C&P#20: topical CBD for seizures + cannabis & male fertility + elite hockey players & the FAAH gene
War on Drugs taking body blows + Florida’s terrible legalization bill
A request to spread the word:
This newsletter only spreads by word of mouth – so forwarding & telling your friends goes a long way. Thank you for your help.
If you wanted to become a paid subscriber, you get no extra content, but the support allows me to produce more cannabinoid science content for the community.
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.
CBD helps with seizures even when only applied to the skin
Cannabinoids for cancer! Work on THC & CBD for making your cancer cells throw themselves on their own swords…
Are elite hockey players better because of their superior endocannabinoid systems?
Some War on Drugs pushback
A terrible earnings season for North American cannabis companies
My cannabis counseling sessions for your health
Cannabis is the medicine for aging. Its use goes far back through human history & now we understand how it works because of the endocannabinoid science. But for all the research & knowledge, the practical application is still trial & error. Everyone is different & everyone finds a different set of cannabinoids that work for them. If you – or someone in your life – needs help in figuring out what works best for you, I’m here to help.
I counsel people about using medical cannabis, CBD & THC as well as the lesser known but powerful cannabinoids like PEA (immune system health) & OEA (sleep). 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 (almost always the cost of products 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. And this includes 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.
Best of cannabinoid science...
In a survey, 90% of nurses thought patients should be able to use cannabis for their conditions & 67% believed that nurses should help the patients access it
Nurse Leaders’ Attitudes Toward and Experiences With Medical Marijuana
My godmother is a nurse & so are most of the women in my spiritual community. I am unsurprised that nurses continue to lead the way on practical sane solutions while the fatheads at doctor associations continue to be regressive prohibitionists.
In humans with focal epilepsy, treatment with transdermal CBD lowered seizure levels
Adjunctive Transdermal Cannabidiol for Adults With Focal Epilepsy: A Randomized Clinical Trial
A review of the effects of cannabinoids on a tumor’s microenvironment
Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation
A cool review looks at how cannabinoid signaling helps regulate our skeletal muscle
Molecular networks underlying cannabinoid signaling in skeletal muscle plasticity
In men using cannabis & seeking infertility treatment, they had a higher risk of low testosterone levels & altered sperm morphology
Effects of recreational cannabis on testicular function in primary infertile men
As we often say around, if you’re trying to get knocked up, both of you should lay off the grass. It’s probably not a huge drag on reproductive success (I’ve got two kids after all) but when you’re having difficulties, cannabis may exacerbate them.
In elite hockey players, a certain variant of FAAH is associated with super athletes, perhaps because it may cause higher pain tolerance & better stress coping
FAAH rs324420 Polymorphism Is Associated with Performance in Elite Rink-Hockey Players
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.
the Headlines & Fav Articles
In his inauguration statement, Colombia’s first leftist president says ‘the war on drugs has failed’
USAToday highlights the story of Edward Rubin, a prisoner serving 40 years on a cannabis charge while others in the now legal industry are striking it rich
Florida’s new cannabis legalization bill for 2024 is a pitch-perfect example of a monopolistic money grab
As Shaleen Title says,
· No homegrow
· Entire recreational market handed to the current medical market (ie: Truelieve – owners of 100 of the current 450 stores)
· No equity provisions
· No expungements for previous cannabis convictions
The Dept. of Justice seeks to dismiss a lawsuit (from Florida) that seeks to overturn a policy that blocks medical cannabis patients from owning guns
Oh man. This is so stupid it makes my head spin. If people can drink alcohol & own guns, they most certainly should be able to own guns if they have a medical cannabis card.
Legalizing cannabis leads to significant reductions in poisonings from synthetic cannabinoids
Synthetic cannabinoid poisonings and access to the legal cannabis market: findings from US national poison centre data 2016–2019
The Patent Office wants an appeals court to reject a trademark for a CBD beverage because the FDA considers CBD to be federally illegal
What rough times for the CBD industry. Illegal to who? The 2018 Farm Bill clearly made hemp extracts legal – but then the FDA sat on its thumbs for the last 4 years & kept insisting that CBD is illegal because there’s a pharmaceutical version of isolated CBD called Epidiolex. They refuse to issue any regulations & the new FDA leadership has made it clear that they plan to keep dodging the issue until Congress forces them to do something. Meanwhile, various branches of the federal government have an array of responses depending on who they’re looking to for their guidance. So instead of nicely growing over the last 4 years, the CBD industry had been cratering even before the recession hit.
In Nex Mexico, the Pojoaque pueblo opens the state’s first tribal cannabis dispensary
A Kentucky judge rules delta-8 THC products to be legal
In New Jersey, St. Peter’s University sues to keep a cannabis store from opening near its campus
The cannabis committee of the standards org ASTM creates new standards for environmental conditions during cannabis packaging, transit & storage
French Senators write an open letter on the advantages of legalizing cannabis
In general, France is one of the most regressive big EU members when it comes to cannabis – but the winds are slowly starting to shift here.
La vieille expression pour devenir riche était « faire un tabac ». Peut-être que ces jours-ci, c'est « faire un chanvre »
(Pourquoi oui, j'étudie surtout le français via l'idiome. Comment le saviez-vous?)
The War on Drugs & Harm Reduction
In New York, they will soon begin taking cannabis dispensary licenses exclusively from people impacted by the War on Drugs
Amerika in a nutshell…
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]
Ethan Nadelmann interviews Mountain Girl!
Friend of the newsletter Ros Watts creates a new scale for measuring a sense of connectedness to self, others & the world
The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world
It’s not often you see a bell hooks quote in a Psychopharmacology article.
A deep dive thread on Gordon Wasson & his ties to US Intelligence by @FatherMcKennaa
I’ve been studying the CIA & US Intelligence for the last 15 years & they still continue to surprise me with their dark penetration into the very core of psychedelic history.
Our friend, Wisdom Woman & psychedelic scholar Neşe Devenot on capitalism & poetry
Lawsuit alleges Compass Pathways “milked” researcher for trade secrets before “secretly” filing patent on same technology
On the business side, the smaller psychedelic companies are cutting back on their spending as the recession looms while the Big Fish are doubling down
Is virtual reality a replacement for psychedelics?
The old adage of journalism is that when a headline ends with a question mark, the answer to that question is no.
So there’s been a lot of pushback against this article & it does seem like the proselytizers took it too far, but I do look forward to the day when Google Bed administers just the right doses of ketamine while curating a perfect selection of psychedelic animation.
Law & Business
Canopy Growth lost $2 billion last quarter
while Curaleaf lost $28 million
Trulieve lost $22.5 million
Cronos Group lost $20 million
Charlotte’s Web lost $13 million
& the reasonable follow-up question to this doom & gloom earnings list…
Elixinol shifting away from CBD towards plant-based wellness products
The tobacco company Altria files 3 patents on modifying cannabis plants to control terpene formation
The Plant & the History
An analysis of the metabolites of hemp seeds finds that they have antioxidative effects
Metabolomics Analysis Revealed the Characteristic Metabolites of Hemp Seeds Varieties and Metabolites Responsible for Antioxidant Properties
How to measure the strength & viability of cannabis pollen
Methods for characterizing pollen fitness in Cannabis sativa L
Exploration of using hemp to clean up toxins at a former ethanol plant
Clinical Studies & Surveys
In college students with test anxiety, one dose of CBD did not alter their anxiety levels
A Double-Blind, Randomized, Placebo-Controlled Test of the Effects of Cannabidiol on Experiences of Test Anxiety Among College Students
In women with food addictions, a capsule of 100 mg of β-caryophyllene (usually the most common terpene in cannabis) for 8 weeks caused a lower score on a food addiction scale
The effect of β-caryophyllene on food addiction and its related behaviors: A randomized, double-blind, placebo-controlled trial
A look at how dysregulation of the endocannabinoid system may underlie suicidal behavior & represent an avenue of treatment
Characterizing chronic non-suicidal self-injury and other forms of repetitive and escalating suicide behaviour as endocannabinoid-mediated pain and reward disorders
In people getting bariatric surgery, cannabis had no negative effects on the subsequent weight loss
Weight loss outcomes are not compromised in bariatric patients using cannabis
In patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (an early neurodegenerative disease that causes pain & interferes with motion), a survey finds that there may be a role for cannabis in managing symptoms
Cannabis use in patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
In a large biomarker study of depression, the methylation (turning off) of the gene to create DAGL (the enzyme that creates 2-AG) was linked to improved depression scores
Identification of Endocannabinoid Predictors of Treatment Outcomes in Major Depressive Disorder: A Secondary Analysis of the First Canadian Biomarker Integration Network in Depression (CAN-BIND 1) Study
In 20 horses, 2 months of CBD caused no difference on sedation or ataxia (poor muscle control)
Effects of a supplement containing Cannabidiol (CBD) on sedation and ataxia scores and health: Effects of Cannabidiol on Sedation and Ataxia
In horses, a look at the distribution of cannabinoid receptors in their skin
The cannabinoid receptors system in horses: Tissue distribution and cellular identification in skin
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
In a type of spinal surgery, cannabis use before the surgery increased the risk of needing another surgery within a year
Marijuana Use and its Effect on Clinical Outcomes and Revision Rates in Patients Undergoing Anterior Cervical Discectomy and Fusion
A meta-analysis of studies finds that cannabis use increases the risk of psychosis
Risk-thresholds for the association between frequency of cannabis use and the development of psychosis: a systematic review and meta-analysis
A review on the negative effects of cannabinoid products on children’s brains
Pediatric Brain on Cannabinoids: Adverse Effects of Cannabinoid Products in Children and Adolescents
In a meta-analysis of 17 studies of patients with brain cancer, cannabinoids showed no effect on health-related quality of life or mental health
Cannabinoids to Improve Health-Related Quality of Life in Patients with Neurological or Oncological Disease: A Meta-Analysis
Children who experienced childhood cancer are prone to osteoporosis & this study suggests that targeting the CB2 & TRPV1 receptor may help
Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors
In pancreatic cancer cells, a mixture of THC & CBD inhibited cell proliferation & induced apoptosis (cellular suicide) via PPARγ’s control of genetic transcription
Antitumor Effects of Cannabinoids in Human Pancreatic Ductal Adenocarcinoma Cell Line (Capan-2)-Derived Xenograft Mouse Model
In lung cancer cells, CBD inhibited growth & upregulated proteins related to apoptosis (cellular suicide)
Cannabidiol Regulates PPARγ-Dependent Vesicle Formation as well as Cell Death in A549 Human Lung Cancer Cells
In bladder cancer cells, cannflavin A caused apoptosis (cellular suicide) & worked well with other chemotherapeutic agents as well as the other cannabinoids
Anti-cancer properties of cannflavin A and potential synergistic effects with gemcitabine, cisplatin, and cannabinoids in bladder cancer
In a rat model of chemotherapy treatment, cannabis extract increased body weight & normal diet intake as well as decreasing oxidative stress & inflammation
Protective Effects of Cannabis sativa on chemotherapy-induced nausea in a rat: Involvement of CB1 receptors
A review of cannabinoids for movement disorders
Randomized controlled trials on the use of cannabis-based medicines in movement disorders: a systematic review
“No improvement of motor symptoms was shown in any of the two RCTs with this as primary outcome (PO), but in the nabilone group, an improvement in quality of life was documented. Of the three RCTs having levodopa-induced dyskinesia as PO, only one using nabilone showed a reduction. Anxiety and anxiety-induced tremor could be reduced in the cannabidiol group as well as anxiety and sleeping problems in the nabilone group in another RCT. In two RCTs with Tourette syndrome, an improvement in tics was revealed. From three RCTs on Huntington's disease only one found symptoms relief using nabilone. No reduction of dystonia could be shown in the two included RCTs.”
A review of THC & CBD for pain & mental health conditions
Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions
In a rat model of migraines, inhibiting the FAAH enzyme lowered pain levels & the inflammatory response
Potentiation of endocannabinoids and other lipid amides prevents hyperalgesia and inflammation in a pre-clinical model of migraine
In a computer analysis for diabetic effects, CBD, THC & full-spectrum extracts were found to inhibit α-glucosidase (an enzyme that breaks down glucose)
α-Glucosidase inhibitory activity of cannabidiol, tetrahydrocannabinol and standardized cannabinoid extracts from Cannabis sativa
In rats, THC impairs memory formation via changes in the brain’s microtubules
Δ9 -THC Administration Reduces Microtubule Protein Network Dynamics and Impairs Memory Formation in Male Wistar Rats
In mice exposed to nicotine, inhaling β-caryophyllene causes the terpene to be incorporated into the heart’s aorta & to protect from the degeneration caused by nicotine
Inhaled volatile β-caryophyllene is incorporated into the aortic wall and attenuates nicotine-induced aorta degeneration via a CB2 receptor-dependent pathway
In young mice, inactivating their CB1 receptors led to perturbations in the development of their oligodendrocytes & the myelin sheaths they produce to protect the neuron’s ability to fire
Cannabinoid CB 1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
In a mouse model of Parkinson’s disease, activating the CB2 receptor reduced their anxious & depressive behaviors & improved motor deficits
CB2 Agonist GW842166x Protected against 6-OHDA-Induced Anxiogenic- and Depressive-Related Behaviors in Mice
An array of techniques determines when the body breaks down CBG, the resulting metabolites are also active in our system & when applied to brain immune cells, they reduce inflammation
Metabolites of Cannabigerol (CBG) Generated by Human Cytochrome P450s are Bioactive
PS: For today’s sweet tunes, Les Paul’s ‘Hawaiian Paradise’. Known for the famous type of guitar named after him, Les Paul is the only person inducted into both the Rock and Roll Hall of Fame & the National Inventors Hall of Fame. By his teens, he’d already invented a harmonica holder for around his neck that allowed him to play both sides without his hands, he wired a phonograph needle from his guitar to a radio speaker & at 13, he was a semi-professional country music singer & guitarist. In 1940, he began work on the solid-body electric guitar known as the ‘The Log’ that would make him famous. Interrupted by WW2, he played backup to the likes of Bing Crosby & the Andrews Sisters when they performed for the troops. In Chicago, he befriended Django Reinhardt & Art Tatum as well as meeting his wife Mary Ford, who he performed with on many radio programs & shows until their divorce. His new guitar design became a hit & he started experimenting with some key technical innovations in sound engineering such as multitrack recording (such as the song “Lover” where he plays 8 of the parts), the flange effect of phasing in & out of harmonic tone (first heard in “Mammy's Boogie”) & his own design of the first 8 track recording deck using a stack of 8 tape recorders (which WC Fields dubbed ‘The Octopus’). He continued inventing & innovating the world of music & at the age of 90, was still playing Manhattan's Iridium Jazz Club every Monday night. What a guy.
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…]
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]
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.