C&P#25: PEA for COVID + CBD for pulmonary hypertension + OEA & PEA for neurodegeneration + chronic cannabis users are chill
C&P#25: PEA for COVID + CBD for pulmonary hypertension + OEA & PEA for neurodegeneration + chronic cannabis users are chill
FDA gets scathing letter & World Doping Agency keeps cannabis ban
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As always at the bottom, there’s a Living Glossary of cannabinoid terms along with the weekly music recommendation.
This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations. For cannabis & psychedelic companies, we produce educational content & newsletters . If you need a podcast, I’m the host for you. You can see my portfolio here.
#opentowork
A new Lex lecture:
My lecture for CANN, the cannabis division of the American Chemical Society is up…
‘Glutamate, GABA & the Ouroboros of the Cannabinoids’
This week…
PEA to help with the inflammation of COVID
CBD for pulmonary hypertension
Chronic cannabis users show lower stress response & quicker recovery of their sympathetic nervous system
A reproductive section with an AI tool to measure endocannabinoid levels to predict miscarriage & how smoking cannabis may alter the epigenetics of your sperm & the sperm of your children
In addiction, alcohol vs cannabis use disorder
Oleamide (the sleepy cannabinoid) to protect from neurodegeneration & PEA (the immune endocannabinoid) to protect your brain’s white matter
Sunsoil CBD: Cutting prices
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CBD will be a ubiquitous healthcare product like Tylenol & Advil. And Sunsoil is getting ahead of the curve with their growing methods, extraction techniques & process improvements to lower the price while still maintaining that organic, top-shelf quality.
I’m proud to work with Sunsoil & encourage you to buy their products today.
Use the coupon code LEX50 to get 50% off your order.
(and support this newsletter in the process)
Best of cannabinoid science...
In unvaccinated adults with COVID-19, PEA reduced their pro-inflammatory markers & caused an anti-inflammatory effect (hattip to Col. Dr. Michael Lewis)
Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial
https://pubmed.ncbi.nlm.nih.gov/36084236
In chronic cannabis users, they showed a lower hormonal response to stress & a faster recovery of their sympathetic nervous system
Hypothalamic-Pituitary-Adrenal and Sympathetic Nervous System Responses to Social Evaluative Stress in Chronic Cannabis Users and Non-Users
https://www.sciencedirect.com/science/article/abs/pii/S0306460322002556
An analysis of Washington state finds that legalized cannabis did not increase obesity rates & may have decreased them
Cloudy with a chance of munchies: Assessing the impact of recreational marijuana legalization on obesity
https://onlinelibrary.wiley.com/doi/abs/10.1002/hec.4598
In a review of cannabinoids & high blood pressure treatments, while the endocannabinoids did not help because of their contradictory actions, CBD effectively treated pulmonary hypertension (high blood pressure in your lungs & right side of your heart)
Why Multitarget Vasodilatory (Endo)cannabinoids Are Not Effective as Antihypertensive Compounds after Chronic Administration: Comparison of Their Effects on Systemic and Pulmonary Hypertension
https://www.mdpi.com/1424-8247/15/9/1119/htm
A review of PEA for neurodegenerative disorders & defects of the brain’s white matter (connective sheaths around nerve fibers)
Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications
https://www.mdpi.com/2218-273X/12/9/1191
A review of how the endocannabinoid system helps to control the hormonal & neuronal response to an immune challenge
Endocannabinoid System in the Neuroendocrine Response to Lipopolysaccharide-induced Immune Challenge
https://pubmed.ncbi.nlm.nih.gov/36042978
That the endocannabinoid system lies at the center of the Venn diagram of neurons, hormones & immune cells is a huge source of its power.
A review of the antibiotic effects of the cannabinoids from the plant
Antibacterial Effects of Phytocannabinoids
https://www.mdpi.com/2075-1729/12/9/1394
Future generations will be shaking their heads at how long we neglected to use this tool against one of the greatest public health threats.
A negative take on cannabis & cannabinoids for chronic pain & how it causes adverse events among ~25% of people & serious adverse events in 5%
Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies
https://pubmed.ncbi.nlm.nih.gov/35926992
“Very low certainty evidence, however, indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are less common and each typically occur in fewer than 1 in 20 patients. We compared studies with <24 weeks and ≥24 weeks of cannabis use and found more adverse events reported among studies with longer follow-up”.
This makes sense. Some people find THC uncomfortable – and a few people find it awful. But overall, it’s a wonderful tool for chronic pain patients – and if they try & it doesn’t agree with them, no harm done. The negatives are transient.
An evergreen note on reading restricted paper:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version) or Google Scholar itself.
3 other helpful browser extensions are: Unpaywall, Open Access Button & PaperPanda
For the infamous backdoor, use Sci-Hub – the pirated papers repository (Chrome extension here). This works better for older paper than the stuff that just came out.
For Twitter users, send a Tweet of the paper’s title with the hashtag #icanhazpdf. It works because people are beautiful(ish).
Finally, email the author. They’re almost always happy to oblige because, thanks to the predatory academic publishing system, they don’t make a dollar off of their papers.
Popular science pieces
Pentadecanoylcarnitine: On how this new endocannabinoid was discovered in dolphins by Nate Seltenrich for ProjectCBD
https://www.projectcbd.org/dolphin-study-identifies-hitherto-unknown-endocannabinoid
My cannabis counseling sessions for your health (or your patients)
For people looking improve their health with use CBD, cannabis & more novel ingredients like PEA (immune system) or oleamide (sleep), I offer counseling sessions on how to use these tools.
You can see my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression here.
We’ll meet to discuss what you want to fix, we’ll come up with a gameplan of what to try, I’ll help you to buy it (the cost of products almost always comes out to less than $100) & then I’ll be there to talk you through trying them out to find the best routine for you. Plus, unlimited follow-up emails.
If you want someone experienced in listening to patients & coming up with a plan to help you find relief, book a 1-on-1 session with me here:
Your Cannabis Counseling Sessions.
I’m also available to meet with medical professionals to advise them on using cannabis, cannabinoids & psychedelics in their practice. I’ve seen an uptick in the number of sessions for this & I can say that they find these one-hour brain pickings quite useful because I’m a walking ‘rule of thumbs’ from my years of interviewing practitioners. Plus, you get a follow-up email with all of the relevant science to your questions as well as recommended books & further resources. I can help you help your patients to better use these powerful tools of health. See here for more information:
Cannabinoid & Psychedelic Education Sessions
the Headlines & Fav Articles
The FDA Commissioner gets a scathing letter from 4 lawmakers about the agency’s response to an inquiry about the lack of CBD regs- but he will probably continue his current policy of fuck all
https://www.marijuanamoment.net/bipartisan-lawmakers-slam-completely-insufficient-fda-response-to-hemp-bill-request-and-lack-of-cbd-regulations
Marijuana Moment's Kyle Jaeger was named cannabis policy reporter of the year by Benzinga
https://www.benzinga.com/markets/cannabis/22/09/28841276/waiting-for-photo-benzinga-cannabis-award-winners-announced-at-chicago-conference-check-out-full
A reminder that Marijuana Moment is the best daily cannabis newsletter by far. I’m signed up for 20+ cannabis newsletters – but nothing compares to the work done by Tom Angell & Kyle Jaeger. Sign up to stay in the loop.
It looks like the World Anti-Doping Agency will keep cannabis on its banned list (I hate this)
https://www.law360.com/cannabis/articles/1528482
Of course, this speaks to SNL’s classic ‘All Drugs Olympics’
Arkansas has a big fight over its Issue 4: cannabis legalization
https://www.marijuanamoment.net/arkansas-poll-shows-growing-majority-support-for-marijuana-legalization-ballot-initiative-as-top-republicans-urge-no-vote
California still split between jurisdictions with cannabis retail bans & those with legalized sales
https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/123
USDA grants $21m for hemp as a climate-smart commodity
https://mailchi.mp/e715020555f4/usda-grants-21-million-for-hemp-as-a-climate-smart-commodity
Mary Biles on how isolated CBD does nothing for her anxiety while whole plant extracts do the trick
https://twitter.com/Mary_Biles/status/1570343338745954305
As the author of ‘The CBD Book’ & host of the ‘Cannabis Voices’ podcast, she knows her stuff.
Cannabis & cerebral palsy…
I feel better: Lee Child also smokes 5 nights a week
I’ve only read one Jack Reacher novel – but I was impressed.
In history, remember that Britain owned the colony of Hong Kong because they waged wars to force the sales of opium to China
https://twitter.com/CarlZha/status/1568438157204672513
& in other imperial wars, here’s American soldiers smoking cannabis out of shotguns
And guess which US intelligence service was responsible for much of that trade in cannabis & heroin?
The War on Drugs & Harm Reduction
The idiocies of the Drug War roars on: a judge in Iowa says that for a marijuana case, an out-of-state medical cannabis card is not a valid defense
https://iowanorml.org/pdf/schultz-FECR357550-2022-08-10.pdf
In Alabama, they kept a woman in jail for three months because she smoked cannabis on the same day she found out she was pregnant
https://www.al.com/news/2022/09/pregnant-women-held-for-months-in-one-alabama-jail-to-protect-fetuses-from-drugs.html
In Oklahoma, they’re going after pregnant women who use medical cannabis
https://www.marijuanamoment.net/oklahoma-prosecutors-are-targeting-pregnant-women-for-using-medical-marijuana
In Tennessee, apparently the testing of cannabis at the crime lab is holding up rape kit testing & sexual assault investigations. A state senator says “Free the plant. Prosecute rapists.”
https://twitter.com/Campbell4TN/status/1570456691908530177
In Germany, smuggling drugs into a prisoner via soaking synthetic cannabinoids onto a letter
Detection of AP-237 and synthetic cannabinoids on an infused letter sent to a German prisoner
https://pubmed.ncbi.nlm.nih.gov/35918775
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to your company, reach out to me]
The status of psychedelics in India
https://psychedelicspotlight.com/what-is-the-status-of-psychedelics-in-india
A survey of chronic pain patients on the painkilling potential of little & large doses of psychedelics
Analgesic potential of macrodoses and microdoses of classical psychedelics in chronic pain sufferers: a population survey
https://journals.sagepub.com/doi/10.1177/20494637221114962
How psilocybin alters the brain to cause visuals
Neural mechanisms of imagery under psilocybin
https://www.medrxiv.org/content/10.1101/2022.09.07.22279700v1
An important message to remember on drug parity…
Law & Business
Politico on why weed companies can’t make any money
https://www.politico.com/news/2022/09/04/weed-companies-cant-make-money-00054541
Temple’s Center for Public Health Law Research releases a report on the many proposed state decriminalization laws
https://phlr.org/sites/default/files/uploaded_images/PolicyBrief_SentinelSurveillanceSSELP-Sept%202022.pdf
On how the hemp loophole allows for the selling of Delta-9 THC products at gas stations across the US
In New Jersey, a study finds that allowing cannabis businesses raises home prices
https://rutgers.app.box.com/s/28oxapqg7a3tk0k385bhtlygn7qtehuk
The Plant & the History
A nice look at how to optimize your supercritical CO2 extraction of hemp for cannabinoid & terpene yield
Terpenes and Cannabinoids in Supercritical CO2 Extracts of Industrial Hemp Inflorescences: Optimization of Extraction, Antiradical and Antibacterial Activity
https://www.mdpi.com/1424-8247/15/9/1117
One of the predominant extraction technologies in the CBD/hemp space, the supercritical CO2 technique uses heated carbon dioxide at high pressures to extract the bioactive molecules without the use of harsher solvents.
On using silicon on young hemp to help with their stress responses & antioxidant activities
Silicon reduces zinc absorption and triggers oxidative tolerance processes without impacting growth in young plants of hemp (Cannabis sativa L.)
https://pubmed.ncbi.nlm.nih.gov/35907072
Cannabinoid Science
Clinical Studies & Surveys
A survey of Canadian healthcare practitioners asked about their barriers to prescribing cannabis (only 6% of them received any training on the topic in school)
Healthcare practitioner perceptions on barriers impacting cannabis prescribing practices
https://pubmed.ncbi.nlm.nih.gov/36076191
“Over half (57%) received more questions regarding MC since recreational cannabis was legalized, and 82% reported having patients who use MC. However, 56% felt uncomfortable or ambivalent regarding their knowledge of MC, and 27% were unfamiliar with the requirements for obtaining MC in Canada. The most common symptoms for recommending MC were pain and nausea, whereas the most common conditions for recommending it were cancer and intractable pain. The strongest barrier to authorizing MC was uncertainty in safe and effective dosage and routes of administration. The strongest barrier to recommending or authorizing MC was the lack of research evidence demonstrating its safety and efficacy.”
In people undergoing hand surgery, the use of cannabis was not associated with greater opioid use
Self-reported cannabis use is not associated with greater opioid use in elective hand surgery patients
https://pubmed.ncbi.nlm.nih.gov/35986814
In people living with HIV/AIDS, hair levels of anandamide & other fatty acids predicted the levels of their viral suppression
Hair levels of steroid, endocannabinoid, and the ratio biomarkers predict viral suppression among people living with HIV/AIDS in China
https://pubmed.ncbi.nlm.nih.gov/36041548
It’s tough to measure how much cannabis people use & so this team suggests asking people their number of ‘hours high’ as a new measurement
Hours high as a proxy for marijuana use quantity in intensive longitudinal designs
https://www.sciencedirect.com/science/article/abs/pii/S0376871622003659
How would you answer that one?
I don’t know. How high is high enough to count? I’m mostly down after an hour – but I’m certainly altered for another hour or two after that.
I’m leery of this new proxy.
Mental Health, Addiction & Mental Effects
A review of studies finds that people with PTSD are more likely to use cannabis than those without PTSD
The Association Between Recreational Cannabis Use and Posttraumatic Stress Disorder: A Systematic Review and Methodological Critique of the Literature
https://www.sciencedirect.com/science/article/abs/pii/S037687162200360X
A review of nano-encapsulated cannabinoids for addiction treatment
Nanomedicine and addictive disorders: A new approach with cannabinoids
https://pubmed.ncbi.nlm.nih.gov/36082864
Unsurprisingly, cannabis use disorder is less likely to kill you than alcohol use disorder
Mortality risk for individuals with cannabis use disorders in relation to alcohol use disorders: Results of a follow-up study
https://pubmed.ncbi.nlm.nih.gov/35908347
Remember, the only drug in the world that kills more people than alcohol is tobacco. And their combined death count of 11+M per year overshadows all other drugs put together, which don’t even equal one million.
A gene association study finds that certain variants of your FAAH enzyme are associated with a predisposition to alcohol use disorder
Association of Alcohol Use Disorder Risk With ADH1B, DRD2, FAAH, SLC39A8, GCKR, and PDYN Genetic Polymorphisms
https://pubmed.ncbi.nlm.nih.gov/36099111
A review of THC’s effects on brain function via neuroimaging studies
Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis
https://pubmed.ncbi.nlm.nih.gov/35914625
Reproductive & Maternal Effects
During pregnancy & breastfeeding, a review of how the cannabinoids move through humans & animals
Pharmacokinetics of Cannabis and Its Derivatives in Animals and Humans During Pregnancy and Breastfeeding
https://pubmed.ncbi.nlm.nih.gov/35903331
In pregnant people, the creation of an AI tool to look at miscarriage risk based on a few factors including anandamide levels (turns out high AEA levels = higher miscarriage risk)
Construction of machine learning tools to predict threatened miscarriage in the first trimester based on AEA, progesterone and β-hCG in China: a multicentre, observational, case-control study
https://pubmed.ncbi.nlm.nih.gov/36085038
In male rats exposed to cannabis, their sperm’s epigenetic changes (genes turned on or off) could also be detected in the sperm of their male children
Sperm DNA methylation alterations from cannabis extract exposure are evident in offspring
https://pubmed.ncbi.nlm.nih.gov/36085240
Epigenetics is the revenge of Lamarck.
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
A review of how to handle cannabinoid hyperemesis syndrome (cyclical vomiting) & withdrawal from cannabis
Cannabinoid hyperemesis syndrome and cannabis withdrawal syndrome: a review of the management of cannabis-related syndrome in the emergency department
https://pubmed.ncbi.nlm.nih.gov/36076180
In 2016, Germany passed a law against novel psychoactive substances but this analysis finds that it did not prevent the emergence & spread of further synthetic cannabinoids
Effect of new legislation in Germany on prevalence and harm of synthetic cannabinoids
https://pubmed.ncbi.nlm.nih.gov/36074033
In zebrafish (a common model of reproduction), CBD inhibited their reproductive ability & the spawn of females had higher mortality & malformation rates
Cannabidiol Inhibited Reproductive Ability of Zebrafish (Danio Rerio) with Gender-Dependent Manner
https://assets.researchsquare.com/files/rs-1990207/v1/f5f141d3-2b6d-4669-9457-6a81400ccbbc.pdf
Cancer
In patients with non-small cell lung cancer, the use of cannabis seemed to not interfere with their treatment by immune-check point inhibitors
The Use of Medical Cannabis Concomitantly with Immune-Check Point Inhibitors (ICI) in Non Small Cell Lung Cancer (NSCLC): A Sigh of Relief?
https://www.sciencedirect.com/science/article/pii/S1556086422004993
Recent Reviews
A review of why targeting the CB2 receptor is a key future of medicine (by Maccarrone et al.)
Recent Advances on Type-2 Cannabinoid (CB2) Receptor Agonists and Their Therapeutic Potential
https://pubmed.ncbi.nlm.nih.gov/36028971
In ataxia (poor control of the muscles), a review of the effects of endocannabinoids on the transient receptor potential (TRP) channels (important ion channels that regulate the electrical potential of the neurons)
The neglected role of endocannabinoid actions at TRPC channels in ataxia
https://pubmed.ncbi.nlm.nih.gov/36087758
A review of using cannabinoids to treat the orofacial pain of dentistry
Cannabinoid Therapeutics in orofacial pain management: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/36082517
A review of working with the endocannabinoid system for ears, nose & throat specialists
Endocannabinoid System and the Otolaryngologist
https://pubmed.ncbi.nlm.nih.gov/36088164
Preclinical Research
In a rat brain slice model of neurodegeneration, oleamide protected the mitochondria (powerhouse of the cell) via the antioxidant effects of CB1 & CB2
Oleamide Reduces Mitochondrial Dysfunction and Toxicity in Rat Cortical Slices Through the Combined Action of Cannabinoid Receptors Activation and Induction of Antioxidant Activity
https://pubmed.ncbi.nlm.nih.gov/36069981
In gingival fibroblasts (the stem cells of your gums), CBD, CBG & CBDV had a range of anti-inflammatory & pro-inflammatory activities
Phytocannabinoids regulate inflammation in IL-1β-stimulated human gingival fibroblasts
https://pubmed.ncbi.nlm.nih.gov/36070347
In mice using cocaine, endocannabinoids helped to regulate the memory formation that precipitates craving & relapse
Endocannabinoids regulate cocaine-associated memory through brain AEAeCB1R signalling Q5 activation
https://www.sciencedirect.com/science/article/pii/S2212877822001661
“Cocaine decreases FAAH level and leads to an increasing level of AEA, further activating CB1R signaling and remodeling dendritic spines structure of granule neurons.”
Or as Taj Mahal opines, “Now, you know that cocaine's for horses now it ain't for me,
The doctors said it'd kill me but they didn't say when,
Ain't nobody's business but your own”
For anti-depressive effects in mice, using flavonoids to inhibit the FAAH enzyme & raise the levels of anandamide
Fatty acid amide hydrolase inhibition and N-arachidonoylethanolamine modulation by isoflavonoids: A novel target for upcoming antidepressants
https://pubmed.ncbi.nlm.nih.gov/36029006
In a mouse model of obesity, a novel photoacoustic probe unexpectedly finds that levels of MGL & FAAH are higher than usual in the GI tract
Activity-based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity
https://pubmed.ncbi.nlm.nih.gov/36083191
https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202211774
In a neuronal model of ataxia (poor muscle control), blockers of the CB1 may be a potential treatment
Pharmacologic antagonism of CB1 receptors improves electrophysiological alterations in the 3-AP model of cerebellar ataxia
https://europepmc.org/article/ppr/ppr542124
Cool Chemistry
The development of a radioactive MGL tracker for watching its levels in the brain
Multi-parameter optimization: Development of a morpholin-3-one derivative with an improved kinetic profile for imaging monoacylglycerol lipase in the brain
https://www.sciencedirect.com/science/article/pii/S0223523422006523
It’s like putting a radioactive collar on a giant octopus so we can better watch where they go eating 2-AG blue whales in our neural ocean brains.
(See the Living Glossary below for more of the neural ocean legend)
In dental stem cells, a tool to measure genetic transcripts & thus the levels of cannabinoid receptors
Reference gene validation for the relative quantification of cannabinoid receptor expression in human odontoblasts via quantitative polymerase chain reaction
https://www.sciencedirect.com/science/article/pii/S2212426822001270
New CB2 activators that bind to both the receptor’s primary binding site (orthosteric) & modulating binding site (allosteric)
Design, Synthesis, and Biological Activity of New CB2 Receptor Ligands: from Orthosteric and Allosteric Modulators to Dualsteric/Bitopic Ligands
https://pubmed.ncbi.nlm.nih.gov/35849804
A deep dive on CBD delivery methods
In Vitro Release, Mucosal Permeation and Deposition of Cannabidiol from Liquisolid Systems: The Influence of Liquid Vehicles
https://www.mdpi.com/1999-4923/14/9/1787
Thanks.
- lex
PS: Thanks to YouTube, I just discovered Boogaloo Joe Jones & his psychedelic jazz guitar album.
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.
Endocannabinoids
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]
2-AG
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
[blue whale]
CB1
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]
CB2
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]
Palmitoylethanolamide (PEA)
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]
NAAA (N-acylethanolamine acid amidase)
The enzyme for breaking down PEA, with a special function as a messenger for pain & inflammation as well as in the control of obesity.
[a giant Giant Pacific octopus that eats Right whales]
Oleamide (OEA)
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.
[whale cars]
Phytocannabinoids
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]
CBD (cannabidiol)
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]
CBC (cannabichromene)
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 (cannabidivarin)
CBDV is like CBD with a shortened tail (side chain). Also nonpsychoactive, it tends to occur at low levels in most cannabis cultivars. It’s known to be an anticonvulsant & is suggested for treating autism in humans & in animal models. The cannabinoid pharmaceutical company GW has it in their developmental pipeline as GWP42006.
[An Asian elephant with a short trunk]
(Easter egg: the first person to email me about this easter egg will get a free copy of my Queer book once I get it printed & up on Amazon soon…)
Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]
Beta-caryophyllene (BCP)
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]
Pharmaceutical cannabinoids
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.
Nabilone (Cesamet®)
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.