C&P#30: IACM recap + cannabis for female sex + CBD for dementia, hair loss & honeybees
Cannabis to be sold at Circle K in Florida while Hong Kong & Brazil crack down on CBD
This newsletter collects all the new cannabinoid science each week & is a free offering from my company White Whale Creations. We produce educational content for cannabis & psychedelic companies. Writing, science archives, newsletter content & if you need a podcast, I’m the host for you.
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YouTube Shorts + Livestream on Tuesday @ 4PM EST
On my YouTube channel, I started creating YouTube Shorts about cannabis. If you have a question that you want answered, reply to this email or leave a video comment. Engagement & subscribers is appreciated because it’s always an uphill battle getting started on a new platform. Any amplification, likes or comments go a long way. Though the metric they measure the most is watch time if you want to leave them on loop…
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A roundup of the new science I heard at the IACM conference – especially cannabis for menopause
CBD oil for the agitation of dementia & for the anxiety of life
Cannabis for better sex in females
CBD to grow your hair?!
Cannabis causing accelerated aging & worse preparedness for the demands of later life?
Why to give your honeybees CBD
CBD to protect your skin from UVB radiation damage & your brain from meth use
A guerilla warfare story of cannabinoids vs cancer
On how an 8th of cannabis via bong per day for ten years caused large lung blisters
Biggest cannabis family tree ever created
In a thread that could have come straight from Twitter, what happened in 1675 when a bunch of English sailors drink way too much THC beverage
A beautiful collection of psychedelic quotes + the psychedelic section got so big I had to split it into history, therapy & research
Sponsor: PlusCBD’s customer service
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Popular Science Writing & Events
How does cannabis impact women’s fertility & ovulation?
A history of cannabis in traditional Chinese Medicine by Laura Linham
On dealing with the symptoms of cannabis withdrawal
The Spirit Plant Medicine Conference is online next weekend & has a great lineup
Tune into Dr. Bruce Damer for a cosmic vision. He created a new theory of the origin of life during a lucid dreaming-type experience while on a long flight. He also hosted me in California while I went through his archives of Timothy Leary’s correspondence.
Best of cannabinoid science...
In patients with dementia, this placebo-controlled trial showed that CBD oil reduced agitation with no serious side effects
Effects of rich cannabidiol oil on behavioral disturbances in patients with dementia: A placebo-controlled randomized clinical trial
A series of case studies on using CBD for anxiety (with an especially well-done chart on the many biochemical actions of CBD)
Cannabidiol as a personalized treatment for anxiety: clinical cases in Mexico
A review of the promise of cannabinoids for early neurodevelopmental disorders such as intellectual disability, autism spectrum disorders, tics & attention/deficit hyperactivity disorder
The role of cannabinoids in neurodevelopmental disorders of children and adolescents
A review of how moderate amounts of cannabis may improve female sexual function
Effects of Cannabis Use on Sexual Function in Women: a Review
A review finds that while topical CBD may cause hair growth, the other cannabinoids (or very high levels of CBD) may cause hair loss
A cannabinoid Hairy-Tale: Hair loss or hair gain?
One more surprising area to find a bunch of cannabinoid receptors is the hair follicles. But there they are, and as we usually find, their array of effects is complex & sometimes contradictory.
A well-done review on cannabis & the lungs confirms the common wisdom that while smoking it may increase your chances of bronchitis, it does not cause chronic obstructive pulmonary disease & probably does not cause lung cancer
Marijuana and the Lung: Evolving Understandings
In this demonstration of the entourage effect, the cannabinoids & the terpenes caused more potent anti-cancer activities when used together
Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts
A review of how CBD affects appetite & body weight
Effects of Cannabidiol on Appetite and Body Weight: A Systematic Review
In skin stem cells (keratinocytes), CBD protects against the multipronged damage from UVB light
Photoprotective Effects of Cannabidiol against Ultraviolet-B-Induced DNA Damage and Autophagy in Human Keratinocyte Cells and Mouse Skin Tissue
In joints & e-cigarettes, CBD does not appear to be converting to THC in naturalistic use settings
Absence of Relevant Thermal Conversion of Cannabidiol to Tetrahydrocannabinol in E-Cigarette Vapor and Low-Tetrahydrocannabinol Cannabis Smoke
And in a natural test in 9 subjects did not find that CBD was converted to THC in their gastric fluid
Will tetrahydrocannabinol be formed from cannabidiol in gastric fluid? An in vivo experiment
This is apparently still an area of debate, about whether the acidity of your guts might close the 2 rings of CBD to create the 3 rings of THC, but according to the scientists that I respect the most, they don’t believe this happens.
CBD boosted the health of honey bees!
CBD Supplementation Has a Positive Effect on the Activity of the Proteolytic System and Biochemical Markers of Honey Bees ( Apis mellifera) in the Apiary
And in a fun classic from 1980, butterflies can distinguish between different cultivars (“strains”) of cannabis: Turkish vs Mexican
Ovipositing butterfly (Pieris brassicae L.) distinguishes between aqueous extracts of two strains of Cannabis sativa L. and THC and CBD
The biggest family tree yet created for the hemp family (Cannabaceae) with over 83 species included
Phylogenomic analysis of the hemp family (Cannabaceae) reveals deep cyto-nuclear discordance and provides new insights into generic relationships
An evergreen note on reading restricted paper:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version) or Google Scholar itself.
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.
My cannabis & psychedelic consultant sessions for your health (or your patients)
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the Headlines & Fav Articles
Good analysis of why to be wary of Biden’s review of the rescheduling of cannabis by Bruce Barcott
And to be clear, Biden is adamant that you can get out of prison for having it, but not for selling it
Plus, the president of the National Institute of Military Justice urged Biden to order his marijuana pardon to cover people convicted in military courts
Americans for Safe Access published a voter guide for medical cannabis
The DEA wants to bump the level of cannabis production for research as well as for classic psychedelics
In Florida, cannabis from Green Thumb will be sold at Circle K gas stations
But Florida regulators want to harsh their mellow
And my favorite tweet on the subject so far
As access widens, retail space will dwindle in importance & brands will increase in importance.
In Hong Kong, CBD will be placed into the same category as heroin & meth
In Brazil, the Federal Council of Medicine resolved to restrict doctors to prescribing CBD only for two types of epilepsy
But then suspended the new measure
In Israel, cannabis is on the ballot with Ale Yarok – a single-issue cannabis party
In Pennsylvania, a mother is charged with murder after her 4-year-old dies with large amounts of THC in his system
The very Queer history of cannabis by Tamara Krivskaya
And read my Queer cannabis history graphic novel, SUNset.
IACM ’22 Report
I went to my first conference since the pandemic started. I liked seeing people again, building up my EU network & hearing about the science- but most of all, I appreciated learning about the IACM’s Patient Council because these are the heroes on the front line pushing medical cannabis forward with their stories, their activist & their support of the research. You’ll hear more about that in my forthcoming article about the conference for ProjectCBD.
For now, here’s a roundup of the most intriguing science I heard…
[You can still buy a ticket to view all the lectures here for the next month & all 43 of the posters can be seen here]
Dr. Vincenzo Di Marzo on the endocannabinoidome & gut/mental health:
Our endocannabinoid system consists of over 200 mediators, 15 receptors & 35 enzymes. Here's his recent paper on how this relates to gut health & hence, influences our mental health.
The winning poster: THC/CBD oil for patients
(by our great good luck, the paper just happened to come out…
Cannabinoids for behavioral symptoms in severe dementia: Safety and feasibility in a long-term pilot observational study in nineteen patients
At science conferences, research teams often present their research on posters that can be examined by the attendees. I'll attach my photos of some of the best ones.
The winning poster at this year's conference was on the use of THC/CBD oil for severely demented patients. In these 19 patients, they saw no serious adverse events when using a treatment with a ratio similar to our Reserve products & most importantly, they saw clinical improvements in:
less use of prescription medicine
other posters: CBD safe for elderly people's drug interactions
In patients with severe dementia taking an average of 7 medications per day, the researchers found that the use of THC/CBD oil caused no important drug interactions.
poster: in a rat brain, CBD increases the nerve growth factor BDNF
In the brain region called the medial prefrontal cortex (an area important for memory, learning & slow-wave sleep), one dose of CBD increased the levels of BDNF (a brain growth factor that causes new brain cell growth as well as stronger connections between brain cells). It's theorized that much of CBD's help for mental health comes from its ability to grow new brain cells.
poster: CBD for treating migraine in animal models
This study of rats found that when treating them with CBD, the CBD was indeed found in the brain areas related to migraine. In addition, they found that a single dose of CBD decreased pain.
poster: in skin, CBD reduced inflammation via the skin stem cells
Known as the keratinocytes, these skin stem cells had lower levels of pro-inflammatory factors when treated with CBD (and CBD worked better than the other major cannabinoids that they looked at).
Dr. Crippa presented his research on CBD for healthcare practitioners burned out by COVID:
With a clinical trial, Dr. Crippa & his team showed that "CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic." Furthermore, their recently published follow-up study showed that the anti-anxiety effects continued for up to a month after the participants stopped taking the CBD.
Dr. Gudrun Lorenz-Eberhardt on CBD for menopause:
This was one of the most powerful talks of the whole conference. This doctor worked closely with her patients & displayed a keen knowledge of how to use cannabinoids for the many symptoms related to the hormonal changes of menopause:
CBD for the hot flashes caused by disturbance of the hypothalamus (a temperature regulation part of the brain that contains many cannabinoid receptors)
CBD oil & peppermint for dizziness & headaches
CBD can help with the heart palpitations, joint problems & rheumatic diseases common to menopause
CBD for the sleep disturbances
For the inflamed aging skin, full-spectrum CBD topicals applied directly can help
CBD for the osteoporosis (all women experience bone loss. the only difference is the amount lost. CBD supplementation is worth it for the anti-osteoporosis effects alone)
The War on Drugs & Harm Reduction
In New Orleans, cannabis possession charges have virtually vanished under the new changes in the law
Louisiana, with more people in prison per capita than any other place on the planet, is benefitting from changes in the cannabis law that lessen the racially charged application of cannabis prohibition.
In DC, a cannabis company filed a $750k lawsuit against the city for police raids that damaged product & seized cash
On the reality of what it’s like to be a medical cannabis patient under UK Prohibition
Prohibition kills 3 in NYC
A sad story about our national painkiller shortage
The DEA successfully scared doctors away from prescribing enough opioid painkillers to treat pain. And now a huge number of patients are suffering.
And the black market is ready & willing to serve them.
Same thing is happening with Adderall. The DEA is suppressing production – and hence, the obvious conclusion…
A good short rundown on why the War on Drugs is an abomination
The War on Drugs Turns 50
The racist history of South Africa & how what constituted drugs was a deeply political decision
Apartheid’s 1971 Drug Law: Between Cannabis and Control in South Africa
But before anyone from the States wants to feel superior, remember that it was in the US South that the system of racial apartheid was first created. We called it Jim Crow.
In India, on how the nomenclature for the three types of cannabis ingestion methods was influenced by British colonialism
Reading Cannabis in the Colony: Law, Nomenclature, and Proverbial Knowledge in British India
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 company, reach out to me]
History & Current Events
‘Why is the American right suddenly so interested in psychedelic drugs?’
Instagram takes down way more pages of black women psychedelic advocates than anyone else (including the dozen new drug dealing accounts that follow me every week)
Meta is such an awful company.
A researcher on the false narrative of ancestral Indigenous use of 5-MeO-DMT from toads
A history of the Santo Daime ayahuasca church & its effect on psychedelic legalization by Don Lattin
Brain scans of Santo Daime members showing that they have a similar connectome when ingesting their sacrament
Ritualistic use of ayahuasca enhances a shared functional connectome identity with others
And a Twitter thread breaking down what this means
On Terence McKenna’s hushed up super-bad trip
As a collector of quotations, I deem Doubleblind’s collection of 57 psychedelic quotes to be top-shelf
“I wouldn’t recommend sex, drugs, or insanity for everyone, but they’ve always worked for me.” —Hunter S. Thompson
On mescaline as the forgotten psychedelic
Mescaline: The forgotten psychedelic
On the history of mescaline & now the first clinical trials in Basel, Switzerland by Eric Bender
Great Sidney Cohen quote on the dark seduction of therapists by psychedelic therapy…
As Aldous Huxley said, “Therapists get into this because of their own dark icebergs.”
A collection of red flags for psychedelic therapists by Jack Bunce
On treating postpartum depression with psychedelics by Ruby Deevoy
A great dive into the current scope of psychedelic research (I love a good chart) by Floris Wolswijk
He’s the co-founder of Blossom, an excellent site for staying up on the psychedelic research.
A bibliometric analysis of the psychedelic clinal literature
Bibliometric Analysis of Academic Journal Articles Reporting Results of Psychedelic Clinical Studies
Studies about studies! Every recursive researcher’s encyclopedist dream.
Compass begins the first ever Phase 3 clinical trial on psilocybin mushrooms & they’re looking at treating treatment-resistant depression
In both healthy people & those with a life-threatening illness, 200 mics of LSD lessened anxiety & depression scores for up to 16 weeks
Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study
In humans, low doses of LSD increase reward-related brain activity
Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity
In brain immune cells, DMT & psilocin regulate their immune response & upregulate neuroprotective receptors
The DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype
A positive review of ketamine for depression
Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability
On using transcranial stimulation for depression (hattip to Efrem Nulman)
Home-Based Transcranial Stimulation Succeeds for Major Depression
The use of low levels of electricity on the outside of the skull has been looked at for improving cognition as well as treating conditions like depression. We don’t know why, but for some reason, a little bit of electricity into our brain – itself a wet electrical system – seems to help it.
Law & Business
An analysis on the different types of cannabis tax by Richard Auxier & Nikhita Airi of the Urban-Brookings Tax Policy Center
THE PROS AND CONS OF CANNABIS TAXES
“Governments use three different types of cannabis taxes: a percentage-of-price tax, a weight-based tax, and a potency-based tax.”
In Toronto, Uber Eats & Leafly partner on cannabis delivery
🍿🍿🍿 SEC charges Cronos Group of Canada with accounting fraud for earnings inflation
“This just reinforces the narrative that cannabis companies can’t be trusted,” Kaufman added, “and that’s what concerns me.”
Curaleaf agrees to a $100k fine for settling a lawsuit over their cannabis drops labeled as CBD that actually contained high levels of THC
An analysis of marketing strategies from 3 of the big CBD companies
Cannabidiol Marketing Strategies in the United States: An Analysis of Three Prominent Companies
MedMen continues to be a trash company. Now they’re trying to pull out of an agreement with a landlord by claiming that everything is unenforceable because cannabis is illegal
The Plant & the History
What happens when a bunch of English sailors in 1675 drink way too much cannabis lhassi
2020: On the importance of Minnesota hemp in the early research on cannabinoids
Minnesota wild hemp: a crucial botanical source in early cannabinoid discovery
A review of hemp as a superfood
Potential applications of hemp (Cannabis sativa L.) extracts and their phytochemicals as functional ingredients in food and medicinal supplements: a narrative review
An analysis of hemp proteins compared to other plant & animal proteins
Physicochemical, Structural, and Functional Properties of Hemp Protein vs Several Commercially Available Plant and Animal Proteins: A Comparative Study
2019: The hemp seed ingredient cannabisin F (a lignanamide) lowered inflammatory responses & oxidation in brain immune cells
Cannabisin F from Hemp ( Cannabis sativa) Seed Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia as SIRT1 Modulator
On how to make stronger roots in your cannabis plants
Comparing hydroponic and aquaponic rootzones on the growth of two drug-type Cannabis sativa L. cultivars during the flowering stage
Certain root fungi help hemp to be resistant to stress by the toxic metal cadmium often found in soil
Rhizophagus irregularis enhances tolerance to cadmium stress by altering host plant hemp (Cannabis sativa L.) photosynthetic properties
Using hemp fiber to lower the weight of the metal springs used on commercial heavy-duty vehicles
Finite Element Analysis of Natural Hemp Fiber-Based Composite for Semi-elliptical Multi-leaf Spring
Clinical Studies & Surveys
A review of brain-imaging studies looks at how CBD alters brain function in several regions: medial frontoparietal, midcingulo-insular, pericentral, lateral frontoparietal, dorsal frontoparietal networks as well as the striatum & cerebellum
An insight into the acute effects of cannabidiol on human brain function and their relationship with the brain expression of its molecular targets: a neuroimaging meta-regression analysis
In socially marginalized Nigerian women, these interviews make it clear that cannabis is a helpful & more easily accessible painkiller
Cannabis use for pain relief in the context of health service barriers: Accounts of street-involved Nigerian women suffering chronic pain
2020: In women with eating disorders, they tended to have certain genetic variants for anandamide, 2-AG & FAAH
Comparison of endocannabinoids levels, FAAH gene polymorphisms, and appetite regulatory substances in women with and without binge eating disorder: a cross- sectional study
2021: In patients with trauma, cannabis use before their injury did not improve their chances of survival but it may provide some improvements from their traumatic brain injuries
Preinjury Use of Marijuana and Outcomes in Trauma Patients
2019: In people undergoing endoscopic surgery, cannabis users tended to need extra sedative drugs
Effects of Cannabis Use on Sedation Requirements for Endoscopic Procedures
In liver transplant patients, no difference was found between cannabis & non-cannabis users
Marijuana use and post-transplant complications and non-compliance in liver transplant patients
In 15 older adults, medical cannabis use caused no negative metabolic changes to their endocannabinoid system levels, blood pressure or markers of inflammation
Herbal Cannabis Use Is Not Associated with Changes in Levels of Endocannabinoids and Metabolic Profile Alterations among Older Adults
2020: Great title: Endocannabinoids as stress management professionals
Meet Your Stress Management Professionals: The Endocannabinoids
2020: A review of using cannabis in sports medicine
Understanding Cannabis-Based Therapeutics in Sports Medicine
A review of the effects of cannabis (& other drugs) on your oral health
Illegal drugs and periodontal conditions
A review of your THC blood levels after use in frequent users
Residual blood THC levels in frequent cannabis users after over four hours of abstinence: A systematic review
2020: In monkeys with the simian version of HIV, THC stimulates the release of vesicles into the blood carrying a number of signaling molecules
Long-Term Low-Dose Delta-9-Tetrahydrocannbinol (THC) Administration to Simian Immunodeficiency Virus (SIV) Infected Rhesus Macaques Stimulates the Release of Bioactive Blood Extracellular Vesicles (EVs) that Induce Divergent Structural Adaptations and Signaling Cues
Mental Health, Addiction & Mental Effects
A review of 23 studies on the effects of cannabis on cognition
The effect of medical cannabis on cognitive functions: a systematic review
2020: A review of how THC works on aversive memories & anxiety in terms of helping with PTSD
Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies
A review of 19 studies on formal thought disorder (a syndrome on the psychosis continuum) found an association between cannabis use & worse symptoms
Association between formal thought disorder and cannabis use: a systematic review and meta-analysis
2021: In older adults, a review of the potential mental health harms of cannabis
Risk Factors for Cannabis-Related Mental Health Harms in Older Adults: A Review
2021: A review of the effects of cannabis on the symptoms of psychiatric disorders from 42 studies
Effects of Cannabis Use on Psychotic and Mood Symptoms: A Systematic Review
“Adverse effects of cannabis or cannabinoids were found in 30/32 (93.8%) of studies reporting psychotic symptoms, 13/18 studies (72.2%) reporting depressive symptoms, and 4/4 studies (100%) reporting (hypo)manic symptoms. Cannabis use robustly increased the risk of developing psychotic and (hypo)manic symptoms, but the effects of cannabis use on depression were mixed.”
In a review of animal models of drug addiction, β-caryophyllene (one of the primary terpenes of cannabis) showed promising results, often via its ability to activate the CB2 receptor
Effects of β-caryophyllene, A dDietary Cannabinoid, in Animal Models of Drug Addiction
Harms, Cannabis Use Disorder & Street Synthetics
A study of long-term cannabis users at 45 found them showing “statistically significant accelerated biological ageing and were less equipped to manage a range of later-life health, financial, and social demands”
Preparedness for healthy ageing and polysubstance use in long-term cannabis users: a population-representative longitudinal study
Without a doubt, I would rather die early a stoner than live a long life in sober consensual reality.
On the clinical considerations of cannabis use & heart health
Clinical Considerations for Cannabis Use and Cardiovascular Health
And an unusual case study of cannabis user with a heart attack from a coronary artery spasm
An Unusual Case of Marijuana-Induced Extensive ST-Elevation Myocardial Infarction in Different Territories
For treating cannabinoid hyperemesis syndrome (intense cyclical vomiting), this study of 17 patients found droperidol (an anti-nausea injection) helpful
32 Droperidol on Prevention of Emesis from Cannabinoid Hyperemesis Syndrome (DOPE Study)
2021: On the potential risks of cannabinoids in wastewater & how good treatment plants are at removing it
A critical review on the detection, occurrence, fate, toxicity, and removal of cannabinoids in the water system and the environment
For people with cannabis use disorders who want to reduce cannabis use, digital interventions can help but there are many more of them for general, non-clinical populations than for those with psychiatric illnesses
A Review of Digital Interventions to Decrease Cannabis Use Among Patients With Comorbid Psychiatric Disorders
A look at the data from the VA about the rise of cannabis use disorder diagnoses since 2005
Understanding Cannabis Use Disorder Diagnoses in the U.S. Veterans Health Administration in the Era of Legalization
In glial cells (immune cells of the brain), THC caused less viability, especially when combined with CBN or CBD
LP-22 Evaluation of the cytotoxicity of the mixtures tetrahydrocannabinol- cannabinol and tetrahydrocannabinol-cannabidiol in vitro model of Glia precursor cells
In mice, cannabis vapor caused the signs of addiction
Δ9-Tetrahydrocannabinol Vapor Exposure Produces Conditioned Place Preference in Male and Female Rats
2021: A review of the known problems from the synthetic cannabinoids on the street
Pharmacological and Toxicological Effects of Phytocannabinoids and Recreational Synthetic Cannabinoids: Increasing Risk of Public Health
2021: And a review of the cases reported to a poison control center over 10 years
Cannabis and synthetic cannabinoid poison control center cases among adults aged 50+, 2009-2019
2020: And a 4-year analysis of synthetic cannabinoids at a Turkish ER
A 4-Year Retrospective Analysis of Patients Presenting at the Emergency Department With Synthetic Cannabinoid Intoxication in Turkey
And using synthetic cannabinoids & crashing into a tree & acting weird at the ER: a case study
Synthetic Cannabinoid Use in the Trauma Patient: A Case Study
And another novel synthetic cannabinoid detected
Newly emerging synthetic cannabinoid ADB-4en-PINACA: its identification and quantification in an authentic human hair sample by GC–MS/MS
Neurodegenerative & Brain Diseases
An analysis of the neuroprotective potential of cannabis
Evaluating Cannabis sativa L.'s neuroprotection potential: From bench to bedside
A review of why CBD works for difficult-to-treat seizures & epilepsies as well as the issues clinicians should note
Therapeutic and clinical foundations of cannabidiol therapy for difficult-to-treat seizures in children and adults with refractory epilepsies
And a review of all the clinical studies CBD for pediatric epilepsy that have been done
Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis
And in a rat prone to seizures, CBD reduced the number of seizures as well as their severity & duration
Cannabidiol attenuates generalized tonic-clonic and suppresses limbic seizures in the genetically epilepsy-prone rats (GEPR-3) strain
2020: A review about cannabis may protect the brain from the damages of methamphetamine use as well as HIV-associated neurocognitive disorders
Methamphetamine and Cannabis: A Tale of Two Drugs and their Effects on HIV, Brain, and Behavior
2020: And how cannabis in HIV+ patients may help in the short-term with neuroinflammation but harm in the long term with brain atrophy & reduced resting-state functional connectivity
Impact of Cannabis Use on Brain Structure and Function in Suppressed HIV Infection
And in a rat model of meth abuse, CBD protected from the neurotoxicity via dopamine receptors
Cannabidiol prevents methamphetamine-induced neurotoxicity by modulating dopamine receptor D1-mediated calcium-dependent phosphorylation of methyl-CpG-binding protein 2
A side note: For some reason, the literature tends to abbreviate methamphetamine as METH. Which is exactly how someone on meth would write it…
In a rat model of Alzheimer’s, they saw increased activity in the enzymes that control the levels of 2-AG
An optimized spectrophotometric assay reveals increased activity of enzymes involved in 2-arachidonoyl glycerol turnover in the cerebral cortex of a rat model of Alzheimer's disease
2020: In rat brains, THC modulated their microtubules (cylinders that help transport things between cells & to control cell division) which may help to explain its memory effects via acetylcholinesterase
The long-term effects of Δ9-tetrahydrocannabinol on microtubule dynamicity in rats
2021: In a female rat model of traumatic brain injury, both the injury & the use of alcohol altered the levels of 2-AG & anandamide in the brain’s basolateral amygdala (a fear/anxiety/emotion processing center)
Traumatic Brain Injury and Alcohol Drinking Alter Basolateral Amygdala Endocannabinoids in Female Rats
2020: In a mouse model of multiple sclerosis, the endocannabinoid levels change in the astrocytes & microglia (important support & immune cells of the brain)
Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination
The effects of the flavonoid cannflavin A against the neurotoxic enzyme kynurenine-3-monooxygenase
Gram-Scale Preparation of Cannflavin A from Hemp (Cannabis sativa L.) and Its Inhibitory Effect on Tryptophan Catabolism Enzyme Kynurenine-3-Monooxygenase
Pain & Inflammation
People with chronic lower back pain who used alcohol & cannabis together to cope had worse outcomes
Alcohol and marijuana co-use among adults with chronic low back pain: Associations with substance misuse, mental health, and pain experience
2020: In mice with neuropathic pain, a drug to activate the CB2 receptor worked well with morphine to reduce pain while also lessening the negative side effects of morphine withdrawal & slowing down of the colon
The cannabinoid CB2 receptor agonist LY2828360 synergizes with morphine to suppress neuropathic nociception and attenuates morphine reward and physical dependence
2020: In rats using tramadol for painkilling, CB1 seems to play a key role in its addictive properties
The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement
2019: In rats, a positive allosteric modulation of the CB1 receptor (something that CBD does) antagonized some of the effects of morphine in their brain
Positive allosteric modulation of the cannabinoid type-1 receptor (CB1R) in periaqueductal gray (PAG) antagonizes anti-nociceptive and cellular effects of a mu-opioid receptor agonist in morphine-withdrawn rats
A review of cannabinoids for IBD
Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
A review of how cannabis may alter glycemia levels & behavioral management in people with diabetes
The effects of recreational cannabis use on glycemic outcomes and self-management behaviours in people with type 1 and type 2 diabetes: a rapid review
In a case study of a 13-year-old with treatment-resistant epilepsy, CBD caused her to have diarrhea, stomach bloating, abdominal pain & vomiting – but the symptoms disappeared once her dose went from 450 mg per day to 350 mg per day
Persistent Diarrhea and Eosinophilic Esophagitis Resulting From Chronic Cannabidiol Usage for Refractory Epilepsy
In mice, the ability of a high-fat diet to increase artery plaques seems to be mediated by CB2 & 2-AG in the bone marrow cells
Myeloid But Not Endothelial Expression of the CB2 Receptor Promotes Atherogenesis in the Context of Elevated Levels of the Endocannabinoid 2-Arachidonoylglycerol
2020: In people with respiratory disorders made worse by aspirin, cannabis may help with airway inflammation via CB2
Endogenous cannabinoids may regulate chronic inflammation in aspirin-exacerbated respiratory disease
A case study of a man smoking an 8th of cannabis per day out of a bong who developed blisters (bullae) in his lungs
Bong Lung: A Case of Massive Lower Lobe Lung Bullae Associated with Cannabis Smoking
A certain genetic variant of the CB1 receptor is associated with chronic obstructive pulmonary disease in a Pakistani population
ASSOCIATION OF 1359 G/A POLYMORPHISM OF CNR1 GENE AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN PAKISTANI POPULATION
Reproductive & Maternal Effects
A summary of the evidence on cannabis use during pregnancy
Current Evidence to Guide Practice, Policy, and Research: Cannabis Use During Pregnancy
Reports from the French system on adverse events with recreational cannabis use during pregnancy
Adverse events of recreational cannabis use during pregnancy reported to the French Addictovigilance Network between 2011 and 2020
2021: And the French seeing more frequent & severe pediatric cannabis poisonings
Pediatric cannabis poisonings in France: more and more frequent and severe
The use of cannabis during breastfeeding may alter the composition of breast milk
Cannabis use during lactation may alter the composition of human breast milk
California has two to four times more expectant mothers who smoke cannabis than who smoke tobacco
Tobacco and Cannabis Use During and After Pregnancy in California
A review of preclinical evidence on cannabis smoke & THC causing reproductive toxicity & developmental problems
Animal evidence considered in determination of cannabis smoke and Δ9 -tetrahydrocannabinol as causing reproductive toxicity (developmental endpoint); Part I. somatic development
“Apical somatic effects of cannabis smoke or Δ9 -THC reported in whole animal studies included decreases in offspring viability and growth. Mechanistic studies discussed in Part I focused on Δ9 -THC effects on early embryos and implantation, immune development, and bone growth.”
In rats exposed to THC in the womb, they had “behavioral, neuronal, and molecular alterations in the mesolimbic system in male and female offspring, resembling neuropsychiatric endophenotypes”, “profound dysregulation of critical fatty acid pathways in the developing brain lipidome” & “enduring abnormalities in glutamatergic/GABAergic function in the nucleus accumbens”
Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry
2020: In rats exposed to cannabinoids in the womb, CB1 & CB2 differentially affected the number of eggs in their ovarian reserve
Prenatal cannabinoid exposure alters the ovarian reserve in adult offspring of rats
In male mice (but not female mice) exposed to THC in utero, they had more aberrant dopamine levels in adolescence as well as a greater behavioral sensitivity to THC, though this could be reversed by the steroid pregnenolone
Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone
2021: In male reproductive cells, pretreatment with selenium protected against the damage caused by THC
In Vitro and In Vivo Pretreatment with Selenium Mitigates Tetrahydrocannabinol-Induced Testicular Cell Apoptosis: the Role of AKT and p53 Pathways
Cancer & Chemo
In patients with advanced cancer experiencing uncontrolled pain, a nano-spray of 1:1 THC:CBD appeared safe & showed preliminary evidence of painkilling effects
Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain
In oral cancer cells, a cannabinoid mixture caused high toxicity in the cancer cells (but not the normal gingival cells) causing oxidative stress, DNA damage, stress of their mitochondria (powerhouse of the cell), autophagy (cellular recycling) & apoptosis (cellular suicide)
Oxidative Stress and Autophagy Mediate Anti-Cancer Properties of Cannabis Derivatives in Human Oral Cancer Cells
I dream of the day that I create a graphic novel chapter about how cannabinoids wage guerilla warfare against cancer cells on such a wide variety of fronts. It’ll be the greatest liberation story since Zapata.
2020: In glioblastoma cells (the fastest-growing brain tumors), oleamide caused cell death through unknown signaling molecules
Oleamide Induces Cell Death in Glioblastoma RG2 Cells by a Cannabinoid Receptor-Independent Mechanism
The plot thickens. The humpback whale oleamide is a sapper that sneaks into the enemy cities with novel & unknown explosives that decimate their infrastructure.
CBD & CBG cause cancer cells to kill themselves via the EGFR pathway
Structural analysis of cannabinoids against EGFR-TK leads a novel target against EGFR-driven cell lines
In colorectal cancer cells, a mix of cannabinoids caused a persistent toxicity that lowered cell viability
The Cytotoxic Effect of Isolated Cannabinoid Extracts on Polypoid Colorectal Tissue
Preclinical Research, Synthetics & Cool Chemistry
A review of how CBD works with oxidative stress via the NF-κB pathway
The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress
In a study of mice with no fatty acid-binding proteins (FABPs - cannabinoid transportation machinery) in their livers & intestines, they had altered systemic energy metabolism but apparently these FABPs are not required for the intestines to absorb lipids
The proximal intestinal Fatty Acid-Binding Proteins liver FABP (LFABP) and intestinal FABP (IFABP) differentially modulate whole body energy homeostasis but are not centrally involved in net dietary lipid absorption: Studies of the LFABP/IFABP double knockout mouse
A virtual screening of CB1 activators found that travoprost (a glaucoma medication) & ginkgetin (a flavonoid from gingko biloba) may be binding to the CB1 receptor
Identification of CB1 Ligands among Drugs, Phytochemicals and Natural-Like Compounds: Virtual Screening and In Vitro Verification
2021: On targeting your FAAH & MAGL enzymes
Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors
2020: A comparative study of how CBD & CBG-type molecules interact with CB1, CB2 & the joined heteromer of both receptors together
Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors
In our Neural Ocean metaphor, this would be what happens when an Indian elephant, a wooly mammoth & all of their cousins get together at a regular bar joined to a gay bar.
The inevitable outcome: a huge karaoke rendition of Bohemian Rhapsody that helps to electrify the entire neural city.
2019: Making a novel form of CBD for better penetration into the eye
Analog Derivatization of Cannabidiol for Improved Ocular Permeation
2020: Why does THCA decarboxylate faster than CBDA?
Why Is THCA Decarboxylation Faster than CBDA? an in Silico Perspective
2019: How 6 of the big steroid hormones alter the membrane binding ability of FAAH, the destroyer of anandamide
Role of Steroids on the Membrane Binding Ability of Fatty Acid Amide Hydrolase
2019: When using nano-encapsulation to deliver drugs to the brain, the presence of CBD helps those capsules to enter the brain
Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood-Brain Barrier Both in Vitro and in Vivo
PS: This week’s musical hero is Mary Lou Williams, often called jazz’s greatest female musician. She taught herself to play the piano by ear & was performing publicly by the age of 6. She soon began working in vaudeville & became the musical arranger & lead soloist for a Kansas City orchestra. By the ‘40s, she had written & recorded with greats like Duke Ellington & Benny Goodman & was soon mentoring the next generation of bebop musicians like Thelonious Monk, Charlie Parker, Miles Davis & Dizzy Gillespie. Despite always changing with the times, she never lost the roots of her youth or the power of her musical creativity. You can hear her recordings from the war years here as well as her first album, ‘The Zodiac Suite’.
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 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.