C&P#47: RIP Dr. Mechoulam + cannabis for pain, sleep & fixing your mouth
C&P#47: RIP Dr. Mechoulam + cannabis for pain, sleep & fixing your mouth
OK says No + censorship in Czech + cannabis scene in Thailand
Hello everyone,
This week, I migrated my ‘Living Glossary of Cannabinoid Terms’ from the bottom of this email to its own page here. Hopefully this will make it easier for you to peruse. I’ll continue to update this glossary with more references as I get the chance. The CBG entry is particularly depthful at the moment.
And as always, support this newsletter by buying our Queer cannabis history graphic novel.
Welcome to the 47th 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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On Cannabinoids, Lung Health & Asthma
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And as always, here’s the Living Glossary of Cannabinoid Terms & at the bottom is the album of the week.
This week…
More drug interaction studies (a warning for warfarin)
Reviews of cannabis for pain, sleep & oral health
Topical CBD for mouth ulcers
Lots of stress destroying your heart? Got a long QT? Activate your CB2 receptor!
On the negative front, cannabis linked to worse short-term memory in older people & heavy cannabis users show worse neural activity for complex motor tasks
Injecting CBD nanoparticles for pain
For growers & researchers, Dewey Scientific makes a gift of an excellent how-to guide on clonal propagation
On using hemp to clean soil of distillery sludge & utilizing hemp waste as food for useful insects like mealworms
The Global Drug Survey yields clues about what helps when treating yourself with psychedelics
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Best Of Cannabinoid Science...
Clinical
In chronic pain patients with & without anxiety, those with anxiety reported more benefits from cannabis for their overall quality of life
Comparing the effects of medical cannabis for chronic pain patients with and without co-morbid anxiety: A cohort study
https://pubmed.ncbi.nlm.nih.gov/36803620/
In patients with recurrent mouth ulcers, a topical 0.1% CBD cream reduced the ulcer size, accelerated the ulcer healing & exerted anti-inflammatory & painkilling effects
Efficacy and safety of topical 0.1% cannabidiol for managing recurrent aphthous ulcers: a randomized controlled trial
https://pubmed.ncbi.nlm.nih.gov/36803360/
In older adults, those using cannabis had more complaints about their subjective memory
The association between cannabis use and subjective memory complaints in older adults in the United States
https://pubmed.ncbi.nlm.nih.gov/36803905/
This absolutely lines up with the data. It’s not one of the bright sides of cannabis use – but the ability of cannabis to dampen the memory of the movie you watch stoned probably also alters your memory in the long term.
Heavy cannabis users show neural signs of impaired execution of complex motor tasks
Functional correlates of neurological soft signs in heavy cannabis users
https://pubmed.ncbi.nlm.nih.gov/36825488/
For COVID-19 patients, the reason glucocorticoid therapy may help with inflammation & disease course is because of its effects on the endocannabinoids
The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19
https://pubmed.ncbi.nlm.nih.gov/36851787/
A review of how the cannabinoids might alter the CYP450 enzymes in the liver & change how other drugs are metabolized
Contemplating cannabis? The complex relationship between cannabinoids and hepatic metabolism resulting in the potential for drug-drug interactions
https://pubmed.ncbi.nlm.nih.gov/36704740/
And a clinical trial of oral cannabis extracts rich in THC & CBD as well as a CYP cocktail finds that CBD enhances the negative effects of THC
Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial
https://pubmed.ncbi.nlm.nih.gov/36780161/
And a study of how the cannabinoids interact with two liver enzymes (CYP3A4 & CYP2C9) that metabolize the coumarin-type anticoagulants like warfarin
Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants
https://pubmed.ncbi.nlm.nih.gov/36814687/
CBD & CBG interacted with these the strongest – and if there’s any drug where CBD might force you to change your prescription level, it’s warfarin.
But as a doctor I worked with said, ‘everything screws with warfarin. It’s such a delicate drug for interactions.”
In general, I’ve heard a few doctors say that if you’re taking less than 100 mg of CBD, they’re not worried about it.
That being said, I have all the data on the liver enzymes & drug interactions in my files. It’s probably time to clean them up & get them up on my site for doctors & patients to use.
When your cannabis has microorganisms, heating in a vape doesn’t make a significant reduction in their levels
Investigation of microorganisms in cannabis after heating in a commercial vaporizer
https://pubmed.ncbi.nlm.nih.gov/36710966/
The main reason we need testing is for microbials & contaminants. For immunocompromised patients, these microbials can cause serious problems. And the vaping isn’t enough to kill those bugs.
A review of public health studies finds that legalized cannabis “is correlated with altered cannabis consumption in adults, potentially increased criminal activity, and a decline in opioid quantities and prescriptions provided to patients”
The clouded debate: A systematic review of comparative longitudinal studies examining the impact of recreational cannabis legalization on key public health outcomes
https://pubmed.ncbi.nlm.nih.gov/36713920/
Reviews
For sleep, a review of CBD & THC for insomnia, sleep apnea & restless leg syndrome
CBD and THC - influence on insomnia, sleep apnea and restless leg syndrome - review based on recent advances
https://apcz.umk.pl/JEHS/article/view/42155
For the double-edged advice on sleep & insomnia, see my How-To Guide here.
A review of pain patients looks at the benefits of cannabis
A Retrospective Medical Record Review of Adults with Non-Cancer Diagnoses Prescribed Medicinal Cannabis
https://pubmed.ncbi.nlm.nih.gov/36836018/
“For the conditions, neuropathic pain/peripheral neuropathy had the highest rate of perceived benefit (66.6%), followed by Parkinson's disease (60.9%), multiple sclerosis (60.0%), migraine (43.8%), chronic pain syndrome (42.1%), and spondylosis (40.0%). For the indications, medicinal cannabis had the greatest perceived effect on sleep (80.0%), followed by pain (51.5%), and muscle spasm (50%). Oral oil preparations of balanced delta-9-tetrahydrocannabinol/cannabidiol (average post-titration dose of 16.9 mg and 34.8 mg per day, respectively) were mainly prescribed. Somnolence was the most frequently reported side effect (21%).”
A review of 107 papers on oral health finds that activating the cannabinoid receptors can help with inflammation, bone healing & the treatment of periodontitis (a serious gum infection)
Activation of cannabinoid receptors promotes periodontal healing by regulating periodontal inflammation and bone remodeling
https://www.cjter.com/EN/10.12307/2023.530
A review of the crosstalk between the estrogen system & the endocannabinoid system as seen through the rodent estrus cycle
Molecular and cellular mechanisms underlying brain region-specific endocannabinoid system modulation by estradiol across the rodent estrus cycle
https://pubmed.ncbi.nlm.nih.gov/36707154/
Preclinical
Cool new delivery system: injecting CBD nanoparticles for pain
Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain
https://pubmed.ncbi.nlm.nih.gov/36813014/
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
Dr. Raphael Mechoulam – mensch & ‘father of the endocannabinoid system’ – passes away at 92
https://cannabis-med.org/bulletin/iacm-bulletin-of-12-march-2023
I have an unpublished interview with him from 9 years ago in case any magazines out there are looking to publish more on the passing of this great scientist. I will never forget that as a young unknown drug writer, Dr. Mechoulam kindly took almost two hours to talk to me when I went to visit him in Jerusalem. If that’s not the sign of a good soul, I don’t know what it is.
Rest in Peace Doctor. Thank you for your Work.
Oklahoma said no to legal cannabis in a big way
https://www.marijuanamoment.net/oklahoma-voters-reject-marijuana-legalization-ballot-initiative
A US Bankruptcy Court rules that cannabis business employees are not protected by federal bankruptcy laws
https://businesswest.com/blog/cannabis-employee-not-entitled-to-federal-bankruptcy
What a crock.
Czech Republic journalist Robert Veverka convicted of publishing a cannabis magazine & ‘inciting the abuse of addictive substances’
https://cannabishealthnews.co.uk/2023/03/03/czech-republic-journalist-convicted-publishing-cannabis-magazine
Intrepid reporter Michelle Lhooq reports on the cannabis scene in Thailand
A tribute to Git Skoglund – a historian of hemp fiber – by Melinda Misuraca
https://www.projectcbd.org/ode-vanishing-handcraft
You can check out Skoglund’s book ‘Cannabis Textiles: In Hemp Garden Cultures’.
Library of Congress publishes a report on hemp laws around the world
https://www.marijuanamoment.net/u-s-library-of-congress-compares-hemp-rules-in-countries-around-the-world-in-new-report
I want to highlight the cannabis business newsletter ‘Money Puff’ by Liam Kelly, based on my beloved business newsletter ‘Money Stuff’ by Matt Levine
This week, Liam focuses on the intriguing ‘caregiver’ aspect of Main’s cannabis laws.
The War on Drugs & Prohibition
What a lede: “Officials at the [DEA] and State Department have known for more than three years that some pharmacies in Mexico are selling counterfeit medications laced with illicit fentanyl — and that American tourists are overdosing and dying from them” – but they didn’t tell anyone
https://www.latimes.com/world-nation/story/2023-03-11/feds-have-known-for-years-fentanyl-tainted-pills-from-mexican-pharmacies-are-killing-americans
Fuck the DEA. And if you need more insight on why we should all be saying ‘Fuck the DEA’, read Valentine’s ‘Strength of the Pack’ about one of the most corrupt & debasing organizations in US politics.
These researchers say that they think THC cutoff levels in blood & saliva can be used to detect impaired driving (which goes against what most researchers say)
The Utility of THC Cutoff Levels in Blood and Saliva for Detection of Impaired Driving
https://pubmed.ncbi.nlm.nih.gov/36730769/
Psychedelics, Plant Medicines & Other Psychoactives
‘The DEA is Playing God with Psychedelic Churches’: they decide on whether a church is legit, although they don’t have that power
https://doubleblindmag.com/soul-quest
Poetry from Dr. Andrew Gallimore on Dr. Dave Nichol’s chemical creation of bromo-DragonFLY – the most potent psychedelic
A deep dive on iboga in National Geographic by Rachel Nuwer
https://www.nationalgeographic.com/animals/article/ibogaine-pschedelic-drug-root-fair-trade-gabon
A post-mortem on the implosion of Synthesis Institute (a psychedelic guide training program)
https://psychedelicalpha.com/news/inside-synthesis-institutes-implosion
Psychoactive science
[This isn’t a deep dive into all of the science of psychedelics & other psychoactives like I do for the cannabinoids. If a newsletter with all that new science would be of interest to your company or organization, reach out to me]
According to the Global Drug Survey, people who treated themselves with LSD or psilocybin mushrooms saw positive effects on a range of factors of well-being, though 22% reported negative effects
Investigation of self-treatment with lysergic acid diethylamide and psilocybin mushrooms: Findings from the Global Drug Survey 2020
https://pubmed.ncbi.nlm.nih.gov/36876583/
“High intensity of psychedelic experience, seeking advice before treatment, treating with psilocybin mushrooms and treating post-traumatic stress disorder were associated with higher scores on the self-treatment outcome scale after averaging values across all 17 items. Younger age, high intensity of experience and treating with LSD were associated with increased number of negative outcomes.”
A review of 44 studies finds a link between mystical experiences caused by psychedelics & improvements in well-being & mental health
Association between mystical-type experiences under psychedelics and improvements in well-being or mental health – A comprehensive review of the evidence
https://akjournals.com/view/journals/2054/aop/article-10.1556-2054.2023.00243/article-10.1556-2054.2023.00243.xml
A review of the preclinical ayahuasca research (32 studies)
The current state of ayahuasca research in animal models: A systematic review
https://pubmed.ncbi.nlm.nih.gov/36863501/
In a mouse model of depression (chronic restraint stress), a single dose of psilocybin improved their cognitive function
A Single Administration of Psilocybin Persistently Rescues Cognitive Deficits Caused by Adolescent Chronic Restraint Stress Without Long-Term Changes in Synaptic Protein Gene Expression in a Rat Experimental System with Translational Relevance to Depression
https://www.liebertpub.com/doi/full/10.1089/psymed.2022.0012
In a rat model of chronic unpredictable stress, ketamine prevented the symptoms of depression & altered neural activation in the lateral habenula (a learning center) & nucleus accumbens (an emotional & motivational processing center)
Chronic oral ketamine prevents anhedonia and alters neuronal activation in the lateral habenula and nucleus accumbens in rats under chronic unpredictable mild stress
https://pubmed.ncbi.nlm.nih.gov/36813161/
The Plant & the History
The methods for best measuring terpene levels
Standard operating procedures for the comprehensive and reliable analysis of cannabis terpenes
https://pubmed.ncbi.nlm.nih.gov/36710020/
Examining the 11 genes of histone acetyltransferase enzymes responsible for synthesizing cannabinoids
Identification of histone acetyltransferase genes responsible for cannabinoid synthesis in hemp
https://pubmed.ncbi.nlm.nih.gov/36782242
Growing & Farming
For growers, a ‘gift to the people’ paper laying out everything about clonal propagation (with videos, equipment lists & images)
Controlled environments for cannabis cultivation to support "omics" research studies and production
https://pubmed.ncbi.nlm.nih.gov/36710019/
The genome of a fungus that causes black root in cannabis
Hybrid Genome Assembly of Berkeleyomyces rouxiae, an Emerging Cannabis Fungal Pathogen Causing Black Root-Rot in an Aeroponic Facility
https://pubmed.ncbi.nlm.nih.gov/36774565/
Hemp as a food
On the gut/colon benefits of hemp bran
Beneficial metabolic transformations and prebiotic potential of hemp bran and its alcalase hydrolysate, after colonic fermentation in a gut model
https://pubmed.ncbi.nlm.nih.gov/36707683/
A review of the nutritional value of hemp seeds
Hemp seeds: Nutritional value, associated bioactivities and the potential food applications in the Colombian context
https://pubmed.ncbi.nlm.nih.gov/36712539/
Veterinarian Uses & Animal Feed
Using hemp waste to grow helpful insects
Hemp Waste as a Substrate for Hermetia illucens (L.) (Diptera: Stratiomyidae) and Tenebrio molitor L. (Coleoptera: Tenebrionidae) Rearing
https://pubmed.ncbi.nlm.nih.gov/36835752/
Industrial Uses
On cleaning the soil of distillery sludge, using a mix of bacteria & cannabis to remove the heavy metals & organic pollutants
Bacterial assisted phytoremediation of heavy metals and organic pollutants by Cannabis sativa as accumulator plants growing on distillery sludge for ecorestoration of polluted site
https://pubmed.ncbi.nlm.nih.gov/36708597/
CANNABINOID SCIENCE
Clinical Studies & Surveys
In adolescents with depression using cannabis, it only seemed to alter their depression symptoms & episodic memory when their depression symptoms aren’t strong
Cannabis use and episodic memory performance among adolescents: Moderating effects of depression symptoms and sex
https://pubmed.ncbi.nlm.nih.gov/36775907/
People smoking cannabis have higher level of furans (a toxicant & possible human carcinogen, found most often in tobacco smoke)
Furan Metabolites Are Elevated in Users of Various Tobacco Products and Cannabis
https://pubmed.ncbi.nlm.nih.gov/36716352/
Mental Health & Addiction
In a mouse model of prolonged stress causing depressed behavior, a look at the complexity of behavioral alterations resulting from how the cannabinoids interact with orexin (a hormone regulator of sleep & appetite)
Dual Cannabinoid and Orexin Regulation of Anhedonic Behaviour Caused by Prolonged Restraint Stress
https://pubmed.ncbi.nlm.nih.gov/36831860/
The Brain & its Diseases
In a mouse model of seizures, the researchers propose CBD lowers seizures by blocking the fatty acid LPI from the GPR55 receptor (which may one day be known as CB3)
Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity
https://pubmed.ncbi.nlm.nih.gov/36787750/
Harms, Cannabis Use Disorder & Street Synthetics
This review on the negatives of medical cannabis somehow only includes 8 studies
Negative experiences of patients using medicinal cannabis: A systematic review of qualitative studies
https://pubmed.ncbi.nlm.nih.gov/36807590/
This is odd because I have dozens of studies on harms filed away in my science archives. Cannabis is great, but it's not harmless.
In a survey of those with cannabis use disorders about potential treatments, they reported that “medications should focus on nonsynthetic compounds administered orally or by mouth spray no more than once per day to maximize patient acceptance”
Cannabis Use Disorder Treatment Preferences: A Pilot Survey in Current Users of Cannabis
https://pubmed.ncbi.nlm.nih.gov/36731101/
The Immune System & Pathogens
In humans with HIV, cannabis use associated with less adherence to their antiretroviral medicine
Cannabis Use Is Associated With Decreased Antiretroviral Therapy Adherence Among Older Adults With HIV
https://pubmed.ncbi.nlm.nih.gov/36726540/
Pain, Inflammation & Surgeries
A survey of patients going for hand surgery finds that the majority of them would be interested in using medical cannabis, though the biggest barrier is cost
Hand Surgery Patient Perspectives on Medical Cannabis: A Survey of Over 600 Patients
https://pubmed.ncbi.nlm.nih.gov/36704391/
A French review of cannabis for pain «”Doctor, I'm in pain, prescribe me some cannabis”»
Docteur, j’ai mal, prescrivez-moi du cannabis ». Possibilités et limites des cannabinoïdes dans le traitement de la douleur
https://pubmed.ncbi.nlm.nih.gov/36715394
The Genitourinary System
In people having a kidney clamp for surgery, they saw increased endocannabinoid levels in their kidneys, suggesting targeting the ECS for protection during times when the kidney is cut off from blood flow
Systemic Changes in Endocannabinoids and Endocannabinoid-like Molecules in Response to Partial Nephrectomy-Induced Ischemia in Humans
https://pubmed.ncbi.nlm.nih.gov/36835635/
The Eyes
In retinal cells of the eyes, PEA protected them from reactive oxygen species & cell death
Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal
https://pubmed.ncbi.nlm.nih.gov/36816211/
The Heart & the Blood
In a mouse model of chronic psychological unpredictable stress, an analysis of the genes being turned on suggests the CB2 receptor for protecting the heart from the stress
Transcriptome-wide analysis reveals the molecular mechanisms of cannabinoid type II receptor agonists in cardiac injury induced by chronic psychological stress
https://pubmed.ncbi.nlm.nih.gov/36704356/
In patients with long QT syndrome (an abnormal heart electrical signaling disorder), activating the cannabinoids seems to provide some protection
Endocannabinoids enhance hKV7.1/KCNE1 channel function and shorten the cardiac action potential and QT interval
https://pubmed.ncbi.nlm.nih.gov/36796231/
Cool Chemistry
On the Uncatalyzed Thermal Conversion of Cannabidiol to Delta-9-Tetrahydrocannabinol [can’t access the abstract – but curious]
https://pubmed.ncbi.nlm.nih.gov/36716192
An atomic analysis of anandamide
Theoretical NMR and IR spectroscopic analyses of the preferred conformers of the neurotransmitter anandamide
https://onlinelibrary.wiley.com/doi/abs/10.1002/qua.27098
On novel alkylindoles based on the famous old synthetic cannabinoid workhorse WIN55212-2
Design, synthesis, and evaluation of substituted alkylindoles that activate G protein-coupled receptors distinct from the cannabinoid CB1 and CB2 receptors
https://pubmed.ncbi.nlm.nih.gov/36708677/
A new type of CB2 activators from the depsidones (extracted from lichens, fungi, sponges & plants )
Structure-Based Virtual Screening and Molecular Dynamics Simulation Assessments of Depsidones as Possible Selective Cannabinoid Receptor Type 2 Agonists
https://pubmed.ncbi.nlm.nih.gov/36838749/
Thanks.
- lex
PS: For this week’s album, Robbie Basho’s ‘Venus In Cancer’. Immersing himself in the ragas of the East & the singing of the Sufis as well as naming himself after the great haiku poet Matsuo Bashō, Robbie Basho wanted to elevate the steel-string guitar to an instrument of the concert hall & to create a raga system for America. See this biography for more on his fascinating range of musical interests & styles.
PPS: When my wife heard the first album of this track, she quite kindly said that it sounded like my soul.
And so it inspires me to share my favorite haiku from Bashō in his work ‘The Narrow Road to the Deep North’…
hardly a hint
of their early death,
cicadas singing
in the trees.