Hello everyone,

This week…

male sexual health (probably) not worsened by cannabis
cannabis for cancer & Fragile X Syndrome
lots on the effects of teen use - such as how it improves their decision making skills
CBD for aged horses
so much on cannabis allergies that it’s broken out into its own section
how cannabis use alters your outcomes after various surgeries
a UK record store ran by the police to entrap young Black customers
some powerful psychedelic stories & articles
only one headline this week, but it’s hilarious

Announcements:
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(let me know if the Lex Files episodes are working OK. Was having some problems with the embeds).
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Editor’s note:
Another late edition thanks to COVID…

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. Writing, science archives, newsletter content & if you need a podcast, I’m the host for you. You can see my portfolio here.
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Best of cannabinoid science...

In a survey of caregivers for patients with Fragile X Syndrome (a genetic developmental disorder that causes intellectual disability), they reported that CBD improved symptoms with less side effects than traditional medications
Parent and Caregiver Perspectives towards Cannabidiol as a Treatment for Fragile X Syndrome
https://pubmed.ncbi.nlm.nih.gov/36140762

In a survey of patients undergoing treatment for cancer, the majority found that cannabis helped with their symptoms, sometimes more than the prescription medications
Perception and Utilization of Cannabinoids in Patients Undergoing Radiation Treatment: Our Patients are Curious
https://www.sciencedirect.com/science/article/abs/pii/S0360301622023951
“More than half of cannabinoid users reported some degree of effectiveness of cannabinoid in managing pain (64.4%), sleep (62.2%), and anxiety/stress (57.8%), with more patients citing benefits while undergoing chemo- or immunotherapy (35.6%) than while undergoing radiation treatment (17.8%).”

A series of 6 case studies where cannabis helps with emotionally unstable personality disorder
Cannabis-Based Medicinal Products in the Management of Emotionally Unstable Personality Disorder (EUPD): A Narrative Review and Case Series
https://pubmed.ncbi.nlm.nih.gov/36358392

A cool review of how the cannabinoids turn on & off genes (epigenetics)
Molecular Insights into Epigenetics and Cannabinoid Receptors
https://pubmed.ncbi.nlm.nih.gov/36358910
And a study of teens finds cannabis increased their age-related epigenetics
Marijuana use and DNA methylation-based biological age in young adults
https://pubmed.ncbi.nlm.nih.gov/36289503

In an animal model, topical 1% CBD cream helped with pain & inflammation
Study the Effect of Cannabidiol Topical on Antinociceptive and Anti-inflammatory Activities in Animal Model
https://assets.researchsquare.com/files/rs-2151741/v1/a9019039-d111-486d-ae08-a026cb2465f9.pdf

CBD works on the α7 nicotinic receptors (a key set of receptors for rapid neural signaling such as for muscles)
Cannabidiol as a modulator of α7 nicotinic receptors
https://pubmed.ncbi.nlm.nih.gov/36282426

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

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the Headlines & Fav Articles

Police in northern India said a stash of 500 kilograms of confiscated cannabis that had gone missing was eaten by rats
https://www.ganjapreneur.com/indian-police-blame-rats-for-disappearance-of-500-kilos-of-cannabis

The War on Drugs & Prohibition

In terrible UK news, undercover Met Police ran a record store to entrap young Black people by asking them for drugs by Camilla Patini & Nick Thompson
https://www.vice.com/en/article/dy74jk/fake-record-store-operation-peyzac

A Canadian man faces a permanent ban from entering the US after border agents find a bottle of CBD oil in his car
https://cannabislaw.report/canada-us-b-c-man-faces-lifetime-ban-from-entering-u-s-after-border-agents-find-forgotten-bottle-of-cbd-oil-in-his-car

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]

A living list of the handful of North American psychedelic dispensaries
https://psychedelicspotlight.com/a-living-list-of-north-american-psychedelic-dispensaries

There’s an uptick in the number of arrests of plant medicine practitioners by Mattha Busby
https://doubleblindmag.com/ayahuasca-practitioner-arrests

Bioneers has a bunch of their talks on visionary plants online
https://bioneers.org/visionary-plant-consciousness-psychedelics-media-collection/#visionary-plants

An important essay on hard psychedelic trips by Rachael Petersen
https://bulletin.hds.harvard.edu/a-theological-reckoning-with-bad-trips

An amazing story on a man paralyzed from the chest down who uses psilocybin mushrooms for his recovery by Rachel Mabe
https://www.outsideonline.com/outdoor-adventure/exploration-survival/psychedelics-research-paralysis-treatment-jim-harris

On the mechanisms of the K-hole by Andrew Gallimore

Alien Insect On Drugs

Slipping into a K-hole

From the earliest clinical studies in humans in the 1960s, subjects injected with ketamine reported feeling detached from their bodies, floating in outer space, and completely disconnected — dissociated — from the outside world. An entirely new class of psychoactive molecule was born — the…

4 months ago · 8 likes · 10 comments · Andrew R. Gallimore

Great thread on the psychedelic mystic art of Ernst Fuchs

𐌖𐌉𐌊𐌀𐌃𐌄 @vikare06

What do you get if you mix erotism, Jungian psychology, Albrecht Dürer, William Blake, ancient Sumerian art and a desire for new concrete art in a sea of artistic vacuity following WW2? You get Ernst Fuchs, voluptuous mythical figures and psychedelic mysticism. A thread:

Business & Law

A walkthrough of the 5 new CBD warning letters from the FDA by Asa Waldstein
https://www.asawaldstein.com/warning-letter-wednesday/fda-issues-five-cbd-related-warning-letters

2021: A review of the major themes around the regulations on cannabis
Don’t make a hash of it! A thematic review of the literature relating to outcomes of cannabis regulatory change
https://www.tandfonline.com/doi/abs/10.1080/09687637.2021.1901855

The Plant & the History

A study of how to use cannabis as an ornamental plant
New Insight into Ornamental Applications of Cannabis: Perspectives and Challenges
https://pubmed.ncbi.nlm.nih.gov/36145783

How to grow & process hemp for its various uses
The Influence of Agrotechnical Factors on Productivity Hemp (Cannabis sativa L.)
http://dspace.mnau.edu.ua/jspui/bitstream/123456789/11829/1/The%20Influence%20of%20Agrotechnical%20Factors.pdf

In hemp, the temperature limits for seed germination
Temperature Limits for Seed Germination in Industrial Hemp (Cannabis sativa L.)
https://www.mdpi.com/2673-7655/2/4/29

I’d never heard of the hemp flea beetle, but I now know about this enemy of my friend
Bacterial and fungal communities within and among geographic samples of the hemp pest Psylliodes attenuata from China
https://pubmed.ncbi.nlm.nih.gov/36147860

On the pests of hemp in Louisiana
Evaluation of Hemp (Cannabis sativa) (Rosales: Cannabaceae) as an Alternative Host Plant for Polyphagous Noctuid Pests
https://pubmed.ncbi.nlm.nih.gov/36269156
And mildew in New York
First Report of Downy Mildew caused by Pseudoperonospora cannabina on Cannabis sativa in New York
https://apsjournals.apsnet.org/doi/pdf/10.1094/PDIS-08-22-1930-PDN

On feeding hemp to sheep
Nutrient digestibility, rumen parameters, and (cannabinoid) residues in sheep fed a pelleted diet containing green hemp ( Cannabis sativa L.) biomass
https://pubmed.ncbi.nlm.nih.gov/36381952

Cannabinoid Science

2021: A nice historical review of 85 years of publications in the toxicology of cannabis
Commemorating 85 years of publications on Cannabis by Archives of Toxicology
https://pubmed.ncbi.nlm.nih.gov/34052890

2021: An analysis of all the CB2 receptor patents since 2010
Cannabinoid receptor type 2 ligands: an analysis of granted patents since 2010
https://pubmed.ncbi.nlm.nih.gov/34111979

Clinical Studies & Surveys

A review of using CBD for diseases other than anxiety (58 clinical studies)
The Effectiveness and Safety of Cannabidiol in Non-seizure-related Indications: A Systematic Review of Published Randomized Clinical Trials
https://pubmed.ncbi.nlm.nih.gov/36271316

2021: In a study at one center of ten years of data, they did not find an association between cannabis use & male sexual health
The impact of cannabis use on male sexual function: A 10-year, single-center experience
https://pubmed.ncbi.nlm.nih.gov/34171210

In young people, acute exercise increased their endocannabinoids while 24 weeks of exercise decreased them
Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial
https://pubmed.ncbi.nlm.nih.gov/36374769

On gender identity, medical transition & cannabis use
The Impact of Gender Identity, Medical Transition, and Other Substances on Marijuana Use for Transgender Adults
https://scholarworks.waldenu.edu/cgi/viewcontent.cgi?article=1535&context=jsbhs

A study of urinary levels of CBD & THC from eating & vaping
Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Their Metabolites following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration
https://pubmed.ncbi.nlm.nih.gov/34089060
As well as how CBD enters the rat’s system via oral or smoking
Pharmacokinetics of Cannabidiol in Sprague-Dawley Rats After Oral and Pulmonary Administration
https://pubmed.ncbi.nlm.nih.gov/36301522

A genetic variant of your FAAH enzymes is linked to susceptibility to various diseases
Fatty acid amide hydrolase C385A polymorphism affects susceptibility to various diseases
https://pubmed.ncbi.nlm.nih.gov/36300805

2021: A safety review of the nabiximols (a pharmaceutical 1:1 THC:CBD oral formulation like Sativex)
Safety and tolerability of nabiximols oromucosal spray: a review of more than 15 years" accumulated evidence from clinical trials
https://pubmed.ncbi.nlm.nih.gov/34092180

Veterinarian uses

A study of giving increasing doses of CBD to cats was safe
Pharmacokinetics of escalating single-dose administration of cannabidiol to cats
https://pubmed.ncbi.nlm.nih.gov/36300854

CBD good for tilapia fish!
Cannabidiol improves Nile tilapia cichlid fish welfare
https://pubmed.ncbi.nlm.nih.gov/36271101
There’s a whole sub-field of using cannabinoids to improve the health of farmed fish.

On how CBD helps older horses
The Effects of Cannabidiol on Senior Equine Health
https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1062&context=gluck_etds

Adolescents

In adolescents a review of how cannabis alters their developing brain
Cannabis in Adolescence: Lasting Cognitive Alterations and Underlying Mechanisms
https://pubmed.ncbi.nlm.nih.gov/36301550

2021: In teens, cannabis smoking associated with increased decision-making skills
Residual effects of cannabis-use on neuropsychological functioning
https://www.sciencedirect.com/science/article/abs/pii/S0885201421000678
And makes them find money less rewarding
The effects of acute cannabis with and without cannabidiol on neural reward anticipation in adults and adolescents
https://www.biologicalpsychiatrycnni.org/article/S2451-9022(22)00250-6/fulltext

A review of the effects of adolescent cannabis use disorder on the brain
Cannabis Use Disorder in Adolescents
https://pubmed.ncbi.nlm.nih.gov/36410900
A review of adolescent cannabis use & ADHD
Adolescent Cannabis Use, Comorbid Attention-Deficit/Hyperactivity Disorder, and Other Internalizing and Externalizing Disorders
https://pubmed.ncbi.nlm.nih.gov/36410906
A review of adolescent cannabis use & psychosis
Cannabis and Psychosis
https://pubmed.ncbi.nlm.nih.gov/36410907
And a review of adolescent cannabis use on physical health
A Review of the Effects of Adolescent Cannabis Use on Physical Health
https://pubmed.ncbi.nlm.nih.gov/36410908

A big survey of how young people are vaping cannabis
Vaping preferences of individuals who vaporise dry herb cannabis, cannabis liquids and cannabis concentrates
https://pubmed.ncbi.nlm.nih.gov/36152405
“Most (91.4 %) stated they had ever vaped dry herb cannabis, 59.1 % reported vaporisation of cannabis oil or liquids, and 34.0 % reported vaporisation of cannabis concentrates.”

The gender differences between how college students use cannabis to cope with social anxiety
Cannabis-related problems and social anxiety: The roles of sex and cannabis use motives updated
https://pubmed.ncbi.nlm.nih.gov/36335786

Mental Health, Addiction & Mental Effects

A series of 6 case studies where cannabis helps with emotionally unstable personality disorder
Cannabis-Based Medicinal Products in the Management of Emotionally Unstable Personality Disorder (EUPD): A Narrative Review and Case Series
https://pubmed.ncbi.nlm.nih.gov/36358392

In a survey of patients with OCD, 10% of the cannabis users said it helped their symptoms while 23% said it worsened their anxiety
Cannabis use and related clinical variables in patients with obsessive-compulsive disorder
https://pubmed.ncbi.nlm.nih.gov/36148826

2021: In young people, an association between cannabis use, major depression & suicidality
Associations of Suicidality Trends With Cannabis Use as a Function of Sex and Depression Status
https://pubmed.ncbi.nlm.nih.gov/34156452

A review of THC, CBD & anxiety
THC, CBD, and Anxiety: a Review of Recent Findings on the Anxiolytic and Anxiogenic Effects of Cannabis’ Primary Cannabinoids
https://link.springer.com/article/10.1007/s40429-022-00450-7

2021: A review of the cannabinoids for adult psychiatric disorders
Potential therapeutic benefits of cannabinoid products in adult psychiatric disorders: A systematic review and meta-analysis of randomised controlled trials
https://pubmed.ncbi.nlm.nih.gov/34119912

In patients with bipolar disorder in their mania phase, their blood had higher levels of the CB1 receptor
Expression of type 1 cannabinoid receptor gene in bipolar disorder
https://pubmed.ncbi.nlm.nih.gov/36323143

2021: In brain scans of cannabis users, they had greater connectivity with their cerebellum (a center for motor function, attention, language & emotional control)
Altered cerebellar-cortical resting-state functional connectivity in cannabis users
https://pubmed.ncbi.nlm.nih.gov/34034553
The cerebellum has a very high density of CB1 receptors. Plus, even though it’s small, it contains more than half of your neurons.

2021: In a brain scan study, 15 mg of THC increased psychotic symptoms but did not increase levels of glutamate (the brain’s primary excitatory neurotransmitter) in the striatum (motor, motivation & reward systems)
The Effects of Acute Δ9-Tetrahydrocannabinol on Striatal Glutamatergic Function: A Proton Magnetic Resonance Spectroscopy Study
https://pubmed.ncbi.nlm.nih.gov/34099186

2021: In mice, how THC’s route of administration altered their ability to recognize it
Δ9-Tetrahydrocannabinol discrimination: Effects of route of administration in rats
https://pubmed.ncbi.nlm.nih.gov/34186444

The Brain & its Diseases

2021: In patients with Tourette syndrome, a pharmaceutical inhibitor of the MAGL enzyme (which breaks down 2-AG) had no significant differences from the placebo
Monoacylglycerol Lipase Inhibition in Tourette Syndrome: A 12-Week, Randomized, Controlled Study
https://pubmed.ncbi.nlm.nih.gov/34117788

A review of how the ECS works in your central nervous system
Endocannabinoid signaling in the central nervous system
https://pubmed.ncbi.nlm.nih.gov/36308424

In a mouse model of middle-aged people, they found a decline in endocannabinoid signaling in the hippocampus (memory center) & cortex (higher-level processing)
Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis
https://pubmed.ncbi.nlm.nih.gov/36142165

In a mouse model of Parkinson’s, blocking the CB1 receptor helped with brain electricity alterations
Probable role of the hyperpolarization-activated current in the dual effects of CB1R antagonism on behaviors in a Parkinsonism mouse model
https://pubmed.ncbi.nlm.nih.gov/36283508

In a mouse model of severe epilepsy, a seizure induced by hyperthermia increased the levels of the lesser-known endocannabinoid-related monoacylglycerols, 2-LG & 1-LG
Hyperthermia-Induced Seizures Enhance Brain Concentrations of the Endocannabinoid-Related Linoleoyl Glycerols in a Scn1a+/- Mouse Model of Dravet Syndrome
https://pubmed.ncbi.nlm.nih.gov/36269656

In the serotonin center of rat brains (the dorsal raphe nucleus), CBD causes negative allosteric modulation at one of the serotonin receptors (5-HT1A)
Functional characterization of cannabidiol effect on the serotonergic neurons of the dorsal raphe nucleus in rat brain slices
https://pubmed.ncbi.nlm.nih.gov/36147343

In young rat neurons, CBD caused lower cellular energy, dysregulated mitochondria (powerhouse of the cell) & early cell death
Cytotoxic Effects of Cannabidiol on Neonatal Rat Cortical Neurons and Astrocytes: Potential Danger to Brain Development
https://pubmed.ncbi.nlm.nih.gov/36287988

In human brain cells, CBDA from hemp seeds (& two other metabolites) altered the microRNAs that regulate gene expression related to important functions such as axon guidance, hippocampal signaling & neurotrophin signaling
Effect of Cannabidiolic Acid, N- Trans-Caffeoyltyramine and Cannabisin B from Hemp Seeds on microRNA Expression in Human Neural Cells
https://pubmed.ncbi.nlm.nih.gov/36286061

In brain cells, a CB1 activator helped to regulate the levels of calcium (a control method for neuronal excitability)
WIN55212-2 Modulates Intracellular Calcium via CB1 Receptor-Dependent and Independent Mechanisms in Neuroblastoma Cells
https://pubmed.ncbi.nlm.nih.gov/36230909

Harms, Cannabis Use Disorder & Street Synthetics

The dark side of how legal CBD leads to improperly made delta-8 THC
The Dark Side of Cannabidiol: The Unanticipated Social and Clinical Implications of Synthetic Δ8-THC
https://pubmed.ncbi.nlm.nih.gov/36264171

2021: A study of THC & synthetic cannabinoids in monkeys finds that they don’t get very addicted to it (“minimal reinforcing effects”)
Self-administration of inhaled delta-9-tetrahydrocannabinol and synthetic cannabinoids in non-human primates
https://pubmed.ncbi.nlm.nih.gov/34043398

Characterizing the street synthetic AMB-FUBINACA
Characterisation of AMB-FUBINACA metabolism and CB1-mediated activity of its acid metabolite
https://link.springer.com/article/10.1007/s11419-022-00649-3

Immune System & Microbial

For the virus that causes COVID-19, CBGA & tetrahydrocannabutol (THC with a slighter shorter tail) were the best at lowering virus replication
Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity
https://pubmed.ncbi.nlm.nih.gov/36144858

2021: A review of cannabis use shows that its ability to suppress the immune system may lead to more viral infections
The Link between Cannabis Use, Immune System, and Viral Infections
https://pubmed.ncbi.nlm.nih.gov/34207524

Nano-hemp extracts as antibiotics
Antibacterial activities and biosynthesis of nanoparticles using hemp extracts
https://jomped.org/index.php/jomped/article/view/160

Cannabis & Allergies

A review of the newest findings on cannabis allergies
A review of cannabis allergy in the early days of legalization
https://pubmed.ncbi.nlm.nih.gov/36384984

A review of how cannabinoids alter the immune system & what that means for allergies
Immunomodulatory Actions of Cannabinoids: Clinical Correlates and Therapeutic Opportunities for Allergic Inflammation
https://pubmed.ncbi.nlm.nih.gov/36280137

2021: On cannabis allergens
In search of the golden ratio for cannabis allergy: Utility of specific allergen-to-total IgE ratios
https://pubmed.ncbi.nlm.nih.gov/34324720
(I wish you could view more of this paper. Cannabis & allergies is fascinating to me)

Pain, Inflammation & Surgeries

In those having knee & shoulder surgeries, cannabis dependence linked to a higher chance of infection
Marijuana and Joints: Outcomes after Shoulder and Knee Arthroscopy
https://journals.lww.com/journalacs/Fulltext/2022/11001/Marijuana_and_Joints__Outcomes_after_Shoulder_and.317.aspx

In patients who had vascular bypass surgery in their legs, cannabis users had decreased blood vessel openness after 30 days & an increased chance of amputation after a year
Impact of Cannabis Use on Outcomes after Lower Extremity Bypass
https://pubmed.ncbi.nlm.nih.gov/36156300

2021: In patients who had orthopedic surgery, use of cannabis before the operation was linked to “worse mental health scores, lower activity level, less pain relief, and worse satisfaction two years after” the surgery
Impact of pre-operative recreational marijuana use on outcomes two years after orthopaedic surgery
https://pubmed.ncbi.nlm.nih.gov/34052856

In a rat model of osteoarthritis, stopping the breakdown of anandamide helped reduce pain levels & restore functioning in the hippocampus
Inhibition of anandamide breakdown reduces pain and restores LTP and monoamine levels in the rat hippocampus via the CB1 receptor following osteoarthritis
https://pubmed.ncbi.nlm.nih.gov/36341807

2021: A rejiggering of the THC molecule to allow for pain relief without psychoactive effects
Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects
https://pubmed.ncbi.nlm.nih.gov/33887904

The Skin

A study of CBD & THC can enter the bloodstream thru the skin
Examining the Systemic Bioavailability of Cannabidiol and Tetrahydrocannabinol from a Novel Transdermal Delivery System in Healthy Adults: A Single-Arm, Open-Label, Exploratory Study
https://pubmed.ncbi.nlm.nih.gov/36308640

The Guts & Oral Health

2021: In patients with gastroparesis (delayed emptying of the stomach), those who use cannabis had shorter hospital stays & lower rates of sepsis
Gastroparesis with Cannabis Use: A Retrospective Study from the Nationwide Inpatient Sample
https://pubmed.ncbi.nlm.nih.gov/34096455

A survey of women finds an association between recent cannabis use & urinary incontinence
The association between recent cannabis use and urinary incontinence in women: a population-based analysis of the NHANES from 2009 to 2018
https://pubmed.ncbi.nlm.nih.gov/36289107

An editorial on how the ECS influences the gut-brain axis
Editorial: Implications of gut-brain interactions for the effects of compounds derived from Cannabis or modulating the endocannabinoid system in physiological and pathological processes
https://pubmed.ncbi.nlm.nih.gov/36339815

A review of using cannabinoids & terpenes to treat diabetes mellitus
Cannabinoids and terpenes for diabetes mellitus and its complications: from mechanisms to new therapies
https://pubmed.ncbi.nlm.nih.gov/36280497

2021: A clinician’s review of cannabis for inflammatory bowel diseases
Inflammatory Bowel Disease and Cannabis: A Practical Approach for Clinicians
https://pubmed.ncbi.nlm.nih.gov/34110607

In obese rats, they had more 2-AG & CB1 receptors in their medial prefrontal cortex (a center for attention, habit formation & memory)
Up-regulation of CB1 cannabinoid receptors located at glutamatergic terminals in the medial prefrontal cortex of the obese Zucker rat
https://pubmed.ncbi.nlm.nih.gov/36329829

In mice with obesity induced by diet, the CB1 receptors in their guts seem to be protective in maintaining the integrity of the gut barrier
Diet-Induced Gut Barrier Dysfunction Is Exacerbated in Mice Lacking Cannabinoid 1 Receptors in the Intestinal Epithelium
https://pubmed.ncbi.nlm.nih.gov/36142461

In dental stem cells, anandamide modulated some of the bone-degrading factors
Endocannabinoids modulate production of osteoclastogenic factors by stem cells of the apical papilla in vitro
https://pubmed.ncbi.nlm.nih.gov/36174776

The Heart & the Blood

A review of how the cannabinoids work in your system of veins & arteries
Pharmacognosy and Effects of Cannabinoids in the Vascular System
https://pubmed.ncbi.nlm.nih.gov/36407955

A very negative review says that cannabinoid use is worse for the heart than tobacco use
Adverse Effects of Cannabinoids and Tobacco Consumption on the Cardiovascular System: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/36159363
while this retrospective study finds no relationship between cannabis use & heart problems
Analysis of STEMI and NSTEMI in a Community Cohort of Marijuana Users
https://pubmed.ncbi.nlm.nih.gov/36405229

In white blood cells, cannabis extract decreased their inflammation & levels of inflammatory cytokines with CBC being the strongest
Anti-inflammatory potential of cannabinoid extracts
https://academic.oup.com/cardiovascres/article/118/Supplement_2/cvac157.044/6768002
“Cannabigerol (CBG) and cannabidiol (CBD) significantly decreased the production of TNFα… [and] CBD, cannabidivarin (CBDV), cannabichromene (CBC), and cannabinol (CBN) significantly decreased also IL-6 production.”

For blood platelets, AEA & 2-AG increase their energy production & thus the presence of reactive oxygen species, mostly via CB1
Endocannabinoids effect on oxidative status of human platelets
https://pubmed.ncbi.nlm.nih.gov/36260649

2021: In mice with atherosclerosis (hardened arteries) from a high-cholesterol diet, cannabis seed oil lowered inflammation, cell damage & lipid deposition
Cannabis Seed Oil Alleviates Experimental Atherosclerosis by Ameliorating Vascular Inflammation in Apolipoprotein-E-Deficient Mice
https://pubmed.ncbi.nlm.nih.gov/34037390

The Lungs

When treating asthma with an inhaled steroid, the presence of THC (but not CBD) in smoked form moderately decreases the dose delivered
Involvement of esterases in the pulmonary metabolism of beclomethasone dipropionate and the potential influence of cannabis use
https://pubmed.ncbi.nlm.nih.gov/36283465

Reproductive & Maternal Effects

A review of 28 studies finds no clear link between prenatal cannabis use & later neurobehavioral changes in the children
Prenatal cannabis use and its impact on offspring neuro-behavioural outcomes: A systematic review
https://academic.oup.com/pch/advance-article-abstract/doi/10.1093/pch/pxac079/6776028

A review of cannabis use during the time of preconception (3-12 months before pregnancy)
Preconception cannabis use: An important but overlooked public health issue
https://pubmed.ncbi.nlm.nih.gov/36148938

A review of studies finds that cannabis use during pregnancy leads to lower birth weight
The effect of prenatal cannabis exposure on offspring preterm birth: a cumulative meta-analysis
https://pubmed.ncbi.nlm.nih.gov/36305657

In preeclampsia (dangerously high blood pressure for a pregnant mother), the placenta has higher levels of CB1
Preeclampsia Correlates with an Increase in Cannabinoid Receptor 1 Levels Leading to Macromolecular Alterations in Chorionic Villi of Term Placenta
https://pubmed.ncbi.nlm.nih.gov/36361721

In mice experiencing the “two hits” of prenatal cannabis use plus a viral infection, their offspring had a small rise in anxiety-like behaviors as well as decreased levels of CB1 & CB2
Investigating the "two-hit hypothesis": Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice
https://pubmed.ncbi.nlm.nih.gov/36150422

2021: In Marseille, a rise in the number of toddlers accidentally ingesting cannabis with 6 serious cases (5 comas & 1 respiratory depression)
Unintentional cannabis poisoning in toddlers: A one year study in Marseille
https://pubmed.ncbi.nlm.nih.gov/34091410

2021: In pregnant mice, supplements of omega-3 fatty acids helped to improve endocannabinoid functioning in their offspring
Maternal omega-3 intake differentially affects the endocannabinoid system in the progeny`s neocortex and hippocampus: Impact on synaptic markers
https://pubmed.ncbi.nlm.nih.gov/34038760

2021: In young zebrafish, suppressing their endocannabinoid enzymes FAAH & MAGL changes their locomotor development
Early suppression of the endocannabinoid degrading enzymes FAAH and MAGL alters locomotor development in zebrafish
https://pubmed.ncbi.nlm.nih.gov/34435626

Cancer & Chemo

In patients with hepatocellular cholangiocarcinoma (a rare aggressive liver cancer), medical cannabis increased their survival rate
Survival rate of patients with combined hepatocellular cholangiocarcinoma receiving medical cannabis treatment: A retrospective, cohort comparative study
https://f1000research.com/articles/11-1212

Cool Chemistry

A look at CBD’s different enantiomers (spatial configurations)
Differential Enantiomer-Specific Signaling of Cannabidiol at CB1 Receptors
https://pubmed.ncbi.nlm.nih.gov/36153039
CBD usually occurs as (-)-CBD – which you might call its right-handed configuration. But it can also occur as (+)-CBD. According to this study, this latter “left-handed” configuration is more potent at inhibiting the CB1 receptor.
In our Neural Ocean metaphor, when the right-handed Asian elephant goes to the bar, he’s not as good at killing the vibe as the left-handed Asian elephant.
(technically, it should be left-tusked & right-tusked. Elephants actually do have a preferred tusk just like us…)

Computer modeling of what happens to CBD & CBG in different human tissues
Physiologically based pharmacokinetic modeling and simulation of cannabinoids in human plasma and tissues
https://pubmed.ncbi.nlm.nih.gov/36272108

2021: What are the vibrations of THC & CBD?
Understanding the conformational, electronic and vibrational properties of Tetrahydrocannabinol (THC) and Cannabidiol (CBD). Pharmacophoric similarities and differences
https://www.sciencedirect.com/science/article/abs/pii/S0022286021010772
Groovy man.

A review of the many nanocarrier delivery systems for enhancing the bioavailability of CBD
Promising Nanocarriers to Enhance Solubility and Bioavailability of Cannabidiol for a Plethora of Therapeutic Opportunities
https://pubmed.ncbi.nlm.nih.gov/36144803

2021: Or a microencapsulation technique like this one: sodium alginate with deoxycholic acid
Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid
https://pubmed.ncbi.nlm.nih.gov/34138862

A new way to make cannabinoids
Short and efficient synthesis of alkylresorcinols: a route for the preparation of cannabinoids
https://pubs.rsc.org/en/content/articlehtml/2022/nj/d2nj03547b

Thanks.

- lex

PS: For this week’s old folk protest album, Barbara Dane’s ‘On My Way’.

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.

Cannabinoids & the People

C&P#34: (my new site!) teen use + cannabis…