The Pharmacological Effects of Plant-Derived versus Synthetic Cannabidiol in Human Cell Lines

/WebMaterial/ShowPic/1344608“Introduction: Cannabidiol (CBD) can be isolated from Cannabis sativa L. or synthetically produced. The aim of this study was to compare the in vitro effects of purified natural and synthetic CBD to establish any pharmacological differences or superiority between sources. 

Conclusion: Our results suggest that there is no pharmacological difference in vitro in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD. The purity and reliability of CBD samples, as well as the ultimate pharmaceutical preparation, should all be considered above the starting source of CBD in the development of new CBD medicines.

This study demonstrates for the first time that the anticancer, neuroprotective, and intestinal barrier protective properties of purified CBD are similar regardless of the source from which CBD is derived. From a pharmacological perspective, where a molecular target is implicated (i.e., 5HT1A in stroke and CB1 in gut permeability), the effects of CBD were similar. This suggests that any beneficial effects that could be achieved in a clinical setting for purified CBD are likely to be similar at a pharmacodynamic level.”

https://www.karger.com/Article/FullText/517120

“Study finds no in-vitro pharmacological difference in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD”

https://www.streetinsider.com/Globe+Newswire/Artelo+Biosciences+Announces+Publication+of+Study+Results+Comparing+the+Pharmacological+Effects+of+Plant-Derived+Versus+Synthetic+Cannabidiol+in+Human+Cell+Lines/18767297.html

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Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response

bioRxiv“The rapid spread of COVID-19 underscores the need for new treatments.

Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells.

CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population.

This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.”

https://www.biorxiv.org/content/10.1101/2021.03.10.432967v1

“Cannabis compound inhibits SARS-CoV-2 replication in human lung cells”   https://www.news-medical.net/news/20210314/Cannabis-compound-inhibits-SARS-CoV-2-replication-in-human-lung-cells.aspx

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Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis

Drug and Alcohol Dependence “Background: The ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT.

Results: Among the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 – 0.99).

Conclusions: Participants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.”

https://pubmed.ncbi.nlm.nih.gov/33342591/

“Opioid agonist therapies (OAT) are the primary treatments for opioid use disorder. Exposure to fentanyl is driving mortality risk in the overdose crisis. Among 819 participants on OAT, cannabis was negatively associated with fentanyl. Experimental trials are needed to evaluate cannabis use during OAT.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871620305858?via%3Dihub

“Cannabis could reduce fentanyl use, reduce overdose risk: study” https://www.bccsu.ca/blog/news-release/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk-study/

“Cannabis could reduce fentanyl use, reduce overdose risk” https://www.med.ubc.ca/news/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk/

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Endocannabinoids Inhibit the Induction of Virulence in Enteric Pathogens

Cell | Publons
“Endocannabinoids are host-derived lipid hormones that fundamentally impact gastrointestinal (GI) biology. The use of cannabis and other exocannabinoids as anecdotal treatments for various GI disorders inspired the search for mechanisms by which these compounds mediate their effects, which led to the discovery of the mammalian endocannabinoid system. Dysregulated endocannabinoid signaling was linked to inflammation and the gut microbiota. However, the effects of endocannabinoids on host susceptibility to infection has not been explored. Here, we show that mice with elevated levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG) are protected from enteric infection by Enterobacteriaceae pathogens. 2-AG directly modulates pathogen function by inhibiting virulence programs essential for successful infection. Furthermore, 2-AG antagonizes the bacterial receptor QseC, a histidine kinase encoded within the core Enterobacteriaceae genome that promotes the activation of pathogen-associated type three secretion systems. Taken together, our findings establish that endocannabinoids are directly sensed by bacteria and can modulate bacterial function.”
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“Fighting intestinal infections with the body’s own endocannabinoids. By harnessing the power of natural compounds produced in the body and in plants, we may eventually treat infections in a whole new way.”  https://www.sciencedaily.com/releases/2020/10/201007123119.htm

“Study may explain why cannabis plant can reduce symptoms of various bowel conditions” https://www.news-medical.net/news/20201007/Study-could-help-explain-why-cannabis-plant-can-reduce-symptoms-of-various-bowel-conditions.aspx

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Cannabis: An Emerging Treatment for Common Symptoms in Older Adults

Journal of the American Geriatrics Society “Background/objectives: Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist.

Design: Anonymous survey.

Setting: Geriatrics clinic.

Participants: A total of 568 adults 65 years and older.

Intervention: Not applicable.

Measurements: Survey assessing characteristics of cannabis use.

Results: Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%).

The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis “somewhat” or “extremely” helpful in managing one of these conditions, with few adverse effects.

Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking).

Conclusion: Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.”

https://pubmed.ncbi.nlm.nih.gov/33026117/

https://onlinelibrary.wiley.com/doi/10.1111/jgs.16833

“Study Finds Older Adults Using Cannabis to Treat Common Health Conditions”  https://health.ucsd.edu/news/releases/Pages/2020-10-07-study-finds-older-adults-using-cannabis-to-treat-common-health-conditions.aspx

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Medical cannabis and cognitive performance in middle to old adults treated for chronic pain

“Cannabis exposure is becoming more common in older age but little is known about how it is associated with brain health in this population.

This study assesses the relationship between long-term medical cannabis (MC) use and cognitive function in a sample of middle-aged and old chronic pain patients.

Results: Mean age was 63 ± 6 and 60 ± 5 years in the non-exposed and MC patients, respectively. Groups did not significantly differ in terms of cognitive performance measures. Furthermore, none of the MC use patterns were associated with cognitive performance.

Discussion and conclusions: These results suggest that use of whole plant MC does not have a widespread impact on cognition in older chronic pain patients. Considering the increasing use of MC in older populations, this study could be a first step towards a better risk-benefit assessment of MC treatment in this population. Future studies are urgently needed to further clarify the implications of late-life cannabis use for brain health.”

https://pubmed.ncbi.nlm.nih.gov/32964502/

https://onlinelibrary.wiley.com/doi/10.1111/dar.13171

“No Ill Effects for Older Adults Using Medical Marijuana for Pain, Study Says. A study looking at older adults with chronic pain found no no significant difference in cognitive performance when comparing them with matched patients who did not use medical marijuana.” https://www.ajmc.com/view/no-ill-effects-for-older-adults-using-medical-marijuana-for-pain-study-says

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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

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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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The pharmacokinetics, efficacy, and safety of a novel selective‐dose cannabis inhaler in patients with chronic pain: A randomized, double‐blinded, placebo‐controlled trial

European Journal of Pain“Precise cannabis treatment dosing remains a major challenge, leading to physicians’ reluctance to prescribe medical cannabis.

Objective

To test the pharmacokinetics, analgesic effect, cognitive performance and safety effects of an innovative medical device that enables the delivery of inhaled therapeutic doses of Δ9‐Tetrahydrocannabinol (THC) in patients with chronic pain.

Methods

In a randomized, three‐arms, double‐blinded, placebo‐controlled, cross‐over trial, 27 patients received a single inhalation of Δ9‐THC: 0.5mg, 1mg, or a placebo.

Δ9‐THC plasma levels were measured at baseline and up to 150‐min post‐inhalation. Pain intensity and safety parameters were recorded on a 10‐cm visual analogue scale (VAS) at pre‐defined time points. The cognitive performance was evaluated using the selective sub‐tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Results

Following inhalation of 0.5 mg or 1mg, Δ9‐THC plasma max ± SD were 14.3 ± 7.7 and 33.8 ± 25.7 ng/ml. max ± SD were 3.7 ± 1.4 and 4.4 ± 2.1 min, and AUC0 → infinity±SD were 300 ± 144 and 769 ± 331 ng*min/ml, respectively. Both doses, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150‐min. The 1‐mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance.

Conclusion

This feasibility trial demonstrated that a metered‐dose cannabis inhaler delivered precise and low THC doses, produced a dose‐dependent and safe analgesic effect in patients with neuropathic pain/ complex‐regional pain syndrome (CRPS). Thus, it enables individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically by accepted pharmaceutical models.

Significance

Evidence suggests that cannabis‐based medicines are an effective treatment for chronic pain in adults. The pharmacokinetics of THC varies as a function of its route of administration. Pulmonary assimilation of inhaled THC causes rapid onset of analgesia. However, currently used routes of cannabinoids delivery provide unknown doses, making it impossible to implement a pharmaceutical standard treatment plan. A novel selective‐dose cannabis inhaler delivers significantly low and precise doses of THC, thus allowing the administration of inhaled cannabis‐based medicines according to high pharmaceutical standards. These low doses of THC can produce safe and effective analgesia in patients with chronic pain.

To the best of our knowledge, it is the first time that the delivery of selective, significantly low, and precise therapeutic single doses of inhaled THC demonstrates an analgesic effect. It allows patients to reach the optimum balance between symptom relief and controlled side effects, enabling patients to regain their quality of life. In addition, this metered‐dose cannabis inhaler enables the individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically using accepted pharmaceutical models.”

https://onlinelibrary.wiley.com/doi/10.1002/ejp.1605

Study Finds Microdosing THC Reduces Pain Levels”  https://www.painnewsnetwork.org/stories/2020/7/1/study-finds-microdosing-thc-reduces-pain-levels

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A Cross-Sectional and Prospective Comparison of Medicinal Cannabis Users and Controls on Self-Reported Health

View details for Cannabis and Cannabinoid Research cover image“Despite widespread legalization, the impact of medicinal cannabis use on patient-level health and quality of life (QOL) has not been carefully evaluated.

The objective of this study was to characterize self-reported demographics, health characteristics, QOL, and health care utilization of Cannabis Users compared with Controls.

Results: Cannabis Users self-reported significantly better QOL [t(1054)=−4.19, p<0.001], greater health satisfaction [t(1045)=−4.14, p<0.001], improved sleep [children: t(224)=2.90, p<0.01; adults: [t(758)=3.03, p<0.01], lower average pain severity [t(1150)=2.34, p<0.05], lower anxiety [t(1151)=4.38, p<0.001], and lower depression [t(1210)=5.77, p<0.001] compared with Controls. Cannabis Users reported using fewer prescription medications (rate ratio [RR]=0.86; 95% confidence interval [CI]: 0.77–0.96) and were less likely to have a past-month emergency department visit (RR=0.61; 95% CI: 0.44–0.84) or hospital admission (RR=0.54; 95% CI: 0.34–0.87). Controls who initiated cannabis use after baseline showed significant health improvements at follow-up, and the magnitude of improvement mirrored the between-group differences observed at baseline.

Conclusions: Cannabis use was associated with improved health and QOL. Longitudinal testing suggests that group differences may be due to the medicinal use of cannabis. Although bias related to preexisting beliefs regarding the health benefits of cannabis in this sample should be considered, these findings indicate that clinical trials evaluating the efficacy of defined cannabinoid products for specific health conditions are warranted.

The key finding of this study is that medicinal cannabis use was associated with more positive ratings of health and QOL, assessed across multiple domains. Prospective analyses found that Controls showed improvement in health and QOL if they initiated medicinal cannabis use, and that Cannabis Users showed diminished health and QOL if they stopped cannabis use.”

https://www.liebertpub.com/doi/full/10.1089/can.2019.0096

“The Health Benefits of Medical Marijuana As Reported by Users. Using cannabis for medical reasons has been linked in a study to outcomes including better sleep, less anxiety, and taking fewer prescription medications.” https://www.newsweek.com/health-benefits-medical-marijuana-users-1511647

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