C&P#45: CBD & THC for aging brains! + powerful case studies
C&P#45: CBD & THC for aging brains! + powerful case studies
Denver's first cannabis bus + California's cannabis terroirs
Hello everyone,
Welcome to the 45th 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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The Living Glossary of Cannabinoid Terms.
This week…
Vaped CBD & THC for aging brains!
Cannabis protective from COVID?
On songbirds taking cocaine & mice drinking alcohol
CBD for this cancer. CBD for that cancer. CBD for cancer cancer cancer.
Weed to grease the grinding gears of capitalism!
The neuromechanics of how psychedelics dissolve your ego + lots on ketamine & cocaine
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Best Of Cannabinoid Science...
Clinical
In MRI scans of aging brains, inhaling CBD caused increased network connectivity while inhaled THC appeared to be a helpful painkiller
Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study
https://pubmed.ncbi.nlm.nih.gov/36819730/
Cannabis for the elderly!
That’s what got me started on this cannabis quest & it’s what still motivates me. Check out my How-To Guides on the best methods for introducing cannabinoids to your aging relatives.
In a review of public health data on COVID, cannabis use was associated with “lower mortality rates, lesser need for mechanical ventilation, and reduced hospitalization expenses”
Cannabis Use and COVID-19 Hospitalization Outcomes. A Retrospective Study
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4336513
In a review of the UK medical cannabis registry, patients with headaches & migraines saw improvements via a number of measurements
UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders
https://pubmed.ncbi.nlm.nih.gov/36722292/
In a study of chronic pain patients in New York, medical cannabis use was associated with a reduction in opioid dosages
Changes in Prescribed Opioid Dosages Among Patients Receiving Medical Cannabis for Chronic Pain, New York State, 2017-2019
https://pubmed.ncbi.nlm.nih.gov/36716026/
According to UK public health data, lifetime heavy cannabis use was associated with a decreased blood pressure, with a higher effect for women, though the overall effects are probably too small to create a public health policy of getting high for your heart
Association between cannabis use and blood pressure levels according to comorbidities and socioeconomic status
https://pubmed.ncbi.nlm.nih.gov/36740601/
In a case study of a teenager with FIRES (a rare brain fever disorder causing epilepsy), a combination of vagal nerve stimulation & CBD caused a rapid return to consciousness as well as a reduction of seizures
Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?
https://pubmed.ncbi.nlm.nih.gov/36725381/
In a case report on complex dissociative PTSD, very positive effects from cannabis-assisted psychotherapy
Cannabis-assisted psychotherapy for complex dissociative posttraumatic stress disorder: A case report
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947284/
For PTSD, Jazz Pharmaceuticals (who bought GW Pharmaceuticals) enrolled their first patient in the clinical trial of their FAAH inhibitor JZP150
Jazz Pharmaceuticals Announces First Patient Enrolled in Phase 2 Clinical Trial Evaluating JZP150 for Once-Daily Treatment of Adults with Post-Traumatic Stress Disorder
https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-first-patient-enrolled-phase-2-2
For people using cannabis, the positive effects seem consistent across social contexts - but the negatives may vary more by the presence of others
Association between affect and cannabis use varies by social context
https://pubmed.ncbi.nlm.nih.gov/36634576/
Indeed, I learned in college that getting high plus being around non-high people usually did not combine well.
Reviews
In cancer care, a review of the drug-drug interactions of CBD
Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics
https://pubmed.ncbi.nlm.nih.gov/36769206
“In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs.”
For HIV neurocognitive disorder, a review of targeting the endocannabinoid system for the related neuroinflammation & hormonal imbalance
The Endocannabinoid System as a Potential Therapeutic Target for HIV-1-Associated Neurocognitive Disorder
https://pubmed.ncbi.nlm.nih.gov/36745405/
A review of the studies on CBD's effect on innate immunity
Effects of Cannabidiol on Innate Immunity: Experimental Evidence and Clinical Relevance
https://pubmed.ncbi.nlm.nih.gov/36834537/
“Despite the lack so far of clinical studies, extensive preclinical evidence in different models, including mice, rats, guinea pigs, and even ex vivo experiments on cells from human healthy subjects, shows that CBD exerts a wide range of inhibitory effects by decreasing cytokine production and tissue infiltration, and acting on a variety of other inflammation-related functions in several innate immune cells.”
A review of the antiviral effects of the cannabinoids
Cannabis as antivirals
https://pubmed.ncbi.nlm.nih.gov/36626776/
I have been beating on this drum for years. The microbial use of cannabinoids is one of its most underutilized features.
“Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication. Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.”
On delta-8 THC, a big review on the little we know
Delta-8 tetrahydrocannabinol: a scoping review and commentary
https://pubmed.ncbi.nlm.nih.gov/36710464/
A nice review of the tools we can use to modulate the endocannabinoid system
Understanding and Targeting the Endocannabinoid System with Activity-Based Protein Profiling
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijch.202200115
A review of the Nrf2 pathway which turns on or off over 2000 genes & seems to be a major target by which CBD does its work
The Complex Genetic and Epigenetic Regulation of the Nrf2 Pathways: A Review
https://www.mdpi.com/2076-3921/12/2/366
Preclinical
In a rat model of endometriosis, CBD caused significant anti-inflammatory & antioxidative effects
Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and anti-angiogenic effects in an experimental rat model
https://www.rbmojournal.com/article/S1472-6483(23)00056-1/fulltext
In a mouse model of neuropathic pain, CBD combined well with electric nerve stimulation of this skin to reduce pain, possibly via a spinal increase of the anti-inflammatory cytokine IL-10
Synergistic effect of cannabidiol and transcutaneous electrical nerve stimulation on neuropathic and inflammatory pain in mice
https://pubmed.ncbi.nlm.nih.gov/36719831/
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
Cannabis use among teens trending downward according to a CDC survey
https://www.marijuanamoment.net/teen-marijuana-use-trends-downward-as-more-states-legalize-it-for-adults-federal-survey-finds
The NY Times tells US officials to "reverse course" on the War on Drugs & to focus on public health
https://www.nytimes.com/2023/02/22/opinion/harm-reduction-public-health.html
These shitbirds. The NYTimes has a long dark, racist history of uncritically regurgitating War on Drugs propaganda. From their infamous “Negro Cocaine Fiends” article to their support of Reagan’s War on Drugs to the stupid shit I still see them publish every year, the NY Times has been a key player in creating public support for the tragedy that is the War on Drugs.
That being said, the NY Times is not a monolith. It’s a lens through which tens of thousands of journalists have published their work. Some of those articles are the most important in the history of psychoactive journalism – but under the paper’s management, the whole institution tends to be more of a lap dog than a guard dog.
In my EU segments for Weed Talk News on Pro Cannabis Media: the EU takes Hungary to the Court of Justice for defying them on cannabinoids
[open sponsorship slots for this segment: 10k+ subscribers]
In Italy, a court rules in favor of using the whole hemp plant, reversing a ban that restricted use to only seeds & fibers
https://cannabishealthnews.co.uk/2023/02/22/italy-court-rules-in-favour-of-using-the-whole-hemp-plant
A study of workers compensation payouts suggest that medical cannabis laws help with pain management & lead to increased worker capacity
Pain Management and Work Capacity: Evidence from Workers’ Compensation and Marijuana Legalization
https://onlinelibrary.wiley.com/doi/abs/10.1002/pam.22479
Weed to grease the grinding gears of capitalism!
State medical cannabis laws linked to an increased rate of stimulant prescriptions
Do medical marijuana laws increase prescription stimulant use?
https://www.medrxiv.org/content/medrxiv/early/2023/01/30/2023.01.29.23285169.full.pdf
Perhaps this study helps to explain the study above?
Or, as Steven Wright said, maybe it’s like having a humidifier & a dehumidifier in the same room & letting them fight it out…
On the terroir of cannabis & California’s innovations for regional cannabis appellations by Jackie Bryant
In France, terroir refers to the region in which something is grown or made. Like champagne or certain types of cheeses, there are strict controls on when you can label something as being of a certain product category & from a certain region. It's helped tremendously in preserving the quality of the original product & protecting the legacy producers. Now California, with its huge wine industry, is looking to do the same with cannabis.
The standards organization ASTM releases new guides on cannabis manufacturing
https://newsroom.astm.org/newsroom-articles/two-new-astm-international-standards-guide-cannabis-control-and-manufacture
Denver approves the country’s first cannabis consumption bus
https://cannabislaw.report/the-cannabis-experience-becomes-colorados-1st-marijuana-licensed-consumption-bus-denvers-1st-licensed-legal-marijuana-consumption-bus-and-the-nations-1st-licensed-mar
The War on Drugs & Prohibition
In a story that repeats every year or two, “Mexico’s ex-public security chief convicted in US drug case”
https://apnews.com/article/new-york-city-mexico-drug-cartels-a4536784e319b390a4d6e66a3ab044d8
The nature of drug enforcement is the same at any level. Whether it be a city’s antinarcotics unit or the DEA itself, the only way to know the dealers is to have a relationship with some of the distributors & protect them. This leads both to information about who to bust & the irresistible temptation to get into the game yourself. This pattern has repeated every generation since it began with the banning of alcohol by the Volstead Act in 1919. As I often mention, the researcher to read is Douglas Valentine. On Mexico specifically, Anabel Hernandez’s ‘Narcoland: The Mexican Drug Lords And Their Godfathers”.
In a driving study, a person's reported subjective experience of cannabis was relatable to their driving performance
Perceived effects of cannabis: Generalizability of changes in driving performance
https://pubmed.ncbi.nlm.nih.gov/36622373/
A review of the studies about the effects of cannabis on driving performance
Cannabis Effects on Driving Performance: Clinical Considerations
https://www.karger.com/Article/PDF/528714
Psychedelics, Plant Medicines & Other Psychoactives
Are psychedelics more addictive than we think?
Yes.
Ayahuasca Arrests on the Rise in Spain
https://www.lucid.news/ayahuasca-arrests-on-the-rise-in-spain
On buying drugs on the street in Portugal now that they decriminalized all drugs by James Gordon Curtis
https://tripsitter.com/legal/clandestine-drug-sales-after-decriminalization/
What Ever Happened to Mescaline?
https://slate.com/human-interest/2023/02/mescaline-peyote-san-pedro-cactus-psychedelic-drug.html
Psychoactive science
[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]
The big paper making the rounds lately is this one about how psychedelics promote neuroplasticity through the serotonin receptors
Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors
https://pubmed.ncbi.nlm.nih.gov/36795823/
And a nice breakdown of the research by the always dependable Andrew Gallimore
In our unsurprised department, personal psychedelic use common among psychedelic therapists
Personal Psychedelic Use Is Common Among a Sample of Psychedelic Therapists: Implications for Research and Practice
https://www.liebertpub.com/doi/abs/10.1089/psymed.2022.0004
The neuromechanics of how psychedelics dissolve your ego
Neural Mechanisms and Psychology of Psychedelic Ego Dissolution
https://pubmed.ncbi.nlm.nih.gov/36786290/
On using ketamine to treat cocaine use disorder
Repurposing ketamine to treat cocaine use disorder: integration of artificial intelligence-based prediction, expert evaluation, clinical corroboration and mechanism of action analyses
https://pubmed.ncbi.nlm.nih.gov/36792381/
And a pilot trial of using ketamine for borderline personality disorder
A pilot randomized controlled trial of ketamine in Borderline Personality Disorder
https://pubmed.ncbi.nlm.nih.gov/36804489/
A review on the potential of using cocaine in psychiatry
Systematic Review: Is There a Medicinal Use of Cocaine in Psychiatry?
https://link.springer.com/article/10.1007/s40501-023-00285-7
Don't laugh. It's just one more psychostimulant.
A new type of iboga alkaloids for use against opioid addiction
Novel Class of Psychedelic Iboga Alkaloids Disrupts Opioid Addiction State
https://www.biorxiv.org/content/10.1101/2021.07.22.453441v1
The physiological effects of MDMA & methylone (the best of the cathinones (often erroneously referred to as the bath salts))
Pharmacological effects of methylone and MDMA in humans
https://www.frontiersin.org/articles/10.3389/fphar.2023.1122861/full?ck_subscriber_id=1731493171
Business & Law
The giant patent battle over vape pens
https://www.bloomberg.com/news/newsletters/2023-02-27/vape-ip-center-of-attention-as-blinc-faces-off-against-chinese-competitor
The Plant & the History
Growing & Farming
A review on the agronomy of growing hemp
Hemp Agronomy: Current Advances, Questions, Challenges, and Opportunities
https://www.mdpi.com/2073-4395/13/2/475
A study of biological methods for treating plant rot
Biological control of Fusarium oxysporum causing damping-off and Pythium myriotylum causing root and crown rot on cannabis (Cannabis sativa L.) plants
https://www.tandfonline.com/doi/full/10.1080/07060661.2023.2172082
And the first report of a roundworm eating hemp roots in the US
First report of the root-lesion nematode, Pratylenchus penetrans, parasitizing hemp (Cannabis sativa) in the United States
https://apsjournals.apsnet.org/doi/abs/10.1094/PHP-12-22-0122-BR
To increase plant growth & cannabinoid accumulation, apply the signaling molecules salicylic acid, jasmonic acid or γ-aminobutyric acid (GABA)
Exogenous application of stress-related signaling molecules affect growth and cannabinoid accumulation in medical cannabis ( Cannabis sativa L.)
https://pubmed.ncbi.nlm.nih.gov/36605951/
In Wisconsin hemp, the effects of nitrogen & seeding rate
Cultivar and Management Effects on Industrial Hemp Yields in Wisconsin
https://acsess.onlinelibrary.wiley.com/doi/abs/10.1002/agj2.21297
An analysis of terpene levels throughout a grow facility
Indoor Monoterpene Emission Rates from Commercial Cannabis Cultivation Facilities in Colorado
https://pubmed.ncbi.nlm.nih.gov/36730104/
Apparently, applying cannabis leaf extract to your wheat or barley seeds will make them grow better
Allelopathic Effects of Cannabis sativa L. Aqueous Leaf Extracts on Seed Germination and Seedling Growth in Durum Wheat and Barley
https://www.mdpi.com/2073-4395/13/2/454
Hemp as a food
An Italian team came up with a sensory wheel & lexicon for describing hempseed oil
Sensory Wheel and Lexicon for the Description of Cold-Pressed Hemp Seed Oil
https://pubmed.ncbi.nlm.nih.gov/36766191/
A review of hemp as a high-value food
Hemp: A Sustainable Plant with High Industrial Value in Food Processing
https://pubmed.ncbi.nlm.nih.gov/36766179/
On the nutrition & antioxidant activity of hemp
Total Phenolic Content and Antioxidant Activity of In Vitro Digested Hemp-Based Products
https://pubmed.ncbi.nlm.nih.gov/36766131/
Industrial Uses
In a study of something long known, hemp is one of the best fibers you can use in ocean water (one of the most degrading & toughest environments for any rope)
Effect of ocean water absorption on flexural properties of Cannabis sativa L. hemp fibre reinforced polymer composites for marine applications
https://journals.sagepub.com/doi/abs/10.1177/09544062231152180
On using hemp to make slippery surfaces for food packaging or medical devices
Hemp-Based Sustainable Slippery Surfaces: Icephobic and Antithrombotic Properties
https://pubs.acs.org/doi/abs/10.1021/acssuschemeng.2c06233
Veterinarian Uses & Animal Feed
A popular science article on using CBD for dogs
https://cbdthinker.com/cbd-for-dogs
And cats
https://cbdthinker.com/cbd-for-cats
For a 3-year-old dog with intense jaw pain from a nerve sheath tumor, using CBD oil & gabapentin to relieve the pain
Cannabinoid oil with gabapentin for the treatment of chronic neuropathic pain – case repor
https://www.researchgate.net/publication/367537234_Cannabinoid_oil_with_gabapentin_for_the_treatment_of_chronic_neuropathic_pain_-_case_report
In calves being transported or weaned, CBD lowered their measures of stress hormones
EFFECTS OF CANN S OF CANNABINOID SUPPLEMEN ABINOID SUPPLEMENTATION ON WEANING TION ON WEANING AND TRANSPORTATION STRESS IN BEEF CALVES
https://digitalcommons.murraystate.edu/cgi/viewcontent.cgi?article=1312&context=etd
CANNABINOID SCIENCE
A profile of Dr. Martina Catani & her work separating chiral cannabinoids
https://www.chromatographyonline.com/view/rising-stars-of-separation-science-martina-catani
Chirality is another word for the ‘handedness’ of molecules. Just like you can't superimpose your left hand over your right, molecules can have a similar mirror image structure to them. This can dramatically alter what they do (such as in the thalidomide disaster) & it's especially difficult to separate them. But Dr. Catani is figuring it out…
Clinical Studies & Surveys
In patients with epilepsy & ADHD, a certain variant of the FAAH enzyme was linked to an increased risk of epilepsy
The study of rs324420 (C385A) polymorphism of the FAAH gene of the endocannabinoid system in patients with epilepsy and ADHD
https://www.sciencedirect.com/science/article/abs/pii/S0920121123000256
Ingestion, Bioavailability & Biochemical Effects
For cannabis allergies, a protein analysis shows that the allergens seem present across all cannabis types
Proteomics-based approach for detailing allergenic profile of cannabis chemotypes
https://www.jacionline.org/article/S0091-6749(22)01800-0/fulltext
Some of the synthetic cannabinoids may be monoamine oxidase inhibitors (MAOIs - an enzyme that removes serotonin, dopamine & norepinephrine from the brain) & this may underlie some of their toxicity
Synthetic cannabinoid receptor agonists are monoamine oxidase-A selective inhibitors
https://pubmed.ncbi.nlm.nih.gov/36708234/
Mental Health & Addiction
In schizophrenia, perhaps the activation of the endocannabinoid system is a reaction against the neuroinflammation of the disease
Activation of the endocannabinoid system in schizophrenia: A compensatory mechanism of subclinical inflammation?
https://pubmed.ncbi.nlm.nih.gov/36628871/
In college students with PTSD, depression or self-injury symptoms, cannabis use disorder seem to increase negative consequences
The influence of cannabis use disorder on post-traumatic stress disorder symptoms, depression symptoms, and non-suicidal self-injury among college students
https://pubmed.ncbi.nlm.nih.gov/36595655/
In a young songbird model of cocaine addiction, THC increased the time with cocaine while a drug that blocked the MAGL enzyme (& raised 2-AG levels) reduced their time with cocaine, probably via changes in brain development
Developmental treatments with Δ9- tetrahydrocannabinol and the MAGL inhibitor JZL184 persistently alter adult cocaine conditioning in contrasting ways
https://pubmed.ncbi.nlm.nih.gov/36740023/
In mice exposed to alcohol in adolescence, activating their CB2 receptors reduced their anxiety-like behaviors during withdrawal & suppressed inflammation in their prefrontal cortex microglia (guardian immune cells of the brain)
CB2R activation ameliorates late adolescent chronic alcohol exposure-induced anxiety-like behaviors during withdrawal by preventing morphological changes and suppressing NLRP3 inflammasome activation in prefrontal cortex microglia in mice
https://pubmed.ncbi.nlm.nih.gov/36754245/
In mice addicted to alcohol, the two endocannabinoid-like fatty acids N-Oleoyl Glycine & N-Oleoyl Alanine reduced their alcohol intake
N-Oleoyl Glycine and N-Oleoyl Alanine Attenuate Alcohol Self-Administration and Preference in Mice
https://assets.researchsquare.com/files/rs-2503793/v1/88484660189ab7bc6a2dca91.pdf?c=1675292844
In a rat model of PTSD, inhibiting the FAAH enzyme lowered their freezing time & showed anti-anxiety & antidepressant effects
Fatty acid amide hydrolase inhibitor URB597 suppressed conditioned and sensitized fear responses in a rat model of post-traumatic stress disorder
https://www.sciencedirect.com/science/article/abs/pii/S0023969023000036
In a rat model of anxiety & fear, inhibiting the MAGL enzyme to raise 2-AG levels did not cause any changes on extinction recall (lessening the response to the fearful trigger)
Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats
https://pubmed.ncbi.nlm.nih.gov/36588687/
The Brain & its Diseases
For children with cerebral palsy, a review of the 4 studies on the effects of cannabinoids
Efficacy and Safety of Medical Cannabinoids in Children with Cerebral Palsy: A Systematic Review
https://www.researchgate.net/publication/367463429_Efficacy_and_Safety_of_Medical_Cannabinoids_in_Children_with_Cerebral_Palsy_A_Systematic_Review
In a child with epilepsy, a rare case of CBD causing cannabinoid hyperemesis syndrome
A Rare Case of Cannabinoid Hyperemesis Syndrome Secondary to Cannabidiol for Refractory Epilepsy
https://journals.lww.com/jpgnr/Fulltext/2023/02000/A_Rare_Case_of_Cannabinoid_Hyperemesis_Syndrome.15.aspx?context=LatestArticles
Editorial on cannabinoids as a treatment for neurological diseases
Editorial: Cannabinoids as potential treatment for neurological diseases
https://pubmed.ncbi.nlm.nih.gov/36605545/
and on their usefulness for neuroinflammation, neurodegeneration & pain
Editorial: Cannabinoids in neuroinflammation, neurodegeneration and pain: Focus on non-neuronal cells
https://pubmed.ncbi.nlm.nih.gov/36605549/
In astrocytes (key brain support cells), CBD lowered damage in a model of neurodegeneration via several pathways
Effect of Cannabidiol in LPS-induced toxicity in astrocytes: Possible role for cannabinoid type-1 receptors
https://europepmc.org/article/ppr/ppr610649
In a mouse model of multiple sclerosis, CBD lowered the recruitment of white blood cells going to the spinal cord
Cannabidiol Attenuates In Vivo Leukocyte Recruitment to the Spinal Cord Microvasculature at Peak Disease of Experimental Autoimmune Encephalomyelitis
https://pubmed.ncbi.nlm.nih.gov/36745386/
In a mouse model of seizures, while PEA did not reduce the seizures, it did increase the effectiveness of the drug ganaxolone & reduced mortality
Investigating the synergistic effect of palmitoylethanolamide and ganaxolone in PTZ-induced tonic-clonic seizures
http://sjku.muk.ac.ir/browse.php?a_id=6998&sid=1&slc_lang=en
In a rat model of Down syndrome, a look at how their altered distribution of CB1 receptors changes their axonal (brain) wiring
Regional redistribution of CB1 cannabinoid receptors in human foetal brains with Down's syndrome and their functional modifications in Ts65Dn+/+ mice
https://pubmed.ncbi.nlm.nih.gov/36716771/
In brain immune cells, inactivating the MAGL enzyme & raising 2-AG levels upregulated their immune & inflammatory genes, likely contributing to anti-inflammatory & neuroprotective effects
Inhibition of 2-arachidonoylglycerol degradation enhances glial immunity by single-cell transcriptomic analysis
https://pubmed.ncbi.nlm.nih.gov/36717883/
In rat neurons, a look at the many enzymes that change the levels of 2-AG
Endocannabinoid 2-Arachidonoylglycerol Synthesis and Metabolism at Neuronal Nuclear Matrix Fractions Derived from Adult Rat Brain Cortex
https://www.mdpi.com/1422-0067/24/4/3165
Harms, Cannabis Use Disorder & Street Synthetics
A review of the potential problems associated with cannabis use
Review of systemic and syndromic complications of cannabis use: A review
https://pubmed.ncbi.nlm.nih.gov/36626471/
For unknown reasons, cannabis-related visits to the emergency room go up immediately before legalization
Increase in cannabis-related emergency department presentations in the period immediately before legalization requires explanation
https://pubmed.ncbi.nlm.nih.gov/36606761/
A case study of cannabinoid hyperemesis syndrome causing acute kidney injury + a review of the literature
A Case of Cannabinoid Hyperemesis Syndrome and Acute Kidney Injury: A Review of the Literature
https://assets.cureus.com/uploads/case_report/pdf/135836/20230129-31618-81i1ix.pdf
In a case study of cannabinoid hyperemesis syndrome, the patient experienced repeated severe burns from their compulsive use of hot baths to lower the vomiting
Recurrent Severe Burns Due to Cannabinoid Hyperemesis Syndrome
https://assets.cureus.com/uploads/case_report/pdf/133674/20230202-30774-mz6wq0.pdf
In rural Nepal, a case of undiagnosed cannabinoid hyperemesis syndrome
Case report: A case of undiagnosed cannabinoid hyperemesis syndrome in rural part of Nepal
https://pubmed.ncbi.nlm.nih.gov/36582911/
For several synthetic cannabinoids, it was found that while they tended to only activate the cannabinoid receptors, they blocked a number of other receptors such as oxytocin & histamine
Off-target pharmacological profiling of synthetic cannabinoid receptor agonists including AMB-FUBINACA, CUMYL-PINACA, PB-22, and XLR-11
https://pubmed.ncbi.nlm.nih.gov/36590635/
On a fluorescent fingerprinting system for detecting synthetic cannabinoid use via the saliva of patients
Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; toward Robust Point-of-Care Detection
https://pubmed.ncbi.nlm.nih.gov/36599091/
Characterization of the rare cannabinoids HHC (a hydrogenated analog of THC) & H 4 CBD (a synthetic hydrogenated CBD analog)
Synthesis and characterization of the diastereomers of HHC and H4CBD
https://europepmc.org/article/ppr/ppr612176
Hormones, Reproduction & Maternal Effects
In a review of 53 studies on pregnancy, cannabis use was associated with greater odds of preterm birth, low birth weight & increased mortality in the weeks immediately after birth, but the researchers are not confident in these findings
Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis
https://pubmed.ncbi.nlm.nih.gov/36730710/
In European nations with rising cannabis use, they saw higher levels of babies with facial anomalies such as cleft lip & cleft palate
Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies
https://pubmed.ncbi.nlm.nih.gov/36810431/
In data from a longitudinal study on prenatal cannabis exposure, the adolescents saw decreased visual processing ability & brain volumes
Effects of prenatal cannabis exposure on developmental trajectory of cognitive ability and brain volumes in the adolescent brain cognitive development (ABCD) study
https://pubmed.ncbi.nlm.nih.gov/36791556/
In a sample of pregnant women, prenatal cannabis use was linked to increased obesity in the children
Prenatal tobacco and cannabis co-exposure and offspring obesity development from birth to mid-childhood
https://pubmed.ncbi.nlm.nih.gov/36734672/
In pregnant rats using cannabis vapor, their babies had lower birth weights & the males would grow up to be less interested in cannabis vaping
Determining impacts of prenatal cannabis exposure on cannabis vapor self-administration using a novel response-contingent vapor model in pregnant rat dams
https://www.sciencedirect.com/science/article/pii/S2772392523000111
In rats exposed in utero to a drug that activates the CB1 receptor, they had a gendered response to their later breathing regulation
Sex- and age-specific respiratory alterations induced by prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 in rats
https://pubmed.ncbi.nlm.nih.gov/36710256/
Pain, Inflammation & Surgeries
In healthy humans, the respiratory depression caused by the opioid oxycodone was not increased by inhaling THC
Inhaled Δ9-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers
https://pubmed.ncbi.nlm.nih.gov/36725378/
From the American Society of Regional Anesthesia and Pain Medicine, their new guidelines on cannabis use around the time of an operation
ASRA Pain Medicine consensus guidelines on the management of the perioperative patient on cannabis and cannabinoids
https://pubmed.ncbi.nlm.nih.gov/36596580/
In public health data on surgeries, people diagnosed with cannabis use disorder had a greater utilization of healthcare after the procedure while people with non-medical cannabis use had lower odds of needing healthcare after the surgery
Prevalence and association of non-medical cannabis use with post-procedural healthcare utilisation in patients undergoing surgery or interventional procedures: a retrospective cohort study
https://pubmed.ncbi.nlm.nih.gov/36798752/
In people getting hip & knee replacement surgery, the use of cannabis was not linked to worse postoperative outcomes
Cannabis Use Among Lower-Extremity Arthroplasty Patients Does Not Lead to Worse Postoperative Outcomes
https://pubmed.ncbi.nlm.nih.gov/36582568/
For pain, a review of 65 trials covering 7000+ patience finds that cannabinoids reduced chronic pain & improved the quality of sleep, but overall, the researchers thought the harmful effects of cannabinoids outweighed the potential benefits
Cannabinoids versus placebo for pain: A systematic review with meta-analysis and Trial Sequential Analysis
https://pubmed.ncbi.nlm.nih.gov/36716312/
Another review of the use of cannabinoids for chronic pain
Cannabinoids and Their Role in Chronic Pain Treatment: Current Concepts and a Comprehensive Review
https://pubmed.ncbi.nlm.nih.gov/36628124/
In a mouse model of pain from stress, it appears that the endocannabinoid system uses the nitric oxide system as a second messenger for lessening pain signaling
The Endogenous Cannabinoid and the Nitricoxidergic Systems in the Modulation of Stress Responses
https://pubmed.ncbi.nlm.nih.gov/36769207/
Guts, Metabolism, the Microbiome & Oral Health
For patients with pain from irritable bowel syndrome, phase two trial results from the drug olorinab (an activator of the CB2 receptor) lowered pain only in the participants with moderate to severe pain at baseline
Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: Results from a phase 2b randomized placebo-controlled trial (CAPTIVATE)
https://pubmed.ncbi.nlm.nih.gov/36740814/
In a study of patients with mouth diseases, they had significant changes in their oral endocannabinoid levels, suggesting cannabinoids as a treatment
Involvement of the endocannabinoid system in current and recurrent periodontitis: A human study
https://pubmed.ncbi.nlm.nih.gov/36727611/
In an analysis of a public health survey, frequent cannabis use was associated with higher odds of a gastrointestinal illness
Cannabis use and gastrointestinal tract illnesses: The National Health and Nutrition Examination Surveys, 2005-2018
https://pubmed.ncbi.nlm.nih.gov/36734018/
In a model of human mouth diseases & dental implants, CBD & CBG helped with inflammation
The immunomodulatory role of phytocannabinoids in an in vitro peri-implantitis model
https://scholar.kyobobook.co.kr/article/detail/4050037055638
In a mouse model of inflammatory bowel disease, protein nanoparticles loaded with CBD lessened intestinal inflammation, probably via the CB2 receptor
P037 Enhancing the efficacy of cannabidiol using protein nanoparticles to treat inflammatory bowel disease
https://academic.oup.com/ecco-jcc/article/17/Supplement_1/i204/7009419
The Skin
A case report on cannabis for hyperhidrosis (excessive sweating) by the famed Dr. Franjo Grotenhermen
Case in Context: Hyperhidrosis
https://pubmed.ncbi.nlm.nih.gov/36595028/
On human keratinocytes (skin stem cells), CBG, CBC, THCV & CBDA all reduced inflammation via the reduction of proinflammatory cytokines, perhaps mediated by the TRPV1 receptor & the MAGL enzyme
Rare Phytocannabinoids Exert Anti-Inflammatory Effects on Human Keratinocytes via the Endocannabinoid System and MAPK Signaling Pathway
https://pubmed.ncbi.nlm.nih.gov/36769042/
CBD nano balls for application to the skin
Cannabidiol-Loaded Nanostructured Lipid Carriers (NLCs) for Dermal Delivery: Enhancement of Photostability, Cell Viability, and Anti-Inflammatory Activity
https://www.mdpi.com/1999-4923/15/2/537
The Liver
In male and female mice, cannabinoid treatment caused different changes to the lipids of their livers & blood
PLASMA AND LIVER LIPIDS ARE DIFFERENTIALLY REGULATED AFTER CANNABINOID TREATMENTS IN MALE AND FEMALE MICE
https://www.biorxiv.org/content/biorxiv/early/2023/02/02/2023.01.30.526249.full.pdf
In a mouse model of chronic liver disease, hemp seed oil reduced liver scarring & inflammation
Integration of transcriptomics and metabonomics revealed the protective effects of hemp seed oil against methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in mice
https://pubmed.ncbi.nlm.nih.gov/36734470/
The Lungs
A case study of a rare cannabis-induced lung injury from smoking blunts
Marijuana-Induced Lung Injury: A Case Report and a Review of the Literature
https://assets.cureus.com/uploads/case_report/pdf/136324/20230205-22135-16q4eru.pdf
The Heart & the Blood
A review of the effects of the cannabinoids on the microvasculature (the small blood vessels)
Cannabinoid effects in the microvasculature - CB, or not CB? That is the question! A mini-review
https://pubmed.ncbi.nlm.nih.gov/36591655/
In mice with low levels of the MGL enzyme, they had lower aggregation of their platelets & a reduced response to the activation of collagen, meaning a longer bleeding time & higher blood volume loss when cut
Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice
https://www.mdpi.com/1422-0067/24/4/3116
Cancer & Chemo
A survey of cancer patients indicates that most would be willing to try medical cannabis
Cannabis Prevalence and Patterns of Use in Cancer Patients Receiving Systemic Anticancer Treatment at Sunnybrook Odette Cancer Centre: A Prospective Survey Study
https://tspace.library.utoronto.ca/handle/1807/126545
A review of targeting the endocannabinoids for stopping glioblastomas (the most aggressive type of brain cancer)
Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation
https://pubmed.ncbi.nlm.nih.gov/36805391/
In prostate cancer cells, the many molecular tools used by CBD to destroy them
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
https://link.springer.com/article/10.1007/s43450-023-00360-3
In prostate cancer cells, CBD causes anti-tumor effects via alterations to the mitochondria (powerhouse of the cell)
Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer
https://pubmed.ncbi.nlm.nih.gov/36736415/
In lung cancer cells, inhaled CBD slows their growth & lowers the growth of new blood vessels
Inhalant cannabidiol impedes tumor growth through decreased tumor stemness and impaired angiogenic switch in NCI-H1437-induced human lung cancer model
https://pubmed.ncbi.nlm.nih.gov/36737540/
On the anti-cancer effects of CBN
Cannabinol inhibits cell growth and triggers cell cycle arrest and apoptosis in cancer cells
https://www.sciencedirect.com/science/article/abs/pii/S1878818123000282
In lung cancer cells, the terpene β-caryophyllene lowers cell proliferation via antioxidant effects
Antioxidant promotion and oxidative stress downregulation by β-caryophyllene oxide attenuate lung cancer A549 cell proliferation
https://assets.researchsquare.com/files/rs-2489411/v1/cf4e579a-fb09-49fe-81d1-ef6eb461a34b.pdf?c=1675205570
Cool Chemistry
A deep molecular dive on how the cannabinoids cause their antioxidant effects by destroying free radicals, with CBC & cannabifuran being the most potent
Insights on the antiradical capacity and mechanism of phytocannabinoids: H-abstraction and electron transfer processes in physiological media and the influence of the acid-base equilibrium
https://www.sciencedirect.com/science/article/abs/pii/S0031942223000249
Thanks.
- lex
PS: For this week’s album ‘Soar’, two maestros unite: from Senegal, Seckou Keita & his kora & from Wales, Catrin Finch & her harp. The symbol of this album is an osprey, the bird that migrates from west Africa to northern Europe every year. And yes, this wonderful album of strings soars.
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.
Endocannabinoids
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]
2-AG
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
[blue whale]
CB1
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]
CB2
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]
Palmitoylethanolamide (PEA)
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]
Oleamide (OEA)
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.
[whale cars]
Phytocannabinoids
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]
CBD (cannabidiol)
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]
CBG (cannabigerol)
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]
CBC (cannabichromene)
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 (cannabidivarin)
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]
Beta-caryophyllene (BCP)
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]
Pharmaceutical cannabinoids
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.
Nabilone (Cesamet®)
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.
Thanks for the link to our article! we recommended you on our substack. best wishes Jules