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Hello everyone,

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. You can see my portfolio here.
#opentowork

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This newsletter only spreads by word of mouth – so please forward it to colleagues & share to your friends & elderly relatives. If you become a paid subscriber, there’s no extra content, but your support allows me to produce more cannabinoid science content for the community.

As always, at the bottom there’s a Living Glossary of cannabinoid terms along with the weekly music recommendation.

Organizational note:
I’m starting to break out the research into its own categories more often. This should make it easier to parse – but it also means that some of the best clinical research may now be in its relevant category instead of in the top ‘clinical studies’ section.
With 80+ research papers each week, organization will always be a moving target.

This week…

  • So so much on neurodegeneration
  • CBD for social anxiety!
  • On cannabis in the trans community
  • On the yin & yang of cannabinoids & the heart
  • PEA to make your painkillers work better, to protect your heart during chemotherapy treatment & for the neuropathic pain of diabetes
  • A CBD inhaler for your COVID infection or a CBD/lidocaine gel for your topical pain
  • Cannabis may cause psychosis in 1 out of every 200 users
  • CBD bio-plastics plastics for inside your body & THC-powered fuel cells (one hopes that the next generation of androids will be driven by cannabinoids)
  • AI to look at the risk factors for cannabis use disorder between the genders

New Sponsor: PlusCBD & their unparalleled product selection

I spent 3 years working full-time for PlusCBD before I launched my own business & so I know from the inside about their commitment to making quality CBD products. But that’s not the most special thing about the PlusCBD products from CV Sciences. What they do better than any other company in the industry is create a wide range of products.

Nobody else has this much…

  • Oils, capsules & gummies of course
  • Topicals that come as balms, creams, roll-ons & special formulations for arthritis or athletes that contain menthol & camphor
  • The Reserve Collection! Oils, capsules & gummies containing 2.5 mg of THC per serving
    (I’m constantly being asked how people in non-medical can get THC-rich products & this is always what I recommend to them. Especially because it’s an easy to use standard serving size that’s just the right amount for people new to THC)
  • Excellent pet products in a range of flavors
  • 3 very special formulations with other ingredients:
    • Sleep gummies: Includes 3 mg of melatonin + extract of lemon balm & magnolia bark (two old plants for inducing sleep)
    • Calm gummies: Includes 5-HTP (the serotonin precursor) & L-theanine (from tea)
    • Relief capsules: Includes PEA + CBDA (see the Living Glossary below for why I think these are the ingredients of the future for immune health & gut health)

That’s why I recommend PlusCBD to so many of the clients I consult with: they offer an array of products for your health like no other.

Buy their excellent products today at PlusCBDoil.com.

Best of cannabinoid science...

A review confirms the efficacy of CBD for social anxiety
Systematic literature review of human studies assessing the efficacy of cannabidiol for social anxiety
https://www.sciencedirect.com/science/article/pii/S2772598722000551
#IntrovertsUnite!

A survey of people with substance use disorder who used CBD found that it helped them to sleep better, relax, reduce pain & feel less anxious
Cannabidiol use among patients with substance use disorders
https://www.tandfonline.com/doi/abs/10.1080/14659891.2022.2120425

A diary study of using cannabis for PTSD with CBD-rich products found to be the most helpful for having less early awakenings from sleep
Posttraumatic stress disorder, sleep and medical cannabis treatment: A daily diary study
https://www.sciencedirect.com/science/article/abs/pii/S0887618522001050

In teens rats withdrawing from an alcohol binge, CBD increased their social exploration, reduced stress hormone levels, restored dopamine transmission & helped to strengthen & remodel their brain connections
Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats
https://pubmed.ncbi.nlm.nih.gov/36065905

On using PEA to reduce the tolerance to opiates & enhance their painkilling abilities
Role of PEA in Reduction of Opiate Tolerance
https://www.jbclinpharm.org/articles/role-of-pea-in-reduction-of-opiate-tolerance.pdf

In heart cells exposed to typical chemotherapy drugs, PEA protected them from cell death & inflammation via the PPAR-α pathway (nuclear receptors that on & off genetic transcription) & the NLRP3-related pathways (related to inflammation)
The analgesic compound palmitoylethanolamide reduces inflammation in human cardiomyocytes and vascular endothelial cells exposed to doxorubicin and anti-HER2 monoclonal antibody through PPAR-α and NLRP3-related pathways
https://www.annalsofoncology.org/article/S0923-7534(22)01894-4/fulltext

AI to look at the gender differences in risk factors for cannabis use disorder
Explainable machine learning analysis reveals sex and gender differences in the phenotypic and neurobiological markers of Cannabis Use Disorder
https://pubmed.ncbi.nlm.nih.gov/36115920
“Risk factors with larger effect sizes in men included personality (high openness), mental health (high externalizing, high childhood conduct disorder, high fear somaticism), neurocognitive (impulsive delay discounting, slow working memory performance) and brain (low hippocampal volume) factors. Conversely, risk factors with larger effect sizes in women included environmental (low education level, low instrumental support) factors. In summary, environmental factors contributed more strongly to CUD in women, whereas individual factors had a larger importance in men.”

CBD extract works well with antibiotics to kill salmonella
Cannabis sativa CBD Extract Exhibits Synergy with Broad-Spectrum Antibiotics against Salmonella typhimurium
https://www.preprints.org/manuscript/202209.0143/v1

A combination of lidocaine & CBD for the topical treatment of pain
Design of Liposomal Lidocaine/Cannabidiol Fixed Combinations for Local Neuropathic Pain Treatment
https://www.mdpi.com/1999-4923/14/9/1915/html

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)

For people looking improve their health with the use CBD, cannabis & more novel ingredients like PEA (immune system), oleamide (sleep) or psychedelics, I offer counseling sessions on how to use these tools simply & easily.

You can see my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression here.

We’ll meet to discuss what you want to fix, we’ll come up with a gameplan of what to try, I’ll help you to buy it (the cost of products almost always comes out to less than $100) & then I’ll be there to talk you through trying them out to find the best routine for you. Plus, unlimited follow-up emails.

If you want someone experienced in listening to patients & coming up with a plan to help you find relief, book a 1-on-1 session with me here:
Your Cannabis Counseling Sessions.

I’m also available to meet with medical professionals to advise them on using cannabis, cannabinoids & psychedelics in their practice. I’ve seen an uptick in the number of sessions for this & I can say that they find these one-hour brain pickings quite useful because I’m a walking ‘rule of thumbs’ from my years of interviewing practioners. Plus, you get a follow-up email with all of the relevant science to your questions as well as recommended books & further resources. I can help you help your patients to better use these powerful tools of health. See here for more information:
Cannabinoid & Psychedelic Education Sessions

On Nov 15th & 16th, the National Indigenous Cannabis Policy & Advocacy Summit in DC
https://www.eventbrite.com/e/national-indigenous-cannabis-policy-advocacy-summit-tickets-404333701987
I’m hoping to attend this & cover it. Let me know if you’re an editor who’d be interested.

On Oct 7th, a talk on the complexities of cannabis & driving by Dr. Thomas D. Marcotte for the Society of Cannabis Clinicians & CSequence
https://cannabisclinicians.tradewing.com/event/YWFn4LcP7rNHeDK8w

Attend IACM: The Great European Cannabinoid Conference!

On Oct 20th & 21st, you can virtually attend the 12th International Association for Cannabinoid Medicines (IACM) Conference on Cannabinoids in Medicine. The tickets are well worth it for the ability to learn from this array of speakers.

Buy your tickets now before the price goes up on Oct 12th. This conference mixes the best of cutting-edge endocannabinoid science with the practical use of cannabis by healthcare practitioners.
And if you’re going in person, I’ll see you there.

the Headlines & Fav Articles

It’s official. The World Anti-Doping Agency will keep cannabis on their list of banned substances because its use "violates the spirit of sport"
https://www.marijuanamoment.net/marijuana-is-staying-on-the-banned-substances-list-for-international-athletes-world-anti-doping-agency-announces
Fuck them. Fuck this.

Colorado & Washington made more tax money from cannabis than alcohol & tobacco
https://www.marijuanamoment.net/colorado-and-washington-got-more-tax-revenue-from-marijuana-than-from-alcohol-or-cigarettes-in-fiscal-year-2022-report-finds
I don’t think this is something to crow about. This plant is heavily overtaxed & that’s made life miserable for cannabis companies as well as for medical patients who acquire their medicine through the recreational system.

NIDA posts a request looking for 4 million grams of cannabis
https://www.marijuanamoment.net/top-federal-drug-agency-seeking-marijuana-grower-able-to-cultivate-and-analyze-4-million-grams-of-cannabis
& the FDA hired a former head of the Cannabis Regulators Association to help them with their cannabis work
https://mailchi.mp/ec68f10e9f7d/could-fdas-recent-hire-hint-toward-regulatory-action-on-cbd
https://www.statnews.com/2022/09/27/health-funding-battles-a-nutrition-policy-overhaul-and-two-cbd-developments

The Cannabis Media Council launches to change the narrative around our favorite old plant
https://www.cannabismediacouncil.com
Join their newsletter & follow them on LinkedIn to support their work.

The NYTimes adds a cannabis industry report. Congrats to Ashley Southall
https://www.nytco.com/press/ashley-southall-and-troy-closson

The US Air Force & Space Force launched a pilot program to give a second chance to recruits who fail their first drug test because of cannabis
https://www.marijuanamoment.net/air-force-and-space-force-recruits-who-test-positive-for-marijuana-will-get-a-second-chance-to-enlist-under-new-pilot-program

Twitter suspended the account of Cookies, one of the biggest cannabis brands
Berner @berner415Today @Twitter suspended { Cookies } a brand recognized by @Forbes , @adage , @ClioAwards @BusinessInsider and more . We didn’t violate any terms, someone paid someone to delete, @jack this a safe home for our audience to stay in tune with our brand . Let’s get us back up RT

A profitable & safe ecosystem for growing cannabis in a Paraguayan nature reserve

Cultivating Cannabis in a paraguayan nature reserve: Incentives and moral justification for breaking the law|
https://link.springer.com/article/10.1007/s12117-022-09464-z

A Mexican cannabis protest & weaving resistance collective
Two Stitches Over and One Under Weaving Resistance with Hemp Thread For Good Living and Well-being
https://ru.micisan.unam.mx/bitstream/handle/123456789/341/VOM_2021_0113_0100.pdf

The War on Drugs & Harm Reduction

The DEA is trying to bill $11k to my friend Dr. Sunil Aggarwal (who’s behind the psilocybin for the end-of-life lawsuit that’s annoying them so much) for a Freedom of Information Act request because of the BS reason that it’d be for his commercial interest
https://www.marijuanamoment.net/dea-suggests-doctor-seeking-psilocybin-for-terminally-ill-patients-has-financial-interest-so-it-wont-waive-records-fee

After the death of a student, LA will distribute overdose reversal kits to every school
https://edition.cnn.com/2022/09/23/us/los-angeles-schools-narcan-naloxone-overdose-response

Just in time for Halloween, the DEA invented the ‘rainbow fentanyl for children’ myth & set themselves up for a big funding boost
Ryan Marino MD @RyanMarinoSo the DEA made up the “rainbow fentanyl” myth last month & spread it to every outlet that would uncritically regurgitate it, while refusing to answer questions or provide evidence. Now they will likely get millions of $ of additional taxpayer money to increase their budget. 🤔

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]

5 questions for my old buddy Thomas Kingsley Brown about ibogaine

The Microdose5 Questions for ibogaine researcher Thomas Kingsley Brown

A 2C-B vape pen: the most visual (& erotic) of the psychedelics now available in the simplest of formats
Zeus Tipado @tipadoThis is a 2CB vape pen!🤯 Had to go all the way to Amsterdam to see this prototype
Prepare for your raves & sex parties to be changed forever.

On dosing fish with ayahuasca for science by Beckett Mufson for Doubeblind
https://doubleblindmag.com/why-are-scientists-dosing-fish-with-ayahuasca

A case study of using THC, CBD & psilocybin against advanced breast cancer
Raising awareness: The implementation of medical cannabis and psychedelics used as an adjunct to standard therapy in the treatment of advanced metastatic breast cancer
https://journals.sagepub.com/doi/10.1177/20503245221114323

A review of how psychedelics promote neuroplasticity
Towards an understanding of psychedelic-induced neuroplasticity
https://pubmed.ncbi.nlm.nih.gov/36123427

An analysis finds that psychedelic use is associated with less days of sick leave from work
Association between Lifetime Classic Psychedelic Use and Sick Leave in a Population-Based Sample
https://pubmed.ncbi.nlm.nih.gov/36141631
#PsychedelicsToBeABetterCapitalist!

In mice, the ability of ketamine to cause hyperactivity was lower in mice with no CB1 receptors
CB1 Receptor Silencing Attenuates Ketamine-Induced Hyperlocomotion Without Compromising Its Antidepressant-Like Effects
https://pubmed.ncbi.nlm.nih.gov/36067014
Somehow, the endocannabinoid system is mixed up with whatever magic that powers ketamine.

An automated ketamine infusion treatment
A Novel, Brief, Fully Automated Intervention to Extend the Antidepressant Effect of a Single Ketamine Infusion: A Randomized Clinical Trial
https://pubmed.ncbi.nlm.nih.gov/36128684
I’ve actually been dreaming of this ever since I began combining ketamine with psychedelic animated shorts in NYC many years ago.
The scifi version would be Google Bed: an automated bed that projects the perfect playlist of animation/music/visuals on the ceiling while dispensing precisely measured doses of ketamine at the proper intervals.

Law & Business

Cannabis companies slashing jobs
https://www.businessinsider.com/cannabis-companies-laying-off-employees-as-industry-hits-a-downturn-2022-9

A look at medical cannabis tourism in Colorado
Overview and Trends of Medical Marijuana Tourism: A Case of Colorado
https://www.taylorfrancis.com/chapters/edit/10.1201/9781003277392-29/overview-trends-medical-marijuana-tourism-case-colorado-soo-kang

A thorough review of what cannabis legalization could look like in Colombia by Luis Felipe Cruz Olivera et al.
FISCAL POLICY IN THE REGULATION OF ADULT-USE CANNABIS IN COLOMBIA
https://www.dejusticia.org/wp-content/uploads/2022/08/CannabisFiscalPolicy-Web.pdf

LinkedIn (the most cannabis-friendly of all the platforms) included three cannabis companies in its 2022 Top Startups list
https://www.linkedin.com/pulse/linkedin-top-startups-2022-50-us-companies-rise-linkedin-news
That being said, they’re all cloud-based supply systems. Nobody touching the plant…

A review of the mass-media campaigns against driving while high
Mass media campaigns and media advocacy related to cannabis-impaired driving: a scoping review
https://www.tandfonline.com/doi/abs/10.1080/14659891.2022.2120436

The Plant & the History

California cannabis farms particularly prone to wildfire damage
The threat of wildfire is unique to cannabis among agricultural sectors in California
https://esajournals.onlinelibrary.wiley.com/doi/pdf/10.1002/ecs2.4205

The USDA reports that European interest in hemp is growing
https://www.marijuanamoment.net/usda-touts-economic-and-environmental-benefits-of-hemp-as-european-market-expands
With my own France leading the way by far… Le pays du chanvre.

On using hempseeds in food formulations
Hemp (Cannabis sativa subsp. sativa) Chemical Composition and the Application of Hempseeds in Food Formulations
https://pubmed.ncbi.nlm.nih.gov/36112300
Hempseeds are known for having an ideal ratio of fatty acids as well as being one of the most widespread foods in human history.
For instance, hemp seed oil combined well with aerobic exercise to improve a number of biomarkers in young sedentary men
Effects of hemp seed alone and combined with aerobic exercise on metabolic parameters, oxidative stress, and neurotrophic factors in young sedentary men
https://pubmed.ncbi.nlm.nih.gov/36114824

Hempcrete approved for US residential building codes
https://www.hempbuildmag.com/home/hempcrete-approved-for-us-residential-building-code-update
According to our resident Construction Knowledge Skeptic Ned Pelger, “It’s funny that they put this in the appendix right next to straw bale construction, which is another goofy idea - but still a better idea than hempcrete. Getting placed in the appendix of the building code just shows some group with money or influence was pushing for some recognition. When you see UL approvals [Underwriters' Laboratories, a leading independent safety science organization], that's when construction methods actually get understood and used.”
To summarize Ned’s problems with hempcrete,

· It’s only an insulating material – not a structural material. All hempcrete does is replace fiberglass insulation batts in a wall and it appears to have a much lower insulation value & be much more difficult to use.

· You must use conduit for any wires running through it, which is too prohibitive a cost for most projects

· Hempcrete needs a number of standard (& expensive) tests done by a national lab before it can be approved & put into actual use

How soil pH & fertilization affect the yield of hemp
Fertilization and soil pH affect seed and biomass yield, plant morphology, and cadmium uptake in hemp (Cannabis sativa L.)
https://www.sciencedirect.com/science/article/abs/pii/S0926669021010104

Assessing the effects of fertilizers & sowing density on the yield of hemp
Variation of secondary metabolites in Cannabis sativa L. inflorescences under applied agrotechnological measures
https://www.sciencedirect.com/science/article/abs/pii/S0926669022010536

Cannabis plant growth & yield are not increased by UVB radiation
Cannabis Inflorescence Yield and Cannabinoid Concentration Are Not Increased With Exposure to Short-Wavelength Ultraviolet-B Radiation
https://pubmed.ncbi.nlm.nih.gov/34795683

A study of the plant that it advances through its stages of growth mainly via internal signals & not because of the light cycles it experiences
Non-photoperiodic transition of female cannabis seedlings from juvenile to adult reproductive stage
https://pubmed.ncbi.nlm.nih.gov/36063227

Cannabinoid Science

Clinical Studies & Surveys

On the unique effects of cannabis in the trans community
The role of forensic physicians in assessing cannabis detection test results in the trans community
https://pubmed.ncbi.nlm.nih.gov/34761707

In patients with gastroparesis (a disorder of the muscle contractions that move food through your digestive tract), the use of cannabis lowered their chances of vomiting
Marijuana Use in Patients with Gastroparesis
https://pubmed.ncbi.nlm.nih.gov/36067326

People with eczema are using cannabis products & would be curious to learn more
Evaluation of Cannabis and Cannabinoid Product Use, Knowledge, and Attitudes in the Eczema Community
https://pubmed.ncbi.nlm.nih.gov/35389585

In dogs with osteoarthritis, a combination of cannabis extract & frankincense reduced inflammation, oxidative stress & chronic pain
Long-term effects of a diet supplement containing Cannabis sativa oil and Boswellia serrata in dogs with osteoarthritis following physiotherapy treatments: a randomized, placebo-controlled and double-blind clinical trial
https://pubmed.ncbi.nlm.nih.gov/36067506

2021: A study on why it’s difficult to use endocannabinoids as biomarkers: they’re too variable & the blood samples need to be processed at low temps immediately
Endocannabinoids as potential biomarkers: It's all about pre-analytics
https://pubmed.ncbi.nlm.nih.gov/34939056

An inhaler designed to give a dose of CBD to lessen the inflammatory cytokine production caused by the CVOID-19 virus or by pollutants
Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants
https://pubmed.ncbi.nlm.nih.gov/36159727

Mental Health, Addiction & Mental Effects

A review of how to use cannabis for sleep
Cannabis Dosing and Administration for Sleep: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/36107800
& a review of about using it for insomnia
Updates in the use of cannabis for insomnia
https://pubmed.ncbi.nlm.nih.gov/36102608

2021: A reviews of the effects of cannabis on cognition across the lifespan
The Neurocognitive Effects of Cannabis Across the Lifespan
https://pubmed.ncbi.nlm.nih.gov/35979200

In a mouse model of memory, blocking the CB1 receptor boosted the memory via the noradrenaline hormones
Peripheral CB1 receptor blockade acts as a memory enhancer through a noradrenergic mechanism
https://pubmed.ncbi.nlm.nih.gov/36088492

In young & old female rats, the researchers looked at the effects of cannabis & estradiol (the main hormone that interacts with the cannabinoids) on their spatial learning & memory, with cannabis usually helping
The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages
https://pubmed.ncbi.nlm.nih.gov/34800583

Neurodegenerative & Brain Diseases

An overview of the studies on using CBD to treat Alzheimer’s disease
Cannabidiol in the treatment and prevention of Alzheimer’s disease – a comprehensive overview of in vitro and in vivo studies
https://apcz.umk.pl/JEHS/article/view/39922
“In vitro studies, carried out on cell models of AD, showed anti-inflammatory and antioxidative properties of CBD through a suppression of pro-inflammatory genes and causing a reduction of production of, among others, nitric oxide. Moreover, CBD was proven to decrease amyloid β (Aβ) production, reduce formation and aggregation of tau fibrils, protect against microglial and Aβ-induced neurotoxicity and prevented the Aβ-induced deficit in long-term potentiation in hippocampus. In vivo studies, conducted mostly on mice models of AD, indicated that CBD improves memory and spatial learning, reverses deficit in social and object recognition, reduces anxiety-like behaviors and improves glucose metabolism. One study including humans demonstrated that CBD enhances cerebral blood flow in hippocampus. Currently there are two ongoing clinical trials on the use of CBD in AD-associated agitation”

A review of treating neuropsychiatric diseases by harnessing the endocannabinoid’s power to modulate neurotransmitter release, synapse excitability & support cell signaling & the control of cellular respiration
Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment
https://pubmed.ncbi.nlm.nih.gov/36100658

Recommended for You

On focusing on the CB2 receptor for treating neurodegenerative disease
Interplay Between Endocannabinoid System and Neurodegeneration: Focus on Polypharmacology
https://pubmed.ncbi.nlm.nih.gov/34781863

A Cochrane review of cannabinoids for multiple sclerosis
Are cannabis and cannabinoids effective for symptomatic treatment in people with multiple sclerosis? - A Cochrane Review summary with commentary
https://pubmed.ncbi.nlm.nih.gov/36099645
Unfortunately, I can’t get access – because I’d be especially curious what the review masters at Cochrane have to say.

A review of using CBD for strokes via aneurysm
Cannabidiol's Multifactorial Mechanisms Has Therapeutic Potential for Aneurysmal Subarachnoid Hemorrhage: a Review
https://pubmed.ncbi.nlm.nih.gov/36109476

In rats with traumatic spinal cord injuries, injection with CBD hydrogels caused increased repair, decreased cell death & better function of the mitochondria (powerhouse of the cell)
Cannabidiol-loaded injectable chitosan-based hydrogels promote spinal cord injury repair by enhancing mitochondrial biogenesis
https://pubmed.ncbi.nlm.nih.gov/36075309

In the brains of rats, endocannabinoids play a role in their synaptic plasticity
Electrophysiological study of the interactive role of the cannabinoid breakdown inhibitors and L-type calcium channels on granular neurons in the hippocampal dentate gyrus in rats
https://pubmed.ncbi.nlm.nih.gov/34781846

In a rat model of autism, increasing anandamide in the hippocampus (memory area) & blocking 2-AG in the amygdala (fear center) helped with memory tasks & social functioning respectively
Anandamide and 2-arachidonoylglycerol differentially modulate autistic-like traits in a genetic model of autism based on FMR1 deletion in rats
https://pubmed.ncbi.nlm.nih.gov/36114286

In a mouse model of Huntington’s disease, as the disease progressed, the levels of CB1 decreased in their hippocampus (a memory center of the brain) & activating the CB1 receptor helped to prevent & rescue memory deficits
Cannabinoid receptor in hippocampal hippocampus as a potential therapeutic treatment for the cognitive deficits in Huntington diseases
https://jnnp.bmj.com/content/93/Suppl_1/A92.2.abstract

In a mouse model of seizures, CBD reduced seizures via the phosphatidylinositol 3-kinase (PI3K) signaling pathway
Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K
https://pubmed.ncbi.nlm.nih.gov/36112318

In a patient with a genetic variant that causes epilepsy & neurodevelopmental problems, CBD helped to alter the voltage problems across their neurons
Cannabidiol counters the effects of a dominant-negative pathogenic Kv7.2 variant
https://www.sciencedirect.com/science/article/pii/S2589004222013645

In a mouse model of epilepsy, low doses of anandamide increased the antiseizure power of diazepam (Valium) but decreased its efficacy at high doses via mixed actions at the CB1 & TRPV1 receptors
Dual effects of anandamide in the antiepileptic activity of diazepam in pentylenetetrazole-induced seizures in mice
https://pubmed.ncbi.nlm.nih.gov/36094027

In traumatic brain injury, endocannabinoids help to control neuroinflammation via the MGL enzymes (that break down 2-AG) in the astrocytes (brain support cells)
Endocannabinoid control of neuroinflammation in traumatic brain injury by monoacylglycerol lipase in astrocytes
https://journals.lww.com/nrronline/Citation/9000/Endocannabinoid_control_of_neuroinflammation_in.99846.aspx

In microglia (the guardian immune cells of the brain), their endocannabinoid system reacts to pro-inflammatory stimuli in a variety of ways
The microglial endocannabinoid system is similarly regulated by lipopolysaccharide and interferon gamma
https://pubmed.ncbi.nlm.nih.gov/36150252

In a roundworm model of neurodegeneration, both THC & CBD oil helped to protect their neurons
Neuroprotective potential of Cannabis sativa-based oils in Caenorhabditis elegans
https://pubmed.ncbi.nlm.nih.gov/36100636

In a roundworm model of Parkinson’s, CBD protected the neurons that produce dopamine, decreased their food-sensing disabilities, reduced oxidation & increased their lifespan
Neuroprotective effects of cannabidiol on dopaminergic neurodegeneration and α-synuclein accumulation in C. elegans models of Parkinson's disease
https://pubmed.ncbi.nlm.nih.gov/36108815

2021: In a cellular model of Alzheimer’s disease, 9 non-psychoactive cannabinoids that helped to protect the neurons, lower inflammation, reduce oxidative damage & increase balance to the proteins & mitochondria (powerhouse of the cell)
Efficacy of non-psychoactive phytocannabinoids in a novel phenotypic drug-screening platform for old age-associated neurodegeneration
https://www.researchgate.net/publication/346271101_Efficacy_of_non-psychoactive_phytocannabinoids_in_a_novel_phenotypic_drug-screening_platform_for_old_age-associated_neurodegeneration

In neurons, a surprising cellular study saw CBD causing harms to their mitochondria (powerhouse of the cell)
Cannabidiol Impairs Brain Mitochondrial Metabolism and Neuronal Integrity
https://pubmed.ncbi.nlm.nih.gov/36108318
I was not expecting this because so often, the ability of CBD to help with certain brain diseases is because it helps to fix these cellular energy centers. But experiments in Petri dishes should always be taken with a grain of salt.

Harms, Synthetic Cannabinoids & Cannabis Use Disorder

A large study finds that psychotic symptoms occur in 1 out of 200 people who use cannabis
Rates and correlates of cannabis-associated psychotic symptoms in over 230,000 people who use cannabis
https://pubmed.ncbi.nlm.nih.gov/36068202
That’s the first time I’ve ever seen anybody put a clear number on it – and that number sounds about right to me.

A longitudinal study finds that while cannabis contributes to the likelihood of a psychotic experience, symptoms of anxiety & depression are a greater contributor
Bidirectional relationships between cannabis use, anxiety and depressive symptoms in the mediation of the association with psychotic experience: further support for an affective pathway to psychosis
https://pubmed.ncbi.nlm.nih.gov/36093677

In patients with schizophrenia, the use of cannabis altered their biomarkers such as serotonin receptors & lipid mediators
Cannabis use selectively modulates circulating biomarkers in the blood of schizophrenia patients
https://onlinelibrary.wiley.com/doi/pdf/10.1111/adb.13233

A review of the harms of cannabis on the brain
The Detrimental Effects of Cannabis on Brain. A Concise Review
https://clinmedjournals.org/articles/iaarm/international-archives-of-addiction-research-and-medicine-iaarm-7-036.php

In Canada’s most populous province, the legalization of cannabis saw a large increase to the emergency room for cannabis hyperemesis syndrome
Changes in Emergency Department Visits for Cannabis Hyperemesis Syndrome Following Recreational Cannabis Legalization and Subsequent Commercialization in Ontario, Canada
https://pubmed.ncbi.nlm.nih.gov/36112372

3 teens with cannabis hyperemesis syndrome & hypophosphatemia (low blood levels of phosphate, used for energy & nerve function)
Cannabinoid Hyperemesis Syndrome and Hypophosphatemia in Adolescents
https://journals.lww.com/jpgnr/Fulltext/2022/11000/Cannabinoid_Hyperemesis_Syndrome_and.3.aspx

2021: A case of cannabis hyperemesis syndrome that caused Wilkie’s syndrome aka Superior mesenteric artery syndrome (a compression of the upper part of the small intestine just below the stomach)
A Rare Case of Superior Mesenteric Artery (SMA) Syndrome, or Wilkie's Syndrome (WS) in a Patient With Cannabinoid Hyperemesis Syndrome (CHS)
https://journals.lww.com/ajg/Fulltext/2021/10001/S3700_A_Rare_Case_of_Superior_Mesenteric_Artery.3704.aspx

2021: In the mouth, cannabis smoke increased the growth of the candida fungus
Effect of Cannabis Smoke Condensate on C. albicans Growth and Biofilm Formation
https://pubmed.ncbi.nlm.nih.gov/34835474

A case study of someone with cannabis-induced pancytopenia (a deficiency of all red cells, white cells & platelets)
Cannabis-Induced Pancytopenia
https://www.psychiatrist.com/pcc/addiction/substance-use-disorders/cannabis-induced-pancytopenia
I mean, cannabis is quite a safe substance as far as things go, but 12 joints a day for 7 years will probably cause something to go haywire eventually.

2021: A case of a 2-year-old who accidentally ate a THC8 gummy & became unresponsive
Sedation and Acute Encephalopathy in a Pediatric Patient Following Ingestion of Delta-8-Tetrahydrocannabinol Gummies
https://pubmed.ncbi.nlm.nih.gov/34762615

In a mouse model of motor control, the ability of alcohol & THC to be worse when taken together is because of their additive effects of the neurons of the cerebellum (a movement area) with ethanol letting more THC into the brain & because both decrease neuronal activity
Combined alcohol and cannabinoid exposure leads to synergistic toxicity by affecting cerebellar Purkinje cells
https://pubmed.ncbi.nlm.nih.gov/36109623

A synthetic cannabinoid being sold in Italy as an air freshener
Identification of 5F-Cumyl-PINACA, a Synthetic Cannabinoid, in the Herbal Material Used for Recreational Purposes in the Province of Trieste: Public Health implications
https://pubmed.ncbi.nlm.nih.gov/36111755

Pain & Inflammation

In patients with diabetes experiencing neuropathic body pain, 600 mg of PEA lowered their pain & inflammation scores significantly as well as improving their sleep & mood
A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain
https://pubmed.ncbi.nlm.nih.gov/36057884

In patients with lower back pain from lumbar spinal stenosis (narrowing of the spinal channel), the use of CBD gel caps for 6 months resulted in “significant improvements in pain scores & several quality-of-life measures”
The Use of Cannabidiol in Patients With Low Back Pain Caused by Lumbar Spinal Stenosis: An Observational Study
https://www.cureus.com/articles/106551-the-use-of-cannabidiol-in-patients-with-low-back-pain-caused-by-lumbar-spinal-stenosis-an-observational-study

In macrophages (mobile white blood cells), CBD lowered inflammation as well as the standard treatment of the steroid dexamethasone
Comparison of the in vitro Anti-Inflammatory Effect of Cannabidiol to Dexamethasone
https://pubmed.ncbi.nlm.nih.gov/36159203

In mice feeling an increased sensitivity to pain because of their roommate’s chronic pain injury, this empathy was reversed by injecting CBD (or a benzodiazepine) into their amygdala & it worked via serotonin receptors
The Reversal of Empathy-Induced Hypernociception in Male Mice by Intra-Amygdala Administration of Midazolam and Cannabidiol Depends on 5-HT3 Receptors
https://pubmed.ncbi.nlm.nih.gov/36103283

In a rat model of pain, injection of anandamide in the midbrain lowered their pain levels but also inhibited their sensory inputs
Anandamide in the dorsal periaqueductal gray inhibits sensory input without a correlation to sympathoexcitation
https://www.sciencedirect.com/science/article/pii/S2452073X22000216

The NLRP3 is a key protein in the cell’s membrane for the sensing of inflammation & it turns out that the FAAH enzyme serves a key role in anchoring & stabilizing that protein in the membrane
FAAH served a key membrane-anchoring and stabilizing role for NLRP3 protein independently of the endocannabinoid system
https://pubmed.ncbi.nlm.nih.gov/36104448
In our Neural Ocean metaphor, the NLRP3 is a satellite dish set in the walls of the city for sensing inflammation. And FAAH is the octopus that screws it into place & turns it on.
(man, I need an illustrator so I can get back to writing these books…)

The Heart

The yin & yang of cannabis for the heart
The cannabis paradox: contrasting role for marijuana in cardiovascular disease
https://pubmed.ncbi.nlm.nih.gov/36064830

A rather negative view on cannabis & the heart
Cannabis and the heart: unchartered territory
https://pubmed.ncbi.nlm.nih.gov/36098056
It’s clear from the big longitudinal studies that cannabis is linked to later heart problems – but the connection is not that strong. As far as drugs go, it’s pretty tame – and personally, I consider it well worth the risk. And I think my wife would dread the idea of me stopping cannabis because while it might protect my physical heart, it would not be good for my heart heart.

In male mice without a CB1 receptor being fed a Western diet – but not female mice, the CB1 receptors seem to promote atherosclerosis (hardening of the arteries) by modulating cholesterol uptake & blood vessel inflammation
Endothelial cannabinoid receptor CB1 deficiency decreases oxLDL uptake and attenuates vascular inflammation in atherosclerosis
https://www.atherosclerosis-journal.com/article/S0021-9150(22)00345-8/fulltext

In male mice – but not female mice, the CB1 receptor seems to increase atherosclerosis
Myeloid cannabinoid receptor CB1 deficiency limits macrophage proliferation and atherosclerosis in a sex-specific manner
https://www.atherosclerosis-journal.com/article/S0021-9150(22)00377-X/fulltext

In rats, THC mixed with alcohol caused greater constriction of brain blood vessels in the males but not in the females
Cerebrovascular Effects of Alcohol Combined with Tetrahydrocannabinol
https://pubmed.ncbi.nlm.nih.gov/36108317

Reproductive & Maternal Effects

A review of the preclinical evidence for the reproductive toxicity of THC & cannabis smoke
Animal evidence considered in determination of cannabis smoke and Δ9 -tetrahydrocannabinol (Δ9 -THC) as causing reproductive toxicity (developmental endpoint); part II. Neurodevelopmental effects
https://europepmc.org/article/med/36111653

Cancer

In lung cancer patients, their level of CB2 receptors in the blood & in the tumor correlated with the increased severity of the cancer
Evaluation of the local and circulating expression level of cannabinoid receptor 2 in patients with lung cancer
https://www.sciencedirect.com/science/article/pii/S2452014422001790

In breast cancer cells, β-Caryophyllene (a common terpene in cannabis) reduces the ability of cigarette smoke to make the cancer cells resistant to chemotherapy treatment
β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells
https://pubmed.ncbi.nlm.nih.gov/36140359

In canine skin cancer cells, CB1 & CB2 levels are increased in the low-grade version of the disease
Expression of cannabinoid receptors CB1 and CB2 in canine cutaneous mast cell tumours
https://www.sciencedirect.com/science/article/abs/pii/S0034528822002946

Preclinical Research & Cool Chemistry

The heating of cannabis oils (a model of aging) led to some free radical formation except in MCT oil
Heating of consumer cannabis oils can lead to free radical initiated degradation, causing CBD and THC depletion
https://pubmed.ncbi.nlm.nih.gov/36113706

Making CBD plastics for use in medicines & the human body
Poly(cannabinoid)s: Hemp-Derived Biocompatible Thermoplastic Polyesters with Inherent Antioxidant Properties
https://pubmed.ncbi.nlm.nih.gov/36112124

On creating a CBD nanoemulsion that can go directly from your nose to your brain
Development of cannabidiol nanoemulsion for direct nose to brain delivery: statistical optimization, in vitro and in vivo evaluation
https://pubmed.ncbi.nlm.nih.gov/36108625

Using fluorescence to measure the efficacy of DAGL inhibitors (that raise the levels of 2-AG)
HPLC fluorescence assay for measuring the activity of diacylglycerol lipases and the action of inhibitors thereof
https://pubmed.ncbi.nlm.nih.gov/36113549

2021: A review of the latest generations of synthetic cannabinoids
Fourth generation of synthetic cannabinoid receptor agonists: A review on the latest insights
https://pubmed.ncbi.nlm.nih.gov/34781870

2021: A new analog for blocking the CB1 receptor
Modulation of cannabinoidergic system by a novel pyrazole styrylquinazolinone
https://sciforum.net/paper/view/11343

2021: How to screw with CB1 to see how it works
Understanding the role of the CB1 toggle switch in interaction networks using molecular dynamics simulation
https://pubmed.ncbi.nlm.nih.gov/34785728

The binding of a drug to the CB1 receptor’s allosteric site (not the main binding site, but the site that alters the main binding site) is heavily mediated by other lipids present in the membrane
Membrane Lipids Are an Integral Part of Transmembrane Allosteric Sites in GPCRs: A Case Study of Cannabinoid CB1 Receptor Bound to a Negative Allosteric Modulator, ORG27569, and Analogs
https://pubmed.ncbi.nlm.nih.gov/36066412

A new colorimetric test for differentiating between hemp & THC-rich cannabis
Validation of a combined Fast blue BB and 4-Aminophenol colorimetric test for indication of Hemp-type and Marijuana-type cannabis
https://www.sciencedirect.com/science/article/abs/pii/S2468170922000510

A fuel cell that works by oxidizing THC
A Cannabinoid Fuel Cell Capable of Producing Current by Oxidizing Δ9-Tetrahydrocannabinol
https://pubmed.ncbi.nlm.nih.gov/36094349
There’s a joke in here – but I think the best would be an SNL sketch starring John Belushi & Chevy Chase with Willy Nelson as the guest star.

Thanks.
- lex

PS: For today’s glowing strings, the great violinist Nigel Kennedy plays George Gershwin.
(If you don’t know Kennedy, he does all kinds of eclectic work in all kinds of directions. A very fun rabbit hole of albums to go down…)

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.

Endocannabinoids

The cannabinoids found inside all mammals & almost every other form of life besides insects

The Endocannabinoids System (ECS)
One of the most widespread signaling systems in the human body & brain - but only first discovered in the early ‘90s. Unlike most of the classical neurotransmitters, endocannabinoid are lipids, or fats. This makes them slippery, hard to study & a supremely sensitive signaling system because of the ability of cells to detect minute changes in lipid levels & act accordingly. Intimately connected to the immune system, the neuronal system & the hormonal system, as one old scientist said to me in his cups, “If you told me that the endocannabinoid system is where the body meets the soul, I’d believe you.”

Anandamide (AEA) [Our Great White Whale]
The first endocannabinoid neurotransmitter ever discovered. Widespread in the human brain & produced ‘on-demand’ when needed. Appears quickly, broken down quickly. Often called the neurotransmitter of balance.
[in our neural ocean metaphor, the sperm whale]

2-AG
The second endocannabinoid neurotransmitter discovered. Only 2-AG & AEA have been well studied (thousands of research papers)
[blue whale]

CB1
The first endocannabinoid receptor discovered. Mediates the psychoactivity (getting high feeling of THC). Most importantly, it’s the most widespread receptor of its class in the human brain.
[the bar in the membrane wall of the neuronal city where endocannabinoid whales meet with messenger fish to pass on their messages into the interior of the cellular city]

CB2
The second endocannabinoid receptor discovered. Found in almost every organ of the body & closely connected to our immune system. The CB2 occurs at low levels in the brain where it responds to neural insults.
[a gay bar in the membrane wall of the neuronal city]

FAAH (fatty acid amide hydrolase)
The enzyme that breaks down anandamide & a frequent target of drug discovery for modulating the endocannabinoid system. If you inhibit the FAAH enzyme, it does less breaking down of AEA, and your AEA levels rise. More balance.
[the giant squid that slices sperm whales in half]

Diacylglycerol lipase (DAGL or DGL)
The enzyme responsible for producing 2-AG.

MGL (monoacylglycerol lipase - also sometimes abbreviated as MAGL)
The enzyme that breaks down 2-AG. Another frequent target of drug discovery because inhibiting MGL raises 2-AG levels
[a giant octopus that eats blue whales]

Palmitoylethanolamide (PEA)
An endogenous fatty acid amide whose only reason for not being labeled as a classic endocannabinoid is because it doesn’t bind to the CB1 or CB2 receptor - but it’s a hugely important neurotransmitter found in every cell of the body. A long body of work stretching back to World War 2 has found it to be an amazingly safe & effective drug for a number of things related to the immune system. Available as a dietary supplement, this is one of the best-studied cannabinoids in humans. Highly recommended.
[North Atlantic Right whale of course. Just look at that grin…]

NAAA (N-acylethanolamine acid amidase)
The enzyme for breaking down PEA, with a special function as a messenger for pain & inflammation as well as in the control of obesity.
[a giant Giant Pacific octopus that eats Right whales]

Oleamide (OEA)
An endocannabinoid related to sleep. They discovered it by keeping cats awake for 3 days & then analyzing their spinal fluid. You can buy it on Amazon. 2 scoops helps you to sleep while 6 scoops is a very pleasant psychoactive experience (Hamilton Morris has called it his favorite way to get high - which is saying something). It’s also worth considering for cancer treatment.
[Humpback whale, because it sings hippies to sleep]

Oleoylethanolamide (unfortunately, also abbreviated as OEA sometimes)
An analog of anandamide, this lipid acts via the peroxisome proliferator-activated receptor alpha (PPAR-α) receptors on the cell’s nucleus. These alter genetic transcription, a powerful method of cellular control. In animal models, oleoylethanolamide causes them to eat less food & drink less alcohol. In roundworms, it causes them to live longer. For the orphaned GPR119 receptor (a receptor that might one day be officially designated as a cannabinoid receptor), it may be the native ligand (the thing that binds to it). It’s already identified as the native ligand for hypoxia-inducible factor 3α (HIF-3α). OEA also interacts with our histamines.
[Pygmy sperm whale. Not well known, a smaller cousin to the sperm whale]

Fatty acid-binding proteins (FABPs)
These transport proteins move fatty lipids such as the endocannabinoids around the body. While still mysterious, they’re thought to move anandamide between membranes as well as transporting it to be broken down by the enzyme FAAH. Several types of FABPs exist in humans. THC & CBD bind to some of them. This may explain why endocannabinoid levels tend to increase after consuming cannabinoids. As the brain ages, the levels of FABPs decrease.
[whale cars]

Phytocannabinoids

The cannabinoids produced by the cannabis plant.

THC (delta-9-tetrahydrocannabinol or Δ9-THC)
The well-known & well-studied molecule in cannabis that gets you high - and helps in a number of other fascinating ways.
[African elephant. Powerful, unpredictable, beautiful]

CBD (cannabidiol)
The cousin of THC that does not get you high but does a lot of the heavy lifting in why hemp has been such a staple of medicine since before recorded history. In most plants outside those bred for the recreational market, CBD is the most common cannabinoid. It binds to a wide swathe of receptors outside the endocannabinoid system including three serotonin receptors, two opioid receptors, a dopamine receptor as well as glutamate & GABA (the two most widespread neurotransmitters, the basic neuronal signals for excitation & inhibition, respectively)
[Indian elephant. sweet, gentle, you can work with it]

CBC (cannabichromene)
The third most common cannabinoid in the plant, it’s not well studied in humans despite a number of intriguing preclinical studies, especially as an anti-inflammatory and for pain. Nonpsychoactive, it interferes with the breakdown of AEA & 2-AG (leading to a rise in their levels) as well as interacting with the vanilloid receptors.
[Sri Lankan elephant. Little, sweet, not as well known as it should be]

CBDV (cannabidivarin)
CBDV is like CBD with a shortened tail (side chain). Also nonpsychoactive, it tends to occur at low levels in most cannabis cultivars. It’s known to be an anticonvulsant & is suggested for treating autism in humans & in animal models. The cannabinoid pharmaceutical company GW has it in their developmental pipeline as GWP42006.
[An Asian elephant with a short trunk]
(Easter egg: the first person to email me about this easter egg will get a free copy of my Queer book once I get it printed & up on Amazon soon…)

Δ8-THC (delta-8-tetrahydrocannabinol or THC8)
A more rare cannabinoid in the plant – but one with psychoactive effects. At the moment, the ability to source Δ8-THC from hemp makes it a ‘legal high’ that’s become a hot seller across the US. Of course, the usual legislative & regulatory backlashes are following. It’s been studied as a treatment for glaucoma, eye injuries & the nausea of chemotherapy. Most people describe it as a nice mellow way to get high.
[The forest species of the African elephant – smaller & more elusive]

Beta-caryophyllene (BCP)
A terpene that’s also a cannabinoid.
The terpenes of cannabis give the plant its smell. Also found in oregano, black pepper, lavender & hops, beta-caryophyllene has a spicy sweet woody smell. But unique among terpenes, this one also binds to the CB2 receptor, making it a dietary cannabinoid. It shows a potential for treating inflammation, pain, anxiety & seizures. The FDA has designated it to be GRAS (generally regarded as safe) & thus it can be safely used as a food additive.
[a terpene/cannabinoid that travels through the air? That could only be a flying elephant]

Pharmaceutical cannabinoids

Nabiximols (ie Sativex®)
A pharmaceutical 1:1 CBD:THC spray produced by GW Pharmaceuticals. One of the first cannabinoid pharmaceuticals on the market, Sativex is an approved treatment for neuropathic pain, spasticity, overactive bladder & the symptoms of multiple sclerosis.

Epidiolex® (in the UK, Epidyolex®)
An isolated CBD formulation approved for treating the severe seizures of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. Produced by GW Pharmaceuticals, the doses tend to be incredibly high – hundreds or thousands of milligrams of CBD every day in young children. But even with that, the side effects tend to only be lethargy & stomach upset.

Dronabinol (ie Marinol® and Syndros®)
A synthetic form of THC for the treatment of anorexia in AIDS patients & the nausea of chemotherapy. These tend to not be popular with patients because it’s a horse dose of THC with no modulation by the other molecules in the cannabis plant like CBD.

Nabilone (Cesamet®)
A synthetic derivative of THC approved for treating the nausea of chemotherapy patients.