C&P#18: Cannabinoids for brain protection + psychedelics & the supernormal
plus pain, cancer, wound healing, MS & lots of good review articles
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Still catching up on science from my vacation, so you’ve got a good download here including,
· A lot on cannabinoids for neurodegeneration (my advice here)
· The power of topical CBD for the skin & skin healing (science here)
· Some disturbing epidemiology studies broken out into their own section
· & in the psychedelics section, supernormal phenomena & the headtwisters
Psychedelic science for your business?
For our category ‘Psychedelics, Plant Medicines & Other Psychoactives’, I moved up its position in the newsletter because of how much people liked it. And that inspired me to make an offer:
I’m not currently doing a deep dive on the new psychedelic science that comes out every week – but I could do that for the right company.
If you know a psychedelics company who might want all of the new psychedelic science each week, shoot this newsletter their way. Or if you have a company you’d recommend that I pitch, reply to this email & let me know.
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:
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Best of cannabinoid science...
In a survey of Parkinson’s patients, the use of cannabis was associated with improvements in motor function, sleep & pain
Cannabis use in Parkinson’s disease—A nationwide online survey study
Many patients with multiple sclerosis use cannabinoids for pain relief
Cannabinoid use for pain relief among people with multiple sclerosis
A review of using cannabinoids for treating dementia
Cannabinoids for the treatment of dementia: summary of a Cochrane review
In a case study of a woman with severe recessive dystrophic epidermolysis bullosa (a rare genetic skin fragility disorder), after nothing else helped with the pain, oral CBD drops helped improve her pain to tolerable levels, improved her ability to swallow as well as her quality of life
Purified oral cannabidiol for pain management in severe recessive dystrophic epidermolysis bullosa
In rats with cuts in their skin, CBD improved inflammation & healing time, probably via the CB2 receptor
Cannabidiol Improves Random-Pattern Skin Flap Survival in Rats: Involvement of Cannabinoid Type-2 Receptors
In a survey of young adults with cancer, the most frequent reasons for cannabis use were pain, anxiety, nausea, sleep & recreation
Cannabis consumption in young adults with cancer: descriptive study
A cool review of how oxytocin interacts with the endocannabinoids to alter social behavior
Sex-specific and social experience-dependent oxytocin-endocannabinoid interactions in the nucleus accumbens: implications for social behaviour
In older rats, 7 days of CBD treatment caused an antidepressant effect
Dose-Dependent Antidepressant-Like Effects of Cannabidiol in Aged Rats
In mice being fed a high-fat diet, CBD & omega-3 fatty acids caused them to live longer & protected from brain damage
Omega 3 Fatty Acid and Cannabidiol Prolong Lifespan and Ameliorates Brain Ischaemia in Mice Fed Chronic High Fat Diet
In an older mouse model of Alzheimer’s, low doses of intranasal THC for 3 months significantly slowed memory decline
The Memory Benefit to Aged APP/PS1 Mice from Long-Term Intranasal Treatment of Low-Dose THC
A deep dive into how widespread the endocannabinoid system is in the roundworm family
Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery
This is a great look at how important the endocannabinoids are in even a more simple family like the nematodes. It speaks to how far back the ECS goes in evolutionary history. Even in this creature with just 302 neurons (specifically, the C. elegans hermaphrodite), the endocannabinoids are necessary for homeostasis, brain growth & metabolism.
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 news, articles & videos
A thread from Ruby Deevoy with people’s stories about using cannabis for cancer
On the effects of cannabinoids on our metabolism by Dr. Tanja Bagar
The role of the endocannabinoid system and selected phytocannabinoids in metabolism
On the underground use of synthetic cannabinoids by Nate Seltenrich for Project CBD
A summary on the diagnosis & treatment of cannabinoid hyperemesis syndrome
Last Gag with Mary Jane: Cannabinoid Hyperemesis Syndrome (CHS)
At Hebrew University, using a virus to enhance cannabinoid production
Leafly launches a data-sharing program to advance cannabis research
Not our normal topic of coverage – but I enjoy a good bit of scientific detective work: the COVID-19 virus really did come from animals in the Wuhan animal market
I always suspected the lab leak theory just because of the caginess of the Communist Party – but this body of evidence is enough to convince me completely that this was zoonotic transmission.
the Headlines & Fav Articles
The National Institute of Standards and Technology releases a new federal handbook with a cannabis section on potency, packaging, labeling & more
Something about NIST makes me guess that they’re a bunch of nerdy secret pot smokers.
House bill to lower cannabis research barriers moves forward
But here’s a takedown of the bill saying how it will make things worse by Shane Pennington of On Drugs
In funny nomenclature news, a new House bill to create Centers of Excellence in Cannabis Research is named DANK (Developing and Nationalizing Key Cannabis Research Act)
At Marijuana Moment, they can’t figure out if the lawmakers purposely used this nickname for great weed or not.
Personally, while I dislike weed puns in journalism headlines, I do appreciate them in government bills.
South Dakota opens its first medical cannabis dispensary
NY bans smoking of cannabis & tobacco in parks, beaches, playgrounds & other public spaces
But they plan to allow it at the State Fair
In the Britney Griner case, the US offers a prisoner swap for a convicted Russian arms dealer
100 cannabis plants found growing in Thailand’s Parliament complex
(see Cannabinoids & the People #2 for a similar story from Steinbeck in Los Angeles)
In Singapore, they hanged a man convicted of cannabis trafficking
The Juicyfields cannabis Ponzi scheme finally collapsed (by Dario Sabaghi)
E-growing: do you want to invest in a cannabis plant without getting your hands in the dirt while making 100%+ returns?
Of course you do.
Is it a scam that took in billions?
Sure looks like it.
(there’s already a podcast about it – and I’d put my money on a documentary within the year)
The War on Drugs & Harm Reduction
In Illinois, all of the 149 new cannabis dispensary licenses went to social equity applicants
The Prairie State joins the list of cannabis regulators actually trying to right the wrongs of the War on Drugs.
Biden’s ‘Safer America Plan’ would eliminate the heinous crack/powder cocaine sentencing disparity but double-down on fentanyl punishments
The DEA cancels their ban of 5 rare psychedelics after strong researcher & community pushback
Psychedelics, Plant Medicines & Other Psychoactives
[I’m moving this section up in the ranks because of its popularity. But this isn’t a deep dive into the science of psychedelics like I do for the cannabinoids. It’s just a smattering of what happens to come across my feeds.
If a weekly newsletter with all the new psychedelic science powered by Google Scholar Alerts for all the major keywords would be of interest to a company out there, reach out to me]
An open letter making the rounds about why the writer left the psychedelic movement
A piece on the long history between telepathy & psychedelics by Shayla Love
& an article on the “impossible” supernormal phenomena that happens with psychedelics by Dr. Mona Sobhani
I’ve been doing a TikTok series about the books I’ve been reading on the supernormal (another term for the paranormal). If interested, check out (in order of release) Keel’s ‘The 8th Tower’, UFOs by an investigative journalist, the effects of consciousness on matter by the field’s grand old man Dr. Dean Radin, reincarnation by Dr. Ian Stevenson & the newest collection of essays on the scientific theories & history that might explain all this.
Though the author who started me onto the science of the supernormal is most certainly Dr. Jeffrey Kripal. I talk about one of his books here & you can see my Lex Files interview with him here.
Also, Shayla Love turned me onto the book ‘Otherworlds: Psychedelics and Exceptional Human Experience’ by David Luke. I just started it last night – but it might be the book on the subject that I’ve found so far. According to his study, half of people who have taken psychedelics experienced some kind of supernormal phenomena. And it’s well known that early researchers on DMT referred to it as telepathine.
“There are more things in heaven and earth, Horatio, Than are dreamt of in your philosophy.”
Inside Sasha Shulgin’s lab with Madison Margolin
Why are 5% of people unaffected by DMT? by Andrew Gallimore
On the difference between the two major psychedelic amphibians by Igor Domsac of ICEERS
This ‘complex systems theory’ approach to psychedelics is an intriguing angle (via lead author Inês Hipólito)
Pattern Breaking: A Complex Systems Approach to Psychedelic Medicine
A new review on the many levels of the mechanisms of how psychedelics work
Pharmacological, Neural, and Psychological Mechanisms underlying Psychedelics: A Critical Review
A psychedelic glossary by the law firm of Harris Bricken
Sometimes I’ll link to a paper because it’s so silly. Here’s a bunch of brain research in mice showing that ketamine might not be that additive – but to anyone who’s talked to anyone, ketamine is known as ‘psychedelic heroin’
Dual action of ketamine confines addiction liability
You don’t have to talk to harm reduction people in the UK party scene to know that ketamine is an incredibly addictive substance. Not physically, but mentally. It creates a foggy gap between you & your pain – and because it’s so easy to take & has almost no hangover effect, you can simply take moderate amounts all of the time & get away with it. Ketamine can suck people in for years & years. Personally, it’s the most addictive substance I’ve ever interacted with.
But yeah, these mice didn’t look addicted.
Law & Business
A new film on the tough times for Mendocino's craft farmers by Matt Grimshaw
A study on the effects of cannabis packaging on consumer perceptions
The Impact of Cannabis Packaging Characteristics on Perceptions and Intentions
“Edible gummies were perceived as healthier … and more socially acceptable to consume … than cannabis concentrate in a medical dropper. Participants also had more interest in trying edible gummies … and trying a free sample … than trying cannabis concentrate. Cannabis packages with a helps-you-relax health claim elicited more happy … and good … feelings than cannabis packages without this claim. Minimal effects were found for visual displays of tetrahydrocannabinol content and health warnings.”
An unsurprising study of the California cannabis market finds that higher THC levels equal higher prices
Association of Tetrahydrocannabinol Content and Price in Herbal Cannabis Products Offered by Dispensaries in California: A Purview of Consumers/Patients
Also, since the presence of CBD tends to lower the amount of THC, that means lower prices for plants with even a small amount of CBD. That’s unfortunate because as Dr. Raphael Mechoulam says, he wishes all cannabis had at least a 1% CBD level just to offset and protect from the negative psychoactive effects of THC.
David Ortiz starts a line of cannabis products
I was going to school in Boston when the Sox took the pennant & broke the Curse. #BlessBigPapi
A new high hot sauce: 9000 Scoville, 1000 mg THC
The Plant & the History
Hemp acres planted in the US way down this year
They promised that hemp would save the farmers. It did not. Between the onerous red tape, the stupidly low THC limits that result in whole crops being burned or plowed under & the fact that a few large farms could supply the entire country’s CBD needs, the ‘save the farmer’ angle was always a bit of a ploy.
An analysis of a well-known hemp cultivar finds a new cannabinoid: 2α-hydroxy-Δ3,7-cannabitriol
Phytochemical Analysis of the Methanolic Extract and Essential Oil from Leaves of Industrial Hemp Futura 75 Cultivar: Isolation of a New Cannabinoid Derivative and Biological Profile Using Computational Approaches
One day, I dream of a catwalk fashion show where each of the phytocannabinoids comes out as an elephant dressed in different clothing & with cutting-edge body modications.
(can’t wait for DALL-E 2 to release…)
In female pigs fed hemp seed oil, they had increased lean meat percentage, more fatty acids & immune system antibodies in their milk, reduced incidence of diarrhea & lowered methane emissions
Alterations in Essential Fatty Acids, Immunoglobulins (IgA, IgG, and IgM), and Enteric Methane Emission in Primiparous Sows Fed Hemp Seed Oil and Their Offspring Response
Methane emission from livestock is a significant source of global warming gases. There are a lot of studies about ways to get cows to burp less methane. It would actually make a difference.
A study of using hemp seed oil as a biodiesel in an engine
The industrial-grade hemp (Cannabis sativa L.) seed oil biodiesel application in a diesel engine: combustion, harmful pollutants, and performance characteristics
But as our Biodiesel Consultant Ned Pelger opines, “mixing at 5 to 10% is rarely worth the effort.”
Clinical Studies & Surveys
In this double-blind study of stroke patients experiencing spasticity, the use of 1:1 CBD:THC sprays was found to be safe for the heart but saw little effect on pain or spasticity levels
Cannabinoid Effect and Safety in Spasticity Following Stroke: A Double-Blind Randomized Placebo-Controlled Study
In patients undergoing thoracolumbar spinal fusion, cannabis use had no impact on surgical complications after 3 months – except for those undergoing the surgery for adult spinal deformity. Those cannabis users had less complications than non-users.
The Impact of Isolated Baseline Cannabis Use on Outcomes Following Thoracolumbar Spinal Fusion: A Propensity Score-Matched Analysis
In humans with a traumatic injury, their levels of 2-AG after the injury were correlated with their chances of being in chronic pain months later
Serum Concentrations of the Endocannabinoid, 2-Arachidonoylglycerol, in the Peri-Trauma Period Are Positively Associated with Chronic Pain Months Later
In patients with systemic lupus erythematosus (an inflammatory autoimmune disorder where the body attacks its own tissues), increased levels of 2-AG in their blood acted via CB2 receptors to lower the levels of type 2 interferon production from white blood cells (a good thing)
2-Arachidonoylglycerol Reduces the Production of Interferon-Gamma in T Lymphocytes from Patients with Systemic Lupus Erythematosus
In humans smoking cannabis versus placebo, they had no differences in the blood immune markers analyzed except that the cannabis smokers had higher levels of mRNA for the CB2 receptor
Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking
The researchers were looking for blood immune factors that might increase the risk of schizophrenia – but didn’t really find any.
In a study of patients with multiple sclerosis, they looked for easy to measure immune markers that could operate as stand-in measurements for the more complicated tests for CBD & THC levels
Correlation of Nabiximols Dose to Steady-State Concentrations of Cannabinoids in Urine Samples from Patients with Multiple Sclerosis
Whew. Using public health programs in schools usually backfired & if they did anything at all, they increased the use of substances like alcohol & cannabis
The association between public health engagement in school-based substance use prevention programs and student alcohol, cannabis, e-cigarette and cigarette use
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
A review of the risks of medical cannabinoid use in children
Marijuana use in children: An update focusing on pediatric tetrahydrocannabinol and cannabidiol use
An observational study of new mothers finds that cannabis use during pregnancy was associated with lower birthweight
The prevalence and significance of gestational cannabis use at an Australian tertiary hospital
That being said, one explanation is that cannabis use tends to make the baby come out a little bit earlier – and that might be the reason they tend to weigh less.
A survey looking at the effects of secondhand cannabis smoke on children find no effects on any of the measures except for a small increase in viral respiratory infections
Association between secondhand marijuana smoke and respiratory infections in children
In general, secondhand smoke is a very overblown fear that the FDA has been using in its War on Tobacco. I know tobacco smoking is bad - but you don’t need to lie & exaggerate the risks to people around the smokers. And now, the FDA is starting to focus on thirdhand smoke, which is the particulates that attach to surfaces after smoking. That seems like an especially long reach.
A review of studies finds a link between psychosis & the use of higher potency THC
Association of cannabis potency with mental ill health and addiction: a systematic review
A review of using cannabinoids to treat cannabis use disorder finds that dronabinol (a synthetic form of THC) reduced withdrawal symptoms & that cannabis use overall was decreased by CBD, nabiximols (1:1 THC:CBD sprays) as well as a FAAH inhibitor
Cannabinoids in the Treatment of Cannabis Use Disorder: Systematic Review of Randomized Controlled Trials
Legalization of cannabis associated with increased traffic crash rates
Changes in Traffic Crash Rates After Legalization of Marijuana: Results by Crash Severity
In brain scan studies that show less gray matter for cannabis users, the results may be confounded by their tobacco use
Prefrontal Cortex and Putamen Grey Matter Alterations in Cannabis and Tobacco Users
In male rats, the synthetic cannabinoid AMB-FUBINACA caused lower testosterone levels & negative changes to the testicles
Experimental Study on Sub-acute Testicular Toxicity of AMB-FUBINACA in Adult Male Albino Rats
A case study of a young man with a heart attack after using cannabis
Marijuana-induced myocarditis in a 24-year-old man
Ha. If you put an alcohol ignition lock on a car, the driver will tend to use more cannabis
Cannabis Adaptation During and After Alcohol Ignition Interlock Device Installation: A Longitudinal Study
These Australian researchers just released a number of analyses of cannabinoid legalization using high-level epidemiology data showing…
Increased major limb deficit after prenatal cannabis exposure
Epidemiological association of cannabinoid- and drug- exposures and sociodemographic factors with limb reduction defects across USA 1989-2016: A geotemporospatial study
Linking prenatal cannabis use to congenital anomalies (problems) in infants
Cannabinoid and substance relationships of European congenital anomaly patterns: a space-time panel regression and causal inferential study
Linking delta-8 THC use to an increase in a number of types of cancer
Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study
As well as a study showing cannabis causing increased cancer risk
Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017: part 1 - continuous bivariate analysis
Though on this one, their data suggests that THC & CBD cause more cancer in a community than tobacco or alcohol. That seems … out there.
As well as more types of cancer
Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017: part 2 - categorical bivariate analysis and attributable fractions
And cancer effects that suggest harms to the genes of prenatal infants
Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017: part 3 - spatiotemporal, multivariable and causal inferential pathfinding and exploratory analyses of prostate and ovarian cancers
In breast cancer cells, researchers find some novel ways that CBD causes cell death including forming aggregates that promote autophagy (cellular suicide) & at high doses, CBD causes “bubbling cell death”
Cannabidiol Antiproliferative Effect in Triple-Negative Breast Cancer MDA-MB-231 Cells Is Modulated by Its Physical State and by IGF-1
I’ve never heard of bubbling cell death before – but it sounds like a great thing to happen to cancer cells.
In lung cancer cells, THC & CBD slowed cell proliferation, increased apoptosis (cellular suicide) & lowered tumor size & progression
Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft
In a mouse model of breast cancer, a nanoencapsulation of CBD with an active ingredient of ginseng caused antitumor effects
Improved Therapeutic Efficacy of CBD with Good Tolerance in the Treatment of Breast Cancer through Nanoencapsulation and in Combination with 20(S)-Protopanaxadiol (PPD)
A review of using CBD for children with refractory epilepsy
Cannabidiol for the treatment of refractory epilepsy in children: a critical review of the literature
A review of using CBD for chronic pain
Efficacy, Safety, and Regulation of Cannabidiol on Chronic Pain: A Systematic Review
A review of using cannabinoids to help with the pain of orthopedic surgery
Cannabinoids for Pain Modulation in Orthopedic Surgery
A solid review of how the endocannabinoids act as important molecular messengers
Metabolic Messengers: endocannabinoids
A review of the effects of using alcohol & cannabis at the same time
Alcohol and Cannabinoids - From the Editors
A review of the cannabis articles published in the journals of social work
The Social Construction of Cannabis in Social Work
A review of GPCR18 – a receptor that may one day be known as CB3 or CB4
GPR18 receptor – the structure and the role in the physiology and pathophysiology
In a mouse model of seizures, neuroinflammation & neurodegeneration, chronic treatment with CBD reduced markers of brain immune cells but did not alter seizure frequency or neuron survival
Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures
The authors theorize that perhaps higher levels of CBD were needed to achieve more neuroprotection.
In a rat model of pain, combining ibuprofen with a drug that activates the CB1 & CB2 receptor worked better at reducing pain than either of them alone
Activation of Peripheral Cannabinoid Receptors Synergizes the Effect of Systemic Ibuprofen in a Pain Model in Rat
In a mouse model of diabetes with heart problems, THC caused beneficial effects on insulin levels as well as improvements to the heart’s main blood vessel
Vascular responses disrupted by fructose-induced hyperinsulinemia improved with delta-9-tetrahydrocannabinol
In a rat model of cerebellar ataxia (a neurodegenerative disease of the cerebellum involving the coordination of movement), an activator of the CB1 receptor worsened symptoms while an antagonist improved them
Modulation of the CB1 cannabinoid receptor has potential therapeutic utility in the 3-acetylpyridine cerebellar ataxia rat model
In a mouse model of Alzheimer’s disease focused on the cholinergic system (a key component of our parasympathetic nervous system), activating the CB2 receptor helped improve scores on various tests of memory
The Influence of CB2-Receptor Ligands on the Memory-Related Responses in Connection with Cholinergic Pathways in Mice in the Passive Avoidance Test
In rats, the ability of oxytocin to improve leaky guts through the vagus nerve seems to be mediated by endocannabinoid signaling
Oxytocin acts centrally in the brain to improve leaky gut through the vagus nerve and a cannabinoid signaling in rats
In a rat model of arthritis, the terpene myrcene reduced pain transmission as well as inflammation
Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis
In a mouse model of traumatic brain injury, a synthetic cannabinoid that activates both the CB2 receptor & the PPARγ nuclear receptor (which controls genetic transcription) increases the growth of new blood vessels in the brain, protects from disruptions of the blood-brain barrier, lessens motor deficits, lowers brain swelling from excess fluids & reduces neuroinflammation & neuronal death
A cannabidiol aminoquinone derivative activates the PP2A/B55α/HIF pathway and shows protective effects in a murine model of traumatic brain injury
In pregnant female rats, a high-fat diet altered their offspring’s metabolism but did not affect their cannabinoid receptor levels in their skeletal muscle or brown fat cells
Maternal high-fat diet alters thermogenic markers but not muscle or brown adipose cannabinoid receptors in adult rats
On the hunt (& discovery) of partial activators for the CB2 receptor
Elucidation of partial activation of cannabinoid receptor type 2 and identification of potential partial agonists: Molecular dynamics simulation and structure-based virtual screening
A look at nano-delivery systems for the cannabinoids
Strategies for enhancing the oral bioavailability of cannabinoids
PS: For this week’s sacred working music, here’s something of which I’ve never quite heard the equal: ‘Keur Moussa’ by the Monks of Senegal.
The Keur Moussa Abbey (or ‘the House of Moses’) in Senegal is a place of prayer where the monks tend fruit trees, make cheese & handcraft their renowned koras – the lute-harps of West Africa. Their music creates a new choral tradition from the wedding of Western liturgical chants with traditional African tribal music. Sung in French & Wolof, accompanied by the kora, balafon, tom-tom & flute, the brothers of Keur Moussa Abbey were the 1993 recipients of the International Albert Schweitzer Music Prize. I hope this makes a nice start for your week.
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.