Hello everyone,

Seasons greetings & best wishes!
I’ll take next week off & see you in the new year with a doozy of a big science newsletter.

Book a 1-on-1 cannabis/CBD/psychedelics counseling session with me:
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My work this week: YouTube Shorts
On my YouTube channel, I’m going to start doing a short video every day about a new cannabinoid science study. Subscribe here.
Also, check out my interview about Ireland on Weed Talk News with Martin Condon of the Martin’s World Podcast.
In my EU report, negatives across the board…

This week…

Cannabis for people with Hep C, HIV or persistent headaches
CBD PROTECTS THE BRAIN!
Is your wedding right made out of hemp? Mine neither, but it should be.
Powerful studies & case reports on cannabinoids for pain
If your genetic variant of the FAAH enzyme is the slow type, you’re more likely to be drinking harder & faster as a teenager
A rare case report of psychosis from cannabis withdrawal
Vaping, vaping, lung poison
The NYPD planting drugs + more terrible news from the abhorrent War on Drugs
Hemp for your weaned piglets & the mouthfeel of your yogurt
Where we learn the real name of the Star Wars cantina song
Year’s best hemp robot name!

This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations.
I produce educational content for cannabis & psychedelic companies: writing, science archives, newsletters & if you need a podcast, I’m the host for you.
You can see my portfolio here.

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As always, at the bottom there’s a Living Glossary of cannabinoid terms & the weekly music recommendation.

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<these diapers don’t buy themselves>

My other work & platforms:
YouTube for my 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
Twitter & my TikTok BookTok

Sponsor: PlusCBD’s unparalleled product selection

I spent 3 years working full-time for PlusCBD before I launched my consulting business so I know from the inside about their commitment to making quality CBD products. But that’s not the most special thing about them. What they do better than any other company in the industry is create a wide range of products.

Nobody else has this much…

Oils, capsules & gummies of course
Topicals that come as balms, creams, roll-ons & special formulations for arthritis or athletes that contain menthol & camphor
The Reserve Collection! Oils, capsules & gummies containing 2.5 mg of THC per serving (I’m constantly being asked how people in non-medical can get THC-rich products & this is always what I recommend to them. Especially because it’s an easy-to-use standard serving size that’s just the right amount for people new to THC)
Excellent pet products in a range of flavors
3 very special formulations with other ingredients:
- Sleep gummies: Includes 3 mg of melatonin + extract of lemon balm & magnolia bark (two old plants for inducing sleep)
- Calm gummies: Includes 5-HTP (the serotonin precursor) & L-theanine (from tea)
- Relief capsules [I can’t find a link to just this item – only the wellness blend bundle]: Includes PEA + CBDA (see the Living Glossary below for why I think these are the ingredients of the future for immune health & gut health)

That’s why I recommend PlusCBD to so many of the clients I consult with: they offer an array of products like no other.

Buy their excellent products today at PlusCBDoil.com.

Best Of Cannabinoid Science...

The cannabis hero Dr. Dustin Sulak on cannabis for children with cancer
https://www.cannapatientcare.com/view/cannabis-for-children-with-cancer
He’s been working closely with cannabis patients for a long time & you can find a wealth of his videos & lectures online.

In long COVID patients, a combination of PEA & luteolin (a flavonoid commonly paired with PEA) helped with neural plasticity in the motor cortex as well as the activity of GABA (the brain’s primary inhibitory neurotransmitter)
Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome
https://pubmed.ncbi.nlm.nih.gov/36455453

In people with hepatitis C, the cannabis users had fewer metabolic disorders & a lower risk of hypertension
Cannabis Use Is Inversely Associated with Metabolic Disorders in Hepatitis C-Infected Patients (ANRS CO22 Hepather Cohort)
https://pubmed.ncbi.nlm.nih.gov/36294456
And in people with HIV, the cannabis users reported more vigorous physical exercise
The relationship between substance use and physical activity among people living with HIV, chronic pain, and symptoms of depression: a cross-sectional analysis
https://pubmed.ncbi.nlm.nih.gov/36260055

A case report of using CBD-rich cannabis for a patient with hypophosphatasia (a rare genetic disorder of impaired mineralization of bones & teeth that includes muscle pain & neurological symptoms) found that it led to a significant pain reduction, a discontinuation of opioids & resumption of her work as a physician
Medical Cannabinoids as Treatment for Hypophosphatasia-Related Symptoms
https://pubmed.ncbi.nlm.nih.gov/36380652
What’s meaningful to me is how many rare diseases I get to learn about only because they pop up as case reports where cannabis or the cannabinoids are the only thing that work after everything everything everything else has failed.

In a survey of people with persistent headaches, the majority of cannabis users reported it helped with the severity of their headaches & a quarter of them said it reduced their frequency
Cannabinoid Use in a Tertiary Headache Clinic: A Cross-Sectional Survey
https://pubmed.ncbi.nlm.nih.gov/34511153

Using population studies, the liberalization of a state’s cannabis laws was found to be a driving factor in the increase of testicular cancer rates
State Trends of Cannabis Liberalization as a Causal Driver of Increasing Testicular Cancer Rates across the USA
https://pubmed.ncbi.nlm.nih.gov/36232059
“Strong dose-response effects were demonstrated for THC, cannabigerol, cannabinol, cannabichromene and cannabidiol. Cannabinoid genotoxicity replicates all major steps to testicular carcinogenesis including whole-genome doubling, chromosomal arm excision, generalized DNA demethylation and chromosomal translocations thereby accelerating the pathway to testicular carcinogenesis by several decades.”

A review of clinical trials of cannabis for palliative care finds key lessons: patient confidentiality, family dynamics, driving, cost, unfounded beliefs, accessing specific MC products, trial funding & telehealth
Medicinal cannabis in palliative medicine: lessons learnt from randomised controlled trials
https://pubmed.ncbi.nlm.nih.gov/36379690

A review of the clinical trials on cannabis found that the number increased from 30 in 2013 to 103 in 2021
The Characteristics of Clinical Trials on Cannabis and Cannabinoids: A Review of Trials for Therapeutic or Drug Development Purposes
https://pubmed.ncbi.nlm.nih.gov/36357543
“Clinical research on Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and the oral routes of administration dominate the field. Approximately two-thirds of clinical trials were conducted in five therapeutic areas (i.e., 'Chronic pain,' 'Mental, behavioral or neurodevelopmental disorders,' 'Nervous system diseases,' 'Endocrine, nutritional or metabolic diseases,' and 'Neoplasms'[cancer]).”

A neat look at how the cannabinoids alter the lipid membranes
Molecular study of endo and phytocannabinoids on lipid membranes of different composition
https://pubmed.ncbi.nlm.nih.gov/36399905
If you take a little walk down memory lane with me, you'll remember that in the 80s everyone argued about whether the cannabinoids worked in human cells via receptors on the surface of the membrane or by altering the entire membrane itself. Of course, as is usual in science, the answer turned out to be... both.
Everyone thought victory went to the receptor people in the early 90s with the discovery of the CB1 & CB2 receptors - but the more we learn, the more we realize that the cannabinoids also alter the properties of the membrane & this is one more way that they work their magic.

2021: A review of what we know – and don’t know – about how cannabis produces the cannabinoids
The biosynthesis of the cannabinoids
https://pubmed.ncbi.nlm.nih.gov/33722296
The relevant cartoon.

Funny study in Texas of how retailers are describing delta-8 THC
How are retailers describing Delta-8 THC? A mixed-methods study in Fort Worth, Texas
https://www.jsad.com/doi/abs/10.15288/jsad.22-00287

In this history of wedding rings, we find that hemp was often used on the fourth finger of the left hand because it was believed that the vein here ran directly to the heart
The Ring Thing
https://academic.oup.com/book/41780/chapter-abstract/354474206

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

In the latest defense spending bill, Congress pushes the military to consider cannabis & psychedelics
https://www.marijuanamoment.net/congress-pushes-military-to-consider-psychedelics-and-marijuana-therapy-while-other-cannabis-provisions-left-out-of-defense-bill

In NYC, the mayor cracks down on unlicensed cannabis sellers
https://www.cannabisbusinessexecutive.com/2022/12/mayor-adams-cracks-down-on-unlicensed-nyc-stores-selling-cannabis
The War on Drugs will continue – but now it will be the enforcement of licenses.
Remember kids, if you get caught making meth, you don’t get charged with creating an illegal substance. You get charged with manufacturing Desoxyn without a license.
Meanwhile, in NYC a legal 8th will probably be $75 & an illegal 8th will be less than half of that

John Schroyer @Johnschroyer

By one expert's calculations, a legal 8th of #cannabis in New York will cost $75, compared to $10-40 on the illicit #marijuana market.

greenmarketreport.comExperts Predict New York Cannabis Taxes Will Undercut Legal MarketPrices of legal recreational cannabis across New York will likely be at least twice as much as marijuana sold by unlicensed dealers and smoke shops.

The USDA delays its requirement for using DEA labs to test hemp products
https://mailchi.mp/e59c5adeb16d/usda-delays-dea-registered-lab-requirement-for-hemp-testing
The problem with DEA labs is that there aren’t enough of them & hemp testing is not a priority for them. Also, the DEA is an awful dinosaur that should be euthanized.

Switzerland begins the first adult-use cannabis trial in the EU: ‘Weed Care’
https://businesscann.com/europes-first-thc-adult-use-cannabis-trial-set-to-launch-in-january-2023-after-four-month-delay

In Ireland, its High Court ruling that CBD with any trace of THC is illegal may open it up to punishment & sanctions from the EU
https://www.cannabisbusinessexecutive.com/2022/12/irelands-prohibitionist-approach-to-hemp-and-cbd-exposes-it-to-punitive-sanctions-from-the-eu

On the report about the Pandora’s box of unregulated cannabinoids from the California Cannabis Industry Association
https://www.projectcbd.org/delta-8-delta-10-hhc-thco-pandoras-box-unregulated-cannabinoids
Access the original white paper here:
Pandora's Box: The Dangers of a National, Unregulated, Hemp-Derived Intoxicating Cannabinoid Market
https://members.cacannabisindustry.org/whitepapers/Details/pandora-s-box-the-dangers-of-a-national-unregulated-hemp-derived-intoxicating-cannabinoid-market-131449

On Utah’s Erin Brockovich of synthetic cannabinoids
https://www.cannabisbusinessexecutive.com/2022/12/utah-synthetic-a-deep-dive-with-the-erin-brockovich-of-cannabis-part-one

On the 7 factions within cannabis:
consumers & home growers, testing labs, small craft businesses, MSOs, investors, pharmaceuticals, people who need their cannabis charges expunged and/or freed from incarceration
https://www-fatnugsmag-com.cdn.ampproject.org/c/s/www.fatnugsmag.com/daily-nugs/the-seven-cannabis-factions-part-1

The ice hockey team the Chicago Wolves sign a sponsorship deal with a cannabis company
https://www.forbes.com/sites/ajherrington/2022/11/17/chicago-wolves-ink-sponsorship-deal-with-marijuana-firm-verilife
The Wolves are in the American Hockey League, just one step below the big leagues of the NHL.

The War on Drugs & Prohibition

In Ireland, a brutal 5-year prison sentence for a cannabis caregiver supplying cannabis oil to patients (hattip to Becca Williams – cannabis, psilocybin & emotional liberation expert)
https://cannabishealthnews.co.uk/2022/12/13/five-year-sentence-for-ireland-cannabis-caregiver-is-brutal-wildly-disproportionate

The Sinaloa Cartel is trying to corner Mexico’s legal weed market before it even begins
https://www.cannabisbusinessexecutive.com/2022/12/the-sinaloa-cartel-is-losing-its-marijuana-business-and-el-chapos-sons-are-going-after-the-premium-weed-market-to-make-up-for-it

A review of the literature finds that liberalizing cannabis policies leads to decreases in violent and property crime, reductions in drug-related arrests & an improvement in crime clearance rates but had mixed results for public health & driving while “all-drug decriminalization is associated with reductions in problematic drug use and criminal justice overcrowding, declines in youth drug use, and other health and social benefits” (see Portugal)
Effects of Drug Policy Liberalization on Public Safety: A Review of the Literature
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4294150

Even though prohibitionists say that decrim is enough to stop cannabis arrests, the American Medical Association released a study showing that full legalization drives down arrests even more
https://www.marijuanamoment.net/marijuana-legalization-reduces-arrests-even-in-states-that-already-decriminalized-american-medical-association-study-finds
As the ACLU says…

ACLU @ACLU

AS A REMINDER: No one should be incarcerated for marijuana. Ever.

NORML reports that the US expunged or pardoned almost 2M cannabis convictions in the last 5 years
https://www.marijuanamoment.net/nearly-2-million-marijuana-convictions-have-been-pardoned-or-expunged-in-the-u-s-in-the-past-five-years-new-report-shows

The feds investigating the NYPD for planting illegal drugs during car stops
https://www.thecity.nyc/2022/12/13/23507834/edny-fbi-investigating-nypd-drug-planting-allegations
Those motherfuckers do this all the time. Any connected journalist in the city knows the stories.

A study of officer discretion in the enforcement of cannabis laws
Marijuana Enforcement since Drug Policy Reform: An Exploration of Officer Discretion in Six States
https://link.springer.com/article/10.1007/s12103-022-09704-6

A law review on how the Farm Bill is changing drug sentencing in the US
Changing Drug Schedules and Sentence Enhancements in the Sixth Circuit
https://kb.osu.edu/bitstream/handle/1811/102373/1/OSLJ_SCR_V83_010.pdf

An unsurprising study finds that a state’s legalization of cannabis leads to more seizures of cannabis by the US Post Office
Marijuana Legalization and U.S. Postal Inspection Service Seizures: An Exploration of Black Market Activity
https://link.springer.com/article/10.1007/s12103-022-09696-3
And to all of you smugglers out there, remember that the only drug that they can readily find in the mail is cannabis. Everything else is smooth sailing.

2019: On the markers cops use to find the country of origin for seized cannabis samples
Determination of Geographical Origin of Cannabis - A Review
https://www.researchgate.net/publication/334696225_Determination_of_Geographical_Origin_of_Cannabis_-_A_Review

Psychedelics, Plant Medicines & Other Psychoactives

The American Medical Association predicts that most states will legalize psychedelics by 2037
https://www.marijuanamoment.net/most-states-will-legalize-psychedelics-by-2037-analysis-published-by-american-medical-association-predicts
Excellent. Just in time for my kids to be finishing high school…

Quebec becomes the first province to publicly cover the cost of psilocybin-assisted psychotherapy
https://therapsil.ca/quebec-first-province-to-cover-costs-of-psilocybin-assisted-psychotherapy-done-by-two-physicians

Although many have said they would, Journey Colab becomes the first psychedelic company to publicly pledge to not sue Indigenous groups for patent infringement for traditional uses of their medicine
https://www.journeycolab.com/patent-pledge
In one sense, that’s great. Good for them being the first.
But in another sense, what a fucked up system that it’s even possible to consider suing people for traditional uses of their sacred plants in ceremonies that go back thousands of years on the basis of your patents that go back hundreds of months.
An excellent book on the subject of biomedical patents & the dark looming presence of the US is my buddy Alex Zaitchik’s ‘Owning the Sun: A People's History of Monopoly Medicine from Aspirin to COVID-19 Vaccines’.

On GHB & patents

On Drugs

GHB, Orphans, and REMS: A Regulatory Love Story (Part 1)

Interested in psychedelics, psychedelic regulation, and/or psychedelic patenting? Or, do you have a pharma fetish (like me)? Either way, pay attention to this one. I’m going deep. Around a month ago, in the District of Delaware, the Federal Trade Commission (FTC) filed an…

3 months ago · 3 likes · 1 comment · Matt

On how the harvesting of MDMA precursors is destroying Cambodian forests
https://www.talkingdrugs.org/climate-lessons-from-cambodias-illegal-mdma-market

An essay on how psychedelics helped to birth the radical ecology movement
https://bulletin.hds.harvard.edu/the-greening-of-psychedelics

On the entities you might see in the DMT space…

Terence McKenna's Dad @FatherMcKennaa

DMT is a unique psychedelic because it induces entity encounters in ~95% of users. These entities have been spotted by multiple people, varying in appearance & motivation. But what are the different types & how do they act? 🧵on the different types of DMT entities:

I’ve been getting in arguments online (rare for me) with materialists who think that these things must all be inside their head. What annoys me is how much it ignores the data found in the study of the supernormal as well the history of religion & folklore. See the work of Dr. Jeffrey Kripal, John Keel, Lesley Kean, Charles Fort or Jacques Vallée.
(if you’re into this subject, I cover a good bit of the supernormal on my TikTok channel)

The Science of Psychedelics

[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to your organization, reach out to me]

In 30 patients with cancer & depression, psilocybin improved their psycho-social-spiritual healing
Psilocybin-assisted therapy mediates psycho-social-spiritual change in cancer patients as assessed by the NIH-HEALS
https://pubmed.ncbi.nlm.nih.gov/36513161

In a double-blind trial with ayahuasca, measurements two days after the session found reduced depressive symptoms, moderated levels of cortisol (stress hormone) & increased BDNF (a brain growth factor)
Moderators of ayahuasca’s biological antidepressant action
https://www.frontiersin.org/articles/10.3389/fpsyt.2022.1033816/full
That classic psychedelics are growing new brain cells is probably what underlies a good deal of their healing power.

In a review of 10 studies of psilocybin on depression, he effects lasted up to 6 months, higher doses & two sessions were linked to stronger antidepressant effects & they displayed a favorable cardiovascular safety profile
Trajectory of Antidepressant Effects after Single- or Two-Dose Administration of Psilocybin: A Systematic Review and Multivariate Meta-Analysis
https://pubmed.ncbi.nlm.nih.gov/35207210

A review discussing how recent computational psychiatry advances can be used to predict individual responses to find patients who might benefit the most from psychedelic treatment through the integration of brain-wide PET or transcriptomic data combined with computational neuroimaging methods
Towards mapping neuro-behavioral heterogeneity of psychedelic neurobiology in humans
https://www.sciencedirect.com/science/article/pii/S0006322322018054

Business & Law

Whew. That FDA is watching your social media closely now…

Asa Waldstein @AsaWaldstein

If a company engages with a post on its social media wall, this is considered “endorsing the testimonial” and is marketing. Full post 👉 asawaldstein.com/warning-letter… #WarningLetterWednesday #SocialMedia #Cholesterol

Hemp market projected to reach $18B by 2027
https://www.ganjapreneur.com/report-global-hemp-market-to-exceed-18b-by-2027

The National Labor Relations Board ruled that Curaleaf violated labor law by refusing to bargain with unionized workers
https://www.greenmarketreport.com/nlrb-curaleaf-violated-labor-law-by-refusing-to-bargain-with-union

An editorial calling for the health & safety of workers in the cannabis industry
Cannabis industry worker health and safety: time for action
https://www.tandfonline.com/doi/full/10.1080/1059924X.2022.2148031

The Plant & the History

A robot with a wonderful name who stalks & destroys male hemp plants
STALKer: Terribly Accurate, Horribly Fast, Deep Learning Pipeline for Automatic Hemp Stalks Segmentation and Grasping Point Detection
https://www.researchgate.net/publication/365173700_STALKer_Terribly_Accurate_Horribly_Fast_Deep_Learning_Pipeline_for_Automatic_Hemp_Stalks_Segmentation_and_Grasping_Point_Detection

The USDA grants nearly $5M for research on hemp fiber
https://mailchi.mp/9b55e6e54d00/hemp-industry-supported-project-wins-usda-grant-for-climate-smart-fiber-hemp-research

A US Forest Service study on surface water contamination below illegal cannabis grow sites
Passive monitoring of soluble pesticides linked to cannabis cultivation: a multi-scale analysis
https://iwaponline.com/wqrj/article/57/4/233/92051

2021: What’s in your cannabis roots?
Chemical composition and antioxidant potential of Cannabis sativa L. roots
https://www.sciencedirect.com/science/article/pii/S0926669021001862
In the history of medicine, there’s a number of references to the medical use of cannabis roots. See the Bangladesh report below.

A higher density of cannabis plants leads to increased yield but decreased uniformity of cannabinoid composition
Too Dense or Not Too Dense: Higher Planting Density Reduces Cannabinoid Uniformity but Increases Yield/Area in Drug-Type Medical Cannabis
https://pubmed.ncbi.nlm.nih.gov/36247643

On hemp growing, the effects of plant density & nitrogen fertilization
Variability of cannabinoid yields of fibre hemp cultivars depending on the sowing density and nitrogen fertilization
https://www.agriculturejournals.cz/web/pse.htm?type=article&id=223_2022-PSE

A study of how to best grow hemp in temperate conditions
The Effects of Irrigation, Topping, and Interrow Spacing on the Yield and Quality of Hemp (Cannabis sativa L.) Fibers in Temperate Climatic Conditions
https://www.mdpi.com/2077-0472/12/11/1923

2021: A study of how different light spectra alter cannabinoid profiles & how this might be used to fine-tune cannabis plant production
Light matters: Effect of light spectra on cannabinoid profile and plant development of medical cannabis (Cannabis sativa L.)
https://www.sciencedirect.com/science/article/abs/pii/S0926669021001151

With the dreaded Aspergillus fungus, you might use X-rays for irradiation
Use of X-ray irradiation for inactivation of Aspergillus in cannabis flower
https://pubmed.ncbi.nlm.nih.gov/36378669

In propagating the plant via tissue culture, the effect of different sterilization rinses
Effects of Different Sterilization Rinses on Germination of Hemp, Cannabis Sativa, for Tissue Culture
https://krex.k-state.edu/dspace/handle/2097/42821

Hemp Seeds, Hemp Oil & Human Consumption

For your yogurt, hemp protein improves the nutritional quality & the mouthfeel
Effect of hemp protein on the physicochemical properties and flavor components of plant-based yogurt
https://www.sciencedirect.com/science/article/pii/S0023643822010805

A review of hempseeds and how they are antioxidant, anti-inflammatory & neuroprotective
Agro-industrial potential of Cannabis Sativa L. Seeds as a sourse of biological active substances
http://www.repository.utm.md/handle/5014/21644

In mice being fed a fatty diet, hempseeds modulated their endocannabinoid system, improved the walls of their intestines & decreased inflammation in their guts
Hemp seed significantly modulates the endocannabinoidome and produces beneficial metabolic effects with improved intestinal barrier function and decreased inflammation in mice under a high-fat, high-sucrose diet as compared with linseed
https://pubmed.ncbi.nlm.nih.gov/36238310

Animal feed

A review of using hemp & CBD in your animal diets
Hemp in Animal Diets-Cannabidiol
https://pubmed.ncbi.nlm.nih.gov/36230282

In laying hens, hemp seed meal increased their egg production as well as improving yoke color & omega-3 fatty acid content
Evaluation of dietary hemp seed meal as soybean meal substitution on productive performance, egg quality, and yolk fatty acid composition of laying hens
https://assets.researchsquare.com/files/rs-2214116/v1/521438aa-ea03-4f45-a4f1-982aab62b638.pdf

For your weaned piglets, hemp to help with their antioxidation
Assessment of flax and hemp fibres in terms of their impact on the growth performance and health status of weaned piglets
https://pubmed.ncbi.nlm.nih.gov/36481350

Industrial Use & Inventions

Using hemp to make a pH acidity sensor
Natural dye modified hemp fibrous foam for colorimetric NH3 sensing
https://www.sciencedirect.com/science/article/abs/pii/S0926669022014339

On the effects of reinforcing sand for construction projects with hemp fiber

Experimental investigation of the mechanical behavior and engineering properties of sand reinforced with hemp fiber
https://link.springer.com/article/10.1007/s12517-022-10966-x

Using hemp biochar to clear heavy metal ions from wastewater
Constructing the vacancies and defects by hemp stem core alkali extraction residue biochar for highly effective removal of heavy metal ions
https://pubmed.ncbi.nlm.nih.gov/36126592

Cannabinoid Science

2021: A review of the traditional medicinal use of cannabis in Bangladesh
A narrative review of the ethnomedicinal usage of Cannabis sativa Linnaeus as traditional phytomedicine by folk medicine practitioners of Bangladesh
https://pubmed.ncbi.nlm.nih.gov/33741060
As always, I maintain that the real wisdom on how widely cannabis can be used rests in the domain of traditional medicinal uses.
“While reviewing over 200 ethnomedicinal plants' survey articles, we found that FMPs [folk medicine practitioners] of Bangladesh from 12 different districts used Cannabis sativa to treat cited ailments like sleep-associated problems (n=5), neuropsychiatric and CNS problems (n=5), and infections and respiratory problems (n=5) followed by rheumatism, gastrointestinal, gynecological (n=4 each), cancer, sexual, and other ailments including hypertension, headache, itch, increases bile secretion, abortifacient, dandruff, fever, and urinary problems (n=1 each). There are a total of 15 formulations identified from the 11 out of 18 ethnomedicinal plant survey reports. The leaf was the main plant part used (53.8%), followed by root (23%), seed (7.7%) and flower, inflorescence, resin, and all parts 3.8% respectively.”

2021: The traditional hallucinogenic plant Mirabilis multiflora (aka Colorado four o'clock) used by the Hopi Indians seems to exert some of its effects via the cannabinoid & opioid receptors
Rotenoids and Other Specialized Metabolites from the Roots of Mirabilis multiflora: Opioid and Cannabinoid Receptor Radioligand Binding Affinities
https://pubmed.ncbi.nlm.nih.gov/33734684

Clinical Studies, Surveys & Ingestion

In people with insomnia & cannabis use disorder, Cognitive Behavioral Therapy helped with their sleep & related anxiety as well as reducing cannabis consumption & markers of inflammation
Assessing cognitive behavioral therapy for insomnia in individuals with cannabis use disorder utilizing actigraphy and serum biomarkers: A pilot study
https://pubmed.ncbi.nlm.nih.gov/36244318

In healthy humans, the safety, effects & flow through the body of Spectrum Yellow Oil (20 mg CBD + ~0.5 mg THC per mL)
Safety, Pharmacokinetics and Pharmacodynamics of Spectrum Yellow Oil in Healthy Participants
https://pubmed.ncbi.nlm.nih.gov/33710277

In data from Australian clinics, medical cannabis helped with pain & reduce the use of other medications
Longitudinal Relationship between the Introduction of Medicinal Cannabis and Polypharmacy: An Australian Real-World Evidence Study
https://pubmed.ncbi.nlm.nih.gov/36448002

2021: A safety review of 24 studies on nabiximols (ie: Sativex – a 1:1 THC:CBD spray)
Safety and tolerability of nabiximols oromucosal spray: a review of real-world experience in observational studies, registries, and case reports
https://pubmed.ncbi.nlm.nih.gov/33749480

A review of the methods used in studying cannabis use among youth
Qualitative Research on Cannabis Use Among Youth: A Methodological Review
https://journals.sagepub.com/doi/pdf/10.1177/00220426221139420

In interviews with cannabis patients, they defined their research priorities as: adverse events, comparison between cannabis-based medicinal products, health conditions, pharmacology of cannabis, types of study, healthcare professionals' attitudes, social environment, agriculture & manufacturing &the cannabis plant
Patient priorities for research: A focus group study of UK medical cannabis patients
https://pubmed.ncbi.nlm.nih.gov/36399996

In a test of THC & CBD edibles, participants who consumed both THC & CBD had a less strong psychoactive effect & lower levels in their bloodstream
Cannabinoid Exposure and Subjective Effects of THC and CBD in Edible Cannabis Products
https://pubmed.ncbi.nlm.nih.gov/36378267

In a test of CBD patches, only one of them was found to have a level of CBD within 10% of its label
A reliable quantitative method for determining CBD content and release from transdermal patches in Franz cells
https://pubmed.ncbi.nlm.nih.gov/36372393

In the THC aerosol device SyqeAir, the natural degradation of THC over 2 years did not impair its accuracy (within a range of 25%)
THC degradation does not impair the accuracy of THC doses aerosolized by the metered-dose SyqeAir inhaler: a 24-month stability trial
https://pubmed.ncbi.nlm.nih.gov/36274184

Mental Health, Addiction & Mental Effects

In a safety study of children with autism, treatment with a 20:1 CBD:THC solution caused no significant differences in the safety biomarkers measured
Medical cannabis for the treatment of comorbid symptoms in children with autism spectrum disorder: An interim analysis of biochemical safety
https://pubmed.ncbi.nlm.nih.gov/36249785

A review of autism & why using cannabinoids seems to help with a number of the behavioral, cognitive, social interaction, hyperactivity, anxiety & sleep symptoms
Implications of the endocannabinoid system and the therapeutic action of cannabinoids in autism spectrum disorder: A literature review
https://pubmed.ncbi.nlm.nih.gov/36379443

In a meta-analysis of cannabis use & antipsychotic drugs for schizophrenia, cannabis use did not seem associated with higher doses of antipsychotics or with poorer symptoms but was associated with a higher risk of relapse
Impact of cannabis use and its cessation on the dosage and the efficacy of antipsychotic drugs in in- and outpatients with schizophrenia taking medication: A systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/36410310

In fMRI studies of chronic cannabis users, at resting state, they had hyper-connectivity between their major brain areas compared to occasional users – but after ingesting THC, they had less connectivity between certain brain regions
Functional brain connectomes reflect acute and chronic cannabis use
https://pubmed.ncbi.nlm.nih.gov/35165360
“Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication.”

In humans, the genetic variant of their FAAH enzyme (which regulates anandamide levels) that caused it to have the slowest activity speed (the A variant) increased their odds of binge drinking at 20 the age, lowered the time to their initiation to drinking & tobacco & was associated with a younger age to start daily drinking
Genetic variation in fatty acid amide hydrolase (FAAH): Associations with early drinking and smoking behaviors
https://pubmed.ncbi.nlm.nih.gov/36403489

2021: In young adults who binge drink, daily cannabis use was associated with less impulse control & more hyperactive ADHD symptoms while this was not true in occasional cannabis users
Daily, but not occasional, cannabis use is selectively associated with more impulsive delay discounting and hyperactive ADHD symptoms in binge-drinking young adults
https://pubmed.ncbi.nlm.nih.gov/33638699

In a mouse model of acute despair [I hate how biomedical research has turned us into monsters], activating the CB1 receptor causes antidepressant effects
Hippocampal CB1 receptor mediates antidepressant-like effect of synthetic cannabinoid-HU210 in acute despair reaction model in mice
https://pubmed.ncbi.nlm.nih.gov/36372093
Let’s just be fair. Take 10 college freshmen. Murder their cat. Give half of them an experimental drug that mimics THC. Then see who drowns the least when you throw them in a swimming pool for 3 hours & don’t let them touch the sides.

2021: In rats, how THC disrupts memory formation via signaling cascades & the hippocampus
The role of Tetrahydrocannabinol in inducing disrupted signaling cascades, hippocampal atrophy and memory defects
https://pubmed.ncbi.nlm.nih.gov/33689904

In a mouse model of Alzheimer’s disease, the levels of CB2 receptors increased in glial cells (guardian immune cells of the brain) which suggest CB2 as a target for neuroinflammation
Evaluation of cannabinoid type 2 receptor expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer's disease
https://pubmed.ncbi.nlm.nih.gov/36248003

2021: In zebrafish embryos (a common model organism for development), brief exposure to CBD &THC reduced later neural & locomotor activity with CBD causing stronger effects than THC
Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and Δ9-tetrahydrocannabinol
https://pubmed.ncbi.nlm.nih.gov/34075141

The Brain & its Diseases

In humans using medical cannabis, six months of use increased the coherence of their white matter while CBD reduced their mean diffusivity (higher water content in their brain, neuroprotective against demyelination diseases like Parkinson’s)
Increased White Matter Coherence Following Three and Six Months of Medical Cannabis Treatment
https://pubmed.ncbi.nlm.nih.gov/36367574

A review of 11 patients on using CBD for refractory status epilepticus (seizures of long duration or that occur very close to each other & are not well managed by drugs) shows how powerful it can be compared current options
Cannabidiol in refractory status epilepticus: A review of clinical experiences
https://pubmed.ncbi.nlm.nih.gov/36399869
“Patients were trialed on an average of 9 anti-epileptic drugs prior to CBD administration, after which 9 of the 11 patients experienced a reduction of seizure activity. Dosing of CBD ranged between 5-25 mg/kg/day and was titrated based on patient response to therapy. Adverse effects were relatively benign and were generally limited to gastrointestinal discomfort, reported after seizure cessation.”

In Sturge-Weber syndrome (a rare genetic disorder of the blood vasculature system), CBD helped with seizure control, anxiety, emotional regulation & quality of life
Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome
https://pubmed.ncbi.nlm.nih.gov/36508880

A comprehensive review of using CBD for neurodegenerative disorders
Cannabidiol for neurodegenerative disorders: A comprehensive review
https://pubmed.ncbi.nlm.nih.gov/36386183
And a literature review of using cannabis & CBD for neurodegenerative disorders
Cannabis sativa and Cannabidiol: A Therapeutic Strategy for the Treatment of Neurodegenerative Diseases?
https://pubmed.ncbi.nlm.nih.gov/36467781

A common treatment for Alzheimer's disease is the inhibition of acetylcholinesterase (slows excitation of nerves) & in this experiment, cannabis extracts caused inhibition of these enzymes
Acetylcholinesterase Inhibitory Activity of Standardized Cannabinoids-rich Fractions
https://pbr.mazums.ac.ir/article-1-454-en.html

For inhibiting phosphodiesterases (a drug class investigated for their use against neurodegeneration), computer simulations & assays showed CBD to be a promising option
Virtual screening and in vitro experiments highlight cannabidiol as a drug-like phosphodiesterase 9 inhibitor
https://pubmed.ncbi.nlm.nih.gov/36382587

In a rat model of multiple sclerosis, a combination of exercise & royal jelly (the magic food made by honeybees) improved their pain tolerance probably via the CB1 receptor
The Effect of Exercise Training and Royal Jelly on Hippocampal Cannabinoid-1-Receptors and Pain Threshold in Experimental Autoimmune Encephalomyelitis in Rats as Animal Model of Multiple Sclerosis
https://pubmed.ncbi.nlm.nih.gov/36235771

In neurons of the hippocampus (memory area of the brain), the neuroprotection caused by glutamate (the brain’s primary excitatory neurotransmitter) is mediated by the CB1 receptors & GABA (the brain’s primary inhibitory neurotransmitter)
The Neuroprotective Effects of mGlu1 Receptor Antagonists Are Mediated by an Enhancement of GABAergic Synaptic Transmission via a Presynaptic CB1 Receptor Mechanism
https://pubmed.ncbi.nlm.nih.gov/36230976

In mice, the novel synthetic cannabinoid mepirapim causes Parkinson's disease-like symptoms via dysregulation of the dopamine system
Mepirapim, a novel synthetic cannabinoid, induces Parkinson's disease-related behaviors by causing maladaptation of the dopamine system in the brain
https://pubmed.ncbi.nlm.nih.gov/36355181

Harms, Cannabis Use Disorder & Street Synthetics

A rare case report of psychosis from cannabis withdrawal
Psychotic Cannabis Withdrawal: A Clinical Case
https://pubmed.ncbi.nlm.nih.gov/36523702

A genome association study finds 17 genes associated with a propensity to cannabis use disorder
Transcriptome-wide association study by different approaches reveals candidate causal genes for cannabis use disorder
https://pubmed.ncbi.nlm.nih.gov/36379386

In children with poor executive function, they were more likely to use cannabis weekly or daily in their teen years & parental cannabis use also increased their chances of later use
Ratings of executive function as a risk factor for adolescents' frequent cannabis use: A prospective longitudinal study
https://pubmed.ncbi.nlm.nih.gov/36355660

In an examination of the public data on the co-use of alcohol with cannabis, cannabis use frequency predicted alcohol use frequency & individuals who co-used alcohol & cannabis reported more symptoms of alcohol use disorder
Frequency matters: Relations among alcohol and cannabis co-use frequency and alcohol use disorder symptoms in emerging adults
https://pubmed.ncbi.nlm.nih.gov/36355682

2021: On using topical capsaicin for treating cannabinoid hyperemesis syndrome (uncontrolled cyclical vomiting)
Is capsaicin an effective treatment for cannabinoid hyperemesis syndrome?
https://journals.lww.com/ebp/Citation/2021/12000/Is_capsaicin_an_effective_treatment_for.33.aspx

A case report of a bad trip on 5F-ADB
Analytical findings in a non-fatal intoxication with the synthetic cannabinoid 5F-ADB (5F-MDMB-PINACA): a case report
https://pubmed.ncbi.nlm.nih.gov/34921326

The synthesis & effects of various synthetic cannabinoids
Synthesis and pharmacological evaluation of newly detected synthetic cannabinoid receptor agonists AB-4CN-BUTICA, MMB-4CN-BUTINACA, MDMB-4F-BUTICA, MDMB-4F-BUTINACA and their analogs
https://pubmed.ncbi.nlm.nih.gov/36245876

How two major synthetic cannabinoids move through the system: 5F-EDMB-PICA and EDMB-PINACA
Human phase-I metabolism and prevalence of two synthetic cannabinoids bearing an ethyl ester moiety: 5F-EDMB-PICA and EDMB-PINACA
https://pubmed.ncbi.nlm.nih.gov/36366743

2021: Overview of the synthetic cannabinoids ADB-FUBINACA & AMB-FUBINACA
Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications
https://pubmed.ncbi.nlm.nih.gov/33669071

Lungs & Vaping

2021: In a study of smoke, cannabis consistently gave off more emissions than tobacco with the greatest emissions coming from joints, than bongs, glass pipes & vapes with the least
Measuring indoor fine particle concentrations, emission rates, and decay rates from cannabis use in a residence
https://www.sciencedirect.com/science/article/pii/S259016212100006X
It’s true. For some reason, weed smoke puts off more emissions than tobacco smoke. That being said, the dangers of second-hand smoke have been far inflated by the FDA on their anti-tobacco warpath. Like most everything else with cannabis dangers, the issue of secondhand smoke emissions is a real but overly minor public health concern.

In chest scans of cannabis smokers, they had more airway inflammation & emphysema than in non-smokers & tobacco only smokers
Chest CT Findings in Marijuana Smokers
https://pubs.rsna.org/doi/abs/10.1148/radiol.212611

In a test of human lung cells & vape oil, both CBD & vitamin E acetate caused cell toxicity & death
Vaping additives cannabinoid oil and vitamin E acetate adhere to and damage the human airway epithelium
https://pubmed.ncbi.nlm.nih.gov/36372912

A well-done history of cannabis paired with the public health considerations of cannabis vaping
The history, evolution, and practice of cannabis and E-cigarette industries highlight necessary public health and public safety considerations
https://www.sciencedirect.com/science/article/abs/pii/S0022437522001724

In a study of vapes, the illegal ones had higher levels of nickel & zinc while the legal ones had the highest levels of copper
Evidence That Metal Particles in Cannabis Vape Liquids Limit Measurement Reproducibility
https://pubmed.ncbi.nlm.nih.gov/36467951

Pain, Inflammation & Surgeries

A review of 8 studies on humans with chronic neuropathic pain found that it helped with their sleep & pain
Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials
https://rapm.bmj.com/content/early/2022/12/04/rapm-2021-103431.abstract

A review of animal studies on using CBD for chronic pain finds it causes “analgesic [painkilling] effects, decreasing hyperalgesia [extreme sensitivity to pain] & mechanical/thermal allodynia [pain from a a stimulus that does not normally provoke pain]”
Chronic Pain and Cannabidiol in Animal Models: Behavioral Pharmacology and Future Perspectives
https://pubmed.ncbi.nlm.nih.gov/36355044

A case report of an older woman using cannabis for her chronic pain & how it reduced her opioid medication dosage
The Utility of Cannabis-Based Medicine in Chronic Pain Management: A Case Report
https://www.cureus.com/articles/113524-the-utility-of-cannabis-based-medicine-in-chronic-pain-management-a-case-report

In mice using swimming as a painkiller, their ability to endure pain was correlated with their spinal cord levels of AEA, 2-AG & CB1 receptors & seemed to work via the microglia (guardian immune cells of the brain & spinal cord)
Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia-The Role of Endocannabinoids and Microglia
https://pubmed.ncbi.nlm.nih.gov/36232988

In a mouse model of chronic neuropathic pain, the synthetic painkiller crotalphine works via the cannabinoid, opioid & various other systems
Crotalphine Modulates Microglia M1/M2 Phenotypes and Induces Spinal Analgesia Mediated by Opioid-Cannabinoid Systems
https://pubmed.ncbi.nlm.nih.gov/36232883

The Immune System, Autoimmune Disorders & Pathogens

In a meta-analysis of patients with fibromyalgia, they had higher levels of the lipids oleoylethanolamide & stearoylethanolamide & for those patients with widespread pain, higher PEA
Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/36381652

In white blood cells battling HIV, CBD changes the expression of several genes related to the immune system & inflammation while a long-term CBD treatment reduced the spread of the virus
Cannabidiol modulates expression of type I IFN response genes and HIV infection in macrophages
https://pubmed.ncbi.nlm.nih.gov/36248834

In a model of staph infection, beta-caryophyllene reduced pain & caused anti-inflammation
β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo
https://pubmed.ncbi.nlm.nih.gov/36357780

The Guts, the Microbiome & Oral Health

A post on harnessing the power of the endocannabinoid system to help us overcome the obesity epidemic
https://canndeal.global/2022/03/01/rethinking-cannabis-and-metabolism

A food study using molecular networking analysis finds that CBD causes anti-obesity effects via alterations of lipids, carbohydrates, amino acids & nucleic acid levels
Foodomics Reveals Anti-Obesity Properties of Cannabinoids from Hemp Oil
https://pubmed.ncbi.nlm.nih.gov/36382382

In this review of the enteric nervous system in your guts, it looks at the many roles played by your endocannabinoid system & suggests targeting it for treating diseases
The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?
https://pubmed.ncbi.nlm.nih.gov/36235308

In a rat model of obesity, blocking the CB1 receptor led to weight loss & fat reduction but also increased systemic inflammation
CB1 Ligand AM251 Induces Weight Loss and Fat Reduction in Addition to Increased Systemic Inflammation in Diet-Induced Obesity
https://pubmed.ncbi.nlm.nih.gov/36232744
This mimics the action of Rimonabant – a CB1 blocker that was the first great failure of the synthetic cannabinoid pharma game. Approved for obesity in the UK (but not the US), it did help people to lose weight. But it also increased suicidal ideation & had to be pulled off the market.

2021: In islets of the pancreas (secretors of insulin), activating the CB2 receptor stimulated insulin secretion
Direct Stimulatory Effects of the CB2 Ligand JTE 907 in Human and Mouse Islets
https://pubmed.ncbi.nlm.nih.gov/33809893

The Heart & the Blood

In rats, exposure to cannabis smoke (or tobacco smoke) caused increased blood pressure, decreased cardiac function, severe fibrosis (scarring) with decreased microvessel density & reduced overall heart rate variability
Increased vulnerability to atrial and ventricular arrhythmias caused by different types of inhaled tobacco or marijuana products
https://www.sciencedirect.com/science/article/pii/S1547527122024869

In human blood, the FAAH enzyme (which regulates anandamide levels) was highest in platelets while the MGL enzyme (which regulates 2-AG levels) was highest in red blood cells. Incubating them with thrombin (an enzyme of blood coagulation) increased FAAH levels
Endocannabinoid hydrolases differentially distribute in platelets and red blood cells and are differentially released by thrombin
https://pubmed.ncbi.nlm.nih.gov/36372184
So FAAH & anandamide may be somehow tied up in blood coagulation?
#WhatDoesntThisEndocannabinoidSystemHaveItsFattyLittleFingersIn?

The Muscles & Bones

In skeletal muscle cells, interactions between the other lipid signaling system sphingosine 1-phosphate (S1P) & the ECS seem to be mediated by the vanilloid receptor TRPV1
The TRPV1 Receptor Is Up-Regulated by Sphingosine 1-Phosphate and Is Implicated in the Anandamide-Dependent Regulation of Mitochondrial Activity in C2C12 Myoblasts
https://pubmed.ncbi.nlm.nih.gov/36232401

The Eyes

In mouse retina cells, the endocannabinoids modulate retinal signaling via the CB1 & CB2 receptors
Tonic Endocannabinoid Levels Modulate Retinal Signaling
https://pubmed.ncbi.nlm.nih.gov/36231760

In pig eyes, CBD increased the flow of the aqueous humor (the fluid that contributes to the intraocular pressure important in eye diseases like glaucoma) via collagen contraction, the inhibition of myosin light chain (MLC) & myosin phosphatase targeting subunit 1 (MYPT1) & reduced activation of RhoA
The Effects of Cannabidiol on Aqueous Humor Outflow and Trabecular Meshwork Cell Signaling
https://pubmed.ncbi.nlm.nih.gov/36230968

Reproductive & Maternal Effects

In a study of pregnant women, prenatal exposure to both tobacco & cannabis was associated with lower levels of inflammation in their children at age 60 months but this association was not found when using a combination of maternal self-report & biomarker data
Associations between prenatal and postnatal substance exposure and salivary C-reactive protein in early childhood
https://pubmed.ncbi.nlm.nih.gov/36395973

Cancer & Chemo

A review of the potential of the cannabinoids for the abnormal energy metabolism of cancer
Disorders of cancer metabolism: The therapeutic potential of cannabinoids
https://pubmed.ncbi.nlm.nih.gov/36379120

In patients with liver cancer, the CB receptor had a tumor-promoting effect as well as an increase of inflammation
Immunohistochemical expression of CB1 receptors in the liver of patients with HBV related-HCC
https://pubmed.ncbi.nlm.nih.gov/36379858

In renal cancer cells, CBD enhanced the efficacy of the standard treatment drug sunitinib via increased apoptosis (cellular suicide)
Cannabidiol Enhances Sunitinib Effect in Human Renal Cell Carcinoma by Inducing Apoptosis and Inhibiting Stat3 Signaling Pathway
https://www.pjmhsonline.com/index.php/pjmhs/article/view/2912

2021: A case report & literature review of using cannabis in a pregnant person to treat their Hodgkin's lymphoma
The effect of cannabis in the treatment of Hodgkin's lymphoma in a pregnant patient - extensive case report and literature review
https://pubmed.ncbi.nlm.nih.gov/33721427

Cool Chemistry

How the CB1 receptor passes on its signals via the arrestins (messenger fish)
Cannabinoid 1 (CB1 ) receptor arrestin subtype-selectivity and phosphorylation dependence
https://pubmed.ncbi.nlm.nih.gov/36250246

A look at all the newest activators of the CB2 receptor
Design, synthesis and biological evaluation of novel orthosteric-allosteric ligands of the cannabinoid receptor type 2 (CB2R)
https://pubmed.ncbi.nlm.nih.gov/36238097
2021: And a review of all the synthetics used to activate the CB1 receptor for research
The synthetic CB1 cannabinoid receptor selective agonists: Putative medical uses and their legalization
https://pubmed.ncbi.nlm.nih.gov/33741446
Someday, if the breath lasts long enough in my body, I will turn these papers into a chart that shows each of these cannabinoids as a different type of elephant/whale hybrid & what they do at the bars & gay bars of Neuronal City.
<cue ‘Mad About Me’> (yeah, I never that was the real name of the song until now either…)

On a novel allosteric modulator of the CB1 receptor
In Vitro Characterization of 6-Methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1H-indole (ZCZ011) at the Type 1 Cannabinoid Receptor: Allosteric Agonist or Allosteric Modulator?
https://pubs.acs.org/doi/10.1021/acsptsci.2c00160
Though the question always is: why not just use CBD?

2021: On developing super-strong molecules for binding to the cannabinoid receptors so that we can better experiment with & understand the endocannabinoid system
Novel Functionalized Cannabinoid Receptor Probes: Development of Exceptionally Potent Agonists
https://pubmed.ncbi.nlm.nih.gov/33761251
And since this study is from last year, I’m sure that these compounds are already on the street. The paper-to-underground production pipeline is faster than ever.

Thanks.
- lex

PS: For this week’s haunting vocals & songwriting, ‘The Vulture Prince’ by Arooj Aftab. A native of Pakistan who studied at Berklee, her work has been called jazz, minimalism, and neo-Sufi (the last one is close to my heart). Last year, she became the first Pakistani to win a Grammy award & this year, the President of Pakistan gave her the Pride of Performance Award, the highest literary award for showing excellence in the field of art and music.

The Living Glossary

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#37: cannabis for persistent viruses + CBD…