C&P#36: the nose knows! + THC & CBD for Tourette’s & better sleep + a bounty of review articles
Marijuana Research Bill passes! Britney Griner comes home!
From now on, these newsletters will either come out on Monday or Tuesday. I’ve got two little kids, too little sleep & you will get a better product if I occasionally work through Monday night to add more science & jokes.
This week in WeedTalkNews…
my EU report on decrim in Ireland & Lithuania
· For choosing your strain of cannabis, science confirms: the nose knows!
· THC & CBD for Tourette’s as well as better sleep
· A very good week for review articles: the ECS & female reproduction, cannabinoids & cancer care, how the ECS guides the formation of our cardiac system, cannabis for treating metabolic disorders, two on the synthetic cannabinoids, CBD for chronic facial pain, how cannabis users need more anesthetic for surgery & using CBD to treat cannabis use disorder
· Some unexpected findings on COVID & cannabis
· Give cannabis seeds to your lambs & CBD to your cooking chickens
(but don’t waste your hemp on your Californian rabbits (and don’t even get me started on what it does to your cows))
· THC for stronger bones + CBDV for drug-resistant gonorrhea
· An important story from my high school years about joints vs joints
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Best Of Cannabinoid Science...
A clinical study confirms the old wisdom of “the nose knows”: cannabis that smells better to you also has more pleasant subjective effects
The Nose Knows: Aroma, but Not THC Mediates the Subjective Effects of Smoked and Vaporized Cannabis Flower
In a clinical sleep trial using 200 mg of CBD & 10 mg of THC, people got to sleep faster, spent less time in REM sleep (that’s why weed steals dreams) & did not impair next-day cognitive performance
Acute effects of combined cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) in insomnia disorder: A randomised, placebo-controlled trial using high-density EEG
In a survey of humans with Tourette’s syndrome, while THC & CBD did not help with tics, they did help to improve several other areas such as OCD, anxiety, employment status & general quality of life
Use of Medical Cannabis in Patients with Gilles de la Tourette's Syndrome in a Real-World Setting
“The tetrahydrocannabinol and cannabidiol mean daily dose was 123 and 50.5 mg, respectively. In group A, a statistically significant improvement was identified in quality of life (p<0.005), employment status (p=0.027), and in the reduction of the number of medications (p<0.005). Sixty-seven percent and 89% of patients with obsessive-compulsive disorder and anxiety comorbidities, respectively, reported an improvement. No statistically significant improvement was identified in motor tics (p=0.375), vocal tics (p>0.999), tics frequency (p=0.062), or general mood (p=0.129). The most frequent adverse effects were dizziness (n=4) and increased appetite (n=3).”
In a survey of chronic pain patients, the majority used dried cannabis & the majority said it decreased their prescription painkiller use. Gender differences were found in how the cannabinoids got into their system & how it altered their inflammatory cytokines
Medical Cannabis Use and Inflammatory Cytokines and Chemokines Among Adult Chronic Pain Patients
There’s a reason pain tops the list of every survey of why people use medical cannabis. Check out my advice on how you or your loved one might utilize CD & cannabis for chronic pain.
In this review, 31 studies on CBD for chronic facial pain & disorders of the jaw muscles & joints
CBD in orofacial pain and TMD - a literature review
In monkeys, cannabinoids work about as well as opioids for painkilling – and without the addiction
Functional consequences of short-term exposure to opioids versus cannabinoids in nonhuman primates
As always, I ask: why are we doing this to these poor monkeys when you wouldn’t even have to pay college students to participate?
A review of using CBD to treat cannabis use disorder
Cannabidiol pharmacotherapy for delta-9-tetrahidrocannabinol dependence
A new medical manual on the use of cannabis psychiatry (with some chilled-out introductions, including a Grateful Dead lyric)
Cannabis in Psychiatric Practice: A Practical Guide
For anxiety, a review of 58 studies on the use of THC & CBD found an inverted U-shaped dose relationship: as usual, a moderate amount is good & a lot is not helpful
Cannabinoid treatments for anxiety: A systematic review and consideration of the impact of sleep disturbance
2021: In fibromyalgia, this review looks at how cannabis can help with pain, sleep & quality of life
Efficacy of cannabinoids in fibromyalgia: a literature review
2021: In results from a national survey of older cannabis users, they had lower chances of utilizing mental health treatments
Mental health treatment use among cannabis users aged 50+: Associations with cannabis use characteristics
Surprising preliminary findings about cannabis use during the COVID pandemic:
Cannabis use, abuse and dependence during the COVID-19 pandemic: a scoping review
· cannabis use did not impact mild COVID-19 symptoms
· people using cannabis had more COVID-19-related hospitalizations
· veterans using cannabis had reduced SARS-COV-2 infection rates
· frequent cannabis use was significantly associated with increased death from COVID-19
· people with a dependence on cannabis had a greater chance of a breakthrough COVID-19 infection after vaccination
The last point makes sense. In general, cannabis dampens your immune response (that’s why it’s so good for autoimmune conditions) but that can also mean that it creates a blunted reaction to vaccines & they don’t work as well for producing antibodies. As for the rest of the sometimes contradictory findings, all you can say is that the immune system is complicated. In fact, there’s a classic immunologist joke about that:
Three doctors are walking through the desert & find a lamp. When they rub it, a genie appears & says he will kill two of them but spare the life of the one who has saved the most lives. The oncologist begins & says how he has saved thousands of people from death by cancer. Then the heart surgeon pipes up to say that he invented a new surgical technique that has saved the lives of tens of thousands. Then the immunologist pauses for a moment and says, “Well, it’s complicated…”
And the surgeon groans & says, “Just kill me now.”
A nice review of the endocannabinoid system with good charts
Endocannabinoid System: Chemical Characteristics and Biological Activity
In mice, 7 days of LSD increased their sociability, caused lower levels of endocannabinoids in the hippocampus (memory area) & had some effects on the gut microbiome - plus an increased intake of classic Grateful Dead concerts
Effects of Repeated Lysergic Acid Diethylamide (LSD) on the Mouse Brain Endocannabinoidome and Gut Microbiome
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
Biden signs the Marijuana Research Bill – the first cannabis reform ever sent to a US President’s desk
And he engineered a deal where Britney Griner is coming home in exchange for a Russian arms dealer
It’s great to see her coming home – but lawmakers & advocates are justly pushing for more help for other cannabis prisoners abroad as well as abolishing the racist War on Cannabis at home & freeing those prisoners.
Big business move: ATM providers move to shut down the loophole that allowed cannabis shops to use “cashless” ATMs to pay for product
On top of that, there was a chance that the SAFE Banking Act was going to be slipped into the new defense bill – but opposition by McConnel & his ilk prevented it from happening.
So we’re stuck with a cash-based business with the number of dispensary robberies growing across the country. If I didn’t study history a good bit, I’d think this was a particularly stupid age. But it’s just that I have a front seat for it.
Nice writeup about Chris Alexander: the head of NY’s cannabis regulation & the person trying to pioneer a new way of doing diversity & making up for the harms of the War on Drugs
Disclosure: I’ve known Chris since his days at the Drug Policy Alliance & have been a big fan of what he’s been up to.
According to the New York Medical Cannabis Industry Association, about 40% of cannabis products they tested from 20 illicit stores in NYC contained E. coli, lead or salmonella
In New Jersey, regulatory approval of proposed rules for public marijuana consumption areas
This is such an important topic that gets forgotten. You can buy weed – but you can’t smoke it anywhere but your home. And if your housing is federally subsidized, you’re just one pissy neighbor’s call away from losing your home. Public consumption lounges are a public health measure, important for the social aspects of cannabis & most importantly, the right thing to do.
On the weed-friendly wedding scene
In three years, they will run the exact same article except replacing the word ‘weed’ with ‘magic mushrooms’.
Politico with a breakdown of cannabis laws across Europe
As a resident of France, I’m obliged to detest the ruler in power because… that’s what we do. In my case, I chose to detest Macron for his opposition to legalized cannabis.
(Other than that, I don’t actually mind the guy – but don’t tell my in-laws).
In the UK, 99% of patients using medicinal cannabis are sourcing it illegally due to failures within the industry
This is so damn heartbreaking.
Legendary grower Jorge Cervantes started a newsletter on LinkedIn & is offering a free downloadable copy of his cannabis growing book
First place winner of Puffco’s bong awards is stunning
The War on Drugs & Prohibition
The legalization of cannabis in Colorado & Washington was not linked to increased crime
Crime in a Time of Cannabis: Estimating the Effect of Legalizing Marijuana on Crime Rates in Colorado and Washington Using the Synthetic Control Method
For driving, medical users tended to be more responsible about their use before driving but while poly-substance users did less driving while high, they seem to have an increased risk
Contemporary drug use and driving patterns: A qualitative approach to understanding drug-driving perceptions from the context of user patterns
🍿 A Brooklyn prosecutor confesses to being in a nationwide cannabis smuggling ring while still trying cases for the DA’s office 🍿
Nothing like brand-new industries flush with cash to breed corruption.
Psychedelics, Plant Medicines & Other Psychoactives
[This isn’t a deep dive into all of the science of psychedelics like I do for the cannabinoids. If a weekly newsletter with all the new psychedelic science would be of interest to your organization, reach out to me]
David Bronner with a prayer/essay on cooperation in the psychedelic movement
MAPS found partially liable in wrongful death lawsuit related to their Zendo Project harm reduction space
A thread on underrated research chemicals
Shoutout to MXE
Canadian company Filament Health said they created medical-grade ayahuasca
A study found psychedelic use associated with less tobacco use, a healthier diet, more exercise & a healthier body-mass index
Classic psychedelics, health behavior, and physical health
In interviews of humans using ibogaine for substance use disorder, they reported benefits from the autobiographical memories & personal insights
Underground ibogaine use for the treatment of substance use disorders: A qualitative analysis of subjective experiences
This lines up with everything you hear. It’s quite helpful that ibogaine usually allows someone to skip the physical withdrawal period completely - but it’s the memories of family & the revelations of purpose that facilitate not returning to their problematic drug use.
A review of the neglected use of low doses of psychedelics in therapy
Lower-dose psycholytic therapy – A neglected approach
In a rat model of Fragile X Syndrome (a genetic developmental disorder that causes intellectual disability), oral psilocybin helped to improve their cognitive deficits
Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome
Business & Law
A panel of experts on what happened on cannabis policy in 2022 & predictions for the year ahead
Euroclear, one of the EU’s 2 major stock clearing houses, is no longer supporting cannabis stocks
On California’s industry-friendly regulations & how that isn’t good for public health
California Cannabis Markets-Why Industry-Friendly Regulation Is Not Good Public Health
How funny. Just last week saw an almost identical article calling for a cannabis tax to pay for mental health services
Earmarking Excise Taxes on Recreational Cannabis for Investments in Mental Health: An Underused Financing Strategy
Molson Coors pulls out of a joint venture with Hexo to make CBD-infused water
Curaleaf lays off ~220 employees
The Plant & the History
The UN releases a report on hemp as an industrial commodity
The USDA wants to create a public hemp germplasm collection to safeguard the genetics of our favorite old plant for the Southern US
2021: Another study on how indica & sativa are not good labels for the different types of cannabis out there
Widely assumed phenotypic associations in Cannabis sativa lack a shared genetic basis
How to best space hemp plants for the highest fiber & seed production
Optimizing plant density for fiber and seed production in industrial hemp (Cannabis sativa L.)
A nice review of the prominent cannabis terpene linalool (which gives the scent to lavender)
Linalool: A ubiquitous floral volatile mediating the communication between plants and insects
2021: How the nitrogen supply in cannabis alters its cannabinoid & terpenoid profile
Nitrogen supply affects cannabinoid and terpenoid profile in medical cannabis (Cannabis sativa L.)
A comparison of the different drying techniques for hemp: infrared, microwave, hot air
Impacts of industrial microwave and infrared drying approaches on hemp (Cannabis sativa L.) quality and chemical components
2021: In female cannabis plants, getting fertilized significantly decreased the cannabinoids & decreased most of the terpenoids looked at
Fertilization Following Pollination Predominantly Decreases Phytocannabinoids Accumulation and Alters the Accumulation of Terpenoids in Cannabis Inflorescences
A genetic study of auto-flowering genes
Identification and mapping of major-effect flowering time loci Autoflower1 and Early1 in Cannabis sativa L
And a look at the genes involved in creating the hemp embryos that become seeds
Expression of Genes Involved in ABA and Auxin Metabolism and LEA Gene during Embryogenesis in Hemp
The insidious corn pest, the Western bean cutworm, readily feeds on hemp as well
Western bean cutworm (Lepidoptera: Noctuidae) feeding and development on industrial hemp in the labor elopment on industrial hemp in the laboratory and field
Any story in biology can become a Godzilla movie if you zoom in close enough.
If your cooking chickens get sick, CBD will help their breast meat to not spoil
Cannabidiol affects breast meat volatile compounds in chickens subjected to different infection models
If you have lambs, give them cannabis seeds
The Effect Of Dietary Nano-Selenium And Cannabis Seeds On Liver Tissues And Functions In Male Karadi Lambs
“Whole cannabis seeds in powdered form have a remarkable impact on liver tissue protection, decreasing lipid profile, increasing protein metabolism by increasing total protein and albumin and boosting the immune system via alteration of globulin.”
When giving hempseed cake to your cows, they get more microbial diversity in their stomach, less microbial richness in their vagina & more microbial diversity & richness in their uterus
Feeding hempseed cake alters the bovine gut, respiratory and reproductive microbiota
2021: In growing Californian rabbits, feeding them hemp herb didn’t make them grow any bigger
The use of hemp herb in diet for growing rabbits
However, the researchers didn’t evaluate fertility – and hemp seeds are known to make pigeons breed more.
So it makes one curious about the effects of hemp on the romantic lives of rabbits…
Clinical Studies & Surveys
In a survey of older humans with sleep disturbances, they tended to use products with more THC than CBD
Cannabis use for Sleep Disturbance Among Older Patients in a Geriatrics Clinic
In a survey of medical cannabis patients, they used it most for anxiety & the preferred ingestion method was vaping
An Observational Cross-Sectional Survey Exploring the Indications for and Responses to Medical Marijuana Use in Certified Patients in Pennsylvania
A review of potential CBD drug interactions for pharmacists
Cannabidiol drug interaction considerations for prescribers and pharmacists
Unfortunately, lists like this are best guesses based on a lot of work in cells & not enough clinical research.
A survey of the effects of medical & recreational cannabis on humans living with HIV
Disentangling Medicinal and Recreational cannabis Use Among People Living with HIV: An Ecological Momentary Assessment Study
2021: In regular cannabis users, men using a cannabis concentrate had higher levels in their blood than women – but both had similar subjective effects & error rates on a verbal memory test
Investigating sex differences in acute intoxication and verbal memory errors after ad libitum cannabis concentrate use
2021: In humans, an assessment of taste finds cannabis users less able to detect quinine on their tongue
Associations of Taste Perception with Tobacco Smoking, Marijuana Use, and Weight Status in the National Health and Nutrition Examination Survey
In healthy dogs, CBD capsules for 6 months were well-tolerated & saw no biochemistry or liver changes asides from a passing elevation in ALP liver levels in half the dogs
Long-term daily feeding of cannabidiol is well-tolerated by healthy dogs
Mental Health, Addiction & Mental Effects
A survey of why people with anxiety use cannabis finds that they use it to help with their anxiety
Why Use Cannabis? Examining Motives for Cannabis Use in Individuals with Anxiety Disorders
Extending the “marijuana gateway hypothesis” to include “the wave three violent offending risk”
Extending the Marijuana Gateway Hypothesis Beyond Drug Use to Violent Offending: Examining Dual Systems Imbalance as a Mediator
Listen, don’t blame me. I don’t write the data. I just collect it.
Anyway, as any long-time readers know, there is a greater link between cannabis & violence than ardent activists want to let on.
In end-of-life patients, interviews on their barriers to using cannabis-based medicines found them to be the right time to begin, off-label use, side effects information, lack of a safe medical framework, costs, relatives & social acceptance
Patient-Related Barriers to the Prescription of Cannabinoid-Based Medicines in Palliative Care: A Qualitative Approach
2021: A review of the effects of cannabis concentrates on behavior – though the data is rather limited
Advancing the science on cannabis concentrates and behavioural health
I would guess that cannabis concentrates would exacerbate the known moderate mental health harms that cannabis can cause, but there’s not a large array of data to show that one way or the other.
In humans with cocaine use disorder, 800 mg of isolated CBD did not decrease their anxiety scores, stress responses or cortisol levels
Cannabidiol Effect on Anxiety Symptoms and Stress Response in Individuals With Cocaine Use Disorder: Exploratory Results From a Randomized Controlled Trial
A commentary on using CBD to lessen the effects of meth
Cannabidiol as a pharmacotherapy tool for attenuating methamphetamine effects
The ability of legalized cannabis laws to lower the misuse of opioids, that effect appears to dissipate after two or three years
Recreational marijuana laws and the misuse of prescription opioids: Evidence from National Survey on Drug Use and Health microdata
A review of the biochemical pathways of why cannabis use can induce psychosis & the arising of schizophrenia in those with susceptibility
A Cannabinoid Hypothesis of Schizophrenia: Pathways to Psychosis
A review that tries to explain why in humans with schizophrenia, cannabis users had better cognitive performance but earlier illness onset
The Relationship Between Cannabis, Cognition, and Schizophrenia: It's Complicated
2021: In humans with ADHD, the use of cannabis (along with sleep & boredom) seemed to exacerbate symptoms
Exploring the Relationship Between ADHD Symptoms and Daily Cannabis Consequences in Emerging Adulthood: The Role of Cannabis Motives
2021: The genetic variant of the type of CB1 receptor you have alters your attention – but not working memory
Allele-dosage genetic polymorphisms of cannabinoid receptor 1 predict attention, but not working memory performance in humans
In female rats exposed to fear conditioning, CBD reduced their anxiety responses via the dopamine/serotonin axis in the hippocampus (memory center)
Cannabidiol attenuates fear memory expression in female rats via hippocampal 5-HT1A but not CB1 or CB2 receptors
In a mouse model of depression, the antidepressant effects of the lignans from Schisandra chinensis (a medicinal plant known as magnolia vine that produces five-flavor-fruit) helped with neuroinflammation via CB2 receptors & the microglia (immune guardian cells of the brain)
Schisandra chinensis Lignans Exert Antidepressant Effects by Promoting BV2 Microglia Polarization toward the M2 Phenotype through the Activation of the Cannabinoid Receptor Type-2-Signal Transducer and Activator of Transcription 6 Pathway
I’m starting notes for an article about all the traditional medicine plants that exert their benefits via the endocannabinoid system.
The Brain & its Diseases
A good review on ALS looks at the involvement of the endocannabinoid system in the regulation of the lipids
Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine
2021: A drug combining CBD with a derivative of a malaria drug helped to reduce neuroinflammation & protect the microglia (guardian immune cells of the brain)
Cannabidiol-dihydroartemisinin conjugates for ameliorating neuroinflammation with reduced cytotoxicity
In children using cannabis for epilepsy, a look at the inorganic elements in the extracts
Inorganic element profile of medicinal Cannabis extracts consumed by pediatric patients
2021: In rats, repeated exposure to an activator of the CB1 receptor caused more anxious behaviors, attentional deficits, signs of withdrawal, less spontaneous activity & less dopamine signaling in the brain
Repeated exposure to JWH-018 induces adaptive changes in the mesolimbic and mesocortical dopaminergic pathways, glial cells alterations, and behavioural correlates
2021: A computer study of how the endocannabinoid system facilitates talk between the neurons & astrocytes (star-shaped immune cells of the brain that outnumber neurons by 5x & are vital for regulating blood flow, supplying the building blocks of neurotransmitters & transfer energy-producing mitochondria to the neurons)
Spatial synaptic modulation through IP3 diffusion triggered by ECB: a computational study with an astrocyte-neurons model
2021: In brain dynamics, the ability of those astrocytes above to control the neuron’s signaling & plasticity is mediated by the mitochondria (the powerhouse of the cell)
Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration
Harms, Cannabis Use Disorder & Street Synthetics
A radiologist’s taking on the harm of vaping injuries
Vaping Injuries: A Radiologic Perspective
2021: A review of the biochemistry behind cannabis use, abuse & withdrawal
Cannabis use, abuse, and withdrawal: Cannabinergic mechanisms, clinical, and preclinical findings
2021: In humans with cannabis use disorder, they had more methylation (turning off) of the gene related to MB-COMT (membrane-bound catechol-O-methyltransferase – an enzyme related to the inactivation of dopamine in the brain)
Detection of altered methylation of MB-COMT promotor and DRD2 gene in cannabinoid or synthetic cannabinoid use disorder regarding gene variants and clinical parameters
Apparently using the sedative dexmedetomidine is a thing for treating cannabis use disorder. A thing, but according to this review, not necessarily an effective thing
Dexmedetomidine in the treatment of toxicologic conditions: a systematic review and review of the toxicology investigators consortium database
2021: A case report of a stroke related to THC & a review of the literature linking cannabis use to strokes in young people
Cannabis use and stroke in young people: A case report and review of the literature
A review of why the synthetic cannabinoids probably make you a worse driver
Effects of synthetic cannabinoids on psychomotor, sensory and cognitive functions relevant for safe driving
2021: A review of the effects of the major synthetic cannabinoids
Pharmacology and adverse effects of new psychoactive substances: synthetic cannabinoid receptor agonists
2021: A review of the negative heart effects of synthetic cannabinoids
Synthetic Cannabinoids and Cathinones Cardiotoxicity: Facts and Perspectives
2021: In humans using synthetic street cannabinoids, a look at their symptoms of intoxication, heart palpitations & hallucinations
Symptoms of Intoxication and Withdrawal in a Sample of Egyptian Patients Using Synthetic Cannabinoids: A Cohort Study
Pain, Inflammation & Surgeries
In cannabis users who had a specific neck surgery, afterwards they used more opioids & had increased chances of having another operation
Preoperative Cannabis Use Associated With an Increased Rate of Reoperation and Postoperative Opioid Use Following Anterior Cervical Decompression and Fusion
In long-term cannabis users who had lumbar fusion (back surgery), they had more pain immediately after the operation but no functional differences at the 3 months or 1-year checkup
The Effect of Preoperative Chronic Marijuana Use on Pain Outcomes Following Lumbar Fusion
A review of studies & a case report about how cannabis users in surgery tend to need more of the anesthetic propofol
Effect of cannabis use on propofol requirement for ICU sedation
2021: In a human study of pain, the painkiller Dilaudid (hydromorphone) combined well with 2.5 mg of dronabinol (pharmaceutical THC) – but not all the combinations worked well to lower pain levels
Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model
In a rat model of rheumatic arthritis, a nano-CBD water caused an improvement in their clinical symptoms
Application of Oil-in-Water Cannabidiol Emulsion for the Treatment of Rheumatoid Arthritis
In a mouse model of osteoarthritis, activating the CB2 receptor improved pain scores & joint integrity via the control of the metabolism of carbohydrates (good joints = strong bones)
HU308 Mitigates Osteoarthritis by Stimulating Sox9-Related Networks of Carbohydrate Metabolism
A little story about joints & joints: In my high school Spanish class, the Señora did not adore me. One day, the class played a game of charades to help with our vocabulary. I got the word ‘coyunturas’ – which means joints of the body. I went to the front of the class & made the universal symbol for sucking down on a joint of reefer.
Right away, everyone yelled out ‘Coyunturas!’. I won! And then she sent me to the principal’s office for an after-school detention.
And I believe my life has been on that path ever since…
The Immune System
For cystic fibrosis, a review of the potential benefits & significant risks of using cannabis
Clearing up the smoke: Physical and mental health considerations regarding cannabis use in adolescents with cystic fibrosis
Against drug-resistant gonorrhea, the power of using a combo of CBDV & two other drugs
Antimicrobial Activity of Auranofin, Cannabidivarin, and Tolfenamic Acid against Multidrug-Resistant Neisseria gonorrhoeae
A comparison of extraction methods on cannabinoid/terpene profile & the ability of those extracts to kill skin microorganisms that cause diseases
Medical cannabis dimethyl ether, ethanol and butane extracts inhibit the in vitro growth of bacteria and dermatophytes causing common skin diseases
The Guts, the Microbiome & Oral Health
A review of 5 studies using cannabinoids for gut problems in young patients
Therapeutic Effects of Medicinal Cannabinoids on the Gastrointestinal System in Pediatric Patients: A Systematic Review
A review of cannabis for treating metabolic syndrome (the cluster of factors leading to heart disease, atherosclerosis & type 2 diabetes)
Cannabis and cannabinoids as an alternative remedy in metabolic syndrome
A review of cannabis causing pancreatitis (inflammation & swelling of the pancreas because of the activation of digestive enzymes)
A Systematic Review of Cannabis-Induced Acute Pancreatitis: Is "HASH"ing Out the New Increasingly Common Culprit of Pancreatitis?
2021: In a review of 14 studies, “frequent cannabis smoking could be detrimental for periodontal [mouth] tissues”
Periodontal status in cannabis smokers. A systematic review
“Data from a cohort study showed that highly exposed participants were at higher risk of clinical attachment loss progression. Six cross-sectional studies reported worse gingival or periodontal conditions in cannabis smokers. Nevertheless, one did not find such association, neither did three case series. Three studies were of high, two of moderate and six were of low quality.”
In rainbow trout, the ECS helps to increase their food intake
Endocannabinoid receptors are involved in enhancing food intake in rainbow trout
The Heart & the Blood
A review of how the endocannabinoids help to guide the formation of our circulatory system
Endocannabinoids and related compounds as modulators of angiogenesis: Concepts and clinical significance
In a mouse model of Williams-Beuren syndrome (a rare genetic disorder that causes intellectual disability, hypersociability & life-threatening heart problems), inhibiting their MAGL enzyme (which raises the level of 2-AG) normalized their cognition & sociability as well as improving their cardiac function
Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome
2021: In rats, CB1 receptors – but not CB2 receptors – seem involved with the brain’s control of cardiac baroreflex activity (maintaining homeostasis of blood pressure in the arteries)
Ventromedial prefrontal cortex CRF1 receptors modulate the tachycardic activity of baroreflex
In humans taking THC capsules, their biomarkers indicated that they had less bone resorption (ie: more bone growth)
Serum Markers of Bone Turnover Following Controlled Administration of Two Medical Cannabis Products in Healthy Adults
In a mouse liver,5 days of the synthetic cannabinoid XLR-11 increased genes related to oxidative stress, inflammation & apoptosis (cellular suicide)
Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model
2021: A case report of a woman with diabetes & sleep apnea who started experiencing vision problems after starting CBD oil
Change in Refractive Error Associated With the Use of Cannabidiol Oil
Reproductive & Maternal Effects
A review of the influence of the ECS on female reproduction
THE INFLUENCE OF ENDOCANNABINOID SYSTEM ON WOMEN REPRODUCTION
A letter to the editor response on a study of developmental effects of cannabis use disorder during pregnancy including lowered academic outcomes in elementary school
Consistently careful: Pregnancy and cannabis use disorder in Australia
Cancer & Chemo
A review of the clinical use of cannabis in cancer care
Understanding the Role of Cannabis in Cancer Care: An Emerging Priority
In an interview study, cancer patients want access to medical cannabis but fear the “financial toxicity” of the costs
'What price do you put on your health?': Medical cannabis, financial toxicity and patient perspectives on medication access in advanced cancer
For melanomas, using light therapy, some crazy zinc structure & CBD to destroy them
Photodynamic Therapy Efficacy of Novel Zinc Phthalocyanine Tetra Sodium 2-Mercaptoacetate Combined with Cannabidiol on Metastatic Melanoma
How to make CBD into a liquisolid tablet
Preparation and Evaluation of Directly Compressible Orally Disintegrating Tablets of Cannabidiol Formulated Using Liquisolid Technique
Using hot-melt to get more CBD into you
Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD)
Sometimes the titles of these science papers are just a word change or two away from sounding like favorite pornography films.
When liver enzymes break down CBG, those breakdown products are bioactive, such as causing the reduction of inflammation
Metabolites of Cannabigerol Generated by Human Cytochrome P450s Are Bioactive
In our Neural Ocean metaphor, it’s as if you slice up the CBG wooly mammoth into pieces – but each of those pieces comes to life & goes forth into the cellular city to live out their life & preach peace & antiinflammation to all the other citizens.
See Gogol’s The Nose.
PS: For this week’s lovely mix, the first album by the Kora Jazz Trio. A three-piece group from Senegal with 4 remarkable albums, they mix American jazz with traditional African music. With just a piano, a drum & a kora (the 21-stringed instrument of West Africa), they make “a delightful alchemy” between West African percussion & Afro-American swing.
PPS: I suspect that there might be one reader out there who actually reads every word of this & catches all of my jokes. Maybe even likes them?
Is it you?
If so, reply to this email with a smiley & heaven will smile on you.
The Living Glossary
This is a running glossary of the basic cannabinoid terms. It will also function as the legend for the ‘neural ocean’ metaphor that I’m using in my graphic novel series on the endocannabinoid system based on Moby-Dick. You can watch a lecture laying out the full idea here - but 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.
The cannabinoids found inside all mammals & almost every other form of life besides insects
The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”
Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]
The second endocannabinoid receptor discovered. Found in almost every organ of the body & closely connected to our immune system. The CB2 occurs at low levels in the brain where it responds to neural insults.
[a gay bar in the membrane wall of the neuronal city]
FAAH (fatty acid amide hydrolase)
The enzyme that breaks down anandamide & a frequent target of drug discovery for modulating the endocannabinoid system. If you inhibit the FAAH enzyme, it does less breaking down of AEA, and your AEA levels rise. More balance.
[the giant squid that slices sperm whales in half]
Diacylglycerol lipase (DAGL or DGL)
The enzyme responsible for producing 2-AG.
MGL (monoacylglycerol lipase - also sometimes abbreviated as MAGL)
The enzyme that breaks down 2-AG. Another frequent target of drug discovery because inhibiting MGL raises 2-AG levels
[a giant octopus that eats blue whales]
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]
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]
An endocannabinoid related to sleep. They discovered it by keeping cats awake for 3 days & then analyzing their spinal fluid. You can buy it on Amazon. 2 scoops helps you to sleep while 6 scoops is a very pleasant psychoactive experience (Hamilton Morris has called it his favorite way to get high - which is saying something). It’s also worth considering for cancer treatment.
[Humpback whale, because it sings hippies to sleep]
Oleoylethanolamide (unfortunately, also abbreviated as OEA sometimes)
An analog of anandamide, this lipid acts via the peroxisome proliferator-activated receptor alpha (PPAR-α) receptors on the cell’s nucleus. These alter genetic transcription, a powerful method of cellular control. In animal models, oleoylethanolamide causes them to eat less food & drink less alcohol. In roundworms, it causes them to live longer. For the orphaned GPR119 receptor (a receptor that might one day be officially designated as a cannabinoid receptor), it may be the native ligand (the thing that binds to it). It’s already identified as the native ligand for hypoxia-inducible factor 3α (HIF-3α). OEA also interacts with our histamines.
[Pygmy sperm whale. Not well known, a smaller cousin to the sperm whale]
Fatty acid-binding proteins (FABPs)
These transport proteins move fatty lipids such as the endocannabinoids around the body. While still mysterious, they’re thought to move anandamide between membranes as well as transporting it to be broken down by the enzyme FAAH. Several types of FABPs exist in humans. THC & CBD bind to some of them. This may explain why endocannabinoid levels tend to increase after consuming cannabinoids. As the brain ages, the levels of FABPs decrease.
The cannabinoids produced by the cannabis plant.
THC (delta-9-tetrahydrocannabinol or Δ9-THC)
The well-known & well-studied molecule in cannabis that gets you high - and helps in a number of other fascinating ways.
[African elephant. Powerful, unpredictable, beautiful]
The cousin of THC that does not get you high but does a lot of the heavy lifting in why hemp has been such a staple of medicine since before recorded history. In most plants outside those bred for the recreational market, CBD is the most common cannabinoid. It binds to a wide swathe of receptors outside the endocannabinoid system including three serotonin receptors, two opioid receptors, a dopamine receptor as well as glutamate & GABA (the two most widespread neurotransmitters, the basic neuronal signals for excitation & inhibition, respectively)
[Indian elephant. sweet, gentle, you can work with it]
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]
The third most common cannabinoid in the plant, it’s not well studied in humans despite a number of intriguing preclinical studies, especially as an anti-inflammatory and for pain. Nonpsychoactive, it interferes with the breakdown of AEA & 2-AG (leading to a rise in their levels) as well as interacting with the vanilloid receptors.
[Sri Lankan elephant. Little, sweet, not as well known as it should be]
CBDV is like CBD with a shortened tail (side chain). Also nonpsychoactive, it tends to occur at low levels in most cannabis cultivars. It’s known to be an anticonvulsant & is suggested for treating autism in humans & in animal models. The cannabinoid pharmaceutical company GW has it in their developmental pipeline as GWP42006.
[An Asian elephant with a short trunk]
(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]
A terpene that’s also a cannabinoid.
The terpenes of cannabis give the plant its smell. Also found in oregano, black pepper, lavender & hops, beta-caryophyllene has a spicy sweet woody smell. But unique among terpenes, this one also binds to the CB2 receptor, making it a dietary cannabinoid. It shows a potential for treating inflammation, pain, anxiety & seizures. The FDA has designated it to be GRAS (generally regarded as safe) & thus it can be safely used as a food additive.
[a terpene/cannabinoid that travels through the air? That could only be a flying elephant]
Nabiximols (ie Sativex®)
A pharmaceutical 1:1 CBD:THC spray produced by GW Pharmaceuticals. One of the first cannabinoid pharmaceuticals on the market, Sativex is an approved treatment for neuropathic pain, spasticity, overactive bladder & the symptoms of multiple sclerosis.
Epidiolex® (in the UK, Epidyolex®)
An isolated CBD formulation approved for treating the severe seizures of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. Produced by GW Pharmaceuticals, the doses tend to be incredibly high – hundreds or thousands of milligrams of CBD every day in young children. But even with that, the side effects tend to only be lethargy & stomach upset.
Dronabinol (ie Marinol® and Syndros®)
A synthetic form of THC for the treatment of anorexia in AIDS patients & the nausea of chemotherapy. These tend to not be popular with patients because it’s a horse dose of THC with no modulation by the other molecules in the cannabis plant like CBD.
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.