C&P#8: PEA for migraines + CBD for acne + cannabinoids for neurodegeneration
plus, more on the War on Drugs, the arrest of psychoactive protestors & Thailand's 1 million free cannabis plants
A request to spread the word:
This newsletter only spreads by word of mouth – so forwarding & telling your friends goes a long way. Thank you for your help.
If you wanted to become a paid subscriber, you get no extra content, but the support would be much appreciated. #diapers
In cannabinoid science news this week, research on using cannabinoids for headaches, migraines & the severe nausea of pregnancy, more evidence about the negatives of teens smoking cannabis, the use of CBD for acne & a host of review papers on using various cannabinoids for the diseases of neurodegeneration. Plus, there was so much work on COVID-19, cannabis & lung function that I broke it out into a special section.
Alright. I’m doing it. I’m making a new section about the War on Drugs & harm reduction. This stuff makes me sick. We’re living in barbaric times. So each week I’ll be highlighting the horrors of the War on Drugs & the life-saving potential of various harm reduction strategies.
My ad: Cannabis counseling sessions for the brave of heart
My cannabis counseling sessions are not for those afraid to do the hard work of experimenting on themselves & figuring out what works. The cannabinoids can be powerful medicine for pain, neurodegeneration, autism, insomnia & anxiety/depression – but everyone’s endocannabinoid system is different & only you can find what works for you. We have many tools – CBD, THC, PEA, OEA & CBDA – but finding the solution that helps serious conditions is not easy. So if you know anyone – especially folks dealing with aging – who are ready to do the hard work to find health, send them here: Cannabinoid Education Sessions.
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.
Best of cannabinoid science...
In women with Hyperemesis Gravidarum (the most extreme nausea of pregnancy), this survey found that many turned to cannabis because all the prescription medications were ineffective
Patterns of Use and Self-reported Effectiveness of Cannabis for Hyperemesis Gravidarum
In patients with episodic migraines, a small pilot study finds that PEA helps decrease the frequency of migraines & the amount of medication needed for pain
Palmitoylethanolamide-based nutraceutical Calmux® in preventive treatment of migraine
A review of the data strengthens the support for using CBD for acne
The Anti-Inflammatory Effects of Cannabidiol (CBD) on Acne
A strong review of cannabis for the pain & spasticity of MS
The Efficacy of Cannabis on Multiple Sclerosis-Related Symptoms
& a review for practitioners of using CBD for Parkinson’s disease
Cannabidiol (CBD) Consideration in Parkinson Disease
& a review of PEA for neurodegenerative disorders
Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans
Here's my advice for using the cannabinoids for neurodegenerative disorders.
A review of CBD for rheumatic disorders of the bones, muscles & joints
Cannabidiol (CBD) in Rheumatic Diseases (Musculoskeletal Pain)
A thorough review of cannabinoids for dogs finds that they’re safe to use & that they help with quality of life & pain, especially CBD
Safety and Efficacy of the Therapeutic Use of Cannabis-Based Products in the Treatment of Dogs: An Integrative Review
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 published papers.
Popular science articles & videos
‘The Doctor’ is a documentary about the life of Franjo Grotenhermen, the pioneering German doctor who saw the therapeutic potential of medicinal cannabis
The trailer is a strong array of some of the biggest figure in cannabis science. And if you’re into reading the scientific literature, you see the name Dr. Grotenhermen come up time & time again on the most well-written of review papers & the most meaningful of the new research. I can’t wait to get a chance to watch this…
Viola Brugnatelli on CBD & CBG for oral care products
‘A Summary of Research on Medical Marijuana for Neuropathic Facial Pain’
the Headlines & Fav Articles
On a mother’s campaign to get cannabis for her son & prevent his 80 seizures per day (hattip to Hellenic Dynamics)
Police arrested activists outside of the headquarters of the DEA as they protested the agency’s refusal to let terminally ill patients access experimental drugs like psilocybin & MDMA
On nuclear weed: the widespread practice of the irradiation of cannabis by Will Yakowicz
The NIH announces that it wants to fund studies on cannabis as a cancer treatment
Thailand’s Public Health Minister Anutin Charnvirakul is planning to give away one million cannabis plants to Thai citizens when the plant is legalized in June
Thailand also wins for having the world’s best medical cannabis mascot: Dr. Ganja
An upbeat young Ukrainian refugee contributes his calmness to cannabis while encouraging legalization
Donnell Alexander on cannabis at the country clubs
Law & Business
CannaBit on the rising taste for cannabis-infused beverages
Unfortunately, it’s notoriously tricky to put those slippery fatty lipid cannabinoids into a beverage and have them stay there.
The War on Drugs & Harm Reduction
US drug overdoses sets another record: 107k last year, a 15% increase
Legalize all drugs now. Ensure a safe supply. Make narcan free. Open safe injection facilities everywhere. Increase harm reduction funding.
Every single overdose death is a failure of policy, an abysmal tribute to what Amerika truly values.
Meanwhile, the veterinary tranquilizer xylazine is spreading through the US drug supply & posing new threats
An immigration court said that a Dominican man's guilty plea for marijuana possession is grounds for deportation
‘America’s Dirtiest Cops: Cash, Cocaine and Corruption on the Texas Border’
This is the War on Drugs. The corruption that happens at the local level is a microcosm of what happens at the macro level with the CIA & drug cartels. You make busts by getting in bed with dirty people who know what’s going on. And soon, you’re dirty yourself.
The book to read on the early rising of this phenomenon with the Federal Bureau of Narcotics is Douglas Valentine’s ‘The Strength of the Pack’. And I’m excited to read his new book, ‘The CIA as Organized Crime’. Or the TikTok to watch is my latest one on the CIA & Drugs.
Medical Cannabis & Culture
An analysis of Δ8-THC vaporizer cartridges finds adulterants, unintended byproducts & heavy metals
Novel Δ 8-Tetrahydrocannabinol Vaporizers Contain Unlabeled Adulterants, Unintended Byproducts of Chemical Synthesis, and Heavy Metals
And another study finds that vaping ∆8-THC acetate leads to the formation of the poisonous gas ketene
Vaping Cannabinoid Acetates Leads to Ketene Formation
An academic analysis of cannabis edible packaging
Presence of Content Appealing to Youth on Cannabis-Infused Edibles Packaging
The Plant & the History
Hannah Paul on India’s love-hate relationship with cannabis
A long long relationship, but not always a happy one…
Using hemp flour to make biscuits & pastries!
Nutrition and health functionality of hemp products in wheat cereal products – butter cut-out biscuits and leavened pastry
In heifers, hempseed cake provided enough proteins to support nutrition for growth
Influence of hempseed cake inclusion on growth performance, carcass characteristics, feeding behavior and blood parameters in finishing heifers
In a biocontrol method, using fungus to fight hemp root rot
Biocontrol of root rot of deccan hemp with the help of trichoderma species
A review of using hemp in polymer composites
Advancement in hemp fibre polymer composites: a comprehensive review
Clinical Studies & Surveys
In humans, a brain scan shows that levels of anandamide may modulate the reward feedback system & correlate with personality (hattip to Stuart Tomc)
The endocannabinoid system in humans: significant associations between anandamide, brain function during reward feedback and a personality measure of reward dependence
In surveys, cannabis users agree that high levels of cannabis mimic psilocybin experiences & that they expect it would help with depression
Expectancies for Cannabis-Induced Emotional Breakthrough, Mystical Experiences and Changes in Dysfunctional Attitudes: Perceptions of the Potential for Cannabis-Assisted Psychotherapy for Depression
In a twin study, quite oddly, ‘individual-level models’ showed greater cannabis exposure in adolescence was consistently associated with increased negative psychiatric outcomes for a range of conditions as well as a lower vocabulary – but once they ran their ‘co-twin control analyses’, all of these associations dropped to below significance
Using Co-Twin Control Analyses to Estimate the Effects of Adolescent Cannabis Use on Adult Mental Health and Cognitive Functioning
Overall, “our findings provide little support for a strong, causal relationship between adolescent cannabis use and adult mental health or cognitive ability in these cohorts.”
In tobacco smokers with lung problems (COPD - chronic obstructive pulmonary disease) who also use cannabis, no association found between their cannabis use & disease progression
Impact of Marijuana on Progression of COPD in Middle-Aged and Older Ever Smokers of Tobacco: SPIROMICS Longitudinal Cohort Analysis
The first author on this report is the famous Dr. Donald Tashkin, a renowned lung expert who had the guts to study cannabis for the last 30 years.
In three studies by researchers with pharmaceutical industry compensation…
In patients with treatment-resistant epilepsy, CBD decreased symptom severity as well as brain temperature
Cannabidiol decreases seizure severity and brain temperature in treatment-resistant epilepsy
A survey of caregivers for Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) (severe childhood epilepsy) found that almost all of them planned to continue to using isolated CBD (Epidiolex) for both seizure control & other symptom improvements
Non-Seizure Related Outcomes With Real-World Use of Cannabidiol (CBD) in Lennox-Gastaut Syndrome and Dravet Syndrome: BECOME, A Caregiver Survey
In patients with tuberous sclerosis complex (growth of benign tumors that cause seizures), CBD worked better than the placebo for controlling seizures
Effect of Add-on Cannabidiol (CBD) on Seizure Frequency and Seizure-Free Intervals in Patients With Seizures Associated With Tuberous Sclerosis Complex (TSC): Phase 3 Trial GWPCARE6 Post Hoc Analysis
Harms & No Help
A network analysis finds an association between earlier onset of cannabis use & the psychotic experiences of hallucinations & irritability
A network approach to relationships between cannabis use characteristics and psychopathology in the general population
As always, the counter-argument is that the people with tendencies towards psychopathology start using cannabis as self-medication.
Networking modeling in adolescents suggests cannabis use accelerates thinning of the prefrontal cortex
Bayesian causal network modeling suggests adolescent cannabis use accelerates prefrontal cortical thinning
A review of adolescent studies shows mixed results for whether legalized cannabis leads to higher levels of teen cannabis use disorder
Is legalization of recreational cannabis associated with levels of use and cannabis use disorder among youth in the United States? A rapid systematic review
In humans with cannabis use disorder, they had a higher likelihood of critical limb ischemia (a severe blockage of blood flow to the extremities)
The Association of Cannabis Use Disorder with Acute Limb Ischemia and Critical Limb Ischemia
A computational study of the androgen receptor (a hormone receptor involved in pregnancy) finds that THC & CBD would probably bind there & inhibit reproductive function
Inhibition of human androgen receptor by delta 9-tetrahydro-cannabinol and cannabidiol related to reproductive dysfunction: A computational study
It’s probably not a huge drag on success – but if you’re trying to get pregnant & it’s not working, lay off the cannabinoids.
These immigration researchers obviously don’t like cannabis – and they also don’t like the fact that as immigrants move from low-income countries to high-income countries, their use increases as they assimilate
Immigrants, refugees and cannabis use
Lungs & COVID-19
A review of the potential of cannabinoids against COVID-19
Cannabinoids as Emergent Therapy Against COVID-19
In humans exposed to COVID-19, cannabis smokers were less likely to get infected but more likely to have a poor outcome if they were infected
Cannabis Use Is Associated With Lower COVID-19 Susceptibility but Poorer Survival
Of course, this study finds the opposite outcome on disease severity: they found that active cannabis users had better clinical outcomes if admitted to the hospital for COVID-19
Marijuana Consumption Is Associated with Lower COVID-19 Severity Among Hospitalized Patients
In COVID-19 patients with diabetes mellitus, those with more severe infections had higher levels of CB1 & CB2 receptors
Comparative study of CNR1 and CNR2 cannabinoid receptors expression levels in COVID-19 patients with and without diabetes mellitus: Recommendations for future research targets
In the lungs of humans, the more cannabis joint-years you have, the more likely to have small airway dysfunction – especially in women & as you get older
Lifetime cannabis exposure and small airway function in a population-based cohort study
Yes, cannabis joint-years is a real measure – and yes, I wish it was a number floating above everybody’s head. And yes, combusting plant matter & smoking it will never be great for your lungs. That’s not to say I don’t do it as many evenings as possible – but you know what you’re getting into. The science seems pretty clear that while smoking cannabis flower does not increase the risk of lung cancer, it does increase the risk of minor lung infections. And as this study shows, it probably makes your lungs not quite as efficient as you age.
To balance it out, for every joint you smoke, I’d recommend going out for a run. Which means I’m in the market for new running shoes…
In the lungs of cannabis users, they had a lower risk of secondary pulmonary hypertension (disease of blood flow between the heart & lungs) but a higher chance of death if they were admitted for the condition
Recreational Marijuana Use and Secondary Pulmonary Hypertension in Hospitalized Young Adults: A Nationwide Inpatient Analysis
In a related case study, an 18-year old with severe progressive lung problems after 6 years of smoking 6 joints a day
Chronic cannabis abuse causing marijuana lung- Young man’s agony
A survey of cancer patients found the majority liked to use CBD but a survey of oncologists find that the majority do not favor CBD-dominant cannabis
Letter to the Editor: The Role of Cannabidiol in Cancer Care: Oncologist and Cancer Patient Perspectives
As often happens, the patients know & the doctors do not.
In breast cancer cells, activating the cannabinoid receptors improved the strength of the osteoblasts (bone making cells) as well as reducing the growth & migration of the cancer cells
Activation of cannabinoid receptors in breast cancer cells improves osteoblast viability in cancer-bone interaction model while reducing breast cancer cell survival and migration
In a cancer patient, after years of nabilone (synthetic THC) to manage her pain, increasing the dosage during her chemotherapy treatments led to cannabinoid hyperemesis syndrome & cyclical vomiting
A case report on cannabinoid hyperemesis syndrome in palliative care: how good intentions can go wrong
A review of CBD for substance use disorders finds that most of the available research is preclinical – but they suggest the therapeutic potential
Cannabidiol in the context of substance use disorder treatment: A systematic review
From the streets, the answer is pretty clear. Is CBD amazing at stopping addiction? No.
But do a few people find it very helpful & many others find it moderately helpful? Absolutely.
A review of the evidence on using the cannabinoids for sleep as well as practical considerations for physicians
Cannabinoids, insomnia, and other sleep disorders
& a chapter on cannabis & sleep from the Handbook of Substance Misuse & Addictions
Cannabis Use and Sleep
In a fascinating review of sociality & the ECS in animal models, directly activating the cannabinoid receptors tends to lead to less social behaviors but indirectly activating them via enzyme inhibition (a function of CBD) tends to increase social behaviors
Effects of Endocannabinoid System Modulation on Social Behaviour: A Systematic Review of Animal Studies
I suspect that the animals feel like just me. Being high at a party is the worst. But a little bit of CBD on my system for social anxiety makes everything go much smoother & all of the sudden I’m playing Mario Kart in the middle of the madding crowd.
This review looks at the potential of CBD for suicide prevention (hattip to Stuart Tomc)
Suicidality and Cannabidiol: Opportunities and Challenges
According to this review, cannabinoids may be helpful for the pain of plastic surgery but more clinical research is needed
Cannabinoids and Pain for the Plastic Surgeon: What Is the Evidence?
This review suggests that the placebo effect may result from the interaction of the opioid, cannabinoid & monoaminergic systems
Psycho-Neuro-Endocrine-Immunological Basis of the Placebo Effect: Potential Applications beyond Pain Therapy
The monoaminergic systems include dopamine, norepinephrine & serotonin.
A review of the cannabinoid’s effects on brain development
The role of cannabinoids in CNS development: Focus on proliferation and cell death
A pharmacological review of Δ8-THC vs Δ9-THC finds that they’re similar, except that Δ8-THC doesn’t bind quite as strongly to the CB1 receptor
Review of Delta-8-tetrahydrocannabinol (Δ 8 -THC): Comparative Pharmacology with Δ 9 -THC
In rats, injections of THC or exposure to high-THC cannabis smoke made them worse at working memory processes
The effects of acute Cannabis smoke or Δ 9-THC injections on the trial-unique, nonmatching-to- location and five-choice serial reaction time tasks in male Long-Evans rats
As one often wonders, why is this work being done in rats instead of college students? It’s cheaper & more informative to see what happens in humans.
But as the old science adage goes, one doesn’t get attached to the college students like you do to the rats.
In a rat model of headaches, induction of the headache caused decreased 2-AG levels & thus inhibition of the MAGL and/or ABHD6 enzyme represents a potential treatment
Investigating the Roles of the Enzymes MAGL and ABHD6 in Headache Physiology via the KCl Model of Migraine
For all this animal work, the answer is clear: cannabinoids help people with migraines & headaches. Queen Victoria’s royal physician Sir John Russel Reynolds said that no other treatment compared – and today, with all of our options, it’s still one of the best treatments we know.
See my advice on using the cannabinoids for pain here.
In mice using the painkiller oxycodone, THC increased the painkilling strength but didn’t seem to affect tolerance or dependence
Impact of Δ9-Tetrahydrocannabinol Administration on Measures of Oxycodone-induced Antinociception, Dependence and Reward in Mice
In a mouse model of diabetic kidney disease, it seems that activating the CB1 receptor in sick animals made the disease worse but in healthy animals, it helped to maintain function by the control of glucose & amino acid uptake via mTORC
Opposite physiological and pathological mTORC1-mediated roles of the CB1 receptor in regulating renal tubular function
& a look at the CB1 receptor’s control of the mTORC pathway (a master cellular control system of energy regulation & protein activation)
mTORC1 under the control of CB 1 R
In rats with no p62 receptor (related to autophagy – cellular recycling), they had lower anandamide levels in the amygdala (fear center of the brain) but instead of displaying more anxiety, they were actually more exploratory
Behavioral Studies of p62 KO Animals with Implications of a Modulated Function of the Endocannabinoid System
In a cellular model of nonalcoholic fatty liver disease, β-caryophyllene (one of the most common cannabis terpenes) helped lower trans-fatty acid accumulation & cellular damage via the CB2 receptor & the PPAR-α receptor (a nuclear receptor that controls genetic transcription activated by many of the cannabinoids)
β-CARYOPHYLLENE REVERTS FREE FATTY ACIDS-INDUCED CELLULAR STRESS IN HEPG2 HEPATOCYTES THROUGH CB2 AND PPAR-α RECEPTORS
New FAAH inhibitors! This time it’s piperazine urea derivatives with thiadiazole moieties!
Development and molecular modeling studies of new thiadiazole piperazine urea derivatives as potential fatty acid amide hydrolase inhibitors
In my graphic novels, the synthetic molecules are the most fun. This one would be a type of fish with a huge round mouth that has pentagon blasters on the side for breaking the arms off of the FAAH giant squid.
Reversible MAGL inhibitors! Benzylpiperidine derivatives that might help with cancer treatments
Reversible Monoacylglycerol Lipase Inhibitors: Discovery of a New Class of Benzylpiperidine Derivatives
Reversible drugs are important because their actions can be more transient & not as strong. In this case, they created a mutant fish with two mouths that act like removable handcuffs for the arms of the MAGL octopus.
Plant Medicines & Psychoactives
Don Lattin on chaplains learning to become psychedelic guides
Yes. Taking headtwisters with your priest, imam, favorite witchy aunt or rabbi makes the most sense. It’s close to what Huxley envisioned in his “Island”, still considered by many to be the finest vision of psychedelics integrated into a society. He saw a future where people took a small number of trips spread across their life during the classic rites of passage.
An academic paper imagining the potential US legal frameworks for psychedelics
Socio-psychedelic imaginaries: envisioning and building legal psychedelic worlds in the United States
A study finds psychedelic use linked to mystical experiences as well as mindfulness, leading to increased wellbeing
Psychedelic Experiences and Mindfulness are Associated with Improved Wellbeing
As always, I’m glad someone is doing this work to put the number on it – but man, it seems like every piece of psychedelic science could have been something that any psychedelic grandma in the ‘70s could have told you.
The ability of psychedelics to cause hallucinations that last for months or years is underreported. This study collects the relevant literature on hallucinogen persisting perception disorder (HPPD) as well as 3 case studies
Hallucinogen persisting perception disorder: A literature review and three case reports
Chacruna releases the complete videos of their 2021 conference ‘Sacred Plants in the Americas II’
In a rat model of PTSD, MDMA lowered the stress response to trauma cues via the serotonin system & hormonal system
MDMA treatment paired with a trauma-cue promotes adaptive stress responses in a translational model of PTSD in rats
A TikTok by Sister Mary Jane on drugs in the Bible (hattip to Diana Adams)
Genesis chapter 30
PS: From the French singer & jazz manouche (“Gypsy”) guitarist Thomas Dutronc, here’s his cool album ‘Frenchy’ that includes a number of big guest stars. When you’re the son of Françoise Hardy & Jacques Dutronc, I guess it’s pretty easy to get Iggy Pop & Diana Krall on your album. But I kid. All on his own, Dutronc’s first album reached the Top 10 in Europe & was followed by a string of hits from his mix of jazz, chanson, rock & French Pop. After all those successes, this album ‘Frenchy’ is his dream project: a tribute to French song.
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]
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]
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 neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
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]
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]
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)
[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).
[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.