Hello everyone,

I hope your new year is off to a great start.

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, social media content, newsletters & podcasts.
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In my EU segment for Pro Cannabis Media, they gave me the lead!

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This week…

My first educational video of the year: the 2-minute guide to CBD & THC.
When my family members ask, this is what I tell them.
Clinicals on cannabis & cannabinoids for sleep, PTSD, musculoskeletal pain, dementia, migraines, fibromyalgia, arthritis, scleroderma, colitis & COVID-19 (what are you waiting for?)
Cannabis use may cause strokes to do less damage to you
The cannabinoids & cancer: it’s a steady half-dozen studies a week. Why aren’t we using them more?
Does drug use go down during Ramadan? Let’s head to the sewage plant to find out!
How the endocannabinoids help us see
One R&B Easter Egg
Cannabis extract to save honeybee babies
Worldwide survey on why people are growing cannabis
Cannabinoids for lung inflammation – but also maybe causing problems
#genderisweird – bones edition
More negatives on cannabis use during pregnancy (I wish it wasn’t true – but it is)
More crazy industrial uses of hemp: magnetic biocomposite?
New word: dankruptcy
In chemistry news, everybody wants to activate the CB2 receptor
And to their detriment, parrots do not have a CB2 receptor
I must say, an especially great music selection this week

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Sponsor: PlusCBD & a commitment to education & research

One sign of a great CBD company is when they go to the next level to educate their customers. PlusCBD has articles for all levels of knowledge, videos about how CBD works & a YouTube channel of great educational content.
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In addition, they’ve done more peer-reviewed research than any other company other there. They put their money down to advance the field.

Check out this (partial) bibliography:

A GRAS (Generally Recognized as Safe) study on hemp extracts to prove their safety
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And funding me to create the extensive cannabinoid science archive at CVResearch.info

PlusCBD takes their commitment to education & research to the next level. And they do the same with their products.

Buy excellent CBD products today from PlusCBDoil.com.

Best Of Cannabinoid Science...

The story of a pediatric brain tumor shrunk by cannabis oil, natural killer immune cells & probiotics (by the excellent David Hodes)
A Mother’s Hope: Cannabinoids Helping Kill Cancer Cells
https://www.cannapatientcare.com/view/a-mothers-hope-cannabinoids-helping-kill-cancer-cells

A beautiful set of visuals on the last 15 years of CBD research papers
A bibliometrics and visualization analysis of cannabidiol research from 2004 to 2021
https://pubmed.ncbi.nlm.nih.gov/36408229/

Clinical

In adults with insomnia, treatment with THC/CBD oil caused 60% of them to no longer qualify as insomniacs after two weeks with improvements including enhanced midnight melatonin levels, the time & quality of sleep & a higher daily functioning
Medicinal cannabis improves sleep in adults with insomnia: a randomised double-blind placebo-controlled crossover study
https://pubmed.ncbi.nlm.nih.gov/36539991/

In a medical record review of multiple sclerosis patients, starting medical cannabis caused extensive improvement in pain, sleep, spasticity & a decrease in opioid use
Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population
https://meridian.allenpress.com/ijmsc/article/doi/10.7224/1537-2073.2022-006/489178/Multiple-Sclerosis-and-Use-of-Medical-Cannabis-A

In a survey of Polish caregivers for dementia patients, they thought CBD oil safer & more effective than conventional methods
CBD Oil as a Miracle Drug: A Thematic Analysis of Caregivers’ Attitudes and Practices Towards Cannabidiol in Dementia Treatment
https://journals.sagepub.com/doi/full/10.1177/00220426221145019

In a review of the UK cannabis registry, those with PTSD using cannabinoids saw significant improvements in PTSD symptoms, sleep & anxiety
Assessment of clinical outcomes in patients with post-traumatic stress disorder: analysis from the UK Medical Cannabis Registry
https://pubmed.ncbi.nlm.nih.gov/36503404/

In women with treatment-resistant fibromyalgia, one month of cannabis improved their general quality of life, general health, physical health & psychological health
The role of cannabis in treatment-resistant fibromyalgia women
https://pubmed.ncbi.nlm.nih.gov/36333278/

In Australian patients with arthritis, the use of CBD/THC & CBD-only products significantly reduced pain intensity
Medicinal cannabis for Australian patients with chronic refractory pain including arthritis
https://journals.sagepub.com/doi/full/10.1177/20494637221147115

In patients with ulcers on their fingers from scleroderma (an autoimmune connective tissue & rheumatic disease that causes skin inflammation), topical CBD treatment caused lower pain scores, reduced painkiller use, higher health scores & an increase in total hours of sleep
Topical Cannabidiol in the Treatment of Digital Ulcers in Patients with Scleroderma: Comparative Analysis and Literature Review
https://pubmed.ncbi.nlm.nih.gov/36537770/

In public health data on patients with colitis, cannabis was associated with a lower average length of hospital stay & no increase in mortality or hospitalization cost
Impact of Marijuana in Ulcerative Colitis With Nstemi Hospitalizations: Insights From National Inpatient Sample 2016-2019.
https://journals.lww.com/ajg/Fulltext/2022/12001/S11_Impact_of_Marijuana_in_Ulcerative_Colitis_With.12.aspx

Using wastewater analysis, the first-ever study to show drug use drop during Ramadan
Monitoring of changes in illicit drugs, alcohol, and nicotine consumption during Ramadan via wastewater analysis
https://pubmed.ncbi.nlm.nih.gov/35851933/
Plus, an Islamic law perspective on medical cannabis
Medical Marijuana From Medicine, Legal And Islamic Law Perspective: A Review
https://uijournal.usim.edu.my/index.php/uij/article/view/495

Reviews

A review of how CBD may be helping neurodegenerative diseases via its effects on the gut microbiome
The gut microbiota in neurodegenerative diseases: revisiting possible therapeutic targets for cannabidiol
https://pubmed.ncbi.nlm.nih.gov/36544841/

Do CB2 receptors exist in the brain? Who the hell knows?!
Update on the controversial identity of cells expressing cnr2 gene in the nervous system
https://pubmed.ncbi.nlm.nih.gov/36604187/

For musculoskeletal pain, a review of using topical cannabinoids
Topical cannabinoids for the management of musculoskeletal pain: Understanding and review
https://www.researchgate.net/publication/366324080_Topical_cannabinoids_for_the_management_of_musculoskeletal_pain_Understanding_and_review

Because cannabinoids & sleep are never predictable, a large data analysis finds that daily cannabis use in middle-aged people (45-64) is linked to longer sleep while daily cannabis use in older people (65+) is linked to shorter sleep
Daily cannabis use is associated with sleep duration differentially across ages
https://pubmed.ncbi.nlm.nih.gov/36404265/

A review of nine clinical studies finds that cannabis significantly reduces the length & frequency of migraines
Efficacy and Safety of Medical Marijuana in Migraine Headache: A Systematic Review
https://www.cureus.com/articles/118190-efficacy-and-safety-of-medical-marijuana-in-migraine-headache-a-systematic-review

A review of all the reasons we might be using cannabinoids against COVID-19
Therapeutic Effects of Cannabinoids and Their Applications in COVID-19 Treatment
https://pubmed.ncbi.nlm.nih.gov/36556483/

A big review of CBG & the many things that it does
Pharmacological Aspects and Biological Effects of Cannabigerol and Its Synthetic Derivatives
https://pubmed.ncbi.nlm.nih.gov/36397993/

A review of how the development of neurons & immune cells in the central nervous system is guided by the endocannabinoid system with a special focus on neurodegenerative disorders
Modulatory Activity of the Endocannabinoid System in the Development and Proliferation of Cells in the CNS
https://pubmed.ncbi.nlm.nih.gov/36522511/

A review of how the cannabinoids control the mitochondria (powerhouse of the cell)
Cannabinoid-mediated targeting of mitochondria on the modulation of mitochondrial function and dynamics
https://pubmed.ncbi.nlm.nih.gov/36516885/

Preclinical

Statin drugs may be causing pain via the lowering of cannabinoid receptor genes
MicroRNA-mediated repression of endocannabinoid CB1 receptor expression contributes to simvastatininduced skeletal muscle toxicity
https://assets.researchsquare.com/files/rs-2328769/v1/117fed8a-bdeb-42af-91c1-b4453514f479.pdf
with an excellent writeup by Travis Cesarone
https://www.uprootedconcepts.com/post/statins-cause-pain-by-depleting-cannabinoid-receptor

For binding nerds, an in-depth look at how the various agonists, antagonists & inverse agonists bind to the cannabinoid receptors
Understanding the Dynamics of the Structural States of Cannabinoid Receptors and the Role of Different Modulators
https://pubmed.ncbi.nlm.nih.gov/36556502/

4 cannabinoid-like molecules found in the felted pepper face plant
Cannabinoid-like meroterpenoids from Peperomia incana
https://pubmed.ncbi.nlm.nih.gov/36509184/

For some reason, parrots do not have a CB2 receptor & this leaves them more susceptible to neuroinflammation
Cannabinoid receptor 2 evolutionary gene loss makes parrots more susceptible to neuroinflammation
https://pubmed.ncbi.nlm.nih.gov/36475439/

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

LinkedIn the best platform for cannabis information – and in that spirit, I’m going to spend more time there this year: Join me on LinkedIn
https://www.sfgate.com/cannabis/article/cannabis-industry-loves-linkedin-17683823.php

A deep dive on worker exploitation in the West Coast cannabis industry: 35 dead in 4 years & only one of those deaths investigated
https://www.latimes.com/california/story/2022-12-22/the-exploitation-violence-and-desperation-that-produces-the-pot-you-smoke-and-eat
Plus, a study of California cannabis workers found respiratory symptoms & rashes from exposure to cannabis, mold & pesticides as well as musculoskeletal pain from long shifts of repetitive tasks
California cannabis cultivation and processing workers: A qualitative analysis of physiological exposures and health effects
https://pubmed.ncbi.nlm.nih.gov/36398400/

You can watch the entire National Medical Cannabis Unity Conference online for free
https://www.asaunity.org/watch
These were some of the first cannabis conferences I ever attended & I found a wonderful community of medical cannabis activists. One of the key organizations that you can support is the organizer of this conference, Americans for Safe Access. They keep up the fight to ensure, as a wave of legalization & adult use sweeps the nation, that medical cannabis patients don’t lose access to safe, high-quality, untaxed medicine.

GW, maker of Epidiolex (pharmaceutical isolated CBD drug), sues a dozen competitors over patent infringement
https://www.marijuanamoment.net/pharma-company-behind-fda-approved-cbd-drug-sues-a-dozen-competitors-over-alleged-patent-infringement

I do love when gov’t agencies get feisty on Twitter: NJ calls NY’s rollout “cute” – and NY slaps back about how NJ is a center of corporate cannabis (later they delete the tweet. cowards)
https://www.marijuanamoment.net/new-york-and-new-jersey-marijuana-regulators-spar-on-twitter-over-which-states-legalization-plan-is-better

The War on Drugs & Prohibition

Cringe: The DEA releases a history of their badges
https://museum.dea.gov/video-archive/stories-from-the-collection-badge-molds
Arguably the most corrupt agency besides the Bureau of Prohibition, the Federal Bureau of Narcotics was a hotbed of racism, inept enforcement & getting in bed with smugglers, dealers & the Mob. The book to read is Valentine’s ‘The Strength of the Wolf: The Secret History of America's War on Drugs’.

A lawyer’s take on why medical cannabis patients deserve protection in federal housing by Andrea Steel & Lila Greiner
No Roof for Your Reefer! Medical Cannabis Tenants Need Patient Protections in Federally Assisted Housing
https://heinonline.org/HOL/LandingPage?handle=hein.journals/tortso24&div=26&id=&page=
When I was on the road, I heard this story all the time. Somebody's medical use of cannabis leading to an eviction that caused terrible hardships for the family. It is such a prohibitionist tragedy.

On the tricky business of insurance companies & claims involving cannabis by Lisa Pittman
Cannabis Coverage Issues
https://heinonline.org/HOL/LandingPage?handle=hein.journals/tortso24&div=29&id=&page=

On the legal headwinds of hemp by Christopher Strunk
Navigating Hemp's Legal Headwinds in 2022
https://heinonline.org/HOL/LandingPage?handle=hein.journals/tortso24&div=27&id=&page=

In legal states, people did less mixing of their cannabis with tobacco
Co-Use, Simultaneous Use, and Mixing of Cannabis and Tobacco: A Cross-national Comparison of Canada and the US by Cannabis Administration Type
https://www.preprints.org/manuscript/202212.0245/v1

A positive drug test for THC after 102 days of abstinence
Prolonged detection of cannabis in urine of a consumer in a Forensic hospital, Victoria, Australia, up to 102 days of abstinence - A case report
https://www.sciencedirect.com/science/article/pii/S2773021222000815

A police dog (perhaps) dies from exposure to a new synthetic cannabinoid
New synthetic cannabinoid ADB-BUTINACA related death of a police dog
https://pubmed.ncbi.nlm.nih.gov/36472351/

Psychedelics, Plant Medicines & Other Psychoactives

On psychedelics & the neoliberal new world order by Erica Rex (a great writer)

The Brave New World of Psychedelic Science

THE CULTURE IS THE POISON

In the last decade, an entirely new kind of human has taken over the psychedelic scene. They could be not be more different from those I encountered when I took part in a clinical trial ten years ago at Johns Hopkins and from the movement’s primogenitors: to start with, María Sabina Magdalena García (the Mazatec cur…

3 months ago · 4 likes · Erica Rex, MA

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 newsletter with all the new psychedelic science would be of interest to your org, reach out to me]

A single dose of psilocybin helped with symptoms of major depression for two weeks
Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00538-7/fulltext

Business & Law

On how you might declare bankruptcy while being involved in the federally illegal cannabis industry
Declaring Dankruptcy: Exploring Avenues to Relief for Debtors Involved With Cannabis
https://scholarship.law.uc.edu/cgi/viewcontent.cgi?article=1470&context=uclr

A thesis comparing intellectual property protections for cannabis in the US versus the EU
Comparative Intellectual Property Protection for Marijuana: United States vs. The European Union
https://engagedscholarship.csuohio.edu/cgi/viewcontent.cgi?article=1108&context=gblr

A spatial network analysis on the tricky policies of limiting the pollination of high THC cannabis plants by hemp pollen
Adapting network theory for spatial network externalities in agriculture: A case study on hemp cross-pollination
https://onlinelibrary.wiley.com/doi/abs/10.1111/ajae.12359

The Plant & the History

A fascinating worldwide survey of why people are growing cannabis
Domestic Cannabis Cultivation Around the World: The GCCRC’s ICCQ 2.0
http://www.essd-research.eu/documents/ESSD%20presentations%202022/Gary%20Potter.pdf

In Italy, interviews on why people are growing their own cannabis
One for you, one for me: cannabis self-cultivation in Italy
https://www.tandfonline.com/doi/abs/10.1080/14659891.2022.2153757?journalCode=ijsu20
“The interviewees cultivated to obtain a better quality product, out of love for the marijuana plant, to save money, to alleviate health problems, for ethical reasons, to combat the narcomafia. One in three had sold marijuana to make a profit, to improve sociality, or out of solidarity.”

A review of how the terpenes are made, what they do & how they work well with the cannabinoids
Secondary Terpenes in Cannabis sativa L.: Synthesis and Synergy
https://pubmed.ncbi.nlm.nih.gov/36551898/

A review of phytoremediation: the removal of heavy metals from hemp plants
Phytoremediation: A Novel Approach of Bast Fiber Plants (Hemp, Kenaf, Jute and Flax) for Heavy Metals Decontamination in Soil—Review
https://www.mdpi.com/2305-6304/11/1/5

In hemp, how topping increases CBD content
Effect of Topping on Growth Development and CBD Content of Hemp (Cannabis sativa L.) in Pot Culture
https://www.researchgate.net/publication/366095286_Effect_of_Topping_on_Growth_Development_and_CBD_Content_of_Hemp_Cannabis_sativa_L_in_Pot_Culture

For large-scale cannabis micropropagation, how to best optimize mineral nutrition
Improvement of mineral nutrition and rooting efficiency of Cannabis sativa L. for in vitro large-scale propagation
https://link.springer.com/article/10.1007/s11627-022-10320-6

In the roots of hemp, examining their soil nutrients, enzyme activity & interactions with microbes during different stages of development
Changes in Rhizosphere Soil Nutrients, Enzyme Activities, and Microbial Communities at Different Stages of Industrial Hemp Development
https://www.mdpi.com/2073-4395/12/12/3159

Less dense sowing of cannabis leads to more biologically active compounds & to it being a better radical scavenger
The effect of sowing rate on the bioaccumulation of biologically active compounds and their radical scavenging activity in Cannabis sativa L
https://lmaleidykla.lt/ojs/index.php/chemija/article/view/4811

A look at how harvest time affects total CBD & THC concentrations
Evaluation of the Effect of Harvesting Time on Three Varieties of Industrial Hemp (Cannabis Sativa L)
https://www.researchgate.net/publication/364965096_Evaluation_of_the_Effect_of_Harvesting_Time_on_Three_Varieties_of_Industrial_Hemp_Cannabis_Sativa_L

On using RNA interference to protect cannabis from pests
Towards dsRNA-integrated protection of medical Cannabis crops: considering human safety, recent- and developing RNAi methods, and research inroads
https://pubmed.ncbi.nlm.nih.gov/36514999/

A study of the genes activated when hemp is exposed to salt during the germination stage
Genome-wide association study of salt tolerance at the germination stage in hemp
https://link.springer.com/article/10.1007/s10681-022-03129-2

Examining the cannabis genome for transcription factor B3 (related to seed growth, development & stress)
In Silico Genome-Wide Analysis of B3 Transcription Factors in Cannabis sativa L
https://pubmed.ncbi.nlm.nih.gov/36516081/

How to best preserve cannabis trichomes for deep looks by electron microscopes
Overcoming the challenges of preserving lipid-rich Cannabis sativa L. glandular trichomes for transmission electron microscopy
https://pubmed.ncbi.nlm.nih.gov/36542368/

Animal feed

In laying hens, hemp seed oil caused no negatives on egg production or quality & raised their yolk’s fatty acid content
A comparative study on the effects of hemp seed oil versus four different UFA-rich seed oils' dietary supplementation on egg production performance, egg quality, and yolk fatty acids in laying hens
https://pubmed.ncbi.nlm.nih.gov/36515767/

Industrial Use & Inventions

An analysis finds hemp not to be a sustainable energy resource
Is Hemp a Sustainable Energy Resource?
https://www.researchgate.net/profile/Astghik_Sukiasyan2/publication/366441765_Investigation_of_the_processes_occurring_in_water_of_acid_mine_drainage_during_their_exposure/links/63a1dd7d9835ef2590358f5c/Investigation-of-the-processes-occurring-in-water-of-acid-mine-drainage-during-their-exposure.pdf#page=136

On using hemp seed oil in a biodiesel fuel blend
RSM modeling of different amounts of nano-TiO2 supplementation to a diesel engine running with hemp seed oil biodiesel/diesel fuel blends
https://www.sciencedirect.com/science/article/abs/pii/S0360544222033254

On using hemp as a magnetic biocomposite
Investigation of capacitors and electrical circuit elements performance of magnetic biocomposites prepared by using the hemp biomass
https://www.sciencedirect.com/science/article/abs/pii/S0254058422014778

A review of hemp’s mechanical, thermal & acoustic properties
Mechanical, Thermal, and Acoustic Properties of Hemp and Biocomposite Materials: A Review
https://www.mdpi.com/2504-477X/6/12/373

Waste hemp found to be good at sound absorption
Structural Characteristics and Sound Absorption Properties of Waste Hemp Fiber
https://www.mdpi.com/2079-6412/12/12/1907
This might be every musician kid's dream: a recording studio covered in hemp & filled with grass.

Cannabinoid Science

Clinical Studies & Surveys

In Australia, doctors are becoming more & more supportive of prescribing cannabis
Knowledge, experiences, and attitudes of Australian General Practitioners towards medicinal cannabis: a 2021-2022 survey
https://pubmed.ncbi.nlm.nih.gov/36529730/
“While most GPs [general practitioners] (85.3%) had received patient enquiries about MC [medical cannabis] during the last three months, only half (52.3%) felt comfortable discussing MC with patients. Around one fifth (21.8%) had prescribed a MC product. GPs strongly supported MC prescribing for palliative care, cancer pain, chemotherapy-induced nausea and vomiting, and epilepsy, more so than in our 2017 survey. Prescribing for mental health conditions (e.g., depression, anxiety) and insomnia received less support. Opioids, benzodiazepines, and chemotherapy drugs were rated as more hazardous than MC.”

A review of 20 studies on the “day after” effects of THC reported most studies saw no next day effects but a few of the lower quality studies saw declines on cognitive function & safety-sensitive tasks
The "Next Day" Effects of Cannabis Use: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/36475998/

From the US National Poison Data system, a significant increase in pediatric exposure to CBD products
Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021
https://pubmed.ncbi.nlm.nih.gov/36537670/

Adolescents

In adolescents who drink heavily, they had lower levels of the FAAH enzyme in their brain & more hazardous drinking as well as a reduced sensitivity to the negative effects of alcohol
Association between Fatty Acid Amide Hydrolase and Alcohol Response Phenotypes: A PET Imaging Study with [11C]CURB in Heavy-drinking Youth
https://www.sciencedirect.com/science/article/abs/pii/S0006322322018042

In adolescents, a review of how cannabis use alters cognition & brain development
Impact of Adolescent Cannabis Use on Neurocognitive and Brain Development
https://pubmed.ncbi.nlm.nih.gov/36410904/

In adolescents, a review of how to treat cannabis use disorder
Treatment of Adolescent Cannabis Use Disorders
https://pubmed.ncbi.nlm.nih.gov/36410901/

A study of adolescents in Oregon & Washington found that proximity to a cannabis retailer did not increase their likelihood of cannabis use
Recreational Cannabis Legalization and Proximity to Cannabis Retailers as Risk Factors for Adolescents' Cannabis Use
https://pubmed.ncbi.nlm.nih.gov/36538207/

Ingestion Methods & Pharmacokinetics (how things bind & move)

Three clinical trials on how long a single oral dose of CBD stays in your blood
How long does a single oral dose of cannabidiol persist in plasma? Findings from three clinical trials
https://pubmed.ncbi.nlm.nih.gov/36478641/

A look at the relative contributions of the various liver enzymes that clear CBD from the body
Verifying in vitro-determined enzyme contributions to cannabidiol clearance for exposure predictions in human through physiologically-based pharmacokinetic modeling
https://pubmed.ncbi.nlm.nih.gov/36540909/
“Relative contributions of drug-metabolizing enzymes to CBD clearance were proposed from in vitro data: UGT1A7 4%, UGT1A9 16%, UGT2B7 10%, CYP3A4 38%, CYP2C19 21%, and CYP2C9 11%.”

Unsurprisingly, people's urine could test positive for CBD if they were consuming cannabis
Cannabidiol in urine is not a proof of CBD consumption-lesson learned from urine sample analysis in routine caseworks
https://pubmed.ncbi.nlm.nih.gov/36481827/

On using an implanted device for sustained low-level delivery of CBD into the body
Nanochannel delivery system for CBD: Sustained low level plasma levels without liver toxicity
https://www.sciencedirect.com/science/article/abs/pii/S1773224722009406

Mental Health, Addiction & Mental Effects

A review of how cannabinoids alter your brain’s resting state connectivity
Effects of cannabinoids on resting state functional brain connectivity: A systematic review
https://pubmed.ncbi.nlm.nih.gov/36563921/
“During THC and THCV exposure vs placebo reduced connectivity with the NAcc [nucleus accumbens - the neural interface between motivation & action] was widely reported. Limited evidence shows that such effects are offset by co-administration of CBD. NAcc-frontal region connectivity was associated with intoxication levels. Cannabis intoxication vs placebo was associated with lower striatal [movement & rewards]-ACC [anterior cingulate cortex – attention, reward, decision making & ethics]connectivity. CBD and CBDV vs placebo were associated with both higher and lower connectivity between striatal-prefrontal/other regions.”

In cannabis users with a genetic liability for schizophrenia, they had an increased likelihood of reporting unusual experiences
Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users
https://pubmed.ncbi.nlm.nih.gov/36545904/

In older Japanese women with depression, they had high ratios of anandamide levels in their blood compared to their intake of arachidonic acid
Elevated ratio of serum anandamide to arachidonic acid intake in community-dwelling women with high depressive symptoms
https://pubmed.ncbi.nlm.nih.gov/36179725/

In a rat model of PTSD, an ultra-low dose of THC reduced the fear response via the hippocampus (memory center)
Effects of delta-9 tetrahydrocannabinol on fear memory labilization and reconsolidation: A putative role of GluN2B-NMDA receptor within the dorsal hippocampus
https://pubmed.ncbi.nlm.nih.gov/36549374/

In a mouse model of schizophrenia, CBD did not work to prevent behavioral symptoms & may increase the brain’s sensitivity to behavioral problems caused by THC
The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia
https://pubmed.ncbi.nlm.nih.gov/36406747/
Take this one with an especially large grain of salt. Studying something as complex as schizophrenia in mice is fraught with peril.

In mice, a combination of CBD & celecoxib (a Cox-2 inhibitor & non-steroidal anti-inflammatory drug) caused effective antidepressant & anti-anxiety effects via the microglia (guardian immune cells of the brain)
A Novel Anti-Inflammatory Formulation Comprising Celecoxib and Cannabidiol Exerts Antidepressant and Anxiolytic Effects
https://pubmed.ncbi.nlm.nih.gov/36520610/

The Brain & its Diseases

A review of how the cannabinoids control the astroglia (specialized immune cells of the brain that regulate much of neuronal activity)
Astroglial cannabinoid signaling and behavior
https://pubmed.ncbi.nlm.nih.gov/35293647/

In rats with neuroinflammation, targeting both the FAAH enzyme & melatonin receptors lessened inflammation & caused neuroprotection
Combined targeting of fatty acid amide hydrolase and melatonin receptors promotes neuroprotection and stimulates inflammation resolution in rats
https://pubmed.ncbi.nlm.nih.gov/36526591/

In aging mice, the ability of estradiol (a major female estrogen steroid hormone) to modulate memory seems to be mediated by the CB1 receptor
Age-dependent effects of estradiol on temporal memory: A role for the type 1 cannabinoid receptor?
https://pubmed.ncbi.nlm.nih.gov/36521252/

In mice, deleting their CB1 receptor caused impaired social memory & increased aging in the hippocampus (memory center)
Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice
https://pubmed.ncbi.nlm.nih.gov/36613469/
“Our data indicate that a local activity of the CB1 receptor in the hippocampus is required to maintain neurogenesis and to prevent neuroinflammation and cognitive decline.”

In mice, how cannabinoids on dopamine neurons cause anti-anxiety effects & reduced locomotion
Cannabinoid CB1 Receptors Are Expressed in a Subset of Dopamine Neurons and Underlie Cannabinoid-Induced Aversion, Hypoactivity, and Anxiolytic Effects in Mice
https://pubmed.ncbi.nlm.nih.gov/36517243/

When neurons of the hippocampus (memory center) are exposed to high levels of THC, the astrocytes (protective immune cells) reduced cell death – but were themselves stressed
Resident Astrocytes can Limit Injury to Developing Hippocampal Neurons upon THC Exposure
https://pubmed.ncbi.nlm.nih.gov/36482034/

Epilepsy

In 34 young patients with drug-resistant epilepsies, a high proportion of them found CBD to remove their seizures completely & all saw a significant reduction in frequency, duration & type of seizures
A Pilot Study on the Use of Low Doses of CBD to Control Seizures in Rare and Severe Forms of Drug-Resistant Epilepsy
https://pubmed.ncbi.nlm.nih.gov/36556430/

In a long-term safety study of using CBD for epilepsy, it was found to be safe & it caused sustained seizure reductions for up to 192 weeks
Long-term efficacy and safety of cannabidiol in patients with treatment-resistant epilepsies: 4-year results from the expanded access program
https://pubmed.ncbi.nlm.nih.gov/36537757/

A review of health data from the UK found cannabinoid-based medicines to improve seizure frequency in treatment-resistant epilepsy
Clinical Outcome Data of Children Treated with Cannabis Based Medicinal Products for Treatment Resistant Epilepsy - Analysis from the UK Medical Cannabis Registry
https://pubmed.ncbi.nlm.nih.gov/36539215/

In epilepsy, CBD may help via its modulation of GABA (the brain’s primary inhibitory neurotransmitter) & in this study they found it combined well with two other epileptic medications (the neurosteroid ganaxolone & the benzodiazepine midazolam) that work via GABA as well
Isobolographic analysis of adjunct antiseizure activity of the FDA-approved cannabidiol with neurosteroids and benzodiazepines in adult refractory focal onset epilepsy
https://pubmed.ncbi.nlm.nih.gov/36493860/

In a human brain tissue model of epilepsy, CBD modulates neurotransmission via GABA (the brain’s most common inhibitory neurotransmitter)
GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol
https://pubmed.ncbi.nlm.nih.gov/36556407/

On using derivatives of CBD against epilepsy
Synthesis, Physicochemical And Spectral Characterization Of Novel Cannabidiol Derivatives As Anti-Epileptic Agents
https://www.pnrjournal.com/index.php/home/article/view/4654

Harms, Cannabis Use Disorder & Street Synthetics

For cannabinoid hyperemesis syndrome, treatment with haloperidol (the most common antipsychotic medication in the US)
Haloperidol as a treatment option in cannabinoid hyperemesis syndrome
https://pubmed.ncbi.nlm.nih.gov/36514445/

A case report of a young person with cannabinoid hyperemesis syndrome who experienced air in the body cavity & around the spine
Pneumomediastinum and Pneumorrhachis Associated With Cannabinoid Hyperemesis Syndrome
https://www.cureus.com/articles/125647-pneumomediastinum-and-pneumorrhachis-associated-with-cannabinoid-hyperemesis-syndrome
And another case in a 17-year-female
Cannabinoid Hyperemesis Syndrome Complicated by Pneumomediastinum: Implications for Pediatric Surgeons
https://pubmed.ncbi.nlm.nih.gov/36438163/

A test of three interventions for helping with cannabis use disorder
Promoting self-change in cannabis use disorder: Findings from a randomized trial
https://pubmed.ncbi.nlm.nih.gov/36483140/
“Overall, results support the utility of a brief self-directed workbook in combination with a single MI [motivational interviewing] session at promoting changes in cannabis use.”

In a case series of three adolescent female patients who self-harm & use cannabis, naltrexone (an opioid receptor blocker) helped them to reduce both substance use & self-harming behavior
Naltrexone as an Adjunctive Treatment for Adolescents With Deliberate Self-Harm Behavior and Cannabis Use: A Case Series
https://www.consultant360.com/peer-reviewed/naltrexone-adjunctive-treatment-adolescents-deliberate-self-harm-behavior-and

In the EU, a study of the emergence of synthetic cannabinoids
From JWH-018 to OXIZIDS: Structural evolution of synthetic cannabinoids in the European Union from 2008 to present day
https://pubmed.ncbi.nlm.nih.gov/36507715/
And a similar examination in Germany
Pharmacology, prevalence in Germany, and analytical data of cyclobutylmethyl- and norbornylmethyl-type synthetic cannabinoid receptor agonists
https://pubmed.ncbi.nlm.nih.gov/36541839/

A library of the 200+ synthetic cannabinoids
Comprehensive Characterization of a Systematic Library of Alkyl and Alicyclic Synthetic Cannabinoids Related to CUMYL-PICA, CUMYL-BUTICA, CUMYL-CBMICA, and CUMYL-PINACA
https://pubmed.ncbi.nlm.nih.gov/36530139/

In rats, the synthetic cannabinoid MDMB-4en-PINACA impaired cognitive performance & interfered with the functioning of the hippocampus (memory center)
Acute toxic effects of new synthetic cannabinoid on brain: Neurobehavioral and Histological: Preclinical studies
https://pubmed.ncbi.nlm.nih.gov/36528081/

Lungs & Vaping

In lung cells, a mix of CBD, CBG & THCV worked synergistically with non-steroidal anti-inflammatory drugs like ibuprofen to reduce inflammation
Phytocannabinoids Act Synergistically with Non-Steroidal Anti-Inflammatory Drugs Reducing Inflammation in 2D and 3D In Vitro Models
https://pubmed.ncbi.nlm.nih.gov/36559009/

In lung immune cells, THC & CBD reduced the expression of pro-inflammatory cytokines via the CB2 receptor
Receptor-mediated effects of Δ9 -THC & CBD on the inflammatory response of alveolar macrophages
https://pubmed.ncbi.nlm.nih.gov/36510483/

In the lungs of humans, inhaling vapor of β‑caryophyllene (one of the most common terpenes in cannabis) caused increased breathing function
Effects of inhaled β‑caryophyllene on vascular stiffness in smokers: A randomized, double‑blind, placebo‑controlled trial
https://www.spandidos-publications.com/10.3892/etm.2022.11756

A case study of cannabis vaping perhaps leading to fluid in the chest
Suspected Cannabis Vaping-Induced Pericardial Effusion
https://pubmed.ncbi.nlm.nih.gov/36412279/

The potential of vaping THC-O acetate leading to another epidemic of lung injuries
Vaping THC-O Acetate: Potential for Another EVALI Epidemic
https://pubmed.ncbi.nlm.nih.gov/36508081/

Pain, Inflammation & Surgeries

In Canadians with spinal surgery, the cannabis users had significantly lower tingling/numbness in their legs
EXPLORING THE RELATIONSHIP BETWEEN CANNABIS AND NARCOTIC USE ON PREOPERATIVE HEALTH CONSIDERATIONS IN CANADIAN THORACOLUMBAR PATIENTS: A CSORN STUDY
https://online.boneandjoint.org.uk/doi/abs/10.1302/1358-992X.2022.13.044

In a small anesthesia study, cannabis use made no difference to the success, onset or duration of a local anesthetic
Local Anesthetic Efficacy in Marijuana Users and Nonusers: A Pilot Study
https://pubmed.ncbi.nlm.nih.gov/36534774/

In pain patients receiving opioid painkillers, cannabis use was not associated with a change in mortality risk but was associated with a small increased risk of adverse outcomes
Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids
https://pubmed.ncbi.nlm.nih.gov/36525274/

In rats, an in-depth study on how cannabinoids & opioids have different effects on the descending pain pathway via GABA (the brain’s primary inhibitory neurotransmitter)
Cannabinoids and Opioids Differentially Target Extrinsic and Intrinsic GABAergic Inputs onto the Periaqueductal Grey Descending Pathway
https://pubmed.ncbi.nlm.nih.gov/36414010/

In a mouse model of toxic brain damage from HIV antiretrovirals, activating the CB2 receptor protects the brain, causes painkilling effects & reverses morphine tolerance
Peripheral sensory neuron CB2 cannabinoid receptors are necessary for both CB2-mediated antinociceptive efficacy and sparing of morphine tolerance in a mouse model of anti-retroviral toxic neuropathy
https://pubmed.ncbi.nlm.nih.gov/36417942/

The Immune System, Autoimmune Disorders & Pathogens

In people living with HIV, CBD & THC seem to be safe & well tolerated though at high levels of CBD, care should be taken with liver toxicity
Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028)
https://pubmed.ncbi.nlm.nih.gov/36551926/

A review of using cannabinoids as antimicrobials
Potential Applications of Cannabis Plant Extracts and Phytochemicals as Natural Antimicrobials
https://www.researchgate.net/publication/366017790_Potential_Applications_of_Cannabis_Plant_Extracts_and_Phytochemicals_as_Natural_Antimicrobials

A computer analysis on using the peptides from hemp seeds against the virus of COVID-19
Computer-Aided Screening for Potential Coronavirus 3-Chymotrypsin-like Protease (3CLpro) Inhibitory Peptides from Putative Hemp Seed Trypsinized Peptidome
https://pubmed.ncbi.nlm.nih.gov/36615263/

Cannabis extract effective against American foulbrood (a bacteria that affects honey bee larva)
Antibacterial activity of cannabis (Cannabis sativa L.) female inflorescence and root extract against Paenibacillus larvae, causal agent of American foulbrood
https://www.sciencedirect.com/science/article/abs/pii/S1878818122003024

Using cannabis roots to produce silver nanoparticles which are used as an antibacterial & antioxidant
Antibacterial, antioxidant, and haemolytic potential of silver nanoparticles biosynthesized using roots extract of Cannabis sativa plant
https://pubmed.ncbi.nlm.nih.gov/36519372/

Genitourinary System

A large review of patient charts found no connection between cannabis use & chronic kidney disease
Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization
https://www.sciencedirect.com/science/article/pii/S2590059522002151

In a rat model of kidney damage, drugs that inhibit the FAAH enzyme & MAGL enzyme protect the kidney cells from inflammation & apoptosis (programmed cellular suicide)
Protective effect of fatty acid amide hydrolase inhibitor URB597 and monoacylglycerol lipase inhibitor KML29 on renal ischemia–reperfusion injury via toll-like receptor 4/nuclear factor-kappa B pathway
https://www.sciencedirect.com/science/article/pii/S1567576922010712

In the kidneys of rats, cannabis changed their micro-architecture
Effects of Marijuana on Weight Changes, Physical Observation and Histology on the Kidney of Wistar Rats
https://www.researchgate.net/publication/366230547_Effects_of_Marijuana_on_Weight_Changes_Physical_Observation_and_Histology_on_the_Kidney_of_Wistar_Rats

The Heart & the Blood

In a review of public health data on acute strokes, cannabis users had a lower overall mortality risk than non-users
Acute Ischemic Stroke Among Cannabis Users in the United States and Possible Risk Factors for Mortality
https://pubmed.ncbi.nlm.nih.gov/36525572/

In humans, the ability of capsaicin to cause relaxation in the coronary arteries may be mediated by the cannabinoid & vanilloid receptors
Crosstalk between cannabinoid and vanilloid systems: role of CB receptors in the capsaicin-induced relaxation responses in human coronary arteries
https://thejournalofheadacheandpain.biomedcentral.com/counter/pdf/10.1186/s10194-022-01527-4.pdf

How the CB1 & CB2 receptors regulate heart cells
Differential Regulation of MMPs, Apoptosis and Cell Proliferation by the Cannabinoid Receptors CB1 and CB2 in Vascular Smooth Muscle Cells and Cardiac Myocytes
https://pubmed.ncbi.nlm.nih.gov/36552027/

The Muscles & Bones

In mice with no CB1 receptors, the males had worse bone loss when their leg was immobilized while the females seemed to be protected against this bone loss due to disuse
Global cannabinoid receptor 1 deficiency affects disuse-induced bone loss in a site-specific and sex-dependent manner
https://pubmed.ncbi.nlm.nih.gov/36542906/
#genderisweird

The Skin

In the skin’s sebocytes (which produce the important oily sebum & regulate skin functions), the damage caused by blue light is lessened by CBD with actions including reduced inflammation, less reactive oxygen species & restoration of skewed cell cycles
The Modulation of Blue-Light-Induced Inflammation, Intracellular Lipid Secretion, and Oxidative Stress in Sebocytes with Cannabidiol
https://pubmed.ncbi.nlm.nih.gov/36524438

In a mouse model of psoriasis & skin inflammation, activating the CB1 receptor significantly lessened scratching behavior & skin inflammation
The key role of CB1R in the sensory neurons to regulate psoriasiform skin inflammation and pruritus
https://pubmed.ncbi.nlm.nih.gov/36410425/

In skin stem cells, how two fatty acids modulate the endocannabinoid system
Bakuchiol and Ethyl (Linoleate/Oleate) Synergistically Modulate Endocannabinoid Tone in Keratinocytes and Repress Type I Interferon, TNF and COX-2 Pathways
https://www.scconline.org/Portals/100/FINAL-Sytheon-Preprint-SCC%20Annual%20Meeting-2022.pdf

CBD hydrogels for wound healing (seems like you hear about these every other week)
Cannabidiol/β-cyclodextrin inclusion complex-loaded poly(vinyl alcohol) semi-solid hydrogels for potential use in wound management
https://assets.researchsquare.com/files/rs-2346950/v1/079bc866-c47d-437d-8cf3-f31520e6c255.pdf?c=1670515742

The Eyes

How the endocannabinoid system works in our vision
The endocannabinoid system in the visual process
https://www.sciencedirect.com/science/article/pii/S2666469022000525

Hormones, Reproduction & Maternal Effects

In California public health data, babies from pregnant mothers with cannabis use disorder were more likely to die in the first year unexpectedly but there was no increased risk for infant hospitalizations or emergency department visits
Prenatal cannabis use disorder and infant hospitalization and death in the first year of life
https://pubmed.ncbi.nlm.nih.gov/36516553/

Prenatal cannabis use associated with increased maternal & neonatal morbidity & mortality
Impact of Prenatal Cannabis Use Disorder on Perinatal Outcomes
https://pubmed.ncbi.nlm.nih.gov/36515534/

In fetuses exposed to cannabis, about half had altered blood flow to the fetal brain & placenta
Utility of the cerebroplacental ratio (CPR) in marijuana exposed growth restricted fetuses
https://pubmed.ncbi.nlm.nih.gov/34570659/

Babies exposed to cannabis in utero had an increased risk of being small for their gestational age
Association between Prenatal Marijuana and Tobacco Smoke Exposures and Small for Gestational Age at Birth
https://pubmed.ncbi.nlm.nih.gov/36007919/

In cells of the human umbilical veins, the damage caused by oxidative stress was lessened by extract of hemp seeds
Bioactive polyphenols separated from hemp seed shells ameliorate H2 O2 -induced oxidative stress injury in human umbilical vein endothelial cells
https://pubmed.ncbi.nlm.nih.gov/36524844/

In a model of ovarian hyperstimulation syndrome (an exaggerated response to excess hormones), CBD decreased the weight of the ovaries as well as downregulated genes that enhanced the syndrome (VEGF)
Treatment of Ovarian Hyperstimulation Syndrome in a Mouse Model by Cannabidiol, an Angiogenesis Pathway Inhibitor
https://pubmed.ncbi.nlm.nih.gov/36588534/

In an animal model, prenatal exposure to THC altered the development of the hippocampus (memory center)
Effects of prenatal exposure to THC on hippocampal neural development in offspring
https://pubmed.ncbi.nlm.nih.gov/36529297/
I think it is strange as hell when they don't even mention the animal type in the abstract. Like, you killed something young here to create data & you can't even do that animal the dignity of mentioning its species.

In developing zebrafish, CBN caused increased mortality, decreased locomotion, a reduction in motor neuron branching, altered hair cell development & a reduction in the response to sound stimuli via the CB2 receptor
Cannabinoid receptor 2 (Cb2r) mediates cannabinol (CBN) induced developmental defects in zebrafish
https://pubmed.ncbi.nlm.nih.gov/36424484/

In male rats treated with cannabis extract, they had changes in their semen volume, morphology, motility & sperm count
Sperm Quality and Testicular Histological Changes in Wistar rats treated with Cannabis sativa Ethanolic Extract
https://www.researchgate.net/publication/366028638_Sperm_Quality_and_Testicular_Histological_Changes_in_Wistar_rats_treated_with_Cannabis_sativa_Ethanolic_Extract

In human Sertoli cells (where the sperm develops), prolonged treatment with CBD caused cellular aging (senescence)
Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells
https://pubmed.ncbi.nlm.nih.gov/36519830/

Cancer & Chemo

A quite conservative review of 36 studies on using cannabinoids for the gut symptoms of cancer treatment
Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer
https://pubmed.ncbi.nlm.nih.gov/36525085/
Despite cannabis working as well as the other standard treatments for the nausea of chemotherapy, they refused to endorse its use.

In renal carcinoma cells, a combination of a FAAH inhibitor & the cancer treatment RSL3 decreased their growth & metastasis (spread)
Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway
https://assets.researchsquare.com/files/rs-2261344/v1/2f18065b-9a1d-4e92-abfc-fe2cfe3c557c.pdf?c=1670273391

In brain cells, the toxicity of the chemo treatment paclitaxel is lessened by PEA
Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons
https://pubmed.ncbi.nlm.nih.gov/36551301

In cancer cells resistant to the chemotherapy drug doxorubicin, CBD & THCV help to make it sensitive to the chemotherapy’s killing effects again
The role of Cannabidiol and tetrahydrocannabivarin to overcome doxorubicin resistance in MDA-MB-231 xenografts in athymic nude mice
https://pubmed.ncbi.nlm.nih.gov/36535544/

In pancreatic cancer cells, the efficacy of THCV & HHC for killing them
Antineoplastic Properties of THCV, HHC and their anti2 Proliferative effects on HPAF-II, MIA-paca2, Aspc-1, and 3 PANC-1 PDAC Pancreatic Cell Lines
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63a1ef17e8047a2997effba5/original/antineoplastic-properties-of-thcv-hhc-and-their-anti-proliferative-effects-on-hpaf-ii-mia-paca2-aspc-1-and-panc-1-pdac-pancreatic-cell-lines.pdf

A computer analysis of breast cancer cells finds that cannabicitran is the best cannabinoid for blocking a key estrogen receptor
Study of potential inhibition of the estrogen receptor α by cannabinoids using an in silico approach: Agonist vs antagonist mechanism
https://pubmed.ncbi.nlm.nih.gov/36543006/

Cool Chemistry

Making CBD hot for 30 minutes produces detectable amounts of THC
Re-examining Cannabidiol: Conversion to Tetrahydrocannabinol Using Only Heat
https://pubmed.ncbi.nlm.nih.gov/36516105/
Funny thing is that if you make me hot for 30 minutes, I also produce detectable levels of THC.

The molecular dynamics of CBD & THC in the extraction process of supercritical CO2
Thermodynamics and transport properties of CBD and Δ-9THC: A first attempt using molecular dynamics
https://www.sciencedirect.com/science/article/abs/pii/S0167732222025879

How to efficiently alter the side chain lengths of CBG to make it a better fighter of cancer & reducer of pain
Efficient Synthesis for Altering Side Chain Length on Cannabinoid Molecules and Their Effects in Chemotherapy and Chemotherapeutic Induced Neuropathic Pain
https://pubmed.ncbi.nlm.nih.gov/36551296/

A review of the last 10 years of looking for drugs to activate the CB2 receptors
Rational drug design of CB2 receptor ligands: from 2012 to 2021
https://pubs.rsc.org/en/content/articlehtml/2022/ra/d2ra05661e

Developing new anti-inflammatory drugs that target both the CB2 receptor & FAAH enzyme
Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
https://pubmed.ncbi.nlm.nih.gov/36542836/

An examination of molds producing activators of the CB2 receptor
Docking and Molecular Dynamic Investigations of Phenylspirodrimanes as Cannabinoid Receptor-2 Agonists
https://www.mdpi.com/1420-3049/28/1/44

A series of molecules that work on the CB2 receptor as inverse agonist (binds to a receptor but causes the opposite action of the usual agonist [activator]) & cause anti-inflammation
2-Arylpropionic Acid Pyrazolamides as Cannabinoid CB2 Receptor Inverse Agonists Endowed with Anti-Inflammatory Properties
https://pubmed.ncbi.nlm.nih.gov/36558970/

Thanks.
- lex

PS: For this week’s Latin Mass sung by a traditional Congolese choir in 1958, ‘Miss Luba’ by Les Troubadours du Roi Baudouin. This album exploded into popularity around the world, inspiring musicians from Led Zeppelin to the Clash, and you’ve never heard anything like it.

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#39: cannabis clinical trials out the…