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Hello everyone,

This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations. We produce educational content for cannabis & psychedelic companies. You can see my portfolio here.
#opentowork

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This newsletter only spreads by word of mouth – so please forward it to colleagues & share to your friends & elderly relatives. If you become a paid subscriber, there’s no extra content, but your support allows me to produce more cannabinoid science content for the community.

As always, at the bottom there’s a Living Glossary of cannabinoid terms along with the weekly music recommendation.

Editor’s note:
No newsletter next week because I’ll be traveling most of this week for the IACM cannabinoid science conference. New business cards & everything!

Livestream today (Mon) @ 3PM EST

I’m going to make the YouTube livestream permanent! I just finished outfitting my basement recording studio & so every week I’ll go over the best of cannabinoid science & take questions.

To join:
I’m not exactly sure the best way for you to log in since this is new to me too…
I just registered a new handle on YouTube, so subscribe here: @lexpelgereducation
I’ll also post the link to my Twitter & the Facebook group ‘Cannabinoids & the People’.

A question:
For now, my only question for you is: what time is better for you?
Monday @ 3PM EST or
Tuesday @ 9AM EST
(just reply to this email with your answer)

This week…

  • Cannabis for the pain & chronic conditions of older people! (I will die on this hill)
  • CBD products continue to fail on CBD concentrations & heavy metal contamination (buy from our sponsor for safe CBD!)
  • The heart harms & psychosis risks of cannabis
  • Cannabinoids for opioid use disorder, irritable bowel syndrome & the nausea of chemotherapy
  • In history, cannabis smoking for funerals 2500 years ago in China
  • Feed hempseed oil to your chickens for better eggs
  • One of my best new Neuronal Ocean metaphors involving whales, gay bars, cocaine & electric eels

Note:
I’m still working through a backlog of research from 2020 & 2021, hence the older yet still interesting science papers you’ll find below. I should be finished & all caught up by the end of this year.

One sign of a great CBD company is when they go to the next level for educating their customers & advancing the science. PlusCBD has articles for all levels of knowledge, videos about how CBD works & a YouTube channel of great educational content.
(Plus, they even sponsored two seasons of my podcast ‘The Lex Files’)

In addition, they’ve done more peer-reviewed research than any other CBD company other there. They put their money down to advance the field.

Check out this (partial) bibliography:

PlusCBD takes their commitment to education & research to the next level. And they do the same with their products.
Buy excellent CBD products today from PlusCBDoil.com

Best of cannabinoid science...

2021: A survey of older adults found their medical cannabis use to be helpful for chronic conditions & for pain
Medical Cannabis Use: Exploring the Perceptions and Experiences of Older Adults with Chronic Conditions
https://pubmed.ncbi.nlm.nih.gov/33250007

In a Florida survey of medical cannabis patients, 79% reported a reduction in their pain medication use
Medical Cannabis Patients Report Improvements in Health Functioning and Reductions in Opiate Use
https://pubmed.ncbi.nlm.nih.gov/36168127

2021: In a large study sponsored by Tilray, pain patients who started using cannabis went from 152 mg of morphine milligram equivalent (MME – a standardized measure of opioid use) to 62 mg MME after 6 months & they saw a 78% reduction in opioid dosages
Cannabis Significantly Reduces the Use of Prescription Opioids and Improves Quality of Life in Authorized Patients: Results of a Large Prospective Study
https://pubmed.ncbi.nlm.nih.gov/33367882

In humans, a pilot study showed that THC helped to extinguish fear conditioning induced by visual stimuli & electric shocks
Facilitated extinction of conditioned fear responses by delta 9-tetrahyrdrocannabidol in humans: a pilot study
https://pubmed.ncbi.nlm.nih.gov/35983959
This sounds like A Clockwork Orange for science. But it does point to why veterans & people with PTSD tend to ingest large amounts of THC & report that it helps them get through the day.

A study finds that cannabis use does not alter the efficacy of COVID-19 vaccine boosters
Evaluation of immune response to anti-COVID-19 booster in cancer patients and chronic medical cannabis users and its association with circulating Eosinophils levels
https://pubmed.ncbi.nlm.nih.gov/35994572
With the immunosuppressive abilities of THC, there’s always been a worry that cannabis users would not achieve as robust an antibody response – but this study seems to ease fears on that front.

Targeting the ECS for the pain of irritable bowel syndrome
Targeting the endocannabinoid system for the treatment of abdominal pain in irritable bowel syndrome
https://pubmed.ncbi.nlm.nih.gov/36168049

2020: A review found that across all trials they looked at for the nausea & vomiting of chemotherapy, cannabis worked better than conventional antiemetics
Pharmacotherapeutic Considerations for Use of Cannabinoids to Relieve Symptoms of Nausea and Vomiting Induced by Chemotherapy
https://pubmed.ncbi.nlm.nih.gov/33415919

In the Nordic countries, the frequency of cannabis-induced psychosis doubled in the last decades
Annual incidence of substance-induced psychoses in Scandinavia from 2000 to 2016
https://pubmed.ncbi.nlm.nih.gov/35983644

A case report & literature review of young people who use cannabis presenting with heart problems: acute myocardial infarction (heart attacks), arrhythmia (irregular heartbeat) & stroke
Marijuana-induced toxic myocarditis: a case report and a review of the literature
https://pubmed.ncbi.nlm.nih.gov/36166341
Is cannabis slightly negative for the heart? I think the research is clear. Is it enough for me to stop using it or for health authorities to make it a restricted substance? Absolutely fucking not.

2020: Scary research! Using vaccines to combat cannabis use disorder
Broadly Neutralizing Synthetic Cannabinoid Vaccines
https://pubmed.ncbi.nlm.nih.gov/34467269

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.

My cannabis & psychedelic consulting sessions

For patients

I make it simple for people with health conditions to use CBD, THC & other tools to improve their pain, their anxiety, their sleep & their health.
Book a 30 minute session with me & we’ll…

  • talk over what you want to change
  • I’ll create a gameplan of how to use ise that It will include
    • what to take & when
    • where to buy it
    • how to experiment with taking higher levels
  • with unlimited email followups for all of your questions

See my advice for using cannabinoids for

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:
Your Cannabis Counseling Sessions.

For healthcare practitioners

I also meet with medical professionals to advise them on using cannabis, cannabinoids & psychedelics in their practice. I’ve seen an uptick in the number of these sessions from doctors & nurses & they tell me that they find these one-hour discussions quite useful because I’m a walking ‘rules of thumb’ from my years of reading the science & interviewing practitioners. Plus, you get a follow-up email with all of the relevant scientific research to your fields of interest & all of the notes on what we talked about.

I can help you help your patients better use these powerful tools of health.
Book a session here:
Cannabinoid & Psychedelic Education Sessions

the Headlines & Fav Articles

US governors reacting to Biden’s cannabis clemency announcement with their own plans to free the prisoners
https://www.marijuanamoment.net/will-governors-issue-marijuana-pardons-following-bidens-call-to-action-dozens-are-already-weighing-in
& the Health Secretary says they’re moving fast on the rescheduling of cannabis
https://www.marijuanamoment.net/biden-health-secretary-has-already-talked-to-fda-about-marijuana-scheduling-review-which-will-move-quickly
plus a deep dive on what that rescheduling means & how it works

On Drugs

President Biden's Scheduling Directive Part 2

In an earlier post, I explained why President Biden’s request to Attorney General Garland and Secretary Becerra to “initiate the administrative process to review expeditiously how marijuana is scheduled under federal law” is a big deal not just for cannabis, but for all controlled substances. That post was actually the introduction to a much longer one …Read more6 days ago · 2 likes · 2 comments · Shane Pennington

& a new poll finds popular support for Biden’s decision on both the clemency & the rescheduling
https://www.marijuanamoment.net/majority-of-americans-support-bidens-marijuana-pardons-and-want-governors-to-follow-suit-poll-finds

However, this federal clemency does not apply to non-citizens, members of the military, sellers of cannabis or the much larger group of those with state-level convictions of possession
https://www.marijuanamoment.net/who-is-left-behind-by-bidens-marijuana-pardon-immigrants-military-members-and-more
#Justice4All

California’s CAMP program destroyed ~1 million “illegal” cannabis plants & 200,000 pounds of processed plants
ttps://twitter.com/AGRobBonta/status/1579934140417261568
I covered the horrors of CAMP in my Queer cannabis graphic novel ‘SUNset’.

Major League Baseball makes Charlotte’s Web its official CBD brand
https://www.marijuanamoment.net/cannabis-company-and-major-league-baseball-sign-deal-for-charlottes-web-to-be-official-cbd-of-mlb-report-says
I have to say, I was not expecting this from one of the more conservative of the big sports leagues – but on cannabinoids, they have been more forward-thinking than some (looking at you NFL). In addition to a cut of CW’s ‘Sports’ product sales, the league also gets a rights fee & shares of CW… so $$$ talks.

‘How We Roll’ by Noah Rubin: a new coffee-table book that features ways to roll joints, blunts & spliffs, tips on technique, interviews with celebrities, quizzes & astrological recommendations
https://www.powells.com/book/-9781797212937/1-0

2020: A look at the use of medical cannabis in the Arabic world
The Use of Cannabis for Medical Purposes in the Arab World
https://pubmed.ncbi.nlm.nih.gov/34676353

The War on Drugs & Harm Reduction

My dad swears by the Economist & I must say that they got some guts here: “Joe Biden is too timid. It is time to legalise cocaine”
https://www.economist.com/leaders/2022/10/12/joe-biden-is-too-timid-it-is-time-to-legalise-cocaine
Amen! And a video on why the current drug scheduling system is batshit crazy

@thedataboysDeaths by Drug #alcohol #alcoholfree #death #opioids #awareness #health #life #data

Tiktok failed to load.

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Rhode Island will soon be opening safe consumption sites
https://www.nytimes.com/2022/10/12/us/politics/rhode-island-overdoses.html
Hallelujah! Safe consumption sites are essential for public health & one of our best tools for ending the huge death toll of the poisoning of the drug supply. Congrats to Rhode Island for their bravery in turning the evil tide of the War on People Who Use Drugs.

For staying current on drug reform, the Talking Drugs newsletter Release is excellent
https://mailchi.mp/ec8d47b47d7d/talkingdrugs-newsletter-6110975

How good are the products for lowering your THC count for hair tests?
Manipulation of THC Hair Concentrations by Commercially Available Products
https://www.mdpi.com/2218-1989/12/10/900
Basically, you can wash it really well & get below detectability.
Or better yet, get rid of the constitutionally repugnant mandated drug testing of urine & hair.

A review of 65 reports on cannabis & driving found that “medical legalization was associated with reductions in fatal motor-vehicle collisions, whereas recreational legalization was associated with increases in fatal collisions”
The Impact of Cannabis Decriminalization and Legalization on Road Safety Outcomes: A Systematic Review
https://www.sciencedirect.com/science/article/abs/pii/S0749379722004093

In a small sample of drivers, giving them 15 mg of β-myrcene (a huge dose of the “couchlock terpene” of cannabis ) caused reductions in their speed controls & more errors on a divided attention task
The effects of β-myrcene on simulated driving and divided attention: A double-blind, placebo-controlled, crossover pilot study
https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/109

Cops in Ghana use the trace metals in seized cannabis samples to trace them to their original farms
Trace Metals in Cannabis Seized by Law Enforcement in Ghana and Multivariate Analysis to Distinguish among Different Cannabis Farms
https://www.mdpi.com/2305-6304/10/10/567/htm
I am not on the side of the cops here – but that’s a pretty cool Sherlock Holmes style-trick.

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 your company, reach out to me]

The infamous writer Bett Williams on what made María Sabina unique
https://doubleblindmag.com/maria-sabina-psychedelics

A history of how ibogaine emerged as an addiction treatment in the west by Faye Sakellaridis for Lucid News
https://www.lucid.news/ibogaine-addiction-treatment-in-the-west

The latest Psychedelic Salon episode is a 1985 interview with Terence McKenna on the three questions you should ask when considering a new psychedelic experience
https://psychedelicsalon.com/podcast-680-the-importance-of-psychedelics
1. Does it have a shamanic history?
2. Does it occur in the tissue of a plant or animal?
3. Does it bear a similarity with compounds in our brains?

10 legal ways to trip right now by Mattha Busby for Doubleblind
https://doubleblindmag.com/legal-ways-to-trip

With psilocybin, a more mystical experience leads to more mindfulness
Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals
https://www.frontiersin.org/articles/10.3389/fpsyg.2022.948729/full

A big review & analysis of psychedelics for symptoms of depression
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/36209780

Ketamine’s ability to help change & update your beliefs may be a part of its cognitive help for treatment-resistant depression
Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
https://pubmed.ncbi.nlm.nih.gov/36169969

A wild story on the ability of ketamine to stop neuropathic pain

Ruben Laukkonen @RubenLaukkonenI have a wild ambulance IV #ketamine story that I feel like I have to share. I told it to my students in a class on the plasticity of #consciousness and they insisted it needs to be public knowledge. So, somewhat apprehensibly, here it is. Strap in 📜: 2:29 AM ∙ Oct 11, 2022

3,586Likes525Retweets

& ‘stressed Wall Street execs flock to ketamine therapy sessions’
https://nypost.com/2022/10/05/stressed-wall-street-execs-flock-to-ketamine-clinic-for-therapy

Mindfulness-induced endogenous theta stimulation occasions self-transcendence & inhibits addictive behavior

Eric L. Garland @DrEricGarlandThe big reveal! We just published the largest neuroscience study of mindfulness as a treatment for addiction in @ScienceAdvances! Mindfulness-induced endogenous theta stimulation occasions self-transcendence and inhibits addictive behavior science.org/doi/10.1126/sc…9:29 PM ∙ Oct 12, 2022

311Likes71Retweets

Law & Business

In a test of 121 edible CBD products, many contained low levels of heavy metals & over half tested outside the label amount for CBD levels
Heavy metal and phthalate contamination and labeling integrity in a large sample of US commercially available cannabidiol (CBD) products
https://pubmed.ncbi.nlm.nih.gov/35987236
They found lead in 42 %, cadmium in 8 %, arsenic in 28 % & mercury in 37 %. “Among all products tested for CBD labeling accuracy (topicals, edibles, N = 516), 40 % contained <90 % of the CBD indicated on the product label, 18 % contained >110 %, and only 42 % of products fell within ±10 % of the CBD claimed on the manufacturer label.”

'Protected no matter what' - Dutchie rolls out cannabis insurance for marijuana businesses
https://www.benzinga.com/markets/cannabis/22/10/29250606/protected-no-matter-what-dutchie-rolls-out-cannabis-insurance-for-marijuana-businesses

The Plant & the History

The origins of cannabis smoking! Ritualistic use for funerals in 500 BCE western China
The origins of cannabis smoking: Chemical residue evidence from the first millennium BCE in the Pamirs
https://pubmed.ncbi.nlm.nih.gov/31206023
The use of cannabis at funerals is widespread, most notably in the famous reports of Herodotus on the Scythians.
To all of my friends out there, I too request large braziers of cannabis to be placed around my coffin for the party.

In Canada, a look at who was most likely to grow their own cannabis
An analysis of cannabis home cultivation and associated risks in Canada, before and after legalization
https://pubmed.ncbi.nlm.nih.gov/36153711
I dream of the day here in France when I can put a couple of cannabis plants in the front garden.

Recommended for You

A new book on how to manage & utilize your hemp plants
Current Applications, Approaches, and Potential Perspectives for Hemp Crop Management, Industrial Usages, and Functional Purposes
https://www.sciencedirect.com/book/9780323898676/current-applications-approaches-and-potential-perspectives-for-hemp
If you’re in the hemp growing business, this looks like a good investment.

Rotating crops to improve your hemp’s microbial communities
The Effect of Rotational Cropping of Industrial Hemp (Cannabis sativa L.) on Rhizosphere Soil Microbial Communities
https://www.mdpi.com/2073-4395/12/10/2293

2021: On working with your soil microbes to increase your plant’s cannabinoid production
Potential impacts of soil microbiota manipulation on secondary metabolites production in cannabis
https://pubmed.ncbi.nlm.nih.gov/34217364

A study looks at the best depths for hemp root zone growth
Industrial Hemp Root Length Density and Distribution under Polyethylene Mulch with Drip Irrigation
https://journals.ashs.org/hortsci/view/journals/hortsci/57/10/article-p1356.xml

In hens being fed hempseed oil, it enhanced their eggs’ level of polyunsaturated fatty acids (good fats) & omega−3 fatty acids
A comparative study on the effects of hemp seed oil versus four different UFA-rich seed oils in the diets of laying hens on egg production, egg quality and yolk fatty acids
https://assets.researchsquare.com/files/rs-2072272/v1/989a672f-c264-466d-8d63-398ad2ae765c.pdf

2020: A look at the characteristics of hemp biodiesel
Estimation of fuel properties and characterization of hemp biodiesel using spectrometric techniques
https://www.tandfonline.com/doi/abs/10.1080/15567036.2020.1842559

Cannabinoid Science

Clinical Studies & Surveys

2020: An industry-sponsored study found that inhaled cannabis helped with agitation, irritability, anxiety & common stress
The effectiveness of inhaled Cannabis flower for the treatment of agitation/irritability, anxiety, and common stress
https://pubmed.ncbi.nlm.nih.gov/33526145

2020: In healthy adults, smoked cannabis reduced the eye’s intraocular pressure for the next 4 hours
The Effect of Inhaled Cannabis on Intraocular Pressure in Healthy Adult Subjects
https://www.touchophthalmology.com/wp-content/uploads/sites/16/2020/12/USOR_20-13_accepted.pdf
This is why cannabis was first used for glaucoma.

Surprisingly, teens who live in zip codes that contain medical cannabis dispensaries are less likely to use cannabis
Adolescent Cannabis Use Among Youth in ZIP Codes with Medical Dispensaries
https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/124

2021: A review of patents for modulating the transient receptor potential vanilloid type 1 (TRPV1 – the other receptor modulated by anandamide)
A patent review of transient receptor potential vanilloid type 1 modulators (2014-present)
https://pubmed.ncbi.nlm.nih.gov/33377418

2020: Patients without the CYP2C9 enzyme (a liver enzyme that converts delta-9 THC to delta-11 THC) may be at risk of more adverse reactions when using dronabinol (a synthetic pharmaceutical version of THC)
Dronabinol Therapy and CYP2C9 Genotype
https://pubmed.ncbi.nlm.nih.gov/33211456

Mental Health, Addiction & Mental Effects

In a rodent model of opioid use disorder, a negative allosteric modulator of the CB1 receptor (similar to CBD) blocked the rewarding effects of morphine & reduced consumption of oxycodone
Negative allosteric modulation of CB1 cannabinoid receptor signaling suppresses opioid-mediated reward
https://pubmed.ncbi.nlm.nih.gov/36179954

In a mouse model of opioid use disorder, a neutral antagonist of the CB1 receptor blocks the behavioral effects of heroin & fentanyl & may represent a treatment for opioid use disorder
Effects of the cannabinoid CB1-receptor neutral antagonist AM4113 and antagonist/inverse agonist rimonabant on fentanyl discrimination in male rats
https://pubmed.ncbi.nlm.nih.gov/36191533

2021: In young mice, THC causes rapid changes in the hippocampus (memory areas of the brain) such as the lowering of CB1 levels & the alteration of dendrite size
Acute Δ9-tetrahydrocannabinol prompts rapid changes in cannabinoid CB1 receptor immunolabeling and subcellular structure in CA1 hippocampus of young adult male mice
https://pubmed.ncbi.nlm.nih.gov/33368252

2021: In a rat model of addiction, the CB1 receptor seems to cause reward while the CB2 receptor caused aversion & that both receptors underlie the ability of THC to lessen motion
Dissecting the role of CB1 and CB2 receptors in cannabinoid reward versus aversion using transgenic CB1- and CB2-knockout mice
https://pubmed.ncbi.nlm.nih.gov/33334652

2021: In a rat model of psychosis, the dramatic effects of positive modulation of the CB1 receptor on their visual attention & visual impulsivity via glutamate
Effects of the cannabinoid receptor 1 positive allosteric modulator GAT211 and acute MK-801 on visual attention and impulsivity in rats assessed using the five-choice serial reaction time task
https://pubmed.ncbi.nlm.nih.gov/33373679

Neurodegenerative & Brain Diseases

2020: If you’re protecting the brain with a drug that binds to both the CB1 & CB2 receptor, you can enhance its effect with another drug that positively modulates binding to the CB1 & CB2 receptors via its effects on reducing excessive glutamate release
Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist
https://pubmed.ncbi.nlm.nih.gov/33302569
It’s a stretch, but in our Neural Ocean metaphor, if you have a whale that goes both to the bars & to the gay bars of Neuron City, giving it cocaine will make it go to both of those bars longer & harder. And while there, it will tell all the electric eels to chill out & dance instead of exciting Neuron City to death.
Actually, that’s not a stretch. That’s golden. I want a short animation of this.

In a cellular model of excitotoxicity (neuronal damage due to too much stimulation), a cannabis extract protected the brain cells via several mechanisms including brain-derived neurotrophic factor levels, ERK modulation & rescue of CB1 levels
Investigation on the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract in an in vitro model of excitotoxicity
https://pubmed.ncbi.nlm.nih.gov/36179898

Harms, Cannabis Use Disorder & Street Synthetics

In a woman with a liver transplant 3 years ago, the combination of the immunosuppressant tacrolimus & 4 grams of cannabis per day led to brain changes that caused confusion & visual disturbances. These resolved when she stopped the tacrolimus
Late presentation of posterior reversible encephalopathy syndrome following liver transplantation in the setting of tacrolimus and cannabis use
https://pubmed.ncbi.nlm.nih.gov/35990782

2021: In rats, the repeated administration & withdrawal of cannabinoids caused depression of the central nervous system, irritability, fighting & a significant increase in brain dopamine levels
Study of effects of repeated administration and withdrawal of cannabinoids on brain tissue of adult male albino rats: histopathological and biochemical study
https://ajfm.journals.ekb.eg/article_135345_22f0cbd1588575b0bae625a5154d898d.pdf

2020: A case report of cannabinoid hyperemesis syndrome causing Hamman’s syndrome (air in the skin & center of the chest cavity causing pain)
Hamman’s Syndrome or Boerhaave Syndrome? A Curious Case of Pneumomediastinum Triggered by Cannabinoid Hyperemesis Syndrome
https://journals.lww.com/ajg/Fulltext/2020/10001/S1954_Hamman_s_Syndrome_or_Boerhaave_Syndrome__A.1954.aspx

Pain & Inflammation

2021: In the treatment of fibromyalgia, a review of 10 studies found that cannabis may be beneficial to patients & that no serious adverse events occurred
Safety and Efficacy of Medicinal Cannabis in the Treatment of Fibromyalgia: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/33337931

2021: A review of the randomized control trials for cannabis & chronic pain found that the patients reported benefits but that the data did not always
Cannabis for Chronic Pain: A Rapid Systematic Review of Randomized Control Trials
https://pubmed.ncbi.nlm.nih.gov/33353819

In a rat model of neuropathic pain, a drug to inhibit the FAAH enzyme (also a function of CBD) reduced their pain
Fatty acid amide hydrolase activity in the dorsal PAG attenuates neuropathic pain and associated dysautonomia
https://pubmed.ncbi.nlm.nih.gov/36154489

2021: An activator of the CB2 receptor caused anti-pain & anti-inflammatory effects
Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5
https://pubmed.ncbi.nlm.nih.gov/33712283

The Guts

2021: In a mouse model of colitis, THC prevented the disease via the immune cells & colon cells while CBD, at the doses tested, did not
Cannabinoid Receptor Activation on Haematopoietic Cells and Enterocytes Protects against Colitis
https://pubmed.ncbi.nlm.nih.gov/33331878

Reproductive & Maternal Effects

In an observational study of women using cannabis around the time of conception, those who used cannabis had babies with a lower birth weight
Association between maternal cannabis use and birth outcomes: an observational study
https://pubmed.ncbi.nlm.nih.gov/33308186

In pregnant rats, THC causes their female offspring (but not males) to have glucose intolerance, insulin resistance & reduced islet mass & this study looks at how this might be caused by effects on the stathmin-2 & glucagon secretion
Sex-dependent Effect of In-utero Exposure to Δ9-Tetrahydrocannabinol on Glucagon and Stathmin-2 in Adult Rat Offspring
https://pubmed.ncbi.nlm.nih.gov/35985923

Cancer & Chemo

Mara Gordon with a short history on RSO (Rick Simpson oil – high potency cannabis extracted usually used to treat cancer)
https://www.linkedin.com/feed/update/urn:li:aggregate:(urn:li:activity:6986008904547659776,urn:li:activity:6985606891653513216,urn:li:activity:6985336467904413696)/
If you know anyone with cancer, shoot them Mara’s way. In California, she’s the best person I know for using high levels of cannabinoids to harness the many cancer-killing abilities of the cannabinoids.

A study on how to use anandamide against breast cancer cells
Investigation of the Effects of the Endogenous Cannabinoid Anandamide on Luminal A Breast Cancer Cell Line MCF-7
https://pubmed.ncbi.nlm.nih.gov/35988272

In a rat model of chemotherapy-induced peripheral neuropathic pain, this thorough study looks at the changes in the levels of endocannabinoid machinery in the brain & spinal cord, finding a distinct difference between the male & female response
Changes in the expression of endocannabinoid system components in an experimental model of chemotherapy-induced peripheral neuropathic pain: Evaluation of sex-related differences
https://pubmed.ncbi.nlm.nih.gov/36179876

2021: In a rat model of chemotherapy-induced neuropathic pain, inhaled cannabis reduced hypersensitivity to cold & decreased pain levels via the brain’s raphe nucleus (a center in the brain stem that sends projections to almost every other area of the brain)
Inhaled Cannabis Suppresses Chemotherapy-Induced Neuropathic Nociception by Decoupling the Raphe Nucleus: A Functional Imaging Study in Rats
https://pubmed.ncbi.nlm.nih.gov/33622657

Preclinical Research, Synthetics & Cool Chemistry

‘Endocannabinoid Signaling’: a new book out by Maccarrone on methods for measuring endocannabinoids ( includes 40 protocols)
https://link.springer.com/book/10.1007/978-1-0716-2728-0?page=2#toc

How the CB1 receptor controls higher-level visual processing via modulation of GABA
Visual-area-specific tonic modulation of GABA release by endocannabinoids sets the activity and coordination of neocortical principal neurons
https://pubmed.ncbi.nlm.nih.gov/36001978
If this came out a month earlier, it would be in my GABA article: Taking it Slow with GABA

A new biosensor for measuring 2-AG levels in human plasma
An Innovative Sandwich Type Biosensor towards Sensitive and Selective Monitoring of 2-Arachidonoylglycerol in Human Plasma Samples Using P(β-CD)-AuNPs-DDT as Amplificant Agent: A New Immuno-Platform for the Recognition of Endocannabinoids in Real Samples
https://www.mdpi.com/2079-6374/12/10/791
It’s been tough to measure endocannabinoid levels in the blood & when this problem is solved, it will be a boon for diagnosing & treating a number of conditions.

A real-time test of CBD levels using mass spectrometry
Rapid quantification of cannabidiol from oils by direct analysis in real time mass spectrometry
https://pubmed.ncbi.nlm.nih.gov/36156611

On how to decarboxylate the acidic cannabinoids
THE ROLE AND IMPORTANCE OF THE DECARBOXYLATION PROCESS IN THE PRODUCTION OF QUALITY FULL-SPECTRUM CANNABIS EXTRACT FOR MEDICINAL PURPOSES
https://eprints.unite.edu.mk/963/1/Acta%20Medica%20Balkanica%20FINAL%20FINAL-119-128.pdf

2021: A novel set of synthetic cannabinoids for treating skin tightening via activation of the CB2 receptor
From a Designer Drug to the Discovery of Selective Cannabinoid Type 2 Receptor Agonists with Favorable Pharmacokinetic Profiles for the Treatment of Systemic Sclerosis
https://pubmed.ncbi.nlm.nih.gov/33382613

2020: A study of MAGL binding dynamics
Conformational gating, dynamics and allostery in human monoacylglycerol lipase
https://pubmed.ncbi.nlm.nih.gov/33116203
2020: & new MAGL inhibitors
Discovery of Monoacylglycerol Lipase (MAGL) Inhibitors Based on a Pharmacophore-Guided Virtual Screening Study
https://pubmed.ncbi.nlm.nih.gov/33375358

Using inverse molecular docking to study cannabinoid receptors
Inverse Molecular Docking of the Cannabinoids
https://www.greenering.eu/images/greenering/documents/gehpt_and_ess_book_of_abstracts_2022.pdf#page=68

A new phytocannabinoid discovered & a study of its effect on the behavior of zebrafish larvae (a common model organism for the study of development)
9,10-Dihydro-5-hydroxy-2,3,6-trimethoxyphenanthrene-1,4-dione: a new dihydrophenanthrene from commercial cannabis and its effect on zebrafish larval behaviour
https://pubmed.ncbi.nlm.nih.gov/33390032

3 novel synthetic cannabinoids identified
Identification of three novel new psychoactive substances 4F-AB-BUTINACA, AB-PHETINACA, and 2F-NENDCK
https://pubmed.ncbi.nlm.nih.gov/35986510
In our Neural Ocean metaphor, there’s more fish in the sea – but they’re more like Blinky the Three-Eyed Fish.

Thanks.
- lex

PS: This week’s music comes from Joyce, the Brazilian singer-songwriter famed for her guitar skills, her feminine lyrics & the sophisticated yet warm singing voice leading to her being called “one of the greatest singers”. Starting with the guitar at 14 & growing up in a house frequented by well-known musicians, she began recording by 16. When she submitted her song ‘Me Disseram’ to a music festival, it caused a national controversy for being the first time a Brazilian song was written from the first-person feminine point of view. At 19, male journalists were calling her “vulgar & immoral”. But she showed those bastards.
Since her first eponymous album in 1968, she’s written over 400 songs, made 45 albums & recorded with all the greatest names in Brazil as well as many foreign artists. The height of her fame came in the early ‘80s with the release of ‘Clareana’, a lullaby dedicated to her two infant daughters & included on her hit album, ‘Feminina’, a classic for its joyful celebration of the feminine. The ‘90s saw a surge of new interest in her work as samples hit the acid music club scene & inspired the new movement of ‘drum’n’bossa’. A journalist by training, for years she wrote a weekly column for a Rio newspaper about experiences behind the scenes of Brazilian popular music. In her memoirs, she highlighted the power of música popular brasileira as “an answer to everything”, including protests against dictatorship. To see how strong she’s still going, check out her album ‘50’. Recorded at 70 years of age, it’s a song-by-song recreation of her debut album.
Researching Joyce for this writeup made me feel lucky to be on the same planet as her.

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…]

NAAA (N-acylethanolamine acid amidase)
The enzyme for breaking down PEA, with a special function as a messenger for pain & inflammation as well as in the control of obesity.
[a giant Giant Pacific octopus that eats Right whales]

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]
(Easter egg: the first person to email me about this easter egg will get a free copy of my Queer book once I get it printed & up on Amazon soon…)

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.