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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.

This week, research on CBDV for the severe seizures of Rett syndrome, CBD for autism & joint pain as well as combining CBD with an antibiotic to kill a drug-resistant bacteria stalking hospitals.

Also, you can follow me on Twitter (@LexPelger) for funnier takes on the science below – such as how honeybees aren’t the only ones we should be dosing

Additions & reorderings:

To the Living Glossary at the bottom, I added an entry on CBDV. Also, in addition to the usual breakout for Cancer, there’s a special section on the Heart below because some cardiology journal decided to have a special issue.
Lastly, I’m experimenting with a new section called ‘Harms & No Help’ to list the studies where cannabinoids did not work or caused harm. For researchers used to seeing all the glowing reports, I think it will be nice to get a bracing dose of the negatives.
For instance, I bet that once you've seen enough times of Jesus feeding thousands with just two fish & a loaf of bread, you eventually hope that he'll take a swing at a heckler just to break up the monotony. In the same way, after watching endless miracles with cannabis, it's nice to see that it’s not an Immaculate Plant that heals all ills & causes no harms. Though it would probably still throw all of the moneychangers out of the Temple…

Formatting:
I am quite surprised by how poor Substack is at handling formatting since its very purpose is newsletters (I don’t even keep my drafts in Substack anymore because I lost a third of my first newsletter to the void). So I’m constantly tinkering with the formatting on here to make it look more readable for mobile, email & web viewing. If you experience problems, please let me know so I can try to address them.

Now, here’s your news…

Best of cannabinoid science...

In girls with Rett syndrome (a severe neurological developmental disorder that includes seizures), this Phase 1 study found that treatment with high levels of CBDV reduced the average number of seizures from 32 per month to 7
The efficacy and safety of cannabidivarin treatment on epilepsy in girls with Rett syndrome: A phase I clinical trial
https://pubmed.ncbi.nlm.nih.gov/35364618/
See the new CBDV entry below in the Living Glossary.

In older patients with pain, a three-year retrospective study finds that even a low dose of cannabinoids is linked to a decreased use of opioids
Cannabinoids reduce opioid use in older patients with pain : Retrospective three-year analysis of data from a general practice
https://pubmed.ncbi.nlm.nih.gov/35384481/

In a review of CBD in orthopedic sports medicine, a survey of patients at a clinic found that 19% used CBD for joint pain issues & 30% of that group also used cannabis for their pain
Prevalence of Cannabinoid (CBD) Use in Orthopaedic Sports Medicine Patients
https://pubmed.ncbi.nlm.nih.gov/35400139/

On autism, a review of the clinical evidence shows that the cannabinoids, and especially CBD, can help with common comorbidities as well as the central symptoms
Clinical Data on Canabinoids: Translational Research in the Treatment of Autism Spectrum Disorders
https://www.mdpi.com/2227-9059/10/4/796
I have two cousins whose lives were changed by CBD. It’s one of first reasons that turned me into a big believer. While this review stresses that more practical translational data is needed – which is true – there’s more than enough anecdotal evidence in the online communities of parents that will help anyone seeking to get started.
Relatedly, a nurse’s guide to using hashish for autism
https://weedsguideline.com/2022/03/29/a-holistic-nurses-perspective-on-cannabis-for-autism/

The bacteria Acinetobacter baumannii is becoming resistant to the last-resort antibiotic - but this study suggests that adding CBD to the treatment significantly increases the lethality
Mechanisms Underlying Synergistic Killing of Polymyxin B in Combination with Cannabidiol against Acinetobacter baumannii: A Metabolomic Study
https://www.mdpi.com/1999-4923/14/4/786
I will die on this hill: we will greatly regret these last decades of not using cannabinoids against pathogenic bacteria.

My ad: Work with White Whale Creations

This newsletter is a free offering from White Whale Creations. I produce content for cannabis & psychedelic companies & have sponsorship opportunities for ‘The Lex Files’ podcast. #lookingtowork

Closest to my heart, I also offer individualized sessions for people & their families who want to use cannabis & CBD for their serious conditions like pain, insomnia, autoimmune disorders or just to live healthier. I know the products to recommend, how to go about finding what works for you & I have all the science to back it up. If you know anyone who would be interested – especially those of us getting older, please send them here: Cannabinoid Education Sessions.

the Headlines & Fav Articles

A poll finds that half of US adults have tried cannabis
https://today.yougov.com/topics/lifestyle/articles-reports/2022/04/07/half-of-americans-have-tried-marijuana
while a poll of Europeans across 8 countries find 55% backing cannabis legal reforms
https://www.marijuanamoment.net/majority-of-europeans-support-marijuana-legalization-new-international-poll-finds/


A thread about children being taken away from their parents because of drug use during pregnancy
https://twitter.com/cecilianowell/status/1513553344706465797
This is a particularly heinous trend that’s been on the rise these last few years. To learn more & to support those fighting it, follow the National Advocates for Pregnant Women.

NYC Mayor Eric Adams wants to grow cannabis on top of public housing buildings – though the feds who fund the housing might not be a fan
https://www.marijuanamoment.net/nyc-mayor-wants-to-explore-putting-marijuana-greenhouses-on-rooftops-of-public-housing-buildings/

In Thailand, people will soon be allowed to grow an unlimited number of cannabis plants
https://www.nationthailand.com/in-focus/40014396

Check out ‘The New Age Cannabis Podcast’ for a view from Africa
YouTube: https://www.youtube.com/channel/UC-t8QhfJte0DbmGaRtyHX0w
Twitter: https://twitter.com/newagecannapc
They cover lots of angles on the plant – but you might start with cannabis as a shamanic medicine.
And kudos on their IG comic this week: weed > hangovers

Jackie Bryant on being an expert witness in a federal cannabis case where they never tested the greens
https://cannabitch.substack.com/p/tangoing-with-the-man
Her Substack newsletter is enjoyable & excellent. It’s great to have an insider’s peek from a seasoned cannabis journalist. Here’s her Twitter to follow as well.

Law & Business

The new grants program from the VA to prevent veteran suicide will specifically not support cannabis treatments
https://www.federalregister.gov/documents/2022/04/15/2022-08040/funding-opportunity-staff-sergeant-parker-gordon-fox-suicide-prevention-grant-program
Those stupid fucking dinosaurs.

A Congressional Research Service report on how hemp issues might be addressed in the next Farm Bill includes increasing the THC limit to 1% & finally forcing the FDA to do … anything
https://crsreports.congress.gov/product/pdf/R/R47057

A Rhode Island cultivation lab is suing the DEA for dragging their feet over pharmaceutical cannabis licensing
https://www.accesswire.com/697170/MMJ-BioPharma-Cultivation-Sues-DEA-Over-Foot-Dragging-on-Marijuana-Pharmaceutical-Licensing
The DEA has one response to everything: no response. They will stonewall for years, and even decades.
Meanwhile, this lab is locked out of studying cannabis for MS & Huntington’s disease, two conditions where it could greatly help people.

The Substance Abuse & Mental Health Services Administration writes that a medical cannabis recommendation from a doctor doesn’t excuse a positive drug test for a federal worker
https://www.marijuanamoment.net/feds-clarify-that-medical-marijuana-recommendations-from-doctors-dont-excuse-positive-drug-tests/
<eye roll>
& the FAA doubles down on drug testing as well, including for cannabis
https://www.faa.gov/jobs/newemployeeonboarding/notice-applicants-or-employees-subject-drug-andor-alcohol-testing
& according to a federal judge, Amazon is allowed to drug screen workers in its warehouse
https://www.reuters.com/legal/transactional/amazon-can-screen-nyc-job-applicants-marijuana-judge-says-2022-04-12/
These last two make a bit more sense for safety reasons – except for the fact that a positive test for THC does not mean intoxication. It just means that you have ingested it within the last month, not that you’re feeling any effects right now.
This is one of the toughest parts about drug testing. For certain industries, you obviously shouldn’t be intoxicated while operating the heavy machinery – but unlike with alcohol, there’s no good way [yet] to test for THC intoxication.

In somewhat funny related research, researchers try to relate a measure of cannabis intoxication (currently a scale from 0-100 asking ‘how high are you?) with a new measure using “contemporary young adult language” with a scale that goes from relaxed to calm/chill to high to stoned/baked
Assessing subjective cannabis effects in daily life with contemporary young adult language
https://pubmed.ncbi.nlm.nih.gov/34890928/
Just wait until 7 years from now when these researchers discover TikTok…

Amazon, who conspicuously went pro-weed last year, wants to overturn the pro-union vote at their NYC warehouse because the organizers were giving out weed
https://apnews.com/article/business-national-labor-relations-board-new-york-city-new-york-labor-unions-4b1a9535174ae7d2b4aedb20a9e292be
What would Utah Phillips say?

At the Green Dragon cannabis company, workers were reinstated after being fired for supporting union organizing efforts
https://denverite.com/2022/04/05/green-dragon-cannabis-dispensary-cuts-ties-with-grow-house-workers-for-union-organizing/

Leafly commissions 4 cannabis murals in North American cities
https://www.businesswire.com/news/home/20220413005314/en/Leafly-Celebrates-420-by-Highlighting-Cannabis-as-a-Force-for-Good-in-Communities

Medical Cannabis & Culture

Idris Elba used to sell weed to Dave Chapelle
https://ew.com/celebrity/idris-elba-sold-weed-to-dave-chappelle/
Love Elba. If you haven’t seen ‘The Wire’, it’s the ‘War & Peace’ of our generation – and it just happens to be about drugs. It’s the only series I’ve ever gone through twice & it’s the most important thing you can watch to understand the baked-in racism & horrors of the War on Drugs.

The Plant & the History

The rules for using hempcrete in houses got preliminary approval from the International Code Council
https://ushba.org/hemp-lime-irc-proposal-recommended-for-approval/
As for the analysis from our Resident Construction Expert Ned Pelger, he says,
“Well that was an interesting read. I finally got some real data on [hempcrete] and can't imagine why anyone would use it as a building material:
1. No structural value
2. Corrodes metals, so any metals in contact need to be coated
3. Per above, all wiring needs to be in conduits, quite expensive add for residential construction
4. R value [measure of insulation] is poor, less than half that of fiberglass batt and one quarter that of foam. So walls need to be 2 times to 4 times thicker, a huge cost and loss of space.”

For the sound absorption of natural fibers, hemp was the clear winner
Experimental Survey of the Sound Absorption Performance of Natural Fibres in Comparison with Conventional Insulating Materials
https://www.mdpi.com/2071-1050/14/7/4258
This one speaks to my young heart because I won a first prize in a high school science fair for a long arduous study of the sound absorption properties of various types of concrete block.

An in-depth review article on using hemp as a polymer
Hemp and Its Derivatives as a Universal Industrial Raw Material (with Particular Emphasis on the Polymer Industry)—A Review
https://www.mdpi.com/1996-1944/15/7/2565
“There’s a great future in [hemp] plastics.”
(hattip to Ned Pelger for never letting a year go by without this quote…)

A look at the knowns & unknowns of the spread of cannabis through Europe & the Iberian Peninsula
Origin, early expansion, domestication and anthropogenic diffusion of Cannabis, with emphasis on Europe and the Iberian Peninsula
https://www.sciencedirect.com/science/article/pii/S1433831922000129
I love this stuff. There’s so much we don’t know – but the scientists putting together the jigsaw puzzles of available data do impressive work.

A practical study in Italy of the ability of hemp to clean up heavy metals from the soil
Hemp Cultivation in Soils Polluted by Cd, Pb and Zn in the Mediterranean Area: Sites Characterization and Phytoremediation in Real Scale Settlement
https://www.mdpi.com/2076-3417/12/7/3548

On using hemp to sequester carbon in sandy soils
Fiber hemp as a feasible crop for enhancing carbon sequestration and cultivation under water scarcity in sandy agricultural soils
https://opus4.kobv.de/opus4-UBICO/frontdoor/index/index/docId/28718

AI to grow plant tissue cultures!
Machine learning (ML) algorithms and artificial neural network for optimizing in vitro germination and growth indices of industrial hemp (Cannabis sativa L.)
https://www.sciencedirect.com/science/article/abs/pii/S0926669022002849
I’m just waiting for when my AI can tell me when to smoke, how much to take & what to do afterwards.
<right now, two puffs, read Maugham>

Science

On exercise & the endocannabinoid system by Nate Seltenrich @ Project CBD
https://www.projectcbd.org/move-it-exercise-endocannabinoid-system
A growing body of evidence suggests that the runner’s high is actually caused not by endorphins – but by endocannabinoids.

Clinical Studies & Surveys

In humans & in a rat model of spinal disc degeneration, activating the CB2 receptor delayed the slowdown of the nucleus pulposus cell (they produce the jelly that supports the spinal pressure), restored balance to the extracellular matrix & lessened intervertebral disc degeneration
CB2R Attenuates Intervertebral Disc Degeneration by Delaying Nucleus Pulposus Cell Senescence through AMPK/GSK3β Pathway

https://pubmed.ncbi.nlm.nih.gov/35371598/

An editorial response to the clinical CBD study that found no help for COVID
Re: “Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial” by Crippa et al.
https://www.liebertpub.com/doi/10.1089/can.2022.0034

This study of US cannabis treatment data found no relationship between legalization & treatment rates for cannabis use disorder
Admissions to substance use treatment facilities for cannabis use disorder, 2000-2017: Does legalization matter?
https://pubmed.ncbi.nlm.nih.gov/35368113/

In honeybees, adding hemp extract to their sugar syrup increased their antioxidant activity & boosted their average lifespan from 35 days to 52 days
Impressive Impact of Hemp Extract on Antioxidant System in Honey Bee (Apis mellifera) Organism
https://www.mdpi.com/2076-3921/11/4/707/htm

In dairy cows, enriching their feed with omega-3 fatty acids helps to activate their endocannabinoid systems
Effects of Omega-3 Supplementation on Components of the Endocannabinoid System and Metabolic and Inflammatory Responses in Adipose and Liver of Peripartum Dairy Cows
https://assets.researchsquare.com/files/rs-1481439/v1/d98d26fa-3de1-4cb1-9e9a-a42e406f89e6.pdf

In dogs with red, itchy skin, CBD oil (with no THC in it) was well-tolerated & decreased the itchiness
Effects of cannabidiol without delta-9-tetrahydrocannabinol on canine atopic dermatitis: A retrospective assessment of 8 cases
https://pubmed.ncbi.nlm.nih.gov/35368394/

Harms & No Help

In humans with a total knee surgery, a double-blind study found no help from three weeks of CBD topicals for pain, opioid consumption or sleep scores
Topical Cannabidiol (CBD) After Total Knee Arthroplasty Does Not Decrease Pain or Opioid Use: A Prospective Randomized Double-Blinded Placebo-Controlled Trial
https://pubmed.ncbi.nlm.nih.gov/35390457/

In people with cocaine use disorder, 800 mg of CBD did not improve their cognitive outcomes
Cannabidiol effects on cognition in individuals with cocaine use disorder: Exploratory results from a randomized controlled trial
https://pubmed.ncbi.nlm.nih.gov/35367279/

In pregnant mothers, a population study found that cannabis use altered the placental weight to birth weight ratio & caused a higher risk of pregnancy complications
Maternal preconception and pregnancy tobacco and cannabis use in relation to placental developmental markers: A population-based study
https://pubmed.ncbi.nlm.nih.gov/35378220/
& in a cohort study of pregnant mothers, fetal cannabis exposure led to increased adiposity (fatty tissue) & fasting glucose in the children
Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study
https://pubmed.ncbi.nlm.nih.gov/35357471/

In teens, the early use of cannabis may lead to more violence in the early stages of psychosis
The Link Between Cannabis Use and Violent Behavior in the Early Phase of Psychosis: The Potential Role of Impulsivity
https://pubmed.ncbi.nlm.nih.gov/35392388/
This is another idea that nobody likes & that goes against the peace & love vibe of weed, but there’s plenty of stories of people getting high & getting violent. In the ‘50s, it was a whole thing to smoke some reefer & go out, get crazy & get into fights. If everybody told you that marihuana would make you violent, that would certainly help to make it true.
A side note is that the historian Ernest Abel collected mouse studies from the ‘50s where hungry mice would get more violent if given THC. No other drug caused this reaction.

An association study from a large Norwegian data set found a link between teen cannabis use & physical health problems
Association between cannabis use and physical health problems in Norwegian adolescents: a cross-sectional study from the youth survey Ungdata
https://pubmed.ncbi.nlm.nih.gov/35382834/

Among patients with HIV, treatment with cannabis did not help improve their chronic pain
Cannabis use, pain interference, and prescription opioid receipt among persons with HIV: a target trial emulation study
https://pubmed.ncbi.nlm.nih.gov/34180721/

A case report of a very difficult prolonged experience with a 100 mg edible
“Everything seems like a Cartoon”- Single, Oral ingested Cannabis induced Depersonalization-Derealization Disorder
https://dc.etsu.edu/asrf/2022/schedule/47/
Let it be said, huge doses of cannabis can whack people out for weeks & months as readily as psychedelics can.

Heart

In older individuals at risk for ischemic heart disease, chronic cannabis use was associated with only mild heart rate changes but led to an increased risk of arrhythmias
Arrhythmic Effects of Cannabis in Ischemic Heart Disease
https://pubmed.ncbi.nlm.nih.gov/35353598/

In red blood cells from humans, CBD & THC increased their viscosity & elasticity as well as adversely affecting membrane integrity while at the highest doses, it disintegrated them completely
The in vitro effect of delta-9-tetrahydrocannabinol and cannabidiol on whole blood viscosity, elasticity and membrane integrity
https://pubmed.ncbi.nlm.nih.gov/35382895/

[all of the research below from a spotlight issue of the ‘Journal of the American College of Cardiology’]

In human heart cells, a combination of PEA & polydatin (a nutraceutical derived from the resveratrol found in wine) protected the cells from the insults of two common chemotherapy drugs & lessened their inflammation
PALMITOYLETHANOLAMIDE-POLYDATIN COMPLEX REDUCES INFLAMMATION IN HUMAN VASCULAR ENDOTHELIAL CELLS EXPOSED SEQUENTIALLY TO DOXORUBICIN AND TRASTUZUMAB THROUGH LKB1-AMPK AND NLRP3-CYTOKINE RELATED PATHWAYS
https://www.jacc.org/doi/full/10.1016/S0735-1097%2822%2902909-6
For some reason, the main drug getting combined with PEA is polydatin. Evidently, they work well together. An endocannabinoid & the hotshot from red wine. Who knew? Anyway, chemo drugs are hard on the heart – and this preclinical work shows some protection.

Recommended for You

In a look at a large number of cancer survivors, those with cannabis use disorder had no higher risk of a later major cardiac events
MAJOR ADVERSE CARDIAC AND CEREBROVASCULAR EVENTS WITH CANNABIS USE DISORDER IN ADULT CANCER SURVIVORS HOSPITALIZED WITH PRIOR HISTORY OF MYOCARDIAL INFARCTION
https://www.jacc.org/doi/full/10.1016/S0735-1097%2822%2902939-4

In a young man prescribed cannabis for his anxiety, smoking caused him to pass out & while in the ER, he experienced asystole (no electricity or movement in the heart)
ASYSTOLE AS A COMPLICATION OF MEDICAL MARIJUANA USE
https://www.jacc.org/doi/full/10.1016/S0735-1097%2822%2902909-6

In a man with Wolff-Parkinson-White syndrome (a rare heart condition where extra signaling between the upper & lower parts of your heart lead to a rapid heartbeat), a cannabis edible sent him to the hospital with a high heart rate & blood pressure
CANNABIS AND THE WOLF, A RISKY COMBINATION
https://www.jacc.org/doi/full/10.1016/S0735-1097%2822%2903444-1

Two case studies of healthy young people with potential heart problems from cannabis
SPONTANEOUS CORONARY ARTERY DISSECTION AND CANNABIS TOXICITY IN A HEALTHY ATHLETIC MALE
https://www.jacc.org/doi/full/10.1016/S0735-1097%2822%2903165-5
YOUNG FEMALE WITH CANNABIS ASSOCIATED ATRIAL FLUTTER 1:1 CONDUCTION
https://www.jacc.org/doi/full/10.1016/S0735-1097%2822%2904435-7

Cancer

For people with cancer, a review of the efficacy of cannabis for their appetite
Efficacy of medicinal cannabis for appetite-related symptoms in people with cancer: A systematic review
https://pubmed.ncbi.nlm.nih.gov/35360989/
The classic story in this field is that of Dr. Lester Grinspoon. A respected scientist tasked by the government to look for the harms of cannabis, he couldn’t find much. And then when his own son developed cancer, the treatments caused extreme nausea. In fact, once when his son saw his nurse in the supermarket, the association caused him to throw up immediately. But then one session, the medical team noticed that his son experienced no nausea & even asked for a sandwich after the treatment. It turns out that Dr. Grinspoon allowed his son to ingest cannabis right before tntering the hospital that day & it changed everything for him. This led to Dr. Grinspoon writing the book ‘Marihuana Reconsidered’, perhaps the most influential early cannabis tome to de-demonize the plant & to allow for the increased acceptance of cannabis as a medicine.
(Now you can follow along with the work of his son Peter who is a great voice online about cannabis as well as harm reduction. My interview with him about his own struggles with addiction was the Season 1 Finale of the Lex Files –(video here). Also, his book ‘Free Refills’ is excellent)

This review focuses on the many mechanisms of actions of the endocannabinoid system against skin cancer
Impact of Cannabinoid Compounds on Skin Cancer
https://www.mdpi.com/2072-6694/14/7/1769
“Cannabinoids have been shown to exert their anticarcinogenic effects at different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis [choking blood flow], as well as inducing apoptosis [suicide] and autophagy [engulfing].”
If it sounds like a war game, it is…

A survey of patients with cutaneous lymphoma (a cancer of the T cells that can lead to itchiness), found that ~20% of them endorsed cannabis use for their itching
Cannabis use among patients with cutaneous lymphoma: A cross-sectional survey
https://pubmed.ncbi.nlm.nih.gov/35395396/

In pancreatic cancer cells, low doses of CBD stimulate the killer cells to get killing
A Low Dose of Pure Cannabidiol Is Sufficient to Stimulate the Cytotoxic Function of CIK Cells without Exerting the Downstream Mediators in Pancreatic Cancer Cells
https://www.mdpi.com/1422-0067/23/7/3783/htm

Contrariwise, this study looks at how THC causes chemotherapy to work less well because it impedes the treatment’s immune checkpoint blockades via the CB2 receptor
Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2
https://pubmed.ncbi.nlm.nih.gov/35383142/

With disulfiram (an anti-alcohol drug now being looked at to treat cancer), CBD may interfere with its efficacy against cancer
Cannabidiol-induced activation of the metallothionein pathway impedes anticancer effects of disulfiram and its metabolite CuET
https://pubmed.ncbi.nlm.nih.gov/34632694/

Recent Reviews

A review of endocannabinoid signaling in the glial cells (support cells of the brain)
Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells
https://pubmed.ncbi.nlm.nih.gov/35353392/

This review of cannabis for dentistry shows the most support for using CBD for certain mouth disorders - but overall, the research on cannabis & dentistry is lacking
A critical review of cannabis in medicine and dentistry: A look back and the path forward
https://pubmed.ncbi.nlm.nih.gov/35362240/

An editorial on treating traumatic brain injuries by targeting MAGL (the enzyme that breaks down 2-AG)
MAnGLed astrocytes in traumatic brain injury: astrocytic 2-AG metabolism as a new therapeutic target
https://pubmed.ncbi.nlm.nih.gov/35353889/

A review of why THC & CBD are so powerful as antioxidants & anti-inflammatories
Cannabis sativa L. Bioactive Compounds and Their Protective Role in Oxidative Stress and Inflammation
https://www.mdpi.com/2076-3921/11/4/660

This review of nutraceutical treatments for Crohn’s disease highlights cannabis & the cannabinoids
Nutraceuticals and Diet Supplements in Crohn's Disease: A General Overview of the Most Promising Approaches in the Clinic
https://pubmed.ncbi.nlm.nih.gov/35407131/

Preclinical Research

Using computer modeling of the COVID-19 virus, the cannabinoids CBG, CBGA & CBC were the best at halting viral entry & replication
In silico discovery of non-psychoactive scaffolds in Cannabis halting SARS-CoV-2 host entry and replication machinery
https://pubmed.ncbi.nlm.nih.gov/35399958/

In an animal model of osteoarthritis, oral THC reduced joint pain & degeneration
ELUCIDATING DISEASE-MODIFYING MECHANISMS OF DELTA-9-TETRAHYDROCANNABINOL IN PRE-CLINICAL OSTEOARTHRITIS
https://www.oarsijournal.com/article/S1063-4584(22)00517-9/fulltext
Cannabinoids for bone health is such a thing. Taking 10 mg of CBD & 2.5 mg of THC per day is a great idea for anybody over 50. You can see some of the science here.

The importance of 2-AG as a stress regulator is confirmed in this mouse study that saw stress upregulate 2-AG levels in key parts of the brain – and apparently, this green nut oil helps with 2-AG levels & stress
Stress upregulates 2-arachidonoylglycerol levels in the hypothalamus, midbrain, and hindbrain, and it is sustained by green nut oil supplementation in SAMP8 mice revealed by DESI-MSI
https://pubmed.ncbi.nlm.nih.gov/35413542/

In rats, age & sex greatly altered how much THC gets into the system
Comparative Pharmacokinetics of Δ 9-Tetrahydrocannabinol in Adolescent and Adult Male and Female Rats
https://pubmed.ncbi.nlm.nih.gov/35353551/

In rats taking a synthetic cannabinoid that activates their CB1 receptor for three weeks, the amount of anesthesia needed to knock them out was increased
Minimum Alveolar Concentration of Isoflurane in Rats Chronically Treated with the Synthetic Cannabinoid WIN 55,212-2
https://www.mdpi.com/2076-2615/12/7/853/html
When your anesthesiologist wants to know if you smoke weed, tell them! It makes you more resistant to the anesthesia & if you decide to play coy, you might wake up in the middle of your surgery.

In this search for genetic underpinnings to Alzheimer’s disease, researchers found problems in endocannabinoid retrograde transmission to be a predictor of the disease
Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer’s Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways
https://www.hindawi.com/journals/omcl/2022/9565545/

In a model of neuroinflammation, a CBD & terpene enriched cannabis extract lowered pro-inflammatory cytokines via several pathways
Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling
https://pubmed.ncbi.nlm.nih.gov/35393641/

In a mouse model of diabetic kidney disease, activating their CB1 receptors helped with glucose reabsorption, amino acid uptake & preventing kidney dysfunction via the mTORC1 pathway (a master cellular regulator)
Opposite physiological and pathological mTORC1-mediated roles of the CB1 receptor in regulating renal tubular function
https://pubmed.ncbi.nlm.nih.gov/35379807/

In a pregnant rat model of the vaping of nicotine & cannabis, the main finding was that it lowered the mother’s body temperature
A Model of Combined Exposure to Nicotine and Tetrahydrocannabinol via Electronic Cigarettes in Pregnant Rats
https://pubmed.ncbi.nlm.nih.gov/35368251/

A binding assay looks at how CBD binds to two plasma proteins – and highlights its potential drug-drug interaction with warfarin
Characterization of molecular interactions between cannabidiol and human plasma proteins (serum albumin and γ-globulin) by surface plasmon resonance, microcalorimetry, and molecular docking
https://pubmed.ncbi.nlm.nih.gov/35398615/
There’s much hay made about CBD’s potential drug interactions, and while it does interact with a number of isozymes of the CYP-450s (important liver enzymes that both activates some of the drugs we take as well clearing some of them from the body), the only clinical reports of drug-drug interactions with CBD are for warfarin. (Even then, all it does is make your warfarin ~30% stronger). As one doc I know said, ‘Warfarin is crazy. It interacts with everything.” And as Dr. Jamie Corroon says, “I don’t start to worry about drug interactions and CBD unless I’m recommending more than 100 mg per day. And even then, the evidence suggests the dose threshold for risk is much higher, closer to 1,000 mg per day.”
Also, if you like cannabis science podcasts, you can listen to Dr. Corroon’s Cannabis Consult podcast here.

Cannabinoid Chemistry

This team created a new fluorescent probe for detecting CB2 receptors
Detection of Cannabinoid Receptor Type 2 in Native Cells and Zebrafish with a Highly Potent, Cell-Permeable Fluorescent Probe
https://pubs.rsc.org/en/content/articlelanding/2022/sc/d1sc06659e
& meanwhile, this team use a radioactive CB2 probe in 10 healthy humans & did a PET scan
PET Imaging of the cannabinoid receptor type 2 in humans using [11C]MDTC
https://europepmc.org/article/ppr/ppr473924

In a feat of enzyme engineering, this team found a better way to produce CBGA – the mother cannabinoid
Structure-Guided Engineering of Prenyltransferase NphB for High-Yield and Regioselective Cannabinoid Production
https://pubs.acs.org/doi/full/10.1021/acscatal.2c00786

Plant Medicines, Harm Reduction & Psychoactives

6 Canadians with a terminal illness received psilocybin mushrooms this week
https://www.businessinsider.com/first-legal-magic-mushroom-psilocybin-canada-terminally-ill-cancer-patient-2022-4
This is one of the most important uses of psychedelics.
In the US, you can support the Right to Try Psilocybin movement by going to their site, donating & following their Twitter (thanks to Dr. Sunil Aggarwal for all of his hard work on this)
https://righttotrypsilocybin.com/
https://twitter.com/RTTpsilocybin

In two clinical trials of psilocybin, their antidepressant effects seemed to be linked to increased brain network integration
Increased global integration in the brain after psilocybin therapy for depression
https://pubmed.ncbi.nlm.nih.gov/35411074/

In a large review of US drug survey data, the use of psilocybin (but no other psychedelic) was associated with a lower chance of developing opioid use disorder
Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample
https://pubmed.ncbi.nlm.nih.gov/35393455/

A short review of the potential negative heart effects from microdosing
https://blog.petrieflom.law.harvard.edu/2022/04/13/safety-first-potential-heart-health-risks-of-microdosing/
It’s a thing.

Advice from Dr. Michelle Ross on sex & magic mushrooms
https://www.drmicheleross.com/sex-on-magic-mushrooms/

The Microdose has 5 questions for Aaron Orsini: an expert & community organizer on autism & psychedelics
https://themicrodose.substack.com/p/5-questions-for-aaron-orsini
Check out my interview with him on the Lex Files. He’s great.

Thanks.
- lex

PS: This week’s album is ‘Blue Camel’ by Rabih Abou Khalil, a Lebanese player of the oud who fuses Arabic music with jazz. For our little family, it’s been one of our go-to albums to put on as we’re hanging out. As one reviewer said, he “makes the hot, staccato Middle Eastern flavour and the seamless grooves of jazz mingle as if they were always meant to.”

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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 squid 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)
[Humpback whale, because it sings hippies to sleep]

Phytocannabinoids
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]

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]

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]