Cannabis research, medicine and use

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Re: Cannabis research, medicine and use

Postby slimmouse » Sun Jul 28, 2013 3:00 pm

http://www.wakingtimes.com/2013/07/27/3 ... es-cancer/

I have to say I dont like the implied tone of the link but here it is for any other researchers into this, out there.
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Re: Cannabis research, medicine and use

Postby Gnomad » Thu Aug 31, 2017 8:09 am

http://www.onlinelibrary.wiley.com/doi/ ... 29036/full

To investigate the association between cannabis smoking and lung cancer risk, data on 2,159 lung cancer cases and 2,985 controls were pooled from 6 case-control studies in the US, Canada, UK, and New Zealand within the International Lung Cancer Consortium. ...

The overall pooled OR for habitual versus nonhabitual or never users was 0.96 (95% CI: 0.66–1.38). Compared to nonhabitual or never users, the summary OR was 0.88 (95%CI: 0.63–1.24) for individuals who smoked 1 or more joint-equivalents of cannabis per day and 0.94 (95%CI: 0.67–1.32) for those consumed at least 10 joint-years.

For adenocarcinoma cases the ORs were 1.73 (95%CI: 0.75–4.00) and 1.74 (95%CI: 0.85–3.55), respectively. However, no association was found for the squamous cell carcinoma based on small numbers. Weak associations between cannabis smoking and lung cancer were observed in never tobacco smokers. Spline modeling indicated a weak positive monotonic association between cumulative cannabis use and lung cancer, but precision was low at high exposure levels.

Results from our pooled analyses provide little evidence for an increased risk of lung cancer among habitual or long-term cannabis smokers, although the possibility of potential adverse effect for heavy consumption cannot be excluded.
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Re: Cannabis research, medicine and use

Postby Gnomad » Thu Aug 31, 2017 9:10 am

GW Pharmaceuticals Announces Second Positive Phase 3 Pivotal Trial for Epidiolex (cannabidiol) in the Treatment of Lennox-Gastaut Syndrome
https://www.gwpharm.com/about-us/news/g ... -epidiolex

"SEP 26, 2016
London, UK; 26 Sept 2016: GW Pharmaceuticals plc (Nasdaq: GWPH, AIM: “GWP,” “GW,” “the Company” or “the Group”), a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, announces positive results of the second randomized, double-blind, placebo-controlled Phase 3 clinical trial of its investigational medicine Epidiolex® (cannabidiol or CBD) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), a rare and severe form of childhood-onset epilepsy. In this trial, Epidiolex, when added to the patient’s current treatment, achieved the primary endpoint for both dose levels with high statistical significance. During the treatment period, patients taking Epidiolex 20mg/kg/day achieved a median reduction in monthly drop seizures of 42 percent compared with a reduction of 17 percent in patients taking placebo (p=0.0047), and patients taking Epidiolex 10mg/kg/day achieved a median reduction in monthly drop seizures of 37 percent compared with a reduction of 17 percent in patients taking placebo (p=0.0016).

This trial follows the announcement in June 2016 of positive results in the first pivotal Phase 3 trial of Epidiolex for the treatment of seizures associated with LGS, and the March 2016 announcement of positive results in the treatment of seizures associated with Dravet syndrome. GW expects to submit a New Drug Application (NDA) to the U.S. Food & Drug Administration (FDA) in the first half of 2017.

“The positive outcome in this second trial of Epidiolex in patients with Lennox-Gastaut syndrome demonstrates the effectiveness of this product in this particularly difficult to treat, childhood-onset epilepsy,” stated Orrin Devinsky, M.D., of New York University Langone Medical Center’s Comprehensive Epilepsy Center and principal investigator in the trial. “The data from the Epidiolex Dravet and LGS studies offers the prospect of an FDA-approved CBD medicine that shows both clinically meaningful seizure reduction and a consistent safety and tolerability profile. I believe Epidiolex has the potential to become an important new option within the field of treatment-resistant epilepsy.”

--------------------------------------------------------------------------------
GW Pharmaceuticals Patenting THC and CBD for Brain Cancer
http://blog.sfgate.com/smellthetruth/20 ... in-cancer/

"Clinical research and anecdotal reports have indicated the use of cannabis and cannabis-derived chemicals to fight an array of cancers for a long time. Drug company GW Pharmaceuticals recently announced that the U.S. Patent Office has issued it a Notice of Allowance for a patent application involving the use of two main marijuana chemicals, tetrahydrocannabinol (THC) and cannabidiol (CBD) for treating gliomas.

Last month, this drug maker who specializes in cannabis-based pharmaceuticals also launched the first clinical trial to investigate the effectiveness of their cannabis drug Sativex in combination with Temozolomide, the standard chemotherapy drug. The trial involves 20 patients diagnosed with an aggressive and rare form of brain cancer known as recurrent glioblastoma multiforme (GBM). GW Pharmaceuticals has received early approval for their patent application that was filed in 2009, listing Otsuka Pharmaceutical as a collaborator.

The subject patent specifically covers a glioma treatment method for humans using a combination of THC and CBD in a ratio from 1:1 to 1:20 (THC: CBD) with goal to reduce tumor volume and cell viability, or inhibit cell growth. In November, the company also announced that it had started human trials of a CBD-rich cannabis drug for the treatment of pediatric epilepsy."
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Re: Cannabis research, medicine and use

Postby Gnomad » Thu Aug 31, 2017 9:13 am

Related to GW Pharmaceuticals Epidiolex - the story features the family whose epileptic son was the first human test subject of the new CBD pill. Long, interesting article about the difficulties they had to go through to be allowed to try the treatment even when all other options had failed spectacularly.

https://www.wired.com/2015/07/medical-m ... -epilepsy/

One Man’s Desperate Quest to Cure His Son’s Epilepsy—With Weed

"This is Sam. He’s my son. His epilepsy caused him to have up to 100 seizures a day. After seven years we were out of options. Our last hope: an untested, unproven treatment. The only problem? It was illegal."

"THE HOSPITAL PHARMACIST slid three bottles of pills across the counter, gave my wife a form to sign, and reminded her that this was not the corner drugstore. The pharmacy knew how many pills had been dispensed, he said; it would know how many had been consumed; and it would expect her to return the unused pills before she left the country. The pharmacist made it clear that he was not only in touch with our doctor but with the company supplying the medication. They would know if she broke the rules.

Evelyn said she understood and slipped the brown glass bottles into her purse. She and our 11-year-old son, Sam, were jet-lagged. They’d flown from San Francisco to London the previous day, December 19, 2012. Now, 30 hours later, it was just after 7 pm. They’d been at the Great Ormond Street Hospital for Children since midmorning. Sam had been through a brain-wave scan, a blood test, and a doctor examination. Some gel left in his hair from the brain scan was making him grumpy.

Evelyn was terrified. They’d come 5,350 miles to get these pills, medicine we hoped might finally quiet Sam’s unremitting seizures. He was to take a 50-milligram pill once a day for two days, increasing the dose to maybe three pills twice a day. Evelyn was to keep a log of his symptoms during their two-week stay. They would need to revisit the hospital two more times before they returned to San Francisco on January 3, 2013. That meant two more rounds of brain scans, blood tests, and doctors’ appointments.

Sam Vogelstein has had epilepsy since he was 4 and a half. He turned 14 in May.
We were confident the medicine wouldn’t kill Sam or hurt him irreversibly, but the prospect still made us nervous. The pills contained a pharmaceutical derivative of cannabis. People have been smoking cannabis medicinally for thousands of years. Deaths are rare. But Sam would get a specific compound made in a lab. The compound, cannabidiol, known as CBD, is not an intoxicant. (Tetrahydrocannabinol, or THC, is the stuff in pot that makes you high.) Nevertheless, US drug laws made it nearly impossible to get CBD at this purity and concentration in the States.

It had taken four months of phone calls, emails, and meetings with doctors and pharmaceutical company executives on two continents to get permission to try this drug. Sam wasn’t joining an ongoing clinical trial. The company made the pills just for him. It believed CBD was safe based on animal studies. It also said it knew of about 100 adults who had tried pure CBD like this over the past 35 years. As a percentage of body weight, Sam’s dose would approach twice what anyone else on record had tried for epilepsy. Would it make him vomit or become dizzy, or give him a rash or cause some other unpleasant event? We didn’t know. We’d volunteered our son to be a lab rat.

Then there was a bigger question: Would the medicine work? No one knew. The reason Evelyn, Sam, and others in my family—including Sam’s twin sister, Beatrice, and Evelyn’s sister, Devorah—traveled to London during Sam’s winter vacation was that two dozen other treatments we’d tried had all failed. (I stayed behind in San Francisco, scrambling to meet an end-of-year book deadline.)

The one thing we were certain about: This was not going to be a bargain. We’d already spent tens of thousands of dollars on consultants to help Sam’s doctors set up the visit, and we were still at the starting line. The best-case scenario was that the medicine would work and eventually we’d be allowed to import it into the US. We secretly hoped that this would encourage the company to make the drug easily and cheaply available to others. We also knew this was quixotic. Our previous experience with medications suggested the whole venture would end in failure. This much we knew: Importing an experimental cannabis-based drug into the US would involve more than giving the company my address and FedEx account number."

------------- SNIP ---------------- (several pages at original link cut)

"The total bill for getting GW’s CBD into the US was roughly $120,000, not including travel. Two consulting firms—one an expert in the workings of the FDA, the other an expert in the DEA—generated most of those expenses. It’s an enormous amount of money to pay for outside help, more than double what we’d thought it would cost.

The total bill for getting Sam’s cannabidiol into the US was roughly $120,000—double what we thought it would cost.
But it’s hard to imagine how we could have done it without them. Cilio had dozens of other patients to attend to besides Sam. And because she was new to the US, she had no idea how complicated and emotionally charged anything associated with cannabis can be here. The consultants showed her how to fill out the mountain of paperwork involved in applying to the FDA and the DEA. And they worked their contacts inside the agencies to make sure our application kept moving. The DEA agents, despite being antagonistic with Cilio and demanding that we get a safe to store Sam’s drugs, also moved our application along quickly when we speedily met their demands. The day we had the safe delivered to Cilio’s office, an agent visited to ensure it met DEA requirements. And he immediately advanced our application to the next step.

We wouldn’t have even known that consultants did work like this had Steve Willard, a Washington, DC, drug company entrepreneur, not introduced us to them. Sam now says he’s his best adult friend, even though he was my dad’s friend first.

Usually, getting access to experimental drugs that are potentially lifesaving doesn’t work this way. With terminal cancer patients, for example, oncologists know what new drugs are in development and have a mechanism already established to work with a company and quickly get FDA approvals. Yet GW was supplying drugs that were illegal in the US. No US hospital would take on a project like this.

But it appears our enormous bill for helping Sam has also jump-started the development of what doctors tell us could be one of the most exciting new drugs to treat epilepsy in a generation. Within a month of our return from London in early 2013, Guy and GW started talking to epileptologists at four other US hospitals about doing studies with their sickest kids. And on January 26 in New York City, 15 doctors, researchers inside and outside the US government, and GW officials sat in a conference room at NYU and began mapping out a strategy.

Those initial investigations—five hospitals, 25 kids apiece—proved so encouraging that GW last year expanded them to what it expects will be 1,400 patients at more than 50 hospitals in the US and the UK by year’s end. The drug now has a name—Epidiolex—though for a day or two Guy talked about naming it after Sam. It has a fast-track designation from the FDA, meaning that it could be available at Walgreens inside of three years.

Epidiolex is not a miracle cure. The most recent data, out in April, shows that of 137 kids who tried it for 12 weeks, it helped about half, reducing their seizures by at least 50 percent, with 9 percent becoming seizure-free. This is a better response rate than it sounds. All of the patients in the trials are those like Sam who had already run out of conventional options. But it is also a reminder that CBD, Epidiolex, or any seizure drug doesn’t help everyone."
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Re: Cannabis research, medicine and use

Postby Gnomad » Tue Dec 13, 2022 9:43 am

Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
https://www.science.org/doi/10.1126/sciadv.abi6110

Abstract
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ongoing coronavirus disease 2019 (COVID-19) pandemic underscores the need for new treatments. Here, we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α ribonuclease endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against current use of non-medical formulations as a preventative or treatment therapy.


Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants

Abstract

As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection-mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2.


The cannabis compounds that binded to the viral spike were cannabigerolic acid and cannabidiolic acid - so both are forms only present in fresh, undried cannabis, and heating will transform these into cannabigerol and cannabidiol - so for any therapeutic use, you would need these extracted fresh - vaporizing or traditional edibles will not work.
If one would make a smoothie out of fresh, wet, cannabis flower or leaves straight from the plant, it would contain a small amount of these acid compounds. And if one would make a fresh drink out of a cannabidiol-only heavy strains flowers like some that have 10% CBD and no THC, it would contain a decent amount of cannabidiolic acid, though.

Cannabidiol does work after infection too, preventing the virus from replicating after it has already entered cells though -
A news article about the study by Van Breemen's group:
https://www.news-medical.net/news/20220 ... cells.aspx

PLEASE note that in Van Breemen's study, THC diminished CBD's effects, due to competition of receptor binding possibly, and likely for best results in preventing viral cell entry, one would need to use only CBD and not a product containing both.

On the other hand, there is also this-
a preliminary study about THC's effects on COVID:

https://www.news-medical.net/news/20220 ... cells.aspx

Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression

Abstract

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.
Last edited by Gnomad on Tue Dec 13, 2022 10:14 am, edited 6 times in total.
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Re: Cannabis research, medicine and use

Postby Gnomad » Tue Dec 13, 2022 9:48 am

As well as this cohort analysis:

Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis

Abstract

Background

While cannabis is known to have immunomodulatory properties, the clinical consequences of its use on outcomes in COVID-19 have not been extensively evaluated. We aimed to assess whether cannabis users hospitalized for COVID-19 had improved outcomes compared to non-users.

Methods

We conducted a retrospective analysis of 1831 patients admitted to two medical centers in Southern California with a diagnosis of COVID-19. We evaluated outcomes including NIH COVID-19 Severity Score, need for supplemental oxygen, ICU (intensive care unit) admission, mechanical ventilation, length of hospitalization, and in-hospital death for cannabis users and non-users. Cannabis use was reported in the patient’s social history. Propensity matching was used to account for differences in age, body-mass index, sex, race, tobacco smoking history, and comorbidities known to be risk factors for COVID-19 mortality between cannabis users and non-users.

Results

Of 1831 patients admitted with COVID-19, 69 patients reported active cannabis use (4% of the cohort). Active users were younger (44 years vs. 62 years, p < 0.001), less often diabetic (23.2% vs 37.2%, p < 0.021), and more frequently active tobacco smokers (20.3% vs. 4.1%, p < 0.001) compared to non-users. Notably, active users had lower levels of inflammatory markers upon admission than non-users—CRP (C-reactive protein) (3.7 mg/L vs 7.6 mg/L, p < 0.001), ferritin (282 μg/L vs 622 μg/L, p < 0.001), D-dimer (468 ng/mL vs 1140 ng/mL, p = 0.017), and procalcitonin (0.10 ng/mL vs 0.15 ng/mL, p = 0.001). Based on univariate analysis, cannabis users had significantly better outcomes compared to non-users as reflected in lower NIH scores (5.1 vs 6.0, p < 0.001), shorter hospitalization (4 days vs 6 days, p < 0.001), lower ICU admission rates (12% vs 31%, p < 0.001), and less need for mechanical ventilation (6% vs 17%, p = 0.027). Using propensity matching, differences in overall survival were not statistically significant between cannabis users and non-users, nevertheless ICU admission was 12 percentage points lower (p = 0.018) and intubation rates were 6 percentage points lower (p = 0.017) in cannabis users.

Conclusions

This retrospective cohort study suggests that active cannabis users hospitalized with COVID-19 had better clinical outcomes compared with non-users, including decreased need for ICU admission or mechanical ventilation. However, our results need to be interpreted with caution given the limitations of a retrospective analysis. Prospective and observational studies will better elucidate the effects cannabis use in COVID-19 patients.


Probably should always mention that the preferred method of cannabis ingestion should always be edibles / ingestion, and never smoking because smoke is always harmful,
followed by either herb vaporization or extract vaporization, which eliminates combustion products completely.

When I was (very) sick with COVID a year ago, I did not yet have pure CBD oil (do stock them now in the freezer so I have them if needed) but did treat myself with self-produced high THC / medium CBD edibles, which did alleviate my symptoms better than generic OTC pain medications. Of course totally anecdotal and so on, but I would not want to know how sick I would have gotten without those edibles. Ran almost 40 celsius fever for several days, accompanied with dry cough, some pink foam expelled so probably blood from lung damage, and heart arrhythmias for two weeks, as well as being so weak for the first week that I could barely walk to the kitchen and toilet during the first week.

Residual weakness and heart palpitations and arrhythmia continued for about a month after the first two weeks of acute sickness, but I have no persisting symptoms otherwise.
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