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As always, at the bottom there’s a Living Glossary of cannabinoid terms along with the weekly music recommendation.
This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations. We produce educational content for cannabis & psychedelic companies. You can see my portfolio here.
- Our first sponsor: a big welcome to Sunsoil!
- Cannabis use linked to lower COVID severity
- High levels of CBD for treatment-resistant anxiety & low levels of THC for PTSD
- The kind of research I’m here for: cannabis for better improvisational street dancing
- Acupuncture & juniper berries both help via the endocannabinoid system
- Quite an interesting roundup of findings about cannabis use & public health out of Colorado’s health department
- A new entry in the Living Glossary for NAAA – the enzyme that degrades PEA – because its inhibition has been found to help with pain control
- The researcher who walked 444 mi of NYC to learn about cannabis child-resistant packaging
- Using hemp to clean up heavy metals out of soil
- I promise that there’s not an especially awesome selection of preclinical CBD research this week just because we have a CBD sponsor. It just happened to be a rich week for CBD. I will always maintain my editorial independence – and any good sponsor will be glad to learn more about all the positives of CBD as well as any moderate negatives that I can find.
Editors note: Next week’s newsletter will be a day or two late because I’m going to my cousin Harrison’s wedding back home in PA. By the way, if you happen to be going through Philly, check out his crazy novelties store in Fishtown: Little Devils Curiosities. It’s some of the strangest things you’ve ever going to see there (& that’s in a city that already has the Mütter Museum). Or follow on Instagram to see all the oddities from the comfort of your own home.
Sunsoil CBD: better products that cost less
Greetings to our first sponsor: Sunsoil!
I’m proud to be working with Sunsoil because they are excellent makers of organic, full-spectrum CBD oil. Using organic hemp that they grow in Vermont, Sunsoil uses a unique infusion method to naturally extract cannabinoids with minimal processing.
Best of all, Sunsoil’s mission is to make their products as affordable as possible. They recently announced an ambitious goal to reduce their prices by 80 percent over the next 5 years.
Buy from Sunsoil today using the coupon code LEX50 to get 50% off your first order & find out what an excellently made CBD product can do for you.
(plus, buying from Sunsoil is also an excellent way to support this newsletter)
Best of cannabinoid science...
In hospitalized patients with COVID-19, cannabis use associated with less severity
Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis
In young people with treatment-resistant anxiety, CBD (up to 800 mg per day) significantly reduced their depression scores – though 80% experienced non-serious side effects like fatigue, low mood, hot flashes & cold chills
Cannabidiol for Treatment-Resistant Anxiety Disorders in Young People: An Open-Label Trial
In humans with PTSD, a low dose of THC helped with emotional processing during an emotional regulation task
Cannabinoid modulation of brain activation during volitional regulation of negative affect in trauma-exposed adults
In a survey of cancer patients, cannabis was used the most for sleep, pain & anxiety – with the biggest barrier being cost
Medical Marijuana Use for Cancer-Related Symptoms among Floridians: A Descriptive Study
A dancer’s review of how the high of cannabis can help facilitate improvisational street dance
Dancer's high: an experiential review of cannabinoid activity and improvisational street dance
This is the kind of science that I am here for! Far too many lab rats have to die for obvious conclusions – when really, we need dancers in the street doing meditations & narrative research on what happens in humans when they use the old herb for the old spiritual activity of dance.
A deep dive into the uneven science of cannabis & impaired driving: a call for a new paradigm
How to read a paper on the short-term impairing effects of cannabis: A selective and critical review of the literature
In mice threatened by pit vipers, CBD reduced their panic & defensive responses
CB 1 receptor signalling mediates cannabidiol-induced panicolytic-like effects and defensive antinociception impairment in mice threatened by Bothrops jararaca lancehead pit vipers
Life lesson: CBD is good for non-lethal anxiety like public speaking & dates – but when confronting grizzly bears, don’t ingest so much CBD that you forget to yell at them & make yourself appear as big as possible.
In human neutrophils (first-responder white blood cells), CBD inhibited expression of the COX-1 & COX-2 enzymes (responsible for pain & inflammation, a pathway used by NSAIDs like aspirin & ibuprofen)
Effect of Cannabidiol on Cyclooxygenase Type 1 and 2 Expression and Function in Human Neutrophils
In various white blood cell types, CBD caused both pro- and anti-inflammatory effects depending on its concentration & the cell types involved – but its suggested “CBD might be used to dampen B cell activity in autoimmune conditions such as rheumatoid arthritis”
Cannabidiol: Influence on B Cells, Peripheral Blood Mononuclear Cells, and Peripheral Blood Mononuclear Cell/Rheumatoid Arthritis Synovial Fibroblast Cocultures
In a human skin stem cell model of acne, CBD lowered inflammatory cytokines & upregulated CB2 levels
Cannabidiol Inhibits Inflammation Induced by Cutibacterium acnes-Derived Extracellular Vesicles via Activation of CB2 Receptor in Keratinocytes
In a culture of the common fungal pathogen Candida, a mix of CBD & the antibiotic triclosan reduced their ability to form biofilms (a key measure of how well the fungus spreads & causes harms)
Potential Combinatory Effect of Cannabidiol and Triclosan Incorporated into Sustained Release Delivery System against Oral Candidiasis
As always, the use of the cannabinoid as antibiotic & antifungal agents is one of their most underutilized features.
In a goat model of visceral hypersensitivity (feeling pain in your organs), the ability of electroacupuncture to relieve the pain occurred via modulation of the endocannabinoid system
Electroacupuncture relieves visceral hypersensitivity through modulation of the endogenous cannabinoid system
There’s quite a large body of work on how the benefits of acupuncture (the most scientifically proven of the “alternative” therapies) are mediated, at least partially, by the endocannabinoid system.
2021: Another case of a medicinal plant that utilizes the endocannabinoid system: a terpene from juniper berries acts as a positive modulator of the CB1 receptor
Agathadiol, a labdane diterpenoid from juniper berries, is a positive allosteric modulator of CB 1 R
Over & over again, these old medicinal plants use the ECS to work their magick.
We appreciate dedication to the craft! This researcher walked 716.5 km of NYC streets looking for discarded cannabis packaging to analyze it for child safety
A cross-sectional assessment of package labels aimed at children of edible and leaf cannabis discarded in New York City
If anyone knows Dr. Blumberg, I want to get in touch with him because I think this is just lovely.
An evergreen note on reading restricted paper:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version) or Google Scholar itself.
3 other helpful browser extensions are: Unpaywall, Open Access Button & PaperPanda
For the infamous backdoor, use Sci-Hub – the pirated papers repository (Chrome extension here). This works better for older paper than the stuff that just came out.
For Twitter users, send a Tweet of the paper’s title with the hashtag #icanhazpdf. It works because people are beautiful(ish).
Finally, email the author. They’re almost always happy to oblige because, thanks to the predatory academic publishing system, they don’t make a dollar off of their papers.
Popular science pieces & upcoming events
Great review on using cannabis for your small animal friends by Drs. Trina Hazzah & Gary Richter
Cannabis Products in Small Animal Medicine
And to learn more, check out their Veterinary Cannabis Society
And listen: every animal with a spinal cord has an endocannabinoid system & could probably benefit from cannabinoids. Give it a try for your animal companion.
(we just got a cat. he’s great. and it gives the baby something to wander around the house after. but I want to try CBD to help cut back on the ‘zoomies’ when he’ll randomly jump us…)
On Sep 7, a free journal club about cannabis & blood pressure by CSequence & the Society of Cannabis Clinicians
They’re talking about this paper from 2021
Cannabis is associated with blood pressure reduction in older adults - A 24-hours ambulatory blood pressure monitoring study
On the ECS & its influence on autism
A Nature piece about how the decrim of cannabis is leading to more research opportunities by Chris Woolston
2020: A classic piece on the history of cannabinoid research by Dr. Giovanni Appendino with a section on the infamous tragedy around the early researchers Wood, Spivey & Easterfield
The early history of cannabinoid research
“Some dramatic events occurred in the course of these studies, eventually leading to their abrupt end. Thus, Spivey, a collaborator of Easterfield and one of the authors of the cannabinol publications, died in a laboratory accident during a large-scale Etard oxidation in the course of studies on the structural characterization of an elusive “oxycannabine” that a competitor group had reported from the red oil (Wood 1902), while a Cambridge colleague, C. R. Marshall, while taking care of a distillation of diethylzinc, a highly inflammable liquid, ingested a ca. 100 mg dosage of cannabinol to fight the boredom of distillation and to assess if the compound was narcotic.Footnote1 After ca 45 min he was found wondering aimlessly in the lab unable to stop giggling and repeating “this is lovely” while flames were developing around him because oxygen had leaked into the distillation flask and had set fire to diethylzinc. The prompt intervention of colleagues avoided a disaster and Marshall recovered promptly (Mills 2003). These events were exaggerated in biased anti-cannabis publications that appeared in the US during the 1930s, claiming that two of the discoverers of cannabinol had died in laboratory experiments related to these researches, while a third one had suffered severe injuries during these studies.”
My cannabis counseling sessions for your health
For people looking to use CBD, cannabis & more novel ingredients like PEA or OEA for their health, I offer counseling sessions on how to use these tools.
We’ll meet to discuss what you want to fix, we’ll come up with a gameplan of what to try, I’ll help you to buy it (the cost of products almost always comes out to less than $100) & then I’ll be there to talk you through trying them out to find the best routine for you. Plus, unlimited follow-up emails.
If you want someone experienced in listening to patients & coming up with a plan to help you find relief, book a 1-on-1 session with me here:
Cannabinoid Education Sessions.
the Headlines & Fav Articles
In Europe, the regulatory debate over the allowable daily food limits of CBD
Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the EFSA Clock Stop Regarding Novel Food Authorisation
New proposed guidance from the DOT for commercial drivers told medical examiners that drivers used CBD products “at their own risk” of testing positive for THC
And the US Forest Service says that its workers can’t use cannabis & that even hemp extracts might make you test positive for their drug tests
With the approval of the application of Maridose, the DEA has now licensed 7 companies for the bulk distribution of cannabis for federal research
Also, you’ll be pleased to know it’s still the 1940’s around here & we refer to it as marihuana.
ACS Laboratory releases what they call the most comprehensive cannabis testing regimen ever
“With the National Hemp Testing Panel, ACS Laboratory tests for 18 cannabinoids, 105 pesticides, 24 heavy metals, 55 potential residual solvents, 17 different microorganisms, and every required mycotoxin to detect parts per billion, as well as for moisture content, water activity and terpenes”
Cannabis & psychedelic use among young people hits an all-time high – though alcohol still leads the pack
This week’s favorite yelling (& use of this meme)
Del. Gabriel Acevero @GabrielAceveroQUESTION 4 WOULD LEGALIZE RECREATIONAL CANNABIS IN MARYLAND AND IT’S ON THE BALLOT THIS NOVEMBER SO GO TELL ALL YOUR FRIENDS TO VOTE FOR IT SO WE AREN’T LOCKING PEOPLE UP FOR A DAMN PLANT.
The War on Drugs & Harm Reduction
After hemming & hawing, Gavin Newsom finally vetoes the opening safe injection facilities in San Francisco
And the city attorney urges SF to ignore the governor’s veto & open up the sites anyway to start saving lives
Repugnant. If you want to be looked back on as the same kind of person who mocked Dr. Semmelweis for suggesting that doctors should wash their hands when going from the morgue to the birthing ward, be against safe injection facilities.
The new drug czar of Colombia wants to work with Peru & Bolivia to decriminalize cocaine & force the UN renegotiate the disastrous international drug conventions
And he ordered the halt of cocoa eradication
Huzzah. The evils of US policy in the Drug War of South America are some of the very worst things we’ve done. The number of activists tossed out of airplanes or tortured to advance Amerikan interests will never be known – but what’s known is horrifying.
An interview with Chris Alexander of NY’s cannabis office on how they’re issuing their social equity licenses
An insightful paper on how drugs are currently being trafficked around the world
Drug Trafficking in the World
The DEA Administrator said that "anyone with a smartphone has a drug dealer with them."
I mean yes, but buying your drugs on social media is tired. Buying them over the Dark Web is wired.
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to a company out there, reach out to me]
On being young, Queer, Muslim & exploring psychedelics by Ismali Ali (the policy director at MAPS)
A Mormon bishop (& former Utah state representative) talks about how ayahuasca confirmed his faith
Andy Roberts of the Psychedelic Press on his favorite psychedelic book: Stephen Gaskin ‘Amazing Dope Tales & Haight Street Flashbacks’
Fun Fakt: Stephen Gaskin helped to establish The Farm, an early self-sustaining community, and he was the husband of the indomitable Ina May Gaskin, "the mother of authentic midwifery." Off the record, Ina was said to be a big fan of using cannabis during the birthing process.
(both of my kids were born at home & I think of Ina May Gaskin as an American hero)
A thread on DMT vs 5-MeO-DMT by Andrew Gallimore
Andrew Gallimore @alieninsectDMT vs 5-MeO-DMT: Why do such similar molecules have such dramatically different effects? A thread... DMT is a characteristically visual experience, notable for the fully immersive worlds of immense complexity, filled with intelligent and communicative beings.
A review of the efficacy & mechanisms of psilocybin for depression
Psilocybin Efficacy and Mechanisms of Action in Major Depressive Disorder: a Review
In a trial of adults with alcohol use disorder, they found that psilocybin psychotherapy decreased the number of heavy drinking days
Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial
Haha. The satire of the week on why to win capitalism via the psychedelic stock market
Law & Business
Cannabis companies use corporate social responsibility strategies similar to tobacco companies to advance their interests
Content Analysis of the Corporate Social Responsibility Practices of 9 Major Cannabis Companies in Canada and the US
In Alice Moon’s newsletter, she talks about cannabis SEO with deeproots’ Matthew Shterenberg
Two business professors look at the problems organizations have with a lack of knowledge & policies on CBD
ORGANIZATIONAL POLICIES ADDRESSING CANNABIDIOL USE IN THE WORKPLACE
And a review of their survey asking workers what they know about CBD & its regulations
GAINING A BETTER UNDERSTANDING OF CANNABIDIOL
Unsurprisingly, this survey of dispensary workers found them unevenly trained in cannabis therapeutics & not the best people to ask about cancer treatments
Backgrounds and Trainings in Cannabis Therapeutics of Dispensary Personnel
Martha Stewart now has pumpkin spice CBD gummies (shark jumped)
The Plant & the History
2021: In genome analysis of 100 cannabis samples, the cannabis labeled indica & sativa were genetically indistinct & instead referred to differences in a small number of terpene synthase genes
Cannabis labelling is associated with genetic variation in terpene synthase genes
Hemp as a good source of amino acids that helps human feel satiated after a meal
Hemp and buckwheat are valuable sources of dietary amino acids, beneficially modulating gastrointestinal hormones and promoting satiety in healthy volunteers
On the effects of what you do after you harvest your cannabis
Postharvest Operations of Cannabis and Their Effect on Cannabinoid Content: A Review
& the effects of transplant date & plant spacing on biomass
The Effect of Transplant Date and Plant Spacing on Biomass Production for Floral Hemp (Cannabis sativa L.)
Potential & limits of using cannabis to clean arsenic-contaminated soil
Cannabis sativa L. and Brassica juncea L. grown on arsenic-contaminated industrial soil: potentiality and limitation for phytoremediation
2021: Using hemp to clean up soil contaminated with copper
Potential Use of Copper-Contaminated Soils for Hemp (Cannabis sativa L.) Cultivation
A whitepaper on how to keep heavy metals out of cannabis
Understanding Sources of Heavy Metals in Cannabis and Hemp: Benefits of a Risk Assessment Strategy
In lambs, using spent hemp biomass appears to be fine for the nutritional quality of the meat
Assessment of spent hemp biomass as a potential ingredient in ruminant diet: Nutritional quality and effect on performance, meat and carcass quality, and hematological parameters in finishing lambs
Using hemp leftovers to make biochar (activated carbon)
Economic evaluation of Hemp’s (Cannabis sativa) residual biomass for production of direct energy or biochar
2021: A history of high-end hemp linen in cultural history by Git Skoglund
Traditional Fine Homespun Hemp Linen Fabrics: About Qualities and Usages in Ritual and Secular Contexts
The book to read is ‘Cannabis: Evolution and Ethnobotany’ by Clarke & Merlin. They go over how hemp is traditional mourning fiber of Korea, the holy rope of the Japanese sumo & so important in China that the Middle Kingdom was long referred to as “the Land of Mulberry & Hemp”.
Clinical Studies & Surveys
2021: In human with hepatitis B, “current cannabis use was associated with a 59% lower risk of central obesity”
Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)
In cannabis smokers, their HDL cholesterol levels increased after ingestion while their LDL & total cholesterol levels saw partial reductions
Changes in High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL) and Cholesterol Concentration in Heavy Cannabis Users: A Single-Centre Study in Cusco, Peru
In French people using cannabis for multiple sclerosis, they say ‘mais oui’
Symptom improvements following therapeutic use of cannabis-based products in French people with multiple sclerosis
But seriously, I can’t even access the abstract for this one, so I don’t know anything besides the positive title.
L'édition académique, quelle arnaque.
MRI scans show how the brains of cannabis users show alterations in volume in several regions
Individuals with cannabis use are associated with widespread morphological alterations in the subregions of the amygdala, hippocampus, and pallidum
In humans with bipolar disorder, they had higher PEA levels & lower & 2-AG levels
Could serum endocannabinoid and N-acylethanolamine levels be important in bipolar disorder?
After knee surgery, the use of acetaminophen afterward altered anandamide levels in the blood
The effect of acetaminophen and total knee arthroplasty on endogenous plasma endocannabinoid levels
Recommended for You
A review of cases where doctors chose to use cannabis for chronic pain, opioid dependence, depression & migraines
Cannabinoids—Perspectives for Individual Treatment in Selected Patients: Analysis of the Case Series
The Colorado Dept. of Public Health collected their findings about the effects of cannabis on public health
Evidence of Health Effects Associated with Marijuana Use: A Comprehensive Public Health Review
- For teens, weekly use associated with lower rates of graduation or getting a college degree
- Daily use associated with increased risk of schizophrenia
- Daily use associated with pre-cancerous lesions in the airway – but smoking less than a joint a day is not associated with increased lung cancer risk
- Moderate evidence for use in males associated with increased risk of testicular cancer
- Use increases risk of stroke
- Secondhand smoke unlikely to lead to a positive drug test
- Combining cannabis with alcohol increases the risk of car accidents more than either substance alone
- Daily use associated with impaired memory for at least the next 7 days
- Prenatal cannabis exposure associated with lower birth weight, reduced cognitive function, academic ability, attention problems & IQ scores in childhood – but not birth defects
- Smoked cannabis associated with chronic bronchitis with cough, wheezing & mucus – but acute use also associated with short-term lung airflow improvement
In colorectal cancer cells, CBD lowered proliferation, migration & invasion of the cells as well as inducing apoptosis (cellular suicide) via the EMT & Wnt/β-catenin signaling pathway
Cannabidiol inhibits invasion and metastasis in colorectal cancer cells by reversing epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway
Cannabis use associated with lower risks for of renal cell carcinoma and bladder cancer in females & for prostate cancer in males
Association between cannabis use with urological cancers: A population-based cohort study and a mendelian randomization study in the UK biobank
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
A significant link found between an earlier age of starting cannabis & later suicidal behaviors
Early Age of Cannabis Initiation and Its Association With Suicidal Behaviors
This study suggests that cannabis use prior to blood donation may impair the blood quality via “impaired oxygen transport by [red blood cells], reduced platelet counts, and impaired platelet function”
In vitro exposure of whole blood to a cannabinoid mixture impairs the quality of red blood cells and platelets
2021: In people with asthma, “although concurrent cannabis use disorders are not associated with increased in-hospital mortality or discharge to facilities, it is associated with increased ventilation utilization rates”
INCREASING TREND AND POOR OUTCOMES ASSOCIATED WITH CANNABIS USE IN YOUNG ASTHMATICS
On kidney harms in young synthetic cannabinoid users
Acute Kidney Injury (AKI) in Young Synthetic Cannabinoids Abusers
2021: A case series of 3 toddlers admitted to the ER after cannabis ingestion
Cannabis Intoxication, a Neglected Cause of Altered Level of Consciousness in Children: A Case Series
On externalizing behaviors & the link between cannabis use & schizophrenia
Influences on the Genetic Relationship Between Cannabis Use and Schizophrenia: The Role of the Externalizing Spectrum
Looking at CB1 activity in patients using synthetic cannabinoids
Linking in vitro and ex vivo CB1 activity with serum concentrations and clinical features in 5F-MDMB-PICA users to better understand SCRAs and their metabolites
In a study of ways to get pregnant women to not smoke cannabis, the most effective interventions were cognitive behavioral therapy & motivational interviewing
Interventions Addressing Cannabis Use During Pregnancy: A Systematic Review
In pregnant mice exposed to cannabis smoke, their babies had decreased brain volumes & cell viability but an increase in BDNF (a brain growth factor)
Prenatal exposure to Cannabis smoke induces early and lasting damage to the brain
Toxicologie Analytique et Clinique
This French toxicological society released a bunch of abstracts that will be presented at their upcoming meeting in Versailles.
(no, I won’t be going. If I didn’t have babies at home, I’d be tempted to pull a Hunter S Thompson & go observe these putative prohibitionists in their element – but their wine & cheese reception isn’t worth making my wife do that much time alone with the kids)
On how easy it is to make delta-8 THC
Delta-8-Tetrahydrocannabinol, an emerging NPS and other structurally related cannabinoids
How to monitor a town’s wastewater to figure out their cannabinoid consumption levels
Refining wastewater-based epidemiology for cannabis consumption monitoring: Relevance of analysing both the aqueous phase and suspended solids of influent wastewater
The effect of cannabis on the endocannabinoid levels in the blood
Acute effects of cannabinoid consumption on endocannabinoid levels
How to measure endocannabinoid levels in the bloodstream
Quantification of endocannabinoids in human plasma
Using hemp-based hair care products may increase your chances of testing positive on a hair test
Impact of hemp-based cosmetic products on cannabis testing in hair
A new synthetic cannabinoid: CH-PIACA
Identification of the novel synthetic cannabinoid-type new psychoactive substance, CH-PIACA, in seized material
A dramatic case report of a man taking a few puffs from a joint laced with MDMB-4en-PINACA & jumping out a fourth-story window
Dramatical outcome following the consumption of a joint containing the synthetic cannabinoid MDMB-4en-PINACA: A case report
A review of the effects of cannabis on cognition in people with multiple sclerosis
A systematic review of the effects of cannabis on cognition in people with multiple sclerosis
A nursing review of using cannabis for multiple sclerosis
Medical cannabis in multiple sclerosis
A review of the genes turned on & off by cannabis that relate to depression
The Cannabis-Induced Epigenetic Regulation of Genes Associated with Major Depressive Disorder
“Multiple genes residing in loci associated with depression were found to be epigenetically regulated by exposure to cannabis or cannabis-derived compounds. This epigenomic regulation of depression-associated genes by cannabis or cannabis-derived compounds was reported across diverse organisms, tissues, and developmental stages and occurred in genes crucial for neuronal development, functioning, survival, and synapse functioning, as well as in genes previously implicated in other mental disorders.”
A review of cannabis for postpartum depression
The Use of Cannabis and Its Effects on Postpartum Depression
A review of 11 studies relating to the varied effects of the cannabinoids for oral & dental surgeries
Marijuana and cannabinoid use in clinical oral and maxillofacial surgery: a scoping review
A review of targeting the endocannabinoid system to treat schizophrenia
Molecular Findings Guiding the Modulation of the Endocannabinoid System as a Potential Target to Treat Schizophrenia
A review of the involvement of the endocannabinoid system in movement disorders
Involvement of the Endocannabinoid System in the pathophysiology and therapeutics of movement disorders
A review of the medicinal chemistry of CBD
The Essential Medicinal Chemistry of Cannabidiol (CBD)
A review of nano-encapsulated cannabinoids for inflammatory bowel diseases like Crohn’s
Potential use of nanoencapsulated cannabinoids for the treatment of inflammatory bowel diseases: a systematic review
Nanoencapsulated cannabinoids (aka liposomal cannabinoids) are simply a way to take the fatty cannabinoid and put them into little lipid balls to improve their bioavailability. For regular consumers, I think this is a waste of money because for the added cost it takes to do these tricky procedures, you could just buy more of the CBD or THC from the plant & increase the amount you take. But for certain hard to treat conditions where a patient might need hundreds or thousands of milligrams, nanoencapsulation will be an important part of future therapies.
A review of targeting the CB2 receptors to utilize the antimicrobial properties of cannabis with a relevance for neurodegenerative diseases
The Antimicrobial Properties of Cannabis and Cannabis-Derived Compounds and Relevance to CB2-Targeted Neurodegenerative Therapeutics
In rats, a study of how much CBD was absorbed by their lymph system for transportation around the body
Lymphatic Absorption of Cannabidiol: First in vivo Study in Rats
The absorption rates also saw an 11% increase if using a microemulsion over a sunflower oil solution.
In rabbits, CBD & CBDA absorbed more if not given with food
Feeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus)
This is odd because in humans, CBD usually absorbs better if taken with a meal that has some fats in it.
In a mouse model of pain, inhibiting both the FAAH enzyme (degrades AEA) & the NAAA enzyme (degrades PEA) produced more pain-relieving effects than either substance alone
Synergistic antinociceptive effects of concomitant NAAA and peripheral FAAH inhibition
I created a short entry for NAAA in the Living Glossary below.
In mice with chronic pain who get moved to an enriched environment, the ability of this enriched environment to reduce pain levels is apparently because it mimics endocannabinoids in their reduction of pain & anxiety via the NR2B & CB1 receptors in the thalamus
Down-regulation of NR2B receptors contributes to the analgesic and antianxiety effects of enriched environment mediated by endocannabinoid system in the inflammatory pain mice
In a rat lesion model of Alzheimer’s disease, the neural insult causes upregulation of CB1 levels as well as a limited contribution from CB2
Cannabinoid Receptors and Glial Response Following a Basal Forebrain Cholinergic Lesion
In mouse brains, the expression of CB1 receptors in basal ganglia areas relates to “sorting diverse information through parallel loops”
New Subregions of the Mouse Entopeduncular Nucleus Defined by the Complementary Immunoreactivities for Substance P and Cannabinoid Type-1 Receptor Combined with Distributions of Different Neuronal Types
In a mouse model of diabetes, a drug that blocks the CB1 receptor caused “a significant reduction in food intake and obesity, diabetic biomarkers, lipid profile, oxidative stress, and proinflammatory cytokine release” & shows no signs of anxiety or depression
Synthesis, molecular docking, and pharmacological evaluation of 5-(4-(2-(5-ethyl pyridine-2-yl) ethoxy) benzyl)-3-(phenylsulfonyl) thiazolidine-2, 4-dione against HFD-induced diabesity via interaction with the CB1 receptor
They’re looking for the new Rimonabant – the infamous CB1 blocker drug of the 2000s that helped people with their weight, but was later linked to suicidal ideation & pulled from the market. The hope is to find a drug that doesn’t cross into the brain & instead just works via the body’s CB1 receptor to help control metabolism.
2021: In a rat model of stroke, inhibiting the MGL enzyme (that breaks down 2-AG) caused neuroprotection
Neuroprotective effects of minocycline and KML29, a potent inhibitor of monoacylglycerol lipase, in an experimental stroke model: a small-animal positron emission tomography study
In rats, a high dose of a FAAH inhibitor caused an increase in aggression
URB597 induces subtle changes to aggression in adult Lister Hooded rats
In rats, chronic cannabis administration leads to downregulating of two serotonin receptors
Implications of Cannabis sativa on serotonin receptors 1B (HTR1B) and 7 (HTR7) genes in modulation of aggression and depression
In rats, early life stress & alcohol exposure leads to altered glutamate & endocannabinoid signaling that’s linked to anxiety in adulthood
Acute stress and alcohol exposure during adolescence result in an anxious phenotype in adulthood: Role of altered glutamate/endocannabinoid transmission mechanisms
In mice with bone deficiencies from low Vitamin D, beta-caryophyllene in their diet led to higher bone volume & density
Beta-caryophyllene prevents the defects in trabecular bone caused by Vitamin D deficiency through pathways instated by increased expression of klotho
A study of how to enhance CBD absorption via mucosal delivery (the tissue lining the mouth)
Mucosal Delivery of Cannabidiol: Influence of Vehicles and Enhancers
Pro-tip: if you want to get more CBD into your system, hold it under your tongue for a minute. Most CBD companies won’t come out & tell you this because to the sticklers at the FDA, holding a liquid under your tongue is a drug delivery method.
A review of the recent trends in the ever-tricky problem of determining cannabinoid levels in cannabis
Critical review on recent trends in cannabinoid determination on cannabis herbal samples: From chromatographic to vibrational spectroscopic techniques
Using a smartphone & a paper chip to test for THC levels in human saliva
Machine Learning-Based Quantification of (−)-trans-Δ-Tetrahydrocannabinol from Human Saliva Samples on a Smartphone-Based Paper Microfluidic Platform
Unfortunately, this will probably be used to test for impairment – and there’s no good link between impairment & THC levels in your spit.
A series of novel derivatives of CBD demonstrate anti-inflammatory activities
New cannabidiol (CBD) derivatives: Synthesis, anti-inflammatory activity, and molecular docking
Creating an eye drop with a MAGL inhibitor as a treatment for glaucoma
MAGL inhibitor NanoMicellar formulation (MAGL-NanoMicellar) for the development of an antiglaucoma eye drop
Designing new FAAH & MAGL inhibitors based on a carbamate scaffold
Synthesis and evaluation of carbamate derivatives as fatty acid amide hydrolase and monoacylglycerol lipase inhibitors
PS: For this week’s hard-bopping album, ‘Up with Donald Byrd’, which includes some great covers including ‘House of the Rising Sun’ & ‘Sometimes I Feel Like A Motherless Child’ (Spotify knows I’m a sucker for a good cover). Donald Byrd, one of the great trumpeters of jazz’s hard bop era from the mid-’50s to mid ’60s, grew up the son of a Methodist minister & was already performing with Lionel Hampton by his late teens. He continued his career with a military band in the Air Force followed by studying music at Wayne State & then a master’s at the Manhattan School of Music. He soon got invited to join Art Blakey’s Jazz Messengers, taking the seat once filled by his idol Clifford Brown. Signing with Blue Note in 1958, he released a flurry of classic records that Youtube collected here.
After a break to study in France, he came back with the ‘A New Perspective’ album that incorporated gospel choirs. He began looking to the music of Africa – as well as Miles Davis. Under those influences, he released ‘Black Byrd’ – a jazz/funk album that’s been detested by the purist jazz critics & beloved by the fans. It became the bestseller in Blue Note’s history & hit #2 on the R&B charts. While continuing his jazz/funk period, he finished law school & began teaching at North Carolina Central University, later earning a PhD (what a guy). With the acid jazz movement, his music became a hugely popular place for samples. He continued being a jazz educator until the end of his inspiring life at the age of 80.
PPS: So is anybody reading this music section? Just curious. I’m going to keep doing it because it’s educational for me - but one always wonders if anyone cares.
The Living Glossary
This is a running glossary of the basic cannabinoid terms. It will also function as the legend for the ‘neural ocean’ metaphor that I’m using in my graphic novel series on the endocannabinoid system based on Moby-Dick. You can watch a lecture laying out the full idea here - but we treat the human brain like the ocean: deep, mysterious & chockablock with fish, molecules & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land). And neurons are complex underwater cities where hundreds of fish interact.
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]
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
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]
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]
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]
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.
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]
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]
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 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 see this Easter Egg & email me will receive a free copy of my Queer chapter: Chapter 37: SunSet (once I finish getting it up & published on Amazon)
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]
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]
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.
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.