C&P#43: cannabis, psychedelics & menstrual cycles + THC & male infertility + CBD for cavities?
Hello everyone,
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Welcome to the 43rd edition of Cannabinoids & the People. This newsletter collects all the new cannabinoid science each week. You can check out last week’s issue here & if you haven’t subscribed yet, please do.
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And as always, at the bottom is the album of the week &
The Living Glossary of Cannabinoid Terms.
This week…
Medical cannabis for painful periods
Cannabinoids for so many skin diseases
CBD for cavities?
The gender differences in the symptom manifestation of cannabis use disorder
Why does THC tend to lower male fertility?
THC for RNA viruses
On using CBD against cancer cells & cannabis against the symptoms of chemo
On menstrual cycles & psychedelics
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Best Of Cannabinoid Science...
Clinical
In men with sexual dysfunction, cannabis consumption was associated with a better lipid profile & better penile response to prostaglandin (lipid hormones)
Is marijuana a foe of male sexuality?: Data from a large cohort of men with sexual dysfunction
https://pubmed.ncbi.nlm.nih.gov/36617843/
It's curious that they put a question into the paper’s title – and the answer to that question is no.
A slide show reviewing 40 studies on the epigenetic effects of cannabis & the links to behavior & emotions
The epigenetic effects of cannabis exposure and their link to behavior and emotional manifestations – a scoping review
https://www.lisbonaddictions.eu/lisbon-addictions-2022/sites/lisbonaddictions.eu.lisbon-addictions-2022/files/24%20%20107%20%201320%20%20Ana%20Sofia%20Machado_v1.0.pdf
In a patient with advanced breast cancer, using cannabis for insomnia
Medical Cannabis for Insomnia in a Patient With Advanced Breast Cancer
https://pubmed.ncbi.nlm.nih.gov/36641008/
A study in horses finds that CBD has an oral bioavailability close to 14% & no noted adverse effects
Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations
https://pubmed.ncbi.nlm.nih.gov/36624043/
plus a small safety study in mature horses confirms no negative effects on liver & kidney function
Evaluation of an Oral Supplemental Cannabidiol Product for Acceptability and Performance in Mature Horses
https://www.mdpi.com/2076-2615/13/2/245
Reviews
A big review of 64 papers on using medical cannabis for dysmenorrhea (painful periods) with positive results
Dysmenorrhoea: Can Medicinal Cannabis Bring New Hope for a Collective Group of Women Suffering in Pain, Globally?
https://pubmed.ncbi.nlm.nih.gov/36555842/
A review of treating skin diseases with cannabinoids
Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases
https://pubmed.ncbi.nlm.nih.gov/36552866/
“In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers.”
A big review on cannabinoids & male reproduction with a focus on why THC seems to lower male fertility
Phytocannabinoids, the Endocannabinoid System and Male Reproduction
https://pubmed.ncbi.nlm.nih.gov/36578200/
Using public health data, the gender differences in cannabis use disorder
Sex differences in Cannabis use disorder and associated psychosocial problems among US adults, 2012-2013
https://pubmed.ncbi.nlm.nih.gov/36641126/
“We found that the prevalence of CUD among men versus women was not significantly greater after adjusting for use frequency. Women had significantly higher prevalence of interpersonal, financial and health-related problems than men, adjusting for frequency of use. Women showed significantly greater association of CUD with interpersonal problems with a boss or co-workers (p < 0.05) and a neighbor, relative or friend (p < 0.05) compared to men.”
In cannabis use disorder, a network analysis of gender differences in symptoms
Gender differences in cannabis use disorder symptoms: A network analysis
https://pubmed.ncbi.nlm.nih.gov/36565568/
“There were gender differences in the prevalence of 6 of the 11 symptoms, but symptom networks did not differ between men and women. Cigarette use appeared to only be connected to the network through withdrawal, indicating a potential role of cigarette smoking in enhancing cannabis withdrawal symptoms. Furthermore, there were gender differences in the network associations of mood and anxiety disorders with CUD symptoms.”
Preclinical
CBD as a strong antibiotic against the bacteria that cause cavities
Anti-Bacterial Effect of Cannabidiol against the Cariogenic Streptococcus mutans Bacterium: An In Vitro Study
https://pubmed.ncbi.nlm.nih.gov/36555519/
In a rat model of pulmonary hypertension, CBD lowered the proliferation of negative cells & decreased the release of inflammatory cytokines
Cannabidiol inhibits lung proliferation in monocrotaline-induced pulmonary hypertension in rats
https://pubmed.ncbi.nlm.nih.gov/36634588/
In a mouse model of inflammatory pain, combining CBD & β-caryophyllene (a common cannabis terpene) to produce synergistic painkilling effects via control of inflammation
Cannabidiol and Beta-Caryophyllene in Combination: A Therapeutic Functional Interaction
https://pubmed.ncbi.nlm.nih.gov/36555111/
A computer analysis of using dronabinol (synthetic THC) against the flavivirus family (RNA viruses that include West Nile, dengue, yellow fever & Zika)
Dronabinol as an answer to flavivirus infections: an in-silico investigation
https://pubmed.ncbi.nlm.nih.gov/36576139/
On engineering a cousin of the tobacco plant to produce cannabinoids
Metabolic Engineering of Nicotiana benthamiana to Produce Cannabinoid Precursors and Their Analogues
https://pubmed.ncbi.nlm.nih.gov/36557219/
An evergreen note on reading restricted paper:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version), Google Scholar itself or try ResearchGate.
3 other helpful browser extensions are: Unpaywall, Open Access Button & PaperPanda
For the infamous backdoor, use Sci-Hub – the pirated papers repository (Chrome extension here). This works better for older paper than the stuff that just came out.
For Twitter users, send a Tweet of the paper’s title with the hashtag #icanhazpdf. It works because people are beautiful(ish).
Finally, email the author. They’re almost always happy to oblige because, thanks to the predatory academic publishing system, they don’t make a dollar off of their papers.
the Headlines & Fav Articles
In ‘State of the States’ report from Americans for Safe Access, a sad state of affairs for medical cannabis patients in every state
https://assets.nationbuilder.com/americansforsafeaccess/pages/27187/attachments/original/1675362731/StateoftheStates22_P5.pdf
https://www.ganjapreneur.com/americans-for-safe-access-gives-zero-states-a-grade-in-annual-report
‘The group notes that “even in states with full medical cannabis programs, each state differs greatly in how patients can access their medicine, where they can access it, or even what types of products they can access.” Adding that because medical cannabis remains prohibited federally “most state programs leave out millions of potential patients due to issues with affordability, patient rights, and civil protections, or product safety standardization.”’
Americans for Safe Access was my first exposure to the importance of fighting for the rights of medical patients to clean affordable medicine & how easily that can get lost in the wave of adult use legalization. I believe ASA is a key organization you can support with your donations.
The US Hemp Roundtable with a roundup of national media responses to the FDA's abdication of CBD responsibility
https://mailchi.mp/8d45cd02c36b/national-media-covers-sharp-reaction-to-fda-announcement-on-cbd-regulations
There’s some funny headlines in there…
My suggestion would be: ‘FDA groundhogs smell a complex problem, declare no end to winter’
In 2022, the 20 biggest cannabis companies spent $5M+ on federal lobbying efforts
https://www.marketwatch.com/story/cannabis-industrys-spending-on-washington-lobbying-hits-record-11675108111
On the new federal cosmetic rules & what that means for topical CBD
https://www.marijuanamoment.net/what-new-federal-cosmetics-rules-mean-for-products-made-with-cbd-and-other-cannabis-derivatives-op-ed
A survey finds that 65% of US citizens support legalizing adult use cannabis & the majority also support cannabis social equity programs
https://www.ganjapreneur.com/survey-65-of-americans-support-legalizing-cannabis
And yet, somehow, nothing will probably change this year.
A bill in Washington state would increase taxes on high THC products
https://www.ganjapreneur.com/washington-bill-would-increase-taxes-on-high-thc-products
This is the kind of prohibitionist thinking that leads to bad downstream outcomes for consumers & patients.
Amidst the national truck driver shortage, the Federal Motor Carrier Safety Administration reports that 40k+ truck drivers tested positive for cannabis last year (a 32% increase) & more than half of them haven't enrolled in the return-to-work process
https://www.marijuanamoment.net/tens-of-thousands-of-truckers-are-testing-positive-for-marijuana-and-leaving-the-industry-amid-labor-shortage-federal-data-shows
Hong Kong’s CBD ban goes into effect
https://apnews.com/article/health-china-government-hong-kong-marijuana-a250ce49735c1b6e67b78895bad60bab
The War on Drugs & Prohibition
British Columbia begins an experiment decriminalizing all drugs including meth, cocaine, fentanyl, morphine & heroin
https://www.bbc.com/news/world-us-canada-64461983
If you know anything about me, you know that right now I'm going, “Fuck yeah Canada”.
The BBC reports, “while those substances will remain illegal, adults found in possession of a combined total of less than 2.5g of the drugs will not be arrested, charged or have their substances seized. Instead, they will be offered information on available health and social services.” Like humans.
In Ireland, after a raid of her home, a skin cancer patient tells the judge that she cannot quit cannabis because it is the only thing that works for her pain relief
https://www.irishexaminer.com/news/courtandcrime/arid-41062205.html
Raiding medical patients: inhuman.
The majority of Dark Web drug markets now are based in Russia - and there's a fight to control them
https://www.vice.com/en/article/wxnmg5/russia-darknet-market-wars
Psychedelics, Plant Medicines & Other Psychoactives
Australia to allow psychiatrists to use psilocybin & MDMA for their patients, leapfrogging the rest of the world towards sane drug laws
https://www.tga.gov.au/news/media-releases/change-classification-psilocybin-and-mdma-enable-prescribing-authorised-psychiatrists
https://ondrugs.substack.com/p/australia-legalizes-medical-mdma
A living list of the North American psychedelic dispensaries
https://psychedelicspotlight.com/a-living-list-of-north-american-psychedelic-dispensaries
Ketamine telehealth maybe hitting a wall
https://harrisbricken.com/psychlawblog/bad-news-for-ketamine-telehealth
Good writing on the link between psychedelics & psychosis
https://ecstaticintegration.substack.com/p/psychedelics-and-psychosis-the-elephant
And an interview with the author
https://themicrodose.substack.com/p/what-is-a-bad-trip-5-questions-for
On the history of DMTx (extended-state DMT infusion) by Andrew Gallimore, who coined the term
https://alieninsect.substack.com/p/the-origins-and-theory-behind-dmtx
On the ancient psychedelic datura by Sofie Mikhaylova
https://www.leafie.co.uk/psychedelics/ancient-psychedelics-datura
‘A Jewish Mystic’s Embrace of Psychedelics’ by Don Lattin
https://www.lucid.news/jewish-mystics-embrace-psychedelics
‘Can Psychedelics Increase the Risk of Heart Disease?’
https://tripsitter.com/heart-disease
Clinical Studies
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a newsletter with all the new psychedelic science would be of interest to your org, reach out to me]
On psychedelics & menstrual cycles, three case histories & a literature search on a number of distinct phenomena
Menstrual Changes and Reversal of Amenorrhea Induced by Classic Psychedelics: A Case Series
https://pubmed.ncbi.nlm.nih.gov/36682064/
“Three women ranging from 27 to 34 years of age were interviewed and reported three distinct phenomena following the use of classic psychedelics: 1) resumption of menses following amenorrhea, 2) early onset of menses, in particular when psychedelics were used in the mid to late luteal period, and 3) improved menstrual regularity in a woman with irregular cycles who was eventually diagnosed with polycystic ovarian syndrome. The mechanisms behind these effects remain unclear, though they may be mediated via direct or indirect effects of 5-HT2A agonism on the hypothalamic-pituitary-gonadal axis.”
A study on microdosing psychedelics lowering emotional diversity
Microdosing psychedelics – Does it have an impact on emodiversity?
https://akjournals.com/view/journals/2054/aop/article-10.1556-2054.2022.00208/article-10.1556-2054.2022.00208.xml
“Participants experienced more “awe, wonder, or amazement”, “ashamed, humiliated, or disgraced” as well as less “joyful, glad, or happy” emotions during microdosing days.”
Business & Law
Alice Moon on the importance of short form video this year for cannabis companies
https://www.linkedin.com/pulse/elevate-your-video-content-2023-alice-moon
I'm seeing more & more interest for this from my clients. 2023 is the year of short form video. Reach out to me if you want this for your brand.
Bloomberg on how celebrity star power often didn't help cannabis companies
https://www.bloomberg.com/news/newsletters/2023-01-30/celebrities-impact-on-cannabis-has-been-limited
Curaleaf exits CA, OR & CO
https://cannabislaw.report/curaleaf-heads-for-exit-in-california-oregon-and-colorado-cuts-workforce-by-4
Akerna exits cannabis & pivots to crypto
https://cannabislaw.report/akerna-exits-cannabis-moves-into-crypto
What is this? 2019?
On supply chain technology helping the growth of the cannabis industry
The Role of Supply Chain Technology in the Growth of the Cannabis Industry
https://www.igi-global.com/chapter/the-role-of-supply-chain-technology-in-the-growth-of-the-cannabis-industry/317047
The Plant & the History
A review of extraction techniques for cannabis compounds
Extraction techniques for bioactive compounds of cannabis
https://pubmed.ncbi.nlm.nih.gov/36625451/
Recommended for You
A study of the effects of key fertilizer elements on the cannabinoid content of industrial hemp
Effects of Different N, P, and K Rates on the Growth and Cannabinoid Content of Industrial Hemp
https://www.tandfonline.com/doi/full/10.1080/15440478.2022.2159605
On the cannabinoid content variability of individual outdoor grown plants
Individual variability of the cannabinoids' content in outdoor cultivated Bubba Kush x OG Kush Cannabis strain
http://bulletin.mfd.org.mk/volumes/Volume%2068_3/68_3_275.pdf
In stored cannabis, the conversion of THCA to THC & what this means for stability
THCA → THC conversion and its importance for the stability and quality of the herbal material
http://bulletin.mfd.org.mk/volumes/Volume%2068_4/68_4_049.pdf
A molecular marker for identifying hemp plants likely to produce THC contents above the legal limit
The B1080/B1192 molecular marker identifies hemp plants with functional THCA synthase and total THC content above legal limit
https://pubmed.ncbi.nlm.nih.gov/36641078/
Sequencing the transcription factors of male cannabis plants
Single-Molecule Real-Time Sequencing of Full-Length Transcriptome and Identification of Genes Related to Male Development in Cannabis sativa
https://pubmed.ncbi.nlm.nih.gov/36559671/
Industrial Uses
2 new studies on the energy efficiency of hempcrete insulation
Lime Hemp Concrete with Unfired Binders vs. Conventional Building Materials: A Comparative Assessment of Energy Requirements and CO2 Emissions
https://www.mdpi.com/1996-1073/16/2/708
Energy Efficient Building Design: Timber Frame Construction Based In Hemp Fiber Insulation
https://ideas.repec.org/a/zib/zbngwk/v6y2022i1p31-33.html
Our Professional Construction Knowledge Skeptic Ned Pelger summarizes, “More academic masturbation. Let's study how much energy it takes to make a product that will never be used in a serious way but that sounds good in the new green washed economy. 😂.”
CANNABINOID SCIENCE
An analysis of Canadian cannabis companies sponsoring cannabis scientific research
Cannabis companies and the sponsorship of scientific research: A cross-sectional Canadian case study
https://pubmed.ncbi.nlm.nih.gov/36626363/
Clinical Studies & Surveys
In healthy adults, 300 mg of isolated CBD caused no performance impairments in various cognitive & psychomotor functions but might affect certain aspects of vigilance
The effects of cannabidiol on subjective states, cognition, and psychomotor function in healthy adults: A randomized clinical trial
https://pubmed.ncbi.nlm.nih.gov/36625844/
Mental Health & Addiction
In Swedish 9th graders, a look at the complexity between ADHD & cannabis use
Exploring the Link between ADHD and Cannabis Use in Swedish Ninth Graders: The Role of Conduct Problems and Sensation-Seeking
https://pubmed.ncbi.nlm.nih.gov/36617861/
“There was a notable association between ADHD and cannabis use that was attenuated when conduct problems were controlled for. The association between cannabis use and conduct problems, in turn, was attenuated when sensation-seeking was controlled for. Individuals with both ADHD and conduct problems were more likely to have used cannabis than individuals with ADHD only, but not compared with individuals with conduct problems only. Conclusions: Whereas conduct problems largely explain the link between ADHD and cannabis use, sensation-seeking seems to account for the association between conduct problems and cannabis use.”
In a mouse model of depression, inhibiting the FAAH enzyme helped reverse depression caused by early life stress
FAAH Inhibition Restores Early Life Stress-Induced Alterations in PFC microRNAs Associated with Depressive-Like Behavior in Male and Female Rats
https://pubmed.ncbi.nlm.nih.gov/36555739
In rats taking oxycodone, oxytocin helped to lessen their memory deficits via inhibition of the endocannabinoid system
Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone-treated rats
https://pubmed.ncbi.nlm.nih.gov/36577736/
The Brain & its Diseases
A review of using CBD against fragile X syndrome (a genetic developmental disorder that causes intellectual disability)
Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment
https://pubmed.ncbi.nlm.nih.gov/36624400/
A review of using CBD against seizures
Advances and Challenges of Cannabidiol as an Anti-Seizure Strategy: Preclinical Evidence
https://pubmed.ncbi.nlm.nih.gov/36555823/
In a mouse model of epilepsy, CBD helped lower seizures, lessen inflammation & reduce neuropathic pain
EVALUATION OF THERAPEUTIC POTENTIAL OF CANNABIDIOLBASED PRODUCTS IN ANIMAL MODELS OF EPILEPTIC SEIZURES, NEUROPATHIC PAIN AND CHRONIC INFLAMMATION
https://farmaciajournal.com/wp-content/uploads/art-24-Blebea_Mihai_Negres_1185-1193.pdf
In a rat model of Parkinson's disease, the CB1 receptor was found to form dimer complexes (joined receptors) with the angiotensin AT2 receptor (an important cardiovascular hormone & a regulator of cell death)
The cannabinoid CB1 receptor interacts with the angiotensin AT2 receptor. Overexpression of AT2-CB1 receptor heteromers in the striatum of 6-hydroxydopamine hemilesioned rats
https://pubmed.ncbi.nlm.nih.gov/36632949/
In a model of traumatic brain injury, enhancing the endocannabinoid signaling of 2-AG promotes recovery of the astrocytes (important support cells of the neurons)
Enhancing endocannabinoid signalling in astrocytes promotes recovery from traumatic brain injury
https://pubmed.ncbi.nlm.nih.gov/35136958/
Harms, Cannabis Use Disorder & Street Synthetics
In California, a significant increase in older adults going to the emergency room because of cannabis
Trends in emergency department visits associated with cannabis use among older adults in California, 2005-2019
https://pubmed.ncbi.nlm.nih.gov/36622838/
One trick for an elderly person who is way too high: vaping large amounts of CBD. It's often referred to as the ripcord.
On the ability of cannabis to increase the aging process, this review looks at the epigenetics (the turning on & off of genes)
Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis
https://pubmed.ncbi.nlm.nih.gov/36554603/
On screening cannabis extracts for mitochondrial safety using a toxicity test
Screening System of Cannabis&nbsp;sativa Extracts Based on Their Mitochondrial Safety Profile Using Cytochrome c Oxidase Activity as a Biomarker
https://pubmed.ncbi.nlm.nih.gov/36674832/
Characterizing the synthetic cannabinoid 5F-3,5-AB-PFUPPYCA & its chemical cousins
In vitro characterization of the pyrazole-carrying synthetic cannabinoid receptor agonist 5F-3,5-AB-PFUPPYCA and its structural analogs
https://pubmed.ncbi.nlm.nih.gov/36640535/
Evaluating the safety of synthetic cannabinoid MAM2201 using human astrocytes (specialized immune cells that support the neurons)
Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS
https://www.mdpi.com/1422-0067/24/2/1421
Hormones, Reproduction & Maternal Effects
A demographic study associating cannabis use disorder with pregnancy problems
Demographic trends associated with substance use disorder and risk for adverse obstetric outcomes with cannabis and opioid use disorders
https://pubmed.ncbi.nlm.nih.gov/36617462/
“Cannabis use disorder was associated with increased adjusted risk for preterm delivery … and abruption and antepartum hemorrhage”
Pain, Inflammation & Surgeries
In a mouse model of neuropathic pain, the levels of 2-AG in various parts of the brain indicate that it might be involved in pain control
Expression and Kinetics of Endogenous Cannabinoids in the Brain and Spinal Cord of a Spare Nerve Injury (SNI) Model of Neuropathic Pain
https://pubmed.ncbi.nlm.nih.gov/36552893/
The antioxidant effects of four cannabis cultivars
Evaluation of the antioxidant capacity of four Cannabis Cultivars
http://bulletin.mfd.org.mk/volumes/Volume%2068_3/68_3_282.pdf
The Immune System, Autoimmune Disorders & Pathogens
In patients with hepatitis C, they had increased levels of endocannabinoids as well as related fatty acids & enzymes
Hepatitis C Virus Infection Upregulates Plasma Phosphosphingolipids and Endocannabinoids and Downregulates Lysophosphoinositols
https://www.mdpi.com/1422-0067/24/2/1407
In patients with HIV, cannabis use was not associated with any differences in their ratio of immune CD4/CD8 T cells
Tobacco, alcohol, cannabis, and illicit drug use and their association with CD4/CD8 cell count ratio in people with controlled HIV: a cross-sectional study (ANRS CO3 AQUIVIH-NA-QuAliV)
https://pubmed.ncbi.nlm.nih.gov/36624391/
In a mouse model of pneumonia, activating the CB2 receptor reduced systemic inflammation, the release of inflammatory cytokines & lessened the impairment of circulation in the intestines
Selective CB2 Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury
https://pubmed.ncbi.nlm.nih.gov/36555499/
Guts, Metabolics, Microbiome & Oral Health
A review of using cannabis & cannabinoids for chronic mouth & facial pain
Cannabis and cannabinoid medications for the treatment of chronic orofacial pain: A scoping review
https://www.sciencedirect.com/science/article/pii/S2772559623000019
In a mouse model of colitis, the terpene β-caryophyllene reduced inflammation via inhibition of ferroptosis (a type of cell death triggered by iron)
β-Caryophyllene Acts as a Ferroptosis Inhibitor to Ameliorate Experimental Colitis
https://pubmed.ncbi.nlm.nih.gov/36555694/
Musculoskeletal
In mice, manipulation of the CB1 receptor reveals its importance in the proper functioning of your skeletal muscles
Genetic Manipulation of CB1 Cannabinoid Receptors Reveals a Role in Maintaining Proper Skeletal Muscle Morphology and Function in Mice
https://pubmed.ncbi.nlm.nih.gov/36555292/
In older mice, blocking the CB1 receptor lowered obesity & partially restored skeletal muscle function
Inhibition of the endocannabinoid system reverses obese phenotype in aged mice and partly restores skeletal muscle function
https://pubmed.ncbi.nlm.nih.gov/36629822/
The Skin
Using hemp fiber to create a hydrogel for dressing wounds
A Novel Composite of Hemp Fiber and Alginate Hydrogel for Wound Dressings
https://link.springer.com/article/10.1007/s10924-023-02756-7
The Liver
In liver cells, CBD & its chemical cousin 7-OH-CBD inhibit the metabolism of nicotine
Inhibition of Nicotine Metabolism by Cannabidiol (CBD) and 7-Hydroxycannabidiol (7-OH-CBD)
https://pubmed.ncbi.nlm.nih.gov/36626330/
The Eyes
CBD nano topicals applied to the eyes of rabbits lowered intraocular pressure
Cannabidiol Loaded Topical Ophthalmic Nanoemulsion Lowers Intraocular Pressure in Normotensive Dutch-Belted Rabbits
https://pubmed.ncbi.nlm.nih.gov/36559077/
Cancer & Chemo
In breast cancer, how cannabinoids may benefit treatment resistant patients or interfere with their therapy
Heterogeneity in hormone-dependent breast cancer and therapy: Steroid hormones, HER2, melanoma antigens, and cannabinoid receptors
https://www.sciencedirect.com/science/article/pii/S2667394022000600
In health care providers for cancer pain, a minority preferred cannabis over opioids while others found it useful to combine cannabinoids & opioids together
Comparison of Health Care Providers Attitudes and Beliefs Regarding Medical Marijuana and Cannabidiol in the Management of Pain and Other Symptoms in Cancer Patients
https://pubmed.ncbi.nlm.nih.gov/36576904/
On using CBD against mouth cancer cells
Real-Time Monitoring of the Cytotoxic and Antimetastatic Properties of Cannabidiol in Human Oral Squamous Cell Carcinoma Cells Using Electric Cell-Substrate Impedance Sensing
https://pubmed.ncbi.nlm.nih.gov/36555480/
On combining CBD & NSAIDs (such as ibuprofen) against cancer cells of the vulva
Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma
https://pubmed.ncbi.nlm.nih.gov/36557911/
Testing the antitumor effects of various CBDA-type compounds
Investigating the in vitro Antitumor Structure-activity Relationship of a Range of Cannabinolic Acid Derivatives
https://journals.bilpubgroup.com/index.php/jor/article/view/5115
Cool Chemistry
On trying to design a drug that inhibits FAAH, softly
Molecular Basis for Non-Covalent, Non-Competitive FAAH Inhibition
https://pubmed.ncbi.nlm.nih.gov/36555144/
Thanks.
- lex
PS: For today’s soulful Italian ballads, the eponymous album ‘Luigi Tenco’. A tragic figure of Italian pop, Tenco was mocked in his lifetime & then revered as an icon of tragic love after his death at the age of 28.
The Living Glossary of Cannabinoid Terms
This is a running glossary of the basic cannabinoid terms. It will also function as the legend for the ‘neural ocean’ metaphor that I’m using in my graphic novel series on the endocannabinoid system based on Moby-Dick. You can watch a lecture laying out the full idea here - but the basics are that we treat the human brain like the ocean: deep, mysterious & chockablock with fish, molecules & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land?) and neurons are complex underwater cities where hundreds of fish interact.
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]
2-AG
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
[blue whale]
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]
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]
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]
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…]
NAAA (N-acylethanolamine acid amidase)
The enzyme for breaking down PEA, with a special function as a messenger for pain & inflammation as well as in the control of obesity.
[a giant Giant Pacific octopus that eats Right whales]
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). 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.
[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]
CBG (cannabigerol)
Known as the “mother cannabinoid”, CBG is the chemical precursor to THC, CBD, and the other cannabinoids in the plant. CBG occurs only at low levels in cannabis because it tends to be quickly converted to other cannabinoids. Binding slightly to the CB1 and CB2 receptor, it also inhibits the enzymes that break down anandamide and 2-AG, hence raising the levels of those endocannabinoids. CBG interacts with an adrenaline receptor (α-2 adrenoceptor) & a serotonin receptor (5-HT1A Receptor) as well as modulating the expression of glutamate, GABA, and dopamine via the PPAR receptors on the nucleus, controllers of genetic transcription. CBG is also active at the TRP channels involved in the sensations of temperature, pressure, pH, smell, taste, vision, and pain perception whose dysfunction are linked to neuropathic pain, inflammation, and respiratory disorders.
Surveys show patients reporting help for anxiety, chronic pain, depression, and disturbed sleep. In preclinical trials, it's been studied for eye pressure, gut problems, appetite modulation, blood pressure lowering, bladder control, oral care, muscle spasms, airway inflammation, arthritis, painkilling, and most notably for brain health and neuroinflammation. In adult neural stem cells, CBG increased their viability. The breakdown products of CBG have been shown to reduce inflammation via the brain’s immune cells.
[since it’s the first cannabinoid produced, it must be the wooly mammoth]
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]
(Easter egg: the first person to email me about this easter egg will get a free copy of my Queer book once I get it printed & up on Amazon soon…)
Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]
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.
