C&P#44: my first book republished! + CBD for the skin, the brain, the honeybees & the aging horses
C&P#44: my first book republished! + CBD for the skin, the brain, the honeybees & the aging horses
Senate on cannabis for bets + DEA on the THC acetates + CA on interstate commerce
Hello everyone,
The good news is that the reason I missed last week’s newsletter was because it was my 40th birthday &, after a surprise visit from a number of friends, I was kidnapped to Amsterdam by a best friend for a few days.
And in even better news, in a moment of remarkable bibliosynchronicity, my first cannabis graphic novel was republished & arrived on the day of my 40th birthday. Called ‘SUNset’, it’s about the AIDS crisis, Reagan’s War on Drugs & the birth of the modern medical marijuana movement by the heroic Queers of San Francisco.
For my birthday, you can buy it here.
(leaving reviews & spreading the word are much appreciated)
Or to check the book out for free, the PDFs of all 3 of my cannabinoid graphic novels are here.
Welcome to the 44th 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.
Paid subscriptions here. If you become a paid subscriber, there’s no extra content, but your support allows me to produce more cannabinoid science content for the community.
Enjoy this free offering from my company White Whale Creations.
I produce educational content for cannabis & psychedelic companies: writing, science archives, social media content, newsletters & podcasts.
My portfolio
Book me for a 1-on-1 cannabis/CBD/psychedelics counseling session:
Join the many other patients, Grandmas & doctors who booked a session with me to get clear, simple guidance for using cannabis, CBD & psychedelics for a healthier & happier life. Read my free How-To Guides & book a session here.
My educational video of the week: Autism & CBD, THC & PEA
Also, every weekday on my YouTube Shorts, I post a new 1-minute video on a piece of cannabis research or answers to your questions.
#AskMeAnything
In my last 2 EU segments for Weed Talk News on Pro Cannabis Media:
Greece opens first cannabis plant + Norway’s first-ever medical cannabis meeting
Germany plans slow & Basel begins adult use trials
[sponsorship slots open: 10k+ subscribers]
And as always, at the bottom is the album of the week &
The Living Glossary of Cannabinoid Terms.
This week…
A lot of research on cannabinoids for epilepsy & neurodegenerative diseases
Indoor plants vs outdoor plants: “sun kissed” plants have more unusual cannabinoids & more delicate terpenes
On why CBD is so good for the skin
Newsflash: the hotter you find someone, the more likely you’ll smoke with them
CBD for elderly horses! (again) CBD for honeybees! (again)
For brain nerds: astrocytes, gliotransmission & the CB1 receptor
Striking study of how much water is used by the illegal grows of California
Hemp for the hangman’s nooses
China pioneers drug sniffing squirrels
A request to spread the word
This newsletter only spreads by word of mouth – so please forward to colleagues & tell your friends & relatives.
Alternative ways to support:
Buy Me a Coffee
Venmo: @Lex-Pelger
Zelle: pelger@gmail.com
PayPal: donate here
My work & platforms:
YouTube for educational videos, lectures & daily shorts on new cannabinoid science
My podcasts (seeking a sponsor for the next season of ‘The Lex Files’)
Anandamide; or, the People: my graphic novel series on cannabis, the endocannabinoid system & the War on Drugs based on Moby-Dick
LinkedIn, Twitter & my TikTok
Sponsor: PlusCBD & a commitment to education & research
One sign of a great CBD company is when they go to the next level for educating their customers. PlusCBD has articles for all levels of knowledge, videos about how CBD works & a YouTube channel of great educational content.
(Plus, they even sponsored two seasons of my podcast ‘The Lex Files’)
In addition, they’ve done more peer-reviewed research than any other company other there. They put their money down to advance the field.
Check out this (partial) bibliography:
A GRAS (Generally Recognized as Safe) study on hemp extracts to prove their safety
A clinical trial on healthy people to show that hemp extracts helped their cholesterol, sleep quality, stress response & perceived life pleasure
A post-marketing safety study where experts went over 2 years of PlusCBD’s adverse event reports to find the high safety levels
A case series of using CBD to treat PTSD
And funding me to create the extensive cannabinoid science archive at CVResearch.info
PlusCBD takes their commitment to education & research to the next level. And they do the same with their products.
Buy excellent CBD products today from PlusCBDoil.com.
Best Of Cannabinoid Science...
From the historian/scientist Dr. John McPartland & the leading researcher Dr. Saoirse E O'Sullivan, an interdisciplinary study of the history of cannabis in Ireland
Origins of Cannabis sativa in Ireland and the Concept of Celtic Hemp: An Interdisciplinary Review
https://pubmed.ncbi.nlm.nih.gov/36695660/
Clinical
Excellent writeup on CBD & sleep by Gleb Oleinik
https://cbdthinker.com/cbd-for-sleep
You can also read or watch my How-To Guide here.
In a study of smoking indica versus sativa, they found indica to cause more couch-lock (“low arousal”). Plus, the plants with more of the terpene caryophyllene were better at controlling pain
An Ecological Examination of Indica Versus Sativa and Primary Terpenes on the Subjective Effects of Smoked Cannabis: A Preliminary Investigation
https://pubmed.ncbi.nlm.nih.gov/36648357/
In a long-term study, cannabis use does not appear to be related to lung function even after years of use (unless you're smoking tobacco with it)
Do tobacco and cannabis use and co-use predict lung function: A longitudinal study
https://pubmed.ncbi.nlm.nih.gov/36682602/
A study of how different CBD formulations get delivered to the various regions of the brain
Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain
https://pubmed.ncbi.nlm.nih.gov/36720447/
“The highest CBD delivery was observed in the olfactory bulb and striatum, and the medulla pons and cerebellum the lowest. The lipid-free vehicle led to the highest levels of CBD in the whole brain. However, when each anatomical region was assessed individually, the long chain triglyceride-rich rapeseed oil formulation commonly showed optimal performance. The medium chain triglyceride-rich coconut oil formulation did not result in the highest CBD concentration in any brain region.”
In this study of surgery patients, they found no differences in vital signs or anesthetic requirements between those who use cannabis & those who did not
Is Recreational Marijuana Use Associated With Changes in the Vital Signs or Anesthetic Requirements During Intravenous Sedation?
https://pubmed.ncbi.nlm.nih.gov/36746375/
Interviews with formerly incarcerated gay Black men find that they consider cannabis to be their safest option as well as it fulfilling social & emotional needs
“I feel like marijuana is the only drug that wouldn’t kill me”: perceptions of cannabis use in previously incarcerated Black men who have sex with other men
https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-023-00744-7
An occupational therapy take on how people relate cannabis use to their occupation
Revealing the Meaning of Cannabis Use as an Occupation: A Scoping Review
https://pubmed.ncbi.nlm.nih.gov/36685720/
For me, I simply decided to make this plant my entire identity. #easypeasy
On delta-8 THC, a review of the FDA data on adverse events includes dyspnea (labored breathing), respiratory disorder & seizures
Delta-8, a Cannabis-Derived Tetrahydrocannabinol Isomer: Evaluating Case Report Data in the Food and Drug Administration Adverse Event Reporting System (FAERS) Database
https://pubmed.ncbi.nlm.nih.gov/36742440/
A strange study on how the attractiveness of an opposite-gender person alters how likely you are to smoke pot with them
Social influence and the likelihood of using cannabis: Role of source physical attractiveness
https://psycnet.apa.org/record/2023-37121-001
“The likelihood of participating in both drug and nondrug activities increased as a function of the relative physical attractiveness of the other individual (i.e., the source); however, notable gender differences were observed in the likelihood of using cannabis. Women were less likely to use cannabis in the presence of less attractive men relative to using cannabis alone, whereas men were more likely to use cannabis in the presence of more attractive women than using cannabis alone. These data suggest the presence of an opposite-gender person can either inhibit or facilitate drug use depending on the physical attractiveness of the source and gender of the subject.”
In elderly horses, CBD reduced their production of inflammatory cytokines with no negative side effects
The effects of cannabidiol on immune function and health parameters in senior horses
https://www.sciencedirect.com/science/article/abs/pii/S016524272300003X
Reviews
A review of using cannabinoids for neuroinflammatory disorders like MS, Parkinson’s & Alzheimer’s
Cannabinoids in neuroinflammatory disorders: Focusing on multiple sclerosis, Parkinsons, and Alzheimers diseases
https://pubmed.ncbi.nlm.nih.gov/36637897/
And a review of using CBD for brain diseases
Cannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration
https://pubmed.ncbi.nlm.nih.gov/36635488/
If you know anyone with a neurodegenerative disease, they should be experimenting with cannabinoids. See my How-To Guide here.
In patients with brain tumors, a review of using CBD oil & cannabis
Therapeutic and Supportive Effects of Cannabinoids in Patients with Brain Tumors (CBD Oil and Cannabis)
https://pubmed.ncbi.nlm.nih.gov/36633803/
“While the literature on this matter is young, published and anecdotal evidence imply that cannabis could be useful in treating chemotherapy-induced nausea and vomiting, stimulating appetite, reducing pain, and managing seizures. It may also decrease inflammation and cancer cell proliferation and survival, resulting in a benefit in overall patient survival. Current literature poses the challenge that it does not provide standardized guidance on dosing for the above potential indications and cannabis use is dominated by recreational purposes.”
The scientific literature may not have the answers on dosing for cancer, but the practitioners do. I always recommend Aunt Zelda’s (Mara Gordon) out of California for the best treatments I know using cannabinoids for cancer. But the main answer is, use a lot.
I believe I might make an educational video about this soon if you would be interested.
A review of using the cannabinoids for pain, especially CBD
Beyond Pain Relief: A Review on Cannabidiol Potential in Medical Therapies
https://www.mdpi.com/1424-8247/16/2/155
See my How-To Guide on pain.
A review of the widespread antioxidant effects of CBD & THC as well as the many diseases this relates to
Cannabinoids in the Modulation of Oxidative Signaling
https://pubmed.ncbi.nlm.nih.gov/36768835/
And in this study on honey bees, CBD supports their health by activating their antioxidant system
Cannabidiol (CBD) Supports the Honeybee Worker Organism by Activating the Antioxidant System
https://www.mdpi.com/2076-3921/12/2/279
A review of exercise & the endocannabinoid system with a focus on the runner’s high
The Endocannabinoid System and Physical Exercise
https://pubmed.ncbi.nlm.nih.gov/36768332/
“A runner's high is an ephemeral feeling some sport practitioners experience during endurance activities, such as running. The release of eCBs during sustained physical exercise appears to be involved in triggering this phenomenon. The last decades have been characterized by an increased interest in this emotional state induced by exercise, as it is believed to alleviate pain, induce mild sedation, increase euphoric levels, and have anxiolytic effects.”
A review of how cannabis alters learning, consolidation & memory retrieval
Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review
https://pubmed.ncbi.nlm.nih.gov/36671547/
In general, the thing to note is that while THC may not be good for your short-term memory (you won’t remember as much of that move if you watch it stoned), overall, enhancing your endocannabinoid signaling helps to protect the brain.
And in this related study in mice, we look at how the CB1 receptor works with GABA (the brain's primary inhibitory neurotransmitter) in the hippocampus (memory center) to cause long-term potentiation (a strengthening of the connection between neurons involved in memory)
Underlying mechanisms of long-term potentiation during the inhibition of the cannabinoid CB1 and GABAB receptors in the dentate gyrus of hippocampus
https://pubmed.ncbi.nlm.nih.gov/36635629/
A review of why the cannabinoids are worth trying for psoriasis & other autoimmune skin disorders (a nice chart of CBD’s many effects)
Phytocannabinoids in the Pharmacotherapy of Psoriasis
https://pubmed.ncbi.nlm.nih.gov/36770858/
On the possibility of using CBD for sickle cell anemia
Is CBD ready for prime time in sickle cell disease?
https://ashpublications.org/blood/article/141/2/132/494014/Is-CBD-ready-for-prime-time-in-sickle-cell-disease
A review of 40 studies on cannabis & sleep found exactly what you'd expect: mixed results
Cannabis and sleep disorders: not ready for prime time? A qualitative scoping review
https://pubmed.ncbi.nlm.nih.gov/36692176/
As you can see in my How-to guide, cannabinoids affect everybody's sleep differently. To know whether it will help you, the only thing you can do is give it a try.
Plus, here’s a clinical trial on the effects on sleep from various formulations of CBD, CBN, CBC & melatonin
The safety and relative effectiveness of non-psychoactive cannabinoid formulations for the improvement of sleep: a double-blinded, randomized controlled trial
https://www.medrxiv.org/content/medrxiv/early/2023/01/23/2023.01.20.23284842.full.pdf
A solid review on the biochemical & biological basics of the endocannabinoid system (nice charts)
Endocannabinoid System: Chemical Characteristics and Biological Activity
https://www.mdpi.com/1424-8247/16/2/148
Preclinical
In a mouse model of fetal alcohol syndrome, CBD helped with their emotional & cognitive disturbances
Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
https://pubmed.ncbi.nlm.nih.gov/36642113/
In a rat model of depression, CBD modulates changes in the prefrontal cortex to the microRNAs (cellular control machinery of protein production) & that this help for depression is mediated by a serotonin receptor
Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression
https://pubmed.ncbi.nlm.nih.gov/36768376/
On the skin, CBD & CBG kill harmful microbials while sparing the skin’s microbiome
Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota
https://pubmed.ncbi.nlm.nih.gov/36768709/
And in skin stem cells, a look at the pathways CBD uses to enhance the skin barrier & reduce oxidative stress
Cannabidiol mediates epidermal terminal differentiation and redox homeostasis through aryl hydrocarbon receptor (AhR)-dependent signaling
https://pubmed.ncbi.nlm.nih.gov/36725458/
On how CBD regulates the calcium channels that underlie the mechanism of pain
Differential regulation of Cav 3.2 and Cav 2.2 calcium channels by CB1 receptors and cannabidiol
https://pubmed.ncbi.nlm.nih.gov/36647671/
I mostly want to highlight this paper because if you don't know about Sonic Hedgehog signaling, you should know about Sonic Hedgehog signaling
The endocannabinoid system's involvement in motor development relies on cannabinoid receptors, TRP channels, and Sonic Hedgehog signaling
https://pubmed.ncbi.nlm.nih.gov/36636759/
One of the hardest problems in biology is how organisms develop from single-cell into the complexity of something like a mammal or a fish. And any student who's had developmental biology remembers that there is a signaling pathway called Sonic Hedgehog. In biology, genes & pathways often get their name from what the organism looks like when it gets screwed up. So if you disable Sonic Hedgehog, you get something that looks like a hedgehog (not a good thing).
We've known for quite awhile that the endocannabinoid system is intimately involved in the processes of development. Now this paper shows that it does so partially via our friend the Sonic Hedgehog pathway.
Magnolia seeds contain compounds that bind to the cannabinoid receptors
In Vitro and In Silico Studies of Neolignans from Magnolia grandiflora L. Seeds against Human Cannabinoids and Opioid Receptors
https://pubmed.ncbi.nlm.nih.gov/36770918/
Another medicinal plant whose effects might just be mediated by the endocannabinoid system.
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
A Senate committee approves a cannabis research bill for the PTSD & pain of military vets. And sadly, this is the first time ever that a standalone cannabis bill passed a Senate panel
https://www.marijuanamoment.net/u-s-senate-committee-approves-bipartisan-marijuana-research-bill-focused-on-military-veterans-with-ptsd-and-pain
California pushing forward on the interstate commerce of cannabis
https://cannabislaw.report/interstate-cannabis-commerce-on-the-horizon-thanks-to-california
https://www.bloomberg.com/news/newsletters/2023-02-13/california-pot-laws-in-2023-may-allow-interstate-commerce
The DEA declared that it considers delta-8 THCO & delta-9 THCO (two rare cannabinoids used for psychoactive purposes, sometimes called the acetates) to be illegal controlled substances even when synthesized from legal hemp plants
https://www.marijuanamoment.net/dea-classifies-novel-cannabinoids-delta-8-and-9-thco-as-controlled-substances-even-when-synthesized-from-legal-hemp
And comments from the lawyer Rod Knight who pushed the DEA to declare their official position
https://cannabusiness.law/thco-is-a-schedule-1-controlled-substance-says-dea
Yes, Twitter took the step of allowing brands to talk about CBD, THC & cannabis – but despite all the cheering, they’re still not allowing anyone to run ads for cannabis-related products
https://www.marijuanamoment.net/twitters-new-marijuana-advertising-policy-still-doesnt-allow-ads-for-marijuana-product-sales
This much-touted announcement basically just legitimizes the status quo of brands being able to talk about cannabis on Twitter – but not treat it like another product that they can sell.
A public health analysis of states with legalized cannabis finds a 10% increase in motor vehicle deaths, no change in suicides & an 11% reduction in opioid overdose deaths
The impact of recreational cannabis markets on motor vehicle accident, suicide, and opioid overdose fatalities
https://pubmed.ncbi.nlm.nih.gov/36764087/
That all sounds about right to me.
A federal judge struck down a ban on gun possession by cannabis users
https://www.marijuanamoment.net/federal-court-strikes-down-gun-ban-for-people-who-use-marijuana-calling-governments-justification-concerning
Oh man. Colorado rolls out the first cannabis vending machine
https://www.marijuanamoment.net/colorado-governor-promotes-states-first-ever-marijuana-vending-machine
‘Has GW Pharmaceuticals – Now Jazz Pharmaceuticals – Knee-Capped The CBD Industry?’ by Peter McCusker
https://www.cannabisbusinessexecutive.com/2023/02/has-gw-pharmaceuticals-now-jazz-pharmaceuticals-knee-capped-the-cbd-industry
New York’s influx of counterfeit cannabis
https://www.bloomberg.com/news/newsletters/2023-02-06/fake-vapes-counterfeit-cannabis-products-threaten-new-york-legal-weed
A roundup of the social consumption situation across North America
In May, Amsterdam’s red light district will ban cannabis use on the street & tighten the availability of alcohol to improve liveability for the residents
https://www.bbc.com/news/world-europe-64591394
As someone who visited this weekend, I can report that the use of cannabis on the street was noticeable but not overwhelming.
But I might have a different opinion if I lived there.
Norway hosts first ever meeting on considering the idea of medical cannabis
https://cannabislaw.report/norway-hosts-first-public-meeting-on-medical-cannabis-amid-early-first-steps-towards-potential-reform
The Land of the Vikings may be more scared of ye olde cannabis plant than any other country in Europe.
The trans/weed/12 steps joke of the week:
Hattip to Kat Villaverde.
And to help solve it, hrt = hormone replacement therapy
The War on Drugs & Prohibition
In an excellent statement from the head of NIDA, Dr. Nora Volkow, “Pregnant people with substance use disorders need treatment, not criminalization”
https://www.statnews.com/2023/02/08/addiction-pregnancy-treatment-not-criminalization
Dr. Volkow has been a refreshing breath of humanity at the federal agency charged with studying drug addiction. Also, as we will forever note, she is the granddaughter of Trotsky.
A paper on the limits of social justice & equity provisions in cannabis laws
Bounded Equity: The Limits of Economic Models of Social Justice in Cannabis Legislation”
https://journals.sagepub.com/doi/abs/10.1177/00914509221147133
Unfortunately, this one is behind a paywall but I e-mailed the author.
Drug decriminalization endorsed by the historically prohibitionistic American Society of Addiction Medicine
https://www.marijuanamoment.net/top-addiction-doctors-group-backs-drug-decriminalization-and-expungements-in-another-departure-from-prohibitionist-roots
They referenced the "structural racism and stigma that are entrenched in U.S. drug policy."
Early release for Luke Scarmazzo who had a 21-year sentence for running a state-legal medical cannabis dispensary
https://www.marijuanamoment.net/federal-judge-releases-man-who-served-14-years-over-california-medical-marijuana-dispensary-in-light-of-evolving-policy-landscape
On legalizing cocaine to save the Amazon
https://www.talkingdrugs.org/legalise-cocaine-to-save-the-amazon
In Nigeria, a man given 18 months of hard labor for cannabis possession
https://wakeandbakedaily.com/nigeria-man-jailed-18-month-with-hard-labour-over-possession-of-cannabis
In Paris, right-wing protests temporarily closed a harm-reduction drug consumption room
https://www.talkingdrugs.org/right-wing-protest-%E2%80%9Ccloses%E2%80%9D-parisian-drug-consumption-room
Look at these bunch of shitheads. France is as infested with fascist cockroaches as the US.
Hong Kong makes its first CBD arrest
https://cannabislaw.report/hong-kong-makes-first-cbd-arrest-based-on-danish-parcel
China is training drug-sniffing squirrels
https://cannabislaw.report/chinese-police-enlist-drug-sniffing-squirrels
A new podcast on the War on Drugs by Americans for Prosperity begins with two excellent guests: Johan Hari & Erik Sterling
https://americansforprosperity.org/lessons-from-the-war-on-drugs
Psychedelics, Plant Medicines & Other Psychoactives
The always excellent Don Latin interviews a Christian pastor on the mystical use of psychedelics
https://www.lucid.news/psychedelics-mystics-path-to-mystery
And an article on the rise of psychedelic churches in the US
https://apnews.com/article/psychedelic-churches-ayahuasca-5101fe47fe9a6e28de686272ed96ff46
On military veterans using psychedelic therapy
https://www.lucid.news/vets-psychedelic-therapy-research-outside-clinic
A thread on the shadow side of psychedelic history from conversion therapy to Wasson to OneTaste
‘Living with Hallucinogen Persisting Perception Disorder (HPPD)’ – a disorder where the psychedelic experience does not end
On psychedelics & dreams by Kat Lubiano
https://tripsitter.com/psychedelics/dreams
On mescaline as the understudied psychedelic for mental health by Katie McBride
https://www.inverse.com/health/mescaline-psychedelic-mental-health
Amongst psychonauts, mescaline is often seen as the most enjoyable & welcoming of the classic psychedelics. It’s less likely to send you into the tailspins possible from LSD, psilocybin or DMT.
For the best visual depiction, see Homer Simpson’s experience with his chili-induced hallucination & the Space Coyote.
On the pharmacology of the ‘mad honey of Nepal’ & its effects on sodium channels by Andrew Gallimore
He’s just one of my favorite science communicators.
And here’s his piece on kambo: the warrior frog medicine of the Amazon
I’ve done this once & it’s one of the most intense yet rewarding experiences of my life.
A nice review of iboga by Julia Blum
A chart of the current psychedelic industry
Psychedelic science
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a newsletter with all the new psychedelic science would be of interest to your org, reach out to me]
No association found between lifetime psychedelic use & being absent from work
Recruitment discrimination of lifetime classic psychedelic users is unjustified: Evidence from employees' motivation-based workplace absenteeism
https://akjournals.com/view/journals/2054/6/3/article-p203.xml
I find these results to be slightly disappointing.
#takethedayoffandeatsomemushrooms
#saysthepapawhoalmostnevertakesadayofftoeatmushrooms
A review of 33 papers on the toxicity of the classic psychedelics & related psychoactives
Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines
https://www.mdpi.com/2305-6304/11/2/148
“Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.”
The play in the title is based on the classic maxim of our alchemical hero Paracelsus: Sola dosis facit venenum – “The dose makes the poison”
In 24 healthy volunteers, a millidose of LSD (50 μg) changed their language production in a variety of ways
LSD and language: Decreased structural connectivity, increased semantic similarity, changed vocabulary in healthy individuals
https://pubmed.ncbi.nlm.nih.gov/36669231/
“LSD, compared to placebo, changed language structure, including decreased verbosity, lexicon, global and local connectivity (+1.5 h to +4 h); decreased semantic distances between neighbouring words and overall words (+2 h to +24 h); and changed vocabulary related to grammar, persons, time, space and biological processes (+1.5 h to +24 h). In conclusion, low to moderate LSD doses changed language over diverse production types, components and time points. While simpler and disconnected structure and semantic similarity might reflect cognitive impairments, changed vocabulary might reflect subjective perceptions.”
A COMPASS study finds that 25 mg of their psilocybin improved treatment-resistant depression in 233 participants
Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life
https://pubmed.ncbi.nlm.nih.gov/36740140/
Psychedelic science cartoon of the week:
Business & Law
An excellent interview with Hirsch Jain of Ananda Strategy
On the company name, #swoon.
Also, the interviewer Dai Troung runs one of the most helpful newsletters I know, Highly Objective. Give it a follow.
Lies from RAW coming to light: heavy metals in their rolling papers & making up a nonexistent nonprofit to pretend to fund
https://www.prnewswire.com/news-releases/republic-brands-obtains-injunction-federal-court-orders-hbi-international-to-change-its-raw-organic-hemp-rolling-paper-packaging-and-promotions-301743075.html
On the many scandals of Curaleaf by Project CBD’s Bill Weinberg
https://www.projectcbd.org/curaleaf-controversies
MedMen warns of possibly going broke
https://mjbizdaily.com/cannabis-mso-medmen-warns-about-cash-situation-ability-to-stay-afloat
The Plant & the History
In this striking study of water use in Northern California, if the illegal farms were brought into compliance & stopped diverting water from streams in the dry season, it would reduce dry season water extraction by 50%
Water demands of permitted and unpermitted cannabis cultivation in Northern California
https://iopscience.iop.org/article/10.1088/2515-7620/acb6d5/pdf
In a study of the factors affecting cannabis growth, the main driver of cannabinoid content seems to be the genetics of the plant & not the harvest date or weather factors
Influence of Cultivar, Harvest Date, and Selected Weather Conditions on the Essential Oils Content in Inflorescences of Hemp Cannabis sativa L
https://www.tandfonline.com/doi/pdf/10.1080/15440478.2022.2163332
A growers look at how a deficit of different elements (N, P, K, Ca, Mg, S) reduces vegetative growth & yield, with only the low levels of iron & manganese having no effect
Foliar Symptomology, Nutrient Content, Yield, and Secondary Metabolite Variability of Cannabis Grown Hydroponically with Different Single-Element Nutrient Deficiencies
https://pubmed.ncbi.nlm.nih.gov/36771506/
On using all the potentials tools to predict the yield from cannabis plants
Leveraging morphometric, biochemical, and spectral data to predict yields of high-cannabinoid hemp
https://www.authorea.com/doi/full/10.22541/au.167365591.14894504
In a comparison of indoor & outdoor growing, the indoor plants had more degraded & oxidized cannabinoids while the outdoor plants had significantly more unusual cannabinoids as well as a higher level of the sesquiterpenes like β-caryophyllene
Comparison of the Cannabinoid and Terpene Profiles in Commercial Cannabis from Natural and Artificial Cultivation
https://pubmed.ncbi.nlm.nih.gov/36677891/
In clonal cannabis cuttings, light spectra has little effect on their rooting & vegetative growth
Light Spectra Have Minimal Effects on Rooting and Vegetative Growth Responses of Clonal Cannabis Cuttings
https://journals.ashs.org/hortsci/view/journals/hortsci/58/2/article-p215.xml
In Georgia, the effects of planting date on yield & cannabinoid content
Role of Planting Date on Yield and Cannabinoid Content of Day-neutral and Photoperiod-sensitive Hemp in Georgia, USA
https://journals.ashs.org/horttech/view/journals/horttech/33/1/article-p138.xml
A study on how many cannabinoids are found in the leaves of cannabis
Leaves of Cannabis sativa and their trichomes studied by DESI and MALDI mass spectrometry imaging for their contents of cannabinoids and flavonoids
https://pubmed.ncbi.nlm.nih.gov/36654257/
A review of the various analytical forensic techniques you can use on cannabis
Analytical strategies for herbal Cannabis samples in forensic applications: A comprehensive review
https://wires.onlinelibrary.wiley.com/doi/abs/10.1002/wfs2.1479
In Alabama, the first reports of the parasitic roundworm Meloidogyne incognita infecting cannabis plants
First report of Meloidogyne incognita infecting Cannabis sativa in Alabama
https://pubmed.ncbi.nlm.nih.gov/33959722/
Hemp as a food
A review of what makes hempseeds such a good functional food
In Vitro Digestibility, Biological Activity, and Physicochemical Characterization of Proteins Extracted from Conventionally and Organically Cultivated Hempseed ( Cannabis sativa L.)
https://pubmed.ncbi.nlm.nih.gov/36770583/
And another review with an analysis of the secondary metabolites
Hemp seed-based food products as functional foods: A comprehensive characterization of secondary metabolites using liquid and gas chromatography methods
https://www.sciencedirect.com/science/article/abs/pii/S088915752300025X
Hempseed peptides helped mice to swim longer
High Fischer ratio peptide of hemp seed: Preparation and anti-fatigue evaluation in vivo and in vitro
https://www.sciencedirect.com/science/article/abs/pii/S0963996923000790
Industrial Uses
On water-retting cannabis for breaking it down into fiber
Preparation, Extraction, and Processing of Water Retted Cannabis Sativa L. Fibers
https://www.tandfonline.com/doi/pdf/10.1080/15440478.2023.2166647?needAccess=true&role=button
Even though the use of cannabis for rope was so widespread, it was always a very difficult task to break it down. One of those common methods in human history was leaving hemp out in the field or in running water for a few months to make it easier to break the hard outer stalk & utilize the inner fibers to make your ropes, nets & hangman's nooses.
(hence the phrase, ‘give ‘em a hemp necklace’)
An experiment to use hemp to clean up soil contaminated with copper & polycyclic aromatic hydrocarbons (the dreaded PAHs)
Phytoremediation of PAH- and Cu-Contaminated Soil by Cannabis sativa L.: Preliminary Experiments on a Laboratory Scale
https://www.mdpi.com/2071-1050/15/3/1852
Using the leftover hemp shives (woody inner portion of stalk) to create a material that absorbs carbon
The Preparation of a Carbonaceous Adsorbent via Batch Pyrolysis of Waste Hemp Shives
https://www.mdpi.com/1996-1073/16/3/1202
Animal Feed & Bedding
For your animal bedding, which type of hemp to use?
Physical Characterization of Ten Hemp Varieties to Use as Animal Bedding Material
https://pubmed.ncbi.nlm.nih.gov/36670823/
In goats, adding hempseed cake to their feed improved their fatty acid profile, flavor & protein shelf-stability
Health value and keeping quality of chevon from goats fed finisher diets containing hemp (Cannabis sativa L.) seed cake
https://pubmed.ncbi.nlm.nih.gov/36682284/
It looks like you can grow hemp on land contaminated with heavy metals if you’re only feeding it to animals used for textile production
Industrial hemp (Cannabis sativa L.) field cultivation in a phytoattenuation strategy and valorization potential of the fibers for textile production
https://pubmed.ncbi.nlm.nih.gov/36637648/
CANNABINOID SCIENCE
A review of THC vs CBD
THC and CBD: Similarities and differences between siblings
https://pubmed.ncbi.nlm.nih.gov/36638804/
CBD is one of the only molecules that activate your TRPV2 channels (electrical channels essential to cardiac & immune cells) & this study finds that it also enhances the binding power of the drug 2-ABP that also activates them
Cannabidiol sensitizes TRPV2 channels to activation by 2-APB
https://pubmed.ncbi.nlm.nih.gov/36747846/
How the roots of cannabis have anti-inflammatory effects
Chemical constituents of industrial hemp roots and their anti-inflammatory activities
https://pubmed.ncbi.nlm.nih.gov/36642726/
The use of cannabis roots goes far back in human history, especially in Chinese medicine. This is one more area where those ancients were more advanced than us moderns.
I wanted to highlight this review of the flavonoid luteolin because it is so often paired with PEA (as in the study below)
Luteolin: A flavone with myriads of bioactivities and food applications
https://www.sciencedirect.com/science/article/abs/pii/S2212429223000172
Clinical Studies & Surveys
In patients with Long COVID & smell dysfunctions, using PEA & the flavonoid luteolin enhanced the efficacy of olfactory training
Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?
https://pubmed.ncbi.nlm.nih.gov/36676175/
A study of public health data found no association between the legalization of medical cannabis & the expenditure on prescription drugs by health insurance companies
Does the legalisation of cannabis for medicinal use impact private health insurer prescription drug expenditures?
https://link.springer.com/article/10.1057/s41288-022-00284-4
A review of all the methods & findings for detecting cannabinoid levels in biological specimens
Analysis of Cannabinoids in Biological Specimens: An Update
https://pubmed.ncbi.nlm.nih.gov/36767678/
Ingestion, Bioavailability & Biochemical Effects
In a mouse drug discrimination study (where they test how well they can differentiate between drugs), their findings are that CBD lacks abuse potential & that it doesn't appear to modulate the endocannabinoid system (?)
Investigation of Cannabidiol in the Mouse Drug Discrimination Paradigm
https://pubmed.ncbi.nlm.nih.gov/36656312/
This study appears a bit screwy.
In this study of bioavailability, CBD in MCT oil or MCT/LCT oil had better absorption
Digestion behavior, in vitro and in vivo bioavailability of cannabidiol in emulsions stabilized by whey protein-maltodextrin conjugate: Impact of carrier oil
https://pubmed.ncbi.nlm.nih.gov/36708645/
Tolerance to the effects of cannabinoids does not seem to be mediated by b-arrestin (a key signaling protein)
Cannabinoid tolerance in S426A/S430A x beta-arrestin 2 knock-out double mutant mice
https://pubmed.ncbi.nlm.nih.gov/36669876/
Using quantum & chemical studies to model how psychoactive 50 different cannabinoids would be
A PLS study on the psychotropic activity for a series of cannabinoid compounds
https://pubmed.ncbi.nlm.nih.gov/36656418/
Mental Health & Addiction
A review of 10 studies finds that nabiximols (1:1 THC:CBD sprays) do not seem to harm cognition
The effect of tetrahydrocannabinol:cannabidiol oromucosal spray on cognition: a systematic review
https://pubmed.ncbi.nlm.nih.gov/36700997/
In US adolescents, the use of cannabis linked to increased suicidality
US trends in the association of suicide ideation/behaviors with marijuana use among adolescents ages 12-17 and differences by gender and race/ethnicity
https://pubmed.ncbi.nlm.nih.gov/36684023/
In a 10-year follow-up study of those with first-episode psychosis, the use of cannabis was associated with more severe negative symptoms
The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study
https://pubmed.ncbi.nlm.nih.gov/36706477/
On the potential genetic underpinnings to cannabis-associated psychosis
Genetic substrates of cannabis-associated psychosis
https://www.aesed.com/upload/files/v47n4_5-quattrone-en.pdf
In humans with psychosis, those using cannabis had lower levels of anandamide in their blood
Cannabis use is associated with low plasma endocannabinoid Anandamide in individuals with psychosis
https://pubmed.ncbi.nlm.nih.gov/36633290/
In a genetic study, no link found between a certain variant of the CB1 receptor & suicidality
Lack of association between rs1049353 polymorphism of the CNR1 gene and suicide attempt frequency in Polish population
https://pubmed.ncbi.nlm.nih.gov/36645680/
In a mouse model of cocaine addiction, activating the CB2 receptor lowered their reward-seeking behavior, possibly via the lowering of inflammation & modulation by the microglia (guardian immune cells of the brain)
Cannabinoid receptor CB2 agonist attenuates cocaine-induced reinstatement of place preference in mice: Possible role for microglia immunometabolism
https://assets.researchsquare.com/files/rs-2483808/v1/5ee73eb6-8bd3-482d-b29e-9df5a258a4c6.pdf?c=1674254117
In rats, oral THC & CBD caused decreased mental accuracy & impaired attention
Effects of oral Δ9-tetrahydrocannabinol and cannabidiol combinations on a sustained attention task in rats
https://pubmed.ncbi.nlm.nih.gov/36634015/
In this rat model of schizophrenia, exposure to THC in the womb as well as during adolescence did not trigger or aggravate symptoms of schizophrenia
LACK OF INTERACTIONS BETWEEN PRENATAL IMMUNE ACTIVATION AND Δ9 -TETRAHYDROCANNABINOL EXPOSURE DURING ADOLESCENCE IN BEHAVIOURS RELEVANT TO SYMPTOM DIMENSIONS OF SCHIZOPHRENIA IN RATS
https://www.biorxiv.org/content/10.1101/2023.01.20.524884v1.full.pdf
In adolescent mice vaping cannabis, they had gender differences in how it altered their behavioral flexibility as well as changes to the functions of the prefrontal cortex
Sex differences in adolescent cannabis vapor self-administration mediate enduring effects on behavioral flexibility and prefrontal microglia activation in rats
https://pubmed.ncbi.nlm.nih.gov/36711651/
In a tissue study, the neurons & astrocytes (key brain support cells) reacted in different ways to activation of the CB1 receptor in regards to their goal directed behavior & working memory
Neuronal and astrocytic CB1R signaling differentially modulates goal-directed behavior and working memory by distinct temporal mechanisms
https://pubmed.ncbi.nlm.nih.gov/36694040/
The Brain & its Diseases
A huge multi-center study on the efficacy of using CBD for epilepsy
Real-world data on cannabidiol treatment of various epilepsy subtypes: A retrospective, multicenter study
https://pubmed.ncbi.nlm.nih.gov/36693811/
“Our study highlights that CBD has an antiseizure effect comparable to other antiseizure medications with a positive safety profile independent of the epilepsy subtype. Comedication with clobazam was not associated with a better outcome. Higher doses to achieve seizure frequency reduction were safe, particularly in children.”
And a review of using CBD for a rare childhood epilepsy
EFFECT OF THE USE OF CANNABIDIOL ON THE TREATMENT OF LENNOX-GASTAUT SYNDROME: A SYSTEMATIC REVIEW
https://periodicos.ufsm.br/revistasaude/article/view/68765
And a survey of how people with treatment-resistant epilepsy are using cannabis & not finding it harmful in relation to their seizure-related symptoms
Cannabis use patterns in drug-resistant and pharmacoresponsive epilepsy: Single tertiary referral center survey investigation
https://pubmed.ncbi.nlm.nih.gov/36706124/
And in a mouse model of seizures, both CBD alone & in conjunction with THC were useful treatments
The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model
https://pubmed.ncbi.nlm.nih.gov/36646020/
In the brain’s astrocytes (key support cells of homeostasis), this review looks at how the CB1 receptors control transmission between the support cells & metabolic cooperation between the astrocytes and the neurons
Astroglial CB1 receptors, energy metabolism, and gliotransmission: an integrated signaling system?
https://pubmed.ncbi.nlm.nih.gov/36645029/
A computer modeling study of using the molecules of cannabis against Alzheimer's disease
Investigation of Cannabis sativa Phytochemicals as Anti-Alzheimer's Agents: An In Silico Study
https://pubmed.ncbi.nlm.nih.gov/36771595/
In a mouse model of Alzheimer's disease, the lipid oleoylethanolamide (an analog of anandamide) lessened the pathology of the disease & rescue cognitive impairments via the PPAR nuclear receptors (controllers of genetic transcription)
Oleoylethanolamide facilitates PPARa and TFEB signaling and attenuates Ab pathology in a mouse model of Alzheimer's disease
https://pubmed.ncbi.nlm.nih.gov/36711875/
Harms, Cannabis Use Disorder & Street Synthetics
In a community sample study, the use of cannabis by women was associated with a greater chance of lifetime trauma
Regular cannabis use is associated with history of childhood and lifetime trauma in a non-clinical community sample
https://pubmed.ncbi.nlm.nih.gov/36736285/
A case study of a healthy young person with chest problems from cannabinoid hyperemesis syndrome
Pneumomediastinum and Pneumorrhachis Associated With Cannabinoid Hyperemesis Syndrome
https://pubmed.ncbi.nlm.nih.gov/36632263/
Hormones, Reproduction & Maternal Effects
In a review of male sexual health posts & studies, cannabis shows negative effects on semen parameters & variable effects on erectile function & hormone levels
Cannabis and male sexual health: contemporary qualitative review and insight into perspectives of young men on the internet
https://pubmed.ncbi.nlm.nih.gov/36763944/
In women, cannabis smoking not linked to adenomyosis (a condition where endometrial tissue grows into the uterus)
Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk
https://pubmed.ncbi.nlm.nih.gov/36716812/
An association between cannabis use during lactation & adverse childhood experiences
The Association Between Adverse and Positive Childhood Experiences and Marijuana Use During Lactation
https://pubmed.ncbi.nlm.nih.gov/36662593/
In children exposed to cannabis in the womb, they had small but not significant alterations to their brain structure connectivity
Altered White Matter Connectivity in Children with Prenatal Marijuana Exposure
https://journals.iupui.edu/index.php/IMPRS/article/view/26675
In young mice being given chronic low doses of THC, they saw their dendritic spines (related to memory) turn over more & be more destabilized
Chronic low-dose Δ9-tetrahydrocannabinol (THC) treatment stabilizes dendritic spines in 18-month-old mice
https://pubmed.ncbi.nlm.nih.gov/36697430/
Previous work from this group showed that the opposite happened in aging mice: chronic low doses of THC improved their dendritic spine stability & their memory formation
Pain, Inflammation & Surgeries
In humans with migraines & medication overuse headaches, they had lower levels of anandamide
Role of Endo-opioid and Endo-cannabinoid Systems in Migraine and Medication-overuse Headache
https://jag.journalagent.com/z4/vi.asp?pdir=tjn&plng=eng&un=TJN-35467
In a study of mast cells & astrocytes (2 key support cells of the brain), PEA delayed their tolerance to morphine
Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
https://www.mdpi.com/2218-273X/13/2/233
In humans with arthritis, the personality traits associated with self-medicating with cannabis
The role of personality traits on self-medicated cannabis in rheumatoid arthritis patients: A multivariable analysis
https://pubmed.ncbi.nlm.nih.gov/36634127/
In this review of pain, while cannabinoids may not be a first-line alternative for opioids, it’s a good alternative or adjunct for people with acute or chronic pain
Cannabinoids as a Potential Alternative to Opioids in the Management of Various Pain Subtypes: Benefits, Limitations, and Risks
https://pubmed.ncbi.nlm.nih.gov/36639601/
A review of how the CB2 receptors in the microglia (guardian immune cells of the brain) modulate the transmission of pain
Microglial Cannabinoid CB2 Receptors in Pain Modulation
https://pubmed.ncbi.nlm.nih.gov/36768668/
On what happens if you use cannabis before anesthesia
Implications of marijuana use prior to anesthetic care
http://www.anestesiarianimazione.com/PACCJ%202023/Implications%20of%20marijuana%20use%20prior%20to%20anesthtic%20care.pdf
The Immune System, Autoimmune Disorders & Pathogens
In people with HIV, they used cannabis for “sleep, anxiety, appetite, and pain, as well as minimization of craving alcohol and ‘harder’ substances”
Changes in marijuana use and associated attitudes and health behaviors among patients in HIV care in the U.S. in the post-legalization era: a qualitative study
https://academicjournals.org/journal/JAHR/article-full-text-pdf/FA3F26E70215.pdf
On using the cannabis variety known as strawberry for its antioxidant & antimicrobial effects
Comparative Investigation of Antimicrobial and Antioxidant Effects of the Extracts from the Inflorescences and Leaves of the Cannabis sativa L. cv. Strawberry
https://www.mdpi.com/2076-3921/12/2/219
Guts, Metabolism, the Microbiome & Oral Health
A review of the endocannabinoid system & its effects on the diseases of energy & metabolic homeostasis with a focus on the therapeutic potential for diabetes, insulin resistance, obesity & hypertension
Role of the Endocannabinoid System in Metabolic Control Processes and in the Pathogenesis of Metabolic Syndrome: An Update
https://www.mdpi.com/2227-9059/11/2/306
In a mouse model of obesity, the CB1 receptor protected the kidneys from damage by lipids & renal dysfunction, injury, inflammation & fibrosis (scarring)
Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD
https://pubmed.ncbi.nlm.nih.gov/28860163/
Genitourinary
In mice undergoing chemotherapy treatment, not having a FAAH enzyme helped to protect their kidneys from inflammation & damage
Genetic Knockout of Fatty Acid Amide Hydrolase (FAAH) Ameliorates Cisplatin-induced Nephropathy in Mice
https://pubmed.ncbi.nlm.nih.gov/36702548/
Musculoskeletal & Exercise
In osteoarthritis of the knee, hempseed oil & cannabis terpenes helped with improving joint pain & function
Hemp Seed Oil in Association with β-Caryophyllene, Myrcene and Ginger Extract as a Nutraceutical Integration in Knee Osteoarthritis: A Double-Blind Prospective Case-Control Study
https://www.mdpi.com/1648-9144/59/2/191
In human skeletal muscle, the effects of resistance & endurance exercise on the levels of endocannabinoids & cannabinoid receptors
Regulation of the endocannabinoid system by endurance and resistance exercise in hypoxia in human skeletal muscle
https://pubmed.ncbi.nlm.nih.gov/36701485/
In a mouse model of atrophy, blocking the CB1 receptor stimulated muscle protein synthesis
The cannabinoid receptor 1 antagonist AM6545 stimulates the Akt-mTOR axis and in vivo muscle protein synthesis in a dexamethasone-induced muscle atrophy model
https://pubmed.ncbi.nlm.nih.gov/36682621/
The Liver
In a liver cell model of non-alcoholic fatty liver disease, their exosomes (carriers of biological material between cells) transport CB1 receptors that modulate inflammation
Plasma-Derived Exosomes from NAFLD Patients Modulate the Cannabinoid Receptors' Expression in Cultured HepaRG Cells
https://pubmed.ncbi.nlm.nih.gov/36675254/
The Lungs
A review of the yin & the yang of cannabinoids for respiratory allergies & asthma
Cannabinoids in Inflammatory Modulation of Allergic Respiratory Disorders and its Pharmacotherapeutic Approaches to central Respiratory disorders
https://ejmcm.com/article_21980_15b1c70c9c6a9ad6ed7268c85172246d.pdf
In rats given opioids or sedatives, activating the CB1 receptor alters the minimum inhaled anesthetic necessary to cause sedation
Chronic Use of the Synthetic Cannabinoid WIN 55,212-2 55 Modifies the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine
https://www.preprints.org/manuscript/202301.0488/v1
The Heart
In Indian Paddy field workers, those who use cannabis (bhang) had no alterations to their heart rate variability compared to those who did not
Understanding the suitability of parametric modeling techniques in detecting the changes in the HRV signals acquired from cannabis consuming and nonconsuming Indian paddy-field workers
https://www.sciencedirect.com/science/article/pii/B9780323859554000090
In Canadians with cardiac problems, about 14% of them are using cannabis
Prevalence, perceptions, and patterns of cannabis use among cardiac inpatients at a tertiary care hospital: A cross-sectional survey
https://www.sciencedirect.com/science/article/pii/S2589790X23000069
Cancer & Chemo
A review of using the cannabinoids against cancer
Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy
https://pubmed.ncbi.nlm.nih.gov/36696005/
In head & neck cancer cells, a combination of CBD with CBC or THC caused cell death & antiproliferation
The Effect of Cannabis Plant Extracts on Head and Neck Squamous Cell Carcinoma and the Quest for Cannabis-Based Personalized Therapy
https://pubmed.ncbi.nlm.nih.gov/36672446/
In this review, cannabis use is linked to an increased risk of testicular tumors, mixed evidence for bladder cancer & no apparent increase in the risk for prostate cancer, penile cancer or renal cell carcinoma
Urogenital Malignancy and Cannabis Use: A Narrative Review
https://siuj.org/index.php/siuj/article/view/237
In gastric cancer cells, microRNA (regulators of gene expression) used the FAAH enzymes to regulate the levels of endocannabinoid, suggesting FAAH at a therapy target
MicroRNA miR-1275 coordinately regulates AEA/LPA signals via targeting FAAH in lipid metabolism reprogramming of gastric cancer
https://pubmed.ncbi.nlm.nih.gov/36702852/
Cool Chemistry
On why it's so hard to manufacture tablets containing CBD (hint: fatty lipids are slippery little bastards)
Production challenges of tablets containing lipid excipients: Case study using cannabidiol as drug model
https://pubmed.ncbi.nlm.nih.gov/36693485/
On improving the activity of the enzyme that creates CBC
Improving CBCA synthase activity through rational protein design
https://pubmed.ncbi.nlm.nih.gov/36681096/
On using computer modeling & molecular dynamics to understand how to partially turn on the CB1 receptor
A mechanistic model explaining ligand affinity for, and partial agonism of, cannabinoid receptor 1
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d111571fe1422ea859547c/original/a-mechanistic-model-explaining-ligand-affinity-for-and-partial-agonism-of-cannabinoid-receptor-1.pdf
New drugs for activating the CB2 receptors
N-adamantyl-anthranil amide derivatives: New selective ligands for the cannabinoid receptor subtype 2 (CB2R)
https://pubmed.ncbi.nlm.nih.gov/36657299/
And new drugs for blocking the CB2 receptors
Synthesis, molecular modeling and SAR study of novel pyrazolo[5,1-f][1,6]naphthyridines as CB2 receptor antagonists/inverse agonists
https://iris.uniss.it/bitstream/11388/174182/6/Post-print.pdf
On creating the third generation of synthetic cannabinoids using metal-organic frameworks (one of the hottest tools in biochemistry)
Metal-organic frameworks as promising solid-phase sorbents for the isolation of third-generation synthetic cannabinoids in biological samples
https://www.sciencedirect.com/science/article/pii/S0003267023001083
Thanks.
- lex
PS: For our 4-album set of the week, ‘The Staple Singers - Faith and Grace: A Family Journey 1953 – 1976’. Started in 1949 by Pops Staple, this family of singers always stayed true to their roots in gospel harmonies, but they eventually branched into folk music, socially conscious gospel & even a string of R&B hits in the ‘70s. Pops played cotton-patch guitar & shared the singing with Mavis, backed by siblings Cleotha, Pervis & Yvonne. You can hear the love in every one of these 80 tracks.
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.