C&P#23: a new endocannabinoid! + dry mouth decoded + huge cannabinoid clinical trial roundup
C&P#23: a new endocannabinoid! + dry mouth decoded + huge cannabinoid clinical trial roundup
Biden continues to do nothing, FBI continues to be terrible
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This week…
For epileptic children, CBD-rich full spectrums extracts work just as well as pharmaceutical CBD & with less side effects
Humans, mice & rats say CBD for arthritis & joint pain!
A new endocannabinoid discovered: pentadecanoylcarnitine!
The cause of dry mouth finally discovered
A huge review of every randomized clinical trial with cannabinoids
Now more cannabis smokers than tobacco
In cannabis news, Biden does nothing & the FBI remains a POS
Sunsoil CBD: better products that cost less
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Best of cannabinoid science...
In an analysis of pediatric epilepsy patients using pharmaceutical (isolated) CBD vs artisanal (full-spectrum plant extract), the isolated CBD did cause them to have higher CBD levels in the blood, but this only increased side effects while having no beneficial effect on seizure frequency
Variability in Serum Concentrations and Clinical Response in Artisanal Versus Pharmaceutical Cannabidiol Treatment of Pediatric Pharmacoresistant Epilepsy
https://meridian.allenpress.com/jppt/article-abstract/27/6/558/485210/Variability-in-Serum-Concentrations-and-Clinical
A survey found that for people with arthritis & joint pain, they said CBD helped with pain, physical function & sleep as well as a reduction in other medications
Cannabidiol as a treatment for arthritis and joint pain: an exploratory cross-sectional study
https://pubmed.ncbi.nlm.nih.gov/35999581
A giant review of all 152 randomized controlled trials involving the cannabinoids
Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications
https://pubmed.ncbi.nlm.nih.gov/35982439
They looked at “dronabinol, nabilone, cannabidiol and nabiximols for chronic pain, spasticity, nausea /vomiting, appetite, ALS, irritable bowel syndrome, MS, Chorea Huntington, epilepsy, dystonia, Parkinsonism, glaucoma, ADHD, anorexia nervosa, anxiety, dementia, depression, schizophrenia, PTSD, sleeping disorders, SUD and Tourette.”
A review of CBD for movement disorders
Cannabinoids in movement disorders
https://pubmed.ncbi.nlm.nih.gov/36038457
One of the most important (& well-studied) uses for CBD…
What does PEA do at our synapses that make it effective for neurodegeneration & neuroinflammation?
Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders
https://pubmed.ncbi.nlm.nih.gov/36009055
The CB1 receptor found to regulate salivation (dry mouth finally explained!)
Cannabinoid CB1 receptors regulate salivation
https://pubmed.ncbi.nlm.nih.gov/35986066
While THC would cause reduced saliva in these mice, CBD prevented the THC from causing this effect.
The endocannabinoid system & eating behaviors
The Endocannabinoid System and Eating Behaviours: a Review of the Current State of the Evidence
https://pubmed.ncbi.nlm.nih.gov/35980538
Control of metabolism & the higher-level behaviors associated with eating are closely associated with the endocannabinoid system. In fact, the celebrated endocannabinoid science Dr. Vincenzo Di Marzo puts it in his Big 5 Purposes of the ECS:
Relax, Eat, Sleep, Forget and Protect
(see my interview with him here)
In a mouse model of neuropathic pain, CBD caused the morphine’s painkilling to work better & lowered the buildup of tolerance to opioids
Cannabidiol enhances the antinociceptive effects of morphine and attenuates opioid-induced tolerance in the chronic constriction injury model
https://pubmed.ncbi.nlm.nih.gov/36028000
In rats with a traumatic spinal cord injury, CBD lowered their oxidative stress, reduced their hypersensitivity & lessened pain levels
Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats
https://pubmed.ncbi.nlm.nih.gov/36028005
In a mouse model of PTSD, CBD helped to lower their fear response & anxiety
Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance
https://pubmed.ncbi.nlm.nih.gov/36012600
In a mouse model of osteoarthritis, both CBD oil & CBG oil helped with pain & inflammation as well as improved gait & locomotion
Distinctive Therapeutic Effects of Non-Euphorigenic Cannabis Extracts in Osteoarthritis
https://pubmed.ncbi.nlm.nih.gov/35994012
In a mouse model of fibromyalgia, low-THC cannabis oil reduced sensitivity to pressure & heat as well as reducing depressive behaviors
Broad-spectrum cannabis oil ameliorates reserpine-induced fibromyalgia model in mice
https://pubmed.ncbi.nlm.nih.gov/35988425
A new endocannabinoid discovered: meet pentadecanoylcarnitine, a fatty acid that lowers inflammation, binds to both CB receptors & 2 serotonin receptors as well as blocking 2 histamine receptors
Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health
https://pubmed.ncbi.nlm.nih.gov/35999445
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
Dr. Peter Grinspoon shares on his family’s journey with cannabis (he’s the son of Dr. Lester Grinspoon, one of the first doctors to ever fight for the medical utility of cannabis)
He’s worth a follow on Twitter. And you can hear more on my interview of him for the first season finale of my podcast.
For anyone struggling with addiction, he’s a great person to learn from.
“Cannabis users no less likely to be motivated or able to enjoy life’s pleasure” (hattip to Stuart Tomc)
https://www.cam.ac.uk/research/news/cannabis-users-no-less-likely-to-be-motivated-or-able-to-enjoy-lifes-pleasure
and they’re talking with the researchers about these two papers:
Anhedonia, apathy, pleasure, and effort-based decision-making in adult and adolescent cannabis users and controls
https://pubmed.ncbi.nlm.nih.gov/35999024
Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls
https://pubmed.ncbi.nlm.nih.gov/35388175
CBD to treat problematic cannabis use by Nate Seltenrich
https://www.projectcbd.org/cbd-problematic-cannabis-use
A long look at medical cannabis in Uganda
https://nru.uncst.go.ug/bitstream/handle/123456789/4299/A%20Legal%20Appraisal%20of%20Njaga%20Cannabis%20and%20Associated%20Medicinal%20Herbs%20in%20Uganda.pdf
My cannabis counseling sessions for your health
For people looking improve their health by using 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:
Cannabinoid Education Sessions.
the Headlines & Fav Articles
Biden’s press secretary, when pressed on his cannabis campaign pledges, says “we don’t have anything”
https://www.marijuanamoment.net/white-house-says-we-dont-have-anything-to-report-on-bidens-marijuana-campaign-promises-as-senate-candidate-presses-for-action
Meanwhile, his new student loan relief program won’t apply to kids who couldn’t get Pell grants because of cannabis convictions & had to take out private loans
https://apnews.com/article/student-loan-relief-pell-grant-ban-972513f72b873d730b1c0a513b5c5b04
In Marijuana Moment, Paul Armentano of NORML says that cannabis prohibitionists know they have lost the battle for public opinion & have resorted to using court challenges as their only hope
https://www.marijuanamoment.net/marijuana-prohibitionists-have-lost-the-war-of-ideas-and-are-now-attacking-democracy-itself-op-ed
Gallup reports for the first time ever, more people smoking cannabis than tobacco
https://www.marijuanamoment.net/more-americans-now-smoke-marijuana-than-cigarettes-for-the-first-time-ever-gallup-reports
A new organization, the Indigenous Cannabis Industry Association, wants to "promote the exploration, development, and advancement of the cannabis industry for the benefit of all Indigenous communities"
https://www.indigenouscannabis.org
The US Citizenship & Immigration Services defended using pass cannabis convictions to deny citizenship eligibility under the Deferred Action for Childhood Arrivals program
https://www.federalregister.gov/documents/2022/08/30/2022-18401/deferred-action-for-childhood-arrivals
The FBI says using cannabis or hemp extracts within the past year is an automatic disqualifier for working with them
https://www.marijuanamoment.net/fbi-says-cbd-use-is-an-automatic-disqualifier-for-employment-despite-federal-hemp-legalization
That’s your choice. But otherwise, I could have been yours. I could have done great work for you. You should see me in a suit.
But alas, no, you declare me too tainted for you.
[editor’s note: Fuck the FBI. Sometimes I forget how low they stoop & the bureaucratized nature of their evil – but I just read this book on the FBI’s murder of Tupac & I’m reminded of how many Black leaders they assassinated & destroyed with their hyena tactics]
NY’s SUNY Cobleskill school will offer a cannabis science minor with a focus on production, management &cultivation
https://www.ganjapreneur.com/new-york-college-launches-cannabis-science-program
A reminder to any cannabis educators & college professors out there: I’m available to teach classes on the endocannabinoid system. Or on the racist history of the War on Drugs. Or on the long human relationship with the cannabis plant.
Someday I hope to have my own classroom for teaching on the science & the history of psychoactives.
The War on Drugs & Harm Reduction
A mother of 5 has her children taken away after using psilocybin for her depression after all other treatments failed & she now faces ten years in prison
https://psychedelicspotlight.com/indiana-nurse-faces-ten-years-in-prison-for-microdosing-psilocybin-mushrooms
The Trucking Alliance is seeking permission from the Federal Motor Carrier Safety Administration to change its drug testing protocols from standard urine tests to hair tests
https://www.ganjapreneur.com/trucking-alliance-seeks-federal-permission-to-use-hair-drug-testing-methods
This stinks for two reasons:
1. Obviously, your hair can test positive just from being in the same room as someone smoking cannabis.
2. The hair of Black people bind these molecules tighter & longer, leading to more positives & false positives.
In Michigan, the State Police admit that over 3,000 marijuana-impaired driving cases could have been false positives because of their lab analysis converting CBD to THC
https://www.michigan.gov/mspnewsroom/news-releases/2022/08/31/state-police-halts-thc-toxicology-testing
Researchers just love figuring out how to look at sewage to find out how much drugs people are doing
Analytical investigation of cannabis biomarkers in raw urban wastewater to refine consumption estimates
https://pubmed.ncbi.nlm.nih.gov/36049245
Pro-tip: they’re also doing way more cocaine than anyone guesses…
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to a company out there, reach out to me]
Tiffany Kary interviews Carey Turnbull, the psychedelic philanthropist & patent fighter
https://www.bloomberg.com/news/newsletters/2022-08-29/nyu-magic-mushrooms-research-funded-by-investor-carey-turnbull
By the way, Kary’s newsletter ‘The Dose’ is a good one to follow (signup in the link).
“Why 5-MEO-DMT is one of the most fascinating psychedelics there is”
https://open-foundation.org/5-meo-dmt-use
A review of the potent anti-inflammatory effects of psychedelics
Psychedelics as potent anti-inflammatory therapeutics
https://pubmed.ncbi.nlm.nih.gov/36007854
Psychedelics linked to higher relatedness to nature
The Association of Classic Serotonergic Psychedelic Use and Intention of Future Use with Nature Relatedness
https://pubmed.ncbi.nlm.nih.gov/35984245
Alternatively, you could have asked… anyone.
A review of arketamine (a ketamine analog) for depression
Arketamine, a new rapid-acting antidepressant: A historical review and future directions
https://pubmed.ncbi.nlm.nih.gov/35977629
Law & Business
Ohh ohh ohh: Public corruption investigation in Florida cannabis world. Matt Gaetz still on the hook? 🍿 🍿 🍿
https://www.thedailybeast.com/eight-sources-say-feds-are-not-done-with-matt-gaetz
The FTC issues $21,000 in refunds to consumers who bought CBD from Kushly because of their misleading medical claims
https://www.ganjapreneur.com/federal-regulators-to-refund-21k-worth-of-cbd-purchases-due-to-misleading-health-claims
It doesn’t matter that most of those medical claims are true. You’re not allowed to say them out loud. If you want to learn more, Asa Waldstein is one expert you can learn from. His Youtube channel is ‘Asa's Regulatory Education Series’.
According to a study, "cannabis legalization is associated with a decrease in the stock market returns for pharmaceutical firms” & reduced $3B in sales
https://www.marijuanamoment.net/pharmaceutical-industry-suffers-billions-in-losses-after-states-legalize-marijuana-new-study-finds
The Plant & the History
Results from an international survey of cannabis growers
The Global Cannabis Cultivation Research Consortium (GCCRC): a transnational online survey of cannabis growers
https://policycommons.net/artifacts/2646759/the-global-cannabis-cultivation-research-consortium-gccrc/3669606
When storing the plant, heat causes more of the THC degradation than light
Effect Of Storage Conditions On The Potency Of Cannabinoids In Cannabis Trimmings
https://anresco.com/effect-of-storage-conditions-on-the-potency-of-cannabinoids-in-cannabis-trimmings
Cops want to expand the morphological definition (description of physical characteristics) of cannabis seeds for better identification of seizures
Expanding Morphological Criteria for Identifying Cannabis Seeds - Analysis of a New Variant of Cannabis Seeds
https://www.proquest.com/openview/c4e177f48352847e96742fbc48db2b7b/1
Cannabinoid Science
Clinical Studies & Surveys
In people with HIV & hepatitis C, the increased risk for obesity is lowered by cannabis use
Cannabis Use as a Protective Factor Against Overweight in HIV-Hepatitis C Virus Co-Infected People (ANRS CO13 HEPAVIH Cohort)
https://pubmed.ncbi.nlm.nih.gov/35994579
In people with PTSD during the pandemic, cannabis use associated with worsening depression symptoms
Increased cannabis intake during the COVID-19 pandemic is associated with worsening of depression symptoms in people with PTSD
https://pubmed.ncbi.nlm.nih.gov/35978287
An analysis of New York’s medical cannabis market: who bought what & why?
Characterization of Cannabis Products Purchased for Medical Use in New York State
https://pubmed.ncbi.nlm.nih.gov/35984662
“The top 3 conditions or symptoms were severe pain (82.0%), chronic pain (51.9%), and neuropathy (22.1%)… Men were more likely to purchase vaporizers (43.1%), whereas women more frequently purchased tinctures (41.7%)…. High-THC products were purchased predominantly by both men and women. Patients older than 65 years and less than 21 years were more likely to purchase tinctures (44.9% and 42.0%.... Patients in other age groups generally purchased vaporizers. Patients in all age groups except those less than 21 years preferred high-THC products, particularly patients with cancer (55.3%), HIV/AIDS (66.5%), spinal cord injury (50.9%), neuropathy (48.0%), posttraumatic stress disorder (58.4%), chronic pain (56.2%), and opioid replacement (55.2%) (Table 2). Patients with seizures and epilepsy were more likely to purchase high-CBD products.”
A look at how cannabis & alcohol alter your vision
Assessing the influence of cannabis and alcohol use on different visual functions: A comparative study
https://pubmed.ncbi.nlm.nih.gov/36028069
Cancer
A review of how the endocannabinoid system modulates pain in cancer patients
Endocannabinoid System and Its Neuromodulatory Effects in Pain Management in Oncology Patients-A Systemic Review
https://biomedres.us/pdfs/BJSTR.MS.ID.007213.pdf
In a mouse model of pain from chemotherapy, PEA helped with the pain as well as the mood disorders
The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice
https://pubmed.ncbi.nlm.nih.gov/36009049
In prostate cancer cells, how cannabis & CBD inhibit cancer progression
The involvement of cannabis sativa/CBD in prostate cancer pc3 cells progression inhibition
https://assets.researchsquare.com/files/rs-1952417/v1/65bb430a-e76d-4c89-ae12-da1931b9e379.pdf
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
An epidemiological review of the increased cancer & congenital anomaly risks associated with cannabis
Cannabis, Cannabidiol, Cannabinoids, and Multigenerational Policy
https://www.sciencedirect.com/science/article/pii/S2095809922005719
In teen mice exposed to cannabis, they saw changes in their gene expression across various brain regions with differences found between the genders
Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions
https://pubmed.ncbi.nlm.nih.gov/35995972
Speculation that cannabis use by children with autism may lead to psychosis
Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis
https://www.mdpi.com/2227-9032/10/8/1553
2021: how two novel cannabinoids get broken down in the body
In Vitro Metabolic Fate of the Synthetic Cannabinoid Receptor Agonists QMPSB and QMPCB (SGT-11) Including Isozyme Mapping and Esterase Activity
https://pubmed.ncbi.nlm.nih.gov/34436449
Recent Reviews
A review of cannabis for lower back pain
An Emerging Role of Cannabis as an Anti-Nociceptive Agent in the Treatment of Chronic Back Pain
https://academic.oup.com/bjs/article/109/Supplement_6/znac269.450/6672024
A review of cannabis in the brain: the positives (pediatric epilepsy, ADHD, autism) & the negatives (addiction, cognition & psychosis)
Cannabis and the Brain: Friend or Foe?
https://www.intechopen.com/online-first/83158
A review of the effects of THC & CB1 activating drugs on animal tests of anxiety
Effects of Δ 9-THC and Type-1 Cannabinoid Receptor Agonists in the Elevated Plus Maze Test of Anxiety: A Systematic Review and Meta-Analysis
https://pubmed.ncbi.nlm.nih.gov/35984927
A review of the interactions between endocannabinoid receptors & nicotinic receptors
Interactions between the Nicotinic and Endocannabinoid Receptors at the Plasma Membrane
https://pubmed.ncbi.nlm.nih.gov/36005727
A review about how targeting the CB1 & CB2 receptor may help modulate the response to stimulants
Roles of cannabinoid CB1 and CB2 receptors in the modulation of psychostimulant responses
https://pubmed.ncbi.nlm.nih.gov/35993329
A review of α/β-hydrolase domain-containing 6 (ABHD6) – an enzyme that degrades MGL, the enzyme that degrades 2-AG
α/β-Hydrolase Domain-Containing 6 (ABHD6)— A Multifunctional Lipid Hydrolase
https://www.mdpi.com/2218-1989/12/8/761
“The enzyme was identified as a negative modulator of insulin secretion and regulator of energy metabolism affecting the pathogenesis of obesity and metabolic syndrome… Finally, ABHD6 was shown to affect cancer cell lipid metabolism and tumor malignancy.”
In our Neural Ocean metaphor, ABHD6 kills the octopus (MGL) that kills blue whales. Hence, it causes more blue whales (2-AG).
Preclinical Research
In rats who had spinal fusion surgery, THC increased their fusion rates while CBD had no adverse effect
Effects of cannabinoids on spinal fusion in a rat model
https://www.sciencedirect.com/science/article/abs/pii/S1529943022004053
In a rat model of nausea from chemotherapy, they experienced benefit from THC, CBD & CBD Acid with no detectable differences between the sexes
Evaluation of Sex Differences in the Potential of Δ 9-Tetrahydrocannabinol, Cannabidiol, Cannabidiolic Acid, and Oleoyl Alanine to Reduce Nausea-Induced Conditioned Gaping Reactions in Sprague-Dawley Rats
https://pubmed.ncbi.nlm.nih.gov/35984924
In mammary (milk-producing) cells, THC & CBD reduced their viability & milk protein levels
Effect of Delta-9-tetrahydrocannabinol and cannabidiol on milk proteins and lipid levels in HC11 cells
https://pubmed.ncbi.nlm.nih.gov/35976913
In a mouse model of obesity, it was the CB1 receptors in the immune cells that helped to mediate the effects of diet-induced obesity while activating CB1 receptors in other cell types lowered obesity
Yin and yang of cannabinoid CB1 receptor: CB1 deletion in immune cells causes exacerbation while deletion in non-immune cells attenuates obesity
https://www.sciencedirect.com/science/article/pii/S2589004222012664
In mice, injecting a drug that activates the CB1 receptor into their brain’s basolateral amygdala (a center for reward & anxiety) caused increased anxiety & place preference (a marker for addiction)
Cannabinoid Type 1 Receptors in the Basolateral Amygdala Regulate ACPA-Induced Place Preference and Anxiolytic-Like Behaviors
https://pubmed.ncbi.nlm.nih.gov/35984590
In a rat model of rheumatoid arthritis, a drug that activates the CB2 receptor was as effective as the common treatment dexamethasone for causing relief & together, they worked even better
Comparative study of cannabinoid receptor 2 agonist and dexamethasone in experimentally induced rheumatoid arthritis
https://japer.in/storage/files/article/a380d9e2-5258-41f9-9c3f-42e68836c3f7-MZWsBcPqEBSOJvne/japer-vol-12-iss-3-44-53-8030.pdf
In a rat model of lung scarring, a new drug that binds to the CB2 receptor lessened lung injuries, inflammation & fibrosis (scarring)
Discovery of a pyrano[2,3-b]pyridine derivative YX2102 as a cannabinoid receptor 2 agonist for alleviating lung fibrosis
https://assets.researchsquare.com/files/rs-1901024/v1/96ebd13c-fb7b-48e2-bd7e-0c9b8d0015da.pdf
Figuring out how THC modifies the glycine receptors – key for motor coordination & pain sensation
Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs
https://pubmed.ncbi.nlm.nih.gov/35982060
Thanks.
- lex
PS: For this week’s funky album, the eponymous first record of ‘The Meters’. An early New Orleans funk band that formed in 1965, not only did they pioneer their own earthy, instrumental style of funk, they played as the backing band for a huge number of stars such as Robert Palmer, Paul McCartney, Dr. John & Betty Harris. Led by NOLA icon Art Neville & influenced by the rhythms of NOLA’s “second lines”, they never achieved breakout mainstream success but they are considered originators of funk music. To hear them live, check out their live show on the Queen Mary.
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]
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.