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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 is a free offering from my company White Whale Creations. We produce educational content for cannabis & psychedelic companies & have sponsorship opportunities for The Lex Files podcast.
In science this week, some intriguing uses for CBD (vitamin D?), PEA for mania & research on the link between cannabis & violence. Also, a lot of intriguing developments in local & international politics around cannabis. The Times They Are A-Changin'
Remember, if I don’t define a term, it’s probably in the Living Glossary at the end of the email where I define all the cannabinoids & their related endocannabinoid machinery. [plus, what kind of whale each of them would be. No nonsense]
My ad: 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 set of cannabinoids that work for them. If you – or someone in your life – needs help in figuring out what works best for you, I’m here to help.
I counsel people about using medical cannabis, CBD & even lesser known but powerful medicines 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. It’s a way to find health that can be unparalleled by traditional medications. You can see my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression here.
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 humans with acute mania being treated with lithium & risperidone, 600 mg of PEA caused a significantly lower score on the Young Mania Rating Scale
Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: a randomized, double-blind and placebo-controlled trial
PEA man. It might be an even more powerful medicine for CBD, especially for anything related to the immune system.
This sad survey shows that for patients with multiple sclerosis, few of them talk to their doctors about how to use cannabis & instead rely on the budtender at the dispensary
Sources of Cannabis Information and Medical Guidance for Neurologic Use: NARCOMS Survey of People Living With Multiple Sclerosis
For anyone you know with MS, it is absolutely the disease where you should be trying cannabinoids. As both a neurodegenerative disease & an autoimmune disorder, it’s at the center of the Venn diagram of things that we know the cannabinoids help with. See my guidance here on Advice for Neurodegenerative Disorders.
In a groundbreaking study, for the first time, a group linked a genetic variant of the endocannabinoid system with a human disease: in children with a rare eye disorder, they had different versions of DAGL (the enzyme that produces the endocannabinoid 2-AG)
Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome (NODRS)
This thorough review of autism spectrum disorders looks at the overlap between the endocannabinoid system & the microbiome’s effect on the gut-brain axis
The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders
So much of this makes sense. Autism often involves gut problems – and part of CBD’s ability to help may be via the gut-brain axis.
For my advice on using the cannabinoids for autism, see my Advice for Autism page here.
In tissue samples of cholangiocarcinoma (cancer of your liver’s bile ducts), the addition of CBD & CBG resulted in an immediate reduction of proliferation, a significant increase in late-stage apoptosis (cellular suicide) & an inhibition of migration, invasion & colony formation ability
Cannabidiol and Cannabigerol Inhibit Cholangiocarcinoma Growth In Vitro via Divergent Cell Death Pathways
In rats with a vitamin D3 deficiency, CBD improved their thyroid function & increased the levels of Vitamin D receptors as well as vitamin D3 levels, suggesting it as a treatment for people with low functioning thyroids as well as to maintain bone health
Cannabidiol improves thyroid function via modulating vitamin D3 receptor in vitamin D3 deficiency diet-induced rat model
In skin stem cells, CBD has a central role in inhibiting pro-inflammatory signals
Cannabidiol has a central role in the NF-κB inhibition of a Cannabis sativa L. extract in human keratinocytes
In a test of various vegetable oils, olive oil best helped to increase CBD absorption
Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol
Also, remember that in general, it is better to take your CBD after a meal with a little bit of fat in it. Lipids like to stick together & this helps to increase absorption.
If you die with cannabinoids in your brain & they put your brain in a freezer, those cannabinoids will be stable for a year. If they put your brain in a fridge, they will not
Cannabinoid Stability in Postmortem Brain Samples Stored at Different Temperatures
Food for thought.
The first result of cannabis toxicity in a pet rabbit
Cannabis toxicity in a pet rabbit (Oryctolagus cuniculus)
Alternative headline: Won’t anyone think of the rabbits?
I liked both that they just used a regular human urine test to find the THC in its system & that lagomorphs is the order name for the rabbit family.
An evergreen note on reading restricted paper:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version) or Google Scholar itself.
For the infamous backdoor, use Sci-Hub – the pirated papers repository (Chrome extension here). This works better for older paper than the stuff that just came out.
For Twitter users, send a Tweet of the paper’s title with the hashtag #icanhazpdf. It works because people are beautiful(ish).
Finally, email the author. They’re almost always happy to oblige because, thanks to the predatory academic publishing system, they don’t make a dollar off of their papers.
Popular science news, articles & videos
ProjectCBD on chirality in cannabinoids & how this “handedness” of molecules may cause problems when synthesizing things like CBD or delta-8 THC by Dr. Matthew Elmes
Project CBD on the crossover between ayahuasca, serotonin & the endocannabinoid system by Nate Seltenrich
I also wrote about serotonin, the cannabinoids & psychedelics a few years ago (the last piece I did before becoming a father & time getting short…)
On the myth of fentanyl-laced marijuana & the rise of a drug panic by Calvin Stovall
the Headlines & Fav Articles
Spain to allow medical cannabis sales from pharmacies
This is funny because they already possessed the most ideal recreational market: social clubs. Tolerated by the authorities, quasi-legal, laidback, cool, no problems, no hassles - they’ve got the best cannabis system in Europe.
Louisiana just passed a bill protecting state workers using medical cannabis from "negative employment consequences”
The Washington, D.C. Council passed a bill to let people certify themselves as medical cannabis patients, a brilliant tactical move in the city’s long-running battle with an idiotic Congress that keeps blocking their right to govern themselves & their cannabis markets
Seriously, it sounds like hell for your city to be ruled by the federal lawmakers.
The California State Fair shows off the winners of its first-ever cannabis competition
How very sane & normal. For all those activists who spent the last 50 years working for this, it must be surreal to see it actually happening.
A look at cannabis in Africa sees a wave of loosened restrictions – but the smaller producers are still illegal or getting locked out
‘Israel’s first cannabis cafe tried to bridge the gap between Arabs and Jews’ by Niko Vorobyov
Finally, the driving test I’ve been waiting for: in a simulator, people who smoked pot every day showed no difference between before & after smoking - but for those who only smoked occasionally, cannabis caused more lane departures during distraction periods
Influence of cannabis use history on the impact of acute cannabis smoking on simulated driving performance during a distraction task
I’ve heard it from so many old stoners – notably once while whipping around mountain turns in the Oakland hills with a fat joint in her hand – that stoners drive just as well when they’re high as when they’re not. And if they have medical conditions, sometimes they drive better because their painful conditions are eased.
Also, the ability to develop tolerance to cannabinoids confirms this thinking as well. It seems that one of the first places where your brain gets desensitized to the effects of cannabinoids is in the basal ganglia, a brain center involved in the coordination of movement.
And in this study of insurance premium data, medical cannabis legalization caused premiums to decline by an average of $22 per year
Medical cannabis and automobile accidents: Evidence from auto insurance
“We estimate that existing legalization has reduced health expenditures related to auto accidents by almost $820 million per year with the potential for a further $350 million reduction if legalized nationally.”
If you can trust anyone to evaluate risk correctly, it’s those vampires who create the actuary tables for insurance firms.
The War on Drugs & Harm Reduction
Customs and Border Protection seized almost 100,000 pounds of cannabis so far this year
In Illinois, they awarded $45 million in grants from their legal marijuana tax revenue to invest in communities "hardest hit by the failed war on drugs”
The FBI arrested an attorney in Massachusetts for trying to bribe a police chief to get a marijuana business approved
<getting out the popcorn> Love these. Fascinating part of the weed rollout. And remember kiddos, for every one case that you see, there’s a bunch more who are smarter than this & not getting caught. In this instance, the police chief was an Andy Griffith type & immediately reported the attempt at a bribe to the feds.
And an associate of Rudy Giuliani got 20 months in prison for, among other things, political donations for help in obtaining cannabis licenses
Law & Business
California ends its cannabis cultivation tax
The governor of Kansas & the state attorney general are being sued by a delta-8 THC seller who says they’re "intentionally misapplied" the law to prosecute businesses in his industry
Love the chutzpah on this one.
The Plant & the History
A method to classify cannabis chemovars (strains) using their terpene & cannabinoid profile
Multivariate classification of cannabis chemovars based on their terpene and cannabinoid profiles
I didn’t know that in Israel, the types of medical cannabis typically used are high-THC, high-CBG & a hybrid.
CBG is the future!
In cannabis growing, this review examines the factors that affect cannabinoid levels: pruning; light & plant density, ontogeny (development), temperature, altitude, CO2 concentration, fertilization & substrate, water availability
Cannabis sativa L.: Crop Management and Abiotic Factors That Affect Phytocannabinoid Production
A study on how to use the sex & cultivation conditions of hemp to improve fiber quality
Fibers development in a dioecious hemp cultivar: the role of plant sex and cultivation conditions
A new academic book on the potential of hemp in the global economy
Revolutionizing the Potential of Hemp and Its Products in Changing the Global Economy
A review of using hempcrete
Opportunities & challenges of hempcrete as a building material for construction: An overview
While mostly positive, they do point out that hempcrete does not have great mechanical performance & that it tends to retain water. Plus, as our Construction Knowledge Skeptic Ned Pelger usually points out, the necessity of putting special conduit pipes in for your electrical wiring would increase the cost too much for use on most types of regular projects.
Plant Medicines & Other Psychoactives
‘Tracing The History of Hallucinogens in China’
The above summary is from her paper here:
Hallucinogen Use in China
‘How the Shipibo Came to Be the Most Common Group Serving Ayahuasca to Foreigners’ by Shelby Hartman
Big Rolling Stone article on psychedelics to heal the injuries of pro sports with quotes from Dr. Julie Holland
In collaboration with ICEERS, a study of 375+ ayahuasca participants finds that ayahuasca may support a healthy lifestyle
Ayahuasca and Public Health II: Health Status in a Large Sample of Ayahuasca-Ceremony Participants in the Netherlands
4 docs at the VA turn to psychedelics by Ernesto Londoño
A nice review paper about what we know about the effects from a single dose of psychedelics
Sustained effects of single doses of classical psychedelics in humans
Meanwhile, in mice, LSD altered the expression of genes related to neurotropic-, neurotrophic- & neuroplasticity signaling
Modulation of DNA methylation and protein expression in the prefrontal cortex by repeated administration of D-lysergic acid diethylamide (LSD): Impact on neurotropic, neurotrophic, and neuroplasticity signaling
A review of the history & study of psychedelics for substance use disorders
Classic and non-classic psychedelics for substance use disorder: a review of their historic, past and current research
A review of using psilocybin for trauma-related disorders like PTSD
Psilocybin for Trauma-Related Disorders
A review of using ketamine for psychotherapy
Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature
If you want to try ketamine in a great setting & can get to NYC, may I recommend the art & space-holding masters at Cardea.
A review of psychedelics for palliative care distress at the end of life
Psychedelic-assisted psychotherapy to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care
The US Patent Office awarded a patent to MindMed for “candyflipping”: using MDMA with a psychedelic
Here’s two commentators on why this makes the USPTO look stupid & MindMed like an unethical patent picket firm
On the history of LSD & the chromosomal damage scare of the 1960s by Robert Dickins
(really enjoying this newsletter… Plus, check out the Psychedelic Press for their journal & all kinds of great books)
Clinical Studies & Surveys
In humans who used cannabis more than 100 times, their eyes had a significantly reduced risk of age-related macular degeneration – but the people who used it that often tended to develop it when they were younger
Cannabis smoking and age-related macular degeneration in the UK Biobank cohort
This speaks to the anti-inflammatory of power on the positive side – but also its negative effect on blood vessel growth.
In Parkinson’s disease patients with REM sleep behavior disorder & restless legs syndrome, CBD did not reduce the severity of the restless legs syndrome
The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial
In 20 patients with periodontitis (severe gum infection), their gum tissue had much higher levels of CB2 & slightly lower levels of CB1, suggesting cannabinoids as a treatment
Evaluation of cannabinoid receptors type 1-2 in periodontitis patients
Recommended for You
In people taking antipsychotics, it causes damage to their heart & this seems to be mediated by the CB1 receptors interacting with the inflammasomes, suggesting the targeting of CB1 to lower the cardiac side effects of antipsychotics
CB1R-stabilized NLRP3 inflammasome drives antipsychotics cardiotoxicity
In these brain scan studies of cannabis users, although they had a “thinner cortex, smaller subcortical grey matter volumes, and higher machine-learning-predicted brain age”, this seems to be because of the use of other drugs like alcohol & tobacco
diminished structural brain integrity in long-term cannabis users reflects a history of polysubstance use
Cannabis use not associated with aneurysms (though it’s hard to see more than the article’s title)
Cannabis Use Is Not Associated With Aneurysmal Subarachnoid Hemorrhage Complications or Outcomes
A survey of doctors in Uruguay (the first country to legalize cannabis nationally) finds that while only half of them had recommended it, they almost unanimously agreed that it should be legal
Physicians’ attitudes towards medical cannabis: a survey from Uruguay
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
In human & mouse males, cannabis reduced the quality of sperm & caused changes in the epigenetics that got passed onto the offspring, leading the researchers to recommend stopping cannabis for 11 weeks prior to trying to get pregnant
CIPHERS: Effects of male marijuana use on sperm health and potential risks to future children
This review of data shows “a moderately positive association between cannabis use and perpetration of physical (including intimate-partner) violence, for example involving assault, aggression, and fighting”
Conceptualizing and considering Cannabis-Related "Harm-to-Others": The Role of Cannabis-Related Violence
I keep saying that this is true. It was known by the ‘50s & even though it doesn’t fit with this generation’s view of laidback stoners, it makes sense that this is true for some people, especially heavy users. (Of course, it’s no reason to ban it. If we considered propensity to violence in our drug control regimes, we’d have alcohol locked up in safes & available only by prescription)
This French review sees a link between cannabis & violence in the early stages of psychosis
Cannabis use and impulsivity in violent behaviour
Peut-être que le herbe a causé la Terreur ?
In a cohort study in Finland, early cannabis use was linked to later psychotic-like experiences
Trajectories of adolescent psychotic-like experiences and early cannabis exposure: Results from a Finnish Birth Cohort Study
This review of the literature suggests that in schizophrenia, cannabis use may increase the chances of suicide
Cannabis Abuse and Suicide in Non-Affective Psychosis: A Recent Literature Mini-Review
In patients with a history of psychosis, abstinence from cannabis was related to a reduced risk of a subsequent psychotic episode
Is Cannabis Abstinence Related to Subsequent Reduced Risk of Psychosis? a Nested Retrospective Case Control Hierarchical Survival Analysis
While cannabis users did not show an increased risk for respiratory diseases, they did show a greater chance of going to the hospital
Cannabis use and risks of respiratory and all-cause morbidity and mortality: a population-based, data-linkage, cohort study
In students at historically black universities, moderate cannabis use disorder disturbed their sleep but severe cannabis use disorder did not
Cannabis Use Disorder Severity and Sleep Quality Among Undergraduates Attending a Historically Black University
In a review of military veterans who got in trouble with the law, it looks like the use of cannabis testing does not drive them towards using synthetic cannabinoids – but synthetic cannabinoids are “an underappreciated problem within the military”
Does cannabis testing in the military drive synthetic cannabinoid use? Self-reported use motivations among justice-involved veterans
In brain scans & tests with older cannabis users, they had worse inhibitory control as well as reduced metabolism in some brain regions
Differences in Inhibitory Control and Resting Brain Metabolism between Older Chronic Users of Tetrahydrocannabinol (THC) or Cannabidiol (CBD)—A Pilot Study
In a study of adolescents & executive control, cannabis users showed negative effects on flexible shifting & deficits in inhibitory control
A Comparison of Task-Based and Questionnaire Assessments of Executive Control Aspects in Relation to Adolescent Marijuana Initiation
In one Ottawa hospital, the two years since legalization saw 32 children go to the ER for cannabis exposure, mostly edibles
Unintentional cannabis exposures in children pre- and post-legalization: A retrospective review from a Canadian paediatric hospital
A synthetic cannabinoid user going to the hospital with catatonia (an inability to move properly)
Key Learning Points from a Case of Cannabinoid Induced Catatonia
We don’t talk about it much anymore – but huge levels of cannabis can cause catatonia so strong that a person can be immobile for days. You see reports from 19th century India of being able to take someone’s arm & lift it up in the air, and it just hangs there for hours.
A young man goes to the hospital with a heart attack after cannabis consumption
Cannabis-induced myocardial infarction in a 27-year-old man: Case report
This study in mice on the addiction potential of the synthetic cannabinoid 5F-MDMB-PICA does a good job of showing how scientists study addiction in animal models
Long-term effect after intravenous self-administration (IVSA) of the synthetic cannabinoid receptor agonist 5F-MDMB-PICA in adolescent mice
In pregnant rats exposed to THC e-cigarettes, their offspring showed delayed sensorimotor development early in life & impaired motor coordination in early adolescence as well as increased hyperactivity among the males
Effects of prenatal alcohol and delta-9-tetrahydrocannabinol exposure via electronic cigarettes on motor development
In male vs female cancer patients, cannabis helped both groups with pain, sleep, anxiety & well-being – but in females, it helped with nausea, lack of appetite & shortness of breath while in males it helped more with pain
Sex differences exist in the perceived relief of cancer symptoms with medical cannabis: results from the Quebec Cannabis Registry
In elderly cancer patients, this review of their charts found no difference in pain, nausea, appetite, insomnia or anxiety scores after they started medical cannabis
Assessing Efficacy and Use Patterns of Medical Cannabis for Symptom Management in Elderly Cancer Patients
Sometimes you look at a piece of research and go, really?
In a cancer patient with a feeding tube, the addition of hemp oil increased weight & muscle mass as well as the improvement of nutrition indices
Alternative Administration of Artificial Feeding with Hemp Oil in a Patient with Esophageal Ca
A review of cannabis use in cancer patients
Cannabis Use in Patients With Cancer: A Clinical Review
A review of cannabis for autoimmune disorders
Cannabis and Autoimmune Diseases
When the body attacks itself, the cannabinoids seem uniquely suited to calming down this aberration. If you would want me to write up an advice page on this subject, let me know. It’s tricky – but there are some basic guidelines to follow & products that anyone could try.
A review of how the endocannabinoid system balances the intestines
The role of the endocannabinoid system in the regulation of intestinal homeostasis
This review of stroke looks at the ability of the cannabinoids to protect the brain via the glial cells (support cells that maintain homeostasis)
Cannabinoids as Glial Cell Modulators in Ischemic Stroke: Implications for Neuroprotection
There’s a lot of data on cannabinoids for strokes that you can see on the CVResearch site under the Nervous System.
For neurodegenerative diseases, this review looks at the last ten years of data on three key molecules from Nature’s treasure chest: curcumin from turmeric, resveratrol from berries & CBD from cannabis
Curcumin, Resveratrol and Cannabidiol as Natural Key Prototypes in Drug Design for Neuroprotective Agents
In microglial cells (the immune cells of the brain), activating the CB1 or CB2 receptor with synthetic cannabinoids lowered the release of nitric oxide & pro-inflammatory cytokines as well as reduced neuronal damage when insulted (probably via MAPK signaling)
Synthetic cannabinoids reduce the inflammatory activity of microglia and subsequently improve neuronal survival in vitro
In mice taking the opioid painkiller Tramadol, the rapid lowering of activity in their hippocampus (memory center) seems to be mediated by both the endocannabinoid system & the orexin system
The Effect of Orexin-2 and Endocannabinoid-1 Antagonists on Neuronal Activity of Hippocampal CA1 Pyramidal Neurons in Response to Tramadol in Rats
In heart cells poisoned by phosphine gas, THC protected them from the harmful effects, especially cytotoxicity (damage to cell), mitochondrial toxicity (damage to the cell’s powerhouse) & oxidative stress
Inhibition of mitochondrial permeability transition pore and antioxidant effect of Delta-9-tetrahydrocannabinol reduces aluminium phosphide-induced cytotoxicity and dysfunction of cardiac mitochondria
PS: Just fire up the first track of ‘Sin & Soul... And Then Some’ by Oscar Brown Jr. I dare you.
Check out that voice. And he wasn’t just a great singer. In his socially charged lyrics, he presaged the political consciousness of music that would arise in soul, funk & hip-hop. As a broadcaster in 1944, he became “America’s first Negro newscaster”. After that, even though he was a card-carrying Communist, he ran for Congress on a Republican ticket. In NYC, after being blown away by the play ‘Raisin in the Sun’, he partnered with Lorraine Hansberry & her husband to create a stage musical. He went on to write stage shows where he featured & cast teens from impoverished neighborhoods in his hometown of Chicago & with his wife, they wrote a musical that starred Muhammad Ali when it went to NYC. On top of all that, a lifetime of humanitarian work. And throughout his magnificent larger-than-life life, he refused to do anything but keep his political beliefs front & center. Just check out ‘Bid ‘Em In’ to see the power of what he could do.
The Living Glossary
Here’s a running glossary of the basic cannabinoid terms. This 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 basically, we treat the human brain like the ocean: both deep, mysterious & chockablock with fish & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land). And neurons are complex underwater cities where hundreds of fish interact.
The cannabinoids found inside all mammals & almost every other form of life besides insects
The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”
Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]
The second endocannabinoid receptor discovered. Found in almost every organ of the body & closely connected to our immune system. The CB2 occurs at low levels in the brain where it responds to neural insults.
[a gay bar in the membrane wall of the neuronal city]
FAAH (fatty acid amide hydrolase)
The enzyme that breaks down anandamide & a frequent target of drug discovery for modulating the endocannabinoid system. If you inhibit the FAAH enzyme, it does less breaking down of AEA, and your AEA levels rise. More balance.
[the giant squid that slices sperm whales in half]
Diacylglycerol lipase (DAGL or DGL)
The enzyme responsible for producing 2-AG.
MGL (monoacylglycerol lipase - also sometimes abbreviated as MAGL)
The enzyme that breaks down 2-AG. Another frequent target of drug discovery because inhibiting MGL raises 2-AG levels
[a giant octopus that eats blue whales]
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]
An endocannabinoid related to sleep. They discovered it by keeping cats awake for 3 days & then analyzing their spinal fluid. You can buy it on Amazon. 2 scoops helps you to sleep while 6 scoops is a very pleasant psychoactive experience (Hamilton Morris has called it his favorite way to get high - which is saying something). It’s also worth considering for cancer treatment.
[Humpback whale, because it sings hippies to sleep]
Oleoylethanolamide (unfortunately, also abbreviated as OEA sometimes)
An analog of anandamide, this lipid acts via the peroxisome proliferator-activated receptor alpha (PPAR-α) receptors on the cell’s nucleus. These alter genetic transcription, a powerful method of cellular control. In animal models, oleoylethanolamide causes them to eat less food & drink less alcohol. In roundworms, it causes them to live longer. For the orphaned GPR119 receptor (a receptor that might one day be officially designated as a cannabinoid receptor), it may be the native ligand (the thing that binds to it). It’s already identified as the native ligand for hypoxia-inducible factor 3α (HIF-3α). OEA also interacts with our histamines.
[Pygmy sperm whale. Not well known, a smaller cousin to the sperm whale]
Fatty acid-binding proteins (FABPs)
These transport proteins move fatty lipids such as the endocannabinoids around the body. While still mysterious, they’re thought to move anandamide between membranes as well as transporting it to be broken down by the enzyme FAAH. Several types of FABPs exist in humans. THC & CBD bind to some of them. This may explain why endocannabinoid levels tend to increase after consuming cannabinoids. As the brain ages, the levels of FABPs decrease.
The cannabinoids produced by the cannabis plant.
THC (delta-9-tetrahydrocannabinol or Δ9-THC)
The well-known & well-studied molecule in cannabis that gets you high - and helps in a number of other fascinating ways.
[African elephant. Powerful, unpredictable, beautiful]
The cousin of THC that does not get you high but does a lot of the heavy lifting in why hemp has been such a staple of medicine since before recorded history. In most plants outside those bred for the recreational market, CBD is the most common cannabinoid. It binds to a wide swathe of receptors outside the endocannabinoid system including three serotonin receptors, two opioid receptors, a dopamine receptor as well as glutamate & GABA (the two most widespread neurotransmitters, the basic neuronal signals for excitation & inhibition, respectively)
[Indian elephant. sweet, gentle, you can work with it]
The third most common cannabinoid in the plant, it’s not well studied in humans despite a number of intriguing preclinical studies, especially as an anti-inflammatory and for pain. Nonpsychoactive, it interferes with the breakdown of AEA & 2-AG (leading to a rise in their levels) as well as interacting with the vanilloid receptors.
[Sri Lankan elephant. Little, sweet, not as well known as it should be]
CBDV is like CBD with a shortened tail (side chain). Also nonpsychoactive, it tends to occur at low levels in most cannabis cultivars. It’s known to be an anticonvulsant & is suggested for treating autism in humans & in animal models. The cannabinoid pharmaceutical company GW has it in their developmental pipeline as GWP42006.
[An Asian elephant with a short trunk]
Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]
A terpene that’s also a cannabinoid.
The terpenes of cannabis give the plant its smell. Also found in oregano, black pepper, lavender & hops, beta-caryophyllene has a spicy sweet woody smell. But unique among terpenes, this one also binds to the CB2 receptor, making it a dietary cannabinoid. It shows a potential for treating inflammation, pain, anxiety & seizures. The FDA has designated it to be GRAS (generally regarded as safe) & thus it can be safely used as a food additive.
[a terpene/cannabinoid that travels through the air? That could only be a flying elephant]
Nabiximols (ie Sativex®)
A pharmaceutical 1:1 CBD:THC spray produced by GW Pharmaceuticals. One of the first cannabinoid pharmaceuticals on the market, Sativex is an approved treatment for neuropathic pain, spasticity, overactive bladder & the symptoms of multiple sclerosis.
Epidiolex® (in the UK, Epidyolex®)
An isolated CBD formulation approved for treating the severe seizures of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. Produced by GW Pharmaceuticals, the doses tend to be incredibly high – hundreds or thousands of milligrams of CBD every day in young children. But even with that, the side effects tend to only be lethargy & stomach upset.
Dronabinol (ie Marinol® and Syndros®)
A synthetic form of THC for the treatment of anorexia in AIDS patients & the nausea of chemotherapy. These tend to not be popular with patients because it’s a horse dose of THC with no modulation by the other molecules in the cannabis plant like CBD.
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.