C&P#11: patients on cannabis for the win!
autism, arthritis, palliative care, neurological disorders & restless legs
Hello everyone,
A request to spread the word:
This newsletter only spreads by word of mouth – so forwarding & telling your friends & family goes a long way.
If you wanted to become a paid subscriber, you get no extra content, but the support would be much appreciated. #diapers
What’s striking about reviews of cannabinoid science is how often they end with the phrase “more research is needed.” What’s striking about surveys of patients with illnesses is how often they say that cannabis helps them. But in the Scientific Literature, all of the weight lies with the former - and the surveys are waved off as “anecdotal”.
As a story collector, I think it’s a damn shame. The patients know themselves, they know what worked for them & what didn’t – and here they are saying that cannabis helped them, but that data gets downgraded. As much as I love modern science, sometimes it’s as myopic as a cavefish.
Today we feature a number of surveys & case studies on the benefits of cannabis for autism, arthritis, the end of life, restless leg disorder, Alzheimer’s & other neurological disorders. You can see my advice here for using the cannabinoids for conditions like these. If you want me to write up the advice for any conditions I haven’t covered yet, send them to me here at lex@whitewhalecreations.com.
I’m always happy for a reason to pull together all of the science on a topic & craft advice on using the cannabinoids to help with it.
My ad: Cannabis counseling sessions
Cannabis & the cannabinoids are powerful medicines. Are you – or a family member – intrigued to try them for your health but don’t know how to start?
You can see my advice for using them for pain, neurodegeneration, autism, insomnia & anxiety/depression here. However, with the many tools out there - such as CBD, THC, PEA, OEA & CBDA - individualized advice can be helpful, especially for people new to cannabis. 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.
(I also provide advice on the use of ketamine, psychedelics & MDMA – but you have to source them yourself. Luckily, that’s not so hard these days…)
This newsletter is a free offering from my company White Whale Creations. I produce educational content for cannabis & psychedelic companies.
There’s also sponsorship opportunities for The Lex Files podcast.
#opentowork
Best of cannabinoid science...
In a double-blind study of children with autism, CBD-rich hemp extracts increased social interaction & concentration while decreasing anxiety & psychomotor agitation & led to less caregiver distress
Evaluation of the efficacy and safety of cannabidiol-rich cannabis extract in children with autism spectrum disorder: randomized, double-blind and controlled placebo clinical trial
https://pubmed.ncbi.nlm.nih.gov/35617670
In Alzheimer’s patients, 12 weeks of THC:CBD extract reduced agitation, apathy, irritability, sleep disturbances, eating disturbances, cognitive impairments & aggressive behaviors, leading to less caregiver distress
Oral Thc: Cbd Cannabis Extract in Main Symptoms of Alzheimer Disease: Agitation and Weight Loss
https://assets.researchsquare.com/files/rs-1672277/v1/4a190d8f-58a7-4c82-8e6f-86a9708493a9.pdf
In patients with arthritis of the thumb, two weeks of topical CBD treatment caused significant improvements in their pain measures
A Randomized Controlled Trial of Topical Cannabidiol for the Treatment of Thumb Basal Joint Arthritis
https://pubmed.ncbi.nlm.nih.gov/35637038
In a rat model of oral mucosal (mouth tissue swelling) problems from chemotherapy, CBD “improved survival, decreased body weight loss, reduced ulcer sizes, and improved clinical scores”, “restored epithelial thickness and normal structure in tongue tissues”, suppressed the inflammatory response & lowered reactive oxygen creation
Protective Effects of Cannabidiol on Chemotherapy-Induced Oral Mucositis via the Nrf2/Keap1/ARE Signaling Pathways
https://www.hindawi.com/journals/omcl/2022/4619760/
In mice being fed a high-fat diet to simulate nonalcoholic fatty liver disease, the addition of CBD increased food intake, improved glucose tolerance, reduced some of the inflammatory response & partially mitigated the microbiome problems while TC produced a similar but much weaker response
THC and CBD affect metabolic syndrome parameters including microbiome in mice fed high fat-cholesterol diet
https://pubmed.ncbi.nlm.nih.gov/35644678
On treating addiction disorders by targeting the endocannabinoid system
Targeting the endocannabinoid system in the treatment of addiction disorders
https://www.researchgate.net/publication/360685011_Targeting_the_endocannabinoid_system_in_the_treatment_of_addiction_disorders
A systematic review of the effect of CBD on cancer cells
Biological Effects of Cannabidiol on Human Cancer Cells: Systematic Review of the Literature
https://pubmed.ncbi.nlm.nih.gov/35643249
“CBD inhibited cell viability and proliferation in most cellular districts except the integumentary apparatus. Also a significant inhibition of migration was observed in all cell types, while an increase in apoptosis at both high and low doses (greater and less than 10μM respectively). Considering inflammation, CBD caused an anti-inflammatory effect on nervous cells at low doses and on gastro-intestinal cells at high doses, while metastatic power was reduced even at low doses, but in a skeletal cell line there was an increased angiogenesis. CB1 receptor has been related to viability effects, CB2 to apoptosis and TRPV1 to inflammation and invasiveness.”
A bibliometric analysis of cannabis research found that in the 29k+ papers published since 1829, the greatest number came out in the last 20 years – but the coolest part of this study is the word cloud in Figure 4
A bibliometric analysis of the cannabis and cannabinoid research literature
https://pubmed.ncbi.nlm.nih.gov/35610633
The funniest op-ed I’ve ever read in a dental surgery journal…
Everybody must get stoned
https://www.ajodo.org/article/S0889-5406(22)00102-0/fulltext
An evergreen note on reading restricted paper:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version) or Google Scholar itself.
For the infamous backdoor, use Sci-Hub – the pirated papers repository (Chrome extension here). This works better for older paper than the stuff that just came out.
For Twitter users, send a Tweet of the paper’s title with the hashtag #icanhazpdf. It works because people are beautiful(ish).
Finally, email the author. They’re almost always happy to oblige because, thanks to the predatory academic publishing system, they don’t make a dollar off of their papers.
Popular science news, articles & videos
I’m not often blown away by cannabinoid science lectures anymore – but this Jason Wilson hits it out of the park: science, history & related molecules. Two thumbs way up (hattip to Stuart Tomc)
Follow on Twitter here or check out his podcast & book here.
the Headlines & Fav Articles
An Irish man whose medical cannabis is the only thing that gives him the ability to walk is fined €250 for possession & had his medicine destroyed
https://www.leinsterexpress.ie/news/crime---courts/822798/only-way-he-can-walk-is-by-taking-cannabis.html
It’s a terrible world.
Virginia lawmakers are looking to create stricter cannabis possession rules despite the state having passed a legalization bill in April 2021
https://www.ganjapreneur.com/virginia-lawmakers-considering-stricter-cannabis-possession-laws
The CEO of Ascend Wellness said that they’re teaming up with other big multi-state operators to sue the federal government & overturn cannabis prohibition
https://www.marijuanamoment.net/marijuana-companies-teaming-up-to-sue-federal-government-with-all-star-legal-firm-multi-state-operator-ceo-says
Sure, why not?
Nothing from patients or activists ever worked – but Big Money talks. And they hire hot-shot lawyers.
School officials of Los Angeles want to close or relocate marijuana dispensaries that are near schools
ttps://twitter.com/LASchools/status/1530259910595780609
What a waste of energy. Nobody complains about liquor stores being close to schools.
Heidi Klum pushes German drug minister to legalize cannabis
https://www.thetimes.co.uk/article/heidi-klum-rolls-up-to-talks-on-german-cannabis-law-clt2rrt68
Sold!
For your sexiest infused cannabis beverage ad of the week…
(I think there’s a lot of famous people in this, but I’m not exactly sure because that isn’t my field…)
Law & Business
An analysis of the cannabis market finds that dried flower still rules – followed by edibles & vape oils
Trends in the use of cannabis products in Canada and the USA, 2018 - 2020: Findings from the International Cannabis Policy Study
https://pubmed.ncbi.nlm.nih.gov/35613480
This analysis of the correlation between oral fluid & blood THC concentrations for driving concludes that using oral fluid THC testing would lead to many false positives & the harms outweigh the benefits
Correlation between oral fluid and blood THC concentration: A systematic review and discussion of policy implications
https://pubmed.ncbi.nlm.nih.gov/35640367
The War on Drugs & Harm Reduction
Much hay is being made about the British Columbia pilot program that decriminalizes up to 2.5 grams of drugs – but most street users have more than that & it’s still illegal to use in public
https://www.marijuanamoment.net/canadian-government-approves-drug-decriminalization-pilot-program-in-british-columbia
Also, as this professor points out, “BC's application for decriminalizing the possession of small amounts of drugs was submitted (Nov 1 '21) & granted 8 months later (May 31 '22) & will be implemented 15 months after (Jan 31 '23). This was during a declared public health emergency & thousands of deaths.”
This being said, Canada still leads as one of the few places with something of a heart when it comes to drug use. How Amerika treats people who use drugs makes me ashamed.
In NYC, one of the country’s only safe injection facilities has already averted 314 overdoses since it opened early last year
https://twitter.com/samrivera1111/status/1531672560772988929
In Colorado, Gov. Polis signed a bill to create a regulatory framework for the sale of kratom, the painkilling plant that many use as an alternative to opioids & as a helpful tool for withdrawing from addiction
https://www.marijuanamoment.net/colorado-governor-signs-bill-to-regulate-kratom-sales
The DEA’s recent push to get this plant banned once & for all is just the latest heartlessness in their callous reign of terror over US medical patients.
The Plant & the History
On the importance of potassium for growing cannabis
Effect of Potassium (K) Supply on Cannabinoids, Terpenoids and Plant Function in Medical Cannabis
https://www.mdpi.com/2073-4395/12/5/1242/htm
A review of hemp seeds for animal nutrition
The chemical composition, nutritional value, and potential use of Cannabis sativa L. seeds in animal nutrition
https://agro.icm.edu.pl/agro/element/bwmeta1.element.agro-80befc62-4181-407e-87fe-141b2be7a0a2/c/33-44.pdf
“Compared to other popular oilseeds, hemp seeds have higher protein content than rapeseeds and higher fat content than soybeans, but contain more fibre, arginine, and polyunsaturated fatty acids. Based on the analyses and a review of the literature, it can be concluded that hemp seeds have high nutritional potential and can be used as a source of protein and fat in animal nutrition.”
In olden times, the retting (breaking of hard fibers) of hemp was often done in freshwater & in this lake, that appears to have negative microbiome effects
Lake microbiome and trophy fluctuations of the ancient hemp rettery
https://pubmed.ncbi.nlm.nih.gov/35614182
Plant Medicines & Psychoactives
The Navajo Nation comes out against the legalization or decriminalization of peyote
https://www.12news.com/article/news/regional/native-america/navajos-legalizing-peyote-hurt-religious-practices/75-467d0aa3-166d-45ca-8d23-37f398c9ac84
This has been a long-running debate in the plant medicine movement. Many Indigenous groups argue that laws & procedures already exist for the use & harvest of peyote. With the peyote cactus under threat from over-cultivation – and with almost no one ever getting charged with possession of it anyway – they see legalization as a path towards overharvesting & a threat to their spiritual traditions.
A passionate treatise on why to sometimes take your drugs rectally: Boofing 101
https://twitter.com/clairezagorski/status/1532134522946461697
This is no joke. For cancer patients, one of the best ways to ingest large levels of cannabis is via rectal administration. This helps to avoid the liver processing that makes the THC more psychoactive & it avoids the smoking or oral routes that might be more challenging. The rectal administration of cannabinoids (& other drugs) is a key part of our medical future.
A Preventable Tragedy
The Science
Friend of the Newsletter Alex Belser & colleague William Brennan introduce their psychotherapeutic model EMBARK for working with psychoactive medicines
Models of Psychedelic-Assisted Psychotherapy: A Contemporary Assessment and an Introduction to EMBARK, a Transdiagnostic, Trans-Drug Model
https://www.frontiersin.org/articles/10.3389/fpsyg.2022.866018/full
A study of two scales for measuring psychedelic integration
The Psychedelic Integration Scales: Tools for Measuring Psychedelic Integration Behaviors and Experiences
https://www.frontiersin.org/articles/10.3389/fpsyg.2022.863247/full
The required cartoon to reference is here.
A review of treating depression with psilocybin suggests that the ability of psilocybin to grow new brain connections may undergird its efficacy
Unraveling the Mysteries of Mental Illness With Psilocybin
https://www.cureus.com/articles/97061-unraveling-the-mysteries-of-mental-illness-with-psilocybin
In a study of LSD users, it seems like dopamine also makes a contribution to the effects in addition to the classic serotonin effects
Differential contributions of serotonergic and dopaminergic functional connectivity to the phenomenology of LSD
https://pubmed.ncbi.nlm.nih.gov/35322297
This analysis of all the brain scans done on people on psychedelics find that they’re all over the place (the scans, not the people)
Psychedelic resting-state neuroimaging: A review and perspective on balancing replication and novel analyses
https://www.sciencedirect.com/science/article/pii/S0149763422001786
The “42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology.”
Science
Clinical Studies & Surveys
3 case studies of cannabis for palliative care
A Case Series of the Role of Cannabis Based Medicine in the Palliative Care Setting
https://olh.ie/education-research/wp-content/uploads/2022/03/A-Case-Series-of-the-Role-of-Cannabis-Based-Medicine-in-the-Palliative-Care-Setting.pdf
In a survey of rheumatoid & psoriatic arthritis patients, medical cannabis gave them significant relief from short & long-term pain as well as reduced stiffness – and for some patients, total pain relief
PARE Patient-Reported Outcome Measures of Pain Alleviation With Cannabinoid Usage in Rheumatoid and Psoriatic Arthritis: a Cross-Sectional Study
https://ard.bmj.com/content/81/Suppl_1/1132.3.abstract
A survey of patients with restless leg syndrome found that some found relief with cannabis
Prevalence of Cannabis Use in Patients with Restless Leg Syndrome for Symptomatic Relief
https://academic.oup.com/sleep/article/45/Supplement_1/A246/6593000
A survey of Canadian cannabis users found these conditions at the top of the list: anxiety (70%), insomnia (56%), pain (53%), depression (37%)
A description of self-medication with cannabis among adults with legal access to cannabis in Quebec, Canada
https://pubmed.ncbi.nlm.nih.gov/35619155
A study of patients with neurological disorders saw that 50% found cannabis helpful for treating symptoms & that 25% found it helped improve quality of life
Cannabis-based medicinal products for neurological disorders: a study of 75 patients
https://jnnp.bmj.com/content/93/6/A115.3.abstract
This rather obvious clinical study found that consuming hemp products puts athletes at risk for violations of anti-doping rules
Risk of unintentional antidoping rule violations by consumption of hemp products
https://pubmed.ncbi.nlm.nih.gov/35633098
This one is simple. Stop treating cannabis like a performance-enhancing drug.
This survey of cannabis users & consciousness finds that THC increased features of altered states of consciousness including insightfulness, mindfulness & mind-wandering
The altered state of consciousness induced by Δ9-THC
https://pubmed.ncbi.nlm.nih.gov/35640529
In a double-blind study, 600 mg of CBD did not cause any alterations in brain responses to emotional faces (hattip to Stuart Tomc)
The acute effects of cannabidiol on emotional processing and anxiety: a neurocognitive imaging study
https://pubmed.ncbi.nlm.nih.gov/35445839
A study of many drugs & their effects of different types of memory
Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory
https://www.biorxiv.org/content/10.1101/2022.05.20.492842v1
“We observed that sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on which phase of memory (encoding, consolidation, or retrieval) was targeted. All drugs at encoding except stimulants impaired recollection, and sedatives, dissociatives, and cannabinoids at encoding impaired familiarity. The effects of sedatives on metamemory were mixed, whereas dissociatives and cannabinoids at encoding tended to enhance metamemory. Surprisingly, psychedelics at encoding tended to enhance familiarity and did not impact metamemory. Stimulants at encoding and retrieval enhanced metamemory, but at consolidation, they impaired metamemory.”
Harms & No Help
In people with their first episode of psychosis, those with a history of cannabis use had more attention deficits than those who didn’t
Longitudinal effects of cannabis use on attentional processes in patients with first episode of psychosis
https://pubmed.ncbi.nlm.nih.gov/35640355
This clinical study of THC finds it dampens both reward & loss feedback hinting at possible links to amotivation
Δ9-THC reduces reward-related brain activity in healthy adults
https://pubmed.ncbi.nlm.nih.gov/35612654
3 case studies of patients who experienced hypersalivation after using cannabis after surgery with the anesthetic propofol
Chronic Cannabis Intoxication and Propofol-Induced Salivation: Causes and Considerations
https://www.mdpi.com/1873-149X/29/2/18/htm
A case study of a cannabis user with little cardio risk who had a seizure & a coronary artery thrombosis
Recreational Marijuana Use Leading to Thrombosis in a Patient with Minimal Cardiovascular Risk Factors
http://article.americanmedicalcasereports.com/pdf/ajmcr-10-5-3.pdf
A case study of a patient with dangerously low potassium levels after cannabis use
Hypokalemic Paresis in a 26-Year-Old Man After Recreational Cannabis Use
https://amjcaserep.com/abstract/full/idArt/936008/s/A
In a cannabis smoking lounge, high levels of the airborne particulates of PM2.5 that was little changed by the installation of a ventilation system
PM2.5 Concentrations in the Smoking Lounge of a Cannabis Store
https://pubs.acs.org/doi/full/10.1021/acs.estlett.2c00148
Cannabis Use Disorder
A look at those Californians being discharged from the ER with cannabis use disorder
Spatial and temporal pattern of cannabis use disorder in California 2010-2019
https://www.sciencedirect.com/science/article/abs/pii/S1877584522000430
In the treatment of cannabis use disorder, the COX2 inhibitor celecoxib did not show promise as a treatment
Impact of cyclooxygenase-2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers
https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.13183
A study of systematic reviews on cannabis use disorder finds that conflicts of interest & industry sponsorship did not seem to display signs of bias
Evaluating the relationship between industry sponsorship and conflicts of interest among systematic review authors on treatments for cannabis use disorder
https://pubmed.ncbi.nlm.nih.gov/35617607
Cancer
A review of CBD in cancer treatment: not just for symptom control, but for anticancer action itself
Mechanisms of Cannabidiol (CBD) in Cancer Treatment: A Review
https://www.mdpi.com/2079-7737/11/6/817
This cheeky headline just goes on to say that cancer patients & their doctors need to know more about cannabis
(Almost) Everything You Always Wanted to Know About Cannabis Science, but Were Afraid to Ask!
https://www.jmirs.org/article/S1939-8654(22)00200-4/fulltext
Recent Reviews
A review of psychosis treatments suggests the microbiome-endocannabinoid axis as a target
Unmet Therapeutic Needs in Psychotic Illness: The Gut Microbiome-Endocannabinoid Axis as a Target for the Development of New Preventative Strategies
https://link.springer.com/chapter/10.1007/978-3-030-97906-5_16
A review of how the components of cannabis combat inflammation
Medical Cannabis Activity Against Inflammation: Active Compounds and Modes of Action
https://pubmed.ncbi.nlm.nih.gov/35614947
A review of how our circadian rhythms & memory are mediated by the endocannabinoids
Circadian regulation of memory under stress: Endocannabinoids matter
https://pubmed.ncbi.nlm.nih.gov/35643119
A review of the studies on how well CBD absorbs through the skin
Systematic Review on Transdermal/Topical Cannabidiol Trials: A Reconsidered Way Forward
https://pubmed.ncbi.nlm.nih.gov/35605018
A review of the clinical work done on cannabis
Efficacy of cannabis and its constituents in disease management: Insights from clinical studies
https://pubmed.ncbi.nlm.nih.gov/35619266
A review of the therapeutic potential of cannabis & cannabinoids
Therapeutic Potential of Cannabis, Cannabidiol, and Cannabinoid-Based Pharmaceuticals
https://pubmed.ncbi.nlm.nih.gov/35093949/
Preclinical Research
In a rat model of nonalcoholic fatty liver disease, treatment with inulin (a natural starch that helps the microbiome) helped in a number of ways & it significantly lowered CB1 expression & 2-AG levels in the liver
Inulin may prevent steatosis by suppressing Cannabinoid receptor-1 and Patatin-like phospholipase-3 expression in liver
https://www.sciencedirect.com/science/article/abs/pii/S0899900722001551
In a rat model of Alzheimer’s disease, activating the CB2 receptor protected the neurons against hyperexcitation
Activation of Cannabinoid Receptor 2 Protects Rat Hippocampal Neurons against Chronic, Oligomeric A_-induced Neuronal Hyperexcitation
http://www.ijbs.org/User/ContentAbstractPage.aspx?VolumeNO=18&StartPage=14&EndPage=23&Number=1
In oligodendrocytes (creators of the myelin sheaths around the axons of neurons), the cannabinoids cause a range of actions including cell proliferation, migration, regulation of carbohydrate & lipid metabolism, control of mitochondrial function & differentiation of oligodendrocyte progenitor cells
Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes
https://pubmed.ncbi.nlm.nih.gov/35622101
In a tissue model of Alzheimer’s disease, PEA & luteolin (a flavonoid commonly paired with PEA) reduces neuronal inflammation & astrocyte reactivity while restoring homeostasis of the oligodendrocytes via the PPAR nuclear receptors (controllers of genetic transcription)
Co-Ultramicronized Palmitoylethanolamide/Luteolin Restores Oligodendrocyte Homeostasis via Peroxisome Proliferator-Activated Receptor-α in an In Vitro Model of Alzheimer’s Disease
https://www.mdpi.com/2227-9059/10/6/1236
In a mouse model of facial pain, treatment with a FAAH inhibitor caused increased AEA levels as well as CB1 receptors but lower levels of 2-AG & CB2 – a strong look at the interplay of the endocannabinoids
Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats
https://www.mdpi.com/1467-3045/44/5/164
In a rat model of pain, blocking the GPR55 (a receptor that may one day be known as CB3) can lessen inflammatory pain via the descending pain pathways
Contribution of G Protein-Coupled Receptor 55 to Periaqueductal Gray-Mediated Antinociception in the Inflammatory Pain
https://pubmed.ncbi.nlm.nih.gov/35612493
In mice, a peptide that stimulates new bone growth appears to work via the CB2 receptor
Osteogenic growth peptide is a potent anti-inflammatory and bone preserving hormone via cannabinoid receptor type 2
https://pubmed.ncbi.nlm.nih.gov/35604006
The endocannabinoid system is quite involved in the Yin & Yang of bone repair – and it’s one more reason that people over 50 should be taking 50 mg of CBD every day.
In female rats, estrogen dampens the neural excitatory effects of the CB1 receptor
Estrogen dampens central cannabinoid receptor 1-mediated neuroexcitation and pressor response in conscious female rats
https://pubmed.ncbi.nlm.nih.gov/35617998
This cellular study looked at how the synthetic cannabinoid UR-144 causes cardiotoxicity
UR-144, synthetic cannabinoid receptor agonist, induced cardiomyoblast toxicity mechanism comprises cytoplasmic Ca 2+ and DAPK1 related autophagy and necrosis
https://pubmed.ncbi.nlm.nih.gov/35606921
Cannabinoid Chemistry & Technology
How to design labeled probes for the ECS
Reverse-Design toward Optimized Labeled Chemical Probes – Examples from the Endocannabinoid System
https://chimia.ch/chimia/article/view/2022_425
Thanks.
- lex
PS: Today’s music comes from that master of exotica, Yma Sumac, on her first album ‘Voice of the Xtabay’. Rising to fame in the 1950s, this Peruvian-American soprano had a remarkable range of 4.5 octaves – plus the ability to sing in “double voice”. As John Haley described her voice, it did not have the "bright penetrating peal of a true coloratura soprano"(the operatic singing consisting of many trills & flourishes), but instead had "an alluring sweet darkness ... virtually unique in our time."
Early stories claimed that she was an Incan princess directly descended from the last Incan Emperor – and her outfits & lifestyle certainly played up the angle – but according to her biographer Nicholas Limansky, "Hollywood took this nice girl who wanted to be a folk singer, dressed her up and said she was a princess. And she acted like it.” She appeared in ‘Secret of the Incas’ with (a very young) Charlton Heston & Thomas Mitchell (who I always love), a movie that is often called the inspiration for ‘Raiders of the Lost Ark’. You can see her start to sing at the 58” mark. She truly sings like a bird.
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.
Endocannabinoids
The cannabinoids found inside all mammals & almost every other form of life besides insects
The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”
Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]
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]
CB1
The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]
2-AG
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
[blue whale]
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]
CB2
The second endocannabinoid receptor discovered. Found in almost every organ of the body & closely connected to our immune system. The CB2 occurs at low levels in the brain where it responds to neural insults.
[a gay bar in the membrane wall of the neuronal city]
Palmitoylethanolamide (PEA)
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]
Oleamide (OEA)
An endocannabinoid related to sleep. They discovered it by keeping cats awake for 3 days & then analyzing their spinal fluid. You can buy it on Amazon. 2 scoops helps you to sleep while 6 scoops is a very pleasant psychoactive experience (Hamilton Morris has called it his favorite way to get high - which is saying something)
[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 interact with our histamines.
[Pygmy sperm whale. Not well known, a smaller cousin to the sperm whale]
Fatty acid-binding proteins (FABPs)
These transport proteins move fatty lipids such as the endocannabinoids around the body. While still mysterious, they’re thought to move anandamide between membranes as well as transporting it to be broken down by the enzyme FAAH. Several types of FABPs exist in humans. THC & CBD bind to some of them. This may explain why endocannabinoid levels tend to increase after consuming cannabinoids. As the brain ages, the levels of FABPs decrease.
[whale cars]
Phytocannabinoids
The cannabinoids produced by the cannabis plant.
THC (delta-9-tetrahydrocannabinol or Δ9-THC)
The well-known & well-studied molecule in cannabis that gets you high - and helps in a number of other fascinating ways.
[African elephant. Powerful, unpredictable, beautiful]
CBD (cannabidiol)
The cousin of THC that does not get you high but does a lot of the heavy lifting in why hemp has been such a staple of medicine since before recorded history. In most plants outside those bred for the recreational market, CBD is the most common cannabinoid. It binds to a wide swathe of receptors outside the endocannabinoid system including three serotonin receptors, two opioid receptors, a dopamine receptor as well as glutamate & GABA (the two most widespread neurotransmitters, the basic neuronal signals for excitation & inhibition, respectively)
[Indian elephant. sweet, gentle, you can work with it]
CBC (cannabichromene)
The third most common cannabinoid in the plant, it’s not well studied in humans despite a number of intriguing preclinical studies, especially as an anti-inflammatory and for pain. Nonpsychoactive, it interferes with the breakdown of AEA & 2-AG (leading to a rise in their levels) as well as interacting with the vanilloid receptors.
[Sri Lankan elephant. Little, sweet, not as well known as it should be]
CBDV (cannabidivarin)
CBDV is like CBD with a shortened tail (side chain). Also nonpsychoactive, it tends to occur at low levels in most cannabis cultivars. It’s known to be an anticonvulsant & is suggested for treating autism in humans & in animal models. The cannabinoid pharmaceutical company GW has it in their developmental pipeline as GWP42006.
[An Asian elephant with a short trunk]
Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]
Beta-caryophyllene (BCP)
A terpene that’s also a cannabinoid.
The terpenes of cannabis give the plant its smell. Also found in oregano, black pepper, lavender & hops, beta-caryophyllene has a spicy sweet woody smell. But unique among terpenes, this one also binds to the CB2 receptor, making it a dietary cannabinoid. It shows a potential for treating inflammation, pain, anxiety & seizures. The FDA has designated it to be GRAS (generally regarded as safe) & thus it can be safely used as a food additive.
[a terpene/cannabinoid that travels through the air? That could only be a flying elephant]
Pharmaceutical cannabinoids
Nabiximols (ie Sativex®)
A pharmaceutical 1:1 CBD:THC spray produced by GW Pharmaceuticals. One of the first cannabinoid pharmaceuticals on the market, Sativex is an approved treatment for neuropathic pain, spasticity, overactive bladder & the symptoms of multiple sclerosis.
Epidiolex® (in the UK, Epidyolex®)
An isolated CBD formulation approved for treating the severe seizures of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. Produced by GW Pharmaceuticals, the doses tend to be incredibly high – hundreds or thousands of milligrams of CBD every day in young children. But even with that, the side effects tend to only be lethargy & stomach upset.
Dronabinol (ie Marinol® and Syndros®)
A synthetic form of THC for the treatment of anorexia in AIDS patients & the nausea of chemotherapy. These tend to not be popular with patients because it’s a horse dose of THC with no modulation by the other molecules in the cannabis plant like CBD.
Nabilone (Cesamet®)
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.