C&P#46: CBD for blood pressure & nerve pain + the CB2 receptor for everything
In the US, it's hard to be a medical cannabis patient
Buy my Queer cannabis history graphic novel!
Welcome to the 46th edition of Cannabinoids & the People. This newsletter collects all the new cannabinoid science each week. You can check out last week’s issue here & if you haven’t subscribed yet, please do.
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My educational video of the week: Treating female-specific problems with CBD, THC & PEA
Plus an answer to a follow-up question about cannabinoids & conception
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And as always, at the bottom is the album of the week &
The Living Glossary of Cannabinoid Terms.
CBD to reduce blood pressure
So much on cannabis & CBD for pain (have you ever heard of Charcot-Marie-Tooth Disease?)
CBG, PEA & CBD for protecting neurons & nerves
A dozen papers on why activating the CB2 receptor is a good thing for a variety of diseases
Cannabis use linked to more depression & sleep problems
CBD for killing cancer & a review of cannabis/cancer patents
Is prenatal THC linked to later problems? Yes
Lots of negative case studies on the synthetic cannabinoids
Cannabis oil for your cats & dogs
CBD for your horses & CBDA for your Amazonian parrots!
Nano nano nano cannabinoids
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Italy legalizes hemp, the Dutch begin their cannabis growing pilot trials & Malta talks to the banks
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Sponsor: PlusCBD’s unparalleled product selection
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3 very special formulations with other ingredients:
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Best Of Cannabinoid Science...
The excellent Dr. Dustin Sulak on using cannabis for anxiety & PTSD
Cannabis for Anxiety and PTSD
On THC & CBD for fibromyalgia by Nate Seltenrich
In patients with frontotemporal dementia, PEA & the flavonoid luteolin improved their functional impairment & their cortical brain wave oscillations
EFFECTS OF PALMITOYLETHANOLAMIDE COMBINED WITH LUTEOLINE ON HIGH FREQUENCY OSCILLATIONS AND GABAERGIC TRANSMISSION IN PATIENTS WITH FRONTOTEMPORAL DEMENTIA
In 54 patients with hypertension, five weeks of CBD reduced their blood pressure via the sympatho-chromaffin system (neuro/hormonal cells of the adrenal glands)
CBD supplementation reduces arterial blood pressure via modulation of the sympatho-chromaffin system: A substudy from the HYPER-H21-4 trial
In patients with mastocytosis (a painful overabundance of mast cells), CBD allowed a third of the patients to discontinue their other pain medicines
The Effectiveness and Safety of Pharmaceutical-Grade Cannabidiol in the Treatment of Mastocytosis-Associated Pain: A Pilot Study
In patients with Charcot-Marie-Tooth disease (a genetic disease of nerve damage in the arms and legs), nearly all of them reported that cannabis helped with their pain as well as lessening the use of opiates, sleep medications & anxiety/antidepressant medications
Patient Reported Outcomes Using Medical Cannabis for Managing Pain in Charcot-Marie-Tooth Disease
Three German pain centers pooled their data on chronic pain & found that cannabis-based medicines contributed “to a clinically relevant reduction in pain, sleep problems and muscle tension and can improve daily functioning”
Benefits and harms of cannabis-based medicines from the viewpoint of patients with chronic pain and their physicians : A cohort study in three pain centers of the German federal state Saarland
A case study of using cannabis assisted psychotherapy for complex PTSD
Cannabis-assisted psychotherapy for complex dissociative posttraumatic stress disorder: A case report
In patients with severe mental health issues, the frequency of their cannabis use was significantly linked to more violent behavior
Is There a Dose-Response Relationship Between Cannabis Use and Violence? A Longitudinal Study in Individuals with Severe Mental Disorders
Nobody wants to hear this, but like most entheogenic drugs, cannabis brings out what's already there. In people predisposed to violence or who want to use it for violence, cannabis enhances that feeling. We see this in rat studies from the 50s, in the use by the Sikhs & other people groups in warfare & in all the kids during the Reefer Madness campaign who smoked a joint before a fight because they were told it would give them berserker abilities.
For horses, using CBD to help stop them from crib-biting
The use of cannabidiol as a novel treatment for oral stereotypic behaviour (crib-biting) in a horse
For more on what crib-biting is, a clip of Tom Waits on Letterman that I’ve never forgotten in my entire life…
For migraines, this review of nine studies finds cannabis to cause a significant clinical reduction in their length & frequency
Efficacy and Safety of Medical Marijuana in Migraine Headache: A Systematic Review
For endometriosis & its pain, a paper on how we need to start seeing cannabis as a treatment
Cannabis for endometriosis-related pain and symptoms: It's high time that we see this as a legitimate treatment
A review on how the antioxidant effects of CBD probably underlie much of its benefit for many diseases
Cannabidiol: Bridge between Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance
For cancer, a review of using cannabinoids to change their epigenetics (the genes turned on & off)
Cannabinoids Transmogrify Cancer Metabolic Phenotype via Epigenetic Reprogramming and a Novel CBD Biased G Protein-Coupled Receptor Signaling Platform
And a review of how the cannabinoid receptors evolved into a target for the treatment of cancer
The evolution of cannabinoid receptors in cancer
In Alzheimer's disease, the ability of CBD to prevent the aging of the astrocytes (important immune/support cells of the brain) seems to be mediated by parkin (a protein used by the cell for recycling old components) as well as its ability to protect the mitochondria (powerhouse of the cell)
Parkin Mediates Cannabidiol Prevention of Amyloid-Beta-Induced Senescence in Human Astrocytes
In a brain tissue & mouse model of multiple sclerosis, CBG lowered inflammation, improved clinical scores & protected from brain cell loss
Therapeutic Potential of Phytocannabinoid Cannabigerol for Multiple Sclerosis: Modulation of Microglial Activation In Vitro and In Vivo
In a mouse model of cognitive decline & Alzheimer’s disease, PEA protected memory & lessened shrinking of the hippocampus (memory center of the brain)
Chronic administration of palmitoylethanolamide counteracts cognitive decline in Tg2576 Mice
In a mouse model of neuropathic pain from cancer chemotherapy, CBD balls sourced from human umbilical cord stem cells reduced pain levels as well as the dysfunction of their mitochondria (powerhouse of the cell)
Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
In a mouse model of nerve injury, a cannabis extract sped up muscle function recovery
Comparative evaluation of ethyl acetate and n-Hexane extracts of Cannabis sativa L. leaves for muscle function restoration after peripheral nerve lesion
The effects of CBD on GABAA receptors (a target of the benzodiazepines like Valium)
CBD specific action on GABAA receptor alpha subunits
For more, see my ProjectCBD article, Taking It Slow with GABA.
CBD & CBN have different effects on the membranes of cells
Cannabidiol and cannabinol have distinct effects on membrane structure
This speaks to the old debate in the cannabinoid science world of the ‘80s. Everyone wondered whether cannabis caused its effects by distinct cannabinoid receptors or whether the plant’s cannabinoids altered the entire structure of the cellular membranes & that's why they caused such a wide array of effects.
With the discovery of the cannabinoid receptors in the early 90s, Team Receptor thought they had won. But as is usually the case in science, when the question is either/or, the answer is yes/and.
Now, we learn more every year about how the very presence of cannabinoids alters the structure of the membrane, hence leading to a wide array of downstream effects.
How endocannabinoids regulate the potassium channels that underpin the excitability of cardiac, neuronal & immune cells
Endocannabinoid regulation of inward rectifier (Kir2.1) channels
In cells, activating the M3 muscarinic receptor (best known from the red-capped amanitas muscaria mushrooms) greatly increased the levels of the CB1 receptor via promotion of the CNR1 gene that codes for it
M3 Receptor Pathway Stimulates Rapid Transcription of the CB1 Receptor Activation through Calcium Signalling and the CNR1 Gene Promoter
In prostate cancer cells, a molecule from the cabbage family activates the CB2 receptor to cause cell death
The Plant Derived 3-3'-Diindolylmethane (DIM) Behaves as CB2 Receptor Agonist in Prostate Cancer Cellular Models
One more helpful plant ingredient that seems to help via the endocannabinoid system.
Luckily, it appears safe to give CBD & CBDA extracts to your Amazonian parrot
Twice-daily oral administration of a cannabidiol and cannabidiolic acid-rich hemp extract was well tolerated in orange-winged Amazon parrots (Amazona amazonica) and has a favorable pharmacokinetic profile
An evergreen note on reading restricted paper:
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.
3 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
Biden ends Black History Month with a speech touting his mass marijuana pardons - which have yet to release a single person from prison
The US Office of Personnel Management has asked the White House for changes to its hiring practices that would treat past cannabis use more leniently
A review with excellent charts showing what federal agencies are funding the cannabis research in the US
The cannabidiol and marijuana research expansion act: Promotion of scientific knowledge to prevent a national health crisis
No surprise. It’s mostly NIDA looking for harm…
An in-depth report on why the cannabis laws of the US make it so dreadfully difficult to be a patient
Even the Guardian is covering how US hemp is so tangled up in red tape
Why can't this be used as a livestock feed?
Almost every week I post positive science about how feeding hemp to farm animals helps them.
Las Vegas approves rules for cannabis consumption lounges
Solving one of the great problems of legalization: you can buy it, but where can you use it?
The status of a state's cannabis laws are not linked to its levels of utilization of healthcare for psychosis
State Cannabis Legalization and Psychosis-Related Health Care Utilization
And in a funny contrast, a paper complaining that most of these studies on cannabis & psychosis suffer from the biased views of the appraisers
Minimizing policy-biased appraisals of the evidence on cannabis and psychosis
“Blind spots? I don’t see any blind spots!”
In the UK, a majority of doctors report formal training on medical cannabis but few consider themselves sufficiently informed to make cannabis-related clinical recommendations
Hospice and Palliative Medicine Fellows’ Clinical Discussions, Perceived Knowledge, and Formal Training Regarding Medical Cannabis Use: A National Survey Study (TH108B)
While in Denmark, after four years of medical cannabis, a survey finds the doctors have little knowledge of it & an overall negative attitude about it
GPs' prescription patterns, experience, and attitudes towards medicinal cannabis-a nationwide survey at the early stage of the Danish test scheme
Ric Flair reportedly to be the spokesperson for a cannabis product that treats erectile dysfunction
Jackie Bryant of Cannabitch is launching a podcast! ‘The Plant Lady’ debuts next week…
Jackie is one of my favorite journalist in the space & I'm excited that she'll be starting an interview style podcast about cannabis.
The War on Drugs & Prohibition
In Jamaica, the terrible legacy of cannabis criminalization
Ganja and the Laws of Men: Cannabis Decriminalization and Social (In)Justice in Jamaica
In an analysis of EU laws, the lessening of penalties for cannabis use was usually linked to a small increase in use by adolescents
Deterrence effect of penalties upon adolescent cannabis use
For driving, more frequent cannabis users report less impairment & often do not wait at all after consumption before driving
Self-reported impacts of recreational and medicinal cannabis use on driving ability and amount of wait time before driving
I think two hours is a reasonable window to wait. That being said, it’s clear that for old-time stoners, they develop a tolerance to the psychomotor deficits experienced by newbies. And I’ve heard from plenty of patients that they’re better drivers after cannabis because they’re not as sick.
Liberalized cannabis laws are linked to a significant reduction in daytime driving fatalities involving alcohol
Marijuana laws and pedestrian fatalities in the United States
Psychedelics, Plant Medicines & Other Psychoactives
The great Shayla Love on psychedelic patents
‘Avoid Taking What Ayahuasca “Tells” You Literally’: good advice from ICEERS
‘From Opium To Meth: How Myanmar Became The World’s Leading Producer Of Methamphetamine’
Former MMA fighter Ian McCall tells how psychedelics helped him heal after experiencing traumatic brain injury
Andrew Gallimore on why LSD lasts so long…
On psychedelics & gender identity by Rowan Zeoli
[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]
A fascinating case study from the Amazon of using tobacco in a traditional manner for a woman's mental health
Indigenous-Amazonian Traditional Medicine's Usage of the Tobacco Plant: A Transdisciplinary Ethnopsychological Mixed-Methods Case Study
A review of using psilocybin for addiction
Therapeutic effect of psilocybin in addiction: A systematic review
In rats, how psilocybin enhances cognitive flexibility
Acute psilocybin enhances cognitive flexibility in rats
A review on ‘The costs and benefits of psychedelics on cognition and mood’
Business & Law
In California, having a dispensary within two miles of your house increases the likelihood of your cannabis use & reduces your risk perception of cannabis
Associations of recreational cannabis dispensaries' availability, storefront signage and health benefit signs with cannabis use: findings from a representative adult sample in California, United States
The Plant & the History
Characterizing the cannabis roots of northeastern Brazil
Phytochemical Characterization of Cannabis sativa L. Roots from Northeastern Brazil
Growing & Farming
For cannabis micropropagation, an analysis of growth medium & culture vessels
A Comparison of Two Media Formulations and Two Vented Culture Vessels for Shoot Multiplication and Rooting of Hemp Shoot Tip Cultures
In water stress conditions, the fungi around the cannabis roots helps with their efficiency of light & water consumption
Radiation and Water Use Efficiencies of Mycorrhizal Inoculated Hemp Under Water-Deficit Stress
Distinguishing high cannabinoid strains of cannabis using microsatellites (repeated genetic sequences that can be used as tags)
Evidence of the Ability of Microsatellite Method to Distinguish Cannabis Strains with High Cannabinoid Content
Finding bacteria to breakdown the hard outer hemp hurds
ISOLATION AND SCREENING OF INDIGENOUS MICROORGANISMS CAPABLE OF DEGRADING CELLULOSE TO TREAT HEMP HURD IN THANH HOA PROVINCE
On using ozone treatments to breakdown your hemp
Simultaneous Eco-friendly Bleaching and Retting Wastewater Treatment of Hemp Fiber with Ozone Application
A genetic analysis of the response to cold by cannabis & its DGAT (diacylglycerol acyltransferase) enzymes
Genome-Wide Identification, Classification, and Expression Analyses of the CsDGAT Gene Family in Cannabis sativa L. and Their Response to Cold Treatment
Hemp as a food
In female rats, hempseed oil improved their fatty acid profile & overall health
Hemp Seed Oil Effects on Female Rats Fed a High-Fat Diet and Modulating Adiponectin, Leptin, and Lipid Profile
A study of the composition & nutritional value of hemp proteins
Hemp bioactive peptides: Nutrition, functional properties and action mechanisms to maximize their nutraceutical applications and future prospects
“It is concluded that HPs [hemp proteins] present excellent functional ingredients as nutraceuticals targeting hypertension and other degenerative diseases, which have yet to be capitalized upon for commercial uses.”
On using CBD to keep your pomegranate juice from degrading
Effects of thermal processing on cannabidiol degradation in cannabidiol-infused pomegranate juice and evaluation of its antioxidant property
There's a whole robust field of research on using the cannabinoids as food preservatives.
The size of your hemp flour particles changes the quality of your hemp pasta
Hemp Flour Particle Size Affects the Quality and Nutritional Profile of the Enriched Functional Pasta
In hempseeds, an analysis of the protein levels from seven different hemp cultivars (strains)
Composition and functional properties of hemp seed protein isolates from various hemp cultivars
A data set of cannabis seeds for machine learning
Dataset of cannabis seeds for machine learning applications
Veterinarian Uses & Animal Feed
A review of using CBD for the diseases of your dogs & cats
Scientific Validation of Cannabidiol for Management of Dog and Cat Diseases
“In companion animals, CBD appears to have good bioavailability and safety profile with few side effects at physiological doses. Some dog studies have found CBD to improve clinical signs associated with osteoarthritis, pruritus, and epilepsy. However, further studies are needed to conclude a therapeutic action of CBD for each of these conditions, as well as for decreasing anxiety and aggression in dogs and cats.”
On using cannabis oil against fleas on your pets
Insecticidal activity of essential oil of Cannabis sativa against the immature and adult stages of Ctenocephalides felis felis
Producing nanocrystals from hemp waste
Cellulose Nanocrystals Derived From Hemp Agrowaste: A Value-Added Biomass Product for Sustainable Hemp Farms
On using hemp waste to make furniture upholstery
Recycling of Nonwoven Waste Resulting from the Manufacturing Process of Hemp Fiber-Reinforced Recycled Polypropylene Composites for Upholstered Furniture Products
A review of 22 studies on looking at the social media discourse around cannabis as a medicine
Social media discourse and internet search queries on cannabis as a medicine: A systematic scoping review
I never seem to learn much from these, but researchers sure do love scraping Twitter & Reddit to find out that a lot of people are into cannabis.
Clinical Studies & Surveys
For older adults, a review of 133 studies finds mixed results (though it feels like these researchers were looking for harms)
Impacts of medical and non-medical cannabis on the health of older adults: Findings from a scoping review of the literature
In university students, cannabis users had a 45% increased chance of insomnia as well as other sleep complaints
Study of the association between cannabis use and sleep disturbances in a large sample of University students
In 24 adults & adolescents, they had similar mental effects from cannabis & the vaporization of CBD did not mitigate these effects
The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double-blind, placebo-controlled, crossover experiment
Brain scans of cannabis users & their visuospatial processing
Altered functional connectivity and oscillatory dynamics in polysubstance and cannabis only users during visuospatial processing
A scale for linking the molecules present in a cannabis chemovar (strain) & the experiential effects
Systematic combinations of major cannabinoid and terpene contents in Cannabis flower and patient outcomes: a proof-of-concept assessment of the Vigil Index of Cannabis Chemovars
A survey of patients on how they liked using the UK Medical Cannabis Registry (a key source of data that we're often quoting around here)
UK Medical Cannabis Registry: A Patient Evaluation
Using 4 mobile video games to crowdsource data on the effects of cannabis on cognition & psychomotor skills
Data crowdsourcing on psychomotor and cognitive effects of cannabis via mobile app
On using machine learning & data from the Strainprint app to see if mental health profiles & baseline symptom severity play a role in the perceived responses to cannabis
Predictors of perceived symptom change with acute cannabis use for mental health conditions in a naturalistic sample: A machine learning approach
“The factors that were most strongly associated with perceived symptom change following acute cannabis use were pre-symptom severity, age, gender, and the ratio of CBD to THC. Further examination on the impact of baseline severity for the most commonly reported symptoms revealed distinct responses, with cannabis being reported to more likely benefit individuals with lower pre-symptom severity for depression, and higher pre-symptom severity for insomnia. Responses to cannabis use also differed between genders.”
Ingestion, Bioavailability & Biochemical Effects
More & more young adults in the US are smoking cannabis out of hookahs
High on Hookah: Smoking Marijuana from a Hookah among Adults in the United States, Population Assessment of Tobacco and Health Study, 2015-2019
The stability of THC
Short-term stability of a small amount of neat Δ9-tetrahydrocannabinol
A safety study of CBD & CBG in rats
Safety Assessment and Redox Status in Rats after Chronic Exposure to Cannabidiol and Cannabigerol
A review of using nanotechnology to increase the bioavailability of cannabinoids
Nanoformulations as a strategy to overcome the delivery limitations of cannabinoids
And an update on these nano delivery systems
An update of nano-based drug delivery systems for cannabinoids: Biopharmaceutical aspects & therapeutic applications
Note: when we say nano in this context, it’s more of an industry buzzword for making lipid balls out of the cannabinoids. It’s not nano in the Richard Feynman / 100 nanometers / direct manipulation of atoms kind of way.
Mental Health & Addiction
In a review of Canadian public health data, medical cannabis use was associated with an increased risk of depressive disorders
Risk of depressive disorders associated with medical cannabis authorization: A propensity score matched cohort study
In California adolescents, mixed support for cannabis use being linked to depression
Directional associations between cannabis use and depression from late adolescence to young adulthood: the role of adverse childhood experiences
In adolescent rats exposed to THC, individual differences in their dopamine transmission may lead to different outcomes in their likelihood of developing schizophrenia-type symptoms
The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology
In a mouse model of depression, a stable variant of CBDA caused antidepressant effects but with differences between the genders
Cannabinoid Receptor 2 Blockade Prevents Anti-Depressive-like Effect of Cannabidiol Acid Methyl Ester in Female WKY Rats
In a mouse model of food addiction, the overexpression of the CB2 receptor made them more vulnerable to chocolate pellet addiction
Role of CB2 cannabinoid receptor in the development of food addiction in male mice
The Brain & its Diseases
An editorial on targeting the endocannabinoid system for neurodegenerative disorders
Editorial: Targeting the endocannabinoidome in neurodegenerative disorders
In rats, chronic administration of THC changed their brain’s glucose uptake & improved their ability to not act impulsively
Chronic Administration of Δ9-Tetrahydrocannabinol Alters Brain Glucose Uptake and Improves Waiting Impulsivity in the Rat
In a study of mice versus young mice, chronic THC administration causes different effects on their synaptic plasticity, especially in the ventral tegmental area (linked to rewards & addiction) via dopamine & GABA, suggesting a reason that adult mice are less likely to become dependent on THC
Chronic Δ9-tetrahydrocannabinol impact on plasticity, and differential activation requirement for CB1-dependent long-term depression in ventral tegmental area GABA neurons in adult versus young mice
In a mouse model of neuropathic pain from cutting a nerve, activating the CB1 receptor lowered pain via glutamate & GABA
Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation
In a zebrafish model of epilepsy, CBD combined well with CBN, CBC, THC & CBG to reduce seizures, partially via the GPR55 receptor (which may one day be known as CB3)
CBD can be combined with additional cannabinoids for optimal seizure reduction and requires GPR55 for its anticonvulsant effects
Harms, Cannabis Use Disorder & Street Synthetics
In Canada, they experience an average of ~80 cannabis pediatric hospitalizations per year
Pediatric Hospitalizations for Unintentional Cannabis Poisonings and All-Cause Poisonings Associated With Edible Cannabis Product Legalization and Sales in Canada
In adolescents with cannabis use disorder, a chapter on using cognitive behavioral therapy
Cognitive behavioral therapy for cannabis use disorder: A focus on adolescents
2 brothers fatally poisoned by a combination of alcohol with a synthetic cannabinoid
Simultaneous fatal poisoning of two victims with 4F-MDMB-BINACA and ethanol
Four case studies of children exposed to delta-8 THC
Delta-8-Tetrahydrocannabinol Exposure and Confirmation in Four Pediatric Patients
And a case report of a new synthetic cannabinoid poisoning in a child
Methyl (S)-2-(1-7 (5-fluoropentyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMB-PICA) intoxication in a child with identification of two new metabolites (ultra-high-performance liquid chromatography-tandem mass spectrometry)
In the Netherlands, two case reports of synthetic cannabinoid intoxication
Intoxications with synthetic cannabinoids
A toxicology study on the common cannabinoid WIN55, 212-2
Behavioral, biochemical and histopathological toxic profiles induced by sub-chronic cannabimimetic WIN55, 212-2 administration in mice
In mice, the synthetic cannabinoid JWH-018 caused heart & respiratory problems
The Old and the New: Cardiovascular and Respiratory Alterations Induced by Acute JWH-018 Administration Compared to Δ9-THC-A Preclinical Study in Mice
On the interactions between the synthetic cannabinoid AMB-FUBINACA & a piperazine analog
The piperazine analogue para-fluorophenylpiperazine alters timing of the physiological effects of the synthetic cannabinoid receptor agonist AMB-FUBINACA, without changing its discriminative stimulus, signalling effects, or metabolism
In rats, the effects of the synthetic cannabinoid ‘Strox’ (I’ve never heard of this one. Seems to be a regional name around Egypt)
Cytotoxicity associated with acute and chronic administration of synthetic cannabinoids “Strox” in the brain, liver, heart, and testes of male albino rats: histological and immunohistochemical study
The Immune System & Pathogens
In the B cells of the immune system, a mixture of cannabinoids cause detrimental effects to inflammatory cytokine levels, the membrane of the mitochondria (powerhouse cell) as well as increased cellular suicide
Cannabinoid Mixture Affects the Fate and Functions of B Cells through the Modulation of the Caspase and MAP Kinase Pathways
Hormones, Reproduction & Maternal Effects
On how to discuss cannabis consumption with pregnant people experiencing extreme vomiting (hyperemesis gravidarum)
Addressing cannabis consumption among patients with hyperemesis gravidarum
A poster review of using cannabis to treat postpartum depression
Using Medical Marijuana to Treat Postpartum Depression: A Scoping Review
A review of public health data in Europe links higher levels of cannabis use to more congenital anomalies in infants
Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study
And a big review from these two researchers who have been putting out these reports about why Camden oils may be causing this genotoxicity & cancerogenesis
Clinical Epigenomic Explanation of the Epidemiology of Cannabinoid Genotoxicity Manifesting as Transgenerational Teratogenesis, Cancerogenesis and Aging Acceleration
A review on how prenatal exposure to THC & its ability to predispose the male offspring to schizophrenia can be reversed by pregnenolone (a neurosteroid)
Sex-specific susceptibility to psychotic-like states provoked by prenatal THC exposure: Reversal by pregnenolone
In rats with prenatal exposure to THC, as adolescents, they had deficits in spatial & object recognition memory, increased locomotor activity & changes in the neuroplasticity of their hippocampus (memory center of the brain)
Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity
In the placenta, the distribution of PEA, AEA & other endocannabinoid-like fatty acids
Distribution of an analgesic palmitoylethanolamide and other N-acylethanolamines in human placental membranes
In rats with ovarian damage, increasing their 2AG levels decreased inflammation & cell death as well as preserving the eggs in their ovaries
2-Arachidonoylglycerol Activity in Over Ischemia Reperfusion Damage: Can Endocannabinoids Protect Ovarian Reserve?
Pain, Inflammation & Surgeries
In patients having shoulder surgery, cannabis use disorder was not linked to medical complications or heart events
Cannabis Use Disorder is not a Risk Factor for Thrombotic Events or Medical Complications Following Total Shoulder Arthroplasty
In chronic pain patients, their mental health status was not a predictor of whether cannabis pain treatments would be helpful
Mental disorders are no predictors to determine the duration of cannabis-based treatment for chronic pain
In French patients with arthritis, a look at their frequency of cannabis use
Frequency of cannabis use in patients with rheumatoid arthritis or spondyloarthropathies: a single-centre study
Just kidding. There is no look. This paper doesn't even have an abstract available.
And it’s a 4 hour drive away, so I’m not going there to ask.
In adolescent rats undergoing morphine withdrawal, activating their CB1 receptor change their brain glucose levels, with a greater effect on females
Neuroimaging revealed long-lasting glucose metabolism changes to morphine withdrawal in rats pretreated with the cannabinoid agonist CP-55,940 during periadolescence
Guts, Metabolism, the Microbiome & Oral Health
In human pancreas cells, a drug that binds to the CB1 receptor & blocks other molecules from binding there (an inverse agonist) protected the pancreatic immune cells & increased insulin secretions, suggesting it as a potential therapeutic for both type 1 & type 2 diabetes
A peripherally restricted cannabinoid-1 receptor inverse agonist promotes insulin secretion and protects from cytokine toxicity in human pancreatic islets
For the bacteria that causes cavities, a combination of CBD & the antibiotic triclosan disrupted their formation of biofilms & caused an antibacterial effect
Improved Anti-Biofilm Effect against the Oral Cariogenic Streptococcus mutans by Combined Triclosan/CBD Treatment
The Musculoskeletal System
In a severe genetic muscular dystrophy, activating the CB2 receptor lowered inflammation by the inhibition of proinflammatory cytokines & caused the macrophages (immune cells) to be in a more anti-inflammatory state
CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy
The Genitourinary System
In a tissue study of pelvic pain of the bladder, a mixture of PEA, hempseed oil & maritime pine bark extract reduced inflammatory cytokines
Micronized Palmitoylethanolamide, Hempseed Oil, and Maritime Pine Bark Dry Extract (Pelvipea®) for Pelvic Pain: An In Vitro Study for Urothelial Inflammation Treatment
A look at how CBD nanoparticles penetrate the skin & help with topical inflammation
The Fundamental Role of Lipids in Polymeric Nanoparticles: Dermal Delivery and Anti-Inflammatory Activity of Cannabidiol
In a mouse model of liver failure, activating the CB2 receptor reduced the level of white blood cells & inhibited the release of inflammatory factors
CB2R agonist GW405833 alleviates acute liver failure in mice via inhibiting HIF-1α-mediated reprogramming of glycometabolism and macrophage proliferation
16 international cases of e-cigarette or vaping-associated lung injury (EVALI)
E-cigarette or vaping-associated lung injury (EVALI): a review of international case reports from outside the United States of America
In a mouse model of septic lung injury, there was a correlation between the level of inflammation & the amount of CB2 mRNA, suggesting the CB2 receptor as a target for regulating inflammation
Correlation analysis between the expression of cannabinoid 2 receptor and the related indicators of pyroptosis in sepsis
The Heart & the Blood
A review of the promise & the perils of cannabinoids for heart health
How do phytocannabinoids affect cardiovascular health? An update on the most common cardiovascular diseases
In heart cells, the effects of the endocannabinoid N-arachidonoyl serine (ARA-S) on the QT interval
The endocannabinoid ARA-S displays variably activating effects on Kv7.1/KCNE1 carrying long QT syndrome mutations
Cancer & Chemo
A review of cannabis patents for cancer treatments
A Descriptive Review of Cannabis sativa Patents for Cancer Treatment
In cancer patients with pain from mucositis (inflamed gums – a common side effect of radiation therapy), cannabis oil lowered their pain intensity as well as improved their chewing, swallowing, speech & quality of life
THE ROLE AND THE FUNCTION OF CANNABIS OIL (KANOIL) IN THE TREATMENT OF PAIN IN ORAL MUCOSITIS
A review of the mechanisms CBD uses to cause its anti-cancer effects
Cancer Signaling Pathway and Anti-Cancer Mechanism of Cannabidiol
On the anti-cancer effects of CBD-rich extracts against neuroblastomas (cancer of immature nerve cells)
Characterization of the Antitumor Potential of Extracts of Cannabis sativa Strains with High CBD Content in Human Neuroblastoma
In prostate cancer cells, CBD helped to degrade their proteins, stop the recycling of their cellular material & arrest their cell cycle
Cannabidiol Negatively Regulates Androgenic Signal in Prostate Cancer Cells and Fine-Tunes the Tumorigenesis by Modulating Endoplasmic Reticulum-Associated Degradation, Unfolded Protein Response, and Autophagy
In colon cancer of mice & humans, activating the CB2 receptor caused anti-tumor effects
The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans
In non-small cell lung cancer, activating the CB2 receptor helps the tumor by limiting the antitumor activity of certain immune cells
Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells
On using fungi to produce cannabinoids
Biotechnological Fungal Platforms for the Production of Biosynthetic Cannabinoids
As always, this works... but it doesn't scale.
In intriguing enzyme news, using the berberine bridge enzyme from yeast to turn CBGA to CBE (cannabielsoin)
Cannabinoid Biosynthesis Using Noncanonical Cannabinoid Synthases
A nuclear analysis of how CBC is broken up by liver enzymes into three different metabolites
Regioselective metabolism of cannabinoids by cytochrome P450 2J2
A deep dive on a fatty acid binding protein (FABP7, known to be a transporter of endocannabinoids)
A combined computational-biophysical approach to understanding fatty acid binding to FABP7
Using virtual screening to find new CB2 drugs
Identification of Novel CB2 Ligands through Virtual Screening and In Vitro Evaluation
Exploring the free energy landscape of the CB1 receptor
Delineating the conformational landscape of cannabinoid receptor 1 (CB1R) using gaussian accelerated molecular dynamics and network analysis
PS: For today’s magic music from Senegal, the album ‘Djam Leelii (The Adventurers)’ by the two guitarists (& friends) Baaba Maal & Mansour Seck.
The Living Glossary of Cannabinoid Terms
This is a running glossary of the basic cannabinoid terms. It will also function as the legend for the ‘neural ocean’ metaphor that I’m using in my graphic novel series on the endocannabinoid system based on Moby-Dick. You can watch a lecture laying out the full idea here - but the basics are that we treat the human brain like the ocean: deep, mysterious & chockablock with fish, molecules & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land?) and neurons are complex underwater cities where hundreds of fish interact.
The cannabinoids found inside all mammals & almost every other form of life besides insects
The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”
Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]
The second endocannabinoid receptor discovered. Found in almost every organ of the body & closely connected to our immune system. The CB2 occurs at low levels in the brain where it responds to neural insults.
[a gay bar in the membrane wall of the neuronal city]
FAAH (fatty acid amide hydrolase)
The enzyme that breaks down anandamide & a frequent target of drug discovery for modulating the endocannabinoid system. If you inhibit the FAAH enzyme, it does less breaking down of AEA, and your AEA levels rise. More balance.
[the giant squid that slices sperm whales in half]
Diacylglycerol lipase (DAGL or DGL)
The enzyme responsible for producing 2-AG.
MGL (monoacylglycerol lipase - also sometimes abbreviated as MAGL)
The enzyme that breaks down 2-AG. Another frequent target of drug discovery because inhibiting MGL raises 2-AG levels
[a giant octopus that eats blue whales]
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]
NAAA (N-acylethanolamine acid amidase)
The enzyme for breaking down PEA, with a special function as a messenger for pain & inflammation as well as in the control of obesity.
[a giant Giant Pacific octopus that eats Right whales]
An endocannabinoid related to sleep. They discovered it by keeping cats awake for 3 days & then analyzing their spinal fluid. You can buy it on Amazon. 2 scoops helps you to sleep while 6 scoops is a very pleasant psychoactive experience (Hamilton Morris has called it his favorite way to get high - which is saying something). It’s also worth considering for cancer treatment.
[Humpback whale, because it sings hippies to sleep]
Oleoylethanolamide (unfortunately, also abbreviated as OEA sometimes)
An analog of anandamide, this lipid acts via the peroxisome proliferator-activated receptor alpha (PPAR-α) receptors on the cell’s nucleus. These alter genetic transcription, a powerful method of cellular control. In animal models, oleoylethanolamide causes them to eat less food & drink less alcohol. In roundworms, it causes them to live longer. For the orphaned GPR119 receptor (a receptor that might one day be officially designated as a cannabinoid receptor), it may be the native ligand (the thing that binds to it). It’s already identified as the native ligand for hypoxia-inducible factor 3α (HIF-3α). OEA also interacts with our histamines.
[Pygmy sperm whale. Not well known, a smaller cousin to the sperm whale]
Fatty acid-binding proteins (FABPs)
These transport proteins move fatty lipids such as the endocannabinoids around the body. While still mysterious, they’re thought to move anandamide between membranes as well as transporting it to be broken down by the enzyme FAAH. Several types of FABPs exist in humans. THC & CBD bind to some of them. This may explain why endocannabinoid levels tend to increase after consuming cannabinoids. As the brain ages, the levels of FABPs decrease.
The cannabinoids produced by the cannabis plant.
THC (delta-9-tetrahydrocannabinol or Δ9-THC)
The well-known & well-studied molecule in cannabis that gets you high - and helps in a number of other fascinating ways.
[African elephant. Powerful, unpredictable, beautiful]
The cousin of THC that does not get you high but does a lot of the heavy lifting in why hemp has been such a staple of medicine since before recorded history. In most plants outside those bred for the recreational market, CBD is the most common cannabinoid. It binds to a wide swathe of receptors outside the endocannabinoid system including three serotonin receptors, two opioid receptors, a dopamine receptor as well as glutamate & GABA (the two most widespread neurotransmitters, the basic neuronal signals for excitation & inhibition, respectively)
[Indian elephant. sweet, gentle, you can work with it]
Known as the “mother cannabinoid”, CBG is the chemical precursor to THC, CBD, and the other cannabinoids in the plant. CBG occurs only at low levels in cannabis because it tends to be quickly converted to other cannabinoids. Binding slightly to the CB1 and CB2 receptor, it also inhibits the enzymes that break down anandamide and 2-AG, hence raising the levels of those endocannabinoids. CBG interacts with an adrenaline receptor (α-2 adrenoceptor) & a serotonin receptor (5-HT1A Receptor) as well as modulating the expression of glutamate, GABA, and dopamine via the PPAR receptors on the nucleus, controllers of genetic transcription. CBG is also active at the TRP channels involved in the sensations of temperature, pressure, pH, smell, taste, vision, and pain perception whose dysfunction are linked to neuropathic pain, inflammation, and respiratory disorders.
Surveys show patients reporting help for anxiety, chronic pain, depression, and disturbed sleep. In preclinical trials, it's been studied for eye pressure, gut problems, appetite modulation, blood pressure lowering, bladder control, oral care, muscle spasms, airway inflammation, arthritis, painkilling, and most notably for brain health and neuroinflammation. In adult neural stem cells, CBG increased their viability. The breakdown products of CBG have been shown to reduce inflammation via the brain’s immune cells.
[since it’s the first cannabinoid produced, it must be the wooly mammoth]
The third most common cannabinoid in the plant, it’s not well studied in humans despite a number of intriguing preclinical studies, especially as an anti-inflammatory and for pain. Nonpsychoactive, it interferes with the breakdown of AEA & 2-AG (leading to a rise in their levels) as well as interacting with the vanilloid receptors.
[Sri Lankan elephant. Little, sweet, not as well known as it should be]
CBDV is like CBD with a shortened tail (side chain). Also nonpsychoactive, it tends to occur at low levels in most cannabis cultivars. It’s known to be an anticonvulsant & is suggested for treating autism in humans & in animal models. The cannabinoid pharmaceutical company GW has it in their developmental pipeline as GWP42006.
[An Asian elephant with a short trunk]
(Easter egg: the first person to email me about this easter egg will get a free copy of my Queer book once I get it printed & up on Amazon soon…)
Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]
A terpene that’s also a cannabinoid.
The terpenes of cannabis give the plant its smell. Also found in oregano, black pepper, lavender & hops, beta-caryophyllene has a spicy sweet woody smell. But unique among terpenes, this one also binds to the CB2 receptor, making it a dietary cannabinoid. It shows a potential for treating inflammation, pain, anxiety & seizures. The FDA has designated it to be GRAS (generally regarded as safe) & thus it can be safely used as a food additive.
[a terpene/cannabinoid that travels through the air? That could only be a flying elephant]
Nabiximols (ie Sativex®)
A pharmaceutical 1:1 CBD:THC spray produced by GW Pharmaceuticals. One of the first cannabinoid pharmaceuticals on the market, Sativex is an approved treatment for neuropathic pain, spasticity, overactive bladder & the symptoms of multiple sclerosis.
Epidiolex® (in the UK, Epidyolex®)
An isolated CBD formulation approved for treating the severe seizures of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. Produced by GW Pharmaceuticals, the doses tend to be incredibly high – hundreds or thousands of milligrams of CBD every day in young children. But even with that, the side effects tend to only be lethargy & stomach upset.
Dronabinol (ie Marinol® and Syndros®)
A synthetic form of THC for the treatment of anorexia in AIDS patients & the nausea of chemotherapy. These tend to not be popular with patients because it’s a horse dose of THC with no modulation by the other molecules in the cannabis plant like CBD.
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.