C&P#21: CBD for cancer pain, autism, heart health & brain growth + CBG for everything
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CBD for the neuropathic pain of cancer treatment
CBD for autism
CBD for the heart
CBG survey finds it used for an array of conditions
High Times cancels a story critical of Curaleaf
Mike Tyson’s surprising (but historically sensible) pre-fight cocktail
Note on 2021 papers:
Over the next few weeks, you’ll notice some papers from 2021. I previously ran a private version of this newsletter with a focus on the positives of hemp & CBD – but I made sure to save all the negatives & the esoteric chemistry, so I’ll be catching up on that backlog to make sure that I have no research gaps from the last 3.5 years where I’ve been trawling for every piece of research on this magnificent old plant.
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 & THC as well as the lesser known but powerful cannabinoids like PEA (immune system health) & OEA (sleep). 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 patients with cancer, 300 mg of CBD per day lessened their chemotherapy-induced peripheral neuropathy (nerve pain in the body)
Oral cannabidiol for prevention of acute and transient chemotherapy-induced peripheral neuropathy
For people with autism in the UK Medical Cannabis Registry, they saw “significant improvements in general health-related quality of life and sleep”
Clinical Outcome Analysis of Patients with Autism Spectrum Disorder – Analysis from the UK Medical Cannabis Registry
And a review of using CBD to treat autism
Cannabidiol for the treatment of autism spectrum disorder: hope or hype?
Reviews are fine for convincing recalcitrant doctors – but anybody with ears on their head & eyes in their face know about the large number of parents who’ve seen moderate levels of CBD change everything for their kids. I believe because I saw it happened in my own family. See my advice on CBD & autism here.
In certain brain regions of rats, CBD increases BDNF (a brain growth factor)
Single and Repeated Exposure to Cannabidiol Differently Modulate BDNF Expression and Signaling in the Cortico-Striatal Brain Network
I suspect that the ability of cannabinoids to cause neurogenesis (new brain cell growth) may underlie much of their efficacy.
2021: A survey of CBG-rich cannabis users found it helpful for many conditions & often more helpful than conventional medicines
Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations: Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms
“The most common conditions the complete sample reported using CBG to treat were anxiety (51.2%), chronic pain (40.9%), depression (33.1%), and insomnia/disturbed sleep (30.7%). Efficacy was highly rated, with the majority reporting their conditions were "very much improved" or "much improved" by CBG. Furthermore, 73.9% claimed superiority of CBG-predominant cannabis over conventional medicines for chronic pain, 80% for depression, 73% for insomnia, and 78.3% for anxiety. Forty-four percent of CBG-predominant cannabis users reported no adverse events, with 16.5% noting dry mouth, 15% sleepiness, 11.8% increased appetite, and 8.7% dry eyes.”
In mice undergoing exhaustive exercise, CBD reduced rupture of the heart tissue, the degree of inflammatory cell infiltration & the deposition of collagen fibers in the heart tissue, perhaps via activation of the Keap1/Nrf2/HO-1 signaling pathway
Protective effect and mechanism of cannabidiol on myocardial injury in exhaustive exercise training mice
In human immune & cardiac cells exposed to an inflammatory agent (a model of sepsis leading to cardiac arrhythmias), CBD protected against the inflammation & arrhythmias via inhibition of inflammatory cytokine release, antioxidant & anti-apoptotic effects (cellular suicide) & via the cardiac sodium channels
Anti-inflammatory effects of cannabidiol against lipopolysaccharides in cardiac sodium channels
I didn’t know this – but cannabinoids are toxic to cannabis. So here’s how the plant’s trichomes use specialized ‘supercells’ to produce & store them
A polarized supercell produces specialized metabolites in cannabis trichomes
And an interview with the researchers
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
The Metagenics Institute on using PEA for managing pain & addiction (hattip to Stuart Tomc)
the Headlines & Fav Articles
A new federal court ruling out of Maine could open up medical cannabis to interstate commerce
The cannabis journalist Marguerite Arnold on why she got fired from High Times for writing an article critical of Curaleaf
& here’s the article
According to Tom Angell, the Association for Cannabis Health Equity and Medicine resigned as a U.S. Cannabis Council member in protest of what it says is "increasing influence of corporate cannabis priorities...that has continually overshadowed or siloed equity-focused recommendations."
The majority of Texans support legalizing both medical & recreational cannabis
Hong Kong cracks down on CBD products
while a survey of Hong Kong medical students found support for legalized cannabis
Attitudes and beliefs of medical students on cannabis in Hong Kong
Mike Tyson uses cannabis & psilocybin mushrooms before fights
There’s a long tradition of psychedelics & martial arts. See my interview with the late great Kilindi Iyi on his belief that psychedelics rest at the birth of many of the martial arts.
The War on Drugs & Harm Reduction
A US poll finds that after foreign policy, the issue of drug policy is the one that people have most likely changed their minds on
Nevada’s Supreme Court says that employers can fire workers for the private use of cannabis
Dr. Bronner’s donated $4M to drug policy reforms last year
Buy their soap!
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to a company out there, reach out to me]
A profile of the scientist who gave MDMA to an octopus: Dr. Gül Dölen
The Church of Ambrosia, which uses cannabis & psychedelics, is suing the City of Oakland for discriminating against them after the denial of a land-use permit
5 questions for Matt Zorn – the guy behind the patent psychedelic series that we’ve been enjoying so much around here…
A review of the evidence for the nootropic (cognitive enhancing) effects of LSD
Nootropic effects of LSD: Behavioral, molecular and computational evidence
In first head-to-head trial of ketamine vs electroconvulsive therapy for depression, ketamine worked – though not as well as ECT - & while ketamine had more treatment-emergent adverse events, ECT caused more serious long-lasting adverse events
Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT)
In a trial of ketamine for severe suicidal ideation, it was found to be effective, rapid & safe in the short term & to have persistent benefits, including a reduction of mental pain
Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial
According to this naturalistic study, a psychedelic experience had an antidepressant effect up to a month later
Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample
Of course, the bias in a study like this is obvious – but that doesn’t make it untrue.
Law & Business
Whew. I don’t even want to list all of the cannabis companies posting big losses this quarter. If you want to see, check out the Business section of Marijuana Moment’s newsletter each day last week
Haha. Colleges in states that legalized cannabis saw a boost in their number of applications
Higher education: The impact of recreational marijuana on college applications
The Plant & the History
A review of using cannabis for pest control
The Use of Cannabis sativa L. for Pest Control: From the Ethnobotanical Knowledge to a Systematic Review of Experimental Studies
Scientists still aren’t sure why the cannabis plants evolved to pay the metabolic price to produce these cannabinoids – but one long-standing theory is that their presence wards off pests. Hence, there’s been a long human use of hemp against pests, especially spiders & insects.
A review of the greatness of hemp seeds
Industrial hemp seed: from the field to value-added food ingredients
2021: A review of using micropropagation for the growth & engineering of cannabis plants
Cannabis sativa: From Therapeutic Uses to Micropropagation and Beyond
A study on how to best capture (or not capture) terpenes when using supercritical CO2 extraction
Supercritical CO2 extraction of hemp flowers: A systematic study to produce terpene-rich and terpene-depleted cannabidiol fractions
How to use bacterial markers to find evidence for the retting of hemp in a lake over the last 5 centuries
Bacterial phylogenetic markers in lake sediments as evidence for historical hemp retting
The retting of hemp (separating the plant fibers) is an arduous job. To make it easier, hemp can be left in the field or in water for a while to soften it up. In this Spanish lake, the process has been happening for 500 years.
Clinical Studies & Surveys
This study founds that cannabis users had fewer sinonasal problems (nasal infections, obstructions, bloody noses, etc) than non-users
Cannabis Use and Sinonasal Symptoms in US Adults
So… smoke weed for your nose(?)!!!
2021: In this review of the effects of cannabis on eyes, ears, nose & throat specialists, they found use associated with “unintended tinnitus, vertigo, hearing loss, infection, malignancy, sinusitis, allergic rhinitis, thyroid dysfunction, and dyspnea”
Cannabis related side effects in otolaryngology: a scoping review
Older adults more likely to use cannabis for medicinal purposes when they saw laws that legalized it, increased acceptance in their social networks & more visibility of cannabis in the media
Older adults experiences of using recreational cannabis for medicinal purposes following legalization
How to diagnose if someone is allergic to cannabis
Establishing diagnostic strategies for cannabis allergy
This happens more than people realize – and it’s not an unusual occurrence for cannabis allergies to develop when people work trimming jobs that expose them to huge levels of cannabis for long periods of time.
In research that obviously came from a business school, cannabis use does not increase creativity but it does increase joviality – which makes you think that your work is more creative than it is
Cannabis use does not increase actual creativity but biases evaluations of creativity
As Dr. Arne Dietrich points out, we don’t actually have any good scientific measurements for creativity.
2021: This review of patients with acute kidney disease found no harmful associations from the use of cannabis
Cannabis Use and Risk of Acute Kidney Injury in Patients with Advanced Chronic Kidney Disease Transitioning to Dialysis
On how to help adolescents who have cannabinoid hyperemesis (cyclical vomiting)
Paediatric cannabinoid hyperemesis
In children exposed to early childhood trauma, those with a certain variant of their FAAH enzyme had higher anxiety levels
Impact of Childhood Trauma Exposure, Genetic Variation in Endocannabinoid Signaling, and Anxiety on Frontolimbic Pathways in Children
First steps in looking for an EEG biomarker for the effects of CBD on seizures
Quantitative electroencephalographic analysis as a potential biomarker of response to treatment with cannabidiol
In dogs, how CBD & CBDA moves through their system
Twenty-Four Hour and One-Week Steady State Pharmacokinetics of Cannabinoids in Two Formulations of Cannabidiol and Cannabidiolic Acid Rich Hemp in Dogs
How CBD moves through the body of an Amazonian parrot
Pharmacokinetics of Cannabidiol in the Hispaniolan Amazon Parrot ( Amazona ventralis)
Harms, Synthetic Cannabinoids & Cannabis Use Disorder
In a small study of teens with chronic cannabis use, they saw genes methylated (turned off) related to verbal learning performance
DNA methylation changes associated with cannabis use and verbal learning performance in adolescents: an exploratory whole genome methylation study
In teens, a linear relationship between cannabis use & depression
Cannabis Use and the Development of Depression in Adolescents: Is There an Established Linear Relationship Between the Two?
Again, is the cannabis use causing the depression or is it being used as a self-medicament?
In humans, high levels of anandamide & low levels of FAAH are linked to worsened psychotic symptoms in people with schizophrenia & this may be because of its effects on glutamate transmission in the hippocampus
In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, 1 H-MRS, and MRI
An analysis of cannabis use & first episode psychosis had complicated findings, especially for sporadic users
Relationship between patterns of cannabis use and functional and symptomatic trajectories in first-episode psychosis
Among US veterans, rates of cannabis use disorder diagnoses are increasing
Trends in Cannabis Use Disorder Diagnoses in the U.S. Veterans Health Administration, 2005-2019
In a rat model of cannabis use disorder & withdrawal, chronic THC increased dopamine receptors & presumably, once the THC is withdrawn, the increased dopamine activity caused the heightened anxiety & an inability to feel pleasure
Daily THC and withdrawal increase dopamine D1-D2 receptor heteromer to mediate anhedonia and anxiogenic-like behavior through a dynorphin and kappa opioid receptor mechanism
In rats, cannabis caused a decrease in sperm motility & testosterone levels
Cannabis and metformin on diabetic male Wistar rat sperm and reproductive organ parameters
2021: In male rats exposed to cannabis before mating, their offspring had significantly lower dopamine activity
Paternal Cannabis Exposure Prior to Mating, but Not Δ9-Tetrahydrocannabinol, Elicits Deficits in Dopaminergic Synaptic Activity in the Offspring
The clinical features of exposure to the synthetic cannabinoid ADB-BUTINACA
Clinical features associated with ADB-BUTINACA exposure in patients attending emergency departments in England
In mice self-administering the synthetic cannabinoid JWH-018, they had more compulsive obsessive behaviors (nest shredding & marble burying) as well as changes to inflammatory responses in their brains via the glial cells (immune cells of the brain)
Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice
In mice being given a number of synthetic cannabinoids, the levels that cause convulsions do not necessarily cause seizures that can be measured on an EEG
Convulsant doses of abused synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA and JWH-018 do not elicit electroencephalographic (EEG) seizures in male mice
A review of the synthetic cannabinoids: their pharmacodynamics & toxicology
Synthetic Cannabinoids: A Pharmacological and Toxicological Overview
Cannabis in Psychiatric Practice: A Practical Guide
A new book with a rather negative take on cannabis for mental health
A review exploring the link between cannabis use & self-harm
Self-Harm and Cannabis Use
The literature in this area is not well fleshed out – but I suspect that both sides of the coin are true:
Problematic cannabis use can lead people down the dark rabbit hole of self-harm
They find an association between people with tendencies towards self-harm & cannabis use because they use it as a mental health treatment
A review of cannabis & psychotic symptoms
Cannabis and Psychosis
A book chapter on what clinicians should know about teens & mental health
What Clinicians Need to Know About Adolescent Cannabis Use in Outpatient Mental Health Settings
A negative take on the effects cannabis on the elderly
Cannabis in the Geriatric Population
On CBD & behavioral health
Cannabidiol: Overview, Complexities, and Opportunities for Behavioral Health
On cannabis use before & after birth
Cannabis in the Perinatal Period
A review of the studies on using CBD & THC for anxiety
Medicinal cannabis for the treatment of anxiety disorders
A great review on how the endocannabinoids alter synaptic function
Endocannabinoid signaling in synaptic function
2021: A review of the effects of cannabis on your proteome – all of the proteins in your body
A Proteomic View of Cellular and Molecular Effects of Cannabis
An excellent review on the clinical relevance of targeting the FAAH enzyme
Fatty Acid Amide Hydrolase: An Integrative Clinical Perspective
Remember, the inhibition of FAAH is a major component of what makes CBD helpful. Inhibiting the FAAH enzyme raises your levels of anandamide, your neurotransmitter of bliss.
A book chapter on using the machinery of the endocannabinoid system to treat cancer
Emerging Role of Cannabinoid System Modulators in Treatment of Cancer
A review of human & animal studies about taking cannabinoids & stimulants at the same time find that cannabinoids often protect from the negatives of amphetamines
Co-exposure of cannabinoids with amphetamines and biological, behavioural and health outcomes: a scoping review of animal and human studies
Don’t let anybody look down on that powerhouse combo of meth & hash for creativity.
A review of cannabinoids in orthopedic medicine
Cannabinoids in the Orthopedic Setting: A Literature Review
2021: A review of cannabis for traumatic brain injuries
The changing landscape of the use of medical marijuana after traumatic brain injury: a narrative review
A review on how the cannabinoids alter development in zebrafish (a common model organism for early brain development)
A Review on the Bioactivity of Cannabinoids on Zebrafish Models: Emphasis on Neurodevelopment
In stressed rats, this study looks at the impact on their endocannabinoid levels caused by various types of stress (such as having a mortgage. Rats hate to be in anybody’s debt)
Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats
In a mouse model of neuropathic pain, preventing the degradation of 2-AG reduced the pain via normalizing the reactivity of the microglia (immune cells of the brain)
Attenuation of allodynia and microglial reactivity by inhibiting the degradation of 2-arachidonoylglycerol following injury to the trigeminal nerve in mice
In a rat model of pain, an interaction between the orexin system & the endocannabinoid system in the amygdala causes some of the painkilling
An interaction between basolateral amygdala orexinergic and endocannabinoid systems in inducing anti-nociception in the rat formalin test
In the blood vessel cells of cows, anandamide caused dysfunction of the mitochondria (the powerhouse of the cell) via the increase of reactive oxygen species & pro-inflammatory signals
Anandamide Alters Barrier Integrity of Bovine Vascular Endothelial Cells during Endotoxin Challenge
2021: What happens when you give zebrafish larva different types of cannabis extracts? Let’s find out…
Assessing the bioactivity of cannabis extracts in larval zebrafish
“It was found that the whole-plant extracts that contained high levels of THC had similar effects on larval behavior, while the high CBD and low THC:CBD extracts produced distinct effects on normal larval behavior.”
The antioxidant & antibacterial abilities of the flavonoids
Extraction and purification of total flavonoids from Cannabis sativa fibers and their evaluation for antioxidant and antibacterial activities
A 3D printed CBD/CBG gel for wound healing
Fabrication and Preliminary In Vitro Evaluation of 3D-Printed Alginate Films with Cannabidiol (CBD) and Cannabigerol (CBG) Nanoparticles for Potential Wound-Healing Applications
A look at how THC binds to glycine receptor
Molecular Determinants of Tetrahydrocannabinol Binding to the Glycine Receptor
2021: On the cis version of delta-9 THC
Δ 9- cis-Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology
Just like elephants, humans & whales, molecules can be right or left-handed. This study looks at the “left-handed” version of THC.
2021: On the novel heptyl cannabinoids CBDP & Δ9-THCP & a search for other “P” versions of the major cannabinoids (the hepytls simply have a longer 7 carbon tail)
The novel heptyl phorolic acid cannabinoids content in different Cannabis sativa L. accessions
“Moreover, the ultrahigh performance liquid chromatography coupled to high-resolution mass spectrometry-based method was applied for the putative identification of other heptyl homologs of the most common phytocannabinoid acids, including cannabigerophorolic acid (CBGPA), cannabichromephorolic acid (CBCPA), cannabinophorolic acid (CBNPA), cannabielsophorolic acid (CBEPA), cannabicyclophorolic acid (CBLPA), cannabitriophorolic acid (CBTPA), and cannabiripsophorolic acid (CBRPA).”
After all these decades, we just keep finding more & more molecules inside this plant.
The famous reishi mushrooms may exert some of their benefits via inhibition of the FAAH enzyme
Lanostane triterpenoids from Ganoderma lucidum and their inhibitory effects against FAAH
PS: Formed in the heady days after Guinea’s independence, in albums like ‘Discothèque 76’, the Bembeya Jazz National fused traditional griot folk music to jazz rhythms & Afropop style. After winning two national Biennale festivals, in 1966 they were crowned the Guinean National Orchestra. For their most ambitious album, check out ‘Regards Sur le Passé’, their tribute to Samory Toure, the founder of the Mande kingdom in 1870. And to get a sense of how much fun it must have been to see them in person, here’s the live album ‘10 Ans de Succès’.
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.
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.