C&P#6: CBD for a long life! + CB2 receptors for health

May 03, 2022

Hello everyone,

This week, Biden continues to be unimpressive in the War on Drugs, Americans continue to liberalize their attitudes on drugs & the NYTimes continues to publish pro-Prohibition screeds.

The big science news is about CBD improving longevity, using PEA to help with the olfactory loss of COVID & how activating the CB2 receptor seems to help in so many damn ways.

[On a personal note, I’m sorry that I’m a day late. We went to the north to see family & in surprising news, after two years, my French is now rated as ‘not incomprehensible’. Also, I am solaced by the quote I just found from Somerset Maugham, “Don’t trust any foreigner who speaks French perfectly. They’re either a charlatan or a diplomatic attaché”.
I even almost translated that quote myself – but I had to look up ‘foreigner’. With ‘charlatan’ & ‘attaché diplomatique’, I was just guessing - but if a word sounds high-falutin in English & you guess that it’s a French word, you’re almost always right.
As they say, English is just French badly spoken.]

Now, here’s your news…

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Best of cannabinoid science...

A small study of CBD users finds that it might be impossible to use a ‘one size fits all’ approach to CBD dosing because of the wide range of people’s absorption rates
Population Pharmacokinetics of Oral-Based Administration of Cannabidiol in Healthy Adults: Implications for Drug Development
https://pubmed.ncbi.nlm.nih.gov/35443784/

To help with the loss of smell from COVID, a combination of PEA with luteolin (a flavonoid) helped to enhance the effectiveness of olfactory training
Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo-Controlled Clinical Trial
https://pubmed.ncbi.nlm.nih.gov/35450527/

In veterans with bipolar disorder, current cannabis use was associated with higher working memory & higher functional capacity – but also to PTSD & suicidal ideation (though you can imagine that’s because those in worse shape were using cannabis as a treatment)
Multimodal Correlates of Cannabis Use among U.S. Veterans with Bipolar Disorder: An Integrated Study of Clinical, Cognitive, and Functional Outcomes
https://pubmed.ncbi.nlm.nih.gov/35430960/

A case study of problems of withdrawal from medical cannabis & a rather negative review of the effects of cannabis on sleep
The Effects of Cannabinoids on Sleep
https://pubmed.ncbi.nlm.nih.gov/35459406/
Let it always be said: cannabinoids & sleep are the great double-edged sword. For some people, they help so much with sleep & anxiety issues. And for others, they cause sleep issues that exacerbate mental health problems. And I suspect that in some cases (like mine), it’s both.

In an analysis that runs contrary to the popular opinion, these researchers found that states who legalized cannabis saw it contribute to their opioid epidemic in all major races/ethnicities, and especially in Blacks
United States marijuana legalization and opioid mortality epidemic during 2010-2020 and pandemic implications
https://pubmed.ncbi.nlm.nih.gov/35469600/

In a rat model of temporal lobe epilepsy, CBD increased the brain levels of PPARγ (a nuclear receptor that controls genetic transcription) & reduced or abolished their seizures
Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats
https://www.mdpi.com/1424-8247/15/5/495/htm
Temporal lobe epilepsies can cause fascinating effects in the human brain - including religious epiphanies. See this essay by Oliver Sacks.

Relatedly, this review of animal model of seizures looks at the alteration of CB1 receptors but aren’t quite sure whether the increased CB1 levels are a way to control the brain’s overexcitability - or a pathological response that allows the overexcitability to occur
Neuroplastic alterations in cannabinoid receptors type 1 (CB1) in animal models of epileptic seizures
https://pubmed.ncbi.nlm.nih.gov/35460705/

In roundworms (a common model for aging research), CBD increased longevity & brain health by increasing the efficiency of autophagy (cellular recycling)
Cannabidiol induces autophagy and improves neuronal health associated with SIRT1 mediated longevity
https://pubmed.ncbi.nlm.nih.gov/35445360/

In rats with a Vitamin D3 deficiency, CBD helped increase the availability of Vitamin D3 which caused improvements in memory, pain tolerance, inflammation & aging
Effects of Cannabidiol Interactions with CYP2R1, CYP27B1, CYP24A1, and Vitamin D 3 Receptors on Spatial Memory, Pain, Inflammation, and Aging in Vitamin D 3 Deficiency Diet-Induced Rats
https://pubmed.ncbi.nlm.nih.gov/35443806/

Ethanol extracts of cannabis stems showed potent antioxidative abilities as well as the countering of acute inflammation & apoptosis (cellular suicide)
In Vitro and In Vivo Anti-Inflammatory Effects of Cannabis sativa Stem Extract
https://pubmed.ncbi.nlm.nih.gov/35438555/
See. You are right to always eat the stems…

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

the Headlines & Fav Articles

A powerful article by Ruby Deevoy et al on UK patients risking jail to grow cannabis for stopping their seizures
https://www.mirror.co.uk/news/uk-news/were-forced-risk-jail-grow-26839574
Plus, she’s great to follow on Twitter @RDeevoy.

Biden marks ‘Second Chance Month’ by commuting only 75 drug sentences
https://www.ganjapreneur.com/biden-marks-second-chance-month-by-commuting-just-75-drug-conviction-sentences/
He promised to free the prisoners – and he’s been abhorrently failing to do so. As one of the chief architects of overcriminalization in this country, all of his nice words to make it right have failed to materialize.
But at least Biden’s people make the right noises about cannabis: Attorney General Merrick Garland reiterated that prosecuting marijuana possession is not "an efficient use of the resources given the opioid and methamphetamine epidemic”
https://www.marijuanamoment.net/u-s-attorney-general-reiterates-that-marijuana-enforcement-wastes-department-resources-but-declines-to-comment-on-formal-guidance/
Meanwhile, with the bulk of those incarcerated for drugs are in the state & local systems, every week cities across the country do the hard work of commuting sentences, lowering penalties & clearing records - such as Cleveland who just expunged 4,000+ cannabis convictions
https://www.ganjapreneur.com/cleveland-ohio-officials-seek-to-expunge-4000-cannabis-convictions/

A Twitter thread on another piece of Drug War Propaganda from the NYTimes
https://twitter.com/equalityAlec/status/1518614199433408518
The Old Gray Lady has been a dirty Prohibitionistic cop for 100+ years. Alec Karakatsanis, founder of the Civil Rights Corp, lays out what misinformation they went with this time.

A majority of Americans approve of decriminalizing all drugs & opening safe-injection facilities
https://www.marijuanamoment.net/bipartisan-majority-of-americans-support-drug-decriminalization-and-most-favor-overdose-prevention-sites-poll-finds/

According to a survey, almost one-third of employees in financial, tech or corporate services jobs used cannabis during the workday
https://www.teamblind.com/blog/index.php/2022/04/13/marijuana-cannabis-use-workplace/

A surprising study finds that cannabis users in medical & recreational states were less likely to report driving high
Cannabis legalization and driving under the influence of cannabis in a national U.S. Sample
https://www.sciencedirect.com/science/article/pii/S2211335522001061
Of course, I’ll never forget what a cop told me in the early days of legal weed in Colorado: “For drunks, we look for swerving. For stoners, we look for cars stopped at green lights.”

In Europe, this year will see 340k patients benefit from medical cannabis access
https://businesscann.com/over-340000-patients-in-europe-set-to-benefit-from-medical-cannabis-access-in-2022/

Optimism as Uruguay begins their first medical cannabis harvest
https://www.cbd-intel.com/optimism-blooming-as-uruguays-first-medical-cannabis-harvest-begins

Americans for Safe Access celebrates their 20th birthday
https://www.safeaccessnow.org/asa_20th_birthday
I think ASA is one of the most important activist groups out there for the cannabis plant & if you wanted to donate for their birthday, you’d be storing up your treasures in heaven.
Some of my first experiences with cannabis activism was around the ASA conferences & learning from the people who have spent decades fighting for the rights of patients to get the only medicine that works for them. And now, they’re continuing the fight to make sure that legal weed (overtaxed & of lower quality) doesn’t drown out the medical cannabis (no tax, high quality, strict testing & with many ingestion options). It’s such important work

A former astronaut talks about his quest to grow cannabis in space
https://futurism.com/former-astronaut-cannabinoids-space
#BeenWaitingMyWholeLifeForThisOne

Law & Business

Leafreport did a test of CBD sleep products & found most to be mislabeled (hattip to Michelle Morganti)
https://www.leafreport.com/education/leafreport-study-finds-that-most-cbd-sleep-products-are-mislabeled-16067

Meanwhile, in Australia, pharmaceutical interest by GlaxoSmithKline in an over-the-counter CBD pill for sleep
https://www.brisbanetimes.com.au/business/companies/over-the-counter-cbd-sleep-pill-piques-big-pharma-interest-20220406-p5ab9v.html

The Congressional Research Service does a deep dive into cannabis with a 101-page report with a focus on what can be learned from the state experiments
https://crsreports.congress.gov/product/pdf/R/R44782
https://www.marijuanamoment.net/congressional-researchers-highlight-growing-federal-state-marijuana-policy-gap-in-new-100-page-report/
#LegalizeIt

“Lawsuit Accuses Cannabis Companies of ‘Chicago Cartel’”
https://www.ganjapreneur.com/lawsuit-accuses-cannabis-companies-of-chicago-cartel/

Big Food brands are trying to get Congress to stop copycat cannabis-infused food (though some of these crack me up)
https://www.marijuanamoment.net/kellogg-pepsi-and-other-major-brands-ask-congress-to-stop-marijuana-infused-copycat-foods/
I see their point - but I don’t really care about it. This stuff could almost fall under the satire exclusion.
What I do care about deeply is that each of these foods is an obvious risk for a child to eat them & having a very very bad experience.

The Plant & the History

In Iowa, Governor Kim Reynolds signs a bill to increased the allowed size of hemp cultivation plots
https://governor.iowa.gov/press-release/gov-reynolds-signs-several-bills-into-law
It’s an odd thing to have a limit of 320 acres for hemp - but there’s so many backwards rules around this otherwise normal agricultural plant.

The PA Department of Agriculture tweeted about the state’s first hempcrete house
https://twitter.com/PAAgriculture/status/1519697064187342849
I grew up in the Keystone State & I’m sure that our Resident Hempcrete Skeptic Ned Pelger will be glad to drive 4.5 hours to go kick the tires on this thing.
(but in the grumbles so far, “The house in the article is just a conventional wood framed house with the only change being the fiberglass batt insulation is now hempcrete...which is a much worse insulation.”)

Using iron oxide nanoparticles on hemp can help them grow better & to lower their THC levels
Effects of iron oxide nanoparticles on phenotype and metabolite changes in hemp clones (Cannabis sativa L.)
https://link.springer.com/article/10.1007/s11783-022-1569-9

An analysis of giving cows hempseed cake (a byproduct of hemp oil production) caused no differences in meat quality & could be used as a substitute for soybeans
Hempseed By-Product in Diets of Italian Simmental Cull Dairy Cows and Its Effects on Animal Performance and Meat Quality
https://pubmed.ncbi.nlm.nih.gov/35454260/

For textile nerds, an analysis of how common it’s been since the Middle Ages to blend hemp with other textiles
Identification of Blended Hemp Textiles from the Middle Ages to the 20th Century
https://www.tandfonline.com/doi/abs/10.1080/14759756.2022.2053276
Hemp is one of the key fibers in the history of human civilization, from ropes to clothing to sails to harnesses to nets. Wars have been fought over access to hemp & China – where, according to Needham, everything was invented - was known as the Land of Mulberry & Hemp.

Science

Clinical Studies & Surveys

A meta-analysis of 16 studies of young cannabis users found no significant differences in brain volumes from nonusers
Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies
https://pubmed.ncbi.nlm.nih.gov/35443799/

A PET scan shows the relationship between CB1 receptors & dopamine release (the neurotransmitter most closely associated with addiction)
Cannabinoid receptor availability modulates the magnitude of dopamine release in vivo in the human reward system: A preliminary multitracer positron emission tomography study
https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.13167

Using an IV of THC in males & females, there were no differences in the many effects measured besides the fact that the females felt more high at a lower dose
Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC)
https://pubmed.ncbi.nlm.nih.gov/35438304/
A related study in mice shows how activating the CB1 receptor causes different effects in different parts of the estrus cycle
Impact of the mouse estrus cycle on cannabinoid receptor agonist-induced molecular and behavioral outcomes
https://pubmed.ncbi.nlm.nih.gov/35466560/
One of the reasons that cannabis researchers – and scientists in general – tend to exclude female animals & female humans from studies is because their estrus cycles cause effects that are hard to account for. This leads to a disaster of medicine focused on masculine bodies & with not enough knowledge of side effects on female bodies.

In an odd study from Canada, they found that the liberalization of cannabis laws did not lead to lower infant birthweight - but that it did lead to a lower age of mothers getting pregnant
The Liberalization of Cannabis Possession Laws and Birth Outcomes: A State-Level Fixed Effects Analysis, 2003–2019
https://link.springer.com/article/10.1007/s11113-022-09714-6
Reading between the lines (and the concluding paragraph), I think these researchers were disappointed to not find more harms.
This study notwithstanding, a decent body of literature exists linking heavier levels of cannabis with a lower birth weight in infants. However, it seems like this is because cannabis, with all of its effects on hormones, tends to make people give birth earlier – and hence have babies of lower weight. But that this is not a big deal for long-term health.
Also, in a study of pregnant women, exposure to cannabis did not cause any differences in the child’s IQ but it was associated with worse attention scores in early childhood
Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes
https://pubmed.ncbi.nlm.nih.gov/34856574/

A survey of allergists found a wide array of knowledge & attitudes about allergies to cannabis
Impact of Cannabis Knowledge and Attitudes on Real-World Practice: An International Survey of Allergists
https://pubmed.ncbi.nlm.nih.gov/35472594/

Harms & No Help

An online 6-week web intervention for problematic cannabis use appears to help adults with ADHD to control their use
Cannabis Use in Adults Who Screen Positive for Attention Deficit/Hyperactivity Disorder: CANreduce 2.0 Randomized Controlled Trial Subgroup Analysis
https://pubmed.ncbi.nlm.nih.gov/35442196/
Despite being only slightly physically addicting, cannabis is obviously a psychologically addictive drug. Any helpful tools for people to control their use are a good thing to have.

A meta-analysis of cannabinoids for lowering the use of opioids found help in smaller studies but the effect was not replicated in larger randomized clinical trials
Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies
https://www.nature.com/articles/s41386-022-01322-4

A Colorado analysis found an association between the number of dispensaries & the rates of emergency room visits for psychosis
Impact of cannabis legalization on healthcare utilization for psychosis and schizophrenia in Colorado
https://pubmed.ncbi.nlm.nih.gov/35429874/

Adolescents who vaped cannabis or nicotine saw increased gastrointestinal issues
Risk of respiratory, gastrointestinal, and constitutional health symptoms: A cross-sectional study of Texas adolescent and young adult nicotine and marijuana vapers
https://www.sciencedirect.com/science/article/abs/pii/S0091743522001050
This one makes sense. We have a huge number of endocannabinoid receptors in our guts. The idea that overstimulating them for long periods of time can lead to problems is no great stretch of the imagination.

THC appears to harden the arteries & may be the reason it’s linked to cardiovascular disease – but this can be blocked by genistein, an ingredient in soybeans that appears to block the CB1 receptor (hattip to Stuart Tomc)
Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation
https://pubmed.ncbi.nlm.nih.gov/35489334/
Sometimes I’m not sure how these studies come about – but I plan to be eating more soybeans.

Recent Reviews

A review of cannabis for the treatment of anxiety
Medicinal Cannabis for the Treatment of Anxiety Disorders: a Narrative Review
https://link.springer.com/article/10.1007/s40501-022-00260-8

This collection of studies finds cannabis helpful for a number of different types of non-cancer pain
Long-term observational studies with cannabis-based medicines for chronic non-cancer pain: A systematic review and meta-analysis of effectiveness and safety
https://pubmed.ncbi.nlm.nih.gov/35467781/

A practical guide to using the cannabinoids in rheumatology (joint pain & arthritis)
Cannabinoids in the rheumatic diseases
https://ouci.dntb.gov.ua/en/works/9jmEezpl/

A review of the confusion around vaping for medical cannabis practitioners & the need for greater quality control & accuracy
Vapor Pressure, Vaping, and Corrections to Misconceptions Related to Medical Cannabis' Active Pharmaceutical Ingredients' Physical Properties and Compositions
https://pubmed.ncbi.nlm.nih.gov/35442765/

This review finds that in glaucoma, despite all the knowledge of the levels of the endocannabinoid receptors, we still don’t know how they cause their neuroprotective & hypotensive (pressure lowering) effects
CB 1 R, CB 2 R and TRPV1 expression and modulation in in vivo, animal glaucoma models: A systematic review
https://pubmed.ncbi.nlm.nih.gov/35468582/

Preclinical Research

CBD shows a promising combination with the antibiotic polymyxin B against Gram-negative bacteria, especially the Klebsiella pneumoniae which causes pneumonia
Potential cannabidiol (CBD) repurposing as antibacterial and promising therapy of CBD plus polymyxin B (PB) against PB-resistant gram-negative bacilli
https://pubmed.ncbi.nlm.nih.gov/35440801/

In a model of intracerebral hemorrhage (bleeding in the brain – the second most common cause of stroke), PEA lowered neuroinflammation & improved motor function via the PPAR-α receptors (nuclear receptors that control genetic transcription) in microglial cells (the immune cells of the brain)
Palmitoylethanolamide ameliorates neuroinflammation via modulating PPAR-α to promote the functional outcome after intracerebral hemorrhage
https://www.sciencedirect.com/science/article/pii/S0304394022002051

In a mouse model of heart damage, the ability of curcumin to protect the heart seems to be mediated by the C2 receptor
Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors
https://www.mdpi.com/2075-1729/12/5/624

In a mouse model of diabetes, activating the CB2 receptor protected the heart from inflammation, oxidative stress, fibrosis (scarring), cell death & cardiac dysfunction
Cannabinoid receptor 2 activation alleviates diabetes-induced cardiac dysfunction, inflammation, oxidative stress, and fibrosis
https://pubmed.ncbi.nlm.nih.gov/35460032/

In stressed rats, activating the CB2 receptor protects the heart from oxidative stress during a heart attack
Cannabinoid receptor-2 agonist AM1241 attenuates myocardial ischemia/reperfusion- induced oxidative stress in rats via Nrf2/HO-1 pathway
https://assets.researchsquare.com/files/rs-1568320/v1/859f5cdf-0ab0-499b-b602-c49f34d8608e.pdf

In a model of brain damage from sepsis, activating the CB2 receptor prevented overactivation by the microglial cells (immune cells of the brain) & lowered neuronal pyroptosis (cell death from extreme inflammation)
Protective Effects of Cannabinoid Type 2 Receptor Against Microglia Overactivation and Neuronal Pyroptosis in Sepsis-Associated Encephalopathy
https://pubmed.ncbi.nlm.nih.gov/35460837/
It’s always strange to me when the abstract doesn’t even list the type of animal used in the experiment. Not only is it important data, these animals gave their lives for this research. Name them.

In enzyme assays, the cannabinoids show an ability to moderately inhibit the acetylcholinesterase & butyrylcholinesterase enzymes that operate at neuromuscular junctures & hint at one more path for their neuroprotective effects
Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities
https://www.karger.com/Article/FullText/524086

In rats with peritonitis (an inflamed swelling of the tissue lining the abdomen), these researchers tracked the mRNA expression of the cannabinoid receptors & found changes in the brainstem where the control of breathing patterns is generated
Cannabinoid Receptor mRNA Expression in Central and Peripheral Tissues in a Rodent Model of Peritonitis
https://pubmed.ncbi.nlm.nih.gov/35446129/

In a rat model of stroke, β-caryophyllene (a predominant terpene of cannabis) caused significant neuroprotection via regulation of ferroptosis (a type of cell death, only recently discovered, caused by the accumulation of iron)
β-Caryophyllene Suppresses Ferroptosis Induced by Cerebral Ischemia Reperfusion via Activation of the NRF2/HO-1 Signaling Pathway in MCAO/R rats
https://www.sciencedirect.com/science/article/abs/pii/S0944711322001908

In a mouse & cellular model of a heart stressed by metabolic disorder, the two terpenes 1,8-cineole & beta-caryophyllene worked synergistically to protect from heart damage
Combination of 1,8-cineole and beta-caryophyllene synergistically reverses cardiac hypertrophy in isoprenaline-induced mice and H9c2 cells
https://www.sciencedirect.com/science/article/abs/pii/S0045206822002280

During the creation of zebrafish embryos, inhibiting their FAAH & MGL enzymes (which break down anandamide & 2-AG respectively) caused deficits in their response to audio & visual stimulation
Inhibiting the endocannabinoid degrading enzymes FAAH and MAGL during zebrafish embryogenesis alters sensorimotor function
https://pubmed.ncbi.nlm.nih.gov/35438163/

In a cellular model of the early placenta, anandamide & 2-AG showed their importance for migration & angiogenesis (blood vessel formation)
The endocannabinoids anandamide and 2-arachidonoylglycerol modulate the expression of angiogenic factors on HTR8/SVneo placental cells
https://www.sciencedirect.com/science/article/abs/pii/S0952327822000527

The synthetic cannabinoids from the indazole-carboxamide class show a decreased potential for tolerance & withdrawal in animal models
Cannabimimetic effects of abused indazole-carboxamide synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA and 5F-ADB-PINACA in mice: tolerance, dependence and withdrawal
https://www.sciencedirect.com/science/article/abs/pii/S0376871622002058

Cannabinoid Chemistry

Another nanoparticle combination for CBD: zein-whey protein
Preparation, stability, antioxidative property and in vitro release of cannabidiol (CBD) in zein-whey protein composite nanoparticles
https://www.sciencedirect.com/science/article/pii/S0023643822004017

Quantum tunneling in the pathway from CBGA to THC!
Computational Evidence for Tunneling and a Hidden Intermediate in the Biosynthesis of Tetrahydrocannabinol
https://pubmed.ncbi.nlm.nih.gov/35451301/
I’ll admit that this one is outside my realm of knowledge (I’m more of a biochemist than a chemist) but it sounds so cool that it deserves an exclamation mark.

Plant Medicines, Harm Reduction & Psychoactives

People using TikTok for recovery!
https://www.psypost.org/2022/04/study-investigates-how-people-are-using-tiktok-as-a-part-of-their-substance-use-disorder-recovery-63002
I mean, I use TikTok to post videos about books so my kids can see what I care about in case I get hit by a bus before they grow up - but this platform never ceases to impress me with its new corners. As someone in recovery, I found this article very cheering & now I’m starting to follow these hashtags.

An ETF focused on psychedelics has plummeted in the last year (an ETF is a basket of stocks focused usually focused on one sector or idea)
https://www.bloomberg.com/opinion/articles/2022-04-14/psychedelics-stocks-like-atai-life-sciences-are-having-a-bad-psilocybin-trip
The similarities of the Green Rush to the Psychedelic Rush are astounding.

A favorite journalist Don Lattin writes on the religious leaders who took psilocybin for a NYU/John Hopkins study of “psychedelically naive” religious professionals
https://www.lucid.news/pioneering-clergy-of-diverse-religions-embrace-psychedelics/

On how psychedelics & plant medicines may help with PTSD via their effect on fear memory
Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation
https://pubmed.ncbi.nlm.nih.gov/35489438/
One theory about PTSD is that every time you remember the traumatic experience, it’s like you are pulling it out of your memory storage & living it all over again. That means its sharpness wounds you all over again before being placed back into storage. The power of psychedelics – and most specifically MDMA – is that it allows you to experience the trauma again - but the drug softens the sharp edges before it goes back into memory. With a few sessions, the stabbing sharpness of the memory can be mellowed to a dull ache that frees you from reliving the intensity of the trauma every time you remember it.

An analysis of the brains of hallucinogen users found “greater density of structural connectivity in white matter tracts that are thought to support cognition, emotion, and creativity”
Differences in personality, cognitive abilities, illicit drug use, and white matter structural integrity between hallucinogen users and matched controls
https://assets.researchsquare.com/files/rs-1529935/v1/a545bafc-fe8e-4627-936b-966fa0a464fd.pdf

Thanks.
- lex

PS: I just discovered this beautiful album of Tárrega’s solo classical guitar as played by Giulio Tampalini. Francisco de Asís Tárrega y Eixea is new to me, but apparently, he’s known as the father of classical guitar. Because of an early accident with his eyes, his father wanted him trained on the guitar because it was a way to support himself if blind. His father also wanted him to learn piano because it was more popular – but the young Tárrega ran away from home three times to play in coffee houses & follow gypsies before his father could find him & bring him home. After studying at the Madrid Conservatory, he achieved early fame & composed many classic pieces, often incorporating the styles from the classical masters as well as the North African rhythms. It’s considered that he laid the foundations for 20th-century appreciation of classical guitar & for the guitar to be viewed as an instrument of recitals & concert halls.

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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 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]

Cannabinoids & the People

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