Hello everyone,

Happy New Year & thanks to everyone coming along for the ride.
I want to take this opportunity in the first newsletter of the year to publicly state my goals for 2023:

I plan to partner with a few companies I'm proud to work with & produce excellent educational content for them
I plan to grow this newsletter to 5,000 subscribers by the end of the year
I plan to make one video a day on new cannabinoid science & one longer educational video per week for patients about how to use cannabis
I plan to begin the next season of The Lex Files & find sponsors
I plan to get my first two books reformatted & up for sale online & then finish the illustrations for the next 7 chapters in the series & publish those as one book

This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations.
I produce educational content for cannabis & psychedelic companies: writing, science archives, newsletters, social media posts & podcasts.
You can see my portfolio here.

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This week…

· Not one but two reviews of CBD for dentistry

· On the importance of terpenes for clinical results

· Cannabinoids for growing new bones & CBD for muscle recovery

· Huge chunks of research on Alzheimer’s, Parkinson’s & epilepsy

· Quantum medical hypnosis via endocannabinoids?

· CBD for sickle cell + PEA for hemophilia

· Cannabinoids against bacteria, viruses & parasites

· So many reviews on cannabis for cancer & for the symptoms of cancer treatment

· CBD may help with psychiatric diseases by turning off certain genes

· Smoking alone linked to more depression & more cannabis use disorder

· Hemp sanitary pads

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Sponsor: PlusCBD & a commitment to quality

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Best Of Cannabinoid Science...

An interview with Dr. Raphael Mechoulam – father of the endocannabinoid system
https://www.higherlearninglv.co/post/the-higher-learning-lv-interview-raphael-mechoulam

In humans living with HIV, cannabis users had less aberrant neural dynamics
Regular cannabis use modulates the impact of HIV on the neural dynamics serving cognitive control
https://pubmed.ncbi.nlm.nih.gov/36416285
HIV disorders the cycles of the brain – but cannabis appears to help prevent this. And as we saw, cannabis users also exercised more.

In kids with Fragile X Syndrome (a genetic developmental disorder that causes intellectual disability), a pharmaceutical CBD gel helped with isolation, irritability, disruptive behaviors & social interactions in the subset with the relevant gene most silenced (most severe cases)
A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX)
https://pubmed.ncbi.nlm.nih.gov/36434514

In a case study where isolated CBD stopped being effective for autism once the patient hit puberty, the power of enriching with terpenes
Terpene-Enriched CBD oil for treating autism-derived symptoms unresponsive to pure CBD: Case report
https://pubmed.ncbi.nlm.nih.gov/36386202/

Human noses can detect the difference when cannabis strains (cultivars) are genetic outliers compared to others within their strain
Human olfactory discrimination of genetic variation within Cannabis strainsv
https://pubmed.ncbi.nlm.nih.gov/36389460/

On terpenes, a suggestion that some patients prefer smoking because more terpenes are preserved & perhaps we should be adding terpenes to our liquid extracts
Optimal Treatment with Cannabis Extracts Formulations Is Gained via Knowledge of Their Terpene Content and via Enrichment with Specifically Selected Monoterpenes and Monoterpenoids
https://pubmed.ncbi.nlm.nih.gov/36296511

A clinical study of using hemp sanitary pads to maintain the balance of the vaginal macroecology during menstruation
Effects of Hemp Sanitary Pads on the Vaginal Microecology
https://pubmed.ncbi.nlm.nih.gov/36277007

In women with fibromyalgia, cannabis treatment for 30 days improved quality of life, general health, physical health & mental health
The role of cannabis in treatment-resistant fibromyalgia women
https://pubmed.ncbi.nlm.nih.gov/36333278

On using PEA for chronic pelvic pain syndrome
Chronic Pelvic Pain Syndrome, General Conservative and Medical Management and Palmitoylethanolamide (PEA) Efficacy
https://web.archive.org/web/20221119222632id_/https://www.onlinescientificresearch.com/articles/chronic-pelvic-pain-syndrome-general-conservative-and-medical-management-and-palmitoylethanolamide-pea-efficacy.pdf

In a strong review of 33 studies on PEA for cognitive decline, PEA improved neurobehavioral functions like memory & learning, reduced oxidative stress & inflammation, rebalanced glutamate (the brain’s primary excitatory neurotransmitter), increased neuron survival & promoted neurogenesis (the creation of new brain cells) + so much more
Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
https://pubmed.ncbi.nlm.nih.gov/36387000/

A review of everyone’s favorite minor cannabinoid: CBN
Cannabinol: History, Syntheses, and Biological Profile of the Greatest "Minor" Cannabinoid
https://pubmed.ncbi.nlm.nih.gov/36365350

A review of studies finds that the placebo effect significantly contributes to the pain reduction in clinical trials of cannabinoids
Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis
https://pubmed.ncbi.nlm.nih.gov/36441553
A few people reached out for my opinion on this paper & my general take is, yeah sure. The placebo response is important for a lot of drugs & treatments. Cannabis is no different. This study cherry-picked 8 studies total - but we have a large database of trials in animal models showing the cannabinoids would be protective from pain. These poor mice surely did not benefit from the placebo effect & they taught us about the very intertwined relationship between our endocannabinoids & our endorphins, our native painkilling molecules. All of this confirms that the reason pain is at the top of every survey for why people use medical cannabis is not just because it's in our heads.
(I’m knee-deep in this subject right now because my next article for my Project CBD series is on the cannabinoids & the endorphins).

An analysis of YouTube videos on CBD for epilepsy found a quarter of them to be high-quality & reliable
Analysis of YouTube videos as a source of information for reliability and effectiveness of cannabidiol oil in treatment of epilepsy
https://pubmed.ncbi.nlm.nih.gov/36473301/

Some heavy hitters review why the CB2 receptor possesses so much therapeutic potential
Editorial: Therapeutic potential of the cannabinoid CB2 receptor
https://pubmed.ncbi.nlm.nih.gov/36278235

How the voltage of the membrane alters the activity of the CB1 receptor
Voltage dependence of the cannabinoid CB1 receptor
https://pubmed.ncbi.nlm.nih.gov/36304142
The complexities of this system never cease to boggle the mind. If it is 2-AG binding the CB1 receptor, the voltage of the neuron matters (ie. how recently it fired & how close it is to firing again). But for anandamide, its binding is independent of voltage. In our Neural Ocean metaphor (see Living Glossary below), the blue whale 2-AG cares if the neuronal city has recently undergone a revolution - but the sperm whale anandamide does not.
In related news, here's a great review of how cannabinoids affect the ion channels that allow electrical charges in & out of cells
Effects of cannabinoids on ligand-gated ion channels
https://pubmed.ncbi.nlm.nih.gov/36338493

How the endocannabinoids might be involved in medical hypnosis + a quantum mind/body theory
RNA/DNA Psychosocial Genomic Theory of Cognition and Consciousness
https://kathrynrossi.com/wp-content/uploads/2022/10/QUANTUM-PLACEBO-PROTOCOL-ASMH-2018.pdf

The mystery of the cause of Bruce Lee's death probably does not include cannabis - but it always gets mentioned
Who killed Bruce Lee? The hyponatraemia hypothesis
https://pubmed.ncbi.nlm.nih.gov/36381374/

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), Google Scholar itself or try ResearchGate.
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.

the Headlines & Fav Articles

Not only did Congress leave out cannabis banking & expungements from their big appropriations bill, the bastards also blocked DC from moving forward with their local legislation to allow recreational cannabis sales
https://www.marijuanamoment.net/congress-keeps-ban-on-d-c-marijuana-sales-while-failing-to-act-on-cannabis-banking-and-expungements
Can you imagine the US Congress being the overseer of your city government? How awful.
And when I say bastards, I specifically mean Mitch McConnell.

NORML says 4300 papers were published on cannabis last year – and I went through all of them for you…
https://norml.org/blog/2022/12/27/record-number-of-science-papers-published-about-cannabis-in-2022

A number of FDA warning letters for including CBD in food products
https://www.foodsafetynews.com/2022/12/fda-sends-warnings-to-food-firms-selling-cbd
The backstory here is not only does the FDA consider CBD to be an illegal dietary supplement because pharmaceutical research was done on it before it was marketed in the natural health space, they also consider CBD to be an illegal adulteration of food products because it has not been certified as a food ingredient.
Those risk-averse bureaucrats. They’ve been promising guidance on hemp products since my first child was born – and we celebrate her fifth birthday this weekend.
But they did just announce that they hope to release a plan on CBD & delta-8 THC “within a few months”…
https://www.marijuanamoment.net/fda-officials-say-hemp-and-cbd-regulatory-plan-is-months-away-as-it-carries-out-marijuana-scheduling-review

A national cannabis glut is dropping prices across the US & making it even harder for businesses (hattip to Ned Pelger)
https://www.politico.com/news/2022/12/25/weed-prices-business-michigan-00075485

Twitter stops showing people who search “marijuana” suggestions for drug treatment
https://www.marijuanamoment.net/twitter-stops-suggesting-people-who-search-for-marijuana-may-need-drug-treatment

Russian billionaire Roman Abramovich apparently invested hundreds of millions in the US cannabis industry, most especially CuraLeaf
https://www.forensicnews.co/roman-abramovich-secretly-funded-worlds-largest-marijuana-company
and the pushback statement released by CuraLeaf
ttps://twitter.com/Boris_Jordan/status/1606290651078721536

New York’s first licensed adult-use cannabis shop — operated by Housing Works
https://www.ganjapreneur.com/new-yorks-first-adult-use-cannabis-retailer-opens-next-week
I used to get books there all the time & my favorite Pakistani joint was two doors down.
So I’m excited to go back for books, biryani & blunts.

French court overturns government ban on sale of CBD flowers
https://uk.news.yahoo.com/french-court-overturns-government-ban-113806208.html

On the hashish of Morocco as a terroir product (similar to the French system of protected regions for certain wines & cheeses)
Moroccan hashish as an example of a cannabis terroir product
https://link.springer.com/article/10.1007/s10708-022-10791-5
For my wife’s birthday, her parents just gifted us two nights in Tangiers – so I hope to be able to provide you with data from the ground in a few weeks.

The War on Drugs & Prohibition

In an analysis of Oregon counties, legalization led to a rise in simple assaults

The Impact of Recreational Marijuana Legalization on Simple Assault in Oregon
https://pubmed.ncbi.nlm.nih.gov/35229672

A study from Cannabis Public Policy Consulting reports legal cannabis states have less underage use & impaired driving than criminalized states
https://www.marijuanamoment.net/states-with-legal-marijuana-have-less-underage-use-and-impaired-driving-than-criminalized-states-study-shows

According to stats from car insurance companies, changes in cannabis laws made no statistically significant impact on accident rates in the US or Canada
https://www.ganjapreneur.com/car-insurance-report-finds-cannabis-reforms-not-associated-with-more-traffic-accidents

In a small pilot study of the effects of CBD on driving, 300 mg of CBD found no significant differences (but you can tell that the researchers wanted to find a difference)
The effects of cannabidiol on the driving performance of healthy adults: a pilot randomized clinical trial
https://www.sciencedirect.com/science/article/pii/S2773065422000517
Whenever a paper says that the trial was undersized, it means that they didn’t see the effects they wanted & think they will when they go back & do it over again with a bunch more participants.

Psychedelics, Plant Medicines & Other Psychoactives

On the Merry Pranksters & psychedelic spiking

Coming Home: Ecstatic Integration and Harm Reduction

Did the Merry Pranksters spike people with LSD?

A woman having a bad trip in 1996, captured by Lawrence Schiller, who photographed the Pranksters early party. She told Schiller: ‘I experienced the desire to die, but not actual death…very strongly the desire to rip my skin off and pull my hair out and pull my face off…

3 months ago · 3 likes · 4 comments · Jules

To be clear, spiking someone with psychedelics is depraved, immoral & a complete violation of boundaries. Never ever do this.

A deep dive on the fly agaric mushrooms

Alien Insect On Drugs

Fly Agaric, Dwarves' Wine, and Reindeer Pee

The late poet and ethnobotanist Dale Pendell rightly called Amanita muscaria “the most famous mushroom in the world” and, paired with the cheerful elves and pixies that enjoy frolicking on and around them, this most iconic of fungi has come to occupy an almost archetypal position in our collective cultural consciousness. And, it’s no coincidence that fe…

3 months ago · 20 likes · 1 comment · Andrew R. Gallimore

The Science of Drugs

[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 organization, reach out to me]

2021: A bibliometric feast of the 100 most cited papers in addiction research
The most 100 cited papers in addiction research on cannabis, heroin, cocaine and psychostimulants. A bibliometric cross-sectional analysis
https://pubmed.ncbi.nlm.nih.gov/33636599

In follow-up interviews of people using psilocybin for bipolar disorder, on the positive side, they reported decreased severity of depression, increased emotional processing, development of new perspectives & greater relaxation & sleep – on the negative side, increased mania severity, hospitalization, & distressing sensory experiences
"A sense of the bigger picture:" A qualitative analysis of follow-up interviews with people with bipolar disorder who self-reported psilocybin use
https://pubmed.ncbi.nlm.nih.gov/36516137/

In a survey of people with bipolar disorder using magic mushrooms, they reported more mania, difficulty with sleeping & anxiety - but the majority still rated it as more helpful than harmful
Risks and benefits of psilocybin use in people with bipolar disorder: An international web-based survey on experiences of 'magic mushroom' consumption
https://pubmed.ncbi.nlm.nih.gov/36515370/

Business & Law

In a study of California cannabis workers, over a third reported symptoms suggestive of asthma
A Pilot Study of Respiratory and Dermal Symptoms in California Cannabis Cultivation Workers
https://pubmed.ncbi.nlm.nih.gov/36305193

For a pilot program in California, Colorado and Puerto Rico, Google is loosening its ban on ads for CBD products
https://adage.com/article/marketing-news-strategy/google-allow-limited-cbd-ads-policy-change/2461151

A compare & contrast of advertising policies across the US & Canada
Cannabis Advertising Policies in the United States: State-Level Variation and Comparison with Canada
https://pubmed.ncbi.nlm.nih.gov/36459118/

A lawyer's take on permits for medical cannabis versus permits for concealed weapons
Medical Marijuana Permits and Concealed Weapons Permits: When One Right Impacts Another
https://heinonline.org/HOL/LandingPage?handle=hein.journals/hpercrm2022&div=3&id=&page=
I’m not a big gun guy – but I’ve spent a lot of time around rednecks & if the right to drink alcohol does not impinge your right to carry a firearm, neither should your right to use cannabis.

The Plant & the History

A cool history of cannabis on the Iberian peninsula (Spain)
Historical biogeography of Cannabis in the Iberian Peninsula: A probabilistic approach using palynological evidence
https://www.sciencedirect.com/science/article/pii/S1433831922000464

A big review of the techniques for extracting & purifying cannabinoids
Meta-analysis and review of cannabinoids extraction and purification techniques
https://onlinelibrary.wiley.com/doi/abs/10.1002/cjce.24786
and in the home extraction of CBD from cannabis, percolation was better than maceration
Total cannabidiol (CBD) concentrations and yields from traditional extraction methods: Percolation vs. maceration
https://pubmed.ncbi.nlm.nih.gov/36353485

Using a smart wastewater recycling system for greener indoor growing
Thermal, energy, economic, and environmental analysis of a smart wastewater recovery system for indoor Cannabis production
https://www.sciencedirect.com/science/article/pii/S2773032822000335

A comparison of the various micropropagation techniques
Ex Vitro Rooting of Cannabis sativa Microcuttings and Their Performance Compared to Retip and Stem Cuttings
https://journals.ashs.org/hortsci/view/journals/hortsci/57/12/article-p1576.xml

A study of the effects of light spectra on cannabinoid & terpene levels
Impacts of Different Light Spectra on CBD, CBDA and Terpene Concentrations in Relation to the Flower Positions of Different Cannabis Sativa L. Strains
https://pubmed.ncbi.nlm.nih.gov/36297719
and one on using LED lights to increase the cannabinoid yield of hemp
Cannabinoid accumulation in hemp depends on ROS generation and interlinked with morpho-physiological acclimation and plasticity under indoor LED environment
https://pubmed.ncbi.nlm.nih.gov/36340385

Pretreating hemp seeds with gibberellins seems to make them more drought resistant
Effects of Gibberellin Pre-Treatment on Seed Germination and Seedling Physiology Characteristics in Industrial Hemp under Drought Stress Condition
https://pubmed.ncbi.nlm.nih.gov/36431042

2020: A season-long look at hemp & its cannabinoid concentration, flowering time & disease resistance over a production cycle
Season-long characterization of high-cannabinoid hemp (Cannabis sativa L.) reveals variation in cannabinoid accumulation, flowering time, and disease resistance
https://onlinelibrary.wiley.com/doi/pdf/10.1111/gcbb.12793

A new head blight on the hemp of Kentucky
Emerging Fusarium spp. causing Head Blight on Hemp in Kentucky
https://apsjournals.apsnet.org/doi/abs/10.1094/PHP-09-22-0089-SC
Word on the street is that it resembles Mitch McConnell…

In Italy, a new fungus threatens hemp seed germination stop dictation
First Report of Seedling Damping-Off of industrial Hemp (Cannabis sativa L.) caused by seed-transmitted Alternaria rosae in Italy
https://pubmed.ncbi.nlm.nih.gov/36324207

The spread & domestication of cannabis had little impact on its overall genome size
Novel Insights into the Nature of Intraspecific Genome Size Diversity in Cannabis sativa L
https://pubmed.ncbi.nlm.nih.gov/36297761

A deep dive on the cannabis DNA in the mitochondria (powerhouse of the cell)
Polymeric structure of the Cannabis sativa L. mitochondrial genome identified with an assembly graph model
https://pubmed.ncbi.nlm.nih.gov/36470482/

A genetic study find that cannabinoid synthesis might be linked to MATEs - multidrug and toxic compound extrusion proteins - that move compounds toxic to the plant (such as cannabinoids) into specialized compartments
Characterization and expression analysis of MATEs in Cannabis sativa L. reveals genes involving in cannabinoid synthesis
https://pubmed.ncbi.nlm.nih.gov/36311070

Hemp Seeds, Hemp Oil & Human Consumption

A review of the many benefits of hemp as a food
Uncovering the secrets of industrial hemp in food and nutrition: The trends, challenges, and new-age perspectives
https://pubmed.ncbi.nlm.nih.gov/36440859
and a review of its nutritional qualities
Nutritional Quality, Chemical, and Functional Characteristics of Hemp (Cannabis sativa ssp. sativa) Protein Isolate
https://pubmed.ncbi.nlm.nih.gov/36365277

Hemp seed proteins & their nutraceutical uses
Emerging natural hemp seed proteins and their functions for nutraceutical applications
https://www.sciencedirect.com/science/article/pii/S221345302200235X
and a method to separate hemp seed proteins for nutraceutical use
Isolation and functional characterization of hemp seed protein-derived short- and medium-chain peptide mixtures with multifunctional properties for metabolic syndrome prevention
https://www.sciencedirect.com/science/article/abs/pii/S0963996922012777

A comparison of 4 hydrothermal methods for dehulling hemp seeds: the winner, steaming!
Hydrothermal treatment of hemp seeds (Cannabis sativa L.): impact on its dehulling yield, fatty acid profile and nutritional characteristics
https://pubmed.ncbi.nlm.nih.gov/36350071

In young female mice, feeding them hempseeds did not make their bones stronger & even reduced the maximum load of their femurs
Dietary Hempseed Decreases Femur Maximum Load in a Young Female C57BL/6 Mouse Model but Does Not Influence Bone Mineral Density or Micro-Architecture
https://pubmed.ncbi.nlm.nih.gov/36296906

Animal feed

In sheep, feeding them hemp stubble (the residue after harvest) had no negative effects on their growth, it improved their nutrient digestibility - but they did have very low levels of cannabinoids detected in their liver & fat which contravenes the food standards of Australia
Effects of feeding sheep rations containing hemp stubble on nutrient digestibility, rumen parameters and animal performance
https://researchoutput.csu.edu.au/en/publications/effects-of-feeding-sheep-rations-containing-hemp-stubble-on-nutri

In dairy cows, a constant drip of anandamide increased their food intake but decreased their daily milk yield
Effects of intracerebroventricular anandamide administration on feed intake and milk yield of dairy cows
https://pubmed.ncbi.nlm.nih.gov/36339733

Industrial Use & Inventions

On a new catalyst for the efficient conversion of cannabis biomass into bioenergy
High efficient conversion of Cannabis sativa L. biomass into bioenergy by using green tungsten oxide nano-catalyst towards carbon neutrality
https://www.sciencedirect.com/science/article/abs/pii/S0016236122036201

In India, using hemp straw to produce hydrogels for the sustained release of antibiotics
Unravelling the role of hemp straw derived cellulose in CMC/PVA hydrogel for sustained release of fluoroquinolone antibiotic
https://pubmed.ncbi.nlm.nih.gov/36174867

On using hydrothermal carbonization to convert cannabis waste into a valuable solid fuel (hydrochar)
Valorization of cannabis waste via hydrothermal carbonization: solid fuel production and characterization
https://pubmed.ncbi.nlm.nih.gov/36370310

Using hemp fiber & clay to disinfect stormwater
Experimental Research on the Treatment of Stormwater Contaminated by Disinfectants Using Recycled Materials-Hemp Fiber and Ceramzite
https://pubmed.ncbi.nlm.nih.gov/36361360

Treat hemp fiber with urea for better printing
Environmental urea-free pretreatment process to form new surface on hemp for enhancing the inkjet printing performance
https://www.sciencedirect.com/science/article/pii/S0300944022006142

A review of hempcrete as a sustainable building material
Hempcrete as a sustainable building material: A viable alternative to conventional concrete
https://aip.scitation.org/doi/abs/10.1063/5.0109602

A study of the strength & heat resistance of hempcrete
PHYSICO-MECHANICAL PROPERTIES INVESTIGATION OF HEMPCRETE
https://jurnalalse.com/wp-content/uploads/ALSE1-22-07.pdf

Cannabinoid Science

An EU guide for naming synthetic cannabinoids
EMCDDA framework and practical guidance for naming synthetic cannabinoids
https://pubmed.ncbi.nlm.nih.gov/36346325

A review of Indigenous research on cannabis
Understanding and Rebalancing: A Rapid Scoping Review of Cannabis Research Among Indigenous Peoplev
https://pubmed.ncbi.nlm.nih.gov/36454240/

Clinical Studies & Surveys

A review of the dosing of THC, CBD & THCV for various conditions
A Systematic Review of Medical Cannabinoids Dosing in Human
https://pubmed.ncbi.nlm.nih.gov/36411116
and a big review of the negatives of CBD drawn from 12 studies found mostly the usual mild adverse events
Adverse Effects of Oral Cannabidiol: An Updated Systematic Review of Randomized Controlled Trials (2020–2022)
https://www.mdpi.com/1999-4923/14/12/2598
“The most common AEs [adverse events] of CBD were mild or moderate and included gastrointestinal symptoms (59.5%), somnolence (16.7%), loss of appetite (16.5%), and hypertransaminasemia (ALT/AST) (12.8%). Serious adverse effects [SAEs] include mainly hypertransaminasemia with serum levels elevations greater than three times the upper limit of the normal (6.4%), seizures (1.3%), and rash (1.1%). All SAEs reported in the studies were observed on CBD as an add-on therapy to anticonvulsant medications, including clobazam and valproate.”

Among patients taking CBD for a month, it significantly improved well-being, anxiety, sleep disturbance & pain
The Safety and Effectiveness of Commercially Available Cannabidiol Products for Health and Well-Being: A Randomized, Multi-Arm, Open-Label Waitlist-Controlled Trial
https://www.liebertpub.com/doi/pdf/10.1089/imr.2022.0081

In human studies of THC: CBD ratios, increasing the CBD content did not reduce the negative effects of THC
Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios
https://pubmed.ncbi.nlm.nih.gov/36380220

Pharmacist of Africa shared their perspective on the medical use of cannabis
Medical Use of Cannabis in Africa: The Pharmacists' Perspective
https://pubmed.ncbi.nlm.nih.gov/36304681

A long study in Australia followed ~4k medical patients & found THC & CBD treatments helped on all outcomes over the course of two years
A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years
https://pubmed.ncbi.nlm.nih.gov/36399463

In the US, people with disabilities tend to use more cannabis than those without
Assessing the prevalence and risk factors of marijuana use in adults with disabilities
https://pubmed.ncbi.nlm.nih.gov/36459827

Using twins to study the genetics of cannabis use
The genetic aetiology of cannabis use: from twin models to genome-wide association studies and beyond
https://pubmed.ncbi.nlm.nih.gov/36411281

Adolescents

In Baltimore, the majority of Black youth have tried cannabis by the age of 16 & most consume it daily
"What Do You Consider Use?" Perspectives of Black Youth on Cannabis Use
https://pubmed.ncbi.nlm.nih.gov/36443160

A review of adolescence as a critical time for the development of dopamine & endocannabinoid systems in our prefrontal cortex
The role of dopamine and endocannabinoid systems in prefrontal cortex development: Adolescence as a critical period
https://pubmed.ncbi.nlm.nih.gov/36389180/

In adolescents, a review of how cannabis use alters their psychosocial functioning
The Effects of Adolescent Cannabis Use on Psychosocial Functioning: A Critical Review of the Evidence
https://pubmed.ncbi.nlm.nih.gov/36410905

In a human & rat study, adolescent exposure to cannabis showed with worse decision making, possibly via the CB1 receptors in the prelimbic cortex & amygdala
Long-Term Outcomes of Adolescent THC Exposure on Translational Cognitive Measures in Adulthood in an Animal Model and Computational Assessment of Human Data
https://pubmed.ncbi.nlm.nih.gov/36416863

In adolescent using cannabis, they had less connectivity between their striatal & frontoparietal regions (learning centers)
Evaluating instrumental learning and striatal–cortical functional connectivity in adolescent alcohol and cannabis use
https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.13258

In adolescence, sleep disruptions aggravates - and is aggravated by - cannabis use & psychotic-like experiences
Sleep as a mediator between cannabis use and psychosis vulnerability: a longitudinal cohort study
https://academic.oup.com/schizbullopen/advance-article/doi/10.1093/schizbullopen/sgac072/6855279

In adolescents with the genetic risk for obsessive-compulsive symptoms, they had lower uses of cannabis potentially because of exacerbation of symptoms
Genetic influences on the interplay between obsessive-compulsive behavior symptoms and cannabis use during adolescence
https://pubmed.ncbi.nlm.nih.gov/36443914

How cannabis use as a teenager alters the hippocampus (memory center of the brain)
Adolescent Δ-9-tetrahydrocannabinol exposure induces differential acute and long-term neuronal and molecular disturbances in dorsal vs. ventral hippocampal subregions
https://pubmed.ncbi.nlm.nih.gov/36402837

In Colombia, recent cannabis use linked to poor-fair academic achievement
Association Between Cannabis Smoking and Academic Achievement in High-School Students
https://openpsychologyjournal.com/VOLUME/15/ELOCATOR/e187435012209210/FULLTEXT/

Ingestion Methods & Pharmacokinetics (how things bind & move)

In vape liquid, CBD degrades at room temperatures to “form potentially undesirable products, including cannabielsoin & cannabidiol hydroxyquinone”
Characterizing the degradation of cannabidiol in an e-liquid formulation
https://pubmed.ncbi.nlm.nih.gov/36414659

2021: A review of what THC binds to in the body & brain
Pharmacological Properties of ∆ (9) - Tetrahydrocannabinol: A Review
https://www.easpublisher.com/media/features_articles/EASJPP_31_13-20_FT_c.pdf

and how THC alters the mitochondria (powerhouse of the cell)
Effects of Δ9-tetrahydrocannabinol on mitochondria
https://www.sciencedirect.com/science/article/pii/B9780323884624000304

2021: In mice, THC vapor caused less motivation to obtain food while both THC vapor & oral THC caused painkilling & hypothermia
Appetitive, antinociceptive, and hypothermic effects of vaped and injected Δ-9-tetrahydrocannabinol (THC) in rats: exposure and dose-effect comparisons by strain and sex
https://pubmed.ncbi.nlm.nih.gov/33493547

How oleamide spreads through the body when taken orally & its digestion by FAAH
Transport Form and Pathway from the Intestine to the Peripheral Tissues and the Intestinal Absorption and Metabolism Properties of Oleamide
https://pubmed.ncbi.nlm.nih.gov/36458736/

Mental Health, Addiction & Mental Effects

How the cannabinoids alter your neural oscillations & what this means for your experience of sensation, perception & cognition
The Relationship Between Cannabinoids and Neural Oscillations: How Cannabis Disrupts Sensation, Perception, and Cognition
https://pubmed.ncbi.nlm.nih.gov/36426543

A roundup of how cannabis alters emotional processing
Editorial: Cannabis and emotion processing
https://pubmed.ncbi.nlm.nih.gov/36324790

A review of 140 studies on the negative mental health effects of cannabis
Variations of cannabis-related adverse mental health and addiction outcomes across adolescence and adulthood: A scoping review
https://pubmed.ncbi.nlm.nih.gov/36299544
And in adolescence, a review of the effects of cannabis on attention & memory
Effects of cannabis use on attention and memory in adolescent population: a systematic review
https://pubmed.ncbi.nlm.nih.gov/36300331

A review of 39 studies on using cannabis for ADHD
Cannabis use in Attention - Deficit/Hyperactivity Disorder (ADHD): A scoping review
https://pubmed.ncbi.nlm.nih.gov/36508935
and in brain scans of adults who use cannabis during adolescence, the cannabis users had less functional connectivity between their thalamus (sensory information) & parietal regions (sensory integration)
Thalamocortical functional connectivity and cannabis use in men with childhood attention-deficit/hyperactivity disorder
https://pubmed.ncbi.nlm.nih.gov/36441710

In those with cannabis use disorder & opioid use disorder using buprenorphine, a single meeting with a clinician helped to reduce later use
Screening and Brief Intervention for Cannabis Misuse in Individuals on Buprenorphine Treatment for Opioid Use Disorder: Double-Blind Randomized Clinical Trial
https://pubmed.ncbi.nlm.nih.gov/36352558

In women with PTSD, lower levels of anandamide in their blood were associated with greater depressive symptoms, greater PTSD symptoms & worse mood while exercise served to increase anandamide levels
Circulating endocannabinoids and psychological outcomes in women with PTSD
https://pubmed.ncbi.nlm.nih.gov/36469982

In stress-related psychiatric disorders such as anxiety, schizophrenia & depression, a review of how CBD’s ability to methylate (turn off) genes in the DNA can help regulate enzymes that help with these disorders
Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry: New Insights from In Vivo and In Silico Models
https://pubmed.ncbi.nlm.nih.gov/36421839
And a review of using CBD for stress-related disorders
Potential Utility of Cannabidiol in Stress-Related Disorders
https://pubmed.ncbi.nlm.nih.gov/36409719

A review of studies on THC helping with opioid withdrawal
Alleviation of opioid withdrawal by cannabis and delta-9-tetrahydrocannabinol: A systematic review of observational and experimental human studies
https://pubmed.ncbi.nlm.nih.gov/36434879
And a review of using neutral CB1 blockers for treating substance use disorders
Neutral CB1 Receptor Antagonists as Pharmacotherapies for Substance Use Disorders: Rationale, Evidence, and Challenge
https://pubmed.ncbi.nlm.nih.gov/36291128

In humans with schizophrenia, magnetic brain stimulation lowered cannabis use as well as improving a number of cognitive measures
Neurocognitive moderation of repetitive transcranial magnetic stimulation (rTMS) effects on cannabis use in schizophrenia: a preliminary analysis
https://pubmed.ncbi.nlm.nih.gov/36384966

In human brain scans & a mouse model of schizophrenia, the cannabinoids modulated the cyclin-dependent kinase 5 & those who used cannabis had less of this kinase & better social functioning
Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids
https://pubmed.ncbi.nlm.nih.gov/36473591/

2021: In hair samples from humans with anorexia, they had higher concentrations of anandamide & other endocannabinoids that decreased over the course of short-term weight restoration
Hair endocannabinoid concentrations in individuals with acute and weight-recovered anorexia nervosa
https://pubmed.ncbi.nlm.nih.gov/33444649
And a study of gene variants find that certain endocannabinoid genes may be associated with increased chances of eating disorders
Gene variants in eating disorders. Focus on anorexia nervosa, bulimia nervosa, and binge-eating disorder
https://pubmed.ncbi.nlm.nih.gov/36479493

2021: The genetic variant of the FAAH receptor that causes slower enzyme activity is linked in use to more days of drinking, more heavy episodic drinking & higher alcohol-related problems
Association of the Fatty Acid Amide Hydrolase C385A Polymorphism With Alcohol Use Severity and Coping Motives in Heavy-Drinking Youth
https://pubmed.ncbi.nlm.nih.gov/33460184

In a mouse model of Tourette Syndrome, acupuncture helped with behavioral symptoms via the effects of CB1 receptors on dopamine neurons in parts of the basal ganglia (a center for movement, learning, emotions & addiction)
Acupuncture alleviates behavioral stereotypies of Tourette Syndrome via CB1 receptors in dopaminergic neurons of nigrostriatal system
https://assets.researchsquare.com/files/rs-2265002/v1/b07486c3-ae85-4884-99b4-bc861f26cdb9.pdf

In mice, a single dose of CBD reduced obsessive-compulsive symptoms & object memory in males but not females while it lessened anxiety behavior in both, probably via the potassium channels
Single cannabidiol administration affects anxiety-, obsessive compulsive-, object memory-, and attention-like behaviors in mice in a sex and concentration dependent manner
https://pubmed.ncbi.nlm.nih.gov/36455670

2021: In a rat model of schizophrenia, a positive modulator of the CB1 receptor (a feature of CBD) limited the hyper-dopamine signaling while THC did not
Antipsychotic potential of the type 1 cannabinoid receptor positive allosteric modulator GAT211: preclinical in vitro and in vivo studies
https://pubmed.ncbi.nlm.nih.gov/33442771

In a rat model of schizophrenia being treated by risperidone (an increaser of dopamine that leads to movement disorders), oral CBD lowered their blood sugar, lessened their repetitive chewing motions, increased antioxidation & mitigated the metabolic dysregulation & movement problems of risperidone without producing cognitive impairments
Effects of cannabidiol on vacuous chewing movements, plasma glucose and oxidative stress indices in rats administered high dose risperidone
https://pubmed.ncbi.nlm.nih.gov/36385633

In rats being given the opioid oxycodone, the normal memory deficits were blocked by treatment with oxytocin (the attachment neurotransmitter) & this worked via inhibition of the endocannabinoid system
Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone-treated rats
https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.13260

In rats who stopped taking Ritalin (a stimulant used for ADHD), they saw alterations to their CB1 receptor levels in several parts of the brain
Abstinence from Chronic Methylphenidate Exposure Modifies Cannabinoid Receptor 1 Levels in the Brain in a Dose-dependent Manner
https://pubmed.ncbi.nlm.nih.gov/33504296

In a mouse model of teenage anxiety, the ability of DXM (the cough medicine frequently used for recreational purposes) caused its anti-anxiety effects via the endocannabinoid system of the thalamus
Targeting mediodorsal thalamic CB1 receptors to inhibit dextromethorphan-induced anxiety/exploratory-related behaviors in rats: The post-weaning effect of exercise and enriched environment on adulthood anxiety
https://pubmed.ncbi.nlm.nih.gov/36495603/

2021: In rats taking cocaine, CB1 receptors in the reward part of their brain seem necessary for developing the symptoms of addiction
Cannabinoid type 1 receptors in A2a neurons contribute to cocaine-environment association
https://pubmed.ncbi.nlm.nih.gov/33454843

The Brain & its Diseases

A special edition of the Journal of Psychopharmacology on cannabinoids in the brain & our society
Cannabinoids: From the brain to society
https://journals.sagepub.com/doi/10.1177/02698811221143433

In humans who had a stroke, nabiximols (a 1:1 CBD:THC mixture) did not alter blood pressure, heart rate or cardiovascular complications
Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled study
https://pubmed.ncbi.nlm.nih.gov/36386386/

How stem cells of the human brain possess a complete endocannabinoid signaling system that modulates synaptic transmissions
A complete endocannabinoid signaling system modulates synaptic transmission between human induced pluripotent stem cell-derived neurons
https://pubmed.ncbi.nlm.nih.gov/36379717

Inhibiting the MGL enzyme & raising levels of 2-AG led to more memory formation (and long-term potentiation) in the hippocampus via the control of micro RNA in the astrocytes (support cells of the brain)
Augmentation of 2-arachidonoylglycerol signaling in astrocytes maintains synaptic functionality by regulation of miRNA-30b
https://pubmed.ncbi.nlm.nih.gov/36481187/

In the brain cells responsible for creating the essential myelin sheaths around your neurons, the CB1 receptors are critical for their differentiation (maturation) & operation
Cannabinoid CB1 receptor expression in oligodendrocyte progenitors of the hippocampus revealed by the NG2-EYFP-knockin mouse
https://pubmed.ncbi.nlm.nih.gov/36387996/

In neurons of the striatum (a movement & reward center of the brain frequently damaged in neurodegenerative disorders), CBD protects them via lowering of stress in the endoplasmic reticulum (protein production site of the cell)
Cannabidiol Protects Striatal Neurons by Attenuating Endoplasmic Reticulum Stress
https://pubmed.ncbi.nlm.nih.gov/36454179/

In humans with multiple sclerosis, treatment with the approved drug dimethyl fumarate caused increases 2-AG & OEA levels
Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate
https://pubmed.ncbi.nlm.nih.gov/36434122

2021: In the amygdala (fear center of the brain), endocannabinoids help to facilitate depolarization (an important aspect of synaptic plasticity for the down-regulation of excitation) as well as retrograde transmission (the unique ability of cannabinoids to calm down the firing of upstream neurons)
Depolarization-initiated endogenous cannabinoid release and underlying retrograde neurotransmission in interneurons of amygdala
https://pubmed.ncbi.nlm.nih.gov/33452114

In a rat model of stroke, CBD protected the brain while THC worsened neurodegeneration
The Protective Effect of CBD in a Model of In Vitro Ischemia May Be Mediated by Agonism on TRPV2 Channel and Microglia Activation
https://pubmed.ncbi.nlm.nih.gov/36292998

An in-depth mapping of the human brain finds that the presence of the gene for the CB1 receptor is closely related to the presence of the CB1 receptor
Association of CNR1 gene and cannabinoid 1 receptor protein in the human brain
https://pubmed.ncbi.nlm.nih.gov/36440544

In a rat model of fear, three brain regions (caudate nucleus & putamen, the substantia nigra pars reticulata & deep layers of the superior colliculus) use CB1 receptors to control anandamide levels, TRPV1 receptors & GABA (the brain’s primary inhibitory neurotransmitter)
Neostriatum neuronal TRPV1-signalling mediates striatal anandamide at high concentration facilitatory influence on neostriato-nigral dishinhibitory GABAergic connections
https://pubmed.ncbi.nlm.nih.gov/36414159

In a mouse’s developing cerebellum (movement center), nitric oxide regulates the endocannabinoid system
Neuronal Nitric Oxide Synthase Critically Regulates the Endocannabinoid Pathway in the Murine Cerebellum During Development
https://pubmed.ncbi.nlm.nih.gov/36402869
Nitric oxide shares a unique trait with the endocannabinoids: retrograde transmission.
In the synaptic cleft between neurons where they communicate via neurotransmitters, only nitric oxide & the endocannabinoids can go backwards against the usual flow of information & tell the upstream neuron to calm down its firing. They are the vital negative feedback loop that allows the brain to calm itself when it starts firing too much.

I normally dislike jokes in paper titles but I approve of this one because the glial cells are often called the glue of the brain, holding everything together
Of glue and pot: Endocannabinoid signaling in glial cells
https://pubmed.ncbi.nlm.nih.gov/36333901

Alzheimer’s disease

A review of targeting the CB2 receptor for proteinopathies (prevalent neurodegenerative disorders such as Alzheimer’s and Parkinson’s)
Cannabinoid CB2 Receptors in Neurodegenerative Proteinopathies: New Insights and Therapeutic Potential
https://www.mdpi.com/2227-9059/10/12/3000

Using the endocannabinoid system for the neural & psychological stress of Alzheimer's
Targeting the cannabinoid system to counteract the deleterious effects of stress in Alzheimer's disease
https://pubmed.ncbi.nlm.nih.gov/36268196

A review of using the endocannabinoid system for the chronic pain of Alzheimer's
Chronic pain in Alzheimer's disease: Endocannabinoid system
https://pubmed.ncbi.nlm.nih.gov/36455638

In the brains of Alzheimer’s patients, the high levels of orexin-A (a sleep hormone) caused higher levels of 2-AG in the hippocampus (memory center)
Positive association between plasmatic levels of orexin A and the endocannabinoid-derived 2-arachidonoyl lysophosphatidic acid in Alzheimer's disease
https://pubmed.ncbi.nlm.nih.gov/36466600

In a mouse model of Alzheimer's, blocking their orexin-1 receptors in their microglia helped to strengthen the CB2 receptors & protect the brain
Antagonization of OX1 Receptor Potentiates CB2 Receptor Function in Microglia from APPSw/Ind Mice Model
https://pubmed.ncbi.nlm.nih.gov/36361598
Fun fact: The CB2 receptors form heteromer complexes with the orexin 1 receptors to create a giant signaling system that works differently than either receptor alone. In general, the orexin neurons are seen as multitaskers that regulate vital bodily functions, sleep & wake, metabolism, reward, cognition & mood.

How the endocannabinoid system might be used as biomarkers for disease progression
Endocannabinoid System Biomarkers in Alzheimer's Disease
https://pubmed.ncbi.nlm.nih.gov/36394442

In a mouse model of Alzheimer's, how the levels of CB1 receptors change on the glial cells (guardian immune cells of the brain)
Altered glial expression of the cannabinoid 1 receptor in the subiculum of a mouse model of Alzheimer's disease
https://pubmed.ncbi.nlm.nih.gov/36437738

Parkinson’s disease

The how & the why on using cannabinoids for Parkinson’s disease
Cannabinoids in Late Life Parkinson’s Disease and Dementia: Biological Pathways and Clinical Challenges
https://www.mdpi.com/2076-3425/12/12/1596

For Parkinson’s disease, a review of targeting the CB2 receptor as a treatment
The Role of Cannabinoid Type 2 Receptors in Parkinson's Disease
https://pubmed.ncbi.nlm.nih.gov/36428554

In a mouse model of Parkinson’s, N-oleoylglycine (OlGly – a lipid mediator member of the endocannabinoid family) protected against neuroinflammation via the PPAR nuclear receptors (activators of genetic transcription)
The endocannabinoidome mediator N-oleoylglycine is a novel protective agent against 1-methyl-4-phenyl-pyridinium-induced neurotoxicity
https://pubmed.ncbi.nlm.nih.gov/36313013

A protein analysis of pathways finds that endocannabinoids are involved in the dysregulation produced by Parkinson’s disease
Mass Spectrometry-Based Proteomics Analysis of Human Substantia Nigra From Parkinson's Disease Patients Identifies Multiple Pathways Potentially Involved in the Disease
https://pubmed.ncbi.nlm.nih.gov/36423813

Using computer analysis & zebrafish to study the minimum mixture of cannabinoids & terpenes for treating Parkinson's
Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson's disease
https://pubmed.ncbi.nlm.nih.gov/36278152

Epilepsy

A glowing review of the history of CBD as a gamechanger in epilepsy treatment
Cannabidiol reveals a disruptive strategy for 21st century epilepsy drug discovery
https://pubmed.ncbi.nlm.nih.gov/36471511

A review on why targeting the endocannabinoid system makes sense for epilepsy & its frequent comorbidity (accompanying disease) of depression
Commonalities for comorbidity: Overlapping features of the endocannabinoid system in depression and epilepsy
https://pubmed.ncbi.nlm.nih.gov/36339877

In humans with epilepsy, a detailed study of their cannabinoid blood levels after dosing with various CBD formulations
Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients
https://pubmed.ncbi.nlm.nih.gov/36353497

A meta-analysis of 6 studies on CBD helping with rare childhood epilepsies
Use of cannabidiol in the treatment of epilepsy: Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex
https://pubmed.ncbi.nlm.nih.gov/36417631
And a study of an epilepsy clinic found that insurance requirements did not slow down the access to prescription CBD
Specialty pharmacy integration and the role of an advanced certified pharmacy technician in prescription cannabidiol access
https://pubmed.ncbi.nlm.nih.gov/35985958

In a mouse model of epilepsy, a study of why CBD makes the standard treatment of clobazam work better
Pharmacodynamic synergism contributes to the antiseizure action of cannabidiol and clobazam
https://pubmed.ncbi.nlm.nih.gov/36442674

2021: In a mouse model of Dravet syndrome (a childhood epilepsy), CBC, CBCA & CBCVA all displayed anticonvulsant activities
Cannabichromene, Related Phytocannabinoids, and 5-Fluoro-cannabichromene Have Anticonvulsant Properties in a Mouse Model of Dravet Syndrome
https://pubmed.ncbi.nlm.nih.gov/33395525

An analysis of how CBGVA & CBDVA cause their anticonvulsant effects by inhibition of the calcium channels & the GPR55 receptors
The anticonvulsant phytocannabinoids CBGVA and CBDVA inhibit recombinant T-type channelsv
https://pubmed.ncbi.nlm.nih.gov/36386164/

In a mouse model of epilepsy, there's an impairment of 2-AG's ability to control GABA (the brain’s primary inhibitory neurotransmitter)
2-AG-mediated Control of GABAergic Signaling is Impaired in a Model of Epilepsy
https://pubmed.ncbi.nlm.nih.gov/36460464/

Harms, Cannabis Use Disorder & Street Synthetics

Smoking cannabis alone was associated with higher depressive symptoms & cannabis use disorder
Smoking Mostly Alone as a Risk Factor for Cannabis Use Disorders and Depressive Symptoms
https://pubmed.ncbi.nlm.nih.gov/36415673
Well, for this n+1, I’ve smoked alone for most of my life – and I’ve had depression for a good chunk of my life – so there.

A letter to the editor on gender differences in medical cannabis adverse events
Sex differences in medical cannabis-related adverse effects? Do not forget the context!v
https://pubmed.ncbi.nlm.nih.gov/36383424/

Analysis of European public health data finds a close relationship between cannabis & urological problems
Epidemiological Patterns of Cannabis- and Substance- Related Congenital Uronephrological Anomalies in Europe: Geospatiotemporal and Causal Inferential Study
https://pubmed.ncbi.nlm.nih.gov/36360648

2021: A narrative review on preventing medical cannabis treatments from leading to cannabis use disorder
Cannabis based medicines and cannabis dependence: A critical review of issues and evidence
https://pubmed.ncbi.nlm.nih.gov/33593117

A big genome study found that while a genetic liability to cannabis use disorder may lead to lower education levels, a genetic liability to higher education may be linked to higher lifetime cannabis use & a lower risk of cannabis use disorder
Genetic support of a causal relationship between cannabis use and educational attainment: a two-sample Mendelian randomization study of European ancestry
https://pubmed.ncbi.nlm.nih.gov/36465060/

In an observational study from German pain clinics utilizing medical cannabis, using the DSM criteria led to an overestimation of cannabis use disorder while the physicians underestimated the amount of cannabis use disorder
Cannabis use disorder in chronic pain patients: over- and underestimation in a cross-sectional observational study in three German pain management centres
https://pubmed.ncbi.nlm.nih.gov/36327134

On the risks of delta-8 THC – though really, it’s just that we don’t know much about it…
The Rise and Risk of Delta-8 THC (Delta-8-Tetrahydrocannabinol)
https://link.springer.com/article/10.1007/s40429-022-00456-1
and the impurities found in delta-8 THC products
Delta-8 Tetrahydrocannabinol Product Impurities
https://pubmed.ncbi.nlm.nih.gov/36296514

A safety report on hexahydrocannabinol finds it's safe for the heart & liver,
Nonclinical In Vitro Safety Assesment Summary of Hemp Derived (R/S)-Hexahydrocannabinol ((R/S)-HHC)
https://assets.researchsquare.com/files/rs-2299264/v1/f59956a1-02bf-4aae-8f9c-479014d7666d.pdf
researchers discovering it in hemp,
Hexahydrocannabinol on the Light Cannabis Market: The Latest "New" Entry
https://pubmed.ncbi.nlm.nih.gov/36445181
and an analysis of its chemical cousins
Characterization of Hexahydrocannabinol (HHC) Diastereomers, and Hexahydrocannabidiol (H4CBD) Diastereomers Using NMR, HPLC, and GC-MS
https://assets.researchsquare.com/files/rs-2322468/v1/8b705746-d41f-4f81-afc9-0afbc72bd770.pdf

A case report of a young man’s death from jumping off a roof after ingesting 5F-MDMB-P7AICA
'Flying high?'-Jump from a height in a 'Spice' high?: A case report on the synthetic cannabinoid 5F-MDMB-P7AICA
https://pubmed.ncbi.nlm.nih.gov/36415074

A book chapter looking at the neuroimaging of brains on synthetic cannabinoids
Synthetic Cannabinoids
https://link.springer.com/chapter/10.1007/978-3-031-08774-5_5

2021: On the challenge that synthetic cannabinoids pose for forensic chemists trying to figure out which drugs are in people's systems
Synthetic Cannabinomimetics: A Brief History and the Challenges They Pose for the Forensic Chemist
https://www.publish.csiro.au/CH/CH20322

2021: In a genetic study of those with synthetic cannabinoid use disorder, the gene NR3C1 was found to be methylated (turned off)
Global and glucocorticoid receptor gene-specific (NR3C1) DNA methylation analysis in patients with cannabinoid or synthetic cannabinoid use disorder
https://pubmed.ncbi.nlm.nih.gov/33556690

2021: In zebrafish, how the synthetic cannabinoid 5F-APINAC alters metabolism & causes embryo problems
Short- and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish
https://pubmed.ncbi.nlm.nih.gov/33561556

How five of the synthetic cannabinoids alter behaviors in rats
Behavioral pharmacology of five novel synthetic cannabinoids
https://pubmed.ncbi.nlm.nih.gov/33595956

2021: On the intoxication effects of the synthetic cannabinoid JWH-O18
Intoxication by a synthetic cannabinoid (JWH-018) causes cognitive and psychomotor impairment in recreational cannabis users
https://pubmed.ncbi.nlm.nih.gov/33497715

In mice, the synthetic cannabinoid JWH- 073 causes decreased motor activity & visual responses while altering memory function for up to 24 hours
Synthetic cannabinoid JWH-073 alters both acute behavior and in vivo/vitro electrophysiological responses in mice
https://pubmed.ncbi.nlm.nih.gov/36339851

Liver & Drug Interactions

A review of the potential drug interactions with the cannabinoids
Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy
https://pubmed.ncbi.nlm.nih.gov/36384377

A rare case report of heavy cannabis use leading to acute hepatitis (liver inflammation)
Marijuana-Induced Acute Hepatitis: A Case Report
https://pubmed.ncbi.nlm.nih.gov/36381892/

For liver transplants, this review suggests it’s time to end the discrimination against cannabis users
Review of liver transplantation candidacy and outcomes among patients who use cannabis: Is it time for a change in policy?
https://canlivj.utpjournals.press/doi/full/10.3138/canlivj-2022-0038

In mice, cannabinoids protected from alcohol’s toxic effects on the liver
Cannabinoids inhibit ethanol-induced activation of liver toxicity in rats through JNK/ERK/MAPK signaling pathways
https://pubmed.ncbi.nlm.nih.gov/36453646/

In a mouse model of fatty liver disease & diabetes, injecting special nanoparticles filled with rimonabant (the first CB1 blocking drug) worked well for treatment & did not cause the associated negative changes in other parts of the body
Hepatic targeting of the centrally active cannabinoid 1 receptor (CB1R) blocker rimonabant via PLGA nanoparticles for treating fatty liver disease and diabetes
https://pubmed.ncbi.nlm.nih.gov/36442615

In a mouse model of liver injury, β-caryophyllene reduced inflammation, oxidative stress & markers of injury
β-caryophyllene ameliorates hepatic ischemia reperfusion-induced injury: the involvement of Keap1/Nrf2/HO 1/NQO 1 and TLR4/NF-κB/NLRP3 signaling pathways
https://pubmed.ncbi.nlm.nih.gov/36459036

In liver cells, a comparison of how CBD & THC breakdown into their metabolites
Comparative Metabolomic Profiling of the Metabolic Differences of Δ9-Tetrahydrocannabinol and Cannabidiol
https://pubmed.ncbi.nlm.nih.gov/36364400

Lungs & Vaping

Cannabis smokers had more emphysema than tobacco smokers
Emphysema More Common in Marijuana Smokers Than Cigarette Smokers
https://www.proquest.com/openview/613792851723db12ddcf68735e597653/1

In lung cells, anandamide causes airway relaxation via prostaglandin E2 production
The endocannabinoid anandamide is an airway relaxant in health and disease
https://pubmed.ncbi.nlm.nih.gov/36396957

Pain, Inflammation & Surgeries

A case study of using THC & CBD on a patient with complex pain
Integration of Cannabis Extract Tetrahydrocannabinol:Cannabidiol in an Interdisciplinary Therapy Setting: A Case of Chronic Multilocular Pain Disorder
https://pubmed.ncbi.nlm.nih.gov/36467780

In a review of eight trials on chronic pain, cannabinoids improved sleep quality & reduced daily pain scores
Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials
https://rapm.bmj.com/content/early/2022/12/04/rapm-2021-103431.abstract

For nociplastic pain such as fibromyalgia, consider cannabinoids
Consider cannabinoids as an individual therapeutic trial in nociplastic pain
https://link.springer.com/article/10.1007/s40267-022-00954-2

In patients getting endoscopic surgery, cannabinoid use was associated with the need for higher levels of sedation
Baseline Cannabinoid Use Is Associated with Increased Sedation Requirements for Outpatient Endoscopy
https://pubmed.ncbi.nlm.nih.gov/36269560

In Canadian spine surgery patients, cannabis use before or after surgery did not alter their pain or disability scores
PREOPERATIVE CANNABIS USE IN CANADIAN THORACOLUMBAR SPINE SURGERY PATIENTS: A CSORN STUDY
https://online.boneandjoint.org.uk/doi/abs/10.1302/1358-992X.2022.12.063

In humans with different types of facial pain & headache disorders, the levels of endocannabinoids like PEA, 2-AG & anandamide in their saliva could be used as diagnostic tools
Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management
https://pubmed.ncbi.nlm.nih.gov/36361803

In Danish patients with hard-to-treat chronic pain, oral cannabinoids were safe & helped with some of their pain - THC & CBD worked better together
Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain-A retrospective observational real-world study
https://pubmed.ncbi.nlm.nih.gov/36394124

In chronic pain patients taking a lot of medications, a look at the potential adverse events when adding medical cannabis
Medicinal cannabis for patients with chronic non-cancer pain: analysis of safety and concomitant medications
https://pubmed.ncbi.nlm.nih.gov/36445409

A living review of 20+ studies on cannabinoids & chronic pain
Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: 2022 Update
https://www.ncbi.nlm.nih.gov/books/NBK586045

In humans getting hip replacement surgery, having a certain genetic variant of their CB1 receptor did not alter their pain levels
Lack of Association between (AAT)n Polymorphism of the CNR1 Gene Encoding the Cannabinoid Receptor (CB1) and Patient's Quality of Life
https://pubmed.ncbi.nlm.nih.gov/36360283

In female rats, inhaling high CBD cannabis vapor reduces their reward from opioids & caused painkilling effects
High-CBD Cannabis Vapor Attenuates Opioid Reward and Partially Modulates Nociception in Female Rats
https://www.sciencedirect.com/science/article/pii/S2772392522000451

In a rat model of neuropathic pain, electrical brain stimulation created painkilling via the opioids & endocannabinoids
Electrical stimulation of the posterior insular cortex induces opioid and cannabinoid-dependent antinociception and regulates glial cells in the spinal cord
https://www.scielo.br/j/brjp/a/GVw6yTfC9RB3jdSChXfCbjr

In a mouse model of pain, a new drug that activates both opioid & cannabinoid receptors produces potent painkilling with fewer side effects
OCP002, a Mixed Agonist of Opioid and Cannabinoid Receptors, Produces Potent Antinociception With Minimized Side Effects
https://journals.lww.com/anesthesia-analgesia/Abstract/9900/OCP002,_a_Mixed_Agonist_of_Opioid_and_Cannabinoid.467.aspx

To create a new animal model for headaches, these researchers suggest a rat with inhibited DAGL enzyme that produces less 2-AG
Inhibition of diacylglycerol lipase alpha (DAGLα) as a model for episodic headache in rats: Features and applications
https://www.sciencedirect.com/science/article/pii/B9780323898331000380

The Immune System, Autoimmune Disorders & Pathogens

A review of CBD for modulating the immune system
Cannabinoids as Immune System Modulators: Cannabidiol Potential Therapeutic Approaches and Limitations
https://pubmed.ncbi.nlm.nih.gov/36413346
“Findings suggest that CBD is a potent immunomodulatory drug as it has manifested immunosuppressive properties in the context of sterile inflammation (e.g., inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases), and immunoprotective effects during viral infections (e.g. COVID-19) Similarly, CBD has exhibited a selective response toward cancer types by engaging different targets and signaling pathways. These results are in favor of the primary function of the endocannabinoid system which is homeostatic maintenance.”

A well-done presentation for physicians on cannabis use & HIV
MEDICAL MARIJUANA: WHAT HIV PROVIDERS NEED TO KNOW
https://acthiv.org/wp-content/uploads/2022/05/Medical-Marijuana-What-HIV-Providers-Need-to-Know.pdf

Against salmonella, using CBD-rich extracts to enhance the anti-bacterial activity of broad-spectrum antibiotics
Cannabis sativa CBD Extract Exhibits Synergy with Broad-Spectrum Antibiotics against Salmonella enterica subsp. Enterica serovar typhimurium
https://pubmed.ncbi.nlm.nih.gov/36557613

In computer simulations of the virus causing COVID-19, luteolin, CBGVA & CBNA were the top cannabis components for binding to the virus
Analysis and Identification of Bioactive Compounds of Cannabinoids in Silico for Inhibition of SARS-CoV-2 and SARS-CoV
https://www.mdpi.com/2218-273X/12/12/1729

A computer simulation finds cannabis has potential for inhibiting the parasite leishmania
Inhibiting Human and Leishmania Arginases Using Cannabis sativa as a Potential Therapy for Cutaneous Leishmaniasis: A Molecular Docking Study
https://www.mdpi.com/2414-6366/7/12/400

The Guts, the Microbiome & Oral Health

A review of the potential of CBD for dentistry
Cannabidiol, the Journey of Cannabis from a Social Stigma to a Miracle Drug in Dentistry
http://journaleprints.uk/id/eprint/12/1/1083-Article%20Text-2090-1-10-20221012.pdf
and an even bigger review of CBD for dentistry
Cannabidiol in Dentistry: A Scoping Review
https://pubmed.ncbi.nlm.nih.gov/36286003

2021: In a small study of cannabis smokers, their only difference in dental exams was more bleeding on probing
Effect of non-surgical therapy on periodontal clinical parameters in patients using cannabis
https://www.scielo.sa.cr/scielo.php?pid=S2215-34702021000100312&script=sci_arttext&tlng=en

In a mouse model of diabetes, CBD lowered blood sugar
Analysis of hypoglycaemic effects of cannabidiol following oral and intraperitoneal administration in healthy rats
http://cmapseec.mfd.org.mk/wp-content/uploads/2022/09/S2PP11.pdf
and in a rat model of diabetes, cannabis helped to restore glucose & lipid homeostasis
Effect of oral cannabis administration on the fat depots of obese and streptozotocin-induced diabetic rats
https://pubmed.ncbi.nlm.nih.gov/36437580

In a mouse model of obesity, deleting the CB1 receptors from the dopamine neurons of the sympathetic nervous protected from weight gain & decreased hormonal activity
Cannabinoid CB1 Receptor Deletion from Catecholaminergic Neurons Protects from Diet-Induced Obesity
https://pubmed.ncbi.nlm.nih.gov/36293486

In female mice, the terpene β-caryophyllene lessened their seeking of sweetened food via the CB2 receptor
β-caryophyllene, a cannabinoid receptor 2 agonist, decreases the motivational salience and conditioning place preference for palatable food in female mice
https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.13249

In roundworms, 2-AG activates the insulin pathway to stimulate the creation of cholesterol
Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans
https://pubmed.ncbi.nlm.nih.gov/36346800

2021: A regulator of neurometabolic function called carnitine palmitoyltransferase 1C negatively regulates ABHD6 (an endocannabinoid transporter) in the hypothalamus (feeding center of the brain) & thus controls 2-AG signaling & fasting behavior
Carnitine palmitoyltransferase 1C negatively regulates the endocannabinoid hydrolase ABHD6 in mice, depending on nutritional status
https://pubmed.ncbi.nlm.nih.gov/33444462

The Heart & the Blood

In humans with sickle cell disease, while their medical cannabis prescription status did not alter their hospital use, almost half of them chose to be recertified for medical cannabis because they perceived it as beneficial
Effects of Medical Cannabis Certification on Hospital Use by Individuals with Sickle Cell Disease
https://pubmed.ncbi.nlm.nih.gov/36413342

In a survey of humans with sickle cell disease, the ones using medical marijuana preferred inhalation methods while those without a prescription preferred ingestibles
Perception of Marijuana Use, Risk/Benefits in Sickle Cell Disease
https://ashpublications.org/blood/article/140/Supplement%201/5039/491341

In a mouse model of sickle cell disease, CBD lessened the chronic & acute pain by decreasing inflammation & oxidative stress
Cannabidiol Attenuates Chronic and Acute Hyperalgesia in Sickle Mice By Reducing Inflammation and Oxidative Stress
https://ashpublications.org/blood/article/140/Supplement%201/8226/488015

In a mouse model of hemophilia, PEA helped with pain & the symptoms of arthritis such as joint inflammation
Palmitoylethanolamide Attenuates Pain-like Behavior in Factor VIII Deficient Mice
https://ashpublications.org/blood/article/140/Supplement%201/5578/492940

A genome-wide study found a weak association between cannabis use disorder & cardiovascular diseases
Association of cannabis use disorder with cardiovascular diseases: A two-sample Mendelian randomization study
https://pubmed.ncbi.nlm.nih.gov/36277767

In a mouse model of heart attack, not having enough FAAH enzyme leads to worse results, potentially via the PPAR nuclear receptors (controllers of genetic transcription)
Fatty Acid Amide Hydrolase Deficiency Is Associated with Deleterious Cardiac Effects after Myocardial Ischemia and Reperfusion in Mice
https://pubmed.ncbi.nlm.nih.gov/36293543

In a mouse model of arrhythmia, activating the CB2 receptor for 21 days protected against oxidative stress & atrial fibrillation (an irregular heartbeat)
Activation of cannabinoid receptor 2 attenuates Angiotensin II-induced atrial fibrillation via a potential NOX/CaMKII mechanism
https://pubmed.ncbi.nlm.nih.gov/36312282

The Muscles & Bones

A big review on how CBD may help with muscle recovery via its effects on skeletal muscle metabolism, inflammation & tissue regeneration
Molecular Mechanisms Through Which Cannabidiol May Affect Skeletal Muscle Metabolism, Inflammation, Tissue Regeneration, and Anabolism: A Narrative Review
https://pubmed.ncbi.nlm.nih.gov/36454174/

A review of studies finds 29 studies confirming the efficacy of cannabinoids for osteoporosis
Examining the role of cannabinoids on osteoporosis: a review
https://pubmed.ncbi.nlm.nih.gov/36401719

In a mouse model of osteoarthritis, activating the CB2 receptor decreased pain & improved markers of cartilage degradation
The Impact of JWH-133 on Articular Cartilage Regeneration in Osteoarthritis Via Metalloproteinase 13-Dependent Mechanism
https://pubmed.ncbi.nlm.nih.gov/36318796

In a mouse model of osteoporosis, inhibition of the FAA H enzyme (a function of CBD) causes more bone growth
Inhibition of FAAH suppresses RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss partially through repressing the IL17 pathway
https://pubmed.ncbi.nlm.nih.gov/36468880/

The Skin

The excellent Tanja Bagar on the cannabinoids in the skin
https://www.fundacion-canna.es/en/cannabinoids-and-skin

In mice with scarring on their skin & livers, injected CBD lessened scarring & in the model of non-alcohol liver fibrosis, reduced infiltration by immune cells
Cannabidiol markedly alleviates skin and liver fibrosis
https://pubmed.ncbi.nlm.nih.gov/36339540

The Eyes

The intensity of cannabis use is correlated with retinal anomalies & this can be reduced by the reduction of cannabis use
Variations of retinal dysfunctions with the level of cannabis use in regular users: Toward a better understanding of cannabis use pathophysiology
https://pubmed.ncbi.nlm.nih.gov/36465284/

Hormones, Reproduction & Maternal Effects

In a Canadian review of public health data, “prenatal cannabis use increases the likelihood of preterm birth, low birth weight, small-for-gestational age and major congenital anomalies” with the effects stronger for female infants
Cannabis use in pregnancy and maternal and infant outcomes: A Canadian cross-jurisdictional population-based cohort study
https://pubmed.ncbi.nlm.nih.gov/36417349

An epidemiological study finds a link between prenatal cannabis exposure & Down syndrome
Socioeconomic, Ethnocultural, Substance- and Cannabinoid-Related Epidemiology of Down Syndrome USA 1986-2016: Combined Geotemporospatial and Causal Inference Investigation
https://pubmed.ncbi.nlm.nih.gov/36293924

2021: A review of the negatives of prenatal exposure to THC
Prenatal Cannabinoid Exposure: Emerging Evidence of Physiological and Neuropsychiatric Abnormalities
https://pubmed.ncbi.nlm.nih.gov/33519564
“Despite these limitations [of this review], prenatal cannabis exposure has been linked to low birth weight, and emerging evidence suggests that prenatal exposure to Δ9-THC, which crosses the placenta and impacts placental development, may have wide-ranging physiological and neurodevelopmental consequences.”

2021: In breastfeeding mothers, THC & CBD were found to accumulate in the breast milk
Cannabis use and measurement of cannabinoids in plasma and breast milk of breastfeeding mothers
https://pubmed.ncbi.nlm.nih.gov/33469174

2020: A case series of 3 patients with cannabinoid hyperemesis syndrome during pregnancy
HYPEREMESIS CANNABINOID SYNDROME IN PREGNANCY: A CASE SERIES
https://www.eventscribe.com/2020/CLP/fsPopup.asp?efp=VEtETlZaQUwxMTgwMw&PosterID=307534&rnd=0.4361652&mode=posterinfo

In a mouse & tissue model of endometriosis, an activator of the CB1 receptor reduced cell proliferation, blood vessel growth & reduced pain stimuli
Synthetic Cannabinoid Agonist WIN 55212-2 Targets Proliferation, Angiogenesis, and Apoptosis via MAPK/AKT Signaling in Human Endometriotic Cell Lines and a Murine Model of Endometriosis
https://pubmed.ncbi.nlm.nih.gov/36304004

In a rhesus monkey, how prenatal exposure to THC causes problems in placental function & development of the infant
Chronic prenatal delta-9-tetrahydrocannabinol exposure adversely impacts placental function and development in a rhesus macaque model
https://pubmed.ncbi.nlm.nih.gov/36424495

2021: Hedgehog proteins are some of the most important regulators of development & it turns out that the endocannabinoids act as inhibitors of them
Endocannabinoids are conserved inhibitors of the Hedgehog pathway
https://www.pnas.org/doi/10.1073/pnas.1416463112

2020: In male mouse reproductive cells, the endocrine disruptor bisphenol A also caused endocannabinoid disruption
Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production
https://pubmed.ncbi.nlm.nih.gov/33256105

2021: On the presence of CB1 & CB2 receptors in various reproductive disorders
Immunohistochemical investigation of cannabinoid receptor 1 and 2 expression in placentas with intrauterine growth retardation, placenta previa and preeclampsia
https://www.researchgate.net/profile/Firat-Asir/publication/348563979_Immunohistochemical_investigation_of_cannabinoid_receptor_1_and_2_expression_in_placentas_with_intrauterine_growth_retardation_placenta_previa_and_preeclampsia/links/60051e3c92851c13fe1be49e/Immunohistochemical-investigation-of-cannabinoid-receptor-1-and-2-expression-in-placentas-with-intrauterine-growth-retardation-placenta-previa-and-preeclampsia.pdf

2021: In zebrafish embryos, THC exposure reduced neural activity while CBD did so even more strongly & the effect was more pronounced when CBD & THC were combined, seemingly mediated by the CB1 & CB2 receptors
Embryonic exposure to cannabidiol disrupts active neural circuits, an effect increased by Δ□-tetrahydrocannabinol and involving CB1R and CB2R in zebrafish
https://www.biorxiv.org/content/10.1101/2021.01.04.425279v1

Cancer & Chemo

Interviews with cancer survivors highlight their experiences of medical cannabis-related stigma
Medical cannabis-related stigma: cancer survivors' perspectives
https://pubmed.ncbi.nlm.nih.gov/36435953

A study of public health data finds that in humans with a new cancer diagnosis, legalizing medical cannabis in their state led to a lower rate of dispensing opioids & pain related hospital events
Medical Marijuana Legalization and Opioid- and Pain-Related Outcomes Among Patients Newly Diagnosed With Cancer Receiving Anticancer Treatment
https://pubmed.ncbi.nlm.nih.gov/36454553/

A large survey of cancer survivors found that those with high-impact chronic pain were more likely to be using cannabis & to believe in its benefits
Cannabis in Cancer Survivors Who Report High Impact Chronic Pain: Findings from a 1500+ Patient Survey
https://pubmed.ncbi.nlm.nih.gov/36469631/

A review of using CBD to improve the quality of life in cancer patients
Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges
https://pubmed.ncbi.nlm.nih.gov/36361743

In humans with advanced cancer, 400 mg of CBD did not help measures of quality of life, depression, or anxiety
Phase IIb Randomized, Placebo-Controlled, Dose-Escalating, Double-Blind Study of Cannabidiol Oil for the Relief of Symptoms in Advanced Cancer (MedCan1-CBD)
https://pubmed.ncbi.nlm.nih.gov/36409969

A review of using the cannabinoids to treat cancer as well as the symptoms of cancer treatments
Use of Cannabis and Cannabinoids for Treatment of Cancer
https://pubmed.ncbi.nlm.nih.gov/36291926

A review of the mechanisms cannabinoids use against cancer
Cannabinoids as Prospective Anti-Cancer Drugs: Mechanism of Action in Healthy and Cancer Cells
https://pubmed.ncbi.nlm.nih.gov/36396926

For pediatric cancer, a review of using cannabis to treat symptoms
Medical cannabis for symptom management in children with cancer: A systematic literature review and meta-analysis
https://chrdmb.ca/wp-content/uploads/2022/10/Manik-Chhabra_Medical-cannabis-for-symptom-management-in-children-with-cancer-A-systematic-literature-review-and-meta-analysis.pdf

For lung cancer, a review of using CBD to kill the cancer cells themselves
Antitumorigenic Effect of Cannabidiol in Lung Cancer: What Do We Know So Far?-A Mini Review
https://pubmed.ncbi.nlm.nih.gov/36437760

In lung cancer patients, higher levels of CB2 receptors in the tumor tissue are strongly associated with longer survival & less metastatic spread to the lymph nodes
Cannabinoid receptor 2 expression in early-stage non-small cell lung cancers identifies patients with good prognosis and longer survival
https://pubmed.ncbi.nlm.nih.gov/36386452/

No link found between cannabis smoking & bladder cancer
Smoking Behaviors and Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer in the Be-Well Study
https://pubmed.ncbi.nlm.nih.gov/36449286

In mice with the aggressive cancer cholangiocarcinoma (bile duct cancer), the antitumor effects of using THC & CBN
Antitumor Effects of Delta (9)-Tetrahydrocannabinol and Cannabinol on Cholangiocarcinoma Cells and Xenograft Mouse Models
https://pubmed.ncbi.nlm.nih.gov/36452140

2021: In a mouse model of these two types of brain tumors, CBD & THC did cause cancer cell death but did not lead to increased survival times
Assessment of Cannabidiol and Δ9-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma
https://pubmed.ncbi.nlm.nih.gov/33477420

In cells of glioblastoma (the most aggressive brain tumor), extracts of cannabis caused significant antitumor effects
Cannabis sativa ethanolic extract demonstrated significant anti-tumor effects associated with elevated expression of AXIN1 protein in glioblastoma U87-MG cell line
https://www.sciencedirect.com/science/article/pii/S2452014422002230

In ovarian cancer cells, how combinations of THC, CBC & CBG act to cause apoptosis (cellular suicide) via the Wnt pathway
Phytocannabinoid Compositions from Cannabis Act Synergistically with PARP1 Inhibitor against Ovarian Cancer Cells In Vitro and Affect the Wnt Signaling Pathway
https://pubmed.ncbi.nlm.nih.gov/36364346

In colorectal cancer cells, the cannabinoids caused toxic effects
Selective Cytotoxicity of Medical Cannabis ( Cannabis sativa L.) Extracts Across the Whole Vegetation Cycle Under Various Hydroponic and Nutritional Treatments
https://pubmed.ncbi.nlm.nih.gov/36459627/

And cannabis extracts inhibited their spread to the lungs
Supercritical Extract of Cannabis sativa Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest
https://pubmed.ncbi.nlm.nih.gov/36364815

Using nano-cannabis balls against cancer
Preparation and characterization of full-spectrum cannabis extract loaded poly(thioether-ester) nanoparticles: In vitro evaluation of their antitumoral efficacy
https://www.sciencedirect.com/science/article/abs/pii/S0927775722024311
The science animation of this one involves Rambo, cluster bombs & the wicked ogre cancer cells going up in flames.

Cool Chemistry

A review of synthetic biology approaches for producing cannabinoids
Current status and future prospects in cannabinoid production through in vitro culture and synthetic biology
https://pubmed.ncbi.nlm.nih.gov/36481387/

In various types of fats & oils, the presence of CBD delayed their crystallization
Crystallization behavior of milk fat, palm oil, palm kernel oil, and cocoa butter with and without the addition of cannabidiol
https://aocs.onlinelibrary.wiley.com/doi/abs/10.1002/aocs.12667

A review of the wild new tools for targeting the endocannabinoid system
Recent Advances in Endocannabinoid System Targeting for Improved Specificity: Strategic Approaches to Targeted Drug Delivery
https://pubmed.ncbi.nlm.nih.gov/36362014

How the various testing techniques may alter cannabinoid content because of degradation by heat
Effect of temperature in the degradation of cannabinoids: From a brief residence in the gas chromatography inlet port to a longer period in thermal treatments
https://pubmed.ncbi.nlm.nih.gov/36385981/

An analysis of two PAMS (positive allosteric modulators of CB1 – a function of CBD – where the power of other molecules to bind CB1 is strengthened)
Pharmacological evaluation of enantiomerically separated positive allosteric modulators of cannabinoid 1 receptor, GAT591 and GAT593v
https://pubmed.ncbi.nlm.nih.gov/36386195/

Using amoeba to produce the cannabinoid precursor olivetolic acid
Scale-up of an amoeba-based process for the production of the cannabinoid precursor olivetolic acid
https://pubmed.ncbi.nlm.nih.gov/36266656

A 3D gelatin scaffold loaded with cannabis extract for treating soft tissues
Design of a New 3D Gelatin-Alginate Scaffold Loaded with Cannabis sativa Oil
https://pubmed.ncbi.nlm.nih.gov/36365500

Using a nano-emulsion of cannabis for delivery via the mucous membranes of the mouth
Transmucosal delivery of the medical Cannabis oil via a nanoemulsion formulation
https://www.sciencedirect.com/science/article/abs/pii/S1773224722009157
And making CBD balls for treating neurodegenerative diseases
Formulation of Nanomicelles Loaded with Cannabidiol as a Platform for Neuroprotective Therapy
https://www.mdpi.com/1999-4923/14/12/2625

Using cabbage molecules to create drugs that activate CB2
Design, synthesis, and structure-activity relationships of diindolylmethane derivatives as cannabinoid CB2 receptor agonists
https://pubmed.ncbi.nlm.nih.gov/36437108

A new cannabinoid binding pocket found on the TRPV2 receptors
Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function
https://pubmed.ncbi.nlm.nih.gov/36470868/

A computer analysis of how these inhibitors of MGL work to raise 2AG levels
Insight into the Inhibitory Mechanism of Aryl Formyl Piperidine Derivatives on Monoacylglycerol Lipase through Molecular Dynamics Simulations
https://pubmed.ncbi.nlm.nih.gov/36364337

Creating new FAAH inhibitors to treat neuroinflammation
Development of potent and selective FAAH inhibitors with improved drug-like properties as potential tools to treat neuroinflammatory conditions
https://pubmed.ncbi.nlm.nih.gov/36462439
the bumper sticker: Stop the Squids to Save the Whales!
(see Neural Ocean metaphor below)

Thanks.

- lex

PS: For this week’s album, the smoothest crooner Johnny Hartman & his big album with Coltrane: ‘John Coltrane And Johnny Hartman’

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#38: Importance of terpenes …