C&P#17: microdosing for Alzheimer’s + CBD for addiction + cannabinoids & cancer
plus a new US federal legalization bill...
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This week…
A new federal cannabis legalization bill in the US,
a study of microdosing cannabis for Alzheimer’s,
research finds that delta-8 THC moves through the body similarly to delta-9 THC (I broke out delta-8 THC into its own section this week),
a study finds cannabis users to be the opposite of amotivational,
& new work on using THC, CBD & cannabis itself against cancer.
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. You can see my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression here.
I counsel people about using medical cannabis, CBD & the lesser known but powerful cannabinoids like PEA & OEA. We’ll meet to discuss what you want to fix, we’ll come up with a gameplan of what to try, I’ll help you to buy it (almost always the cost of products comes out to less than $100) & then I’ll be there to talk you through trying them out to find the best routine for you. And this includes unlimited follow-up emails.
If you want someone experienced in listening to patients & coming up with a plan to help you find relief, book a 1-on-1 session with me here: Cannabinoid Education Sessions.
Best of cannabinoid science...
In a patient with mild Alzheimer’s, microdosing of cannabis improved memory (hattip to Stuart Tomc)
Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer's disease symptoms: a case report
https://pubmed.ncbi.nlm.nih.gov/35820856
Though note, this patient microdosed for almost 2 years. It speaks to how cannabinoids help with neurodegeneration. Since they seem to repair the brain itself as well as slowing disease progression, they tend not to be quick fixes. Months and years can be necessary to build their effects – but that’s why you should start right away. I strongly believe that you can get more good years with your relatives with neurodegeneration by using cannabinoids.
See my advice on cannabinoids & neurodegeneration here.
This study of long-term cannabis users found the opposite of ‘amotivational syndrome’ – the cannabis users more frequently chose the harder tasks than the sober people
Effort-based decision making and self-reported apathy in frequent cannabis users and healthy controls: A replication and extension
https://pubmed.ncbi.nlm.nih.gov/35767680
A survey of musculoskeletal patients with pain found that cannabis helped to reduce their pain & that “89% of the participants considered medical cannabis to be more effective than narcotics for adequate pain management”
Patient Experience and Perspective on Medical Cannabis as an Alternative for Musculoskeletal Pain Management
https://pubmed.ncbi.nlm.nih.gov/35796526
& a survey of medical cannabis users again finds the use for chronic pain at the top of the list
Characteristics of People Seeking Prescribed Cannabinoids for the Treatment of Chronic Pain: Evidence From Project Twenty 21
https://pubmed.ncbi.nlm.nih.gov/35775024
See my advice for using cannabinoids for pain here.
Another review looking at CB2 as a great target for disorders of the brain
Potential Role of Cannabinoid Type 2 Receptors in Neuropsychiatric and Neurodegenerative Disorders
https://pubmed.ncbi.nlm.nih.gov/35774086
It’s funny because for a long time, we didn’t think there were even CB2 receptors present in the brain. But now we know that exist at low levels on the microglia (immune guardian cells of the brain) – but that these levels spike when the brain is insulted or as a disease progresses.
In a rat model of stimulant addiction, CBD lowered the likelihood of relapse as well as lowering anxiety & improving endocannabinoid & dopamine machinery levels in the brain
Cannabidiol treatment prevents drug reinstatement and the molecular alterations evoked by amphetamine on receptors and enzymes from dopaminergic and endocannabinoid systems in rats
https://pubmed.ncbi.nlm.nih.gov/35810923
In mice with high insulin levels in their blood, THC protected their livers from inflammation & oxidative stress
The protective effects of Δ 9 -tetrahydrocannabinol against inflammation and oxidative stress in rat liver with fructose-induced hyperinsulinemia
https://pubmed.ncbi.nlm.nih.gov/30427077
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
On the public feud over cannabinoid hyperemesis syndrome by the always excellent Amanda Chicago Lewis
https://www.technologyreview.com/2022/07/20/1056219/weed-influencer-and-scientist-feud-over-cannabis-hyperemesis-syndrome
It involves Alice Moon, the knowledgeable publicist/influencer/CHS activist, & the well-known cannabis scientist Dr. Ethan Russo.
tl;dr: science ain’t always pretty
On Tuesday, Martin Lee talks for free on ‘Psychedelics & the Endocannabinoid System’
https://www.eventbrite.com/e/psychedelics-the-endocannabinoid-system-with-martin-lee-tickets-371270779897
As I said last week, it’s a pleasure to work with Martin Lee. With his history as a journalist, he’s knowledgeable in all kinds of directions – and I still believe that his book ‘Smoke Signals’ is the single best book you can read on the history & science of the cannabis plant.
the Headlines & Fav Articles
A new cannabis legalization bill filed in the US Senate
https://www.marijuanamoment.net/senate-bill-to-federally-legalize-marijuana-and-promote-social-equity-finally-filed-by-schumer-booker-and-wyden
I usually don’t post about potential legislation because most proposed laws do not pass, but I hope this one does.
Also, NIDA finally announces that they will announce a second supplier for federal cannabis research after 5 decades with the universally denigrated products produced by the University of Mississippi
https://www.marijuanamoment.net/top-federal-drug-agency-details-plan-to-award-one-new-marijuana-supplier-contract-for-research-purposes
In a grand understatement, the President of World Athletics said that cannabis athlete policies should be reconsidered
https://www.insider.com/marijuana-policies-track-and-field-reconsidered-sebastian-coe-2022-7
NY State gives $5M to community colleges to develop cannabis job training programs
https://www.marijuanamoment.net/new-york-community-colleges-awarded-5-million-to-create-marijuana-job-training-programs-governor-announces
Oh man. Give me your science classes. I’ll teach those kids I betcha.
Albania plans to legalize medical cannabis
https://www.ganjapreneur.com/albania-plans-to-legalize-medical-cannabis
In an analysis of 100+ hemp topical products, the majority contained more CBD than on the label, 18% had less & 24% were within the 10% limit
Cannabinoid Content and Label Accuracy of Hemp-Derived Topical Products Available Online and at National Retail Stores
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2794440
This being said, testing of topicals & edibles is the most variable of all the cannabinoid content testing protocols. It’s difficult to accurately & reproducibly test fatty lipids in a solid matrix.
According to a survey, 39% of Millennials smoke cannabis more than once a day (hattip to Stuart Tomc)
https://cannabis.net/blog/news/almost-40-of-millennials-smoke-weed-more-than-once-a-day-says-new-study
Listen, I would if I could - but I’m lucky if I can get to it by 9 PM & then start screwing around with my History Wall.
The War on Drugs & Harm Reduction
Chris Alexander, head of the NY cannabis program, talks about the efforts to bring in legacy operators
https://www.newyorkupstate.com/cannabis-insider/2022/07/the-legacy-to-legal-conversation-a-qa-with-ocms-chris-alexander.html
The DEA is being sued for unlawful delays on Freedom of Information Act requests regarding cannabis & psychedelics by my old buddy Dr. Sunil Aggarwal & some crafty lawyers
https://www.marijuanamoment.net/dea-sued-over-unlawful-delays-on-psychedelic-and-marijuana-public-records-requests-through-foia
Basically the only bureaucratic play in the DEA handbook is stall & delay. As dinosaurs, that is their reaction to every lawsuit, Senate inquiry & investigation: stall the hell out of them. I doubt this lawsuit will make any difference - but I hope it annoys the hell out of them.
In San Francisco, terrible news as the new District Attorney doubles down on the Drug War as she comes to power
ttps://twitter.com/petercalloway/status/1548854029899378689
A helpful thread of resources on why safe injection facilities are so vital for public health
ttps://twitter.com/traceyh415/status/1549111266689445888
& an American Medical Association study finds that the first US site in NYC helped to prevent overdose deaths & reduce public use
https://www.marijuanamoment.net/safe-drug-consumption-sites-decrease-overdose-risk-and-prevent-public-use-study-of-first-sanctioned-centers-in-nyc-finds
Law & Business
Short sellers lowering their bets against the stocks of cannabis companies
https://www.bloomberg.com/news/articles/2022-07-18/short-sellers-wind-down-pot-stock-bets-as-congress-mulls-action
Short selling is betting that a stock will go down. To learn more about modern business, the most unbelievably well-written newsletter I’ve ever seen is Matt Levine’s Money Stuff. It’s the only daily newsletter I read religiously & he’s the main reason I know as much as I do about the intricacies of stocks & big business.
A story making the rounds about the Russian ties of Curaleaf, the biggest cannabis company in the US
https://www.theguardian.com/world/2022/jul/19/curaleaf-boris-jordan-russia
The Plant & the History
A look at the genetic regulation of cannabinoid production in the plant – and how adding a little bit of methyl jasmonate every other week can promote more cannabinoid biosynthesis
Delineating genetic regulation of cannabinoid biosynthesis during female flower development in Cannabis sativa
https://pubmed.ncbi.nlm.nih.gov/35774623
Training dogs to detect diseases of the cannabis plant
https://www.cannabisbusinesstimes.com/article/bio-detection-k9-company-partners-purdue-university-train-canines-detect-diseases-in-hemp
Now there’s a good use for a K9 unit.
Also, did you know that dogs can also smell various human diseases such as cancer?
Plant Medicines & Other Psychoactives
In Canada, MDMA psychotherapy trials halted because of patient safety issues
https://www.cbc.ca/news/canada/british-columbia/health-canada-mdma-trial-suspended-safety-issues-1.6520960
However, it seems like the issues come more from not following the rules than from patients being harmed by the substance itself. The ethical lapses have been highlighted in the New York magazine's podcast "Cover Story: Power Trip".
The Psychedelic Press on the value of bad trips & spiritual emergencies by Jasmine Virdi
https://psychedelicpress.substack.com/p/exploring-the-value-of-bad-trips
Psychedelics for chronic pain
Analgesic potential of macrodoses and microdoses of classical psychedelics in chronic pain sufferers: a population survey
https://journals.sagepub.com/doi/abs/10.1177/20494637221114962
Brain scans show that the ability of psilocybin to reduce cluster headaches correlates with changes in the hypothalamus
Psilocybin-induced reduction in chronic cluster headache attack frequency correlates with changes in hypothalamic functional connectivity
https://www.medrxiv.org/content/10.1101/2022.07.10.22277414v1
A new systematic review by Dr Joanna Moncrieff et al. thoroughly dismisses a link between low serotonin levels & depression
The serotonin theory of depression: a systematic umbrella review of the evidence
https://www.nature.com/articles/s41380-022-01661-0
Cannabinoid Science
Clinical Studies & Surveys
Human nails can be analyzed for stress hormones & these researchers just figured out a workflow for doing the same for endocannabinoid & steroid hormone levels
Endocannabinoid and steroid analysis in infant and adult nails by LC-MS/MS
https://pubmed.ncbi.nlm.nih.gov/35781588
In a large study of the heart, recent cannabis users had slightly lower heart rates
The Coronary Artery Risk Development in Young Adults (CARDIA) Study
https://pubmed.ncbi.nlm.nih.gov/35245494
In humans, a novel oral delivery system called Solutech helped to improve cannabinoid absorption according to this industry-sponsored study
A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History
https://pubmed.ncbi.nlm.nih.gov/35787693
In dogs, a study of how CBD moves through their body when taking it nasally, rectally or orally
Pharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs
https://pubmed.ncbi.nlm.nih.gov/35754531
Poor dogs. Making them do bumps of CBD for science…
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
In a rare case study, CBD increased seizures – possibly by interaction with the drug tiagabine
Non-convulsive status epilepticus in the setting of cannabidiol adjunctive therapy
https://pubmed.ncbi.nlm.nih.gov/35770762
In people with first episode psychosis, a year of treatment with cognitive behavioral therapy helped them to decrease their cannabis use as well as their psychotic symptoms
Cognitive Behavioral Therapy Program for Cannabis Use Cessation in First-Episode Psychosis Patients: A 1-Year Randomized Controlled Trial
https://pubmed.ncbi.nlm.nih.gov/35742573
In regard to alcohol hangovers, drinking with cannabis may increase the severity of your hangover not because the weed makes it worse but because then you tend to drink more
Indirect and direct effects of simultaneous alcohol and cannabis use on alcohol hangovers
https://pubmed.ncbi.nlm.nih.gov/35797779
Teens using cannabis had a greater likelihood of cannabis use disorder than adults & more psychotic symptoms than non-using peers – but no increase in depression or anxiety
The CannTeen Study: Cannabis use disorder, depression, anxiety, and psychotic-like symptoms in adolescent and adult cannabis users and age-matched controls
https://pubmed.ncbi.nlm.nih.gov/35772419
According to a big US survey, cannabis use (as well as e-cigarettes) predicted depression symptoms & suicidal ideation
E-Cigarette and Cannabis Use Patterns, Depression, and Suicide Behaviors Among US Youth: Analysis of 2019 Youth Risk Behavior Survey Data
https://pubmed.ncbi.nlm.nih.gov/35792818
Of course, the alternative to the idea that cannabis is causing the depression is that the depressed kids are self-medicating with cannabis.
I suspect that for the most part, it’s the depressed kids self-medicating – but that for some, the cannabis drives them further into the dark place.
In my life, it’s been both – but more of the former than the latter.
An analysis of emergency room visits due to cannabis reported that the majority of patients were adolescents or young adults
Comparative analysis of acute cannabis toxicity in adolescents versus older adults
https://pubmed.ncbi.nlm.nih.gov/35781396
In adolescent mice, frequent low doses of THC altered their microglia & subsequent response to infections as well as their response to social stress
Frequent Low-Dose Δ 9-Tetrahydrocannabinol in Adolescence Disrupts Microglia Homeostasis and Disables Responses to Microbial Infection and Social Stress in Young Adulthood
https://pubmed.ncbi.nlm.nih.gov/35750512
How synthetic cannabinoid toxicity may be altered by the human carboxylesterases enzymes
Going deeper into the toxicokinetics of synthetic cannabinoids: in vitro contribution of human carboxylesterases
https://pubmed.ncbi.nlm.nih.gov/35788413
Delta-8 THC
A study in three people found that delta-8 THC tends to move through the body in a similar manner & timeframe to delta-9 THC
Examining impairment and kinetic patterns associated with recent use of hemp-derived Δ 8-tetrahydrocannabinol: case studies
https://pubmed.ncbi.nlm.nih.gov/35799289
A survey of delta-8 THC users found that the most common ingestion method was vaping
Delta-8 THC use in US adults: Sociodemographic characteristics and correlates
https://pubmed.ncbi.nlm.nih.gov/35644057
An epidemiological analysis of how delta-8 THC might cause birth defects
Congenital anomaly epidemiological correlates of Δ8THC across USA 2003-16: panel regression and causal inferential study
https://pubmed.ncbi.nlm.nih.gov/35782486/
Cancer
In cancer patients, cannabis helped to significantly improve quality of life, cognitive functioning & breathing – but worse on sleep than patients with no cannabis
Symptom Management and Quality of Life of Palliative Cancer Patients After Being Administered with Thai Medicinal Cannabis
https://pubmed.ncbi.nlm.nih.gov/35773908
In Dutch cancer patients, a quarter of them reported cannabis usage for medical effects, often because of the anti-cancer effects
Cannabinoid consumption among cancer patients receiving systemic anti-cancer treatment in the Netherlands
https://pubmed.ncbi.nlm.nih.gov/35779108
In glioblastoma cells (the most aggressive brain cancer), a 1:1 of THC:CBD lowered growth & metabolism via the mitochondria (powerhouse of the cell)
The Combination of Δ 9-Tetrahydrocannabinol and Cannabidiol Suppresses Mitochondrial Respiration of Human Glioblastoma Cells via Downregulation of Specific Respiratory Chain Proteins
https://pubmed.ncbi.nlm.nih.gov/35804909
In melanoma cancer cells, CBD helped the drug mitoxantrone to work better at killing cancer cells but produced antagonist effects to the drug cisplatin
Cannabidiol Interacts Antagonistically with Cisplatin and Additively with Mitoxantrone in Various Melanoma Cell Lines-An Isobolographic Analysis
https://pubmed.ncbi.nlm.nih.gov/35743195
In fibroblasts from lung cancer cells, THC & CBD alone or combined helped to lower proliferation
In Vitro Effect of Δ9-Tetrahydrocannabinol and Cannabidiol on Cancer-Associated Fibroblasts Isolated from Lung Cancer
https://pubmed.ncbi.nlm.nih.gov/35743206
Recent Reviews
This review looks at the ability of PEA to help with neuromuscular diseases, especially those involving acetylcholine
Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function
https://pubmed.ncbi.nlm.nih.gov/35740883
Preclinical Research
In a mouse model of obesity, β-caryophyllene (one of the predominant terpenes in cannabis) improves their metabolic & immunological processes
β-Caryophyllene, a Dietary Cannabinoid, Protects Against Metabolic and Immune Dysregulation in a Diet-Induced Obesity Mouse Model
https://pubmed.ncbi.nlm.nih.gov/35792574
In mice with abdominal pain, activating the CB1 receptor along with the mu-opioid receptor worked better at lowering pain
Cannabinoid 1 and mu-opioid receptor agonists synergistically inhibit abdominal pain and lack side effects in mice
https://pubmed.ncbi.nlm.nih.gov/35790401
In the intestine of mice being fed a high-fat diet, the CB1 receptor helps to regulate the proteins governing intestinal permeability & to restore intestinal barrier function
Role of CB 1 receptors in the acute regulation of small intestinal permeability: Effects of high-fat diet
https://pubmed.ncbi.nlm.nih.gov/35787179
In a rat model of retinal neurodegeneration, the ability of saffron to protect the eyes appears to be mediated by the CB1 & CB2 receptor (hattip to Stuart Tomc)
Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration
https://pubmed.ncbi.nlm.nih.gov/27861558
Add this to our long list of medicinal plants who owe their efficacy to modulation of the endocannabinoid system.
A look at how the CB1 receptor’s NPXXY motif (a piece of the receptor inside the cell) works to recruit B-arrestin molecules for passing on the downstream signals
The NPXXY Motif Regulates β-Arrestin Recruitment by the CB1 Cannabinoid Receptor
https://pubmed.ncbi.nlm.nih.gov/35792570
An intriguing study on how THC manages to only be a partial agonist of the CB1 receptor (hattip to Stuart Tomc)
Mechanistic origin of partial agonism of tetrahydrocannabinol for cannabinoid receptors
https://pubmed.ncbi.nlm.nih.gov/35227761
Partial agonism of a receptor is not an easy thing to achieve via human science. It’s much easier to make a drug that completely blocks or completely binds a receptor. To create one that can operate at half-strength is more of an art. This study figures out why the tail of THC plays a crucial role in its partial agonism of CB1.
Thanks.
- lex
PS: It’s thanks to Spotify’s ‘Discover Weekly’ that I find many of the albums for this section – and for that I am eternally grateful. But I’m disappointed this week because even though they pointed me to Kourosh Yaghmaei, they didn’t even have a short bio for the Godfather of Iranian psychedelic rock. Here’s his ‘Back From the Brink’ album so that you can see that glorious mustache.
Coming of age in Tehran in the early ‘70s, his first single "Gol-e Yakh" ("Ice Flower") sold 5 million records (it’s the first track on the album above). His songs combined Persian classical poems with his own writings & their style drew on traditional Persian music, blues & the psychedelic rock of Led Zeppelin & Pink Floyd. It’s just great stuff.
Unfortunately, he only got to record two albums before the Revolution led to a crackdown on all things Western. Forbidden from performing, Yaghmaei turned to writing books & working with children. However, he refused to leave the country, saying “I believed that if I had changed my career it would be an unrespectful behaviour to my music and myself and also it would mean betrayal to my cultural roots. Now that I look back, I am glad I did not bribe anyone or bow to pressures, but lived all these 37 years with honour. I believe even in an unequal battle, resistance is preferred to giving up.”
As he reports in a Vice interview, he continued working within the government strictures & jumping through their hoops to release what music he could. Sometimes he wasn’t allowed to put his picture on the album cover. Other times he’d work for 12 years to get an album approved before it would finally be banned for using professional sound equipment. But he managed to put out a number of albums out anyway. Still alive, he runs a private music school & studio in Tehran
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…]
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.