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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.

Some weeks just overflow with science. I broke out new sections for neurodegenerative disorders (use cannabinoids. Crazy not to), pain (always #1 reason for cannabis use), obesity (improves metabolic function) & on the dark side, many new synthetic cannabinoids hitting the streets & causing harms.

Plus, the War on Drugs roars on as stupidly as ever…

My ad: Cannabis counseling sessions for your health

Cannabis & the cannabinoids are powerful medicines. Are you – or a family member – intrigued to try them for your health but don’t know how to start?
You can see my advice for using them for pain, neurodegeneration, autism, insomnia & anxiety/depression here. However, with the many tools out there such as CBD, THC, PEA, OEA & CBDA, 1-on-1 advice can be helpful, especially for people new to cannabis. If you want someone experienced in listening to patients & coming up with a plan to help you find relief, book a 1-on-1 session with me here: Cannabinoid Education Sessions.

This newsletter is a free offering from my company White Whale Creations. We produce educational content for cannabis & psychedelic companies & have sponsorship opportunities for The Lex Files podcast.
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Best of cannabinoid science...

In a survey of pediatric autism patients, the caregivers administered cannabis most frequently for repetitive behaviors & irritability & found high levels of CBD paired with low levels of THC tended to work best
A natural history study of medical cannabis consumption in pediatric autism in the United States
https://www.sciencedirect.com/science/article/abs/pii/S1750946722000812

In a review of all the meta-analyses, people with psychosis who used cannabis showed “showed better neurocognitive performances … for planning/reasoning and working memory”, smaller effects for processing speed & attention & “Individuals with lifetime use appeared to show better neurocognitive functions”
The Potential Paradoxical Neurocognitive Effects of Cannabis Use in Patients with Psychotic Disorders: A Critical Meta-Review of Meta-Analytical Evidence
https://pubmed.ncbi.nlm.nih.gov/35666226
But note, this is one of the great double-edged sword. Some people with psychosis find help from small levels of cannabis – but for others, it can push them right over the edge.

A review of using cannabis & CBD for treating animals: osteoarthritis, epilepsy aggressiveness
Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials
https://pubmed.ncbi.nlm.nih.gov/35703023

In human sodium channels (which help control electrical signals in epilepsy), CBD-rich hemp extracts inhibited the channel at much lower doses than isolated CBD
A nutraceutical product, extracted from Cannabis sativa, modulates voltage-gated sodium channel function
https://pubmed.ncbi.nlm.nih.gov/35689251

In a mouse model of epilepsy, giving CBD extracts before inducing seizures caused the microglial cells (immune system guardians of the brain) to not move as much & not over-accumulate in the hippocampus (memory center) causing a decrease in inflammation
Prophylactic administration of cannabidiol reduces microglial inflammatory response to kainate-induced seizures and neurogenesis
https://pubmed.ncbi.nlm.nih.gov/35700815

In microglial cells, treatment with CBD increased levels of the mitochondrial fusion protein Mitofusin 2 that deals with inflammation – and in mice, CBD lessened the anxiety response & cognitive deficits from an inflammatory challenge as well as helping in a mouse model of multiple sclerosis
Mitofusin 2 confers the suppression of microglial activation by cannabidiol: Insights from in vitro and in vivo models
https://pubmed.ncbi.nlm.nih.gov/35688339
Whew. Sometimes the researchers put so much work into an experiment that you wonder why they didn’t spin it out into three different papers…

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) or Google Scholar itself.
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.

On cannabis & creativity by Ruby Deevoy
https://www.seedsman.com/blog/can-cannabis-make-you-more-creative

How to use cannabis & CBD for nerve pain by Bethan Finighan
https://www.leafie.co.uk/articles/cbd-nerve-pain-2

the Headlines & Fav Articles

The FDA hosted a meeting on the challenges of safety evaluations for dietary supplements & used CBD as a case study
https://www.fda.gov/advisory-committees/science-board-food-and-drug-administration/2022-meeting-materials-science-board-fda
https://www.fda.gov/media/159252/download

NIDA plans to fund a national medical cannabis registry to find out how patients are obtaining & using their cannabis
https://www.marijuanamoment.net/top-federal-drug-agency-wants-to-create-a-national-medical-marijuana-registry-to-track-how-patients-use-cannabis

A Montana Department of Revenue letter shows that Native tribes are restricted to the lowest tier of cannabis cultivation licenses
https://www.ganjapreneur.com/montana-restricting-tribes-to-smallest-tier-of-cannabis-licenses
Just setting up their operations to fail. What a bloody repeat of history.

A panel of Brazilian judges unanimously ruled in favor of the right of three patients to grow their own medical cannabis
https://www.ganjapreneur.com/brazil-court-rules-patients-can-grow-their-own-cannabis-for-medical-purposes

A State Department official spoke on the Brittney Griner’s arrest in Russia for cannabis vape cartridges & called it a wrongful detention
https://twitter.com/ReutersLegal/status/1537230979453964288
Meanwhile, the US Border Patrol would be delighted to catch any celebrities with cannabis products. Amerika is the epitome of “do as I say, not as I do.”

A French guy trained his bees to make cannabis-infused honey (hattip to Brett Greene)
https://livelovefruit.com/cannabis-infused-honey-cannahoney
Road trip?
(Just kidding. Two hours after we brought home our first car last night, a crazy hail storm took out the windshield. We’re going nowhere for a bit.
But in good news, my 4-year-old decided that it was Thor throwing ice balls down to have fun with us)

Dall-E generates ‘Fischer Price My First Bongs’

Weird Dall-E Generations @weirddalle

June 15th 2022

20,036 Retweets211,676 Likes

The War on Drugs & Harm Reduction

Cannabis legalization is undermining the profits of Mexican cartels
https://www.marijuanamoment.net/congressional-researchers-say-marijuana-legalization-movement-is-undermining-mexican-cartel-profits
See? That’s one more reason we want to legalize. And more importantly, according to the last research I saw on the subject, do you know what funds 90% of the gangs across Amerika? All of their guns, bullets & violence? It was drugs.
If you want to kneecap gangs, legalize all drugs. Now.

A US Appeals Court confirmed a judge’s directive forbidding a paraplegic man on pretrial release to use medical cannabis
https://reason.com/volokh/2022/06/11/no-medical-marijuana-exception-to-federal-probation-conditions-barring-violation-of-federal-law

The Environmental Protection Agency reminds its employees that cannabis is illegal for them regardless of state legality & that they can’t even invest in the cannabis industry
https://www.marijuanamoment.net/epa-warns-workers-theyre-banned-from-using-marijuana-or-investing-in-the-industry-in-new-memo
End this stupid fucking Drug War already.

In an evergreen headline, “Alcohol far outpaces other drugs in emergency department visit data”
https://onlinelibrary.wiley.com/doi/abs/10.1002/adaw.33459

Law & Business

A disturbing study finds that states tend to make it easier to open a recreational cannabis dispensary than a medical cannabis dispensary
U.S. State approaches to cannabis licensing
https://pubmed.ncbi.nlm.nih.gov/35691088
“We observe that states tend to license medical cannabis more restrictively than adult-use cannabis: i.e., by offering licenses in fewer categories, at higher cost, in lower issuance volume, and more often mandating vertical integration.”
This is one of the great conundrums of cannabis laws: how to make clean, inexpensive cannabis medicine available to patients while also allowing for moderately taxed cannabis products for adult consumers?

A favorite academic, Dr. Jeffrey Miron, writes about the difficulties of being a bank who would want to work with a cannabis company
Cannabis Banking: A Clash Between Federal and State Laws
https://policycommons.net/artifacts/2465349/cannabis-banking/3487221

An analysis of a potential national cannabis market suggests letting states block interstate commerce for the first few years to prevent a race to the bottom that will undermine equity efforts & make certain business investments obsolete
Legalization Without Disruption: Why Congress Should Let States Restrict Interstate Commerce in Marijuana
https://digitalcommons.pepperdine.edu/cgi/viewcontent.cgi?article=2616&context=plr

In New Mexico, a cannabis company & a group of patients are suing 7 health insurance companies for not covering medical cannabis costs as required under state law
https://www.marijuanamoment.net/new-mexico-marijuana-company-and-patients-sue-for-insurance-coverage-for-medical-cannabis

A Senate bill would legalize medical cannabis for military veterans (9 cosponsors currently)
https://www.congress.gov/bill/117th-congress/senate-bill/1183/cosponsors?loclr=cga-bill&pageSort=lastToFirst
I usually don’t cover pending legislation because pending legislation rarely passes. But this one is too important to skip. This is a no-brainer early step.
And even more obvious, a House bill to allow VA doctors to simply talk about cannabis with veterans (3 cosponsors currently)
https://www.congress.gov/bill/117th-congress/house-bill/6991/cosponsors?loclr=cga-bill&pageSort=lastToFirst

A study out of Washington finds that legalizing cannabis increases your food sales – and hence more tax revenue on those food sales
The munchies: Marijuana legalization and food sales in Washington
https://onlinelibrary.wiley.com/doi/abs/10.1002/soej.12588
I generally frown on weed jokes in titles – but this one does encapsulate the situation.
<he says as he reaches for the Snickers bars stash that he keeps hidden from the kids>

On why cannabis is not an easy business… (by Kaitlin Domangue)

Kaitlin Domangue @KaitlinDomangueHi welcome to cannabis you must quickly become a fintech legal policy scientific political marketing startups highly-regulated agricultural and banking generalist to understand even one thing have a great day

June 16th 2022

22 Retweets143 Likes

The Plant & the History

Using an AI robot to grow your cannabis (via Brit Smith, host of The Different Leaf Podcast)

Brit Smith @BritTheBritishArtificial intelligence grew my weed & it is GOOD! I’m on the road on @different_leaf the #podcast to visit @BoundlessRobo 🤖 & learn about @helloannaBoto the pot-growing robot that looks like a household lamp &uses AI to monitor every aspect of plant growth from seed to harvest

June 17th 2022

4 Retweets11 Likes

NY State issues new cannabis planting guidelines & dozens of farmers have to rip out parts of their crop
https://grownin.com/2022/06/15/dozens-of-new-york-cannabis-farmers-ripping-out-crops-in-response-to-new-ocm-guidance

Excellent thread on why farmers in Canada don’t find growing cannabis worth it (by Courtland Sandover-Sly)

Courtland Sandover-Sly @C0URTLANDSWhy don't more farmers grow cannabis in Canada now that it's legal?? It all boils down to one thing: it's not worth the risk. Join me as I explain from a farmer's perspective. 1. Cannabis is temperamental; not just to grow, but to finish. 2. That finished product has an added

June 19th 2022

20 Likes

On the strong mineral & elemental composition of hemp seeds
The Seeds of Industrial Hemp (Cannabis Sativa L.) a Source of Minerals and Biologically Active Compounds
https://www.tandfonline.com/doi/abs/10.1080/15440478.2022.2084486
They are one of the world’s most nutritious seeds. They’re still one of the main snacks of China, even though they haven’t been called the “Land of Mulberry & Hemp” for quite some time now.
Speaking of, here’s a review of the healthy power of hempseed’s protein hydrolysates (small snippets of proteins that are used as building blocks & biostimulants)
Hempseed (Cannabis sativa) protein hydrolysates: A valuable source of bioactive peptides with pleiotropic health-promoting effects
https://www.sciencedirect.com/science/article/pii/S0924224422001984

And extracts of hempseeds cause antidepressant effects!
Antidepressant Effects of Ethanol and Ethyl Acetate Extracts from Cannabis sativa L. (Hemp) Seeds in Invertebrate and Vertebrate Models
https://www.dbpia.co.kr/Journal/articleDetail?nodeId=NODE11065872
I did not expect it to become Hempseed Week. It’s like Shark Week – except healthier for everyone involved.

They identified the genes in cannabis regulating auxin (a hugely important plant hormone for the regulation of growth & behavior)
Genomic identification of ARF transcription factors and expression analysis in Cannabis sativa L
https://www.sciencedirect.com/science/article/abs/pii/S092666902200601X
I added this less for your genomic interest & more to point out how far behind the basic agronomy is for cannabis compared to most other plants. The other key cash crops have decades of agricultural universities working to learn more about how they grow & how to make them grow better. But Prohibition has us so far behind on cannabis. The best knowledge is probably locked up in the heads of the underground growers – but they’re too used to not sharing now.

An analysis of cannabis pollen & why it causes allergies
Comparative light and scanning electron microscopic studies of pollen of two marijuana species causing allergies
https://pubmed.ncbi.nlm.nih.gov/35661329

Oh man. They’re using AI to use satellite images to find our weed crops
Cannabis sativa L. Spectral Discrimination and Classification Using Satellite Imagery and Machine Learning
https://www.mdpi.com/2077-0472/12/6/842
#NarcBot
(#NominatingThisHashtagForMyBestOfList #CanYouDoBetter?)

Plant Medicines & Other Psychoactives

An article on how to increase inclusivity for psychedelic therapy around physical disability
Physical Disability and Psychedelic Therapies: An Agenda for Inclusive Research and Practice
https://pubmed.ncbi.nlm.nih.gov/35693959

A strong continuation of the series ‘Psychedelic Patent Wars’ from the newsletter On Drugs

On DrugsPsychedelic Patent Wars 2: Lost at the Patent Office (Part 1)The first installment covered a lot of ground. After starting with some patent law basics, we stripped down the NYU/Reset Pharma application that seeks to patent a method of treating cancer patients with anxiety by administering psilocybin once. We ain’t even got our feet wet yet. This second installment will examine a new pile of Hot Psilocybin Patent G…Read more2 months ago · 4 likes · 3 comments · Matt

5 Questions for ayahuasca researcher Fernanda Palhano Xavier de Fontes from Jane Hu’s Microdose newsletter

The Microdose5 Questions for ayahuasca researcher Fernanda Palhano Xavier de FontesMore than a decade ago, Fernanda Palhano Xavier de Fontes was finishing dual undergraduate degrees from Federal University of Rio Grande do Norte in Natal, Brazil, and École National Supérieure d’Electrotechnique, d’Electronique, d’Informatique in Toulouse, France. Her classmates were planning to start masters programs in electrical engineering, or taki…Read more2 months ago · 16 likes · jane c. hu

A pretty great GIF thread on Lauri Elsilä’s work on the effects of LSD on binge drinking in mice
Effects of acute lysergic acid diethylamide on intermittent ethanol and sucrose drinking and intracranial self-stimulation in C57BL/6 mice
https://pubmed.ncbi.nlm.nih.gov/35695174

In 30 depressed patients, one dose of psilocybin dropped their scores on a depression scale with no negative side effects
The safety and efficacy of psilocybin therapy in patients with cancer and major depressive disorder
https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.12097

This review of 30 studies suggests psilocybin as a first-line treatment for social anxiety disorder
Don't be afraid, try to meditate- potential effects on neural activity and connectivity of psilocybin-assisted mindfulness-based intervention for social anxiety disorder: A systematic review
https://pubmed.ncbi.nlm.nih.gov/35679988

A study of antidepressant & antianxiety effects of several famous plants: cannabis, datura, tobacco & papayas (I didn’t know the last one had a history of traditional medicine use)
The modulatory effects of alkaloid extracts of Cannabis sativa, Datura stramonium, Nicotiana tabacum and male Carica papaya on neurotransmitter, neurotrophic and neuroinflammatory systems linked to anxiety and depression
https://pubmed.ncbi.nlm.nih.gov/35665872

Psilocybin induces mystical experiences
Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report
https://pubmed.ncbi.nlm.nih.gov/35355714
Sometimes scientists seem to forget the world outside the ivory tower. Here they say, “Using natural language pre-processing, we provide the first qualitative descriptions of the "Complete Mystical Experience" induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty.”
#DoubtYoureTheFirst #Erowid

Ketamine’s antidepressant effect seems to be mediated by upregulation of the Kcnq2 gene – an ion channel related to neuronal excitability
Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2
https://www.cell.com/neuron/fulltext/S0896-6273(22)00409-3
And a review of its real-world effectiveness for treating depression
Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis
https://pubmed.ncbi.nlm.nih.gov/35688035
“These results demonstrate that even the most treatment-resistant patients may benefit from ketamine, and that mid-to-long term treatment is effective in many patients.”

Blossom Analysis collects all the psychedelic research from June
https://blossomanalysis.com/psychedelic-research-links-june-2022

A study of the health effects of DMT: “DMT increased blood pressure, heart rate, anxiety, psychedelic effects, and psychotomimetic effects, which resolved within 20-30 min of injection”
Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder
https://pubmed.ncbi.nlm.nih.gov/35660802

What does DMT feel like? These scientists found out by reading a bunch of Reddit posts & turning it into an article
Phenomenology and content of the inhaled N, N-dimethyltryptamine (N, N-DMT) experience
https://www.nature.com/articles/s41598-022-11999-8
It’s quite an intriguing list of phenomena.
If you weren’t curious about DMT before, I hope you are now. It’s the most interesting way that you will ever spend ten minutes.

Cannabinoid Science

A secret buyer study of hemp CBD products in Kentucky found that almost half had CBD concentrations more than 10% outside the labeled amount
Label accuracy of unregulated cannabidiol (CBD) products: measured concentration vs. label claim
https://pubmed.ncbi.nlm.nih.gov/35658956
For consumers, there’s only one solution: buy from companies that have third-party test results for every batch.

The National Institute of Health touts their work on using the endocannabinoid system to protect the heart from diabetes
https://irp.nih.gov/blog/post/2022/06/therapeutic-strategy-protects-heart-from-diabetic-damage

A handout for doctors about considerations of cannabis use on anesthesia administration
https://www.apsf.org/wp-content/uploads/newsletters/2022/3702/APSF3702-2022-06-a10-CannabisUse.pdf

Recommended for You

Clinical Studies & Surveys

A study of the effects of food on CBD absorption
Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function
https://pubmed.ncbi.nlm.nih.gov/35631293
All male participants though. It’s a shame. Small studies often shy away from female participants because they fear the confounding effects of hormonal cycles – but with the sizeable gender differences in reactions to cannabinoids, this leads to a dearth of knowledge on the female response to cannabis & cannabinoids.

In a study at a seizure center, young people with severe epilepsy taking CBD experienced the most drug-drug interactions with clobazam & valproic acid
Prescription cannabidiol for seizure disorder management: Initial drug-drug interaction management by specialty pharmacists
https://pubmed.ncbi.nlm.nih.gov/35675751
Those are fairly well known interactions – and remember that this usually involves thousands of milligrams of isolated CBD.

In young adults, their blood levels of endocannabinoids coordinated to certain specific bacteria in their feces
Plasma Levels of Endocannabinoids and Their Analogues Are Related to Specific Fecal Bacterial Genera in Young Adults: Role in Gut Barrier Integrity
https://pubmed.ncbi.nlm.nih.gov/35631284

In young African-Americans, cannabis use helped them to get sleep quicker – but higher levels were linked to lower sleep efficiency
Recreational cannabis use is associated with poorer sleep outcomes in young adult African Americans
https://www.sciencedirect.com/science/article/abs/pii/S0306460322001654

A survey of Canadian cannabis users found that medical users were more likely to drive under the influence than recreational users
Driving under the influence of cannabis among recreational and medical cannabis users: A population study
https://www.sciencedirect.com/science/article/abs/pii/S2214140522000743

In this survey of Canadian medical cannabis patients, they found their primary care providers to be knowledgeable about cannabis
Healthcare provider and medical cannabis patient communication regarding referral and medication substitution: the Canadian context
https://pubmed.ncbi.nlm.nih.gov/35698183
With authorship by Friend of the Newsletter Phillipe Lucas who is doing great work in BC.

For cannabis use disorder, a candidate drug moves into Phase 2 trials
Indivior moves to next phase in cannabis use disorder medication
https://onlinelibrary.wiley.com/doi/abs/10.1002/adaw.33462
Known as AEF0117 , it appears to block the CB1 receptor. However, that didn’t go so well the first time. The famous story is that of Rimonabant – a CB1 blocker approved by the EU (but not the US) in 2006. Approved as a weight loss drug, its ability to block the CB1 receptor in the human brain led to adverse psychiatric effects in the early trials. After approval, severe mood disorders were detected in the patient population up to & including suicide. It was quickly pulled from the market & this was the first body blow to pharmaceutical interest in targeting the endocannabinoid system.
You can see a scientific writeup of the history here.

In people admitted to a trauma center, their self-reported drug use generally matched (85%) what their tox analysis shows
Validity between self-report and biochemical testing of cannabis and drugs among patients with traumatic injury: brief report
https://pubmed.ncbi.nlm.nih.gov/35676744

In Florida teens, being cyberbullied is linked to greater chances of vaping cannabis
Bullying victimization and nicotine and marijuana vaping among Florida adolescents
https://www.sciencedirect.com/science/article/abs/pii/S0376871622002733

In veterans, their pretreatment levels of anandamide & 2-AG were not predictive of PTSD symptom strength
The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
https://journals.sagepub.com/doi/pdf/10.1177/24705470221107290
Something to always remember about the endocannabinoids is that are produced “on-demand”. When needed, production is ramped up quickly & they exert their actions locally. And when needed, production slowed & the excess removed by enzymes. It’s part of the reason it’s such an adaptable system with precise responses – but it can also mean that the endocannabinoid levels in your blood don’t correlate to much.
(that being said, this specific edition of the newsletter has a notably higher level of papers correlating blood plasma levels of endocannabinoids to something important. Nothing like saying it out loud for the exceptions to pop up like mushrooms after a rain…)

Neurodegenerative Disorders

For my advice on using cannabinoids for the neurodegenerative disorders, see my page here.

In patients with Parkinson’s disease using transcranial magnetic stimulation, the decrease in neuroinflammation seems to be mediated by increasing the level of CB2 receptors as well as increased levels of anandamide & 2-AG
High-Frequency Repetitive Transcranial Magnetic Stimulation Regulates Astrocyte Activation by Modulating the Endocannabinoid System in Parkinson's Disease
https://pubmed.ncbi.nlm.nih.gov/35672602

In patients with Parkinson’s disease, brain scans showed lower levels of CB1 receptors in several brain regions – and the medication that they used helped to increase CB1 receptors towards normal levels
Cannabinoid Receptor Type 1 in Parkinson's Disease: A Positron Emission Tomography Study with [ 18 F]FMPEP-d 2
https://pubmed.ncbi.nlm.nih.gov/35674270

In a model of Alzheimer’s disease, CBD worked on the microglial (immune) cells to improve digestion of the amyloid-β plaques via the TRPV2 receptors as well as reducing neuroinflammation & improved functioning of the mitochondria (powerhouse of the cell)
Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation
https://pubmed.ncbi.nlm.nih.gov/35628181

Pain

For my advice on using cannabinoids for pain, see my page here.

A review of clinical trials of chronic pain patients found cannabinoids especially effective for neuropathic pain & the spasticity of MS & less helpful for cancer pain
Systematic reviews of randomized controlled trials of cannabinoid products in chronic pain conditions and for symptoms associated with multiple sclerosis: what do they tell us?
https://pubmed.ncbi.nlm.nih.gov/35679523/

A review of using CBD for chronic pain
Analysing the perspectives of health professionals and legal cannabis users on the treatment of chronic pain with cannabidiol (CBD): A scoping review
https://www.researchgate.net/publication/360972217_Analysing_the_perspectives_of_health_professionals_and_legal_cannabis_users_on_the_treatment_of_chronic_pain_with_cannabidiol_CBD_A_scoping_review

In a study of US medical cannabis patients, they found a 4.5-fold increase from 2016 to 2020 with the predominant conditions being pain & PTSD
Chronic pain was the most common patient-reported qualifying condition in 2020 (60.6%), followed by posttraumatic stress disorder (10.6%).
https://pubmed.ncbi.nlm.nih.gov/35696691

A hospital interviews its chronic pain patients who find cannabis helpful
Benefits and Concerns Regarding Use of Cannabis for Therapeutic Purposes Among People Living with Chronic Pain: A Qualitative Research Study
https://pubmed.ncbi.nlm.nih.gov/35652734

Obesity & Metabolic Disorders

In patients with Hepatitis C (who often have metabolic disorders), “current cannabis use were consistently associated with smaller waist circumference, lower BMI, and lower risks of overweight, obesity, and central obesity”
Cannabis use as a factor of lower corpulence in hepatitis C-infected patients: results from the ANRS CO22 Hepather cohort
https://pubmed.ncbi.nlm.nih.gov/35690798

In humans with obesity, a CBDA analogue helped to improve metabolism, lose weight, reduce appetite, strengthen liver function & improved glycemic & lipid profiles
The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity
https://pubmed.ncbi.nlm.nih.gov/35628417

In mice being fed a high-fat diet, the onset of obesity suppressed histamine release & lowered the production of oleoylethanolamide (OEA). Giving them extra OEA helped reduce lipid accumulation, inflammation & liver scarring
Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver
https://pubmed.ncbi.nlm.nih.gov/35691287/
For more on oleoylethanolamide, see the Living Glossary below.

Synthetic Cannabinoids

Unsurprisingly, the UK’s 2016 drug law seemed to make little difference in the number of people going to the ER from synthetic cannabinoids
Trends in hospital presentations following analytically confirmed synthetic cannabinoid receptor agonist exposure before and after implementation of the 2016 UK Psychoactive Substances Act
https://pubmed.ncbi.nlm.nih.gov/35665553

A new synthetic cannabinoid found in seized materials in Denmark as underground chemists seek to get more creative & get around new laws based on “common structural scaffolds rather than explicit structures”
Identification of the synthetic cannabinoid-type new psychoactive substance, CH-PIACA, in seized material
https://pubmed.ncbi.nlm.nih.gov/35687099

In Italian cannabis, samples are being found spiked with a new synthetic cannabinoid to increase potency
GC-MS identification and quantification of the synthetic cannabinoid MDMB-4en-PINACA in cannabis-derived material seized in the Turin Metropolitan Area (Italy)
https://pubmed.ncbi.nlm.nih.gov/35658890

A new synthetic cannabinoid hitting the streets called mepirapim causes addictive behaviors in mice via the CB1 receptor
Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents
https://www.mdpi.com/1424-8247/15/6/710

In German gummies, a mix of new synthetic cannabinoids caused one user to experience hallucinations & commit a felony
Δ8-THC, THC-O Acetates and CBD-di-O Acetate: Emerging Synthetic Cannabinoids Found in Commercially Sold Plant Material and Gummy Edibles
https://pubmed.ncbi.nlm.nih.gov/35674405
Sometimes more than others, you really want to know the backstory behind an article.
What crime? What hallucinations? What brand of gummies?

Harms & No Help

In rats, the ways in which cannabis is bad for testicular function: hormone levels altered, more non-swimming sperm, more abnormal sperm, lower overall sperm levels & an empty cavity (?!) in the testes
Cannabis sativa exacerbate testicular function by increased oxidative stress, altered male reproductive hormones, sperm quality/quantity and cellular architecture of the testis
https://pubmed.ncbi.nlm.nih.gov/35675950
Nobody likes hearing this one – but it’s true. Smoking weed is not great for your reproductive success. It obviously does not stop everybody from having kids (probably including a lot of our readers & certainly our writer), but if you’re having trouble getting pregnant, lay off the grass.

In human ovaries, cannabis caused 16 different parts of the genome to experience dose-dependent changes in methylation (a process for blocking genetic expression by the addition of small molecules)
Cannabis significantly alters DNA methylation of the human ovarian follicle in a concentration-dependent manner
https://pubmed.ncbi.nlm.nih.gov/35674367
This isn’t necessarily a bad thing. But again, if you’re having trouble with reproductive success, cease the cannabinoids.

In human sperm, cannabis altered the DNA methylation of genes associated with autism
Cannabis alters DNA methylation at maternally imprinted and autism candidate genes in spermatogenic cells
https://pubmed.ncbi.nlm.nih.gov/35687495

We don’t know why cannabis exposure in adolescence is linked to psychosis later, but this research in mice suggests that it may be mediated by the gut bacteria causing changes in the brain
Gut-microbiota-brain axis in the vulnerability to psychosis in adulthood after repeated cannabis exposure during adolescence
https://pubmed.ncbi.nlm.nih.gov/35666299

A case study of vaping THC potentially causing arrhythmias in the heart leading to a cardiac arrest
Vaping tetrahydrocannabinol unmasks Brugada pattern and induces ventricular fibrillation in Brugada syndrome: a case report
https://academic.oup.com/ehjcr/article/6/6/ytac200/6603071

In heart tissue from dogs & rabbits, CBD lengthened the duration of the action potential via potassium channels
Assessment of proarrhythmogenic risk for cannabidiol using dog and rabbit cardiac preparations: the electrophysiological effects on action potential and transmembrane potassium currents
https://academic.oup.com/cardiovascres/article/118/Supplement_1/cvac066.021/6605439

Cancer

An in-depth review of the effects of oleamide (OEA) on ion channels & how this makes it effective against cancer cells
Oleamide, a Primary Fatty Acid Amide: Effects on Ion Channels and Cancer
https://www.liebertpub.com/doi/abs/10.1089/bioe.2022.0010

In human skin melanin producing cells from Caucasian & African American skin, THC & CBD increased the levels of reactive oxygen species & reduced the number of dendrites in the Caucasian skin but had no effect on the Black skin
Comparative Study of Δ9-Tetrahydrocannabinol and Cannabidiol on Melanogenesis in Human Epidermal Melanocytes from Different Pigmentation Phototypes: A Pilot Study
https://www.mdpi.com/2039-4713/12/2/12/htm

Recent Reviews

A cool review looks at how eating polyunsaturated fatty acids (PUFAs – the building blocks of endocannabinoids) affect how exercise alters your endocannabinoid system for neural plasticity & neural inflammation
Dietary PUFA and Exercise Dynamic Actions on Endocannabinoids in Brain - Consequences for Neural Plasticity and Neuroinflammation
https://pubmed.ncbi.nlm.nih.gov/35675221

A review looking for the safe dose of CBD in food
Regulating for Safety: Cannabidiol Dose in Food
https://meridian.allenpress.com/jfp/article-abstract/doi/10.4315/JFP-21-374/482880/Regulating-for-Safety-Cannabidiol-Dose-in-FoodCBD

A review of the latest best practices for extracting & purifying CBD for use in edibles
Cannabinoids: Challenges, opportunities and current techniques towards its extraction and purification for edibles
https://www.sciencedirect.com/science/article/abs/pii/S2212429222002942

Preclinical Research

In a model of endometriosis, CBD reduced lesions, caused antioxidant effects, lowered scar tissue formation, reduced inflammation & helped with pain
Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis
https://pubmed.ncbi.nlm.nih.gov/35628240

In mice with induced heart problems, CBD decreased inflammation & improved the antioxidant ability
Cannabidiol Improves Antioxidant Capacity and Reduces Inflammation in the Lungs of Rats with Monocrotaline-Induced Pulmonary Hypertension
https://pubmed.ncbi.nlm.nih.gov/35630804

In mice with lungs injured by paraquat, activating the CB receptors reduced mortality, decreased inflammation, improved the lung’s tissue structure & reduced scar tissue formation via the macrophages (immune cells)
Cannabinoid Analogue WIN 55212–2 Protects Paraquat-Induced Lung Injury and Enhances Macrophage M2 Polarization
https://link.springer.com/article/10.1007/s10753-022-01688-z

In a mouse model of depression, activation of the receptor GPR55 (which may one day be known as CB3) “remarkably prevented the development of depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis deficits”
The neuroprotective effects of GPR55 against hippocampal neuroinflammation and impaired adult neurogenesis in CSDS mice
https://pubmed.ncbi.nlm.nih.gov/35490927

On seizures, orexin & cannabinoid receptors
Hippocampal orexin-1 and endocannabinoid-1 receptors underlie the kainate-induced occlusion in theta-burst long- term potentiation
https://www.sciencedirect.com/science/article/abs/pii/S0143417922000385

In rats, a new drug that both inhibits the FAAH enzyme & activates one of the dopamine receptors helps them to not get as addicted to nicotine
The multitarget FAAH inhibitor/D3 partial agonist ARN15381 decreases nicotine self-administration in male rats
https://pubmed.ncbi.nlm.nih.gov/35690082

Thanks.
- lex

PS: Today’s lovely album for your summer evening is ‘Haitian Folk Songs’. Combining the talents of Haitian guitarist & composer Frantz Casseus with Puerto Rican-born, Haitian-raised vocalist Lolita Cuevas, we’re lucky that the Smithsonian Folkways archivists captured these two performers at the peak of their powers in 1953. Arranged by Casseus, these songs are presented as lullabies and méringue de salon, a slow and stately dance of Haiti’s past (which evolved into the faster méringue). A perfect to put on loop while the sun goes down & the fireflies come out…

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.

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]

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]

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]

2-AG
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 octopus that eats blue whales]

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]

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). 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 interact 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]

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]

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.