C&P#19: PEA for the win + shift in US mindset + Last Prisoner Project under fire
Britney Griner's saga continues + cannabis taking 10k truckers off the road
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This week…
· It’s the week of PEA! This endocannabinoid-like molecule does many things -such as changing genetic transcription (see the Living Glossary for more) - and I suspect that PEA will be the next hot cannabinoid health supplement after CBD
· Dr. Raphael Mechoulam writes a review of his career
· Cannabinoids are great for your brain & for your guts in so many damn ways
· & I don’t know if it’s the August heat, but a lot of influential entities are calling out Cannabis Prohibition for the monstrous evil that it is.
The times they are a-(slowly) changin’.
My cannabis counseling sessions for your health
Cannabis is the medicine for aging. Its use goes far back through human history & now we understand how it works because of the endocannabinoid science. But for all the research & knowledge, the practical application is still trial & error. Everyone is different & everyone finds a different set of cannabinoids that work for them. If you – or someone in your life – needs help in figuring out what works best for you, I’m here to help.
You can see my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression here.
I counsel people about using medical cannabis, CBD & THC as well as the lesser known but powerful cannabinoids like PEA (immune system health) & OEA (sleep). We’ll meet to discuss what you want to fix, we’ll come up with a gameplan of what to try, I’ll help you to buy it (almost always the cost of products comes out to less than $100) & then I’ll be there to talk you through trying them out to find the best routine for you. And this includes unlimited follow-up emails.
If you want someone experienced in listening to patients & coming up with a plan to help you find relief, book a 1-on-1 session with me here:
Cannabinoid Education Sessions.
Best of cannabinoid science...
What a sweet piece of work: Dr. Raphael Mechoulam, “the father of the endocannabinoid system”, writes a review of his life & his work on cannabinoids
A Delightful Trip Along the Pathway of Cannabinoid and Endocannabinoid Chemistry and Pharmacology
https://pubmed.ncbi.nlm.nih.gov/35850522
It’s rare to see such personal works in the academic literature – but when it happens, it’s well deserved. Widely hailed as a mensch, Dr. Mechoulam always made sure to share credit for his discoveries & to create a diverse team of researchers in his long search for more knowledge of the cannabinoids.
In a study of long COVID patients, PEA for 3 months substantially improved their symptom scores on the post-COVID-19 Functional Status (PCFS) scale
The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study
https://pubmed.ncbi.nlm.nih.gov/35893119
In humans with tension headaches, PEA worked almost as well as ibuprofen for moderate headaches & for severe headaches, PEA worked faster (hattip to Stuart Tomc)
Efficacy of Palmitoylethanolamide (Levagen+TM) Compared to Ibuprofen for Reducing Headache Pain Severity and Duration in Healthy Adults: A Double-Blind, Parallel, Randomized Clinical Trial
https://www.scirp.org/journal/paperinformation.aspx?paperid=118715
In humans with schizophrenia, PEA combined with risperidone (a common treatment) helped with their negative symptoms (functional, verbal, and social performance loss) but little change in their positive symptoms (hallucinations, delusions, confused thoughts, disorganized speech)
Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial
https://www.sciencedirect.com/science/article/abs/pii/S0165178122003328
In a double-blind study of patients with rotator cuff surgery, CBD helped them with the pain immediately following surgery
Paper 68: Cannabidiol is Effective in Improving Immediate Post-operative Pain and Patient Satisfaction Following Arthroscopic Rotator Cuff Repair: A Placebo-Controlled, Randomized, Double-Blinded Study
https://journals.sagepub.com/doi/abs/10.1177/2325967121S00631
A letter to the editor pushing back on all of the epidemiological data from last week linking cannabis to cancer rates & they level the charge of “ecological fallacy”
Letter to the editor on "Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017, parts 1-3"
https://pubmed.ncbi.nlm.nih.gov/35850921
Ohhh, a review of how endocannabinoids work in the astrocytes (star-shaped immune cells of the brain)
Endocannabinoid signaling in astrocytes
https://pubmed.ncbi.nlm.nih.gov/35822691
If I had the funds (& the lyrical abilities), I’d turn this into a musical.
A review of how lipids (like cannabinoids) control your energy balance via the brain’s hypothalamus
Yin-Yang control of energy balance by lipids in the hypothalamus: The endocannabinoids vs bile acids case
https://pubmed.ncbi.nlm.nih.gov/35863558
A review that says the risks for psychosis & traffic accidents are roughly similar between the use of tobacco & the use of cannabis
Comparative harms assessments for cannabis, alcohol, and tobacco: Risk for psychosis, cognitive impairment, and traffic accident
https://journals.sagepub.com/doi/pdf/10.1177/20503245221095228
In mice with gut inflammation & colitis, THC & CBD inhibited inflammatory macrophages (mobile white blood cells) & improved clinical scores - with cannabis extracts working better than isolated molecules (#entourage)
Differential Effects of D9 Tetrahydrocannabinol (THC)- and Cannabidiol (CBD)-Based Cannabinoid Treatments on Macrophage Immune Function In Vitro and on Gastrointestinal Inflammation in a Murine Model
https://pubmed.ncbi.nlm.nih.gov/35892693
In rats taking haloperidol (a common antipsychotic), CBD lowered the weight & fasting blood sugar increase that usually occurs
Effects of cannabidiol on weight and fasting blood sugar with chronic and subchronic haloperidol administration
https://link.springer.com/article/10.1007/s44192-022-00021-2
In a rat model of methamphetamine addiction, CBD inhibited the rewarding effects & increased the extinction of use as well as protecting relevant brain cells
Cannabidiol attenuates methamphetamine-induced conditioned place preference in male rats and viability in PC12 cells through the Sigma1R/AKT/GSK3β/CREB signaling pathway
https://www.tandfonline.com/doi/abs/10.1080/00952990.2022.2073450
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.
3 other helpful browser extensions are: Unpaywall, Open Access Button & PaperPanda
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
Dr. Nick Jikomes interviews Dr. Margaret McCarthy on endocannabinoid biology & other cannabis topics on Mind & Matter
https://www.youtube.com/watch?v=tZC3HiWgaFI
the Headlines & Fav Articles
When asked about Biden’s plan to free the pot prisoners, his press secretary says that he continues to “evaluate further uses of clemency powers”
https://www.marijuanamoment.net/biden-continues-to-evaluate-marijuana-clemency-options-white-house-says
Oh man. Do something already. You’re just a signature away from righting wrongs.
Meanwhile, his daughter-in-law is buying federally illegal pot with her Secret Service detail in tow
https://www.marijuanamoment.net/biden-daughter-in-law-reportedly-shopped-at-marijuana-dispensary-with-secret-service-protection-as-president-leaves-cannabis-prisoners-behind-bars
Britney Griner sentenced to 9 years in Russian prison for her cannabis possession charge
https://www.ganjapreneur.com/brittney-griner-sentenced-to-9-years-for-cannabis-possession-in-russia
As bad as this, I suspect it’s a negotiating tactic. The US already offered a prisoner swap for an arms dealer – but they want to get more. I hope she gets to come home soon.
And on the US hypocrisy, the Onion sez, “Biden: U.S. Won’t Rest Until Brittney Griner Returned Home To Serve Marijuana Possession Sentence”
https://www.theonion.com/biden-u-s-won-t-rest-until-brittney-griner-returned-h-1849373440
Excellent piece by Jon Capetta about where all the money goes when you buy cannabis (hint: it rhymes with ‘bovernment’)
https://hightimes.com/weirdos/where-does-the-money-go
Plus a thread from him describing some of the best WEIRDOS stories that he’s been producing for High Times
Cannabis violations have taken over 10k truckers off the road this year
https://stacker.com/stories/37562/marijuana-violations-have-taken-over-10000-truck-drivers-road-year-adding-more-supply
Not only are we losing very needed employees in the transportation section, but lives are being ruined by positive drug tests that could easily have resulted from use days before the driver got behind the wheel. Like we often say around here, testing for stoned driving is one of the most difficult parts of the cannabis equation because there’s no real test for intoxication.
A former employee of the Last Prisoner Project alleges that they restricted him from speaking in favor of legalization & homegrown
ttps://twitter.com/GrantSmithEllis/status/1553384450138013696
The Last Prisoner Project is mostly funded by Big Cannabis & has faced accusations of being more about window-dressing & shiny balls instead of actually working with prisoners or the other groups in the space who have been tackling these problems for decades.
The org responds by defining its stance – but the red flag is that they don’t address the actual allegations:
https://twitter.com/lastprisonerprj/status/1553448555444060160
The National Conference of State Legislatures calls for the federal legalization of cannabis & new banking legislation
https://www.marijuanamoment.net/state-lawmakers-across-the-u-s-call-for-federal-marijuana-legalization-and-banking-reform-in-revised-resolution
The American Federation of Government Employees (the largest union of federal workers) called for marijuana legalization & no more drug testing of federal employees
https://www.marijuanamoment.net/largest-federal-workers-union-calls-for-ending-marijuana-tests-for-most-government-employees-in-legal-states/
The USA Today editorial board said Prohibition causes more harm than good
https://www.usatoday.com/in-depth/opinion/todaysdebate/2022/07/31/legalize-marijuana-federal-prohibition-more-harm-than-good/10100661002
Meanwhile, the Washington Examiner goes in the opposite direction
https://www.washingtonexaminer.com/restoring-america/fairness-justice/congress-should-not-legalize-marijuana
& the Boston Herald is against even studying the idea of giving medical cannabis to kids in school
https://www.bostonherald.com/2022/08/03/editorial-the-kids-are-all-right-without-marijuana-in-schools
What if the only thing keeping that kid from seizures or unmanageable pain is a moderate amount of cannabinoids?
Well, fuck ‘em. They should have thought before they decided to be born with a genetic disorder.
Maine regulators want to require high-definition cameras outside cannabis stores & the ACLU protests
https://www.bangordailynews.com/2022/07/28/politics/proposed-marijuana-rules-violates-facial-surveillance-ban-aclu
In Maryland, regulators reduce cannabis patient ID card fees & increase their validity to six years
https://www.bizjournals.com/baltimore/news/2022/08/01/maryland-cannabis-id-card-renewal-change.html
Yes to anything that makes it easier for the patients.
In New Mexico, the health insurance companies getting sued over refusing to cover medical cannabis got the case moved to federal court
https://nmpoliticalreport.com/2022/08/03/cannabis-class-action-suit-over-insurance-moves-to-federal-court
NYTimes on the athletes using cannabis for their pain
https://www.nytimes.com/2022/08/01/sports/basketball/brittney-griner-athletes-cannabis-marijuana.html
Stoner Kid tweet of the week:
Personally, I owe my parents many apples.
The War on Drugs & Harm Reduction
A new On Drugs post about a strange cannabis reform proposal that just hit the activist airways: Schedule 6
& another post from one of the lawyers who got the FDA to back down from banning 5 psychedelic substances & an interview of his co-party: Hamilton Morris
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to a company out there, reach out to me]
Another great deep patent dive, this time on trying to patent the intranasal delivery of ketamine as an antidepressant
https://ondrugs.substack.com/p/psychedelic-patent-wars-3-nuthin
A survey in the US finds that a majority support psychedelic research for members of the military
https://www.marijuanamoment.net/majority-of-americans-support-psychedelics-research-for-military-members-new-poll-finds-as-bipartisan-reform-advances-in-congress
The dangerous allure of psychedelics being prescribed for everything & administered by people without training in trauma (Mad in America)
https://www.madinamerica.com/2022/08/allure-psychedelics-disenchanted
There’s a sad anecdote in this piece & I’ve seen similar stories in my own research. Sometimes, psychedelics send you into a dark & terrible place – and if your caregiver disappears, it can leave you much worse off than when you began.
Aaron Rodgers credits ayahuasca for the best season of his career
https://www.ganjapreneur.com/nfls-aaron-rodgers-credits-mvp-performances-to-psychedelic-experience
People have different variants of their psychedelic receptor (5-HT2A serotonin receptor) & this might explain why we experience psychedelics differently
5-HT 2A SNPs Alter the Pharmacological Signaling of Potentially Therapeutic Psychedelics
https://pubmed.ncbi.nlm.nih.gov/35894503
A review of psychedelics, mystical experiences & how well they work
Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/35923458
There’s a small cottage industry right now writing reviews of the psychedelic science covering the same base of studies. Science has its waves of fashion like anyone else.
In South Africa, a review about the street drug nyaope which contains HIV antiretrovirals
A Systematic Review of Risk Factors and Consequences of Nyaope Usage: The Illicit Street Drug Containing HIV Antiretrovirals
https://pubmed.ncbi.nlm.nih.gov/35895149
Law & Business
First cannabis CEO ever on the cover of Forbes: Berner of Cookies
https://twitter.com/BzCannabis/status/1554507006865809411
In bad cannabis industry news, the Hawthorne unit (Scotts Miracle-Gro cannabis division) saw sales decrease 63% this quarter
https://www.globenewswire.com/news-release/2022/08/03/2491188/33079/en/ScottsMiracle-Gro-Announces-Third-Quarter-Financial-Results-Introduces-Project-Springboard-to-Enhance-Shareholder-Value.html
Ahahahaha…
Like, I said, I’ve got the popcorn out for the Juicy Fields story.
Also, if you want to stay ahead of the curve, follow @JavierHasse
The Plant & the History
A look at what happens when you grow cannabis in simulated microgravity (spinning it): more genetic expression of the cannabinoid synthesis genes which resulted in more CBG & CBD but less THC
Simulated microgravity contributed to modification of callogenesis performance and secondary metabolite production in CannabisIndica
https://pubmed.ncbi.nlm.nih.gov/35849945
I would be very disappointed if I got to space & there wasn’t any weed there.
In hemp being grown as microgreens for eating, this study looks at their mineral composition (strong for K, Ca, Fe & Zn)
Macro and trace element mineral composition of six hemp varieties grown as microgreens
https://www.sciencedirect.com/science/article/abs/pii/S0889157522003684
Here we go! Blockchain for hemp production traceability
Agricultural traceability model based on IoT and Blockchain: Application in industrial hemp production
https://www.sciencedirect.com/science/article/pii/S2452414X22000498
In further evidence that everything done on the blockchain can be handled just as well with a spreadsheet, this.
Cannabinoid Science
Clinical Studies & Surveys
In a test of THC & CBD’s effect on social cognition in a natural setting (a cannabis social club), THC caused lower cognitive empathy but adding CBD made that effect go away. CBD also caused more cognitive Theory of Mind (understanding that other people have a mind). No differences on emotional scales
The Effects of Cannabidiol and δ-9-Tetrahydrocannabinol in Social Cognition: A Naturalistic Controlled Study
https://pubmed.ncbi.nlm.nih.gov/35881851
Good old Spain. Not only do they have the social clubs to do this kind of research, they’ve got the guts to do good helpful research about what these cannabinoids do to people in the real world.
Also, no wonder I can be more of a dick when heavily toasted. I always assumed it was because I just wanted to be left alone…
A survey of parents with epileptic children found that while many reported CBD lowering seizures, none became seizure-free
Survey of local cannabidiol use in parents of children with epilepsy in Thailand: the prevalence, perceptions, and knowledge
https://pubmed.ncbi.nlm.nih.gov/35883129
Another survey of CBD users (young adults this time) that list the tops uses of CBD as pain, sleep & anxiety
Cannabidiol Knowledge, Perceptions, and Use Among Young Adults in 6 U.S. Metropolitan Areas
https://pubmed.ncbi.nlm.nih.gov/35878060
Ethanol extractions of hemp grown at U of Alabama show antimicrobial & antioxidative effects
Antimicrobial and Antioxidative Activity of Ethanolic Extract from Two Hemp (Cannabis sativa L) Cultivars Grown in Northern Alabama
https://elibrary.asabe.org/abstract.asp?aid=53377
Unsurprisingly, an industry-sponsored study of an Ayurvedic hemp formulation found that it helped with pain
Post Marketing Efficacy and Safety Study of BOHECO Peace (Full Spectrum Hemp Leaf Extract Based Ayurvedic Proprietary Medicine) for the Management of Pain
http://jaims.in/jaims/article/view/1817
A study in young people with autism found no help for sleep scores from CBD-rich extracts with a small amount of THC
A Placebo-Controlled Trial of Cannabinoid Treatment for Disruptive Behavior in Children and Adolescents with Autism Spectrum Disorder: Effects on Sleep Parameters as Measured by the CSHQ
https://pubmed.ncbi.nlm.nih.gov/35884990
In a look at why teens vape, those looking for fun went with nicotine vapes & those looking for pleasure went with cannabis (I refuse to put this in the harms section because the War on Teen Vaping is a giant harm reduction failure)
Vaping motivations: Association of behavioral inhibition and behavioral activation systems with nicotine and cannabis vaping among adolescents
https://www.sciencedirect.com/science/article/abs/pii/S0306460322002027
A stab at trying to set limits for CBD & THC in e-cigarette liquids
Using the BMD Approach to Derive Acceptable Daily Intakes of Cannabidiol (CBD) and Tetrahydrocannabinol (THC) Relevant to Electronic Cigarette Liquids
https://www.imrpress.com/journal/FBL/27/8/10.31083/j.fbl2708228/htm
In horses with arthritis, the CB1 & CB2 levels in their joints increased with the degree of inflammation, suggesting them as a therapeutic target
Cannabinoid receptors are expressed in equine synovium and upregulated with synovitis
https://pubmed.ncbi.nlm.nih.gov/35836386
In elderly horses, a look at the pharmacokinetics (how a drug moves through the body) from one dose of CBD
Pharmacokinetics of cannabidiol in a randomized crossover trial in senior horses
https://pubmed.ncbi.nlm.nih.gov/35895770
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
A chart review of youths finds an association between heavy chronic cannabis use & elevated anger levels
The Relationship Between Cannabis Use and Self-Reported Trait Anger in Treatment-Seeking Young People
https://pubmed.ncbi.nlm.nih.gov/35833834
The marijuana/violence connection isn’t looked at anymore because it’s not the fashionable view on cannabis – but research from the ‘50s showed a relationship between cannabis use & violence. And plenty of people groups in world history – such as the celebrated Sikh warriors of India – used drinks of bhang (cannabis beverage) to ready themselves for battle. Hell, it might be the only way you get brave enough to kill a battle elephant single-handedly.
College students who smoked alone saw increased negative consequences
I Smoke Alone: Indirect effects of solitary cannabis use on negative consequences through coping motives
https://www.jsad.com/doi/abs/10.15288/jsad.21-00200
That being said, I’ve smoked alone for most of my adult life & I only moderately struggle with depression.
In young men conscripted into the Swiss military, “cannabis use … was significantly associated with greater depressive mood, elevated sensation seeking, and lack of perseverance, whereas problematic cannabis use was significantly related to higher depressive mood and steeper delay reward discounting”
Impulsivity, Depressive Mood, and Cannabis Use in a Representative Sample of French-Speaking Swiss Young Men
https://psychologicabelgica.com/articles/10.5334/pb.1120
In brain scans of teens, those who drank alcohol & used cannabis showed fasted declines in various brain volumes than those using either substance alone
Alcohol and cannabis co-use and longitudinal gray matter volumetric changes in early and late adolescence
https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.13208
In a comparison of humans with schizophrenia & those with cannabis-induced psychosis, the ones with schizophrenia had more abnormalities in the white matter microstructures of their brain & the cannabis users had better integrity of their white matter & a greater volume of gray matter
White Matter Microstructure and Gray Matter Volume in Cannabis-Induced Psychosis and Schizophrenia With Cannabis Use
https://pubmed.ncbi.nlm.nih.gov/35872614
In people undergoing cannabis withdrawal, they had lower levels of ghrelin & adiponectin (hunger hormones) & when they were challenged with an aggression-inducing paradigm, the people going through withdrawal reacted more aggressively than those who weren’t
Investigating associations between appetite-regulating hormones, aggression and craving in males with cannabis use disorder
https://www.sciencedirect.com/science/article/abs/pii/S0376871622003143
Using cannabis before a spinal operation increased the chances of needing another operation but didn’t alter “90-day all cause readmission, surgical readmission, the magnitude of improvement in [pain], or differences in opioid consumption”
The Effect of Preoperative Marijuana Use on Surgical Outcomes, Patient-Reported Outcomes, and Opioid Consumption Following Lumbar Fusion
https://pubmed.ncbi.nlm.nih.gov/35849499
A survey about driving stoned finds that it’s the perceived safety & not the perceived legality than influences people’s opinions on it
Perceived Safety, Not Perceived Legality, Mediates the Relationship Between Cannabis Legalization and Drugged Driving
https://pubmed.ncbi.nlm.nih.gov/35822623
In a questionnaire about teens driving under the influence, they considered it worse to be drinking than smoking cannabis & they thought it was more acceptable for a female to drive after cannabis than a male
Perceptions of the Risk and Social Acceptability of Driving Under the Influence of Cannabis
https://link.springer.com/article/10.1007/s11469-022-00879-x
As a cop in Colorado once told me, for drunk drivers, we look for swerving. For stoned drivers, we look for cars stopped at green lights.
A small study of 31 cannabis users, found they performed worse in visuospatial function, attention & language
Effect of Chronic Marijuana Use on Cognition: A CrossSectional Study-Among College Students in Urban Bengaluru
https://www.researchgate.net/profile/Ramesh-N-R/publication/361841781_Effect_of_Chronic_Marijuana_Use_on_Cognition_A_Cross-_Sectional_Study-Among_College_Students_in_Urban_Bengaluru/links/62c7d39a00d0b451103f17f1/Effect-of-Chronic-Marijuana-Use-on-Cognition-A-Cross-Sectional-Study-Among-College-Students-in-Urban-Bengaluru.pdf
Two case studies on extreme negative mental health effects from delta-8 THC
Marijuana variant of concern: Delta 8-tetrahydrocannabinol (Delta-8-THC, Δ8-THC)
https://www.sciencedirect.com/science/article/pii/S2773021222000220
In a pediatric patient who accidentally ate a THC gummy, they experienced a slowed heart rate & a block causing slowing conduction
Accidental Ingestion of Tetrahydrocannabinol-Laced Gummies Causing Bradycardia and First-Degree Atrioventricular Block in a Pediatric Patient: A Case Report
https://pubmed.ncbi.nlm.nih.gov/35847165
A look at the toxic effect of the synthetic cannabinoid AMB-FUBINACA
Review on AMB-FUBINACA one of synthetic cannabinoids present in Egypt
https://ajfm.journals.ekb.eg/article_251215_c86bbc5a0b4ef026ba6cb1e793cde478.pdf
The common synthetic cannabinoid JWH-018 does not work via the serotonin receptors
Synthetic Cannabinoid Receptor Agonist ‘JWH-018’ does not mimic Serotonin
https://iphr.mosuljournals.com/article_174794_2e150e75837180a9d402bb5771cf5bc5.pdf
A new synthetic cannabinoid found in e-cigarette liquid called ADB-BRINACA
Identification of a novel bromoindazole synthetic cannabinoid analogue in seized e-cigarette liquid: ADB-BRINACA
https://pubmed.ncbi.nlm.nih.gov/35863161
Cancer
Strong review on the complex interplay between your microbiome, your fatty acids & your endocannabinoid system & their effects on cancer progression
Interplay of gut microbiome, fatty acids and the endocannabinoid system in regulating development, progression, immunomodulation and chemoresistance of cancer
https://www.sciencedirect.com/science/article/abs/pii/S0899900722002003
In leukemia cells, they looked at the effects of the synthetic cannabinoid JWH-018
Investigating the Effects of a Synthetic Cannabinoid on the Pathogenesis of Leukemia and Leukemic Stem Cells: A New Therapeutic Approach
https://pubmed.ncbi.nlm.nih.gov/35834597
Recent Reviews
A review of what factors affect how cannabis gets into your system
Factors that Impact the Pharmacokinetic and Pharmacodynamic Effects of Cannabis: a Review of Human Laboratory Studies
https://link.springer.com/article/10.1007/s40429-022-00429-4
A review of substituting cannabis for opioids for gynecological pain
Making a joint decision: Cannabis as a potential substitute for opioids in obstetrics and gynecology
https://www.sciencedirect.com/science/article/abs/pii/S1521693422001006
A review of the scant data on cannabinoids & organ transplantation
Cannabinoids and solid organ transplantation: Psychiatric perspectives and recommendations
https://pubmed.ncbi.nlm.nih.gov/35853383
A review of the challenges in the cannabis delivery systems
Perspectives on Challenges in Cannabis Drug Delivery Systems: Where Are We?
https://www.karger.com/Article/FullText/525629
A historical review of how we’ve been targeting the CB2 receptor
Developing the Cannabinoid Receptor 2 (CB2) pharmacopoeia: past, present, and future
https://www.sciencedirect.com/science/article/abs/pii/S0165614722001377
A review of CBD for treating COVID-19 looks at 9 studies but concludes there’s not yet enough evidence
Cannabidiol As a Treatment for COVID-19 Symptoms? A Critical Review
https://pubmed.ncbi.nlm.nih.gov/35881839
Preclinical Research
In a mouse model of habit formation, CBD inhibited goal-directed behavior (but who needs goals man? I’m just over here vibing…)
Cannabidiol (CBD) drives sex-dependent impairments in omission, but has no effect on reinforcer devaluation
https://pubmed.ncbi.nlm.nih.gov/35901956
In a rat pineal gland, the addition of THC, CBD & CBC all reduced the output of melatonin - & they did it using a pathway other than the CB1 & CB2 receptors (hattip to Stuart Tomc)
Cannabinoids attenuate norepinephrine-induced melatonin biosynthesis in the rat pineal gland by reducing arylalkylamine N-acetyltransferase activity without involvement of cannabinoid receptors
https://pubmed.ncbi.nlm.nih.gov/16805813
In immune cells, the acid form of the cannabinoids (especially CBDA & CBGA) potently blocked calcium channels to lower T-cell activation & inflammation
Acidic Cannabinoids Suppress Proinflammatory Cytokine Release by Blocking Store-operated Calcium Entry
https://pubmed.ncbi.nlm.nih.gov/35910331
In mice, CBN had no effect on sleep
The effects of subacute exposure to a water-soluble cannabinol compound in male mice
https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00153-w
In a Guinea pig model of allergies, asthma & airway inflammation, inhibiting the FAAH enzyme lowered inflammation but did not alter airway hyperreactivity while inhibiting the MAGL enzyme or both the MAGL & FAAH enzyme lowered both lung inflammation & airway hyperreactivity
Endocannabinoid metabolism inhibition ameliorates ovalbumin-induced allergic airway inflammation and hyperreactivity in Guinea pigs
https://pubmed.ncbi.nlm.nih.gov/35843343
A look at using PIMSR (a blocker of the CB1 receptor) to treat cocaine use disorder
Therapeutic potential of PIMSR, a novel CB1 receptor neutral antagonist, for cocaine use disorder: evidence from preclinical research
https://pubmed.ncbi.nlm.nih.gov/35851573
In diabetic mice with gut mobility issues, a FAAH inhibitor reduced fecal output & improved gut transit time via the CB1 receptor
Inhibiting Fatty Acid Amide Hydrolase Ameliorates Enteropathy in Diabetic Mice: A Cannabinoid 1 Receptor Mediated Mechanism
https://pubmed.ncbi.nlm.nih.gov/35878381
In a rat model of PTSD, inhibiting the FAAH enzyme reduced anxiety as well as the memory of the shock - via the novel mechanism of β-catenin activation (a key intracellular messenger) in the nucleus accumbens (the neural interface between motivation & action)
Enhancing Endocannabinoid Signaling via β-Catenin in the Nucleus Accumbens Attenuates PTSD- and Depression-like Behavior of Male Rats
https://pubmed.ncbi.nlm.nih.gov/35892688
In astrocytes (immune cells of the brain), CB1 receptors play an important function & this study looks for better ways to find them on these rare cells
GLAST versus GFAP as astroglial marker for the subcellular study of cannabinoid CB 1 receptors in astrocytes
https://pubmed.ncbi.nlm.nih.gov/35852615
Cool Chemistry
A review of the ways to synthetically produce the exact stereoisomer of CBD
Stereoselective Synthetic Strategies to ( )-Cannabidiol
https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/slct.202202400
Testing ingredients to improve the transdermal delivery of cannabinoids
Enhancement of transdermal permeation of cannabinoids and their pharmacodynamic evaluation in rats
https://pubmed.ncbi.nlm.nih.gov/35863593
Yes – and we should just do what the Israelites did: put a pound of weed in oil & then smear it all over our bodies. That’s how you talk to pillars of fire.
A look at the mechanisms of BIA 10-2474: the infamous FAAH inhibitor that killed someone in a clinical trial a few years ago
Inactivation Mechanism of the Fatty Acid Amide Hydrolase Inhibitor BIA 10-2474
https://pubmed.ncbi.nlm.nih.gov/35843872
A new FAAH inhibitor for treating depression & pain
Development of indole-2-carbonyl piperazine urea derivatives as selective FAAH inhibitors for efficient treatment of depression and pain
https://www.sciencedirect.com/science/article/abs/pii/S0045206822004370
In rats, the drug increased BDNF (a brain growth factor) as well as decreased cell death in the hippocampus (memory center of the brain). It also decreased neuroinflammation & acted as a potent painkiller.
A novel drug delivery system that involves CBD
Functional supramolecular micelles driven by the amphiphilic complex of biotin-acyclic cucurbituril and cannabidiol for cell-targeted drug delivery
https://www.sciencedirect.com/science/article/abs/pii/S0378517322006032
This one is pretty sci-fi – and one of the ingredients sounds like Wolverine’s adamantium.
A novel molecule designed to bind to the CB1 receptor & to be activated by light
Development of an Indole-Amide-Based Photoswitchable Cannabinoid Receptor Subtype 1 (CB 1 R) "Cis-On" Agonist
https://pubmed.ncbi.nlm.nih.gov/35881914
Tools like this are essential for advancing our knowledge of the endocannabinoid system. This one allows you to open up a mouse’s brain & use lasers to turn on & off CB1 receptors in specific locations & on exact timelines. Impressive work, especially since they didn’t even use a typical cannabinoid core structure. In our ‘Neural Ocean’ metaphor, it’s like they took a rhinoceros, taught it to walk into the CB1 saloon & then whenever they shine a flashlight on its ass, it gives a kick & does a shot.
Thanks.
- lex
PS: Today, let’s listen to ‘The Cooks in Trinidad’ by Wilmouth Houdini, the Calypso King of New York. Despite his fame, not much can be known for sure about his early life & the accounts vary. One important source comes from Joseph Mitchell, one of my great journalistic heroes, who wrote a famous essay about him called ‘Houdini’s Picnic’ (unfortunately, I can’t access this or find it online. Any friends with a New Yorker subscription want to help a brother out?). Here’s a writeup about this article’s importance in calypso history.
It seems fairly clear that wherever he was born, Houdini spent most of his young life in Trinidad. By his early teens, he was the chantwell (lead singer) for a 25-person street carnival group. Once he landed in NYC after years of working on ocean freighters, he immediately began recording calypso pieces & released over 100 records between 1928 & 1940 (these were 78 RPM records, so one track per side). When Ella Fitzgerald & Louis Jordan’s cover of his song ‘Stone Cold Dead In The Market (He Had It Coming)’ shot to the top of the R&B charts in 1946, it brought Houdini a great deal of fame. He used this influence to become an active promoter of calypso concerts & festivals in NYC. It’s reported he composed thousands of songs over his life, many of them brilliant spur-of-the-moment pieces. With calypso’s focus on sociopolitical commentary, it allowed musicians like Houdini to critique racial & economic inequalities & protest the colonial social order. Buried in Woodlawn Cemetery, he’s remembered as one of the great calypsonians of the century.
The Living Glossary
This is a running glossary of the basic cannabinoid terms. It 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 we treat the human brain like the ocean: deep, mysterious & chockablock with fish, molecules & 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]
2-AG
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
[blue whale]
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]
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]
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]
Diacylglycerol lipase (DAGL or DGL)
The enzyme responsible for producing 2-AG.
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]
Palmitoylethanolamide (PEA)
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]
Oleamide (OEA)
An endocannabinoid related to sleep. They discovered it by keeping cats awake for 3 days & then analyzing their spinal fluid. You can buy it on Amazon. 2 scoops helps you to sleep while 6 scoops is a very pleasant psychoactive experience (Hamilton Morris has called it his favorite way to get high - which is saying something). It’s also worth considering for cancer treatment.
[Humpback whale, because it sings hippies to sleep]
Oleoylethanolamide (unfortunately, also abbreviated as OEA sometimes)
An analog of anandamide, this lipid acts via the peroxisome proliferator-activated receptor alpha (PPAR-α) receptors on the cell’s nucleus. These alter genetic transcription, a powerful method of cellular control. In animal models, oleoylethanolamide causes them to eat less food & drink less alcohol. In roundworms, it causes them to live longer. For the orphaned GPR119 receptor (a receptor that might one day be officially designated as a cannabinoid receptor), it may be the native ligand (the thing that binds to it). It’s already identified as the native ligand for hypoxia-inducible factor 3α (HIF-3α). OEA also interacts with our histamines.
[Pygmy sperm whale. Not well known, a smaller cousin to the sperm whale]
Fatty acid-binding proteins (FABPs)
These transport proteins move fatty lipids such as the endocannabinoids around the body. While still mysterious, they’re thought to move anandamide between membranes as well as transporting it to be broken down by the enzyme FAAH. Several types of FABPs exist in humans. THC & CBD bind to some of them. This may explain why endocannabinoid levels tend to increase after consuming cannabinoids. As the brain ages, the levels of FABPs decrease.
[whale cars]
Phytocannabinoids
The cannabinoids produced by the cannabis plant.
THC (delta-9-tetrahydrocannabinol or Δ9-THC)
The well-known & well-studied molecule in cannabis that gets you high - and helps in a number of other fascinating ways.
[African elephant. Powerful, unpredictable, beautiful]
CBD (cannabidiol)
The cousin of THC that does not get you high but does a lot of the heavy lifting in why hemp has been such a staple of medicine since before recorded history. In most plants outside those bred for the recreational market, CBD is the most common cannabinoid. It binds to a wide swathe of receptors outside the endocannabinoid system including three serotonin receptors, two opioid receptors, a dopamine receptor as well as glutamate & GABA (the two most widespread neurotransmitters, the basic neuronal signals for excitation & inhibition, respectively)
[Indian elephant. sweet, gentle, you can work with it]
CBC (cannabichromene)
The third most common cannabinoid in the plant, it’s not well studied in humans despite a number of intriguing preclinical studies, especially as an anti-inflammatory and for pain. Nonpsychoactive, it interferes with the breakdown of AEA & 2-AG (leading to a rise in their levels) as well as interacting with the vanilloid receptors.
[Sri Lankan elephant. Little, sweet, not as well known as it should be]
CBDV (cannabidivarin)
CBDV is like CBD with a shortened tail (side chain). Also nonpsychoactive, it tends to occur at low levels in most cannabis cultivars. It’s known to be an anticonvulsant & is suggested for treating autism in humans & in animal models. The cannabinoid pharmaceutical company GW has it in their developmental pipeline as GWP42006.
[An Asian elephant with a short trunk]
Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]
Beta-caryophyllene (BCP)
A terpene that’s also a cannabinoid.
The terpenes of cannabis give the plant its smell. Also found in oregano, black pepper, lavender & hops, beta-caryophyllene has a spicy sweet woody smell. But unique among terpenes, this one also binds to the CB2 receptor, making it a dietary cannabinoid. It shows a potential for treating inflammation, pain, anxiety & seizures. The FDA has designated it to be GRAS (generally regarded as safe) & thus it can be safely used as a food additive.
[a terpene/cannabinoid that travels through the air? That could only be a flying elephant]
Pharmaceutical cannabinoids
Nabiximols (ie Sativex®)
A pharmaceutical 1:1 CBD:THC spray produced by GW Pharmaceuticals. One of the first cannabinoid pharmaceuticals on the market, Sativex is an approved treatment for neuropathic pain, spasticity, overactive bladder & the symptoms of multiple sclerosis.
Epidiolex® (in the UK, Epidyolex®)
An isolated CBD formulation approved for treating the severe seizures of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. Produced by GW Pharmaceuticals, the doses tend to be incredibly high – hundreds or thousands of milligrams of CBD every day in young children. But even with that, the side effects tend to only be lethargy & stomach upset.
Dronabinol (ie Marinol® and Syndros®)
A synthetic form of THC for the treatment of anorexia in AIDS patients & the nausea of chemotherapy. These tend to not be popular with patients because it’s a horse dose of THC with no modulation by the other molecules in the cannabis plant like CBD.
Nabilone (Cesamet®)
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.