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

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And these diapers won’t buy themselves.

Podcast interview + My EU report for Weed Talk News

I was on ‘El Podcast’ this week talking about CBD, cannabis & psychedelics.
It was a fun one…
(and you get a peek at my new basement recording studio)
https://youtu.be/e-6bA6Wg-SA

Also, here’s my European report for Weed Talk News this week:
https://youtu.be/Cb8UJPqPdps?t=1231

This week…

  • THC for neurodegenerative disorders, even at low levels
  • Cannabis for facial pain, lower back pain + PEA for neuropathic pain
  • Big brain scan study of where the CB1 receptors are in your brain & how that shifts as you age
  • On cannabis for polycystic ovary syndrome & a number of studies on how your hormone cycle alters your cannabinoid effects
  • First clinical trial for treating cannabis use disorder
  • Smoking a joint gives off far more particulates than a tobacco cigarette
  • Germany & Ireland with lousy rulings on cannabis
  • Everyone wants to know: how does this Kenyan senator have such smooth legs?

I spent 3 years working full-time for PlusCBD before I launched my consulting business so I know from the inside about their commitment to making quality CBD products. But that’s not the most special thing about them. What they do better than any other company in the industry is create a wide range of products.

Nobody else has this much…

  • Oils, capsules & gummies of course
  • Topicals that come as balms, creams, roll-ons & special formulations for arthritis or athletes that contain menthol & camphor
  • The Reserve Collection! Oils, capsules & gummies containing 2.5 mg of THC per serving (I’m constantly being asked how people in non-medical can get THC-rich products & this is always what I recommend to them. Especially because it’s an easy-to-use standard serving size that’s just the right amount for people new to THC)
  • Excellent pet products in a range of flavors
  • 3 very special formulations with other ingredients:
    • Sleep gummies: Includes 3 mg of melatonin + extract of lemon balm & magnolia bark (two old plants for inducing sleep)
    • Calm gummies: Includes 5-HTP (the serotonin precursor) & L-theanine (from tea)
    • Relief capsules [I can’t find a link to just this item – only the wellness blend bundle]: Includes PEA + CBDA (see the Living Glossary below for why I think these are the ingredients of the future for immune health & gut health)

That’s why I recommend PlusCBD to so many of the clients I consult with:
they offer an array of products like no other.

Buy their excellent products today at PlusCBDoil.com.

On new cannabinoid suppositories hitting the market by The Broccoli Report

The Broccoli Report

Sensual Suppositories & Hemp in Cars

As long-time readers know, I often stress the importance of the anal & vaginal delivery method for the cannabinoids. It’s a safe, clean method that bypasses the liver’s ability to make the psychoactive effect of the THC stronger. For very sick patients – or people with menstrual pain, you should absolutely be exploring these new products.

Best of cannabinoid science...

In women with polycystic ovary syndrome, on the usefulness of the cannabinoids for altering their genetic activity via the PPAR receptors to help with obesity & reduced fertility
Cannabinoids and PPAR Ligands: The Future in Treatment of Polycystic Ovary Syndrome Women with Obesity and Reduced Fertility
https://pubmed.ncbi.nlm.nih.gov/36010645

In a survey of patients with inflammatory bowel disease, those who started using cannabis had fewer visits to the ER & less impact of symptoms on daily life
Medical Cannabis Use Patterns and Adverse Effects in Inflammatory Bowel Disease
https://pubmed.ncbi.nlm.nih.gov/36227025

In a review of 933 patients using PEA for neuropathic pain, it helped with pain reduction & quality of life
Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence
https://pubmed.ncbi.nlm.nih.gov/36015298

A cool review of what we know about the minor cannabinoids
Minor Phytocannabinoids: A Misleading Name but a Promising Opportunity for Biomedical Research
https://pubmed.ncbi.nlm.nih.gov/36008978

2021: A review of how cannabis alters our acute & chronic stress response
A review of the effects of acute and chronic cannabinoid exposure on the stress response
https://pubmed.ncbi.nlm.nih.gov/34461155
“Acute cannabinoid exposure increases basal concentrations of stress hormones in rodents and humans and has dose-dependent effects on stress reactivity in humans and anxiety-like behavior in rodents. Chronic cannabis exposure is associated with dampened stress reactivity, a blunted cortisol awakening response (CAR), and flattened diurnal cortisol slope in humans”.

In a mouse model of Alzheimer’s, an ultra-low dose of THC lessened cognitive impairments
An Ultra-Low Dose of ∆9-Tetrahydrocannabinol Alleviates Alzheimer's Disease-Related Cognitive Impairments and Modulates TrkB Receptor Expression in a 5XFAD Mouse Model
https://pubmed.ncbi.nlm.nih.gov/36012711

In rats with loss of blood flow to their brains, CBD lowered cell death & protected against dysfunction of the mitochondria (powerhouse of the cell)
Mitofusin-2 mediates cannabidiol-induced neuroprotection against cerebral ischemia in rats
https://pubmed.ncbi.nlm.nih.gov/36229600

In a female mouse model of neuropsychiatric disorders, cannabis oil lowered depressive behaviors, significantly reduced social avoidance & promoted social interaction
Potential Therapeutic Effects of Lebanese Cannabis oil in Female Mouse Models of Neuropsychiatric Disorders
https://laur.lau.edu.lb:8443/xmlui/handle/10725/14202

In tooth eruption (baby teeth coming in), CB1 seems to be a mediator of tooth & bone tissue homeostasis
The role of the endocannabinoid system in tooth eruption: An ex vivo study
https://pubmed.ncbi.nlm.nih.gov/36226979
Our 1.5-year-old has her 7th & 8th tooth coming in & I can attest that it’s a hell of a system. At random times of day & night, a razor-sharp tooth pushes through your sensitive little gums. It’d be enough to screw up anyone’s mood. And it does…
Maybe I should be giving her CBD?

2021: A drug that activates the CB2 receptor may be useful against COVID-19 because of its “anti-inflammatory, antiviral, and immunomodulatory properties”
Cannabinoid Type-2 Receptor Agonist, JWH133 May Be a Possible Candidate for Targeting Infection, Inflammation, and Immunity in COVID-19
https://www.mdpi.com/2673-5601/1/3/20

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 fix, I’ll create a gameplan & then send it over to you. It will include what to take & when, where to buy it & how to experiment with taking higher levels. Plus, unlimited email follow-ups for all of your questions.

See my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression.

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. 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 better use these powerful tools of health.

Book a session here:
Cannabinoid & Psychedelic Education Sessions

the Headlines & Fav Articles

At the polls,

· Maryland legalized adult-use cannabis by a huge margin

· Missouri became the first mid-western state to go adult use cannabis

· Arkansas, South Dakota & North Dakota voted against adult use cannabis

More than 130 orgs asked Biden to stop excluding immigrants from his cannabis pardons
https://www.marijuanamoment.net/130-organizations-demand-biden-stop-excluding-immigrants-from-his-marijuana-pardons

One decade after its filing, the FDA rejects a petition to allow cannabis to be marketed without a new drug application
https://www.marijuanamoment.net/fda-finally-rejects-petition-for-federal-exemption-for-marijuana-more-than-a-decade-after-it-was-filed
And more recently, the FDA & FTC told CannaAid to stop making claims about using CBD to treat COVID-19
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/alternative-health-distribution-llc-dba-cannaaid-641241-11012022

A federal judge rejected a lawsuit that sought gun rights for medical cannabis patients
https://www.marijuanamoment.net/federal-court-dismisses-florida-ag-commissioners-lawsuit-on-medical-marijuana-patients-gun-rights

In a disappointing ruling from Germany, health insurance companies only need to cover cannabis for very seriously ill patients
https://www.faz.net/aktuell/wirtschaft/unternehmen/bundessozialgericht-cannabis-auf-rezept-weiterhin-nur-fuer-schwerkranke-18451744.html
And in Ireland, the High Court did not live up to its name & threw out a lawsuit that challenged a ban on selling products with any level of THC
https://www.independent.ie/irish-news/courts/challenge-to-ban-on-selling-products-containing-psychoactive-cannabis-ingredient-is-thrown-out-42131955.html

An air quality analysis finds that smoking a joint in a house with windows opened causes higher concentrations of airborne particulates than smoking a cigarette with the windows closed
Measuring PM2.5 concentrations from secondhand tobacco vs. marijuana smoke in 9 rooms of a detached 2-story house
https://pubmed.ncbi.nlm.nih.gov/36037897

After everyone demanded the secret of his smooth legs when they went viral, a Kenyan senator revealed that it was CBD body butter that kept them so silky
https://nairobiwire.com/2022/11/senator-ledama-reveals-marijuana-secret-behind-his-smooth-legs.html

The War on Drugs & Prohibition


This
DanceSafe @DanceSafeDreaming of a world where people understand that bars are safe consumption sites and alcohol is an example of safe supply.

A single mom in Texas who uses medical cannabis faces eviction from her federally subsidized apartment
https://www.ganjapreneur.com/single-texas-mom-facing-eviction-for-medical-cannabis-in-federally-subsidized-apartment
I hate this.

Critique of a terrible article from the NYPost about NYC’s first safe injection facility
BR⚢KE @BabblingBrookeAThe NY P*st published a garbage article about OnPoint NYC, the organization I work for that runs the first and only legal safe drug consumption spaces in the US. The article is dripping with hateful stigma about and clandestine photos of our participants. 

Trump again says he’ll use the death penalty against drug dealers
https://www.drugwarrant.com/2022/11/guy-who-wants-to-be-in-office-has-ideas-about-drugs

Using arthropods to find cannabis farms
How Arthropods Can Help Law Enforcement Agencies Identify Illegal Cannabis Farms
https://www.proquest.com/openview/90c8bd0489532070084d6fd306c2eeff/1
Millipedes, don’t snitch.

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]

Colorado legalizes psychedelic mushrooms for personal & medical use
https://www.ganjapreneur.com/colorado-legalizes-psychedelic-mushrooms-for-personal-and-medical-use

On ways to stop a psychedelic trip
For when it all gets too much… from vitamin B3 to ketanserin… Let’s look at some of the pharmacological interventions that have been used to kill (or at least diminish) a psychedelic trip that takes a turn for the worst… 

A history of the psychedelic writings of Ernst Jünger (an OG) by Henrik Dahl of the Oak Tree Review
Psychedelic Anarch: The Drug Writings of Ernst Jünger (Part 1)

Nuanced article on the ‘ideological war at the heart of the psychedelic renaissance’ by Rich Haridy
https://newatlas.com/health-wellbeing/psychedelic-decrim-legal-medicalization-colorado-ballot

On how the Wonderland psychedelic conference screwed up royally by banning the academics & journalists from Psymposia
The psychedelic industry needs to learn how to deal with bad trips – and bad publicity

In people with PTSD, MDMA helped with chronic pain
MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder
https://www.frontiersin.org/articles/10.3389/fpsyt.2022.939302/full

Can psychedelics help with obesity?
Do psychedelics have therapeutic potential for obesity?
https://pubmed.ncbi.nlm.nih.gov/36329153

In rats, LSD combined well with low-level electrical stimulation of the brain to help with neuroplasticity
Psychedelics enhance the effects of brain stimulation in rodents
https://www.biorxiv.org/content/10.1101/2022.10.31.514588v1

Business & Law

Oh man. I’m not even going to link to the all the cannabis company earnings coming out. What a bloodbath. Everyone is losing tens of millions of dollars.

The Plant & the History

2021: A strong review of the environmental impacts of cannabis growing
A narrative review on environmental impacts of cannabis cultivation
https://pubmed.ncbi.nlm.nih.gov/34362475

A history of hemp as a fabric
Flax, hemp, ramie and jute: the bast fibres
https://www.google.com/books/edition/Textiles_and_Clothing_Along_the_Silk_Roa/1zOVEAAAQBAJ?hl=en&gbpv=1&dq=hemp&pg=PA45&printsec=frontcover

A look at the tools for learning more about the molecular mechanisms of cannabis
Multi-Omics Approaches to Study Molecular Mechanisms in Cannabis sativa
https://pubmed.ncbi.nlm.nih.gov/36015485

2021: Using the cannabinoid levels as a way to differentiate between different cultivars (strains) of cannabis
Phytocannabinomics: Untargeted metabolomics as a tool for cannabis chemovar differentiation
https://pubmed.ncbi.nlm.nih.gov/33934778

2021: A look at how the trichomes create their specialized storage spaces for cannabinoids & terpenes
Cannabis Glandular Trichome Cell Walls Undergo Remodeling to Store Specialized Metabolites
https://pubmed.ncbi.nlm.nih.gov/34392368

For growing hemp, using bituminous rock-alginite
BITUMINOUS ROCK - ALGINITE AS A NATURAL SOURCE OF SILICON FOR IMPROVING GROWTH, PRODUCTION AND QUALITY OF HEMP (Cannabis sativa L.)
https://ibn.idsi.md/sites/default/files/imag_file/74-77_54.pdf

Seedlings of cannabis can inherit the helpful fungi-fighting bacteria that lived on the seeds they were grown from
Cannabis Seedlings Inherit Seed-Borne Bioactive and Anti-Fungal Endophytic Bacilli
https://pubmed.ncbi.nlm.nih.gov/36015430

2021: A book on diagnosing hemp & cannabis crop diseases
Diagnosing Hemp and Cannabis Crop Diseases
link

Cannabinoid Science

Clinical Studies & Surveys

In a study of the UK cannabis medicine registry, the most frequent users of inhaled cannabis were patients with chronic pain & anxiety & they reported “a significant improvement in patient-reported pain scores, mood, anxiety, sleep disturbances” as well as increased quality of life
" Flower Power": Controlled Inhalation of THC-Predominant Cannabis Flos Improves Health-Related Quality of Life and Symptoms of Chronic Pain and Anxiety in Eligible UK Patients
https://pubmed.ncbi.nlm.nih.gov/36289837

When people used 1:1 THC:CBD flower, they had less anxiety than using high-THC cannabis
Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis
https://pubmed.ncbi.nlm.nih.gov/36227352

In a brain scan study, they looked at the levels of CB1 in 58 patients & found that the levels decreased with age & that women tended to have higher levels
Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET
https://pubmed.ncbi.nlm.nih.gov/36243269
“There was a significant decline in CB1R availability (VT) with age in the pallidum, cerebellum and posterior cingulate. Adjusting for BMI, age-related decline in VT remained significant in the posterior cingulate among males, and in the cerebellum among women. CB1R availability was higher in women compared to men in the thalamus, pallidum and posterior cingulate.”
Relatedly, in the brains of female mice, the levels of CB1 “increased with age in some subregions of the cortex, decreased with age in the lateral septal area, and reached its lowest level at 52 weeks in the thalamus, hypothalamus, and hindbrain subregions”
Lifespan changes in cannabinoid 1 receptor mRNA expression in the female C57BL/6J mouse brain
https://pubmed.ncbi.nlm.nih.gov/36240125

2021: In a study of speech production between adults who use cannabis & those who don’t, the only difference seemed to be spectral tilt (vocal effort & intensity)
Adults with a history of recreational cannabis use have altered speech production
https://pubmed.ncbi.nlm.nih.gov/34419853
2021: And in a study of people who used cannabis, they had a significant difference in how their eyes altered their focus
Dynamics of the accommodative response after smoking cannabis
https://pubmed.ncbi.nlm.nih.gov/34382240

2021: A review looks at the genes association with cannabis use
Genetic basis of cannabis use: a systematic review
https://pubmed.ncbi.nlm.nih.gov/34384432
The genes are: ANKFN1, INTS7, PI4K2B, CSMD1, CST7, ACSS1 & SCN9A.
I don’t know anything about any of them.

In a study of fear elicited by breathing 10% CO2 for 5 minutes, a single dose of isolated CBD given 90 minutes before the exercise saw no effect on self-reported fear, panic symptoms, or heart rate
A double-blind, randomized, placebo-controlled test of the effects of cannabidiol on fear elicited by a 10% carbon dioxide-enriched air breathing challenge
https://pubmed.ncbi.nlm.nih.gov/36241853

Giving dairy cows omega-3 fatty acids, conjugated linoleic fatty acids, and inhibitors of lipolysis like niacin supported their endocannabinoid levels & a strong immune-metabolic response
Modulating immunometabolism in transition dairy cows: the role of inflammatory lipid mediators
https://pubmed.ncbi.nlm.nih.gov/36268169

Recommended for You

Mental Health, Addiction & Mental Effects

A review of targeting the CB2 receptor for helping to regulate the brain circuits of schizophrenia
Cannabinoid type-2 receptors: An emerging target for regulating schizophrenia-relevant brain circuits
https://pubmed.ncbi.nlm.nih.gov/36033626
“The ability of CB2 receptors to inhibit dopaminergic and hippocampal circuits, combined with the anti-inflammatory effects of CB2 receptor activation, make this receptor an intriguing target for treating schizophrenia.”

Hair analysis suggests that low anandamide levels are correlated with symptoms of depression
Depressive symptoms are negatively associated with hair N-arachidonoylethanolamine (anandamide) levels: A cross-lagged panel analysis of four annual assessment waves examining hair endocannabinoids and cortisol
https://pubmed.ncbi.nlm.nih.gov/36252885

2021: In people with HIV, cannabis helped to normalize the connectivity of the insula (a region of the cortex associated with self-awareness, pain processing & addiction)
Interactive Effects of HIV Infection and Cannabis Use on Insula Subregion Functional Connectivity
https://pubmed.ncbi.nlm.nih.gov/34427866

In a synthesis of data from 87 studies, CBD did not show an effect on anxiety in 70% of the studies
Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool
https://pubmed.ncbi.nlm.nih.gov/36239014

Cannabis users did not show a difference in measures of their working memory
Context dependent differences in working memory related brain activity in heavy cannabis users
https://pubmed.ncbi.nlm.nih.gov/34448889

The brain scans of cannabis users did not differ from non-users in the microstructure of their white matter
The relation between cannabis use, dependence severity and white matter microstructure: A diffusion tensor imaging study
https://pubmed.ncbi.nlm.nih.gov/34402136

In rats conditioned to a scheduled drinking of alcohol, THC helped to delay their acquisition of the drinking habit
Chronic ∆-9-tetrahydrocannabinol administration delays acquisition of schedule-induced drinking in rats and retains long-lasting effects
https://pubmed.ncbi.nlm.nih.gov/34436650

2021: In female mice, 2 weeks of cannabis extracts caused symptoms of anxiety & depression
Anxiety, depression-like behaviors and biochemistry disorders induced by cannabis extract in female mice
https://pubmed.ncbi.nlm.nih.gov/34764743

In a mouse model of anxiety, the ability of fear to lower anxiety seemed to have gender differences based on the hormone cycle of the females
Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze
https://pubmed.ncbi.nlm.nih.gov/36239039

In zebrafish, the terpene β-caryophyllene caused sedation at high doses while α-pinene lowered anxiety & locomotion measures
Effects of super-class cannabis terpenes beta-caryophyllene and alpha-pinene on zebrafish behavioural biomarkers
https://pubmed.ncbi.nlm.nih.gov/36241680

2021: Giving THC to male & female rats had different effects on the opioid system of their hippocampus (memory center)
Acute Delta 9-tetrahydrocannabinol administration differentially alters the hippocampal opioid system in adult female and male rats
https://pubmed.ncbi.nlm.nih.gov/34255372

Harms, Cannabis Use Disorder & Street Synthetics

A Florida company starting trials to treat cannabis use disorder with an oral drug that inhibits the effects of THC
https://www.ganjapreneur.com/florida-clinical-trial-company-tests-first-drug-for-people-with-cannabis-use-disorder

In cannabis addiction, how the steroids of the brain interact with the endocannabinoid system
Cross-talk between neurosteroid and endocannabinoid systems in cannabis addiction
https://pubmed.ncbi.nlm.nih.gov/36043319

2021: A review of the possibility that the pesticide chlorpyrifos that’s sprayed on cannabis plants may contribute to the obesity epidemic
Chlorpyrifos and Δ9 Tetrahydrocannabinol exposure and effects on parameters associated with the endocannabinoid system and risk factors for obesity
https://pubmed.ncbi.nlm.nih.gov/34467221

A review of the history of cannabinoid hyperemesis syndrome
Cannabinoid Hyperemesis Syndrome: Lighting Up an Emergency Department Near You
https://pubmed.ncbi.nlm.nih.gov/36035580

Case report of a heart attack in a young man using lots of medical cannabis
Paroxysmal Sustained Ventricular Tachycardia with Cardiac Arrest and Myocardial Infarction in 29-Year-Old Man Addicted to Medical Marijuana-It Never Rains but It Pours
https://pubmed.ncbi.nlm.nih.gov/36292471

2021: A case study of cannabis causing catatonia (a person frozen or almost completely unresponsive in their movements)
Cannabis-Induced Malignant Catatonia: A Medical Emergency and Review of Prior Case Series
https://pubmed.ncbi.nlm.nih.gov/34548987
While this is not common, that’s because we don’t take as much cannabis as we used to. There are reports of this throughout history from the days when people drank huge amounts of cannabis beverages & reached catatonic levels of cannabinoids.

What happens in the body to the street synthetics QMMSB & QMiPSB
In vitro metabolic fate of the synthetic cannabinoid receptor agonists (quinolin-8-yl 4-methyl-3-(morpholine-4-sulfonyl)benzoate [QMMSB]) and (quinolin-8-yl 4-methyl-3-((propan-2-yl)sulfamoyl)benzoate [QMiPSB]) including isozyme mapping and carboxylesterases activity testing
https://pubmed.ncbi.nlm.nih.gov/36239626

Using antibodies to identify synthetic cannabinoids during toxic overdoses
Development of Cross-Reactive Antibodies for the Identification and Treatment of Synthetic Cannabinoid Receptor Agonist Toxicity
https://pubmed.ncbi.nlm.nih.gov/36016144

Neurodegenerative & Brain Diseases

In a rat model of a heart attack causing blood loss to the brain, inhibiting the MGL enzyme (which breaks down 2-AG) was as effective as therapeutic hypothermia for fixing cerebral microcirculation, smaller brain swellings & protecting the blood-brain barrier
The monoacylglycerol lipase inhibitor, JZL184, has comparable effects to therapeutic hypothermia, attenuating global cerebral injury in a rat model of cardiac arrest
https://pubmed.ncbi.nlm.nih.gov/36252353

In a mouse model of the loss of myelin (the sheaths around nerves that facilitate electrical signaling), activating their TRPV1 (a function of anandamide) increases the functioning of the microglia (immune guardian cells of the brain)
Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function
https://pubmed.ncbi.nlm.nih.gov/36229601

In a mouse model of Alzheimer’s, inhibiting ABHD6 (an enzyme that breaks down 2-AG) lessened synaptic dysfunction & memory impairment – though not neuroinflammation & plaque levels
ABHD6 inhibition alleviates memory deficits in an Alzheimer's disease mouse model
https://europepmc.org/article/ppr/ppr558091

In an animal & cellular model, THCV lowered neuroinflammation & improved the ability of morphine to lower pain
Cannabidivarin alleviates neuroinflammation by targeting TLR4 co-receptor MD2 and improves morphine-mediated analgesia
https://pubmed.ncbi.nlm.nih.gov/36032146

2021: In a cellular model of Parkinson’s disease, THC protected the dopamine-producing neurons by antioxidant effects, decreasing cell death & protecting the mitochondria (powerhouse of the cell)
Neuroprotective Effects of Delta-9-Tetrahydrocannabinol against FeSO4- and H2O2-Induced Cell Damage on Dopaminergic Neurons in Primary Mesencephalic Cell Culture
https://www.thieme-connect.com/products/ejournals/html/10.1055/a-1516-4182

In mice with no α-Dystrobrevin protein (signaling molecules in the muscle cells), they had higher levels in the prefrontal cortex & less levels in the nucleus accumbens, perhaps relating to their increased motivation for reward
α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression
https://pubmed.ncbi.nlm.nih.gov/36045406

Pain & Inflammation

A review of 23 articles found evidence for the use of cannabis for lower back pain
The Effectiveness of Cannabis and Cannabis Derivatives in Treating Lower Back Pain in the Aged Population: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/34515130

In a mouse model of facial pain, CBD reduced transmission through the pain pathway via the TRPV1 receptors
Efficacy and mechanism of the antinociceptive effects of cannabidiol on acute orofacial nociception induced by Complete Freund's Adjuvant in male Mus musculus mice
https://pubmed.ncbi.nlm.nih.gov/36265395

The Skin

A summary of a survey of cannabinoids for psoriasis
Practices and perspectives on medical cannabis and cannabinoids: A survey of the National Psoriasis Foundation Medical Advisory Board
https://pubmed.ncbi.nlm.nih.gov/36017106

In mice with psoriasis, enhancing the action of NAAA (an enzyme that breaks down PEA) worsened the disease progress
N-Acylethanolamine acid amidase (NAAA) exacerbates psoriasis inflammation by enhancing dendritic cell (DCs) maturation
https://pubmed.ncbi.nlm.nih.gov/36244543

The Guts & Oral Health

In a rat model of type 2 diabetes with high levels of insulin, THC decreased the levels of inflammatory cytokines & regulated antioxidant potential
Anti-inflammatory potential of delta-9-tetrahydrocannabinol in hyperinsulinemia: an experimental study
https://pubmed.ncbi.nlm.nih.gov/36239881

2021: In a mouse model of kidney damage from diabetes, while CBD helped on some measures, it significantly worsened overall kidney damage
Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice
https://pubmed.ncbi.nlm.nih.gov/34577563

In white fat cells, they have CB1 receptors for modulating their mitochondria (powerhouse of the cell) & this suggests targeting them as a mechanism for regulating energy metabolism
Expression of Functional Cannabinoid Type-1 (CB1) Receptor in Mitochondria of White Adipocytes
https://pubmed.ncbi.nlm.nih.gov/36010658

In dental tissue cells, an immune system challenge caused an increase in the levels of the cannabinoid receptors & CBD increased the calcium flow into the cells (a cell signaling process)
Immune challenges upregulate the expression of cannabinoid receptors in cultured human odontoblasts and gingival fibroblasts
https://pubmed.ncbi.nlm.nih.gov/36260938

The Liver

A review of the cannabinoids for chronic liver diseases
Cannabinoids and Chronic Liver Diseases
https://pubmed.ncbi.nlm.nih.gov/36012687

Case report of cannabis causing hepatitis in the liver
Marijuana-Induced Acute Hepatitis: A Case Report
https://www.cureus.com/articles/119681-marijuana-induced-acute-hepatitis-a-case-report

Reproductive & Maternal Effects

In children exposed to cannabis in the womb, they showed different functional connectivity in their brains
Impact of prenatal cannabis exposure on functional connectivity of the salience network in children
https://pubmed.ncbi.nlm.nih.gov/36226844

In Asian-American men, they found no association between cannabis use & semen quality
The Association between Monthly, Yearly, and Lifetime Cannabis Use, and Semen Parameters in Asian-American Men
https://pubmed.ncbi.nlm.nih.gov/36047080

Cancer & Chemo

A review of cancer research only found three studies to examine
Controversial Link between Cannabis and Anticancer Treatments-Where Are We and Where Are We Going? A Systematic Review of the Literature
https://pubmed.ncbi.nlm.nih.gov/36011049

Cool Chemistry

A simple new process to synthesize 2-AG
2-Arachidonoylglycerol Synthesis: Facile and Handy Enzymatic Method That Allows to Avoid Isomerization
https://pubmed.ncbi.nlm.nih.gov/36014430

Using computer modeling to analyze single-point mutations in a CB1 receptor
Evaluating Allosteric Perturbations in Cannabinoid Receptor 1 by In Silico Single-Point Mutation
https://pubmed.ncbi.nlm.nih.gov/36312415
And how CBD binds to CB1 & GPR55
Interacting binding insights and conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled receptors
https://pubmed.ncbi.nlm.nih.gov/36016551

Using AI & genetic algorithms to predict better FAAH inhibitors
Structural Model Based on Genetic Algorithm for Inhibiting Fatty Acid Amide Hydrolase
https://www.mdpi.com/2673-2688/3/4/52

2021: How the tails of cannabinoids alter their activity
The Combined Effect of Branching and Elongation on the Bioactivity Profile of Phytocannabinoids. Part I: Thermo-TRPs
https://pubmed.ncbi.nlm.nih.gov/34440274

How to design endocannabinoid nanoparticles
Design and function of targeted endocannabinoid nanoparticles
https://pubmed.ncbi.nlm.nih.gov/36241847
If I had Ms. Frizzle’s Magic School Bus, I would use it to do a tour of all this new cannabinoid chemistry each week.

Thanks.
- lex

PS: For this week’s sweet vocals, the album ‘Play Me Sweet and Nice’ by Marcia Griffiths. Arguably the most influential woman in the history of reggae, she began by singing in her church choir in Kingston, Jamaica. But with her “strong, smooth-as-mousse love songs and captivating live performances”, soon she was singing with one of the most influential ska bands on the island.
In 1967, she had her first hit with ‘Feel Like Jumping’ & began collaborating with artists like Bob Marley, Bunny Wailer & Peter Tosh. Using her wide influence, she helped to usher in the birth of reggae from its roots in ska & rocksteady. And with a wise choice of collaborators in her later years, she kept herself relevant & at the top of the charts. She’s still alive & singing in her impressive style.

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 the basics are that 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]

CBG (cannabigerol)
Known as the “mother cannabinoid”, CBG is the chemical precursor to THC, CBD, and the other cannabinoids in the plant. CBG occurs only at low levels in cannabis because it tends to be quickly converted to other cannabinoids. Binding slightly to the CB1 and CB2 receptor, it also inhibits the enzymes that break down anandamide and 2-AG, hence raising the levels of those endocannabinoids. CBG interacts with an adrenaline receptor (α-2 adrenoceptor) & a serotonin receptor (5-HT1A Receptor) as well as modulating the expression of glutamate, GABA, and dopamine via the PPAR receptors on the nucleus, controllers of genetic transcription. CBG is also active at the TRP channels involved in the sensations of temperature, pressure, pH, smell, taste, vision, and pain perception whose dysfunction are linked to neuropathic pain, inflammation, and respiratory disorders.
Surveys show patients reporting help for anxiety, chronic pain, depression, and disturbed sleep. In preclinical trials, it's been studied for eye pressure, gut problems, appetite modulation, blood pressure lowering, bladder control, oral care, muscle spasms, airway inflammation, arthritis, painkilling, and most notably for brain health and neuroinflammation. In adult neural stem cells, CBG increased their viability. The breakdown products of CBG have been shown to reduce inflammation via the brain’s immune cells.
[since it’s the first cannabinoid produced, it must be the wooly mammoth

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.