C&P#16: me on GABA & you! + hemp for football players + cancer & cannabis
Minnesota accidentally legalizes THC edibles & Clint Eastwood wins settlement
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.
Did you miss me? I forgot to say that last week was vacation week. We got the kids together with their cousins at the beach. My oldest learned to doggy paddle & the baby is taking her first steps. Life is good. I hope you’re the same.
Former NFL players see help from hemp extracts, cancer patients see help from medical cannabis & we have an especially large harms section with studies on teens & cannabis including an increased risk of suicide.
I wrote a thing! GABA GABA Hey!
I very much enjoy writing for ProjectCBD. Martin Lee is a great editor & he gives me the freedom to write science-heavy pieces like this one on GABA, the brain’s primary inhibitory neurotransmitter. Plus, the graphics are always fun.
Enjoy this one – and I’ll get started on the next neurotransmitter in our series: dopamine
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My ad: Cannabis counseling health sessions
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 – need help figuring out what works best for you, I’m here to help. You can see my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression here.
I counsel people about using medical cannabis, CBD & the lesser known but powerful cannabinoids like PEA & OEA. 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...
A study in former professional football players found that hemp extracts may help with cognitive performance & emotional processing
Automated Detection of Cognitive Performance and Resilience Changes in Former Professional American Football Players Following the Administration of a Hemp Extract
For cancer patients, cannabis helped them with pain & to use fewer opioids
Experience With Medical Marijuana for Cancer Patients in the Palliative Setting
A review of kids using artisanal CBD oil for their epilepsy showed it to be effective & safe
The long-term effectiveness and safety of cannabidiol-enriched oil in children with drug-resistant epilepsy
In general, studies have shown that full-spectrum extracts work better for pediatric epilepsy than isolated CBD alone.
In humans with X-linked adrenoleukodystrophy (a rare genetic condition that damages the myelin sheaths of your nerve cells as well as your adrenal glands), they had higher levels of CB2 receptors & activating those CB2 receptors improved the metabolic problems underlying the disease & helped with oxidative stress
Activating cannabinoid receptor 2 preserves axonal health through GSK-3β/NRF2 axis in adrenoleukodystrophy
One of the most notable aspects of the cannabinoids is how often they help with rare disorders where we have few options. The ubiquity of the endocannabinoid system speaks to its power to heal.
A nice doctor’s primer on how to create a medicinal preparation of cannabis oil
Is There Enough Knowledge to Standardize a Cannabis sativa L. Medicinal Oil Preparation with a High Content of Cannabinoids?
& here’s guidelines for how to select & purchase your medical cannabis for clinical trials
Cannabis Medicines: Guidance for the Selection, Purchase and Supply for Clinical Trials
In lung cells, full-spectrum CBD-rich extracts are more potent than isolates & they recommend a cannabinoid mouth wash as a barrier to entry
Crude Cannabis Extracts are More Potent than Mono- Substances in Inhibiting SARS-CoV-2 Entry
In a mouse model of Parkinson’s disease, CBD improved cognitive dysfunction & increased locomotion, decreased neuroinflammation & protected the dopamine-producing neurons
Cannabidiol Alleviates the Damage to Dopaminergic Neurons in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson's Disease Mice Via Regulating Neuronal Apoptosis and Neuroinflammation
Here’s something new: a successful trial of a topical gel with a CB1 antagonist in it that keeps people from getting too high
I guess this makes sense – but the classic treatment for an overly strong cannabis intoxication is dabbing straight CBD. It’s known as the parachute.
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.
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 news, articles & videos
On how THC alters your sleep architecture by the excellent science writer Dr. Nick Jikomes
the Headlines & Fav Articles
In a decision that inspired a flurry of memes, Minnesota accidentally legalizes THC edibles
NJ stopped collecting tax on medical cannabis
Good for them. A tax on medicine is an abomination.
Uruguay not planning on selling cannabis to tourists any time soon
Of all the countries in the world where I’d like to do a cannabis research trip & report back on what’s happening on the ground, it’s Uruguay. It looks like a great system. Sponsor me?
Alice Moon on the 9 best newsletters for cannabis people (including yours truly)
Clint Eastwood won a $2M settlement against a CBD company for using him in a fake endorsement
Luckily, the Cannabinoids & the People Official Tough Guy Brand Ambassador Charles Bronson isn’t going to be suing anybody.
The War on Drugs & Harm Reduction
Federal prosecutors are crowing about crackdowns on unlicensed marijuana dispensaries
If you’re still ruining lives & imposing penalties, the War on Drugs isn’t over.
& the FDA worked with Hawaiian law enforcement on some kind of surveillance operation to stop some kind of drug
It's all pretty vague right now – but seeing the FDA get more cozy with local law enforcement doesn’t seem like the right direction.
NYC police said they’ll stop testing officers for cannabis to comply with a city memo – then reversed themselves & said they’ll keep doing it while they review potential conflicts with federal law
Meanwhile, the NY firefighters say that they simply will stop testing
Surprisingly, the LA Times still tests their employees for cannabis – and now there’s pushback to end the practice
The DEA wants to ban 5 psychedelic compounds that no one besides researchers use & it kicked up such a storm of protest that now they have to hold hearings
‘Mexican Cartels as Vicious Firms’ – an academic look at the business of cartels, who now operate more as transport companies than anything else
Just like the Mob’s rapid growth was fueled by alcohol’s Prohibition before they diversified into other fields, the current Prohibition of drugs supercharged the cartels. But now they are entrenched – and even if we legalized all drugs (like we should), they will continue to diversify into new areas. The US-led War on Drugs created these cartels & their violence. Now generations will reap the punishment.
Law & Business
The National Basketball Players Association partners with Al Harrington's CBD brand Re+Play which will be sold by Amazon & Walmart
THC craft beer launched by former Blue Moon brewmaster
Charlotte’s Web full-spectrum hemp extract approved in the UK
The Plant & the History
An analysis of the trace elements found in cannabis
Evaluation of trace elements in cannabis products
On how to control odor from cannabis farms by Nate Seltenrich
Odor Control in the Cannabis Industry: Lessons from the New Kid on the Block
A review of using microalgae to produce cannabinoids
Harnessing the advances of genetic engineering in microalgae for the production of cannabinoids
The general wisdom is that these processes do not scale. This means that while they might not be useful for THC or CBD, they could be a way to produce the rarer cannabinoids.
A review of hemp-based foods finds little cause for concern – though a few of the samples of hemp seed oil contained enough THC to cause impairment
How safe are hemp-based food products? A review and risk assessment of analytical data from Germany
A US Dept. of Energy grant for hemp-based 3d printed materials to build affordable housing
How to produce hemp-based acoustic tiles
A Design and Fabrication Method for Hemp Based Acoustic Elements
The US Army wants hemp yarn to help snipers stay undetected by enemy forces
I was going to say that I had not expected a “use hemp to leave your enemies dead from afar” – but that’s a silly lapse of historical knowledge. The first crossbows used hemp fiber. Trebuchets & naval ships used hemp rope. And the very first multi-stage aerial attack vehicle was a Chinese invention that used hemp to float a balloon of explosives over your enemy’s ship & then have it burst into flames & rain down hell fire on your enemies.
So yeah, this tracks.
Plant Medicines & Other Psychoactives
Ann Shulgin passed away. Another hero crosses over. RIP
Thanks to Ann Harrison/Annie Oak for the writeup.
The Mormons & magic mushrooms by Cassady Rosenblum
A study of MDMA for PTSD across racial groups shows efficacy
MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial
A review of ketamine & psychedelics on treatment-resistant depression with a focus on neuroinflammation & neural growth
The effects of ketamine and classic hallucinogens on neurotrophic and inflammatory markers in unipolar treatment-resistant depression: a systematic review of clinical trials
After one month of microdosing psilocybin, people saw improvements in mood & mental health
Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls
Clinical Studies & Surveys
In a test of female athletes who used cannabis regularly, while there was no difference in body size, body composition, pulmonary function, cardiorespiratory function, or muscular strength, they produced less power in a laboratory fitness test but also experienced significantly less anaerobic fatigue
Regular Use of Cannabis in Female Athletes Is Associated With a Reduction in Early Anaerobic Power Production
In patients with early psychosis, one dose of CBD lowered activity in the insula (a brain region associated with motivation & sensory processing)
Cannabidiol attenuates insular activity during motivational salience processing in patients with early psychosis
Jazz Pharmaceuticals announces their studies on a 1:1 THC:CBD formula didn’t help in a phase 3 study of multiple sclerosis & the ability to help improve lower limb muscle tone
Jazz Pharmaceuticals Announces Top-line Results from Phase 3 Trial Evaluating Nabiximols Oromucosal Spray in Adult Participants with Multiple Sclerosis Spasticity
However, they only administered the drug for 3 weeks. That doesn’t seem like nearly long enough to create a change in muscle tone (or the brain). For neurodegeneration, it can take weeks for the positive effects of cannabinoids to be seen – and sometimes the only change is hard to see: not a miracle cure but simply a slowing of degeneration. What I believe is that the cannabinoids give you more good years.
See my advice on cannabinoids & neurodegeneration here.
In humans, drinking alcohol lowered the levels of anandamide in their blood
The effects of acute alcohol administration on circulating endocannabinoid levels in humans
In an analysis of urine drug testing, they found that oral THC caused a positive test 97% of the time & vaporized cannabis ~60% of the time
Urinary Excretion Profile of Cannabinoid Analytes Following Acute Administration of Oral and Vaporized Cannabis in Infrequent Cannabis Users
In general, drug tests look for the presence of Δ9-THC-COOH, a breakdown product of delta-9 THC – but this study suggests we might start considering 11-OH-Δ9-THC.
A survey of UK medical cannabis users found that they feared the opinions of their healthcare providers as well as the criminal justice system
Perceived Stigma of Patients Undergoing Treatment with Cannabis-Based Medicinal Products
In adolescent cannabis users, an increased risk of suicidal ideation, suicide planning & increased risk of suicide attempt
Cannabis smoking increases the risk of suicide ideation and suicide attempt in young individuals of 11-21 years: A systematic review and meta-analysis
This doesn’t surprise me. I believe that non-coercive methods to encourage kids to wait longer until trying cannabis are a good thing.
In young adults with heavy cannabis use, brain scans show aberrant shapes of the hippocampus (a memory center of the brain)
Aberrant hippocampal shape development in young adults with heavy cannabis use: Evidence from a longitudinal study
In teens, cannabis & alcohol use associated with worse sleep
A latent class approach to understanding longitudinal sleep health and the association with alcohol and cannabis use during late adolescence and emerging adulthood
Among cannabis users, a review of the rare adverse event of acute pancreatitis (inflammation of the pancreas, usually with pain & nausea)
Acute pancreatitis as a rare adverse event among cannabis users: A systematic review
In humans with diabetes, cannabis use is associated with angina (severe chest pain)
Cannabis Use Is Associated with Prevalent Angina in Individuals with Diabetes
In a reply to another report about children & cannabis edibles, New Jersey’s poison control center reports increased pediatric exposures to edible cannabis
Reply to: Edible Cannabis Exposures Among Children: 2017-2019
In human gum cells, cannabis smoke changed their shape & adhesion ability, decreased cell viability & increased oxidative stress & cell death
Cannabis smoke condensate induces human gingival epithelial cell damage through apoptosis, autophagy, and oxidative stress
This review of 3 studies looks at the contradictory findings of cannabis & bladder cancer: potential carcinogenic versus protective effect
The association of bladder cancer and Cannabis: A systematic review
In brain cancer cells, a synthetic cannabinoid reduced growth, proliferation, migration & increased cell death
Anti-Tumorigenic Effect of a Novel Derivative of 2-Hydroxyoleic Acid and the Endocannabinoid Anandamide on Neuroblastoma Cells
In rats with spinal nerve injuries, activating the CB1 receptor reduced pain as well as altering the plasticity of the relevant neurons
Endogenous Cannabinoid Receptors Modulate Plasticity at Immature Synapses
In a mouse lung cell model of acute lung injury & sepsis, activating the CB1 receptor protected them via regulation of the macrophages (mobile white blood cells)
WIN55212-2 alleviates acute lung injury by inhibiting macrophage glycolysis through the miR-29b-3p/FOXO3/PFKFB3 axis
In a computer simulation, the main cannabinoids seem to help with neurodegeneration via the alleviation of stress on the endoplasmic reticulum (the site of protein & lipid synthesis)
Promising Action of Cannabinoids on ER Stress-Mediated Neurodegeneration: An In Silico Investigation
In a rat model of fentanyl relapse, the cannabinoid & dopamine systems didn’t seem to be involved in a brain region linked to addiction
Lack of causal roles of cannabinoid and dopamine neurotransmitter systems in orbitofrontal and piriform cortex in fentanyl relapse in rats
In a mouse model of liver disease & obesity, cannabis extracts did not cause profound metabolic changes but did improve the gut microbiome diversity
Cannabis Extract Effects on Metabolic Parameters and Gut Microbiota Composition in a Mice Model of NAFLD and Obesity
In a computer simulation & a mouse model of ulcerative colitis, phycocyanin (a CB1 & CB2 activator from blue-green algae) prevented pathological alterations the colon such as shortening as well as causing improvements to inflammation levels & the gut microbiome
Phycocyanin stimulates ulcerative colitis healing via selective activation of cannabinoid receptor-2, intestinal mucosal healing, Treg accumulation, and p38MAPK/MK2 signaling inhibition
An activator of the CB2 receptor that glows in the dark so that you can track it with a PET scan
Structure-Based Design, Optimization, and Development of [18F]LU13: A Novel Radioligand for Cannabinoid Receptor Type 2 Imaging in the Brain with PET
Imagine attaching a radioactive tag to a slippery elephant made out of fat that you have to hunt through the jungle at the bottom of the test tube.
Chemistry be like that.
PS: This week we feature one of the most influential guitarists of the roots era, Elizabeth Cotten & her 1958 album ‘Freight Train And Other North Carolina Folk Songs And Tunes’. Born in 1893, she started playing banjo at the eight & soon moved onto her brother’s guitar. Because she played with her left hand on a right handed guitar, she held it upside down & played the melody with her thumb instead of her fingers, leading to the style now known as ‘Cotten picking’. She soon went to work as a domestic & then had her first child, giving up the guitar until her mid ‘40s. After a chance meeting in a department store of the legendary musical family of the Seegers (including the young Pete Seeger), she started taking care of their kids – and when they learned she could play, they soon recorded her for Folkways, the folk & world music label acquired by the Smithsonian for its catalog of important music. Her track ‘Freight Train’, written when she was 12 but recorded in her 60s, became a Top 5 hit in the UK & her success led to more albums, more tours & finally a Grammy in the final years of her life. She continued playing into her 80s, remembering more songs from her childhood as well as writing more material. For my very favorite track, here’s ‘Shake Sugaree’ that she did with a great-grandchild.
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.