Discover more from Cannabinoids & the People
C&P#12: pregnancy effects + cancer fighting + that horrible War on Drugs
State equity programs, Thailand legalizes, United Arab Emirates loosens
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New work by me:
I forgot to announce my newest science article: Glutamate, A Love Story
For ProjectCBD, the piece focuses on how the endocannabinoid system utilizes the electric glutamate neurotransmitter for so many of its functions. I previously published on serotonin & the ECS – and now I plan on continuing the series with several more neurotransmitters over the next months.
Lots on cancer, so much on pregnancy & breastfeeding that I had to break it out into its own section & an especially long & annotated section on the War on Drugs, perhaps the most important thing I’m actually doing here.
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 here 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, personalized 1-on-1 advice can be helpful, especially for people new to cannabis.
If you want someone experienced in listening to patients to create a plan with you to help you find relief, book a 1-on-1 session with me here:
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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.
Best of cannabinoid science...
A survey of podiatry doctors finds that they think CBD is helpful for foot pain problems
Podiatric Physician Perspective on the use of Cannabidiol (CBD) in the Treatment of Foot and Ankle Pathology
In humans, cannabis use is related to the levels of taurine – an amino acid that is both neuroprotective & related to body-mass index
The relationship between cannabis use and taurine: A MRS and metabolomics study
At least once a month (for the ~4 years I’ve been going through the literature like this), I find a new pathway that cannabis uses to mediate its effect. It’s wild. Most drugs use one or two major pathways to get their job done, but in that series I’m working on for ProjectCBD about the cannabinoids, I already have the first dozen pathways lined up to write about. Plus, there’s a dozen more minor ones that I could cover as well.
Quite simply, it’s a helluva plant.
In cannabis users, they were 55% less likely to have liver cancer
Lower Rates of Hepatocellular Carcinoma Observed Among Cannabis Users: A Population-Based Study
In a human lung cell & mouse model of a cytokine storm (a symptom of COVID-19), high CBD extracts reduced the levels of pro-inflammatory cytokines, inhibited activation of the T cells & downregulated the cytokine storm
High-CBD Extract (CBD-X) Downregulates Cytokine Storm Systemically and Locally in Inflamed Lungs
In mice made fat by living in small cages, oleamide for 12 weeks caused them to lose weight & to have less inflammation in their abdominal fat
Dietary oleamide attenuates obesity induced by housing mice in small cages
In a meta-analysis covering 1,132 rodents in a model of depression, “cannabinoid administration moderately improved the pooled negative effects of chronic unpredictable stress on anhedonia [inability to feel pleasure], learned helplessness, novelty suppressed feeding, time in the anxiogenic [anxiety-producing] context, and entries into the anxiogenic context”
The antidepressant and anxiolytic effects of cannabinoids in chronic unpredictable stress: a preclinical systematic review and meta-analysis
A review of many pain studies found that high THC products caused moderate improvements in pain severity
Cannabis-Based Products for Chronic Pain : A Systematic Review
A review of the potential of the cannabinoids for helping with chronic inflammatory diseases of the GI tract
Involvement of the cannabinoid system in chronic inflammatory intestinal diseases: opportunities for new therapies
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.
Popular science news, articles & videos
On CBD for menopause by Ruby Deevoy
‘Where Women Fit in the Science of Psychedelics’ by science writer Starre Vartan
Questioning the entourage effect of myrcene & mangoes by Adam Greenblatt
He also has a great TikTok cannabis channel that I just discovered: @weedpro
(I don’t know how he gets away with it. TikTok might be the most anti-drug of all the big platforms. That’s why I only do book reviews on there – and even then, I still get shadowbanned when I use words like Queer & cannabis)
the Headlines & Fav Articles
The US Conference of Mayors adopts a resolution asking Congress to pass cannabis banking legislation as well as expressing their support for federal cannabis legalization
And the Independent Community Bankers of America sent a letter to Congress saying the same
As Ambrose Bierce defined it in his ‘Devil’s Dictionary’, the Capitol is “the seat of misgovernment.”
The Washington DC Council approved a bill that prohibits employers from firing people for cannabis use (with limited exceptions)
Meanwhile, in NYC, the MTA gets sued by a worker who said he was demoted & forced to attend drug counseling sessions because of medical cannabis use
The EU pauses its evaluation of applications for CBD in food because of data gaps on topics like reproductive effects
Thailand officially legalizes the trade & cultivation of cannabis plants – and approves the sale of products with less than 0.2% THC
The Attorney General of the United Arab Emirates gave courts the power to punish drug possession with fines instead of jail
But cracks down on clothing that promotes drug use
The Associated Press updated their stylebook with changes on how to cover cannabis issues
And one of the contributors, Ben Adlin, shares on the changes he likes & the ones he doesn’t
Thanks to inflation, the salary of Snoop Dogg’s dedicated blunt roller has increased
And the obligatory reference to everyone’s favorite Snoop meme…
The War on Drugs & Harm Reduction
New York had high goals for its cannabis equity program, but with no chief equity officer in place, no advisory board & no detailed plan (as required by law), it’s in danger of becoming one more hothouse of smoke & mirrors where the people most impacted by the War on Drugs are locked out
They did have a helluva goal too: half of the licenses to social equity applicants & a $200 M fund to support those businesses
A California task force zeroes in on the War on Drugs & its racist enforcement as a method of social control for the oppression of Black people
As Nixon henchmen John Ehrlichman said, “You want to know what this [war on drugs] was really all about? The Nixon campaign in 1968, and the Nixon White House after that, had two enemies: the antiwar left and black people. You understand what I’m saying?
We knew we couldn’t make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news.”
As we often say around here, the War on Drugs is not a failure. It’s succeeding magnificently at just what it was created to do.
California awards $35M+ in grants from cannabis tax funds to repair the harms of the War on Drugs
A US poll found that a declining number of adults say that drug addiction is a major problem – despite fentanyl now being the number one cause of death for Americans 18-45
A very sad secret buyer survey in Texas finds that buprenorphine/naloxone films & naloxone nasal spray (two key medications for those with opioid use disorder) are available in only 41% of pharmacies (via the U Texas Pharmacy Addictions Research & Medicine Program)
Availability of buprenorphine/naloxone films and naloxone nasal spray in community pharmacies in Texas, USA
Bill Bennett, former White House Office of National Drug Control Policy Director under Bush I, suggests that the Uvalde shooter had psychosis from heavy marijuana use
Oh man. This guy. He used to be called ‘The Canary’ because of his addiction to sunflower seeds. He also wrote a bestselling book on virtue before getting outed as a compulsive gambler. For a strong look at his Prohibitionistic career, check out Dan Baum’s classic of Drug War reportage ‘Smoke & Mirrors: The War on Drugs & the Politics of Failure.’ And what Bennett once said about abortion, black babies & crime is so abhorrent that I won’t even repeat it. You can look it up if you want.
That being said, pro-pot people are wrong to be constantly sneering at any hints of links between psychosis & heavy cannabis use. It is perhaps the most well-proven harm from the decades of Prohibition research funded by the federal government. You can see a study confirming this in the ‘Harms’ section of this newsletter almost every week. The links are not overpoweringly strong – but they are real enough for a small subset of the population. Plus, now obscure research from the ‘50s found that cannabis use led to more aggression in animal models & adolescents alike.
Similar to most drugs, cannabis brings out what’s already there. And with its ability to make fuzzy the nature of reality, it makes all of the breadcrumbing & rabbit-holing of QAnon conspiracies & 4chan racism look more like an actual pattern instead of a senseless phantasm. The ability of cannabis to open someone to radicalization makes a lot of sense. As does the idea that it leads a few users so far from reality that they see extreme violence as a viable option. In one famous historical example, the feared Sikh warriors of India were known to drink heavy amounts of bhang (cannabis in liquid form) before going into battle because it made them fearsome warriors, even able to kill a battle elephant single-handedly.
Do I like any of this? No. But let’s not kid ourselves.
During the NBA finals, New York’s Office of Cannabis Management ran an ad slamming decades of racist cannabis policy & policing – though one local affiliate refused to run it
Kudos to Chris Alexander, current head of the OCM, former staffer of the Drug Policy Alliance & fellow papa, who’s been a strong fiery hand at the helm.
His office also sent a letter to TikTok asking them to stop banning cannabis education advertising sponsored by government entities.
Members of the House & Senate hold a press conference about ending the blatantly racist crack/cocaine disparity
If this one is news to you, here’s one of the clearest examples of the studied racism of the War on Drugs. The only difference pharmacologically between cocaine & crack is that crack is cocaine with some baking soda added.
But socially, white people use cocaine & Black people use crack. Famously, the 1986 Anti-Drug Abuse Act imposed penalties 100x stronger for the same amount of crack versus cocaine. Selling 5 grams of crack would hit you with the same harshness as selling 500 g of cocaine.
Under the 2010 Fair Sentencing Act, that number was reduced to 18 to 1. But it’s still a monstrous disparity. Especially when it was the CIA that supported the early explosion of the crack epidemic in Los Angeles that later spread throughout the country.
David Simon shares that his central message from his shows ‘The Wire’ & ‘We Own This City’ is that we need to end the War on Drugs
I consider ‘The Wire’ to be the ‘War & Peace’ of our generation. It’s the only show I’ve watched twice & I think it gives a better sense about the senseless horrors of the War on Drugs more than any of the books I’ve ever read on the subject.
(I hope to watch ‘We Own This City’ once baby Lucie starts sleeping through the night again)
Excellent harm reduction ads in Norway
Law & Business
Why an incredibly high state tax on cannabis is wrong
Alice Moon’s newsletter on Instagram’s cannabis ban
And the petition you should sign to get that changed:
This week’s The Dose newsletter on the maddening patchwork of cannabis safety laws by Elise Young
A meeting of the Cannabis Regulators Association (CANNRA) raises eyebrows because of its closed-door nature as well as its funding from alcohol & tobacco companies
That being said, government officials & regulators do benefit from being able to “let their hair down” & ask nuts & bolts questions without being dragged through the coals by incendiary muckrakers. Still, I would have liked to be invited…
A Brookings report finds that medical cannabis laws increases a state’s credit risk
Marijuana liberalization and public finance: A capital market perspective on a public health policy
In California, cannabis businesses impacted by the drought can apply for disaster relief
Hawthorne, the cannabis-focused unit of Scotts Miracle-Gro, predicts a +40% decline in sales
It does feel like a recession doesn’t it?
I don’t remember the last time I saw positive earnings in the cannabis sector. And when even the fertilizer people are having a bad year, it feels like we’re hitting a wall.
A secret shopper analysis of CBD products finds THC in a few of the products labeled THC-free
Cannabidiol (CBD) product contamination: Quantitative analysis of Δ 9-tetrahydrocannabinol (Δ 9-THC) concentrations found in commercially available CBD products
It feels like these researchers were looking for a gotcha. They keep referring to the presence of THC as a ‘contaminant’ - which is silly. In full-spectrum hemp extracts, you’re supposed to have a little THC. That’s the point.
The only real issue of concern that they brought up is that in the 52 products labeled as “THC-free”, 10% of them had detectable levels of THC.
Word to the wise: the label “THC Free” is just opening yourself up to a lawsuit. You can safely write that THC is below detectable limits on your equipment – but if you assert “THC free”, some weaselly lawyer will use nuclear testing to find a single atom of THC & hit you with a class-action lawsuit.
A state analysis finds no relationship between cannabis legalization & heavy-truck crashes
Marijuana Legalization and Truck Safety: Does the Pineapple Express Damage More Pineapples?
If in the cannabis business, don’t commit bribery! – or, a lawyer’s profile of how you can do it unintentionally, but in this story, how it was very very intentional
Lessons from the Downfall of the California Coast’s 'King of Cannabis'
"This means that even little bits (think ounces not kilos) of product and a few restaurant meals with wine spread out over years can amount to federal bribery"
The Plant & the History
Tests of earth-hemp blocks as an insulator material
The compressive strength of earth-hemp blocks tested with different densities, earth types, and cementitious binders
Our Construction Knowledge Maven Ned Pelger opines, “Actually, what they tested was a completely different product from most the hempcrete articles you've sent me. This was earth-hemp, which would be mixing on-site clay soils with some hemp to make an adobe-like wall.
This product could make sense. I love the concept of getting all the materials from on-site or nearby (for the hemp). For someone who wants to build their own house at low material cost but high labor, this product could work. Similar to folks building adobe brick or straw bale houses. Though building codes remain a challenge.”
(This was the most positive take we’ve seen from him so far. We hope that he’s feeling OK)
When raising broiler chickens, hemp seeds in the first 5 weeks significantly increases body weight
Evaluation of Growth Parameters of Broiler Chickens Fed with Different Dietary Levels of Hemp Seed (Cannabis sativa L.) using Gompertz Model Compare with Artificial Neural Network
Applying ascorbic acid to your cannabis plants apparently increases their THC & CBD levels
Studies of the Major Gene Expression and Related Metabolites in Cannabinoids Biosynthesis Pathway Influenced by Ascorbic Acid
Plant Medicines & Other Psychoactives
A review of psychedelic treatments for PTSD
Review of potential psychedelic treatments for PTSD
A head-to-head study of psilocybin versus the antidepressant escitalopram found that they had similar efficacy scores after 6 weeks
Trial of Psilocybin versus Escitalopram for Depression
An underwhelming LSD microdosing study found that it was safe to use but they didn’t see differences in mood or task performance
Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study
A rather involved study to determine that microdosing mushrooms can be noticed in how you talk, specifically verbosity, semantic variability, and sentiment scores
Natural language signatures of psilocybin microdosing
In obese rats, chronic treatment with psilocybin – high & low doses - led to weight loss
Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity
Clinical Studies & Surveys
In women with endometriosis, the lesions on their ovaries showed much higher levels of the CB1 & CB2 receptors, suggesting those receptors as targets for treating the pain
Detection of Cannabinoid Receptor Expression by Endometriotic Lesions in Women with Endometriosis as an Alternative to Opioid-Based Pain Medication
In humans with sepsis, this study looking for clinical markers of disease progression found that low levels of anandamide (AEA) was linked to longer hospital stays & lower levels of both AEA & 2-AG predicted invasive mechanical ventilation
Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications
Many US adults with asthma use cannabis
State-specific Prevalence and Factors Associated With Current Marijuana, ENDS, and Cigarette use Among US Adults With Asthma
I don’t put this in ‘harms’ because of the many stories I’ve heard where the bronchodilatory effects of cannabis allowed someone with asthma to throw away their inhaler. Of course, this is not how it always happens – and smoking plant material is certainly not great for your lungs – but a number of people with asthma find cannabis helpful & there’s science to back it up.
Using fMRI scans, the researchers found a predictive connectivity-based signature for chronic cannabis use
An interpretable and predictive connectivity-based neural signature for chronic cannabis use
An in-depth survey of veterans who use cannabis & the results of the stigma attached
Weeding Out the Stigma: Older Veterans in Illinois Share Their Experiences Using Medical Cannabis
In hip surgery, the use of cannabis did not increase the risk of complications after the procedure
Cannabis Use Does Not Increase Risk of Perioperative Complications Following Primary Total Hip Arthroplasty: A Cohort-Matched Comparison
An analysis of TikToks to get the sense of synthetic cannabinoid use in prisons
Synthetic Cannabinoids in Prisons: Content Analysis of TikToks
In dogs with atopic dermatitis (red itchy skin), a CBD/CBDA oil helped with their itchiness but not their lesions
The effect of a mixed cannabidiol and cannabidiolic acid based oil on client-owned dogs with atopic dermatitis
Harms & No Help
A case report of a potential drug interaction between CBD & fluoxetine (Prozac) as well as a case helped by medical cannabis
A Potential Drug-Gene-Drug Interaction Between Cannabidiol, CYP2D6*4, and Fluoxetine: A Case Report
In a detailed study of families in the DC area, they found that cannabis use disorder tends to run in families & to be associated with bipolar disorder II
Comorbidity and Coaggregation of Major Depressive Disorder and Bipolar Disorder and Cannabis Use Disorder in a Controlled Family Study
In a cohort study, early cannabis use among young men had no physical effects later in life but was linked to psychosocial outcomes including “income, housing insecurity, intelligence, depressive symptoms, psychosis symptoms, hostility/aggression, social problems, and attention problems”
Associations of Cannabis Use across Adolescence and Early Adulthood With Health and Psychosocial Adjustment in Early Adulthood and Midadulthood in Men
In this study of Iranian university students, users of cannabis reported more impulsivity, sleep problems & suicidal ideation
Comparison of Impulsivity, Sleep Disorder and Suicidal Thoughts In people with and without Marijuana Dependence
A review of the risk of edibles for kids
Edible marijuana products and potential risks for pediatric populations
Pregnancy & breastfeeding
A review of the impact of cannabinoids on fertility & reproduction
Impact of cannabinoids on pregnancy, reproductive health and offspring outcomes
“The biological effects of cannabis are mediated by the endocannabinoid system and studies have reported the presence of cannabinoid receptors in the male and female reproductive tract, on sperm and the placenta, suggesting the endocannabinoid system plays a role in regulating reproduction. Cannabis use can impact male and female fertility and has been associated with altered reproductive hormones, menstrual cyclicity and semen parameters. Use of cannabis in males has also been associated with erectile dysfunction, abnormal spermatogenesis, and testicular atrophy. In females, cannabis use has been associated with infertility and abnormal embryo implantation and development. The main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), can also cross the placenta and has been detected in breastmilk. Maternal cannabis use during pregnancy and lactation has been associated with adverse effects including small for gestational age infants, preterm birth, fetal neurodevelopmental consequences, and impaired offspring sociobehavioral and cognitive development.”
After watching the data these last years, I believe all of the above to be true – but not catastrophically so.
A review of the effects of cannabis use by pregnant women on their offspring finds the data to be non-conclusive & contradictory
Implications and quantifications of marijuana use regarding neonatal outcomes
A pilot survey of breastfeeding mothers (with a decidedly negative slant) found that most mothers knew that breastfeeding could be harmful & half knew that THC could be found in breast milk
Marijuana and Breastfeeding: A Pilot Survey of Mothers
A survey of Canadian dispensaries found that 80% counseled against breastfeeding & 20% recommended use
How are Canadian cannabis dispensaries counselling breastfeeding consumers?
In pregnant women with obesity, the endocannabinoid-like lipid palmitoleoyl ethanolamine (POEA) is correlated to obesity-associated changes in the processing of insulin
Early Pregnancy Alterations in the Metabolome of Obese Women
In drivers, CBD (up to 1500 mg) appears to have no negative effects on driving performance or cognitive function
Effects of cannabidiol on simulated driving and cognitive performance: A dose-ranging randomised controlled trial
A review of young drivers finds that their likelihood to drive under the influence of cannabis is associated with “being a male, high school senior, with lower grades, having a younger ‘age of first cannabis use’, a higher frequency of consumption, a reduced perception of danger, repeatedly binge drinking, a history of driving under the influence of alcohol and living with fewer parents”
A scoping review of predictors of driving under the influence of cannabis (DUIC) in young drivers
A survey of cancer patients found that the ones using cannabis preferred the oral or vaporizer route & the use of high THC:CBD products
Self-reported efficacy and usage of cannabis among patients with cancer within the Minnesota Cannabis Program
In a tissue study, PEA protects heart cells from the toxicity & inflammation of anti-cancer treatments
The analgesic compound palmitoylethanolamide reduces inflammation in human cardiomyocytes and vascular endothelial cells exposed to doxorubicin and anti-HER2 monoclonal antibody through PPAR-α and NLRP3-related pathways
A survey of invasive cancer patients found that a sizeable minority uses cannabis for symptom relief
Prevalence, symptom management, and reporting of cannabis use among invasive cancer patients
In today’s obvious survey, patients with cancer are curious about using cannabis “despite insufficient evidence of benefits and harms” (?)
In the weeds: a retrospective study of patient interest in and experience with cannabis at a cancer center
A general rule of thumb is that is a paper uses a stupid weed joke in the title, it’s going to have a negative Prohibitionistic slant.
In a study using both mice & human patients with non-small cell lung cancer, the first-line treatment with the immune checkpoint inhibitor pembrolizumab found no negative effects from using medical cannabis
The use of medical cannabis concomitantly with immune-check point inhibitors (ICI) in non-small cell lung cancer (NSCLC): A sigh of relief?
In two liver cancer cell lines, CBD high extracts arrested the cell cycle & significantly induced cell death via mitochondria-dependent apoptosis (suicide via the cell’s power source)
Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma
In colorectal cancer cells, activating the CB1 receptor repressed the genesis of tumors & the activation of the inflammatory M2 macrophages via EGFR downregulation
Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR
A review of using CBD to treat mood disorders
Cannabidiol in the Treatment of Mood Disorders
Basically, no one has done any randomized clinical trials despite the anecdotal evidence & so “high-quality clinical trials are urgently needed.”
A review of CBD for epilepsy in Brazil
Cannabidiol and epilepsy in Brazil: a current review
A review of all the pathways that the terpene β-caryophyllene uses to help with inflammation, oxidation & microbes
A mechanistic review on immunomodulatory effects of selective type two cannabinoid receptor β-caryophyllene
In mice exposed to a pit viper, inhibiting the FAAH enzyme (& raising levels of anandamide) made them act less fearfully
Augmented anandamide signalling in the substantia nigra pars reticulata mediates panicolytic-like effects in mice confronted by Crotalus durissus terrificus pit vipers
If aliens really are experimenting on humans, the idea that they show us horrifying visions of an apocalypse just to record our reactions is completely in line with what we do to those that we consider animals.
In the hippocampus (memory center) of teen mice, THC caused lower mRNA levels of the brain growth factor BDNF - but adding CBD blocks those effects. Plus, THC lowered the level of CB1 receptors in the ventral dentate gyrus (a center for stress & emotions)
Effects of Tetrahydrocannabinol and Cannabidiol on Brain-Derived Neurotrophic Factor and Tropomyosin Receptor Kinase B Expression in the Adolescent Hippocampus
In a mouse model of cystitis, blocking the CB1 receptor in the body reduced urination, increased bladder size in relation to body weight, normalized ECS tone & reduced bladder inflammation
Peripheral Cannabinoid-1 Receptor Blockade Ameliorates Cystitis Severity
In mice pain sensors, knocking out the FABP5 (a transporter enzyme that takes the AEA to be destroyed by FAAH) increases the endocannabinoid signaling & lessens the inflammatory pain via TRPV1
FABP5 deletion in nociceptors augments endocannabinoid signaling and suppresses TRPV1 sensitization and inflammatory pain
See the Living Glossary below for more on FABP – also known as whale cars – though in this case, Black Marias might be a better name.
In the blood of rainbow trout & the plasma of horses, a CBD-rich hemp oil caused antioxidative effects
Oxidative Stress Biomarkers in the Blood of Rainbow Trout (Oncorhynchus mykiss Walbaum) and Equine Plasma after Incubation with Hemp Oil "Annabis Bio"
Cannabinoid Chemistry & Technology
An analysis of a positive allosteric modulator of CB1 named ZCZ011
Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1
An allosteric modulator is one that binds to a receptor, but not in the regular binding location. It binds somewhere else on the receptor (an allosteric location). This allosteric binding changes the overall shape of the receptor & makes other molecules either more likely or less likely to bind there depending on changes. For instance, CBD is a negative allosteric modulator of CB1. When it binds to CB1, it makes THC bind there not as strongly (and protecting you from getting unpleasantly high).
New synthetic strategies for creating rare cannabinoids from the common starting material of olivetol
Synthetic Strategies for Rare Cannabinoids Derived from Cannabis sativa
<carnival barker’s voice> “Get your rare cannabinoids heah! Get ‘em while they’re hot – get ‘em before they’re cool! Be the first in your neigh-bor-hood with CBL & CBT! Impress the wife & kiddies! Get your rare cannabinoids heah!”
PS: From Ahmad Jamal, one of the most successful small-group leaders in jazz for six decades now, comes today’s 1956 album: ‘Count ‘Em 88’.
Beginning his piano playing at the age of 3 & his formal training at the age of 7, he launched his professional career at 14. Converting to Islam in his early 20s, he recorded his first album a year later in 1951 – and then never stopped.
Trained in both the American & European style, he became known as one of the great jazz innovators & even coined a new movement called “cool jazz”. He credits his variety to growing up in the big band era, living through the bebop era & maturing through the electronic era. And so we’ll finish with perhaps his most famous recording, the Ahmad Jamal Trio live at the Pershing Lounge in 1958.
The Living Glossary
Here’s a running glossary of the basic cannabinoid terms. This will also function as the legend for the ‘neural ocean’ metaphor that I’m using in my graphic novel series on the endocannabinoid system based on Moby-Dick. You can watch a lecture laying out the full idea here, but basically, we treat the human brain like the ocean: both deep, mysterious & chockablock with fish & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land). And neurons are complex underwater cities where hundreds of fish interact.
The cannabinoids found inside all mammals & almost every other form of life besides insects
The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”
Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]
FAAH (fatty acid amide hydrolase)
The enzyme that breaks down anandamide & a frequent target of drug discovery for modulating the endocannabinoid system. If you inhibit the FAAH enzyme, it does less breaking down of AEA, and your AEA levels rise. More balance.
[the giant squid that slices sperm whales in half]
The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
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]
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]
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…]
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]
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.
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]
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]
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 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]
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]
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.
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.