C&P#35: CBD for your animal friends + many weird uses of hemp + acupuncture & electric daisies works via the ECS
US produces 48M pounds of cannabis!
· ‘Tis the season: the first paper with a 2023 release date. 🎵Deck the halls with peer-reviewed literature. Tra la la la la…. 🎵
· CBD for horses! CBD for dogs! CBD for roundworms!
· A poetic review of the dance between histamine & an anandamide analogue
· CBD & THC for meth addiction
· The great Dr. Grotenhermen on cannabis & cancer
· so many novel uses of hemp: as an aeorgel to absorb oil spills or air pollution, as a dressing for wound healing, to make food packaging materials, to fix your spouse, to make stronger glass
· acupuncture helps with chronic itchy skin via the CB1 receptors
· Turns out the “toothache plant” helps via the endocannabinoid system
· The French on the negatives of cannabis smoke for the lungs
· Many studies around cannabis use disorder (yes, it’s a real thing) such as its increased levels in gender & sexual minorities
· Cannabinoids & catatonia
This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations.
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As always, at the bottom there’s a Living Glossary of cannabinoid terms
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Popular Science Writing & Events
‘CBG! A compound with intriguing medical potential’ by Nate Seltenrich for ProjectCBD
A free webinar on Dec 15th about the regulations around intoxicating hemp products
Intoxicating Hemp Regulations: Where We Are and What’s to Come
Best Of Cannabinoid Science...
For Alzheimer’s, a review of the advantages of using multiple cannabinoids for treatment
Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer's disease
As always, I think one of the most under-utilized uses of cannabis is for neurodegenerative disease. For my advice on how to use CBD & THC, see my neurodegenerative disorders page here.
For patients with lower back pain, inhaling THC-rich cannabis helped more with the pain than a CBD-rich sublingual (under the tongue)
Comparing Sublingual and Inhaled Cannabis Therapies for Low Back Pain: An Observational Open-Label Study
Sexual & gender minorities appear to have an increased risk of cannabis use disorder because they use it as a coping mechanism
A Review of Disparities in Cannabis Use and Cannabis Use Disorder Affecting Sexual and Gender Minority Populations and Evidence for Contributing Factor
The most poetic review of a dance between two ancient molecules that I’ve ever seen…
A Duet Between Histamine and Oleoylethanolamide in the Control of Homeostatic and Cognitive Processes
Though I have seen the term pas de deux in a cannabinoid paper before. Some scientists just love their high school French classes.
In a mouse model of chronic itchy skin, electroacupuncture helps via the brain’s CB1 receptors & the lowering of serotonin levels by the control of both GABA & glutamate (the brain’s primary inhibitory & excitatory neurotransmitters respectively)
Electroacupuncture reduces chronic itch via cannabinoid CB1 receptors in the ventrolateral periaqueductal gray
A review of cannabis & cancer by the great Dr. Franjo Grotenhermen
Cannabis and cancer
In a rat model of tardive dyskinesia (repetitive movement of facial muscles), CBD helped the standard treatment of haloperidol to work better
The effects of cannabidiol on behavioural and oxidative stress parameters induced by prolonged haloperidol administration
2021: A review of the other receptors that may one day be defined as cannabinoid receptors
Endocannabinoid signaling pathways: beyond CB1R and CB2R
A review of the rhetoric of cannabis in religion
The Rhetoric of Marijuana in Religion
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), Google Scholar itself or try ResearchGate.
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.
My Cannabis & Psychedelic Consulting Sessions
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the Headlines & Fav Articles
Marijuana Moment with a deep dive into the cannabis stances of the incoming Congressional lawmakers
“Biden’s Marijuana Pardons Are Baby Steps, Falling Far Short of Real Reform of America’s Drug Laws” by Jeffrey Miron of Cato
I interviewed Dr. Miron years ago & have always found his policy work on cannabis to be spot-on.
The new federal jobs application from the Office of Personnel Management will not ask about cannabis use older than 90 days except in limited circumstances
Gallup says young Americans twice as likely to be smoking cannabis as tobacco
A report from Whitney Economics estimates the US in 2022 produced 48.8 million pounds of cannabis
Instagram is your new local pot dealer
In Pennsylvania, a pilot program to cover $50 of the cost of medical cannabis for low-income patients
In Minnesota, regulators agree to add irritable bowel syndrome & obsessive-compulsive disorder as medical cannabis qualifying conditions but balk at gastroparesis & opioid use disorder
I hate this shit. The fact that some pencil pushers get to decide who gets to use medical cannabis is egregious. The only reason that I know that gastroparesis is a disease of your stomach not pushing food forward properly is because I’ve seen so many studies about people using cannabis to help with it. Qualifying conditions is an abomination.
The only qualifying condition that should matter is getting a doctor to agree that medical cannabis is worth a try for you.
In Ireland, a bill is introduced to decriminalize cannabis
A French lawmaker tweeted that he wants a €1,000 fine for people who smoke a joint
I tweeted back, ‘T'es une merde’.
The War on Drugs & Prohibition
How fucking terrible: a poor 16-year-old kid had to swallow a bag of weed because of the idiocies of Prohibition & spent 4 painful days of vomiting in the hospital as the baggie worked through his system
Body stuffing during apprehension resulting in distal esophageal impaction: a case report and review of the literature
This paper also contains a review of the literature on “body stuffing”.
The Cato Institute with a deep dive on how the War on Drugs twists cops into overseers of doctors treating pain & substance use disorders
Cops Practicing Medicine: The Parallel Histories of Drug War I and Drug War II
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to your organization, reach out to me]
The first peer-reviewed journal to focus on psychedelics
“Why the ‘Psychedelic Renaissance’ is just Colonialism by Another Name” by Alnoor Ladha & Rene Suša
All the talks from the Horizons Conference 2023 are now online
Fun fakt: I met my wife at this conference many a year ago.
Do different species of psilocybin mushrooms have different effects? by Andrew Gallimore
I’m really enjoying his newsletter Alien Insect on Drugs.
DEA proposes higher production quotas for psychedelics
But that they get to decide this at all is terrible. They’re the reason there’s currently a nationwide Adderall shortage.
The Darknet market AlphaBay adds third-party drug testing
If you like drugs, the Darkweb sites are the safest easiest way to get them. This old article from Dr. Hugo Z. Hackenbush 👀 can walk you through the basics: The Golden Age of Acquisition
A survey on the adverse effects of ayahuasca:
Adverse effects of ayahuasca: Results from the Global Ayahuasca Survey
A small clinical study on psilocybin mushrooms for cluster headaches
Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double-blind, placebo-controlled trial
If you suffer from cluster headaches, the most knowledge belongs to the patient group ClusterBusters.
A meta-analysis of 9 studies using psilocybin for psychiatric conditions
Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis
Business & Law
Legal cannabis is eating into alcohol sales
Often when I read my Nature magazine each week, I see a do-gooder editorial full of proposals & I think, that’s nice, but it’s never gonna happen. This is one of those kind of articles…
A call for prudent taxation of cannabis corporates to fund mental health programmes
The Plant & the History
A big review on using hemp as a food & supplement
Potential applications of Hemp (Cannabis Sativa L.) extracts and their phytochemicals as functional ingredients in food and medicinal supplements: A Narrative Review
A detailed study on all of the good things in hemp seeds
Research of biologically active substances of hemp seeds, hemp seed oil and hemp pomace
2021: A history of hemp, silk & cotton in Chinese history
Silk, Hemp and Cotton : An Outline of Chinese Textile History and Societal Impacts
China was once known as the Land of Mulberry & Hemp. It also pioneered many of the major technical breakthroughs in how to utilize the many aspects of the plant.
How to protect the hemp plant from pests & diseases in its early stages of development
Optimizing hemp plant protection against harmful organisms in the early stages of its development
A study of the mechanisms & microbes that cause retting (the process of leaving hemp outdoors to break its hard outer fibers)
Towards a better understanding of microbial mechanisms involved during field retting of hemp “Cannabis Sativa”
Using hemp in packaging
Applications of Hemp Polymers and Extracts in Food, Textile and Packaging: A Review
Using a hemp waste product to produce aerogels for absorbing oil or cleaning air
Self-cleaning superhydrophobic aerogels from waste hemp noil for ultrafast oil absorption and highly efficient PM removal
Adding CBN to make your glass stronger?
A new design of Borax-Cannabinol nanomaterial used to strengthen concrete structures: Non-Scc-GFN1xTB model
Seriously. What is up with this plant?
Clinical Studies & Surveys
A review of Spain’s CBD program finds help for children & adults with epilepsy
Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy
And in healthy humans, 750 mg of CBD did not change how the body processed methylphenidate (a drug commonly used in childhood epilepsy)
The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects
In humans, inhaling cannabis caused reduced nerve reflexes in the muscles
Cannabis Inhalation Acutely Reduces Muscle Sympathetic Nerve Activity in Humans
2021: In healthy humans, a low dose of dronabinol (pharmaceutical THC) increased blood flow to their retina but not oxygenation
The Effect of Orally Administered Low-Dose Dronabinol on Retinal Blood Flow and Oxygen Metabolism in Healthy Subjects
A survey of the French doctor’s participating in France’s extremely limited medical cannabis program
Exploring the medical cannabis prescribing behaviours of French general practitioners
A review of using medical cannabis clinically
Medical cannabis: Critical points for clinical application
2021: A review of the ability of cannabinoids to cause catatonia (a complete bodily freeze)
Catatonia Related to Cannabis and Synthetic Cannabinoids: A Review
Back when people tended to drink or eat high levels of hashish, this “frozen in your body” effect of cannabis was noted quite often.
But nowadays, with our weakass smoking joints method, nobody gets twisted like they used to.
For how high you can get, see Fitz Hugh Ludlow’s ‘The Hasheesh Eater’.
In horses, a thesis project on how CBD moves through their bodies when given a single dose or chronically for 8 weeks
Pharmacokinetics of CBD Supplementation in Horses: Single Dose vs. Long-Term Feeding
A survey of pet owners find “positive effects, such as improved well-being, increased activity, and reduced pain”
Use of cannabidiol products by pet owners in Slovenia: a survey-based study
In dogs with osteoarthritis, this thesis project found no difference in improved pain results between CBD & water-soluble CBD (aka nano-CBD, thought to have better bioavailability)
Comparison of Water-Soluble CBD and CBD Oil as an Anti-Inflammatory in Canines with Osteoarthritis
In roundworms, giving them high levels of cannabis extract shortened their life but giving them low doses “resulted in significant effects with respect to appetite control, body oscillation, motility, and nervous system-related functions”
C. elegans as a test system to study relevant compounds that contribute to the specific health-related effects of different cannabis varieties
2021: A review of how cannabis changes the plasticity of the developing brain
Cannabis and synaptic reprogramming of the developing brain
Mental Health, Addiction & Mental Effects
A video case report from an epileptologist on CBD potentially causing a longer seizure (hattip to Kathryn Villaverde)
A Rare Case of Status Epilepticus in a Patient Prescribed CBD
It’s intriguing to get to watch a doctor talk about a patient & how they work through treatment options & try to figure things out.
A specialist on using cannabis for autism
Medical cannabis in autism spectrum disorder: a specialist perspective
In women with depression, they had higher ratios of anandamide levels to their intake of the fatty acids (building blocks for creating the endocannabinoids)
Elevated ratio of serum anandamide to arachidonic acid intake in community-dwelling women with high depressive symptoms
In a longitudinal study, they did not find a difference in the intensity of psychosis between cannabis users & non-users
Cannabis use and patterns of psychotic symptomatology in a longitudinal birth cohort
2021: In patients admitted to an involuntary psychiatric unit, those with THC in their system were significantly associated with one-year readmissions & more benzodiazepine prescriptions
Impact of cannabis use on outcomes of patients admitted to an involuntary psychiatric unit: A retrospective cohort study
A review of the data on cannabis use & self-harm find that there’s not enough evidence yet to draw conclusions but might be seen as a potential marker for intentional self-injury
Cannabis and Intentional Self-injury: a Narrative Review
In people using cognitive behavioral therapy for anxiety, cannabis users had poorer outcomes
Does cannabis use impact cognitive behavioural therapy outcomes for anxiety and related disorders? A preliminary examination
In a mouse model of methamphetamine addiction, they saw help from a 1:1 CBD:THC treatment
A 1:1 ratio of cannabidiol: tetrahydrocannabinol attenuates methamphetamine conditioned place preference in mice: A prospective study of antidopaminergic mechanism
In rats trained by footshocks to not use meth, they saw increased levels of CB1 & CB2 in their hippocampus (memory center)
Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)
In a mouse model of fear memories & negative stimuli, the ability of the TRPV1 receptors to modulate fear memories in the hippocampus (a memory center) may depend on anandamide & CB1 signaling
TRPV1 modulation of contextual fear memory depends on stimulus intensity and endocannabinoid signalling in the dorsal hippocampus
The Brain & its Diseases
For Huntington’s disease, a look at why the disease’s disruption of the endocannabinoid system causes more disease progression
Cannabinoid signaling and risk in Huntington's disease
By coincidence, I’m working on a write-up of the ECS & Huntington’s right now. The ability of the ECS to act as a homeostasis mechanism that tamps down on glutamate (the brain’s primary excitatory neurotransmitter) might be the reason that the early loss of cannabinoid receptors makes the disease worse.
2021: In regular cannabis users, brain scans found them to have a smaller orbitofrontal cortex (a brain area for taste, touch & learning) & lesser amounts of white matter (especially in females)
Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group
2021: In a rat model of Parkinson’s, cannabis improved motor control via an increase in synaptic plasticity
Marijuana improved motor impairments and changes in synaptic plasticity-related molecules in the striatum in 6-OHDA-treated rats
In mouse microtubules (structures that give shape to cells, especially important in neurons for plasticity), psychosocial stress worsened their acetylation (a necessary step for their use) but activating the CB1 receptor helped to slightly improve the acetylation levels
Psychosocial stress and cannabinoid drugs affect acetylation of α-tubulin (K40) and gene expression in the prefrontal cortex of adult mice
2020: In a mouse model of brain aging, reduced CB1 signaling led to more problems in the mitochondria (the powerhouse of the cell)
Age-dependent Alteration in Mitochondrial Dynamics and Autophagy in Hippocampal Neuron of Cannabinoid CB1 Receptor-deficient Mice
2021: In neural stem cells, exposure to cannabinoids caused changes to the glucocorticoids (steroid hormones)
The Impact of Cannabinoid Exposure on Glucocorticoid Receptor Signaling in Neural Stem Cells
A tissue test of the antioxidative & neuroprotective properties of two cannabis extracts
Evaluation of two different Cannabis sativa L. extracts as antioxidant and neuroprotective agents
Harms, Cannabis Use Disorder & Street Synthetics
In young people, cannabis use disorder seems to increase the risk of aggression toward others
Association between Cannabis Use Disorder and Self- and Other-Directed Aggression
And those with psychosocial stress were more likely to have cannabis use disorder
Psychological Distress, Cannabis Use Frequency, and Cannabis Use Disorder Among US Adults in 2020
In cannabis use disorders, attentional bias (a tendency to focus on certain elements while ignoring others) only occurs in those with the most severe problems
The who and how of attentional bias in cannabis users: associations with use severity, craving and interference control
On drugs to treat cannabis use disorder
Emerging pharmacological treatments for cannabis use disorder
On the rise of cannabinoid hyperemesis syndrome in North America
Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence
2021: In cannabis users not trying to quit, pregabalin (a nerve pain medication suggested as a cannabis use disorder treatment) had no effect on their use
Influence of pregabalin maintenance on cannabis effects and related behaviors in daily cannabis users
2021: A look at 15 of the top synthetic cannabinoids on the street & how they bind to CB1 vs CB2
Assessment of select synthetic cannabinoid receptor agonist bias and selectivity between the type 1 and type 2 cannabinoid receptor
2021: One of the strongest synthetic cannabinoids – MAM-2201 – causes toxicity to brain cells & brain support cells
MAM-2201, One of the Most Potent-Naphthoyl Indole Derivative-Synthetic Cannabinoids, Exerts Toxic Effects on Human Cell-Based Models of Neurons and Astrocytes
How even the breakdown products of the street synthetic 5F-MDMB-PINACA are still potent binders of the CB1 receptor
Metabolites of Synthetic Cannabinoid 5F-MDMB-PINACA Retain Affinity, Act as High Efficacy Agonists and Exhibit Atypical Pharmacodynamic Properties at CB1 Receptors
Pain, Inflammation & Surgeries
In a healthy human test of pain, being told that you were getting CBD helped with pain. So did actually getting the CBD
The effects of cannabidiol and analgesic expectancies on experimental pain reactivity in healthy adults: A balanced placebo design trial
In a rat model of persistent inflammatory pain, THC & CBD by themselves both helped on various measures – but when combined, CBD lessened THC’s painkilling effect & increased its anxiety effect
Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats With Persistent Inflammatory Pain
In rat pain neurons, 2-AG & its relatives 2-PG & 2-LG all delayed pain signaling via the TRPV1 receptors
The Endocannabinoid Analgesic Entourage Effect: Investigations in Cultured DRG Neurons
On using a film with a cannabis oil base as a dressing for wound healing
Chitosan-based films with cannabis oil as a base material for wound dressing application
Rarely does a study title intrigue me this much, but I can’t even find a copy of the abstract…
Cannabis Use in Dermatology: A Cross-Sectional Study of YouTube Videos
The Guts & Oral Health
A review of how cannabinoids alter the gut microbiome – and how that alters the gut-brain & gut-bone axes
Modulatory Effect of Gut Microbiota on the Gut-Brain, Gut-Bone Axes, and the Impact of Cannabinoids
In mice being fed a fatty diet, the fatty acid n-linoleyltyrosine lowered their obesity via regulation of the cannabinoid receptors
N-linoleyltyrosine ameliorates high-fat diet-induced obesity in C57BL/6 mice via cannabinoid receptor regulation
The Heart & the Blood
This retrospective study finds cannabis smoking similar to tobacco smoking for increased heart problems
The New Cigarette? Cannabis Use as a Potential Risk Factor for Acute Coronary Syndrome
In young diabetics, those with cannabis use disorder have a higher risk of heart attacks
Young diabetics remain at higher risk of acute myocardial infarction with cannabis use disorder
In rats, vaporized or smoked cannabis causes impairment of the dilation of arteries
Marijuana Smoke or Vaporizer Aerosol Impairs Endothelial Function Regardless of Drying Regimen or Cannabinoid Profile
In a rat model of pulmonary hypertension (high blood pressure between the heart & lungs), blocking the CB1 receptor in the body did not work well on its own but it combined well with the common treatment drug metformin
Effects of the peripheral CB1 receptor antagonist JD5037 in mono- and polytherapy with the AMPK activator metformin in a monocrotaline-induced rat model of pulmonary hypertension
2021: In heart cells, THC can cause toxicity but this may be blocked activating the AMPK pathway
Possible roles of AMPK and macropinocytosis in the defense responses against Δ9-THC toxicity on HL-1 cardiomyocytes
A French review of the negatives of cannabis smoke for the lungs
Inhaled marijuana and the lung, a toxic cocktail?
Why do the French only put out negative things about cannabis? Why can’t the scientists of my adopted country be more green when their people smoke more pot than anyone else on the Continent?
Reproductive & Maternal Effects
2021: A review of the effects of cannabis on the symptoms around menopause (but they only had 3 studies to review)
The impact of cannabis use on vasomotor symptoms, mood, insomnia and sexuality in perimenopausal and postmenopausal women: a systematic review
In the US, more pregnant people are using cannabis
The prevalence of cannabis use reported among pregnant individuals in the United States is increasing, 2002-2020
In pregnant women with gestational diabetes mellitus, they had increased levels of AEA & 2-AG
Circulating endocannabinoid levels in pregnant women with gestational diabetes mellitus: a case-control study
A cohort study finds that babies born with THC in their system had decreased birth weight, length & head circumference
Prenatal marijuana exposure and neonatal outcomes: a retrospective cohort study
On unintentional cannabis intoxication in young kids presenting at the ER
Unintentional cannabis intoxication in infants and toddlers presenting with neurological impairment in a Pediatric Emergency Department
2021: In rats with ovarian injuries from loss of blood flow, inhibition of the MAGL enzyme (leading to a rise in 2-AG) helped with antioxidation, anti-inflammation & the lessening of cell death
The protective effect of JZL184 on ovarian ischemia reperfusion injury and ovarian reserve in rats
Cancer & Chemo
A study from the American Medical Association on cancer patients suggests looking at cannabis as a substitute for opioids
A computer analysis of using cannabinoids against gliomas (the most aggressive brain cancers)
In Silico Binding Analysis of Cannabinoids with Eph Receptors for Therapeutic Use in Gliomas
A drug that activates the CB2 receptor & blocks the CB1 receptor might be a treatment for melanoma & colon cancer
The Synthetic Cannabinoid URB447 Exerts Antitumor and Antimetastatic Effect in Melanoma and Colon Cancer
2021: In melanoma cells, higher levels of CB2 receptors on the immune system’s B cells reduced melanoma growth
Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma
2021: In the bone tumor Ewing sarcoma, cannabinoids reduced their cellular viability, but not via CB1 or CB2
Natural and Synthetic Cannabinoids Reduce Cell Viability of Ewing Sarcoma TC-71 Cells Potentially via Non-canonical CB receptors
How ingredients from Acmella oleracea (aka the toothache plant or the electric daisy) work via the cannabinoid & TRPV1 receptors
Alkylamides from Acmella oleracea: antinociceptive effect and molecular docking with cannabinoid and TRPV1 receptors
It’s a long list, the list of medicinal plants that turn out to cause their good actions via the endocannabinoid system.
2023: How to modulate the drugs that block the CB1 receptors
Modulating the affinity and signaling bias of cannabinoid receptor 1 antagonists
Using analytical chemistry techniques to learn more about the entourage effect
Entourage Effect And Analytical Chemistry: Chromatography As A Tool In The Analysis Of The Secondary Metabolism Of Cannabis Sativa L
2021: A review of other molecules for modulating endocannabinoid signaling
Pharmacological selection of cannabinoid receptor effectors: Signalling, allosteric modulation and bias
2021: On CBD, THC, their metabolites & the potential drug interactions with the UGT enzymes that process drugs in the liver
Can Cannabinoids Precipitate UGT-mediated Drug Interactions?
On how one mutation in the CB2 receptor blocks things that would otherwise bind to it
A Single Point Mutation Blocks the Entrance of Ligands to the Cannabinoid CB2 Receptor via the Lipid Bilayer
2021: On the mysterious CRIP1a: a protein that regulates binding to the CB1 receptor
Structure and Function of Cannabinoid Receptor Interacting Protein 1a (CRIP1a)
In our Neural Ocean metaphor, you might call CRIP1a the bouncer at the CB1 bar.
Which microbes can break down CBD?
Microbial Biotransformation of Cannabidiol (CBD) from Cannabis sativa
You could picture this one like a bloodbath at a Roman arena: Put a whole bunch of cute little CBD molecules into the arena & see which of our microbial heroes can rip them to shreds.
(I need an illustrator…)
PS: For today’s lovely music, ‘Miss Perfumado’ by Cesária Évora, the Cape Verdean singer-songwriter known as Barefoot Diva. She was also known as the Queen of Morna, the musical style combining the sounds of the islands, the percussion of West Africa, the fados of Portugal, the modhinas of Brazil & the sea shanties of Britain. Success came later in her life – but it saw her touring the world, being anointed a knight of culture by France, winning a Grammy & having an airport named after her as well as a butterfly. If you listen to this album, you’ll hear why.
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 the basics are that we treat the human brain like the ocean: deep, mysterious & chockablock with fish, molecules & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land?) and neurons are complex underwater cities where hundreds of fish interact.
The cannabinoids found inside all mammals & almost every other form of life besides insects
The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”
Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]
The second endocannabinoid receptor discovered. Found in almost every organ of the body & closely connected to our immune system. The CB2 occurs at low levels in the brain where it responds to neural insults.
[a gay bar in the membrane wall of the neuronal city]
FAAH (fatty acid amide hydrolase)
The enzyme that breaks down anandamide & a frequent target of drug discovery for modulating the endocannabinoid system. If you inhibit the FAAH enzyme, it does less breaking down of AEA, and your AEA levels rise. More balance.
[the giant squid that slices sperm whales in half]
Diacylglycerol lipase (DAGL or DGL)
The enzyme responsible for producing 2-AG.
MGL (monoacylglycerol lipase - also sometimes abbreviated as MAGL)
The enzyme that breaks down 2-AG. Another frequent target of drug discovery because inhibiting MGL raises 2-AG levels
[a giant octopus that eats blue whales]
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]
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]
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]
Known as the “mother cannabinoid”, CBG is the chemical precursor to THC, CBD, and the other cannabinoids in the plant. CBG occurs only at low levels in cannabis because it tends to be quickly converted to other cannabinoids. Binding slightly to the CB1 and CB2 receptor, it also inhibits the enzymes that break down anandamide and 2-AG, hence raising the levels of those endocannabinoids. CBG interacts with an adrenaline receptor (α-2 adrenoceptor) & a serotonin receptor (5-HT1A Receptor) as well as modulating the expression of glutamate, GABA, and dopamine via the PPAR receptors on the nucleus, controllers of genetic transcription. CBG is also active at the TRP channels involved in the sensations of temperature, pressure, pH, smell, taste, vision, and pain perception whose dysfunction are linked to neuropathic pain, inflammation, and respiratory disorders.
Surveys show patients reporting help for anxiety, chronic pain, depression, and disturbed sleep. In preclinical trials, it's been studied for eye pressure, gut problems, appetite modulation, blood pressure lowering, bladder control, oral care, muscle spasms, airway inflammation, arthritis, painkilling, and most notably for brain health and neuroinflammation. In adult neural stem cells, CBG increased their viability. The breakdown products of CBG have been shown to reduce inflammation via the brain’s immune cells.
[since it’s the first cannabinoid produced, it must be the wooly mammoth
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]
(Easter egg: the first person to email me about this easter egg will get a free copy of my Queer book once I get it printed & up on Amazon soon…)
Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]
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.