C&P #40: CBD for MS, menopause & opioid withdrawal + THC for aggressive dementia
CT eschews strain names + AZ slightly less bad for pregnant women & SD slightly worse
Welcome to the 40th edition of Cannabinoids & the People.
This newsletter collects all the new cannabinoid science each week. You can check out last week’s issue here & if you haven’t subscribed yet, please do.
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‘A Guide to the Whys & Hows of Choosing a Medical Cannabis Dispensary’
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In my EU report for Pro Cannabis Media this week,
- UK changes how it charges first-time cannabis offenders
- Italian Ministry growing medical
- Ireland remains a Prohibitionist stronghold
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As always, at the bottom we have an album of the week & The Living Glossary of Cannabinoid Terms.
CBD for MS, menopause & opioid withdrawal (hopefully not all at the same time)
THC for the aggression of dementia
Cannabis for depression, Crohn’s disease & colitis
Cannabis makes your smoked cocaine less effective
Lots of research for the growers out there
Psychedelics & MDMA for PTSD
Two jokes about relationships
Cannabis for MRSA & COVID-19?
In teens, a complex & gendered relationship between cannabis use & anxiety levels
Yes, smoking cannabis may be turning on more cancer genes in your sperm
A defense of cathinones (bath salts)
A request to spread the word
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Best Of Cannabinoid Science...
According to an anesthesiology group who just issued guidelines, all patients should be screened for cannabis before surgery because of links to more postoperative pain & nausea
Also, as any close readers of this newsletter know, the ability of cannabis to increase the amount of anesthesia needed for a surgery is a common finding.
In a case report of a dementia patient with treatment-resistant agitation & aggression, THC tincture rapidly improve their behavior & allowed discharge to their home
A Case Report of Treatment-Resistant Agitation in Dementia with Lewy Bodies: Medical Marijuana as an Alternative to Antipsychotics
For depression, a review of data from the UK Medical Cannabis Registry finds cannabis treatment caused symptom severity reduction for up to six months
Assessment of clinical outcomes of medicinal cannabis therapy for depression: analysis from the UK Medical Cannabis Registry
A review of data from the UK medical cannabis program finds that for patients with Crohn's disease & colitis, they had improved symptom scores & higher quality of life after three months of use
The effect of medical cannabis in inflammatory bowel disease: analysis from the UK Medical Cannabis Registry
A national survey found that cannabis use did not predispose people to hypertension (high blood pressure)
Sustained cannabis use does not predispose clinical hypertension: Findings from a national survey
In men smoking cocaine, using cannabis beforehand lowers the cocaine levels in the blood & reduces the subjective experience
Smoked cannabis reduces peak cocaine plasma levels and subjective effects in a controlled drug administration study of polysubstance use in men
“Now, you know that cocaine's for horses now it ain't for men
The doctors said it'll kill me but they didn't say when
Ain't nobody's business but your own”
A review of the cannabinoids as a radically new paradigm for treating Parkinson's disease
Therapeutic Molecular Insights into the Active Engagement of Cannabinoids in the Therapy of Parkinson's Disease: A Novel and Futuristic Approach
It’s vital for Parkinson’s patients to at least give CBD & THC a try. See my Neurodegenerative How-To Guide here.
On how the changes in sperm caused by cannabis could be leading to increased cancer levels in offspring
Novel Insights into Potential Cannabis-Related Cancerogenesis from Recent Key Whole Epigenome Screen of Cannabis Dependence and Withdrawal: Epidemiological Commentary and Explication of Schrott et al.
A review of how the endocannabinoids interact with the family of Cys-loop receptors (which includes GABA, glycine & acetylcholine) & the implications for treating epilepsy & chronic pain
Cys-loop receptors on cannabinoids: All high?
A review of what's known about delta-8 THC
Cannabidiol and Δ8-Tetrahydrocannabinol: Cannabinoids of Rising Interest and Concern
A look at GPR12: the receptor that may one day be known as CB4
Structural insight into the constitutive activity of human orphan receptor GPR12
In mice going through opioid withdrawal, CBD reduced the severity of their gut problems
Cannabidiol Reduced the Severity of Gastrointestinal Symptoms of Opioid Withdrawal in Male and Female Mice
In a mouse model of post-menopause, CBD lessened intestinal inflammation via the hormone estradiol
Cannabidiol Decreases Intestinal Inflammation in the Ovariectomized Murine Model of Postmenopause
In a mouse model of multiple sclerosis, CBD combined well with fluoxetine (a common treatment) to lessen the level of cell death
Autophagic Molecular Alterations in the Mouse Cerebellum Experimental Autoimmune Encephalomyelitis Model Following Treatment with Cannabidiol and Fluoxetine
In mice with acute lung injuries (a model of COVID-19), a combination of PEA with oxazoline reduced inflammatory cytokines as well as increasing levels of anandamide, 2-AG & PEA
First Evidence of the Protective Effects of 2-Pentadecyl-2-Oxazoline (PEA-OXA) in In Vitro Models of Acute Lung Injury
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
On LSD, endocannabinoids & the gut microbiome by Travis Cesarone (if you’re into writing with deep dives into science, he’s great)
A great profile of cannabis hero Dr. Tod Mikuriya – the medical powerhouse behind Prop 215 – by Sharon Letts
I just discovered Sharon’s work but she’s got a wonderful collection of cannabis reporting. See the roundup of her last ten years of work here.
In Connecticut, the rollout of adult-use cannabis did not light the world on fire. Plus, they’re not helped by being unable to use traditional strain names: it’s all Hybridol FG T28.14 17004 & Sativarin U T23.41 17001
(for great coverage of cannabis in the NE of the US, subscribe to Eric Casey’s newsletter Burn After Reading)
After a long fight, an Arizona woman who used medical cannabis for morning sickness during her pregnancy will now have her name removed from the state’s child abuse registry
and in related news, a South Dakota lawmaker filed a bill to block women who are pregnant or breastfeeding from becoming medical cannabis patients
A blighting cannabis viroid (RNA virus) is spreading across the country that causes a “dudding disease” of lower THC levels, discolored leaves & stunted brittle plants
“By the time growers notice the signs… it’s too late to stop the spread, Masso said. By that point, growers are essentially left with one option, said Nick Masso, the CEO of Marlborough-based Indo Laboratories, an independent marijuana testing facility. ‘Destroy it. Destroy everything,’ he said. ‘And if you had that anywhere within your facility, you need to do an extremely deep clean.’”
The Asian Cannabis Roundtable launches & I wish that I could go to their Lunar New Year Party this Friday in NYC
The War on Drugs & Prohibition
A report from the US Sentencing Commission shows that hundreds of people are currently serving longer federal prison times because of cannabis possession charges enhancing their sentences
Unsurprisingly, most of these charges come from states that have since liberalized their cannabis laws.
TSA brags about catching a weed candle
Psychedelics, Plant Medicines & Other Psychoactives
A well-done article on the human history with psychedelics by Daniel Simms
‘Can Psychedelics Repair Consciousness After Brain Trauma?’ by Jonathan Moens
A walkthrough of using mushrooms to enhance your workout
On 1P-LSD: the legal(ish) alternative to LSD that’s been on the market longer than my firstborn child has been alive
(I saw this headline & thought, I remember doing this in NYC. So I knew it must have been BS: Before Sofia)
The Science of Psychoactives
[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 review of treating PTSD with psychedelics
The Efficacy of Psychedelic-Assisted Therapy in Managing Post-traumatic Stress Disorder (PTSD): A New Frontier?
And a clinical trial using MDMA for PTSD
Self-experience in MDMA assisted therapy of PTSD
In teens, the use of psilocybin is linked to less suicidal ideation while LSD use is linked to more
Associations between MDMA/ecstasy, classic psychedelics, and suicidal thoughts and behaviors in a sample of U.S. adolescents
If you break down psychedelics by category, it’s only the use of psilocybin that reliably predicts an increased relatedness to nature
Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness
The effect wasn’t seen with LSD, mescaline, Salvia divinorum, ketamine or ibogaine.
In a mouse model of depression & anxiety, methylone – perhaps the greatest of the cathinones (bath salts) – may be a treatment
Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity
The cathinones labor under the false smears of lazy journalists. These drugs never caused anybody to eat someone’s face off (that attacker only had cannabis in his system). They’re not some crazy wild stimulant.
The drug category of cathinones comes from the khat plant of Yemen. Like the two other great natural sources of stimulants –coca (cocaine) & ephedra (amphetamine) - the cathinone produced by the khat plant produced a swirl of synthetic cousins. Some of them are quite lovely – a mix of a stimulant quality with the empathogen feelings of MDMA. If all drugs were legal, as they should be, the cathinones would rank as a minor but beloved subcategory of the psychoactive market.
[And for today’s throwback writing, my article on the cathinones from my Good Doctor days found on my old website: Cathinones: Please Don't Call Them Bath Salts]
Business & Law
The Scottish National Investment Bank invests £2m in the hemp insulation company Indinature Mill
The Plant & the History
A genome study of cannabinoid levels & the genes of cannabinoid biosynthesis
Profiling Cannabinoid Contents and Expression Levels of Corresponding Biosynthetic Genes in Commercial Cannabis ( Cannabis sativa L.) Cultivars
Using sex reversal in hemp plants to study changes in gas usage & energy dissipation
Photosynthetic gas exchange and chlorophyll fluorescence of female hemp plants during sexual reversal treatments
Growing & Processing
A protocol for the speed breeding of hemp
A protocol for rapid generation cycling (speed breeding) of hemp (Cannabis sativa) for research and agriculture
Buy it a drink first.
In a study of hemp growing, irrigation was linked to the levels of cannabinoids while nitrogen supplementation led to an increase of helpful nutritional amino acids
Industrial Hemp ( Cannabis sativa L.) Inflorescences as Novel Food: The Effect of Different Agronomical Practices on Chemical Profile
On drying your plants with infrared versus hot air heating
Postharvest blanching and drying of industrial hemp (Cannabis sativa L.) with infrared and hot air heating for enhanced processing efficiency and microbial inactivation
A non-destructive way to measure your leaf area
NON-DESTRUCTIVE METHOD TO DETERMINING THE LEAF AREA IN HEMP, Cannabis sativa L.
Using raffinate to increase the yield of your supercritical CO2 extraction
Valorization of Wild-Type Cannabis&nbsp;indica by Supercritical CO2 Extraction and Insights into the Utilization of Raffinate Biomass
For seedling germination, hydrogen peroxide solutions to decrease microbial contamination
Availability of Hydrogen Peroxide Solutions as a Germination Liquid Medium for Contamination-free in vitro Seedling Development of Cannabis sativa
Using organic fungicides against hemp mildew in Tennessee
Efficacy of organic fungicides against hemp powdery mildew caused by Golovinomyces ambrosiae in a greenhouse in Tennessee
On using cannabis & datura against flour beetles
Biopesticide Potential of Cannabis sativa and Datura alba against the major pest of stored grain Tribolium castaneum (Flour beetles)
One of the leading hypotheses for why cannabinoids evolved in the first place is that they protected against insect attack. This dovetails with the long human history of using hemp as an insecticide. So perhaps the future will be turning cannabis into a safe biopesticide against agricultural pests.
If raising quails, hemp cake is a great way to improve the fatty acid ratios in their eggs
Effects of Dietary Rapeseed ( Brassica napus), Hemp ( Cannabis sativa) and Camelina ( Camelina sativa) Seed Cakes Supplementation on Yolk and Albumen Colour and Nutritional Value of Yolk Lipids in Estonian Quail Eggs
CBD & selenium to improve your chicken breast muscle
Cannabidiol and Nano-Selenium Increase Microvascularization and Reduce Degenerative Changes in Superficial Breast Muscle in C. perfringens-Infected Chickens
Industrial Use & Inventions
Using hemp seed proteins to make food packaging
Hemp Seed Protein and Carrageenan Based Biodegradable Composite Film for Food Packaging Applications
On using a timber frame wall filled with hemp concrete
Numerical analysis of timber frame wall filled with hemp concrete
Clinical Studies & Surveys
I'm really only including this one for the title
Birds of a Feather Get High Together: A Reconceptualization of the Social Bond with Latent Class Analysis and a Test with Different Forms of Drug Use
In adolescence, a complex & gender-differentiated relationship between cannabis & anxiety
Directional associations between cannabis use and anxiety symptoms from late adolescence through young adulthood
“For the overall sample and men, greater cannabis use predicted greater subsequent increases in anxiety; however, greater anxiety symptoms were associated with decreasing cannabis use. For women, results were more complex. A positive association was noted between prior, trait-like levels of anxiety predicting greater change (increasing) in anxiety symptomology. However, when change is predicted by prior change we see that cannabis use decreases among women who have recently experienced an increase in anxiety.”
In brain scan studies of young men using cannabis, they saw delayed maturation in the cingulum (a tract of nerves that allows for communication amongst the components of the limbic (emotional) system)
Cannabis, connectivity, and coming of age: Associations between cannabis use and anterior cingulate cortex connectivity during the transition to adulthood
Ingestion Methods & Pharmacokinetics (how things bind & move)
When teen rats are vaping, how much of the THC accumulates in their nose?
Answer: a decent amount - and it absorbs into the bloodstream
Nasal accumulation and metabolism of Δ9-tetrahydrocannabinol following aerosol ('vaping') administration in an adolescent rat model
On the problems of trying to quantify cannabis consumption: hits per day? grams per week? joints per week?
Typical Hits, Grams, or Joints: Evaluating Cannabis Survey Measurement Strategies for Quantifying Consumption
Buds per month? Milligrams per lunar cycle? How many times, after being a pain in the ass, my wife says ‘don’t you want to step downstairs?’
Using molecular dynamics to see how CBD & THC move through the system
Thermodynamics and Transport Properties of CBD and Δ 9 -THC: A first attempt using Molecular Dynamics
Mental Health, Addiction & Mental Effects
In humans with opioid use disorder, cannabis use was not protective against relapse
Cannabis use and opioid relapse: An exploratory survival analysis of prospectively collected data
A review on measuring & treating mood disorders using the endocannabinoid & neurosteroid systems
Biomarkers and treatments for mood disorders encompassing the neurosteroid and endocannabinoid systems
A review on how cannabinoids may alter the reward sensation of opioids
Opioid Reinforcement: What It Is And How It Can Be Modulated By Cannabinoids
If rats are injected with nicotine, they increase their intake of THC & other synthetic cannabinoids
Nicotine enhances intravenous self-administration of cannabinoids in adult rats
In zebrafish, activating the CB1 receptor lowered oxidative stress & inhibited aggressive behavior
Putative Activation of Cannabinoid Receptor Type 1 Prevents Brain Oxidative Stress and Inhibits Aggressive-Like Behavior in Zebrafish
The Brain & its Diseases
A review of targeting the endocannabinoid system for strokes & other diseases where blood flow to the brain stops
The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic–Ischemic Brain Injury
A review of how CBD & CBG interact with the sodium channels that are vital to electrical signaling in the nervous system
Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol
In microglia (guardian immune cells of the brain) hemp proteins modulate the genes related to inflammation
Hemp Protein Hydrolysates Modulate Inflammasome-Related Genes in Microglial Cells
A review from a South Korean hospital on using CBD to treat severe childhood epilepsy finds it to be a safe & effective treatment option
Cannabidiol Treatment for Lennox-Gastaut Syndrome at a Single Tertiary Center in South Korea
In Japanese epilepsy patients, half of the patients reported that CBD decreased seizure frequency & in two patients, CBD stopped seizures completely
Cannabidiol (CBD) Reduces Epileptic Seizures in the Asian Population: Cross-sectional Study for Intractable Epilepsy Patients in Japan
Harms, Cannabis Use Disorder & Street Synthetics
An epidemiological analysis of Europe finds cannabis use linked to congenital neurological anomalies in children
European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Neurological Anomalies: Geospatiotemporal and Causal Inferential Study
On treating cannabis use disorder with contingency management (a method to specifically reinforce target behavior attainment)
Contingency Management for Treatment of Cannabis Use Disorder in Co-Occurring Mental Health Disorders: A Systematic Review
An analysis of the synthetic cannabinoids smuggled into Brazilian prisons on infused papers
Synthetic cannabinoid receptor agonists profile in infused papers seized in Brazilian prisons
Lungs & Vaping
In mice with an acute lung injury induced by bacteria, activating the CB2 receptor reduced lung inflammation & suppressed the negative immune system effects
Activation of cannabinoid-2 receptor protects against Pseudomonas aeruginosa induced acute lung injury and inflammation
Pain, Inflammation & Surgeries
In pain patients, different combinations of CBD & THC did not help with neuropathic body pain
Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment
For pain, a review of the powerhouse threesome: the FAAH enzyme (that regulates anandamide levels), the COX pathways (used by ibuprofen) & the vanilloid receptors (also activated by the endocannabinoids)
TRPV1-FAAH-COX: The Couples Game in Pain Treatment
A review of the antioxidant properties of hemp proteins
Antioxidant Properties of Hemp Proteins: From Functional Food to Phytotherapy and Beyond
The Immune System, Autoimmune Disorders & Pathogens
A review of using cannabis against MRSA (antibiotic-resistant staph infections)
Review Cannabis: A new strategy against methicillin-resistant Staphylococcus aureus
and on using the cannabinoid precursor olivetolic acid against bacteria
Novel insights into the antibacterial activities of cannabinoid biosynthetic intermediate, olivetolic acid, and its alkyl-chain derivatives
On the possibility of using CBD to treat monkeypox symptoms
Letter to the Editor: Would Cannabidiol Be a Therapeutic Alternative to Treat Monkeypox Symptoms?
Molecular modeling of using the cannabinoids against the virus that causes COVID-19
Molecular Modeling Targeting the ACE2 Receptor with Cannabis sativa's Active Ingredients for Antiviral Drug Discovery against SARS-CoV-2 Infections
Guts, Metabolics, Microbiome & Oral Health
On using CBD & hemp oils for oral & facial surgeries
Cannabidiol and hemp oils: Potential applications in oral and maxillofacial surgery
and a review of using cannabis for facial pain
Cannabis Bioactive Compound-Based Formulations: New Perspectives for the Management of Orofacial Pain
A review of the interaction in the guts between cannabinoid receptors & nociceptin receptors (newly discovered opioid receptors) with clinical implications for inflammation & colitis
A Crosstalk between the Cannabinoid Receptors and Nociceptin Receptors in Colitis-Clinical Implications
In adolescence, cannabis use was associated with a higher risk for lesions, bruxism (grinding of the teeth, especially at night) & more frequent consumption of sugary beverages & snacks
Associations between Oral Health and Cannabis Use among Adolescents and Young Adults: Implications for Orthodontists
In a diabetic obese mouse, abnormal CBD (a synthetic cousin of CBD) combined with sitagliptin (type 2 diabetes medication) improved glucose tolerance, enhanced insulin sensitivity, decreased triglycerides & total cholesterol as well as reducing fat mass
Antidiabetic actions of GPR55 agonist Abn-CBD and sitagliptin in obese-diabetic high fat fed mice
In mice fed diets enriched with selenium, they had increased levels of beneficial endocannabinoid mediators of metabolism, more expression of their antioxidant genes, changes to the gut microbiome & a decreased expression of pro-inflammatory genes
Impact of selenium on the intestinal microbiome-eCBome axis in the context of diet-related metabolic health in mice
In humans undergoing dialysis (an artificial kidney to clean the blood), the use of medical cannabis was found to be safe & the researchers urge studying its use for pain in this patient population
Medical cannabis for pain management in patients undergoing chronic hemodialysis: randomized, double-blind, cross-over, feasibility study
In rabbit bladder muscle, the ability of nicotine to cause contractions may be somewhat mediated by the cannabinoid receptors
Enhancing effect of nicotine on electrical field stimulation elicited contractile responses in isolated rabbit bladder straight muscle; the role of cannabinoid and vanilloid receptors
The Heart & the Blood
In a mouse model of late-stage diabetes, activating the CB2 receptor protected the heart cells from necroptosis (a type of inflammatory cell death) via BACH2
Cannabinoid Receptor 2-Centric Molecular Feedback Loop Drives Necroptosis in Diabetic Heart Injuries
In skin stem cells, the terpene bakuchiol & the fatty acid ethyl linoleate work together to prevent the degradation of endocannabinoids which causes less inflammatory molecules
Bakuchiol and ethyl (linoleate/oleate) synergistically modulate endocannabinoid tone in keratinocytes and repress inflammatory pathway mRNAs
In the eyes, cannabis caused a temporary reduction in photoreceptor activity & a downstream decrease in visual processing activity - but these effects disappeared with chronic use
The impact of cannabis consumption on visual processing
In a rat model of diabetes blocking the CB1 receptor & activating the CB2 receptor protected the eyes from damage
Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats
Hormones, Reproduction & Maternal Effects
In African American women with heart complications after pregnancy, if lower levels of endocannabinoids & other lipids are seen in early pregnancy, this lipid signature can predict later heart complications with 74% accuracy
African American Women with Cardiometabolic Complications of Pregnancy Have Decreased Serum Abundance of Specialized Pro-Resolving Lipid Mediators and Endocannabinoids
On using cannabis in gynecology
Cannabis use in gynaecology: A bad idea?
Luckily for this paper's title, the old rule of journalism is that if a headline ends in a question mark, the answer to that question is no.
A review of the effects of synthetic cannabinoid exposure in the womb & later neurodevelopment
Synthetic Cannabinoids and Neurodevelopment
In baby rodents exposed to CBD in the womb, they had distinct behavioral alterations dependent on their gender
In utero exposure to cannabidiol disrupts select early-life behaviors in a sex-specific manner
“Thus, male (but not female) pups from CBD-treated dams [mamas] gained more weight than sham [control group]. There were sex-dependent differences in the coarse characteristics of ultrasonic vocalizations [their high-pitched calls]. Prenatally-CBD exposed male pups emitted shorter calls, whereas CBD females made more high frequency calls when compared with their control counterparts. There were significant qualitative changes in the syllabic USV repertoire [their types of calls] reflected in call typologies and communication patterns. Finally, the homing behavior test [ability to return to a certain location] showed that CBD-exposed females presented a greater vulnerability to gestational CBD than males. Only CBD-exposed female pups showed reduced motor and discriminatory abilities.”
In pregnant mice, the proteins P-gp & Bcrp did not prevent THC from reaching the maternal brain & the fetus
Maternal and Fetal Exposure to (-)-Δ9-tetrahydrocannabinol and Its Major Metabolites in Pregnant Mice Is Differentially Impacted by P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP)
Cancer & Chemo
In breast cancer cells, CBD combined well with somatostatin (a hormone) to inhibit cell proliferation & increase apoptosis (cellular suicide)
Comparative changes in breast cancer cell proliferation and signalling following somatostatin and cannabidiol treatment
In breast cancer cells, inhibiting the NAAA enzyme (which breaks down PEA) shrank tumors & increased survival of the mice
Inhibition of triple negative breast cancer-associated inflammation and progression by N- acylethanolamine acid amide hydrolase (NAAA)
Today’s scifi: CBD self-assembling nanoparticles for the destruction of cancer cells
Cannabidiol as Self-Assembly Inducer for Anticancer Drug-Based Nanoparticles
In a zebrafish model of colorectal cancer, anandamide reduced cell division & blood flow to the tumor as well as causing anti-inflammatory effects
A zebrafish HCT116 xenograft model to predict anandamide outcomes on colorectal cancer
On making disintegrating cannabis films for taking by mouth
Development of fast dissolving orodispersible films loaded with cannabis extract
Engineering a detector that can determine cannabinoid levels in vapor with a sensitivity of parts per billion
Surface engineering of zinc phthalocyanine organic thin-film transistors results in part-per-billion sensitivity towards cannabinoid vapor
Creating a CB2-activating drug that is turned on by light
Synthesis and Characterization of a Cannabinoid Type 2 Receptor Photoactivated Prodrug
PS: From ‘the Voice of Mali’, this week’s album is ‘Mali Denhou’ by Boubacar Traoré. He went from superstar to obscurity & back again.
Coming to prominence in the early ‘60s with a blending of American blues, Arab music & the pentatonic structures of West Africa, Traoré became a legend of the radio in the newly independent Mali & greeted the country every morning with ‘The Mali Twist’. But after the military overthrew the socialist government in 1968, he had the bad luck to be associated with the former government & his songs disappeared from the air. Because he recorded no albums, there were no royalties to pay the bills & he worked a variety of jobs to support his family.
Then in 1987, a surprise television appearance brought him back to national attention & after moving to France, a British producer tracked him down to record his first album: ‘Mariama’. This hit sparked a string of records you can listen to here as well as tours of Europe & the US. For his last album ‘Dounia Tabolo’, he collected musicians from across the Deep South of the US to perform with (including the Haitian-American singer Leyla McCalla who I adore). To see him in person & to learn more about the Mali music scene, you can watch the documentary ‘Je Chanterai Pour Toi’ (it’s in French – but you get the gist).
The Living Glossary of Cannabinoid Terms
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.
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]
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]
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 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]
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.