C&P#26: New sponsor: IACM + CBD for everything + BDSM & the ECS
Colombian prez on cocaine + big moves in NY & CA + dinosaurs at the UN
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This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations. We produce educational content for cannabis & psychedelic companies. Writing, science archives, newsletter content & if you need a podcast, I’m the host for you. You can see my portfolio here.
My new ProjectCBD article hit the newsstands: “In Defense of Dopamine: An Endocannabinoid Story”
CBD for meth & opioid addiction, pain, insomnia, wound healing on the skin, Parkinson’s, bad memories & to counteract a diet of ultra-processed foods(?)
How Ginkgo biloba helps with pain via the ECS
In BDSM, what are your endocannabinoid levels like?
Great chemistry work: where does the skunky smell come from & where do you find the newly identified trans-THCA?
What’s so special about hemp pollen? Hemp seed oil?
It’s a week of unexpected news: smoking pot with MD cops & ayahuasca ceremonies in the Packers endzone
Attend IACM virtually: The Great European Cannabinoid Conference!
On Oct 20th & 21st, you can virtually attend the 12th International Association for Cannabinoid Medicine’s (IACM) Conference on Cannabinoids in Medicine.
For the price of an affordable ticket, you can listen to a stellar lineup of speakers gathering in Basel, Switzerland including…
Dr. Allyn Howlett (discoverer of the CB1 receptor <swoon>)
Dr. Franjo Grotenhermen (IACM’s executive director, leading researcher & author of practical cannabis therapeutics books)
Dr. Kirsten Müller-Vahl (a specialist in neurology & psychiatry & a world expert on Tourette syndrome)
Dr. Dustin Sulak (famous physician/advocate of cannabinoids for kids)
Dr. Vincenzo Di Marzo (in the top 1% of highly cited researchers in the world, leading ECS expert & excellent public speaker (see my interview with him here))
& many others that I’ll cover in the weeks to come.
Buy your tickets now to attend online before the price goes up on Oct 12th. This conference mixes the best of cutting-edge endocannabinoid science with the practical use of cannabis by healthcare practitioners. See the program here & buy your tickets here.
And if you’re going in person, I’ll see you there.
Best of cannabinoid science...
In a small open-label study of people with opioid use disorder already using buprenorphine, 600 mg of CBD for 3 days significantly lowered cue-induced craving
Cannabidiol Effect on Cue-Induced Craving for Individuals with Opioid Use Disorder Treated with Buprenorphine: A Small Proof-of-Concept Open-Label Study
Wound-healing with a CBD hydrogel: antioxidant effects, reduced inflammatory response, facilitated wound healing & increased blood vessel formation
A cannabidiol-containing alginate based hydrogel as novel multifunctional wound dressing for promoting wound healing
When my kid gets a paper cut or the baby gets her finger caught in the cat door (that was a new one), we go right to the CBD cream & the Wonder Woman band-aids.
A review finds that it makes sense to use cannabinoids to treat the inflammation of COVID-19
Cannabinoids receptors in Covid-19: Perpetrators and victims
In mice being fed high-carb ultra-processed food, CBD lowered the anxiety-inducing nature & compulsive behaviors caused by that diet
Cannabidiol ameliorates the anxiogenic and compulsive-like behaviors induced by chronic consumption of a high-carbohydrate diet in male mice
Is the hashtag then #CBDtoOffsetYourMcDonalds?
In a rat model of Parkinson’s disease, injection of CBD into the brain improved their fine motor skills via the GPR55 receptor & GABA
Intrapallidal injection of cannabidiol or a selective GPR55 antagonist decreases motor asymmetry and improves fine motor skills in hemiparkinsonian rats
In female rats, CBD helped to block them from storing fearful memories via the CB1 receptor
Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction
In a mouse model of chemotherapy, CBD lowered neuropathic pain & inflammatory cytokines via the CB2 & Toll-like receptors (TLR4) in the spinal cord’s microglia (immune cells)
Cannabidiol Prevents Chemotherapy-Induced Neuropathic Pain by Modulating Spinal TLR4 Via Endocannabinoid System Activation
In a model of neuropathic pain from chemotherapy, the ability of a key terpene from Ginkgo biloba to reduce the pain seems to be mediated by the CB1 receptor
CB1 as a novel target for Ginkgo biloba's terpene trilactone for controlling chemotherapy-induced peripheral neuropathy (CIPN)
Add another one to the list of “famous plant medicines that turn out to be targeting the endocannabinoid system”…
Surprisingly, in this study of people with schizophrenia and their siblings, the lifetime cannabis users had better scores for facial emotion recognition (FER) performance
The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study
Breaking news, in the world of BDSM (bondage, domination & sadomasochism), submissives have increased endocannabinoid & cortisol levels during the scene while dominants have increased endocannabinoid levels during power play but not pain play
BDSM: pathological or healthy expression of intimacy?
I love science.
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
Slate’s Hannah Docter-Loeb has a nice writeup of the cannabinoids & synthetic cannabinoids you can find out there…
My cannabis & psychedelic consultant sessions for your health (or your patients)
For people looking improve their health with use CBD, cannabis & more novel ingredients like PEA (immune system) or oleamide (sleep), 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:
Your Cannabis Counseling Sessions.
I’m also available to meet with medical professionals to advise them on using cannabis, cannabinoids & psychedelics in their practice. I’ve seen an uptick in the number of sessions for this & I can say that they find these one-hour brain pickings quite useful because I’m a walking ‘rule of thumbs’ from my years of interviewing practitioners. Plus, you get a follow-up email with all of the relevant science to your questions as well as recommended books & further resources. I can help you help your patients to better use these powerful tools of health. See here for more information:
Cannabinoid & Psychedelic Education Sessions
the Headlines & Fav Articles
Now that’s some public speaking: Check out the new president of Colombia slamming the addiction to cocaine being painted as worse than the ‘addiction to irrational power, profit and money’
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I’ve been really liking this guy so far. Also, if you look at the actual data, cocaine use is almost identical to alcohol use: the vast majority use it on the weekends in amounts that might screw up their morning but not screw up their lives. And unlike booze, cocaine is unlikely to kill you.
At the UN, the head of the International Narcotics Control Board wants to take action against countries that legalize cannabis
In California, 10 new cannabis bills signed into law including employment protections, record sealing of prior convictions, authorizing cannabis for use by veterinarians, prohibiting localities from banning medical cannabis deliveries & to allow for interstate commerce
In New York, medical patients will be able to grow their own starting on Oct 5
Tiffany Kary on NYC’s plan to have former convicts to lead the legal cannabis industry (in under 100 days)
The Oneida Indian Nation of New York plans to start a cannabis business next year
Las Vegas will allow cannabis social consumptions lounges
It’s pretty crazy how hard it is to implement these. All over the country, people can buy weed – but they have nowhere to gather to smoke it.
For New Orleans police officer recruits, recent cannabis use will no longer disqualify them from the job
Oklahoma Supreme Court denies allowing a cannabis legalization vote this year because of procedural problems
According to the LA Times, California’s system of local approvals for cannabis businesses "spawned a wave of corruption, threats and secret financial deals for politicians"
The Department of Defense doubles down & says that service members can’t eat hemp granola or use CBD-infused hand sanitizer – but they are planning to make sniper uniforms out of hemp
Hong Kong is planning to ban CBD by next year
The iPhone Health app now allows users to indicate whether they use cannabis to identify medication interactions
I’m curious what medications they’ll be highlighting because it’s quite unclear what medications might actually be affected by cannabis. We have long lists from test tube studies with liver enzymes – but not enough clinical work have been done to figure out how many of these interactions might actually matter with real world human use.
In today’s unexpected news, police in Maryland are inviting people to come smoke pot & then take a bunch of different sobriety tests
The War on Drugs & Harm Reduction
A hearty thank you & good journey to the harm reduction hero Dr. Ambros Uchtenhagen
In NYC, the new overdose prevention sites already prevented 500 overdoses
You can’t be against these. You just can’t.
NIDA is opening up & their new strategy plan for treating addictions will include psychedelics, cannabinoids & kratom
Even WaPo wants to eliminate the cocaine/crack disparity
& the Senate Judiciary Committee tweeted a video about doing the same…
If you don’t know about this one, under Reagan the sentencing for 5 grams of crack was equivalent to the sentencing for 500 g of cocaine. But these drugs are basically the same. The only difference, in general, is that black people use crack & white people use cocaine. This disparity is one of the starkest highlights of the real reason for the War on Drugs.
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to your company, reach out to me]
On Oct 2nd, our friend Britta Love hosts a workshop on Sex & Psychedelics
See my interview with her on the same topic on this Lex Files episode.
Native American Church of North America leaders met lawmakers on Capitol Hill about peyote preservation
Emma Stone interviews the author of a study about how psychedelic trials tend to underreport adverse events
How Twitter is plagued by plug bots pushing shrooms
On psychedelics & mindfulness, a meta-analysis found “an increase in mindfulness, specifically relating to domains of acceptance, which encompasses non-judgement of inner experience and non-reactivity”
Psychedelics and mindfulness: A systematic review and meta-analysis
An interview of psilocybin microdosers found several themes
Psilocybin as a healer
“Seven central themes were observed in most individuals:
1) Mental Health
2) Dose effects
3) A feeling of connection to self, nature, or something ‘bigger’
4) An increase in productivity
5) An increased state of wellbeing
6) Navigating problems more effectively
7) Participants with a musical background experienced an increase in their levels of creativity”
A book chapter on the illicit use of ketamine
An Update of Ketamine Illicit Use
Often called “psychedelic heroin”, it’s neither a psychedelic or an opioid – but this dissociative is certainly addictive. Despite its impressive safety profile that makes it the anesthetic of choice for infants & old people, the ability of ketamine to make a fuzzy cloud between you & your pain makes it an easy drug to start doing a little bit all of the time. And because tolerance develops quickly, you’re soon taking a lot for a smaller experience.
After years of use, ketamine can cause you severe bladder problem & in the London club scene, there are a number of teens who had to have their bladders removed.
Overall, ketamine is an amazing tool of psychiatry, an essential medication for surgery & an enjoyable club drug with less of a hangover than alcohol as well as no overdose potential. But for that small subset of users, they cannot stop using it & it removes them from their life.
In more unexpected news, the Packers do a pretend ayahuasca ceremony in the endzone after a touchdown
Law & Business
Women-led cannabis brands get a fraction the capital of companies led by men according to Nancy Whiteman of Wana
“The CBD cooldown is underway. How are direct-to-consumer CBD brands keeping us interested?”
In California, this webscraping analysis finds that the availability of cannabis delivery is almost universal
Using online crowdsourced data to measure the availability of cannabis home delivery: A pilot study
Here in France, I dream of the day when I won’t have to bike down to the guys hanging out by the river.
The Plant & the History
A book chapter on why hemp seed oil is essential for health
Bioactive Phytochemicals from Hemp (Cannabis sativa) Seed Oil Processing By-products
2021: In cannabis, the discovery of two volatile sulfur compounds that give that skunky smell
Identification of a New Family of Prenylated Volatile Sulfur Compounds in Cannabis Revealed by Comprehensive Two-Dimensional Gas Chromatography
“We found that the concentrations of these compounds increase substantially during the last weeks of the flowering stage, reach a maximum during curing, and then drop after just one week of storage.”
THC Acid comes in two forms: trans- (the most common) & cis- (only recently found in the plant) & this study looks at where the cis-THCA is most commonly found, CBD-rich, CBG-rich & 1:1 THC:CBD plants
Cis-Δ 9-tetrahydrocannabinolic acid occurrence in Cannabis sativa L
Trans- and cis- are examples of chirality – the handedness of molecules. Just like your hand, they have the same components & structure, but they’re mirror images of each other. The most famous example of what a big difference this can make is thalidomide. For this antinausea medication for use by pregnant women in the ‘60s, it turned out that one version of the molecule prevented vomiting & the other caused birth defects where the babies had flippers instead of hands. Chirality matters.
An in-depth review of the medicinal metabolites produced in the synthesis pathways of the cannabis plant & how to better engineer it to harness the power of those metabolites
Heterologous production of Cannabis sativa-derived specialised metabolites of medicinal significance - Insights into engineering strategies
The cis-THCA above is a great example of a cannabinoid that might be a boon for some disease – but to get the plant to produce useful levels of it for study & medical use, we need to fiddle with it.
Investigations on the nature of hemp pollen
Phytochemical and biological investigations on the pollen from industrial hemp male inflorescences
It turns out that even the pollen has antimicrobial effects.
Using the hemp vacuum infiltration technique to temporarily alter genetic expression in hemp to knock down THC levels
In planta Female Flower Agroinfiltration Alters the Cannabinoid Composition in Industrial Hemp ( Cannabis sativa L.)
Because of Prohibition, the agronomic techniques that have revolutionized agriculture this last century have not been applied to cannabis. But researchers are slowly catching us up…
On using bacterial inoculations as biostimulants to improve the growth of cannabis
Characterization of the Cultivable Endophytic Bacterial Community of Seeds and Sprouts of Cannabis sativa L. and Perspectives for the Application as Biostimulants
A genetic analysis looks at the regulation of anthocyanin, a key flavonoid that regulates pigmentation as well as interactions with the environment
Two R2R3-MYB transcription factors, CsMYB33 and CsMYB78 are involved in the regulation of anthocyanin biosynthesis in Cannabis sativa L.
2021: An analysis of the changes in hemp’s protein levels when experiencing a potassium deficiency
Protein expression changes in response to potassium deficiency stress of industrial hemp plants using SWATH technology
The effects of silicon & heavy metals on hemp’s fiber properties
Impact of Silicon and Heavy Metals on Hemp (Cannabis sativa L.) Bast Fibres Properties: An Industrial and Agricultural Perspective
2021: In tilapia fish, adding CBD to their diet helped with protein conversion efficiencies but under conditions of stress, it reduced their efficiency of weight gain
DETERMINATION OF FEED UTILIZATION AND GROWTH PERFORMACE OF CHRONICALLY STRESSED AND NON-STRESSED NILE TILAPIA, OREOCHROMIS NILOTICUS, FED CANNABIDIOL (CBD) -SUPPLEMENTED DIETS
Clinical Studies & Surveys
In patients with chronic pain, cannabis use caused significant pain score reductions, improved sleep & caused no serious adverse events
Medicinal Cannabis for the Treatment of Chronic Refractory Pain: An Investigation of the Adverse Event Profile and Health-Related Quality of Life Impact of an Oral Formulation
In patients with MS, nabiximols (1:1 THC:CBD spray) reduced spasticity as well as a range of spasticity-associated symptoms
A real-world evidence study of nabiximols in multiple sclerosis patients with resistant spasticity: Analysis in relation to the newly described 'spasticity-plus syndrome'
A review of the knowledge & practices of healthcare practitioners using cannabis for chronic pain
Healthcare professionals' perspectives on the use of medicinal cannabis to manage chronic pain: A systematic search and narrative review
In women with anorexia nervosa, they had lower 2-AG levels in their cerebellum
Nucleus accumbens functional connectivity and circulating endocannabinoids levels in anorexia nervosa
In France, 70% of people have heard of CBD but only 10% of people have tried it
Cannabidiol use and perceptions in France: a national survey
2021: A new EEG technique called the Cognalyzer® to measure how high someone is
Use of a Novel EEG-Based Objective Test, the Cognalyzer ®, in Quantifying the Strength and Determining the Action Time of Cannabis Psychoactive Effects and Factors that May Influence Them Within an Observational Study Framework
Everyone is trying to solve this problem. And it is a tough one. How high are you right now?
I dunno. 7? Medium-high? Light red? Thinking about UFOs level…
Speaking of, your genetic variant of p-glycoprotein (a membrane pump that transports drugs in & out of the cell) seems to alter how high you get from cannabis
Association between ABCB1 rs2235048 Polymorphism and THC Pharmacokinetics and Subjective Effects following Smoked Cannabis in Young Adults
In cats using a CBD/CBDA hemp paste, they found that CBDA absorbed twice as well as the CBD & that paste products may be superior to oil products for absorption
Serum Cannabinoid 24 h and 1 Week Steady State Pharmacokinetic Assessment in Cats Using a CBD/CBDA Rich Hemp Paste
I can attest that for our 1 year old male not-yet neutered cat, two shots of CBD per day has caused him to jump the children less.
Mental Health, Addiction & Mental Effects
In this study of cannabis for Tourette syndrome, it did not lower the tics but did help on secondary measures like the urge to tic & the level of distress
A Double-Blind, Randomized, Controlled Crossover Trial of Cannabis in Adults with Tourette Syndrome
Unsurprisingly, cannabis users are more likely to use psychedelics as well
The Link Between Marijuana and Hallucinogen Use Among US Adolescents
In more work that could have been achieved by asking anybody, cannabis found to modulate & strengthen the effects of psychedelics
Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey
In a rat model of meth addiction, CBD seems to help lower the potential to relapse via a dopamine receptor
Intra-Accumbal D1- But not D2-Like Dopamine Receptor Antagonism Reverses the Inhibitory Effects of Cannabidiol on Extinction and Reinstatement of Methamphetamine Seeking Behavior in Rats
In rats using amphetamine, the “maladaptive impulsivity” of their decisions seems to be modulated by the CB1 receptor
Comparative effects of cannabinoid CB1 receptor agonist and antagonist on timing impulsivity induced by d-amphetamine in a differential reinforcement of low-rate response task in male rats
Reproductive & Maternal Effects
A cohort study finds no association between maternal cannabis use & ADHD in the offspring
Is in-utero exposure to cannabis associated with the risk of attention deficit with or without hyperactivity disorder? A cohort study within the Quebec Pregnancy Cohort
In a study of fetal & maternal blood flow, tobacco & cannabis had a tangled effect on the various types of blood flow between mother & baby
Intrauterine cannabis exposure and fetal and maternal blood flow: a case-control study
2021: In mice nursing their young, CBD & THC alter the fatty acid, lipid & endocannabinoid levels in their breast milk
Cannabinoids accumulate in mouse breast milk and differentially regulate lipid composition and lipid signaling molecules involved in infant development
In development, THC inhibits the Hedgehog pathway (one of the most important signaling pathways in early development, so named because you look like a hedgehog if you don’t have it)
Δ9-Tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
A review finds “a global moderate association between cannabis use and violence”
Cannabis use and violent behavior
This is supported by preclinical work in the ‘50s as well as a lot of anecdotes from the Reefer Madness era. When young men were told weed would make them crazy, they used it before fights & it worked. It probably doesn’t happen to a lot of people, but I’m sure it happens to some.
A look at cannabis smoking & lung obstructions & COVID-19
Association of cannabis with chronic obstructive pulmonary disease and COVID-19 infection
“Cannabis smoke affects the lungs similarly to tobacco smoke, causing symptoms such as increased cough, sputum, and hyperinflation. Cannabis can produce serious lung diseases with increasing years of use. Cannabis may weaken the immune system, leading to pneumonia. Smoking cannabis has been linked to symptoms of chronic bronchitis. Heavy use of cannabis can result in airway obstruction 8 and worse COVID‐19 outcome. 9 Yet, cannabis use might reduce lung inflammation and inhibit viral replication 10 in Covid‐19 infections, leading to a better outcome in some cases. 11 , 12”
In people with first-episode psychosis, heavy cannabis use may lead to a more “pronounced premorbid deterioration” before their first psychotic event
First-Episode Psychosis Patients Who Deteriorated in the Premorbid Period Do Not Have Higher Polygenic Risk Scores Than Others: A Cluster Analysis of EU-GEI Data
Using AI to analyze medical marijuana laws & cannabis use disorder rates, they found no significant effects of the laws on teen cannabis addiction rates
Long-Term Impact of Medical Marijuana Laws on the Burden of Cannabis Use Disorders in US Male and Female Adolescents and Young Adults
In teens, physical inactivity linked to a high risk of cannabis use disorder in adulthood
Physical inactivity during adolescence heightens risk for cannabis use disorder in adulthood
In a pregnant patient, using haloperidol to treat cannabis hyperemesis syndrome
Treatment of Cannabis Hyperemesis Syndrome Using Haloperidol in a Pregnant Patient: Case Report
A case report of a young cannabis user who died of cyclic vomiting
Death of a young woman with cyclic vomiting: a case report
In the heart, cannabis use associated with abnormal P-wave axis (a marker for heart aging) & is stronger in people with a history of cardiovascular disease
Cannabis Use is Associated With Abnormal P-wave Axis
In young cannabis users, they had higher odds of going to the hospital for a hypertensive crisis (a sudden, severe increase in blood pressure) but had lower odds of dying from it than non-users
Burden and Predictors of Hypertensive Crisis-Related Hospitalizations and Outcomes in Young Cannabis Users: A Nationwide Multi-Center Analysis
In an analysis of car crashes in Colorado counties, expanded access to cannabis may lead to a small increase but “a large increase in traffic crashes by more than 5% can be ruled out”
Does expanding access to cannabis affect traffic crashes? County-level evidence from recreational marijuana dispensary sales in Colorado
A review of 28 studies find no good biomarkers in the blood or oral fluids for them being used as a gauge of impairment
Are blood and oral fluid Δ 9-tetrahydrocannabinol (THC) and metabolite concentrations related to impairment? A meta-regression analysis
Unsurprisingly, a review of cohort studies finds that increased cannabis use is linked to increased rates of cannabis use disorder
Identifying risk-thresholds for the association between frequency of cannabis use and development of cannabis use disorder: A systematic review and meta-analysis
A review of the cannabinoids for myeloma (blood plasma cancer)
The Influence of Cannabinoids on Multiple Myeloma Cells: A Scoping Review
“It was demonstrated that CB decrease MM cell viability, and this was consistently shown to occur alongside the activation of apoptotic pathways in MM cells. These effects were shown to continue to occur in dexamethasone-resistant MM cells. The effects of CB on MM cells were enhanced when used in combination with standard treatments for MM. Critically, these marked decreases in MM cell viability induced by CB did not occur in non-MM cells.”
In liver cancer cells, CBD reduced their viability as well as inducing apoptosis (cellular suicide)
Cannabidiol inhibits cell viability and induces apoptosis in hepatocellular carcinoma cell lines: The interplay between apoptosis and autophagy
The anti-cancer effect of several cannabinoids against pancreatic & breast cancer cells
Anti-cancer effects of selective cannabinoid agonists in pancreatic and breast cancer cells
In mice being treated with the anti-cancer drug cisplatin, activating the CB2 receptor helped to protect their kidneys
The Cannabinoid-2 receptor agonist, 1-phenylisatin, protects against cisplatin-induced nephrotoxicity in mice
A review of insomnia & CBD suggests a little bit helps to quicken sleep & a lot can keep it away
Cannabidiol (CBD) and Insomnia : Literature review
“The review of the effect of CBD on sleep cycle suggest that medium to high doses increased REM sleep latency, and medium-low doses decreased REM sleep latency.”
I write constantly about CBD & sleep (you can see my advice here) & it always comes down to the fact that CBD affects everyone’s sleep differently. The only way to know if it will help you is by experimenting & finding out.
A review of using the cannabinoids for chronic pain
Cannabinoids for the treatment of chronic pain - an overview of current medical knowledge
A review of how storage conditions alter cannabinoids levels in human bodily fluids over time
Effects of the Storage Conditions on the Stability of Natural and Synthetic Cannabis in Biological Matrices for Forensic Toxicology Analysis: An Update from the Literature
2021: A gender analysis in rats finds females have lower 2-AG levels in their periaqueductal gray (a key brain region in behavior as well as the modulation of pain signals)
Sex differences in the expression of the endocannabinoid system within V1M cortex and PAG of Sprague Dawley rats
Using hemp leaf extracts to lower inflammation in kidney cells
Phytochemical differences of hemp ( Cannabis sativa L.) leaves from different germplasms and their regulatory effects on lipopolysaccharide-induced inflammation in Matin-Darby canine kidney cell lines
In a cellular model of Alzheimer’s, an anandamide analogue called N-linoleyltyrosine (NITyr) increased brain growth factors & protected the cells from autophagy (cellular suicide) via the CB2 receptor
N-linoleyltyrosine protects neurons against Aβ 1-40-induced cell toxicity via autophagy involving the CB 2/AMPK/mTOR/ULK1 pathway
2021: An analysis of how different cannabinoids bind to the CB1 receptor, the CB2 receptor & the joined CB1/CB2 heteromer complex
Similarities and differences upon binding of naturally occurring Δ 9-tetrahydrocannabinol-derivatives to cannabinoid CB 1 and CB 2 receptors
A new type of scaffolding for CB2 activators: triazoles – pentagons with 2 carbons, 3 nitrogens & a whole lotta attitude
1,2,3-Triazole derivatives as highly selective cannabinoid receptor type 2 (CB2) agonists
Yes, I’m available to write compelling copy for your synthetic cannabinoid lab work.
2021: Looking at new tools for chronic pain that inhibit both FAAH & the epoxide hydrolase enzymes (another set of lipid signaling molecules)
Further exploration of the structure-activity relationship of dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors
A review of portable biosensors for detection of cannabinoid levels
Portable biosensors for rapid on-site determination of cannabinoids in cannabis, a review
Using plasmonic sensors to detect cannabinoids
Self-Assembled Plasmonic Array Sensors for Cannabinoids
I don’t usually cover the incremental shifts in standard assay techniques, but this new scifi stuff is cool to see.
PS: For this week’s pleasing tunes, the album ‘Top d'Coroa’ by Bau. Born Rufino Almeida in Cape Verde, Bau’s father built instruments & taught him the guitar, the violin & the cavaquinho (a 4-stringed ancestor of the ukulele). With influences from Brazilian choro, Angola sambas, Gypsy rumbas & American fox-trots, he’s “an extraordinary guitarist, songwriter, arranger and bandleader”. He also led the backing band for the long world tours of Cesária Évora, the famed “Barefoot Diva” of Cape Verde.
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 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.