

Our results suggest that CBD induces pro-apoptotic mechanisms in psoriatic keratinocytes while simultaneously improving the antioxidant properties and preventing the loss of transepidermal water of keratinocytes of patients irradiated with UVB. Thus, CBD has potential therapeutic value in the treatment of psoriasis.”

https://pubmed.ncbi.nlm.nih.gov/32916896/

https://www.mdpi.com/1422-0067/21/18/6592

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Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs

“Highly purified cannabidiol (CBD) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome in randomized, double-blind, add-on, controlled phase 3 trials.

It is important to consider the possibility of drug-drug interactions (DDIs). Here, we review six trials of CBD (Epidiolex/Epidyolex; 100 mg/mL oral solution) in healthy volunteers or patients with epilepsy, which investigated potential interactions between CBD and enzymes involved in drug metabolism of common antiseizure drugs (ASDs).

CBD did not affect CYP3A4 activity. Induction of CYP3A4 and CYP2C19 led to small reductions in exposure to CBD and its major metabolites. Inhibition of CYP3A4 activity did not affect CBD exposure and caused small increases in exposure to CBD metabolites. Inhibition of CYP2C19 activity led to a small increase in exposure to CBD and small decreases in exposure to CBD metabolites.

One potentially clinically important DDI was identified: combination of CBD and clobazam (CLB) did not affect CBD or CLB exposure, but increased exposure to major metabolites of both compounds. Reduction of CLB dose may be considered if adverse reactions known to occur with CLB are experienced when it is coadministered with CBD.

There was a small increase of exposure to stiripentol (STP) when coadministered with CBD. STP had no effect on CBD exposure but led to minor decreases in exposure to CBD metabolites. Combination of CBD and valproate (VPA) did not cause clinically important changes in the pharmacokinetics of either drug, or 2-propyl-4-pentenoic acid. Concomitant VPA caused small increases in exposure to CBD metabolites. Dose adjustments are not likely to be necessary when CBD is combined with STP or VPA.

The safety results from these trials were consistent with the known safety profile of CBD. These trials indicate an overall low potential for DDIs between CBD and other ASDs, except for CLB.”

https://pubmed.ncbi.nlm.nih.gov/32918835/

https://onlinelibrary.wiley.com/doi/full/10.1111/epi.16674

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Add-on cannabidiol significantly decreases seizures in 3 patients with SYNGAP1 developmental and epileptic encephalopathy

“Mutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug-resistant in this syndrome with frequent drop attacks.

In a prospective study of add-on cannabidiol (CBD), we identified three patients with SYNGAP1 mutations: two boys and one girl. Seizure onset was at 3.5, 8, and 18 months (M), respectively, with numerous atypical absences per day associated with eyelid myoclonia (2/3 patients), upper limb myoclonic jerks (2/3 patients), and drop attacks (all patients). Seizures were resistant to at least 5 antiepileptic drugs (AEDs).

After CBD introduction, two patients were responders since M2 and achieve a seizure reduction of 90% and 80%, respectively, at M9 with disappearance of drop attacks. EEGs showed an improvement regarding background activity and interictal anomalies. The last patient showed a late response at M7 of treatment with an 80% decrease in seizure frequency. Caregiver in all three evaluated as much improved the status of their children. Treatment was well-tolerated in all, and no major adverse events (AEs) were reported.

CBD showed efficacy in patients with drug-resistant epilepsy due to SYNGAP1 mutations. Other patients with rare genetic developmental and epileptic encephalopathies with drug-resistant epilepsies might benefit from CBD.”

https://pubmed.ncbi.nlm.nih.gov/32913957/

“CBD add‐on therapy in patients with SYNGAP1 encephalopathy showed a good response in three patients with a good safety profile and a late response in one patient. This therapy should be included in the treatment algorithm of patients with SYNGAP1 mutations presenting drug resistance epilepsy and might be expanded to other rare genetic epilepsies that might not be included in formal trials.”

https://onlinelibrary.wiley.com/doi/full/10.1002/epi4.12411

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Preliminary data on the antimicrobial effect of Cannabis sativa L. variety Futura 75 against food-borne pathogens in vitro as well as against naturally occurring microbial populations on minced meat during storage

 Archive of "Italian Journal of Food Safety".“In the present study, the antimicrobial effect of Cannabis sativa Futura 75 was evaluated both in vitro against foodborne bacterial pathogens, and on food against naturally occurring microbial groups of minced meat stored for 8 days at 4°C.

Ethanol extraction was performed on the grind of the inflorescence. After extraction, ethanol was completely evaporated and substituted by water. Serial dilutions of the extract, the grind and cannabidiol 99% were added to Nutrient Agar and spotted with Listeria monocytogenesSalmonella Typhimurium, Escherichia coli and Staphylococcus spp. Regarding the evaluation on food, 50 mL of extract, characterised by CBD at concentration of 322,70 μg/mL, were added to 2.5 kg of minced beef meat. Meat was divided into aliquots and stored for 8 days at 4°C. At 0, 1, 2, 3, 4, 7, and 8 days, aerobic bacteria, enterobacteria, coliforms and E. coli were enumerated.

All tested products were efficient against Gram +. In particular, extract corresponding to CBD concentration of 0.017 and 0.3 mg/mL were effective against L. monocytogenes and Staphylococcus spp. respectively. After 8 days of storage at 4°C, treated minced meat showed a bright red colour in comparison to a brownish control meat. Moreover, Enterobacteriaceae and coliforms were significantly reduced of 2.3 log CFU/g and 1.6 log CFU/g respectively in treated meat in comparison to the control.

Although preliminary, the present study suggests the antimicrobial properties of the extract of Cannabis sativa both in vitro and in minced meat.”

https://pubmed.ncbi.nlm.nih.gov/32913724/

https://www.pagepressjournals.org/index.php/ijfs/article/view/8581

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Cannabidiol Content and In Vitro Biological Activities of Commercial Cannabidiol Oils and Hemp Seed Oils

medicines-logo“Hemp (Cannabis sativa L.) seed contains high contents of various nutrients, including fatty acids and proteins.

Cannabidiol (CBD) is a non-psychoactive compound that can be extracted from C. sativa and used for treating epilepsy and pain.

Industrial hemp products, including CBD and hemp seed oils, have become increasingly popular. Some products are marketed without a clear distinction between CBD and hemp seed oils.

Herein, the CBD content and biological activities of commercial CBD and hemp seed oils were examined.

Methods: CBD content was measured by high-performance liquid chromatography. For in vitro antioxidant activity determination, 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging assays were performed.

Results: The CBD concentrations in the two CBD oil samples were 18.9 ± 0.5 and 9.2 ± 0.4 mg/mL. Of the seven hemp seed oil samples, six samples contained CBD in concentrations ranging from 2.0 ± 0.1 to 20.5 ± 0.5 µg/mL, but it was not detected in one sample. Antioxidant activity was observed in both CBD oil samples.

Conclusions: The results indicate that (1) CBD content varied by hemp seed oil sample and that (2) antioxidant activity could be a useful landmark for discriminating CBD oils from hemp seed oils.”

https://pubmed.ncbi.nlm.nih.gov/32906708/

https://www.mdpi.com/2305-6320/7/9/57

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Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer through Myeloid Cell De-activation Upstream of IL-22 Production

iScience journal (@iScience_CP) | Twitter
” Here we show that delta-9-tetrahydrocannabinol (THC) attenuates colitis-associated colon cancer and colitis induced by anti-CD40.
 THC can prevent the development of colitis-associated colon cancer in mice.”

“Study reveals how cannabinoids may be useful to prevent colon cancer”   https://medicalxpress.com/news/2020-09-reveals-cannabinoids-colon-cancer.html

“Key cannabis chemical may help prevent colon cancer, researchers say”   https://www.heraldmailmedia.com/news/nation/key-cannabis-chemical-may-help-prevent-colon-cancer-researchers-say/article_7afd0a72-eead-57f0-a1d3-006be62b7469.html

“Treatment with a cannabinoid prevented the development of colon cancers in mice” https://www.news-medical.net/news/20200915/Treatment-with-a-cannabinoid-prevented-the-development-of-colon-cancers-in-mice.aspx

Figure thumbnail fx1

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No Evidence of Altered Reactivity to Experimentally Induced Pain Among Regular Cannabis Users

Clinical Journal of Pain,Philadelphia - Gainbuzz“Recent years have seen an increase in the adoption of cannabinoid medicines, which have demonstrated effectiveness for the treatment of chronic pain.

However, the extent to which frequent cannabis use (CU) influences sensitivity to acute pain has not been systematically examined. Such a determination is clinically relevant in light of hypersensitivity to pain associated with prolonged use of other analgesics such as opioids, and reports of increased pain sensitivity to experimentally induced pain during acute cannabis intoxication.

This study explored differences in measures of pain intensity and tolerance. The authors hypothesized that individuals who report frequent CU would demonstrate greater experimental pain sensitivity.

Results: Frequent CU was not associated with hyperalgesia as cannabis users and nonusers did not exhibit differences on measures of pain tolerance (t (78)=-0.05; P=0.96), sensitivity (t (78)=-0.83; P=0.41), or intensity (t (78)=0.36; P=0.72).

Discussion: Frequent cannabis users did not demonstrate hyperalgesia. This finding should help to inform evaluations of the relative harms and benefits of cannabis analgesic therapies.”

https://pubmed.ncbi.nlm.nih.gov/32433075/

https://journals.lww.com/clinicalpain/Abstract/2020/08000/No_Evidence_of_Altered_Reactivity_to.4.aspx

“Pain tolerance among cannabis users. Unlike opioids, long-term cannabis use does not increase sensitivity to pain. “This study should come as good news to patients who are already using cannabis to treat pain,” says co-author Zach Walsh, who leads the UBC Therapeutic Recreational and Problematic Substance Use Lab which hosted the study. “Increases in pain sensitivity with opioids can really complicate an already tough situation; given increasing uptake of cannabis-based pain medications it’s a relief that we didn’t identify a similar pattern with cannabinoids.”

https://www.sciencedaily.com/releases/2020/09/200910120105.htm

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