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Hello everyone,

​Welcome to the first edition of ‘Cannabinoids & the People’ (C&P#1).

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This newsletter only spreads by word of mouth – so please forward it to colleagues & share to your friends & elderly relatives. 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.

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

The main focus is cannabinoid science. I go through the hundreds of papers a week delivered by Google Scholar Alerts & annotate them for enjoyment. I’ll also include the top stories around law, business, history & the plant as well as the highlights of psychedelics & plant medicines - but the complete scouring for new cannabinoid science is what makes this newsletter special. In fact, this week is a little light because I had to set everything up - but you’ll see how much there can be.

That being said, I’ve already been doing a cannabinoid science newsletter for the CBD company CV Sciences for three years now. So this email could almost be seen as ‘HempNews#152’. (you can see the backcatalog of science on the research site I created for them here - though it’s been stripped of all the colorful commentary).

Now I’m striking off into the freelance education world with my new company White Whale Creations & this is my public offering.

So thanks for coming along for the ride. If you’d like to support with a paid subscription, it would certainly mean a lot to me & would put some more diapers on the baby’s butt - but there’s no extra content. Everything is put out here free for the world to share.

I’m also doing cannabis & CBD education sessions for those who want to learn about the ingestion methods, the tricks of how to use it & the science of underlying it. You can book a session here.
And please spread the word - both for this newsletter & for the education sessions.

Now, here’s your first edition…

Best of cannabinoid science...

In patients with autoimmune disorders, melatonin & CBD combined well to decrease autoantibody production

Neuroimmune Therapy of Autoimmune Diseases with the Pineal Hormone Melatonin Plus Cannabidiol and its Effects on Auto-Antibody Secretion

A review of using CBD for cancer patients
Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges

This review of 25 clinical studies of cannabinoids for neurodegenerative disorders finds that CBD helps with the motor symptoms of Parkinson’s & Huntington’s disease & that synthetic cannabinoids like dronabinol helped with the dementia of Alzheimer’s, Parksinson’s & Huntington’s
Cannabinoids in the management of behavioral, psychological, and motor symptoms of neurocognitive disorders: a mixed studies systematic review
& here’s a more general review of the mechanisms of the ECS underlying its ability to help with neurodegenerative disorders
Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty
I got into this field because of the ability of cannabinoids to help the elderly, especially with diseases of neurodegeneration. I wish I had known more before my grandmother passed from Parkinson’s disease. Now I do individual counseling sessions for patients & families struggling with these disorders. Book with me here.

The Headlines & Novel News

US officials complain to Russia about the imprisonment of basketball star Brittney Griner for the possession of cannabis vape cartridges
Meanwhile, US officials would have done the exact same thing to her if she got caught in one of their airports.

A survey of US adults finds 33% tried CBD, 20% tried THC foods & 15% tried THC drinks

The ASTM creates an international symbol for intoxicating cannabinoids… and it’s not bad

NIDA director Nora Volkow reports to Senate that cannabis legalization does not lead to increased use by teens
Despite the official purpose of NIDA to find the harms of drugs, Dr. Volkow has been a surprising figure of sanity since she took the agency’s helm.
Also, she’s the granddaughter of Trotsky (I mention this every time she comes up and - I think I have a crush on her)

Favorite tweet of the week: “I feel like Maine’s marijuana ad campaign that says “Driving High = OUI” doesn’t translate well when you’re reading it in a state where some people speak French at home”
As someone struggling to learn the language in France - and not helped by the effect of cannabis on my memory - I approve this message.

Law & Business

In Washington & Colorado, a study of cannabis legalization found that while arrests went down for all racial groups, “ Overall, evidence suggests that while legalization has likely had a net positive effect on overrepresented populations by decreasing criminal justice contact, it is not a panacea and may only be minimally important for addressing disparities”
Racial Disparities in the Wake of Cannabis Legalization: Documenting Persistence and Change

The US charged fewer people with cannabis-related crimes this year
It went from 7,000 people in 2012 to just under 1,000 last year. That being said, the vast majority of cannabis offenders go through state & local court systems, not federal.
(Also, that’s why you should never smoke on the Mall in Washington, DC. Technically, it’s a federal property & you get charged with a federal cannabis crime).

The Defense Office of Hearings & Appeals denied an applicant’s security clearance due to cannabis use despite a judge's ruling to approve it because he lives in a legal state you feeling safer yet?

In Florida, Black farmers will finally get a shot at a medical cannabis business license, but just one of them will win it
We’ll keep a focus on the equity movement that tries to make reparations for the War on Drugs. But it’s an ugly & mostly ineffective business. California & Massachusetts are two that are trying to do their best.

Speaking of, a depressing read on the state of the Oakland cannabis sellers
My very first interviews in the cannabis world were in Oakland almost 15 years ago & it’s a shame to see what bad laws, racism & bureaucratic blindness can do to an industry.

Medical Cannabis & Culture

The use of sublingual cannabinoids is gaining popularity as an ingestion method

In South Dakota, Gov. Kristi Noem signs a law protecting the right of medical cannabis patients to grow a few plants of their own
This is good news because ‘the right to grow’ is one of the most important ways to safeguard low-cost access for patients & to keep the specter of Big Cannabis of growing too strong. But overall, Noem has been an ogre on cannabis. She opposed a recreational cannabis law approved by state voters & successfully sued to have it invalidated. Then she had the gall to want the activists to pay the legal bills for the lawsuit.

In Pennsylvania, their Medical Marijuana Advisory Board looked at how the prices of wholesale cannabis are dropping while retail prices are holding steady
This is what happens when patients can’t grow their own medicine. And this is also what happens when legislators treat cannabis like a cash cow to be more heavily taxed than any other commodity & to mire it in over-restrictive regulations because of old prohibitionistic thinking. This makes a plant that is cheap & easy to produce into a highly-priced item that’s often unaffordable for the patients who need it the most. I grew up in Pennsylvania & I have family members there for whom this is a big problem.

Speaking of Big Weed, Cresco Labs to buy Columbia Care & create a cannabis conglomerate colossus
To follow the evolution of Big Weed, I recommend the cartoonist Brian Box Brown on Twitter. Here’s his thread of visuals on the biggest companies in the US:
[Also, I achieved a Melville score of 7 for this headline. That man loved alliteration & assonance]

It’s the 50th anniversary of the Shafer Commission: Nixon’s panel handpicked to create a report demonizing cannabis - and instead who did the exact opposite
The first report of the National Commission on marihuana (1972): signal of misunderstanding or exercise in ambiguity
This would be funny - if it wasn’t for the millions of lives destroyed by the continued prohibition of cannabis. And the Democrats have been just as bad as the Republicans. And Joe Biden still hasn’t commuted any cannabis sentences.

Rwanda put aside 134 hectares of land to start medical cannabis production

The Plant & the History

An excellent short history of the spread of cannabis across the world by Emma Stone & Pat Goggins
This is basically the story that I want to tell with the middle 50 chapters of my Moby Dick pot books. This is an excellent summary.

On using hemp to remove chromium & cadmium from contaminated aquatic soil
Binary adsorption of chromium and cadmium metal ions by hemp (Cannabis sativa) based adsorbents
The use of hemp as a soil remediator to remove toxic metals is something that gets studied fairly often in the lab but doesn’t actually see a lot of real-world projects. Though here’s one at Europe’s biggest steel plant

Here’s a new one for me: using cannabis seed oil to increase corrosion resistance in steel
An environmentally friendly formulation based on Cannabis sativa L. seed oil for corrosion inhibition of E24 steel in HCl medium: Experimental and theoretical study


(this is where I usually put the well-written popular science articles)

Dr. Deborah Malka on cannabis for asthma & the lungs in Project CBD

Clinical Studies & Surveys

In a wonderful confluence of our interests here, the effects of ayahuasca on the endocannabinoid of humans (hattip to Stuart Tomc)
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience

In patients with alopecia areata (spot baldness), a survey finds that they used cannabis for the stress, anxiety & depression resulting from the condition
Cannabis Use among Patients with Alopecia Areata: A Cross-Sectional Survey Study

In humans with autosomal dominant polycystic kidney disease (ADPKD - a genetic disorder with lots of renal cysts), they had reduced levels of anandamide & 2-AG & the researchers found that higher levels of PEA were associated with better kidney function
Endocannabinoid System in Polycystic Kidney Disease

Preclinical Research

In a model of cell membranes, the presence of CBD in membranes with low cholesterol decreased their permeability in water but in membranes with high levels of cholesterol, CBD increased water permeability
Differential Interaction of Cannabidiol with Biomembranes Dependent on Cholesterol Concentration

Recommended for You

In adult rats exposed to THC as adolescents, the ability of THC to reduce their pain was not altered & they imbibed less sugary water (hedonic drinking), while the female adults also displayed less sensitivity to the ability of THC to suppress activity
Adolescent THC exposure: effects on pain-related, exploratory, and consummatory behaviors in adult male vs. female rats
There’s two themes here that you will see repeated:
1. teen exposure to cannabinoids does alter outcomes for later in life (these tend not to be catastrophic - but anyone who says otherwise is trying to sell you something)
2. studies frequently find gendered differences in response to the cannabinoids (and yes, I know we’ve moved beyond gender in human relations - but it exists in the lab). And the different response of female-ish bodies to drugs & psychoatives - and their exclusion from studies for that reason - is a huge problem in modern medicine)
On that topic, here’s a review of the gendered responses to cannabis in terms of psychiatric disorders
Gender Differences in Dual Diagnoses Associated with Cannabis Use: A Review

In mice, CB1 seems to be vital to the cerebellar cortex of their brain responding to faces
Opposing Actions of CRF-R1 and CB1 Receptor on Facial Stimulation-Induced MLI-PC Plasticity in Mouse Cerebellar Cortex
There’s a reason that when you smoke pot & watch a movie, you don’t remember the movie as well. One of the most important parts of the endocannabinoid system is to help you forget things. That’s probably why cannabis can be so helpful for those with PTSD. But memory is complicated, and in this case, activating the CB1 receptor seems to help it.

Relatedly, in a rat model of aversive memories, the CB1 receptor seems to be modulating the fear response & the ability to extinguish a reaction to the fearful memory
Handling and novel object recognition modulate fear response and endocannabinoid signaling in nucleus basalis magnocellularis

In mice, 2-AG suppressed the emptying of their stomachs after a meal
2-Arachidonoyl glycerol suppresses gastric emptying via the cannabinoid receptor 1-cholecystokinin signaling pathway in mice
The endocannabinoids are hugely tied up in your digestive system & the regulation of your metabolism.

In melanoma cancer cells, anandamide (AEA) reduced glycosylation (modification of newly made proteins) & cell migration, suggesting its use as a combination therapy
Anandamide-Modulated Changes in Metabolism, Glycosylation Profile and Migration of Metastatic Melanoma Cells
In our neural ocean metaphor, anandamide - the first cannabinoid neurotransmitter discovered in the mammalian brain - is our Great White Whale. The use of cannabinoids as a cancer killer - and not just a treatment of symptoms - will be a repeated theme here.
If you know anyone battling cancer, they should definitely consider very high doses of cannabinoids for two weeks (Google ‘RSO for cancer’ to learn more). Or check out the book by the inimitable Justin Kander, ‘Cannabis for the Treatment of Cancer: The Anticancer Activity of Phytocannabinoids and Endocannabinoids’.

Relatedly, in bone cancer cells, CBD inhibited tumor growth, reduced cell migration & increased apoptosis (cellular suicide)
Cannabidiol promotes apoptosis of osteosarcoma cells in vitro and in vivo by activating the SP1-CBX2 axis

Cannabinoid Chemistry

Ohh. Looking at some newly minted molecules that might inhibit both FAAH & MGL & this raise levels of anandamide & 2-AG (see the glossary below for definitions of these terms)
Synthesis and evaluation of dual fatty acid amide hydrolase-monoacylglycerol lipase inhibition and antinociceptive activities of 4-methylsulfonylaniline-derived semicarbazones
I won’t always be diving into the cannabinoid chemistry - but there’s a constant thrum of chemists looking for new drugs to manipulate our endocannabinoid system, surely always hoping to find the next big winner that might make it through the pharmaceutical gauntlet & become a drug out there in the real world helping to heal people. So perhaps in ten years, you’ll be downing some semicarbazones for your neuropathic pain.

A review of technologies for THC detection
Recent advances in electrochemical sensor technologies for THC detection-a narrative review

AI to screen people for over 950 synthetic cannabinoids
Machine learning to assist in large-scale, activity-based synthetic cannabinoid receptor agonist screening of serum samples
If you stick around, you’ll see that AI fascinates me.
Also, in HempNews, I never covered synthetic cannabinoids. But now it will be. Fascinating stuff.

Recent Reviews

The Agency for Healthcare Research & Quality updated their ‘living systematic review’ on the use of THC & CBD for chronic pain
A living systematic review has been gaining traction in the scientific community in recent years. Instead of the constant hamster wheel of various researchers releasing reviews of a subject every few months (as you’ll be seeing in this section), in living systematic reviews, one group takes it upon themselves to keep one document continuously updated with the latest research. As you can imagine, the deluge of data from the pandemic led to the growing popularity of this tool.

This review suggests that smoking cannabis increases someone’s risk for catching COVID-19 because of the effects on the lungs - but that the cannabinoid might also be a treatment due to their anti-inflammatory effect
Implications of Cannabis and Cannabinoid Use in COVID-19: Scoping Review
It’s not great for your lungs to be inhaling any burning plant material. Though the slight negatives of cannabis do not at all compare to the huge harms of cigarettes.

A review looking at the antibiotic potential of the cannabinoids from the plant & ourselves
Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles
There’s a constant minor thread of research on the antibiotic potential of the cannabinoids - but no ever takes it to the next level & starts doing the research in humans & applying it in the real world. I suspect that a generation from now, we might look back at this time & shake our heads that we didn’t have hospitals using CBD/THC sprays & wipes for cleaning surfaces & destroying monsters like MRSA (which kills more Americans than HIV every year).

A review of CBD’s heart effects
Review of the Effect of Cannabidiol on the Vascular System
If you look at the heart page on our science archive, you’ll see that the cannabinoid receptors tend to be at low levels in a normal human heart. But once that heart is insulted by some kind of injury, the endocannabinoid system springs into action.

A review of the anticancer properties of the cannabinoids
Cannabinoids as anticancer drugs: current status of preclinical research

Plant Medicines & Psychoactives

The Psychedelic Science Review’s best paper of last year on neuroplasticity demonstrates in mice, psilocybin causes the rapid & sustained growth of dendritic spines in the frontal cortex
The Psychedelic Science Review is a good spot to stay on top of the science of psychedelics as well as primers for those who want to known the basics, with a strong focus on the neurochemistry.

The lawsuit of the Soul Quest Church of Mother Earth to force the DEA to consider their application to serve ayahuasca was dismissed, but leaving open an appeal to the 11th Circuit Court of Appeals
The DEA’s textbook play when it doesn’t like something is to clam up & never mention it again & never issue a response.
Sounds like my ex-wife…
(No, I don’t actually have an ex-wife - but you’ll be hearing about her often)

A review of 52 studies of psilocybin mushrooms find that it’s safe to administer under proper medical supervision
Can psilocybin be safely administered under medical supervision? A systematic review of adverse event reporting in clinical trials
One theme you’ll notice on psychedelic research is how often that you could have found out the same thing from asking any Fellow Traveler in the ‘70s.

Positive results from a Phase 3 trial using MDMA to treat PTSD

In a double-blind trial comparing the effects of LSD & psilocybin, the main difference was the effects on heart rate & blood pressure
Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects
Even though they said that the drugs produced “comparable subjective effects”, one suspects that their system of checklists aren’t subtle enough to suss out the different mental effects between these psychoactives that you hear described in the underground.

Dr. Nick Jikomes with a nice historical timeline of psychedelic science
I love timelines! I won’t dive into all of my timelines right now because we’ve had enough digressions for one email, but I’ll share them as they come up.

- lex

PS: Every week comes with a music recommendation that lives here. Thanks to Spotify’s Discover Weekly - which I often listen to as I create the newsletter - there’s always something new to discover. That being said, the links always go to YouTube so that everyone can listen.
For this week’s working music, a collaboration between the Welsh harpist Catrin Finch & the Senegalese kora player Seckou Keita on an album called Cychau Dibon.


The Living Glossary

I’m going to play with a feature & keep a running glossary of the basic cannabinoid terms down here at the bottom. Then I won’t have to repeat the basics every time they come up.
This will also function as the legend for the ‘neural ocean’ metaphor that I’m using in my graphic novel series on the endocannabinoid system. You can watch a lecture laying out the full idea here, but basically, we treat the human brain like the ocean: both deep, mysterious & chockablock with fish & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land). And neurons are complex underwater cities where hundreds of fish interact.


The cannabinoids found inside all mammals & almost every other form of life besides insects

The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”

Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]

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]

The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]

The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
[blue whale]

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 squid that eats blue whales]

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]

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…]

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 sleep, 6 scoops is a very pleasant psychoactive experience (Hamilton Morris has called it his favorite way to get high - which is saying something)
[Humpback whale, because it sings hippies to sleep]


The cannabinoids produced by the cannabis plant.

THC (tetrahydrocannabinol)
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]