Hello everyone,

Greetings to all my new subscribers from TikTok & thanks for blowing up my video.

Welcome to the 41st 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.

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:
‘The 3 Ingestion Methods of Medical Cannabis: Tips & Tricks’
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 EU segment for Weed Talk News on Pro Cannabis Media: Two Bads & a Good
[sponsorship slots open: 10k subscribers]

And as always, at the bottom there’s an album of the week &
The Living Glossary of Cannabinoid Terms.

This week…

Cannabis oil for the heart. CBD for the heart. CBD-rich extracts for the heart.
Cannabis for sleep
Again, weed not great for teens – but looser cannabis laws lead to less drinking alcohol
Surprise! Online Canadian weed sellers not an excellent source of health info
THC & CBD better than top-shelf skincare ingredients for reducing skin aging
CBDV for Parkinson’s?
Sativex causes no cognitive problems for MS patients
Cannabinoids in snacks, hemp in chocolate
Improvements in trying to catch horses doping with CBD 🙄

A request to spread the word
This newsletter only spreads by word of mouth – so please forward to colleagues & tell your friends & relatives.

Share

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.

Subscribe now

Alternative ways to support:
Buy Me a Coffee
Venmo: @Lex-Pelger
Zelle: pelger@gmail.com
PayPal: donate here

My work & platforms:
YouTube for my 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 for healthcare practitioners

For any healthcare practitioners out there who want to use CBD products, you can’t beat the ProCBD line from PlusCBD.

Formulated specifically for healthcare practitioners, these extra-strength products allow you to easily administer higher levels of CBD-rich hemp extracts to your patients. With softgels that contain 100 mg of CBD in each capsule, oils with 25 mg per spray & strong topicals for intense pain, the ProCBD line allows your patients to harness the higher levels of cannabinoids for their health.

Apply here for free samples.

Best Of Cannabinoid Science...

Clinical

In a sleep diary study, cannabis use was associated with improved sleep quality
Cannabis use and sleep quality in daily life: An electronic daily diary study of adults starting cannabis for health concerns
https://pubmed.ncbi.nlm.nih.gov/36638745/

For adolescents, living in a state with liberalized cannabis laws led to a lower chance of beginning to drink alcohol
Medical Cannabis Laws and Adolescent Alcohol Use Initiation
https://pubmed.ncbi.nlm.nih.gov/36506781/

Reviews

A review around the complexities of cannabis use & organ transplantation
Cannabis Use in Transplantation
https://link.springer.com/chapter/10.1007/978-3-031-15052-4_21

A review of the effects of using cannabinoids for Parkinson's disease in animal models
Effects of cannabinoids in Parkinson's disease animal models: a systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/36618606/
See my How-To Guide on Cannabis & Neurodegenerative Diseases here…

Preclinical

In mice with high blood pressure, one month of cannabis oil reduced their hypertension & improved their network of mitochondria (powerhouse of the cell) probably via its antioxidant effects
Cannabis oil one-month oral treatment given to spontaneously hypertensive rats (SHR): Could it be a promising therapeutic strategy for hypertensive cardiac hypertrophy?
https://www.sciencedirect.com/science/article/pii/S0022282822003959

CBD is protective of the heart in several diseases via its antioxidant & cardioprotective effects
Treatment with Cannabidiol Results in an Antioxidant and Cardioprotective Effect in Several Pathophysiologies
https://pubmed.ncbi.nlm.nih.gov/36508270/

In a rat model of obesity, CBD-rich hemp extracts protected the heart via the inhibition of the transport of adenosine (a messenger of protein synthesis)
The effect of a long-term treatment with cannabidiol-rich hemp extract oil on the adenosinergic system of the zucker diabetic fatty (ZDF) rat atrium
https://pubmed.ncbi.nlm.nih.gov/36588715/

In a mouse model of nerve pain, CBD-rich extract lowered their pain sensitivity via the CB2 receptors of the microglia (immune guardian cells of the brain)
Cannabidiol-rich non-psychotropic Cannabis sativa L. oils attenuate peripheral neuropathy symptoms by regulation of CB2-mediated microglial neuroinflammation
https://pubmed.ncbi.nlm.nih.gov/36583304/

In skin connective tissue, both THC & CBD decreased aging & improved wound healing more effectively than the top skin ingredients they were tested against
Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts
https://pubmed.ncbi.nlm.nih.gov/36497198/

The ability of echinacea to help with the seizures of epilepsy seems to be mediated by the CB2 receptor
Anticonvulsive and anti-epileptogenesis effects of Echinacea purpurea root extract, an involvement of CB2 receptor
https://pubmed.ncbi.nlm.nih.gov/34461009/
Add this to the long list of plant medicines that work their magic via the endocannabinoid system.
I gotta turn this subject into an article someday soon...

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

The first cannabis reform bill of the new Congress is a gun rights measure for cannabis patients
https://www.marijuanamoment.net/first-marijuana-bill-of-the-new-congress-is-a-gop-led-gun-rights-measure

A guideline to the cannabis diversity & equity laws across the US
https://www.cannabisbusinessexecutive.com/2023/01/dei-and-the-cannabis-industry-a-comprehensive-guide/

US Virgin Islands does it right: legalize the plant, expunge the convictions, pardon the prisoners
https://www.marijuanamoment.net/u-s-virgin-islands-governor-signs-marijuana-legalization-and-expungements-bills-and-issues-cannabis-pardon-proclamation
If you do the first without the second & third, it’s a travesty.

Ohio lawmaker attempts to add autism as a qualifying condition
https://eu.dispatch.com/story/news/politics/2023/01/18/ohio-medical-marijuana-autism-among-proposed-new-conditions-in-2023/69795262007
This is an excellent example of why these decisions should not be in the domain of bureaucrats, even well-meaning ones. Who should decide if a kid can take medical cannabis?
Their caregivers & their doctors.
It’s appalling that a kid might have a rare condition that is not on the Holy List of Qualifying Conditions & they either will get no medicine or only what they can find on the black market. #MedicalCannabisForWhoeverWantsIt

For those participating in Dry January (not drinking alcohol), many used cannabis or CBD as a substitute, especially Gen Z
https://civicscience.com/ninety-percent-of-gen-z-dry-january-participants-are-leaning-on-other-drinks-and-substances-to-fill-the-void

The National Transportation Safety Board wants states with legal cannabis to add product warning labels about impaired driving
https://www.marijuanamoment.net/federal-agency-urges-states-to-mandate-marijuana-impaired-driving-warning-labels-as-national-prohibition-blocks-broader-action
Because of federal prohibition, the Board itself can take no action. 🙄

The Artisan in Las Vegas is going to rebrand as a cannabis-friendly resort & call itself Elevation
https://www.reviewjournal.com/business/tourism/artisan-hotel-becoming-cannabis-friendly-taking-on-new-name-2713706
I kind of love this.

The War on Drugs & Prohibition

In excellent news, any doctor is now allowed to prescribe the drug buprenorphine for opioid use disorder without the need for a waiver
https://www.samhsa.gov/medication-assisted-treatment/removal-data-waiver-requirement

Psychedelics, Plant Medicines & Other Psychoactives

[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]

A look at the neuropharmacology of the substituted amphetamines such as MDMA by the ever excellent Andrew Gallimore

Alien Insect On Drugs

Psychedelic Amphetamines, Speedy Amphetamines, Entactogenic Amphetamines...

One of the most fascinating aspects of neuropharmacology, for me at least, is how closely related molecules, perhaps differing only by the presence or absence of a methyl group (think DMT vs 5-MeO-DMT), can have dramatically different effects on the brain and consciousness. Whilst we understand much about the way molecules interact with receptors, how t…

2 months ago · 8 likes · 3 comments · Andrew R. Gallimore

In psychedelics, how hallucinations were dealt with historically & how they're approached now
Hallucinations and Hallucinogens: Psychopathology or Wisdom?
https://pubmed.ncbi.nlm.nih.gov/36633720/

A meta-analysis of using psilocybin to treat psychiatric illness
Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis
https://www.cureus.com/articles/122398-psilocybin-as-a-treatment-for-psychiatric-illness-a-meta-analysis

A review of using psychedelics for chronic pain
Are psychedelics the answer to chronic pain: A review of current literature
https://onlinelibrary.wiley.com/doi/full/10.1111/papr.13203

For PTSD, a look at how MDMA alters brain activity & functional connectivity
Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder
https://www.frontiersin.org/articles/10.3389/fpsyt.2022.947622/full

The Plant & the History

Classifying cannabis varieties by their long terminal repeats (the repeated DNA sequences on either side of a gene inserted by a retrovirus or a piece of DNA that moved (transposons))
Genetic Variants Associated with Long-Terminal Repeats Can Diagnostically Classify Cannabis Varieties
https://pubmed.ncbi.nlm.nih.gov/36498868/

Growing & Processing

A continuous flow of phosphorus to cannabis roots did not increase yield or cannabinoid concentration
Sustainable Cannabis Nutrition: Elevated root-zone phosphorus significantly increases leachate P and does not improve yield or quality
https://pubmed.ncbi.nlm.nih.gov/36483962/

Testing the effects of hemp seeding rate & harvest time on yield
Energy and Biomass Yield of Industrial Hemp (Cannabis sativa L.) as Influenced by Seeding Rate and Harvest Time in Polish Agro-Climatic Conditions
https://www.tandfonline.com/doi/pdf/10.1080/15440478.2022.2159609

Creating synthetic cannabis seeds for an easier way to spread genetic information
Cannabis Synthetic Seeds: An Alternative Approach for Commercial Scale of Clonal Propagation and Germplasm Conservation
https://pubmed.ncbi.nlm.nih.gov/36501226/

A review of using hemp to clean soils contaminated with heavy metals
Investigating the potential of heavy metal accumulation from hemp. The use of industrial hemp (Cannabis Sativa L.) for phytoremediation of heavily and moderated polluted soils
https://www.sciencedirect.com/science/article/abs/pii/S2352554122003655
Of course, this is also why cannabis testing is essential. This plant sucks out heavy metals from the soil where other plants wouldn't – and for medical patients, this is a big deal. #BuyCleanTestedMedicine

Human food

A review of the history & viability of using cannabinoids in snacks
Cannabis sativa Cannabinoids as Functional Ingredients in Snack Foods-Historical and Developmental Aspects
https://pubmed.ncbi.nlm.nih.gov/36501366/

Testing the addition of hemp to chocolate
ASSESMENT OF PHISICOCHEMICAL AND SENSORY PROPERTIES OF CHOCOLATE WITH HEMP PRODUCTS ADDITION
http://aspeckt.unitbv.ro/jspui/bitstream/123456789/2638/1/37-42.pdf

Animal feed

A good feeding blend in chickens results in increased endocannabinoid levels in their intestines
Effects of microencapsulated blend of organic acids and botanicals on growth performance, intestinal barrier function, inflammatory cytokines, and endocannabinoid system gene expression in broiler chickens
https://www.sciencedirect.com/science/article/pii/S0032579122007544

Industrial Use & Inventions

Using hemp for brake pads
Wear and Friction Analysis of Brake Pad Material Using Natural Hemp Fibers
https://pubmed.ncbi.nlm.nih.gov/36616537/

Using hemp rope to strengthen masonry barrels
Effect of hemp bio composite strengthening on masonry barrel vaults damage
https://www.sciencedirect.com/science/article/abs/pii/S0950061822037564

On using hemp to make particleboards
Hemp Shives as a Raw Material for the Production of Particleboards
https://pubmed.ncbi.nlm.nih.gov/36501702/

A study of the characteristics of hemp fiber
Characterization of Elementary Industrial Hemp (Cannabis Sativa L.) Fiber and Its Fabric
https://www.tandfonline.com/doi/pdf/10.1080/15440478.2022.2158982?needAccess=true&role=button

When using hemp to make fiber felt
Static and Dynamic Behavior of Hemp Natural Fiber Felt Biocomposites
https://www.tandfonline.com/doi/pdf/10.1080/15440478.2022.2160408

A review of using hemp walls for building
Using Hemp for Walls as a Sustainable Building Material
http://www.engiscience.com/index.php/josse/article/view/josse2022242

CANNABINOID SCIENCE

Clinical Studies & Surveys

In today's unsurprising finding, online cannabis sellers in Canada were not a great source of health information
The quality of health information provided on web sites selling cannabis to consumers in Canada is poor
https://pubmed.ncbi.nlm.nih.gov/36503517/

In your review of public health data from Quebec, all medical cannabis patients reported an improvement in their pain levels, anxiety, tiredness & health-related quality of life
The Quebec Cannabis Registry: Investigating the Safety and Effectiveness of Medical Cannabis
https://pubmed.ncbi.nlm.nih.gov/36579921/

Improvements in horse anti-doping tests with an eye towards CBD
Towards Non-Targeted Screening of Lipid Biomarkers for Improved Equine Anti-Doping
https://pubmed.ncbi.nlm.nih.gov/36615506/

Adolescents

A review on the rise in heart attacks among young cannabis users
Rising trend of acute myocardial infarction among young cannabis users: A 10-year nationwide gender and race stratified analysis
https://www.sciencedirect.com/science/article/pii/S2772487522000435

In Canadian public health data of adolescents, an association was found between mental health & youth cannabis use
Mental health and cannabis use among Canadian youth: Integrated findings from cross-sectional and longitudinal analyses
https://pubmed.ncbi.nlm.nih.gov/36587508/

In adolescent rats exposed to THC, the enduring cognitive dysfunctions involved alterations in their prefrontal cortex via the levels of kynurenic acid (an amino acid that lowers excitation in the brain)
Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence
https://pubmed.ncbi.nlm.nih.gov/36483135/

In rat adolescents, exposure to a drug that activates the CB1 receptor caused increased levels of SYNGAP1 (a protein related to a neurological disorder of intellectual disability)
Synaptoproteomic Analysis of the Prefrontal Cortex Reveals Spatio-Temporal Changes in SYNGAP1 Following Cannabinoid Exposure in Rat Adolescence
https://pubmed.ncbi.nlm.nih.gov/36614142/

Mental Health, Addiction & Mental Effects

For schizophrenia, a review of how cannabis can be both helpful & harmful
Consumption of Cannabis: A Risk Factor or a Therapeutic Agent for Patients with Schizophrenia
https://link.springer.com/chapter/10.1007/978-981-19-7022-1_15

In mice with opioid use disorder, CBD did not help with their addiction to oxycodone but the analog CBD-val-HS did help & also lowered pain
Differential Effects of Cannabidiol and a Novel Cannabidiol Analog on Oxycodone Place Preference and Analgesia in Mice: an Opioid Abuse Deterrent with Analgesic Properties
https://pubmed.ncbi.nlm.nih.gov/34962133/

The Brain & its Diseases

In a review of seven clinical trials on patients with MS, the use of Sativex (a 1:1 CBD: THC spray) caused no detrimental effects on cognitive function after 12 months of use
Effects of SativexⓇ on cognitive function in patients with multiple sclerosis: A systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/36174323/

In a roundworm model of Parkinson’s disease, CBDV lowered the aggregation of the α-synuclein plaques as well as oxidative stress & the death of dopamine-producing neurons
Cannabidivarin alleviates α-synuclein aggregation via DAF-16 in Caenorhabditis elegans
https://pubmed.ncbi.nlm.nih.gov/36583706/

Epilepsy

A Russian review of treating epilepsy with CBD
Cannabidiol for Treatment Epilepsy and Russian Experience
https://ecronicon.org/assets/ecpp/pdf/ECPP-11-01044.pdf

In Japanese patients with intractable epilepsy, CBD reduced their seizures
Cannabidiol supplement reduces epileptic seizures in the Japanese population: Cross-sectional study for intractable epilepsy patients
https://web.s.ebscohost.com/abstract?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=18236138&AN=161021105&h=MBtpvyk7gp981JHoBgkshyoKjK8%2fV1jpOt4eOZaqlcNq9ulaV4%2fcEvKtS%2bIyFKJLuDlCKKCMBJFqBR49eWBOaQ%3d%3d&crl=c&resultNs=AdminWebAuth&resultLocal=ErrCrlNotAuth&crlhashurl=login.aspx%3fdirect%3dtrue%26profile%3dehost%26scope%3dsite%26authtype%3dcrawler%26jrnl%3d18236138%26AN%3d161021105
“Fifteen patients (53.6%) reported a decrease in seizure frequency. Moreover, two patients (7.1%) showed complete resolution of seizures.”

Harms, Cannabis Use Disorder & Street Synthetics

In four case reports of cannabis-induced psychosis, the anti-psychotic lurasidone improved their clinical picture, both the positive & negative symptoms
Lurasidone use in Cannabis-Induced Psychosis: A Novel Therapeutic Strategy and Clinical Considerations in Four Cases Report
https://pubmed.ncbi.nlm.nih.gov/36498129/

Apparently one way to treat cannabis use disorder is by getting people to savor it more
Savoring as an intervention for cannabis use: acceptability, feasibility, and preliminary results
https://www.tandfonline.com/doi/abs/10.1080/16066359.2022.2160871
I should try this instead of my current system of quickly gulping it in the basement.

Lungs & Vaping

The rates of pediatric asthma seem to be not significantly altered by the legal status of cannabis in that state
Cannabis legalization and childhood asthma in the United States: An ecologic analysis
https://pubmed.ncbi.nlm.nih.gov/36592675/

Pain, Inflammation & Surgeries

In chronic pain patients, those using cannabis and/or opioids had worse baseline health characteristics & outcomes but it's unclear whether this is a cause or an effect
Association of cannabis and/or opioid with quality of life and healthcare utilization in patients with chronic pain
https://pubmed.ncbi.nlm.nih.gov/36506271/

The Immune System, Autoimmune Disorders & Pathogens

In mice with HIV, THC helped with their pain but increased anxiety levels in females as well as diminished object recognition memory & changes in endocannabinoid levels
Effects of acute Δ9 -tetrahydrocannabinol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice
https://assets.researchsquare.com/files/rs-2401488/v1/1cd08ec4-d7b1-4302-a3e9-bca0fdee254e.pdf?c=1672334667

Guts, Metabolics, Microbiome & Oral Health

In a female rat model of recurrent binge eating they saw notable changes in their endocannabinoid machinery such as anandamide, CB1, MGL & FAAH, suggesting the ECS as a target for treatment
Endocannabinoid System Regulation in Female Rats with Recurrent Episodes of Binge Eating
https://pubmed.ncbi.nlm.nih.gov/36499556/

In mice with a disease of dysregulated lipid levels treated by fenofibrate (a common drug for the condition), they had strong changes in their liver levels of PEA & oleamide
Profound Modification of Fatty Acid Profile and Endocannabinoid-Related Mediators in PPARα Agonist Fenofibrate-Treated Mice
https://pubmed.ncbi.nlm.nih.gov/36614161/

Genitourinary System

In rats, a nano-form of anandamide collected in the kidney & caused positive benefits
Polymeric Nanomicelles Loaded with Anandamide and Their Renal Effects as a Therapeutic Alternative for Hypertension Treatment by Passive Targeting
https://www.researchgate.net/publication/366646124_Polymeric_Nanomicelles_Loaded_with_Anandamide_and_Their_Renal_Effects_as_a_Therapeutic_Alternative_for_Hypertension_Treatment_by_Passive_Targeting

The Liver

In a mouse model of non-alcoholic fatty liver disease, a low dose of CBG lowered the inflammation & formation of scar tissue while a high dose of CBG enhanced liver damage
Low-Dose Administration of Cannabigerol Attenuates Inflammation and Fibrosis Associated with Methionine/Choline Deficient Diet-Induced NASH Model via Modulation of Cannabinoid Receptor
https://pubmed.ncbi.nlm.nih.gov/36615835/

The Skin

In a mouse model of itchy skin, β-Caryophyllene (a common cannabis terpene) lowered the inflammation & lesions
β-Caryophyllene Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis through the Downregulation of Mitogen-Activated Protein Kinase/EGR1/TSLP Signaling Axis
https://pubmed.ncbi.nlm.nih.gov/36499191/

Hormones, Reproduction & Maternal Effects

In egg-producing cells of cows, THC caused no negatives in viability or cell death while having the benefit of lowering levels of cortisol (stress hormone)
Delta-9 tetrahydrocannabinol (THC) effects on the cortisol stress response in bovine granulosa cells
https://pubmed.ncbi.nlm.nih.gov/36596389/

Cancer & Chemo

A review of the studies on using cannabis for cancer pain & dosing guidelines
Clinical Research Evidence Supporting Administration and Dosing Recommendations of Medicinal Cannabis as Analgesic in Cancer Patients
https://pubmed.ncbi.nlm.nih.gov/36615107/

The ability of CBG to destroy glioblastoma stem cells (the most aggressive brain cancer) seems to be mostly mediated by the vanilloid TRPV1 receptor & GPR55 (the receptor that may one day be known as the CB3 receptor)
The Cytotoxic Effects of Cannabidiol and Cannabigerol on Glioblastoma Stem Cells May Mostly Involve GPR55 and TRPV1 Signalling
https://pubmed.ncbi.nlm.nih.gov/36497400/

In breast cancer cells, THC caused them to migrate more in low estrogen conditions but not in high estrogen conditions
Δ9-Tetrahydrocannabinol stimulation of estrogen receptor-positive MCF-7 breast cancer cell migration: Interfering interaction with the estrogenic milieu
https://pubmed.ncbi.nlm.nih.gov/36583834/

In a mouse model of neuropathic pain from chemotherapy, a drug that acts as a positive allosteric modulator of the CB1 receptor (an activity of CBD) lessened their pain, the levels of proinflammatory cytokines & nerve injuries
Cannabinoid receptor 1 positive allosteric modulator (GAT229) attenuates cisplatin-induced neuropathic pain in mice
https://www.sciencedirect.com/science/article/pii/S1319016422003115

Cool Chemistry

How well does CBD dissolve in various plant oils & other hydrophobic mixing ingredients?
Experimental investigation and thermodynamic modeling of cannabidiol solubility in plant oils and hydrophobic eutectic systems
https://www.sciencedirect.com/science/article/abs/pii/S0167732222027118

The creation of a new CBD cousin that has antitumor activity
Synthesis and Biological Evaluation of 3′,5′-d2-Cannabidiol
https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/slct.202204628

Utilizing brain scans to see if a new probe of the endocannabinoid transporter ABHD6 is working
Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/ β-Hydrolase Domain 6 (ABHD6)
https://pubmed.ncbi.nlm.nih.gov/36516997/

A new drug to activate the CB2 receptor comes to town with a name that only a mother could love
N-[1,3-Dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulphonamides as Novel Selective Human Cannabinoid Type 2 Receptor (hCB2R) Ligands; Insights into the Mechanism of Receptor Activation/Deactivation
https://pubmed.ncbi.nlm.nih.gov/36500256/

Thanks.
- lex

PS: For this week’s trumpets, ‘Collates’ by Roy Eldridge. Starting off in carnival & circus bands, by the ‘30s he was playing in a variety of bands. Picking up the nickname “Little Jazz”, he became one of the most exciting trumpeters of the swing era.

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.

Cannabinoids & the People

C&P#41: Cannabis for the heart + CBD & THC…