C&P#56: the many harms of cannabis + the entourage effect + cannabis for Parkinson’s & CBD for high blood pressure
C&P#56: the many harms of cannabis + the entourage effect + cannabis for Parkinson’s & CBD for high blood pressure
my web series gets a nod from the Academy
Hello everyone,
Welcome to the 56th edition of Cannabinoids & the People, a weekly newsletter where I collect all the new cannabinoid science. You can check out last week’s issue here & if you haven’t subscribed yet, please do.
As always, here’s the Living Glossary of Cannabinoid Terms & at the bottom is the album of the week.
For becoming paid subscribers of this newsletter, thanks to cannabis elevationist Becca Williams (& congrats on her recent move to Portugal) & thanks to Arnaud Dumas de Rauly, CEO of Blinc (& congrats on their recent legal win).
Also, I’m delighted to announce that my YouTube series ‘The Graphic Novels I Should Be Writing Right Now…’ has been nominated for an Academy Award. I’d like to thank my parents, my wife Claire & the literally handful of watchers who have shot this series to the stars. Thank you!
This week…
Such positive results of cannabis for Parkinson’s
CBD for alcohol withdrawal & high blood pressure + THC for PTSD
Confirmation of the entourage effect of terpenes increasing the strength of THC
9 reviews & case studies on the harms of CBD & cannabis (gotta stay honest around here)
Cannabis causing catatonia (it's a thing)
Cannabinoids to kill viruses & MRSA
In mice, CBD not only helps with pain, but for the social stress of living with someone in pain
CBGA for kidney inflammation + I created a genitourinary page for CVResearch.info
Our collection of other CBD acronyms is growing + our first new THC acronym
Transcranial stimulation may help via the ECS
One Dr. Strangelove reference
Sponsor: PlusCBD for healthcare practitioners
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My work this week:
One-Minute Cannabinoid Science shorts:
THC & CBD for Multiple Sclerosis +
Endocannabinoids & exercise +
CBD & neuropathic pain +
CBDA & THCA for Alzheimer's
The Graphic Novels I Should Be Writing Series...
Chapter 5: The Breakfast – on the laughter of hasheesh, the essay of Dr. Viktor Robinson & the Sufi story of the origin of discovering cannabis
On TikTok:
Death, the Mental Universe & the Infinite (Kybalion Ch 5) + The CIA, Howard Hunt & the character assassination of Nixon + Your Anus! Mantak Chia's 'Chi Self-Massage'+ Alice in Wonderland unboxing + Sciencemancy on soil & cats + study the darkness, but not too much
(I link to YouTube for accessibility, but find me on TT @lexpelgerandhisbooks)
My platforms: Linktree
YouTube for educational videos, lectures & shorts on new cannabinoid science
My podcasts
Anandamide; or, the People: my graphic novel series on cannabis, the endocannabinoid system & the War on Drugs based on Moby-Dick
LinkedIn, Twitter & my TikTok on books, hermeticism, science & historyWays to support this work:
Buy Me a Coffee
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Zelle: pelger@gmail.com
PayPal: donate here
Best Of Cannabinoid Science...
Clinical
In patients with Parkinson's disorder, the majority using a 1:1 THC:CBD tincture saw an improvement in their cramping/dystonia, pain, spasticity, lack of appetite, dyskinesia & tremor while half lowered or stopped their opioid usage
Medical Cannabis in the Treatment of Parkinson's Disease
https://pubmed.ncbi.nlm.nih.gov/37071411/
And another Parkinson’s clinical study focused on safety found formulas of THC/CBD to be well tolerated
A Phase Ib, Double Blind, Randomized Study of Cannabis Oil for Pain in Parkinson's Disease
https://movementdisorders.onlinelibrary.wiley.com/doi/abs/10.1002/mdc3.13754
In adults with treated & untreated hypertension, chronic administration of CBD reduced blood pressure with a noted lack of serious adverse events
Chronic Effects of Oral Cannabidiol Delivery on 24-h Ambulatory Blood Pressure in Patients with Hypertension (HYPER-H21-4): A Randomized, Placebo-Controlled, and Crossover Study
https://pubmed.ncbi.nlm.nih.gov/37093160/
In cancer patients, using THC & CBD reduced their disturbed sleep & anxiety
Impact of Cannabis Use Patterns on Symptoms in Patients with Cancer (Sch435)
https://www.sciencedirect.com/science/article/abs/pii/S0885392423002518
In adults with PTSD, low levels of THC helped with fear learning & memory in the corticolimbic system
Cannabinoid modulation of corticolimbic activation during extinction learning and fear renewal in adults with posttraumatic stress disorder
https://pubmed.ncbi.nlm.nih.gov/37088409/
In eyes, “acute cannabis use results in less pupil constriction and slower pupil rebound dilation in the light stimulus test”
A Video Segmentation Pipeline for Assessing changes in Pupil Response to Light After Cannabis Consumption
https://pubmed.ncbi.nlm.nih.gov/36993434/
A model for predicting clinical drug-drug interactions with CBD
A Physiologically-Based Pharmacokinetic Model for Cannabidiol in Healthy Adults, Hepatically-Impaired Adults, and Children
https://pubmed.ncbi.nlm.nih.gov/36972999/
Reviews
A review of the antiviral properties of cannabinoids
Antiviral activities of hemp cannabinoids
https://pubmed.ncbi.nlm.nih.gov/37083031/
I’ve got pages & pages of data in my archives. From HIV to COVID, influenza to hepatitis, Ebola to monkeypox, the clinical use of cannabinoids against viruses is tragically neglected.
Plus, a study of cannabinoids for MRSA (the antibiotic resistant staph infecting haunting hospitals that kills more people each year than HIV)
Cannabinoid Molecules from Cannabis Sativa L. as a Promissing Solution for Methicillin-Resistant Staphylococcus Aureus (MRSA)
https://www.researchgate.net/publication/370022634_Cannabinoid_Molecules_from_Cannabis_Sativa_L_as_a_Promissing_Solution_for_Methicillin-Resistant_Staphylococcus_Aureus_MRSA
In neonatal infants with blood loss to the brain, a review of using cannabinoids for neuroprotection
Role of integrating cannabinoids and the endocannabinoid system in neonatal hypoxic-ischaemic encephalopathy
https://pubmed.ncbi.nlm.nih.gov/37122621/
And a confirmatory study in rats where CBD & hypothermia helped to protect their infant’s brains from a loss of blood flow
Effects of Cannabidiol, Hypothermia, and Their Combination in Newborn Rats with Hypoxic-Ischemic Encephalopathy
https://pubmed.ncbi.nlm.nih.gov/37072177/
A review of cannabis for pain covers the multiple dimensions on which it helps
Influence of Cannabinoid Treatment on Trajectories of Patient-Related Outcomes in Chronic Pain: Pain Intensity, Emotional Distress, Tolerability and Physical Disability
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136873/
A review of 120 studies on anxiety finds positive results for CBD
Anxiolytic effects of endocannabinoid enhancing compounds: A systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/37094409/
For Alzheimer's, a review of animal studies on how the endocannabinoid system regulates the glial cells (immune cells of the brain) to help maintain cognitive function via the reduction of inflammation
Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer's disease: A systematic review and meta-analysis of animal studies
https://pubmed.ncbi.nlm.nih.gov/36959856/
Harms / Adverse Effects
A review of the gender differences in the harms of cannabis
Impacts of recreational cannabis legalization on use and harms: A narrative review of sex/gender differences
https://pubmed.ncbi.nlm.nih.gov/36970279/
A Brazilian review of adverse effects of cannabinoid use
Adverse effects of cannabinoid use: what is the safety paradigm?
https://www.scielo.br/j/brjp/a/R4TdHZ7fqGyWYvkHCtcj8rz/
In patients with epilepsy using CBD, a review of the adverse events
Adverse Events of Cannabidiol Use in Patients With Epilepsy: A Systematic Review and Meta-analysis
https://pubmed.ncbi.nlm.nih.gov/37079302/
A review of the potential toxicities of CBD (mostly liver enzymes & male fertility)
Review of the oral toxicity of cannabidiol (CBD)
https://pubmed.ncbi.nlm.nih.gov/37088127/
On the safety of CBD after being given to rats for 90 days
Oral toxicity evaluation of cannabidiol
https://pubmed.ncbi.nlm.nih.gov/37105391/
A review of medical cannabis on workplace safety
Medicinal Cannabis and Implications for Workplace Health and Safety: Scoping Review of Systematic Reviews
https://pubmed.ncbi.nlm.nih.gov/37077169/
“Adverse events associated with the use of medicinal cannabis could increase workplace risks, including decreased alertness and reaction times, increased absenteeism, reduced ability to safely drive or operate machinery and an increased probability of falling.”
A case study of cannabis use leading to a cardiac arrest
Marijuana as a Cause of Diffuse Coronary Vasospasm Leading to Cardiac Arrest
https://assets.cureus.com/uploads/case_report/pdf/64574/20230423-30312-u2fsrz.pdf
A case report of a 94 year old woman with diarrhea & hallucinations from a CBD brownie that contained THC
Cannabis-Induced Acute Encephalopathy in a 94-Year-Old Woman Due to Family Administration of Cannabidiol (CBD) Products: Case Report
https://assets.cureus.com/uploads/case_report/pdf/152003/20230421-19796-4myorn.pdf
A 15 year old whose cannabis use cause catatonia (a frozen state of disruption to a person’s awareness of their surroundings & a lack of response to external stimuli)
Cannabis-Induced Catatonia in a 15-Year-Old Male: A Case Report
https://pubmed.ncbi.nlm.nih.gov/37141480/
This is a rare but known side effect of cannabis. Medical reports from India 150 years ago have patients in a complete catatonic states for hours after drinking large amounts of hashish beverages. It is less common today with our lower levels of THC intake but at least a few case studies come out every year.
Preclinical
In confirmation of the entourage effect, certain cannabis terpenes synergized with THC to increase CB1 receptor activation severalfold, even at low levels
Selected cannabis terpenes synergize with THC to produce increased CB1 receptor activation
https://pubmed.ncbi.nlm.nih.gov/37084981/
And in a mouse model of chronic neuropathic pain, the terpenes of cannabis lessened the pain via adenosine receptors in the spinal cord
Terpenes from Cannabis sativa Induce Antinociception in Mouse Chronic Neuropathic Pain via Activation of Spinal Cord Adenosine A 2A Receptors
https://pubmed.ncbi.nlm.nih.gov/37034662/
In a mouse model of alcohol withdrawal, CBD reduce their anxiety, their behavioral symptoms of withdrawal & caused “remarkable” changes in the genetic expression of the brain targets studied
Cannabidiol regulates behavioral and brain alterations induced by spontaneous alcohol withdrawal
https://pubmed.ncbi.nlm.nih.gov/37085012/
And in an adolescent rat model of alcohol abuse, the CB1 receptors in the hippocampus were linked to impulsivity & alcohol-seeking behavior
A potential role of hippocampus on impulsivity and alcohol consumption though CB1R
https://pubmed.ncbi.nlm.nih.gov/37088449/
In mice with pain from a bacterial infection, CBD reduced the transmission of pain signals & inflammation via Toll receptor
Cannabidiol reduces lipopolysaccharide-induced nociception via endocannabinoid system activation
https://pubmed.ncbi.nlm.nih.gov/37076976/
And for a mouse housed with another mouse in extreme chronic pain, CBD helped lessen their anxiety, sensitivity to pain & depressive behaviors
Cannabidiol Treatment Shows Therapeutic Efficacy in a Rodent Model of Social Transfer of Pain in Pair-Housed Male Mice
https://pubmed.ncbi.nlm.nih.gov/37074109/
Mice are very sympathetic creatures. They find it very distressing to live with another mouse experiencing unrelenting pain. CBD helps them to deal with it.
And if we’re lucky, CBD will keep them passive enough to not start a revolution that overthrows the humans & their evil biomedical experiments in order to begin a murine utopia where rats & mice can finally live in peace.
The antidepressant effects of transcranial magnetic stimulation may be caused by its modulation of the endocannabinoid system as well as GABA & glutamate (the primary inhibitory & excitatory neurotransmitters of the brain, heavily involved with the endocannabinoids)
High-frequency repetitive transcranial magnetic stimulation regulates neural oscillations of the hippocampus and prefrontal cortex in mice by modulating endocannabinoid signalling
https://pubmed.ncbi.nlm.nih.gov/36965621/
In a mouse model of osteoporosis, CBD enhanced bone metabolism as well as bone healing after a break
Non-psychoactive Cannabidiol Prevents Osteoporosis in an Animal Model and Increases Cell Viability, Proliferation, and Osteogenic Gene Expression in Human Skeletal Stem and Progenitor Cells
https://pubmed.ncbi.nlm.nih.gov/37093268/
In an animal model of kidney disease, CBGA & CBD strongly reduced inflammation & kidney scarring partially via TRPM7 inhibition
CBGA ameliorates inflammation and fibrosis in nephropathy
https://pubmed.ncbi.nlm.nih.gov/37072467/
In a rat model of addiction to methamphetamine, CBD helped to inhibit the rewarding properties via dopamine receptors in the hippocampus
The inhibitory effect of cannabidiol on the rewarding properties of methamphetamine in part mediates by interacting with the hippocampal D1-like dopamine receptors
https://pubmed.ncbi.nlm.nih.gov/37100273/
Against cigarette smoke, computer modeling shows the compounds of cannabis to be anti-inflammatory
Molecular Docking of the Cannabis sativa L. Bioactive Compound Against Inflammation Induced by Cigarette Smoke Exposure
https://journal.unnes.ac.id/nju/index.php/biosaintifika/article/view/43845
An evergreen note on reading restricted papers:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version), Google Scholar itself or try ResearchGate.
Three other helpful browser extensions are: Unpaywall, Open Access Button & PaperPanda
For the infamous backdoor, use Sci-Hub – the pirated papers repository (Chrome extension here). This works better for older paper than the stuff that just came out.
For Twitter users, send a Tweet of the paper’s title with the hashtag #icanhazpdf. It works because people are beautiful(ish).
Finally, email the author. They’re almost always happy to oblige because, thanks to the predatory academic publishing system, they don’t make a dollar off of their papers.
the Headlines & Fav Articles
Good analysis of the SAFE Banking Act as well as the big investors pulling out of cannabis coverage
On the huge water usage in California by illegal cannabis farms
https://www.bloomberg.com/news/newsletters/2023-05-08/california-s-illicit-marijuana-is-making-water-shortages-worse
The fun-lovers at the Trademark Trial & Appeal Board agree that no trademarks can be given for illegal drug paraphernalia (in this case, an oil dabber)
https://harrisbricken.com/cannalawblog/ttab-denies-registration-of-bakked-trademarks/
This is why the patent attorneys never get invited to the federal Christmas party.
The Border Patrol stays at the forefront of reactionism by telling its agents ‘Say No To CBD’
https://www.marijuanamoment.net/border-patrol-agents-and-their-family-members-warned-to-just-say-no-to-cbd-due-to-concerns-about-unregulated-products
The War on Drugs & Prohibition
In Baltimore, de facto decriminalization led to less arrests of Black people for cannabis possession
Racial Disparities in Drug Arrest Before and After De Facto Decriminalization in Baltimore
https://pubmed.ncbi.nlm.nih.gov/37068597/
Canada's legalization led to a decrease in arrests of youth
Canada's cannabis legalization and police-reported cannabis-related criminal incidents among youth, 2015-2021
https://pubmed.ncbi.nlm.nih.gov/37183068/
One of my favorite TikTok historians on the Opium Wars
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Business & Law
Ugh. It’s earnings week – and what a bloodbath out there. Check out Marijuana Moment’s Business section for the roundup of how everyone is losing tens of millions of dollars…
https://www.marijuanamoment.net/schumer-reaffirms-cannabis-banking-needs-expungements-attached-newsletter-may-12-2023
In the hospitality industry, balancing the use of cannabis for guest & employee enjoyment & safety
A High Wire Act: Balancing guest, employee, and organizational perspectives concerning marijuana use in the hospitality industry
https://www.chrie.org/assets/docs/JHTC-case-notes/JHTC-vol-9/JHTC_Vol%209_Issue%204_Beneche_Cain_Moreo_case.pdf
I usually frown at pot jokes in paper titles, but this one is pretty damn good.
On how medical cannabis laws may make it harder for employers to fire impaired workers
Meeting a Higher Bar
https://heinonline.org/HOL/LandingPage?handle=hein.journals/abaj109&div=17&id=&page=
Psychedelics, Plant Medicines & Other Psychoactives
A review of Don Lattin’s ‘God On Psychedelics’ by OG Dr. Tom Roberts
https://www.researchgate.net/publication/370630987_book_review_of_God_on_Psychedelics_-Tripping_Across_the_Rubble_of_Old-time_Religion
‘French Connections: London-Paris linkages in interwar drug culture’
https://pointshistory.com/2023/05/02/french-connections-london-paris-linkages-in-interwar-drug-culture
This article is short on Big Picture & long on gossip.
Just how I like my history…
DMT in sea sponges by Sofie Mikhaylova
https://www.leafie.co.uk/psychedelics/dmt-sea-sponges
The Psychoactive Research
[This isn’t a deep dive into all of the science of psychedelics & other psychoactives like I do for the cannabinoids. If a newsletter with all that new science would be of interest to your company or organization, reach out to me]
An analysis of the control conditions used in psychedelic research & an author’s tweets about the review
Control Conditions in Randomized Trials of Psychedelics: An ACTTION Systematic Review
https://www.psychiatrist.com/jcp/psychopharmacology/control-conditions-randomized-trials-psychedelics-acttion-systematic-review/
https://twitter.com/sdpnayak/status/1656283224811642881
In patients who get a dose of ketamine for surgery, it had no effects on their depression
Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients
https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v1
The Plant & the History
The top 5 hemp-producing countries: China, Canada, US, France & Chile
https://cbdworldnews.com/2020/10/18/the-worlds-top-5-hemp-producing-countries
Growing & Farming
Interviews with hemp farmers in Colorado & Kentucky about the challenges of choosing market channels
Producers marketing a novel crop: a field-level view of hemp market channels
https://www.cambridge.org/core/services/aop-cambridge-core/content/view/D61179A526FA3BC77EA020B99F9741E8/S1742170523000145a.pdf/div-class-title-producers-marketing-a-novel-crop-a-field-level-view-of-hemp-market-channels-div.pdf
How a cannabis cultivar’s flowering response varies under different day lengths & light intensities
Flowering Response of Cannabis sativa L. ‘Suver Haze’ under Varying Daylength-Extension Light Intensities and Durations
https://www.mdpi.com/2311-7524/9/5/526
Two root fungi that improve cannabis growth
Root colonization of industrial hemp (Cannabis sativa L.) by the endophytic fungi Metarhizium and Pochonia improves growth
https://www.sciencedirect.com/science/article/abs/pii/S0926669023004818
A type of root fungi that improves hemp's uptake of cadmium for cleaning the soil
Arbuscular mycorrhizal fungi influence the uptake of cadmium in industrial hemp (Cannabis sativa L.)
https://pubmed.ncbi.nlm.nih.gov/37080470/
Genomic analysis of Moroccan cannabis
Genetic structure and diversity of cannabis (Cannabis sativa L.) populations from northern Morocco through genomic SSR analysis
https://www.authorea.com/doi/full/10.22541/au.168119827.78340398
Identifying a genetic locus in cannabis associated with photo-insensitivity (auto flowering)
AFLOWERING LOCUS Tortholog is associated with photoperiod-insensitive flowering in hemp (Cannabis sativaL.)
https://europepmc.org/article/ppr/ppr649276
On imaging the uptake and distribution in hemp of nutrient elements & toxic metals
Imaging the distribution of nutrient elements and the uptake of toxic metals in industrial hemp and white mustard with laser-induced breakdown spectroscopy
https://www.sciencedirect.com/science/article/abs/pii/S058485472300071X
Human nutrition
For hemp seed oil, the elements of quality & authenticity
Composition of cold-pressed hemp seed oils: key elements of quality and authenticity
https://en.innovhub-ssi.it/kdocs/2077781/2023_100_1_tura.pdf
Hempseed meal improved fermented yogurt & increased its ability to alleviate the patient in rats
Defatted hempseed meal altered the metabolic profile of fermented yogurt and enhanced the ability to alleviate constipation in rats
https://pubmed.ncbi.nlm.nih.gov/36971462/
Veterinary use
A review for veterinarians of the quality control aspects to pay attention to for cannabinoid rich hemp extracts
Key quality control aspects about cannabinoid-rich hemp products that a veterinarian needs to know: a practitioner's guide
https://pubmed.ncbi.nlm.nih.gov/37072120/
Industrial Use
On using hemp oil to improve epoxy glues
Epoxidized and Maleinized Hemp Oil to Develop Fully Bio-Based Epoxy Resin Based on Anhydride Hardeners
https://pubmed.ncbi.nlm.nih.gov/36987185/
CANNABINOID SCIENCE
Our collection of other CBD acronyms is growing:
Corticobasal degeneration (CBD) – a Parkinson’s type disease
The evolution of diagnosis from symptom onset to death in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) compared to Parkinson's disease (PD)
https://pubmed.ncbi.nlm.nih.gov/36971841/
As well as compulsive buying disorder (CBD)
Compulsive buying disorder (CBD) among medical students in colleges of medicine, dentistry and pharmacy at King Saud University in Riyadh
https://pubmed.ncbi.nlm.nih.gov/36993053/
Plus, in a twist, our first new THC acronym: Tetrahydrocurcumin (THC) – an active ingredient of curcumin
Tetrahydrocurcumin Add-On therapy to losartan in a rat model of diabetic nephropathy decreases blood pressure and markers of kidney injury
https://pubmed.ncbi.nlm.nih.gov/36971089/
Clinical Use & Ingestion Methods
On the trends in Canadian medical cannabis after 20 years
Lessons from 20 years of medical cannabis use in Canada
https://pubmed.ncbi.nlm.nih.gov/36952564/
“In 2001, the Canadian government granted access to those with physician-documented evidence of a severe health problem that could not be managed using conventional therapies. Most patients accessed cannabis grown under a personal production license. By 2013, authorized daily cannabis dosages were very high. In 2014, the government, concerned over illegal diversion, required that cannabis be purchased from a licensed commercial grower; personal production was banned. Physicians were given responsibility for authorizing patient access. To fill the regulatory void, the physician regulatory bodies in Canada imposed their own prescribing restrictions. After these changes, the number of physicians who were willing to support patient cannabis use markedly decline but the number of patients participating in the program sharply increased. Medical cannabis use varied by province-rates were generally lower in provinces with stricter regulations on physician cannabis prescribing. Most varieties of cannabis oil available for sale are now high in CBD and low in THC. Dry cannabis varieties, conversely, tend to be high in THC and low in CBD. Inflation adjusted prices of most varieties of medical cannabis have declined over time. We find that rates of daily cannabis use (medical or otherwise) increased markedly after the 2014 policy regime. The fraction of Canadians using cannabis daily increased again after the 2018 legalization of recreational cannabis; at the same time, participation in the medical access program declined.”
On the results of cannabis use at a native community clinic of the Puyallup Tribe
Cannabis for Healing in a Native Community Clinic: Development and Results from an Informatics Research Tool
https://pubmed.ncbi.nlm.nih.gov/37068200/
On the movement towards personalized cannabinoid medicine based on your genetics
Cannabis Pharmacogenomics: A Path to Personalized Medicine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137111/
In this cohort study, medical cannabis patients who used cannabis every day were more likely to develop symptoms of cannabis use disorder
Development of cannabis use disorder in medical cannabis users: A 9-month follow-up of a randomized clinical trial testing effects of medical cannabis card ownership
https://pubmed.ncbi.nlm.nih.gov/36960460/
In college students who use alcohol & cannabis at the same time, most of the harms come from the alcohol consumption
Acute Consequences Associated With Co-use of Alcohol and Cannabis: A Daily Survey Analysis
https://pubmed.ncbi.nlm.nih.gov/36971729/
In patients taking Sativex (a 1:1 THC:CBD spray), a look at the levels of THC & CBD in their precious bodily fluids
Δ9-THC and CBD in Plasma, Oral Fluid, Exhaled Breath, and Urine from 23 Patients Administered Sativex
https://pubmed.ncbi.nlm.nih.gov/37083482/
How THC & CBD are broken down to their metabolites in liver cells
Cytosolic Enzymes Generate Cannabinoid Metabolites 7-Carboxycannabidiol and 11-Nor-9-carboxytetrahydrocannabinol
https://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.3c00017
Mental Health, Sleep & Substance Use Disorders
In Australia, a 20-year survey finds that more & more people are using cannabis to treat their sleep disorders
Medical Cannabis Use Patterns for Sleep Disorders in Australia: Results of the Cross-Sectional CAMS-20 Survey
https://pubmed.ncbi.nlm.nih.gov/37090897/
Across the world, people with depression or anxiety are more likely to use cannabis
Cross-national reflections on medicinal cannabis and depression
https://www.tandfonline.com/doi/full/10.1080/14737175.2023.2203861
Recent interpersonal abuse or cannabis use is linked to increased odds of having a recent psychotic experience
The separate and joint effects of recent interpersonal abuse and cannabis use on psychotic experiences: findings from students in higher education in the United States
https://pubmed.ncbi.nlm.nih.gov/37093229/
In youth with bipolar disorder, the effects of their genetic variant of the CB1 receptor in brain scans of connectivity
The association of CNR1 genetic variants with resting-state functional connectivity in youth bipolar disorder
https://pubmed.ncbi.nlm.nih.gov/36972648/
In a rat model of chronic sleep deprivation, anandamide improved their food intake & and the activity of their neurons producing orexin (a hormone associated with sleep) in the lateral hypothalamus
Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus
https://www.sciencedirect.com/science/article/abs/pii/S0143417923000173
In young male mice with early life stress who use cocaine, the endocannabinoid system modulates the stimulant effects via GABA & dopamine
Endocannabinoid-dependent decrease of GABAergic transmission on dopaminergic neurons is associated with susceptibility to cocaine stimulant effects in pre-adolescent male MAOA hypomorphic mice exposed to early life stress
https://pubmed.ncbi.nlm.nih.gov/37080337/
In mice, the cannabinoid receptors on their mitochondria (powerhouse of the cell) help to regulate their corticosteroid stress response & novel object recognition via noradrenaline & GABA
Mitochondrial cannabinoid receptors gate corticosterone impact on novel object recognition
https://pubmed.ncbi.nlm.nih.gov/37098353/
The Brain & its Diseases
In 18 young patients with epilepsy, they showed no benefit from dispensary CBD because their blood levels did not reach the therapeutic range
Dispensary Cannabidiol (CBD): Nothing to Worry About!
https://pubmed.ncbi.nlm.nih.gov/37101430/
This paper feels like it has quite a negative bias. They dismiss any anecdotal reports of the effectiveness of dispensary CBD as being the result of prescription anti-seizure medications. This tiny study doesn’t compare to the large number of parents reporting improvements for their kids, enough so that it caused a migration of families to legal states in the early days of legalization.
A model of neurons & their supporting astrocytes looks at the negative & positive effects of CBD
Neutralization of Cannabidiol Neurotoxicity in Neuron-Astrocyte Sandwich Coculture
https://pubmed.ncbi.nlm.nih.gov/37080943/
“CBD (15 and 30 µm) causes the viability decrease, along with morphological damage, in the neuron-alone culture, whereas its neurotoxic effects are significantly attenuated by the supports of astrocytes in the neuron-astrocyte coculture. In addition, it is found that CBD-induced increase of intracellular Ca2+ concentration and depolarization of mitochondrial membrane potential, via activation of transient receptor potential vanilloid 1, are noticeably ameliorated by coculturing neurons with astrocytes.”
A review of how the endocannabinoid system controls the glial cells (immune cells of the brain)
Glia function in the endocanabinoid system: narrative review
https://www.scielo.br/j/brjp/a/3G8VgBR6DkwGhzLXP33RXrR/
In brain cells, two synthetic cannabinoids enhanced cell division & might therefore lead to faster aging
The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA accelerate SH-SY5Y proliferation via stimulation of CB1 and CB2 cannabinoid receptors
https://publicacoes.cespu.pt/index.php/sl/article/view/102
Harms, Cannabis Use Disorder & Street Synthetics
A review of data from the US poison center found an increased interest among those who attempted suicide
Suspected Suicidal Cannabis Exposures Reported to US Poison Centers, 2009-2021
https://pubmed.ncbi.nlm.nih.gov/37074718/
While this study does not suggest causation, and while it’s not pleasant data, there’s a body of data finding links between cannabis use & increased suicidality. As someone who has noticed this link in my own life, I’m loathe to dismiss these findings.
In a trial of CBD for cannabis use disorder, 800 milligrams per day increased anandamide levels but 400 milligrams per day did not & in any case, anandamide levels were not associated with clinical outcomes
Effects of cannabidiol on anandamide levels in individuals with cannabis use disorder: findings from a randomised clinical trial for the treatment of cannabis use disorder
https://pubmed.ncbi.nlm.nih.gov/37085531/
On the symptoms of cannabis use disorder
Cannabis Use Disorder Symptoms in Weekly Cannabis Users: A Network Comparison Between Daily Cigarette Users and Nondaily Cigarette Users
https://pubmed.ncbi.nlm.nih.gov/37074121/
In youth with cannabis use disorder, they had lower levels of the SHANK1 protein involved with synaptic integrity
Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles
https://pubmed.ncbi.nlm.nih.gov/36994633/
Those who used high-potency cannabis had a slightly increased risk problematic cannabis use
High potency cannabis use, mental health symptoms and cannabis dependence: Triangulating the evidence
https://pubmed.ncbi.nlm.nih.gov/37121087/
The metabolism of two synthetic cannabinoids of the OXIZID category
Study of the Metabolic Profiles of "Indazole-3-Carboxamide" and "Isatin Acyl Hydrazone" (OXIZID) Synthetic Cannabinoids in a Human Liver Microsome Model Using UHPLC-QE Orbitrap MS
https://pubmed.ncbi.nlm.nih.gov/37110234/
Pain, Inflammation & Surgeries
A review on how cannabis alters the behaviors around pain
Painful behavior and medicinal cannabis
https://www.scielo.br/j/brjp/a/4jJdrn6RrZ6hFLZ85mXyYzq/
A review on using the cannabinoids for migraine
Phytocannabinoids and migraine: An integrative review
http://sevenpublicacoes.com.br/index.php/editora/article/view/1079
In Brazil, on the great potential of using cannabis for chronic pain
Cannabinoid therapy within the Unified Health System, perspectives in relation to pain treatment
https://www.scielo.br/j/brjp/a/mvnHhGfVD5RvFSKNyH3bSmB/?lang=en
In a rat model of neuropathic pain, activating the CB2 receptors in the spinal cord alleviated the pain via the microglia (immune cells of the nervous system) & by lowering P2X7 (a neural receptor that changes the electrical balance of a cell)
Spinal cannabinoid receptor 2 activation alleviates neuropathic pain by regulating microglia and suppressing P2X7 receptor
https://pubmed.ncbi.nlm.nih.gov/36969555/
In rats, the effect of chronic CB1 activation on the necessary levels of anesthesia
Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine
https://www.mdpi.com/2306-7381/10/5/310
In rotator cuff surgery, CBD's effect on post-operative pain is unknown because of the barbarity of the journal paywall system limiting access to scientific findings
Effects Of Cannabidiol On Post-Operative Pain Following Arthroscopic Rotator Cuff Repair
https://www.jshoulderelbow.org/article/S1058-2746(23)00155-6/fulltext
I do loathe this current system.
And if anyone wants to help me out with an academic backdoor into the journals, I recently lost my access when a friend moved on from his lab. Your support would help me greatly in sharing the potentials & the perils of cannabinoid medicine for all these readers.
Immune System & Microbials
In people living with HIV who use cannabis, they had higher levels of some immune markers & lower levels of anandamide & oleamide
Changes in Immune-Related Biomarkers and Endocannabinoids as a Function of Frequency of Cannabis Use in People Living With and Without HIV
https://pubmed.ncbi.nlm.nih.gov/37093248/
This strain of salmonella is resistant to CBD because of its tail spike protein
CBD resistant Salmonella strains are susceptible to epsilon 34 phage tailspike protein
https://pubmed.ncbi.nlm.nih.gov/36960333/
Improving CBD's antibiotic effects by combining it with PLGA nanoparticles
PLGA Nanoparticles with Cannabidiol for Efficient and Durable Antibacterial Applications
http://www.jelsciences.com/articles/jbres1730.pdf
Hormones, Reproduction & Maternal Effects
In pregnant women, the outcomes of treatment for cannabis use disorder
Treatment outcomes among pregnant women with cannabis use disorder
https://www.sciencedirect.com/science/article/abs/pii/S0306460323001181
A review of the endocannabinoid system in the placenta & how it might relate to preeclampsia
The endocannabinoidome in human placenta: Possible contribution to the pathogenesis of preeclampsia
https://pubmed.ncbi.nlm.nih.gov/37092955/
In placental cells, THC & CBD may cause dysregulation of blood vessel formation
Impact of cannabidiol and delta-9-tetrahydrocannabinol in the angiogenic role of extravillous trophoblasts
https://publicacoes.cespu.pt/index.php/sl/article/view/87
In human adult testes tissue, acute exposure to THC & CBD did not impact testosterone or sperm cell production
The Acute Exposure of Human Adult Testis Tissue to Cannabinoids THC and CBD Does Not Impact Testosterone Production Nor Germ Cell Lineage
https://pubmed.ncbi.nlm.nih.gov/37118951/
The Skin
To treat acne, combining CBD, Indian pennywort & silymarin worked well in this array of preclinical & clinical findings
Development of an Effective Acne Treatment Based on CBD and Herbal Extracts: Preliminary In Vitro, Ex Vivo, and Clinical Evaluation
https://pubmed.ncbi.nlm.nih.gov/37101713/
The Guts & Metabolism
A review of the current science on cannabis hyperemesis syndrome
Cyclic Vomiting Syndrome and Cannabis Hyperemesis Syndrome: The State of the Science
https://pubmed.ncbi.nlm.nih.gov/37074964/
And another review on how to manage it
Cyclic Vomiting Syndrome, Dumping, and Marijuana-Induced Hyperemesis Syndrome
https://link.springer.com/chapter/10.1007/978-3-031-19671-3_45
The Heart
In rats, cannabis extract relaxed their arteries
Vasorelaxant Effect of Moroccan Cannabis sativa Threshing Residues on Rat Mesenteric Arterial Bed is Endothelium and Muscarinic Receptors Dependent
https://pubmed.ncbi.nlm.nih.gov/37123084/
The Lungs
A review of the diverse effects of cannabis on the mammalian respiratory system via the COX pathways
The Effects of Endogenous Cannabinoids on the Mammalian Respiratory System: A Scoping Review of Cyclooxygenase-Dependent Pathways
https://pubmed.ncbi.nlm.nih.gov/37074668/
A review of cannabis smoking causing lung hemorrhage
Diffuse alveolar hemorrhage in cannabis smokers. A systematic literature review
https://pubmed.ncbi.nlm.nih.gov/37087352/
Cancer & Chemotherapy
In colon cancer cells, CBD reshaped the tumor microenvironment to prevent tumor progression
Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer
https://www.sciencedirect.com/science/article/pii/S2095177923000746
In melanoma that has spread to the brain, activating the CB1 receptors inhibited their growth via glutamate
Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling
https://pubmed.ncbi.nlm.nih.gov/37173906/
In kidney cancer cells, CBD caused cell death but was also toxic to the non-tumor cells
Impact of cannabidiol on viability of normal and tumorigenic human kidney cells: are the effects serum-dependent?
https://publicacoes.cespu.pt/index.php/sl/article/view/29
A virtual screening of using cannabinoids against cancer via the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)
Repositioning Cannabinoids and Terpenes as Novel EGFR-TKIs Candidates for Targeted Therapy Against Cancer: A virtual screening model using CADD and biophysical simulations
https://pubmed.ncbi.nlm.nih.gov/37128337/
Cool Chemistry
How the RAMP & MRAP proteins (regulators of G-protein coupled receptors) alter the signaling of the cannabinoid receptors
RAMP and MRAP Accessory Proteins have Selective Effects on Expression and Signalling of the CB1, CB2, GPR18 and GPR55 Cannabinoid Receptors
https://pubmed.ncbi.nlm.nih.gov/37085333/
A deep dive on improving nano-CBD
Phytocannabinoids: Chromatographic Screening of Cannabinoids and Loading into Lipid Nanoparticles
https://pubmed.ncbi.nlm.nih.gov/36985847/
On how the cannabinoids bind allosterically to a glycine receptor
A millisecond coarse-grained simulation approach to decipher allosteric cannabinoid binding at the glycine receptor α1
https://www.biorxiv.org/content/10.1101/2023.04.19.537578v1
The phases of oleamide
Polymorphism of Cis-Unsaturated Fatty Acid Amide: Oleamide
https://pubs.acs.org/doi/abs/10.1021/acs.cgd.3c00020
On the current challenges of purifying & isolating cannabinoids
Purification and Isolation of Cannabinoids: Current Challenges and Perspectives
https://www.chromatographyonline.com/view/purification-and-isolation-of-cannabinoids-current-challenges-and-perspectives
On how to separate chiral phytocannabinoids
Enantioseparation of chiral phytocannabinoids in medicinal cannabis
https://pubmed.ncbi.nlm.nih.gov/36965450/
Just like you, me & elephants, molecules can be right or left-handed (or different in even more dimensions). Known as chirality, separating molecules of different handedness is extraordinarily tricky.
Thanks.
- lex
PS: This week’s album is 1976’s ‘Danger’ by the Lijadu Sisters, twin sisters from Nigeria whose musical style mixed jazz, afrobeat, reggae & waka (an Islamic oriented music of the Yoruba people). They became immensely popular in Nigeria in the ‘70s & traveled the world playing with a wide array of musicians.
Just a side note - the link to the article on cannabis allergies is broken :)
I have some criticism of this paper:
"A case study of cannabis use leading to a cardiac arrest
Marijuana as a Cause of Diffuse Coronary Vasospasm Leading to Cardiac Arrest
https://assets.cureus.com/uploads/case_report/pdf/64574/20230423-30312-u2fsrz.pdf"
"Marijuana is one of the most widely abused substances in the US. The effects of tetrahydrocannabinol (THC), the active ingredient in marijuana, have been well studied and reported substantially in the literature. When smoked, THC results in a rapid, dose-dependent tachycardia by 20-100%, an increase in blood pressure, and an increase in cardiac output by > 30%, leading to increased oxygen demand, which is augmented by the vasoconstriction from endothelial damage by smoking and activation of CB1 receptors by marijuana [3,4]..."
It's interesting to me that at least as far as the late1980s, marijuana was commonly found to produce a lowering of blood pressure, not an increase; and a tendency toward vasoldilation, not vasoconstriction. The physical effects of marijuana were commonly associated with dose-dependent symptoms like postural hypotension, not hypertension- much less hypertensive crisis or cardiac arrest. (Mild tachycardia was always generally acknowledged in the literature as a common physical effect of marijuana.)
I'm curious about when medical opinion began to shift on this, and what might have accounted for it.
In the case cited, the study reports the patient suffering from cardiac arrest as a 53-year old male with "a past medical history of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease (COPD)". Also, the report of the incident says that "the patient woke up with severe shortness of breath unresponsive to albuterol inhalers"- indicating that the onset of the first symptoms of the acute physical distress appeared on their awakening, not in the immediate aftermath of marijuana ingestion.
The conclusion of the case incident study goes on to conclude that "In patients with low to absent risk for cardiovascular events, particularly pediatric and young adult patients, presenting with symptoms of MI/cardiac arrest, substance-induced (marijuana) MI should be suspected"- which, while possibly a warranted recommendation, has nothing to do with the case that was presented as possibly due to cannabis use. To my reading, the only evidence of a connection was the test result that " UDS was positive for marijuana"- but urine tests are not a reliable indicator of most recent use; they only indicate some amount of ingestion within the previous 7-30 days.
The report goes on to state that " Synthetic cannabinoids such as K2 and Spice are a rapidly emerging class of substances, usually undetectable on conventional urine drug screens (UDS), and becoming more widely available [1,2]." However, the report provides no context for this observation. It's possible that it was prompted by patient report, but if that was the case, no statements to that effect were included in the report.
The incident report goes on to state that "the patient was discharged eight days after admission on aspirin, statin, and diltiazem with close follow-up with cardiology. He was counseled to quit marijuana. Due to no other plausible etiology, the diagnosis of marijuana causing severe global coronary vasospasm was entertained with the possibility of a synthetic component."
I'm not sure how the clinicans arrived at the conclusion that the cardiac arrest could have "no other pluaible etiology", given the pre-existing medical conditions of already cited, of hpertension, hyperlipidemia, and COPD, based only on the UDS result of THC metabolites, which are not probative for recent use. I'm also unsure of why the study authors repeatedly brought up the synthetic THC analogs known as K2 and Spice, along with mentioning their undetectability by UDS unless there was some direct relevance to the case at hand that wasn't cited. It's unquestionable that the synthetic analogs have more dramatic effects and a more serious hazard profile in comparison with natural THC. But the case in question refers only to "marijuana."
It's also worth noting that of the total of 13 references cited by the study, only three were published prior to 2004.
The abstract of one of the references (11) made no mention of THC, marijuana, or cannabinoids; it appears to be a more generalized study of myocardial infarction cases, and the findings cited in the abstract are equivocal.
Another reference, from 1973, was a study of seven test subjects given oral THC at two different dose levels. At the higher dosage level, six of the subjects showed increased heartbeat- tachycardia- a well-known side effect of marijuana. Two of them showed ST and T wave changes, hardly an uncommon finding-- https://www.uptodate.com/contents/ecg-tutorial-st-and-t-wave-changes#! . One of the test subjects was shown to exhibit "premature ventricular contractions"- also known as "skipped beats", or a "flutterby." Not an optimal finding, but also one that is not uncommon in the total population- particularly in coffee drinkers, I note. None of the observed changes found in the seven subjects are commonly viewed as extraordinary or cause for alarm, in and of themselves. The study made no mention of myocardial complications or hypertensive effects.
The third reference cited from the 1970s consists only of a single excerpted paragraph from an article in Clinical Toxicology published in 1979- the reprint of the introduction to a referring to a single case of "pulmnary edeoma and myocradial infarction" connected by the authors with cannabis use. The original citation was found, copied, and republished online in 2008.
All of the other references cited are from 2004-2019.
I don't want to dismiss the possibility of cardiac complications from THC and marijuana out of hand. If there are authentic grounds for concern, I want to know about them. The THC strength of cannabis has increased markedly over the past 25 years- well beyond the limits achievable under natural conditions of cultivation. If that phenomenon has led to an increased hazard profile, I want to know the details. I think the recent increases in THC levels to above 15% and the concomitant absence of CBD has led to an increase in undesirable side effects in some respects.
But as far as cardiac complications, despite all of the pages devoted to the possibility in recent years, almost all of the clinical evidence I've read consists of series-of-one cases- and every few of those, at that. Reference to possible confounding factors has typically been cursory, or absent entirely.
I'm all in favor of researching cannabis for both its possible harms and its therapeutic benefits. But on this particular issue, I'm unimpressed by the strength of the evidence I've reviewed. I remain exceedingly skeptical that cannabis has a potential for cardiovascular harm that approaches that of tobacco, or even high doses of caffeine.