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

This week, the majority of Americans are ready to end cannabis prohibition, dementia patients found to be helped by CBD & biomarkers in autistic children might help their caregivers evaluate the efficacy of their cannabis medicine. Plus, the addition of opioid use disorder to the Americans with Disabilities Act is an act of sanity in an insane world.

Cancer & podcasts:
Well, that’s it. So much science comes out each week that I’m probably going to have to add a permanent section on cancer below. This week has two studies on gliomas, a synchronicity because that’s the type of cancer Jonathan Purrow mentioned in his LinkedIn post about cancer. Speaking of Jonathan, check out his podcast ‘Cannabis Last Week’.

Now, here’s your news…

Best of cannabinoid science...

In a fascinating study of autistic children, they looked at how biomarkers in the saliva could be used to measure the effectiveness of cannabis treatment
The Potential of Salivary Lipid-Based Cannabis-Responsive Biomarkers to Evaluate Medical Cannabis Treatment in Children with Autism Spectrum Disorder
One of the hardest parts about working with cannabis – especially in long-term situations like autism – is knowing whether its working & how much you should be taking. By looking at the levels of 22 different lipids, these researchers are honing in on a practical rubric to guide doctors & parents.

In a case series of dementia patients, 15 days of CBD improved their symptoms
Neuropsychiatric Symptoms in Dementia. The Added Value of Cannabinoids. Are they a Safe and Effective Choice? Case Series with Cannabidiol 3%

A survey of multiple sclerosis patients found that two-thirds of them used cannabis to help alleviate symptoms
Medical cannabis use in Canadians with multiple sclerosis
“Medical cannabis was used most by current and former users to treat sleep problems (84.2%), pain (80.0%), and spasticity (68.4%), while the most reported adverse effects were drowsiness (57.2%), feeling quiet/subdued (48.8%), and difficulty concentrating (28.4%).”
If you know someone with MS, you must encourage them to consider cannabinoids. It’s one of the best-studied conditions & the one for which I’ve heard more anecdotes of changed lives than almost any other. (I’m working on a short primer for my cannabinoid education sessions that I’ll be releasing soon… But reach out to me if you know anyone who might be willing to consider it & needs advice)

In an intriguingly designed Human Laboratory Study, CBD seems to ‘dial down’ the mental effects of THC relevant to psychosis
Delta-9-Tetrahydrocannabinol, Cannabidiol, and Acute Psychotomimetic States: A Balancing Act of the Principal Phyto-Cannabinoids on Human Brain and Behavior
One of the most important reasons for there to be small amounts of CBD in cannabis is to help protect the users from the negative psychoactivity of THC. Basically, it’s bad trip protection. Dr. Raphael Mechoulam, father of the endocannabinoid system, said that he wished all cannabis had at least 1% CBD in it.

Against two types of salmonella, CBD was as effective as ampicillin
Cannabis sativa CBD Extract Shows Promising Antibacterial Activity against S. typhimurium and S. Newington

In the fat tissue of rats, CBD enhanced the glucose uptake, improved glucose-lipid homeostasis & enhanced antioxidative activities
Cannabidiol improves glucose utilization and modulates glucose-induced dysmetabolic activities in isolated rats' peripheral adipose tissues
This dovetails with a significant body of research showing CBD to cause improvements in overall energy metabolism. This clinical study of hemp extracts is a good example.

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the Headlines & Fav Articles

70% of US voters ready to end federal marijuana prohibition a report from the Marijuana Policy Project found that states made $3.7B from recreational cannabis last year

How Native tribes in the US are getting left behind by cannabis laws (Natalie Fertig for Politico)’s a good journalist to be following.

On Indigenous women in cannabis (hattip to @IkaTheTweeter)

According to a new survey, 9% of Canadian cannabis consumers are now growing their own weed at home
Home cultivation across Canadian provinces after cannabis legalization
I’d say, “We should move to Canada!” – but Ryan Reynolds told me to stop that.

Morocco to allow cannabis cultivation in northern regions
Haha. This is great. I mean, yes, it’s a great step forward in the legal sense. But in the sense of reality, Morocco is already the leading producer of cannabis on the planet with estimates putting it as the source for ~20% of the world’s total cannabis supply & half of the hashish.
(And if I don’t miss my guess, it’s the source of the grass I buy down by the river from the nice North African guys)

A favorite cannabis publicist interviews a favorite cannabis journalist: Alice Moon with Jackie Bryant

Most relevant CBD cartoon of the week:

Gabrielle Drolet @gabrielledroletcartoon

April 4th 2022

109 Retweets948 Likes

Law & Business

Israel moves to decriminalize CBD within 2 years
This one headline is also curious because Israel has been a world leader in utilizing the medical power of cannabis. When I went there to interview Dr. Mechoulam, they had Volcano vaporizers in their oncology wards for the patients. Now that’s civilized!
And here they are dragging their feet on THC’s inoffensive cousin.

The US Border Patrol said they plan to keep arresting anyone they find with cannabis anywhere, despite New Mexico’s new legalization law
The Border Patrol often does highway checkpoints in NM & they vowed to continue busting people no matter the state law.
& the Forest Service reminded everyone that weed is still illegal in places like the Santa Fe National Forest

Meanwhile, the Naval War College says that Rockstar’s new hemp energy drink will make you fail a drug test

The DEA stated that cannabis seeds are considered hemp because they contain less than 0.3% THC

Receptor Life Sciences raises ~$10M for inhaled CBD as an anxiety treatment
“The candidate product ‘has the potential to be the first-in-class treatment for acute anxiety disorders,’ said Receptor CEO and President Mark Theeuwes”.
Which is a funny statement when you can buy CBD vape pens anywhere. Yes, this formulation is a dry powder inside an inhaler, but its key strength of rapid onset is no different than a vape pen.

On the benefits of a cannabis infused workforce (hattip to Michelle Morganti)

Medical Cannabis & Culture

This is why we do what we do: the UK government let Ben run out of cannabis oil & his seizures jumped to 40 a day

Boisterous Ben @BenBoisterous1/2 Recently there was a supply issue with Bens #cannabis oil and Ben was left to run out of his medication. The MHRA, Home office and Department of Health and Social Care - DHSC knew about the issue. Ben had nearly 40 seizures that day.

April 8th 2022

72 Retweets167 Likes

#FreeThePlant #HealTheChildren

A study finds that the legalization of cannabis leads to a 10% decrease in admissions of children to foster care
Recreational marijuana legalization and admission to the foster-care system

The Plant & the History

‘Weed Like Change!’ is a new public education campaign about regenerative organic cannabis farming


Great article on CBD & anti-aging by Drs. Erhan Yarar & Tanja Bagar

CBD for bipolar disorder from Mary Biles on ProjectCBD

Meet EPM301 – Dr. Raphael Mechoulam’s newest CBDA-type creation (hattip to Michelle Morganti)
The acids forms of the cannabinoids are quite powerful – but also quite unstable. They fall apart too quickly to be useful drugs, so his team made an ester version of CBDA to stabilize it.

In an act of chutzpah, the researcher who did that tissue study about CBDA lessening COVID infections turned his formula into a hemp product (hattip to Michelle Morganti)
It’s chutzpah because the FDA is on the warpath about anything claiming to treat COVID & they recently issue 7 warning letters to CBD companies saying just that.

Clinical Studies & Surveys

Great work on a palliative care program that integrated medical cannabis
Integrated Medical Cannabis Consultations in a Palliative Care Program: Policies, Procedures, and Progress after Six Years of Practice
“Between 2015 and 2021, we certified 1711 patients for cannabis. The most common indications were cancer (64%), pain (24%), and neuropathy (9%).”
It’s an insane world where end-of-life patients aren’t automatically granted all the cannabis that they desire.

In 23 humans, a look at how ayahuasca altered their endocannabinoids
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience

In middle-aged sedentary adults, 12 weeks of exercise increased their levels of anandamide & oleamide – but did not alter their omega-6/omega-3 levels
Effect of Different Exercise Training Modalities on Fasting Levels of Oxylipins and Endocannabinoids in Middle-Aged Sedentary Adults: A Randomized Controlled Trial

A safety study in humans to look at the feasibility of using transcranial electrical stimulation for cannabis addiction
Portable Neuroimaging-Guided Noninvasive Brain Stimulation of the Cortico-Cerebello-Thalamo-Cortical Loop—Hypothesis and Theory in Cannabis Use Disorder
Cannabis use disorder is a real thing – and if a simple brain hacking tool helps people to stop using when they want to stop using, great.
& in humans with schizophrenia, transcranial stimulation helped them with problematic cannabis use
Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia
In related research, this meta-analysis looked at personality factors of problem cannabis users & found that they tended to have high levels of neuroticism & openness but low levels of conscientiousness & agreeableness
The association between the five-factor model of personality and problem cannabis use: A meta-analysis

In a retrospective study of young epilepsy patients, treatment with CBD caused 50% of them to have significantly less seizures, partial help for 20% of them, no response in most of the rest & in two cases, increased seizures
CBD doesn’t arrest seizures in everyone – and the sad truth that in some cases they make them worse. Another thing to note is the reported side effects because it’s a good insight into what happens when a kid takes hundreds or thousands of milligrams of CBD per day: “Most frequent AEs [adverse events] were: irritability 24.4% (n=7), diarrhoea 13.79% (n=4) and anorexia 10.34% (n=3). Other AEs described were: drooling 6.9% (n=2), somnolence (n=2); rash 3.4% (n=1), hepatobiliary disorders [liver] (n=1) and asthenia [weakness] (n=1).”
CBD is quite a safe drug as far as things go, but huge amounts of anything can affect some people negatively.

A review of the reasons for medical cannabis use in Ontario
Declared Rationale for Cannabis Use Before and After Legalization for Nonmedical Use: A Longitudinal Study of Community Adults in Ontario
Anxiety, depression, impaired sleep, pain, and headaches were among the most common complaints for which respondents used cannabis therapeutically. Most respondents reported using cannabis as a substitute for prescription medication at least some of the time, and approximately half reported using cannabis as a substitute for alcohol at least some of the time.”

A large survey finds that cannabis smoking is not associated with hearing loss (but tobacco smoking is)
Tobacco, but Neither Cannabis Smoking Nor Co-Drug Use, Is Associated With Hearing Loss in the National Health and Nutrition Examination Survey, 2011 to 2012 and 2015 to 2016

Smoking cannabis from a bong significantly increased the levels of fine particulate matter (PM2.5s) in the air
Fine Particulate Matter Exposure From Secondhand Cannabis Bong Smoking a recent Atlantic article made clear, the danger of PM2.5s is large.

Recent Reviews

In gum diseases, a review of using CBD as both a preventative & a treatment along with a focus on the potential negatives
Cannabidiol and periodontal inflammatory disease: A critical assessment

Recommended for You

A review on treating depression rapidly by targeting the endocannabinoid system
Rapid treatments for depression: Endocannabinoid system as a therapeutic target

In mental health disorders like depression, bipolar disorder & schizophrenia, the dysregulation of the endocannabinoid system may be driven by inflammation & oxidative stress via the nitric system
Inflammation and Nitro-oxidative Stress as Drivers of Endocannabinoid System Aberrations in Mood Disorders and Schizophrenia

In young people, why does smoking weed or taking synthetic cannabinoids lead to heart attacks?
Why Do Marijuana and Synthetic Cannabimimetics Induce Acute Myocardial Infarction in Healthy Young People?
Another unpleasant thing that people don’t want to talk about but growing evidence over the last few years shows a small but clear link between smoking cannabis & the risk of heart attacks in young people.
& in a related case study & review of the literature, a report of cannabis arteritis (inflammation of the arteries that damages blood vessel walls & reduces blood flow to the organs)
Cannabis arteritis: A case report and brief review of the literature
This one is much less common. Only ~50 cases have ever been reported, but if you’re the guy who had to get your little toe amputated because of it, you don’t care how rare it is.

A review of studies about ideas around cannabis for reproductive-aged women found mostly gaps in the literature
Measuring cannabis-related knowledge, attitudes, perceptions, motivations, and influences among women of reproductive age: a scoping review

A review of the nanotechnology future of the cannabinoids
Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials
I’m glad that they focus on cancer – because for all the pooh-poohing I do about nano-CBD for most consumers – cancer patients need huge levels of THC to harness anticancer effects & the increased bioavailability of nano-cannabinoids will be important.


In my endocannabinoid graphic novels based on Moby-Dick, I’ve always feared the coming chapters on cancer. It’s such a gigantic topic. The cancers are complex. How the cannabinoids interact with them is complex. And how to get it all down to one or two chapters?

I visualize one big double-page spread, with foldouts, that shows all the mechanisms by which cannabinoids carve, starve or fry cancer cells.
Anyway, I suspect that I will have to make this cancer carveout section permanent. There’s just so much on the topic every week.

In oncology, a review of 163 studies to find out the how & the why of using medical cannabis
Routes of administration, reasons for use, and approved indications of medical cannabis in oncology: a scoping review
“Our results also indicated that medical cannabis is mostly used for three approved indications: to manage refractory nausea and vomiting, to complement pain management, and to improve appetite and food intake. We highlighted 11 routes of administration for medical cannabis, with oils and oral solutions the most frequently reported.”
One of the great things about cannabis is how many ways you can get it into your system. One route of administration you hear about often in the underground is rectal. It’s an incredibly important pathway for getting larger amounts of cannabinoids into the system with less psychoactivity & to have less problems with swallowing.

A review of phytocannabinoids against gliomas (the most lethal & rapid brain cancer): they kill them (cytotoxic), they slow down their growth (anti-proliferative) & they slow down their movement (anti-migratory)
Cannabis Biomolecule Effects on Cancer Cells and Cancer Stem Cells: Cytotoxic, Anti-Proliferative, and Anti-Migratory Activities
& in gliomas, a look at their endocannabinoid signaling
Endocannabinoid signaling in glioma

In breast cancer cells, targeting the MGL enzyme (which breaks down 2-AG) blocked cell adhesion & transmigration as well as inhibiting tumor growth
Inhibition of triple negative breast cancer-associated inflammation, tumor growth and brain colonization by targeting monoacylglycerol lipase

In cancer, using cyclodextrins as delivery vehicles to improve the targeting of CBD to kill the cells
Biophysical Studies and In Vitro Effects of Tumor Cell Lines of Cannabidiol and Its Cyclodextrin Inclusion Complexes

Preclinical Research

In brain cells, all 11 phytocannabinoids tested modulated the calcium channels (which regulate neuronal excitability & the release of neurotransmitters)
Inhibition of human recombinant T-type calcium channels by phytocannabinoids in vitro
Intriguingly, the acid forms were stronger than the neutral forms, with CBGA being the strongest.
Also, a paper from Dr. Park’s lab shows CBD to be a regulator of calcium signaling
Cannabidiol, a Regulator of Intracellular Calcium and Calpain
We featured an interview with one of his students on the Lex Files last week.

In a rat model of stroke, giving them beta-caryophyllene (a main terpene of cannabis) before the neural insult lowered neuroinflammation
Anti-Inflammatory Effect of Beta-Caryophyllene Mediated by the Involvement of TRPV1, BDNF and trkB in the Rat Cerebral Cortex after Hypoperfusion/Reperfusion

In a mouse model of Alzheimer’s, activating the CB2 receptor lowered inflammatory cytokines, increased BDNF (the brain growth factor), protected the brain from damage, decreased amyloid plaques & neuronal lesions as well as improving their recognition & learning memory
Improved cognition impairment by activating cannabinoid receptor type 2: Modulating CREB/BDNF expression and impeding TLR-4/NFκBp65/M1 microglia signaling pathway in D-galactose-injected ovariectomized rats
It's not often you see researchers test in this many different directions. A quality paper.

In a mouse model of schizophrenia, a drug that activates the CB2 receptor produced antipsychotic effects
HU-910, a CB2 receptor agonist, reverses behavioral changes in pharmacological rodent models for schizophrenia
But when you look more closely at this research, you see how studying something as complex as schizophrenia strains these preclinical models.

In rats, an evaluation of how well a lipophilic CBD reaches the lymph nodes
Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle

In the skin of pigs with severe burns, a proprietary cannabinoid topical formulation did a little better than the military’s standard of treatment
Evaluation of Non-Euphoric Phytocannabinoid Elixir 14 (NEPE-14) Application in Deep Partial-Thickness Burn Wounds

Not the most convincing study – and it’s strange when you don’t get to know what’s in the formulation – but the endocannabinoid system in the skin is extensive (see the science here) & there’s been some decent amount of work on cannabinoids to enhance wound repair.

Also, we should say our prayers for all of the poor pigs who have been burned in the name of human skin for these last decades.

Cannabinoid Chemistry

They got a plant to produce THC antibodies for use in immunoassays to measure THC levels
Development of a plant-produced recombinant monoclonal antibody against Δ-9-tetrahydrocannabinol (Δ9-THC) for immunoassay application

Trying to figure out the structure of a novel synthetic cannabinoid found on the streets of Germany
Structure elucidation of the novel synthetic cannabinoid Cumyl-Tosyl-Indazole-3-Carboxamide (Cumyl-TsINACA) found in illicit products in Germany
As this report points out, in the vast flood of novel psychoactives these days, synthetic cannabinoids (technically cannabimimetics) make up the largest category.

Plant Medicines, Harm Reduction & Psychoactives

An inspiring thread on the far-reaching implications of opioid use disorder discrimination being added to the Americans with Disabilities Act

If your loved one uses drugs, make your home their safe consumption site: discomfort > burial

& in NYC, Housing Works plans to open two more safe injection facilities
The next generations will look back with horror at the pushback against safe drug consumption sites.

In a further sign of opening, NIDA Director Nora Volkow stated that the psychedelic prohibition has made it "extremely hard to do research”

The Taliban bans opium cultivation in Afghanistan’re probably actually serious about it - while under the US invasion, opium cultivation expanded. The book to understand the cyclical nature of this history is McCoy’s ‘The Politics of Heroin in Southeast Asia’.

Terminally ill patients fight for the ‘right to try’ psychedelics with the help of physician/hero Dr. Sunil Aggarwal

Reilly Capps on the face of psychedelic journalism
& a special issue of the Nation on psychedelics

2021: In male mice, this multifaceted study found that LSD promoted social behavior if administered for 7 days – but not from a single dose – via serotonin & mTOR (a master regulator of mammalian cells)
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission
Measuring complex behaviors in murine models is always difficult, but in this case it means that more LSD caused the rats to spend more time with a stranger rat. The treated rats also displayed an increased interest in Buddhist texts.

A single psychedelic experience associated with increased “attribution of consciousness” to everything
A Single Belief-Changing Psychedelic Experience Is Associated With Increased Attribution of Consciousness to Living and Non-living Entities
As Terrence McKenna said, “Everything in Nature is alive & talking to you. This is not a metaphor.”

- lex

PS: Spotify knows that I’m a sucker for a good cover song– and even more so, a sucker for anything to do with Django Reinhardt. So for today’s music, the album ‘John, Paul, George & Django’ by the Hot Club of San Francisco – covers of classic Beatles songs in Django’s gypsy jazz style.


The Living Glossary

Here’s a running glossary of the basic cannabinoid terms. 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 based on Moby-Dick. 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 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)
[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]

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]

Beta-caryophyllene (BCP)
A terpene that’s also a cannabinoid.
The terpenes of cannabis give the plant it’s 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]