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

First newsletter livestream tonight!
Tonight after I finish a cannabis consulting session, I’m going to try my first YouTube livestream where I talk over this week’s cannabis news with my own colorful-ish commentary.
I’m not exactly sure how this will work but you can subscribe to my channel here & we’ll see what happens. It should be around 3 PM EST.

(I did a test video news last week but my computer’s webcam is much worse than my phone’s camera so hopefully tonight will look better)

This week…

  • Big big reviews of CBD for insomnia & sleep problems
  • On why people who use cannabis spend less time in the hospital, use less painkillers & enjoy better deaths
  • Canada pays for the cannabis of its veterans & the US wrecks their lives for using it
  • THC & CBD to fix the singing ability of brain-damaged songbirds
  • Using cannabis to help boost the efficacy of methadone maintenance for people with opioid use disorder
  • Lots of brains studies on the effects of cannabis on teen brains
  • On how to microdose THC
  • Acupuncture works via the ECS
  • In people with gastroparesis who have trouble emptying their stomachs, three different studies came out just this week about how cannabinoids help them in various ways
  • In history, smoking out of clay pipes & in India, the colonial pressures against native doctors using cannabis

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And finally, they test their products at least 3 times internally & once externally[LP1] by third-party labs before it ever goes out the doors.

The result is an excellent CBD-rich hemp extract product that changes people’s lives.

Buy your CBD from PlusCBD today.

Best of cannabinoid science...

A review finds cannabis excellent for end-of-life care
Use of Medicinal Cannabis for Palliative Care Patients: A Systematic Review
https://www.scirp.org/journal/paperinformation.aspx?paperid=120021

In older adults, their most common reason to use medical cannabis was pain & sleep
Medical cannabis authorization patterns, safety, and associated effects in older adults
https://pubmed.ncbi.nlm.nih.gov/36131299

2021: In patients with cirrhosis, those who used cannabinoids had a decreased total hospital cost
Cannabinoid Use and Total Hospital Cost in Patients With Cirrhosis: A Study Based on Nationwide Inpatient
https://journals.lww.com/ajg/Fulltext/2021/10001/S1098_Cannabinoid_Use_and_Total_Hospital_Cost_in.1099.aspx

For patients after hip or knee surgery, cannabis use was associated with less use of opioid painkillers
Self-Reported Cannabis Use Is Associated With a Lower Rate of Persistent Opioid Use After Total Joint Arthroplasty
https://pubmed.ncbi.nlm.nih.gov/36158462

In a patient taking sertraline for depression, the ability of CBD to inhibit the liver enzyme CYP2C19 caused them to have low sodium in their blood & cognitive impairments
Hyponatremic Cognitive Dysfunction Resulting from Drug-Drug-Gene Interaction between Sertraline and Cannabidiol in an Intermediate CYP2C19 Metabolizer Patient
https://pubs.lib.umn.edu/index.php/innovations/article/view/4890
CBD doesn’t have many key drug interactions – but it does alter liver enzyme functionality and no one is quite sure which ones are clinically relevant & how much CBD you need to take to his the levels to cause negative effects, so that’s why I always try to highlight any I find.

In songbirds with brain damage, we already knew that CBD helped them to recover their singing ability – and then this research demonstrates that a low dose of THC helps the CBD to work better while a high dose of THC slows down the CBD’s positive effects
Δ9-Tetrahydrocannabinol Differentially Alters Cannabidiol Efficacy in Recovery of Phonology and Syntax Following Damage to a Songbird Cortical-Like Brain Region
https://pubmed.ncbi.nlm.nih.gov/36125410
The ability of songbirds to learn songs is one of our best models for the ability of humans to learn language.
Why did these abilities arise?
To get laid.

In skin connective tissue cells, combining CBD with common nutrient treatments (such as resveratrol from wine) increased their viability & wound-healing functionality as well as reducing their metabolic dysfunction
The Effects of Nutrient Signaling Regulators in Combination with Phytocannabinoids on the Senescence-Associated Phenotype in Human Dermal Fibroblasts
https://pubmed.ncbi.nlm.nih.gov/35955938

In a mouse model of sickle cell anemia, CBD lowered their sensitivity to pain
Cannabidiol attenuates hyperalgesia in a mouse model of sickle cell disease
https://pubmed.ncbi.nlm.nih.gov/36122382
There’s not a ton of research on cannabinoids for sickle cell anemia, but there’s enough positive stuff like this out there that I think people should give it a try.

In a mouse model of neuropathic pain, a spinal cord pump of CBD & THC reduced their mechanical & cold sensitivities while causing no psychoactive effects
Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model
https://pubmed.ncbi.nlm.nih.gov/35955774
This is an innovative drug delivery system for the cannabinoids. The ability to give people more THC without making them as high is excellent for its use as a medicine.

In mice, electroacupuncture works via the endocannabinoid system
Combined-Acupoint Electroacupuncture Induces Better Analgesia via Activating the Endocannabinoid System in the Spinal Cord
https://pubmed.ncbi.nlm.nih.gov/36160326

A review of the neuroprotective effects of CBD against neurological disorders & neuroinflammation regulated by the microglia (the guardian immune cells of the brain)
Neuroprotection of Cannabidiol, Its Synthetic Derivatives and Combination Preparations against Microglia-Mediated Neuroinflammation in Neurological Disorders
https://pubmed.ncbi.nlm.nih.gov/35956911

A review of why these endocannabinoid signaling lipids have so much damn therapeutic opportunity
Anandamide and other N-acylethanolamines: A class of signaling lipids with therapeutic opportunities
https://pubmed.ncbi.nlm.nih.gov/36150527
& a big sexy review of how they work (by DiMarzo <swoon>)
Biosynthesis and metabolism of endocannabinoids and their congeners from the monoacylglycerol and N-acyl-ethanolamine families
https://pubmed.ncbi.nlm.nih.gov/36152677

Cannabinoids from the plant have higher antioxidant power than the isolated synthetic cannabinoids
Natural vs. artificial cannabinoid oils: the comparison of their antioxidant activities
https://pubmed.ncbi.nlm.nih.gov/36164439

Using brewer’s yeast to make CBD
Boosting the Cannabidiol Production in Engineered Saccharomyces cerevisiae by Harnessing the Vacuolar Transporter BPT1
https://pubmed.ncbi.nlm.nih.gov/36122349
& how to find the best yeast for the job
Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow
https://pubmed.ncbi.nlm.nih.gov/36127350
This kind of tech always fascinates me – but it always runs into the same problem: it doesn’t scale up well. For making CBD, it’s pretty hard to beat the efficiency of a hemp plant waving in the sun…

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 patients:
I make it simple for people with health conditions to use CBD, THC & other tools to improve their pain, their anxiety, their sleep & their health. Book a 30 minute session with me & we’ll talk over what you want to fix, I’ll create a gameplan & then send it over to you. It will include what to take & when, where to buy it & how to experiment with taking higher levels. Plus, unlimited email followups for all of your question.

See my advice for using cannabinoids for pain, neurodegeneration, autism, insomnia & anxiety/depression.

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.

For healthcare practitioners:
I also meet with medical professionals to advise them on using cannabis, cannabinoids & psychedelics in their practice. I’ve seen an uptick in the number of these sessions from doctors & nurses & they tell me that they find these one hour discussions quite useful because I’m a walking ‘rules of thumb’ from my years of reading the science & interviewing practitioners. Plus, you get a follow-up email with all of the relevant scientific research to your fields of interest & all of the notes on what we talked about.

I can help you help your patients better use these powerful tools of health.

Book a session here:
Cannabinoid & Psychedelic Education Sessions

On microdosing THC & cannabis
https://tripsitter.com/microdosing/thc

Synthetic THC (dronabinol) should perhaps be the first sleep apnea pill
https://sleepreviewmag.com/sleep-disorders/breathing-disorders/obstructive-sleep-apnea/dronabinol-synthetic-thc-strong-contender-for-first-sleep-apnea-pill

Check out the CannMed archives for a plethora of great cannabis science lectures & videos for healthcare practitioners
https://cannmedevents.com/cannmed-video-archives

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.
(with new business cards!)

the Headlines & Fav Articles

Biden announced a pardon of the ~6500 federal prisoners with cannabis possession charges, encouraged state governors to do the same & initiated a review of the federal scheduling of cannabis
https://www.marijuanamoment.net/biden-announces-mass-marijuana-pardons-and-calls-for-cannabis-scheduling-review
& Marijuana Moment cataloged a huge review of reactions
https://www.marijuanamoment.net/lawmakers-governors-and-advocates-react-to-biden-marijuana-pardon-and-scheduling-review-announcement
On Twitter, the reactions tended to be:
1. What took him so long?
2. He’s erasing the record of Kamala Harris
(a joke referencing her tough stance on weed as the attorney general of California)

On the 6 states voting in Nov on cannabis legalization & what those markets might look like

Bryan Fields @BryanFields24Six States to decide on Cannabis legalization this November. Oklahoma Missouri Arkansas Maryland North Dakota Nebraska What does this mean for the cannabis industry? Let's explore each market.3:58 PM ∙ Oct 5, 2022

116Likes29Retweets

An op-ed from the CEO of Veterans Cannabis Coalition on how Canada reimburses their veterans for medical cannabis while the US Dept of Defense actively sticks its head farther into the sand
https://www.marijuanamoment.net/as-canada-reimburses-medical-marijuana-for-military-veterans-the-u-s-keeps-failing-those-who-served-op-ed
The VCC would be a great organization for you to support monetarily or at least give them a follow on social media & amplify their message.

A study shows that the federal illegality puts consumers at risk because of different approaches to regulating contaminants like solvents, microbes & pesticides
https://www.marijuanamoment.net/federal-marijuana-prohibition-is-putting-patients-at-risk-of-consuming-contaminated-products-study-finds

According to an OSHA report, at a Trulieve facility in Massachusetts, a worker packing pre-rolls died due to the inhalation of cannabis dust
https://theshoestring.org/2022/10/03/as-marijuana-industry-expands-holyoke-worker-dies-after-prolonged-exposure-to-ground-cannabis-dust
The problem of cannabis dust causing lung problems is not a new one. Also, cannabis allergies can arise in workers after long exposures to such much cannabis material. The unique challenges facing cannabis workers are still being grappled with.

Undocumented workers on illegal cannabis grows face unsafe working conditions, illegal pesticides, wage theft & violence
https://www.politico.com/news/magazine/2022/10/02/weed-cannabis-undocumented-immigrants-00059827
Politico consistently has strong reporting on cannabis.

Beautiful shot electron microscope shot of a cannabis stem

microscopic images. @microscopicturecross-section of a 5-day-old cannabis plant stem, captured with an electron microscope 6:22 PM ∙ Oct 1, 2022

1,812Likes191Retweets

The ASTM adds 4 new testing standards: testing for cannabinoid content, pesticide concentrations, terpene levels & heavy metals
https://newsroom.astm.org/newsroom-articles/astm-internationals-cannabis-committee-approves-four-new-standards
ASTM is the standards testing group & it legitimizes the whole industry when they create new standards.

The unfamous American arrested for medical cannabis in Russia, Marc Fogel, just got moved to a hard-labor penal colony
https://triblive.com/local/oakmont-man-detained-in-russia-to-be-moved-to-hard-labor-penal-colony

In excellent news, the Japanese group The Asa Girls just released their song "Go Ho Ka" (Legalize It)

Jeffrey J. Hall 🇯🇵🇺🇸 @mrjeffuJapan now has a Marijuana Idol group. The Asa Girls recently released their song "Go Ho Ka" (Legalize It) , with lyrics about how great marijuana is and how Japan needs to legalize it. https://t.co/wdmkBvxLl8

正高佑志 a.k.a. MASATAKA 医療大麻のお医者さん @yuji_masataka

お待たせしました。 大麻アイドルASA GIRLS、デビューです。 GO! HO! KA! - ASA GIRLS (Official Music Video) https://t.co/5sKYkCPlNI https://t.co/INU6dI4t1o3:10 AM ∙ Oct 8, 2022

571Likes134Retweets

& a health ministry panel agrees
https://www.bloomberg.com/news/articles/2022-09-29/japan-should-consider-approving-medical-cannabis-government-panel-says
We hope it’s because they really dug the song.

The War on Drugs & Harm Reduction

An analysis of the last 20 years of data shows that no matter the kind of cannabis laws you change, the racial disparities in arrest rates between Blacks & Whites continue
Association of Racial Disparity of Cannabis Possession Arrests Among Adults and Youths With Statewide Cannabis Decriminalization and Legalization
https://pubmed.ncbi.nlm.nih.gov/35977162

On anxiety, adolescent cannabis use & the school-to-prison pipeline
The Role of Adolescent Anxious Mood, Marijuana Use, and Locus of Control in the School to Prison Pipeline
https://journals.sagepub.com/doi/abs/10.1177/00131245221124871

2021: Using cannabis to help boost the efficacy of methadone maintenance for people with opioid use disorder
The Cannabis-Dependent Relationship Between Methadone Treatment Dose and Illicit Opioid Use in a Community-Based Cohort of People Who Use Drugs
https://pubmed.ncbi.nlm.nih.gov/34813374

A study of chronic pain patients using THC suggest that they should wait 9 or 10 hours after ingestion before driving
Assessment of delta-9-tetrahydrocannabinol (THC) in saliva and blood after oral administration of medical cannabis with respect to its effect on driving abilities
https://pubmed.ncbi.nlm.nih.gov/36121021

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]

Canada’s province of Alberta will regulate psychedelics for use in therapy
https://www.cbc.ca/news/canada/edmonton/alberta-to-be-1st-province-to-regulate-psychedelics-for-therapy-government-says-1.6607497

Dr. Neşe Devenot on the dark side of psychedelic capitalism
Dark Side of the Shroom: Erasing Indigenous and Counterculture Wisdoms with Psychedelic Capitalism, and the Open Source Alternative
https://anthrosource.onlinelibrary.wiley.com/doi/10.1111/anoc.12154

On regulators trying to navigate psychedelic therapies by Helen Collis for Politico
https://www.politico.eu/article/navigate-high-low-psychedelic-therapy-lsd

A Florida hemp dispensary is selling amanitas mushrooms
https://www.businessinsider.com/magic-mushroom-dispensary-in-florida-is-testing-drug-law-boundaries-2022-10
Amanitas mushrooms are the classic red-capped mushrooms of Siberia, the geographical source for the word shaman. However, these mushrooms, while psychoactive, are a very different kind of trip from psilocybin. (And coincidentally, I just saw this TikTok video explaining their ability to pass on through the urine & how we discovered that because of reindeer). Most people find amanitas unpleasant & despite being available from online grey market vendors & other sources for years, they never really took off. For a great angle on them, read Victor Pelevin’s ‘Homo Zapiens’. That’s where I got the great & true quote: “A person’s first good experience of sex & psychedelics will forever flavor the rest.”
That’s why I like mushroom walks with close friends through city parks.

Prolonged DMT infusions could be a breakthrough for stroke patients
https://psychedelicspotlight.com/prolonged-dmt-infusions-could-be-a-breakthrough-for-stroke-patients

A case study of a man treating his treatment-resistant depression with microdosing psilocybin
Self-administration of Psilocybin in the Setting of Treatment-resistant Depression
https://pubmed.ncbi.nlm.nih.gov/36204170

Intriguing article on how psychedelics change the brain’s control energy landscape & make it easier to increase brain dynamics & the diversity of the activity
Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape
https://pubmed.ncbi.nlm.nih.gov/36192411

Law & Business

Interviews with 6 of the biggest banks who are willing to service the cannabis industry by Crystal Tse

https://www.bloomberg.com/news/newsletters/2022-10-03/top-marijuana-investment-bankers-who-s-who-in-cannabis-advisory

The Plant & the History

A fascinating history paper on the colonial shift in India away from cannabis because of the pressures on native physicians
Shifts in therapeutic practices and decline of medicinal cannabis in Indian North-Eastern Frontier (1826-1925)
https://pubmed.ncbi.nlm.nih.gov/36171626

A poster on the history of clay pipes & cannabis smoking on the Iberian Peninsula (Spain)
‘Clay Cannabis Pipes’? Interpretative Approach between Archaeological and Historical Sources on Cannabis and the Clay Smoking Pipes in the Iberian Peninsula from the Medieval to the Early Modern Periods.
https://www.researchgate.net/profile/Miguel-Martins-De-Sousa/publication/356223624_'Clay_Cannabis_Pipes'_Interpretative_Approach_between_Archaeological_and_Historical_Sources_on_Cannabis_and_the_Clay_Smoking_Pipes_in_the_Iberian_Peninsula_from_the_Medieval_to_the_Early_Modern_Period/links/6192d22b07be5f31b78707c6/Clay-Cannabis-Pipes-Interpretative-Approach-between-Archaeological-and-Historical-Sources-on-Cannabis-and-the-Clay-Smoking-Pipes-in-the-Iberian-Peninsula-from-the-Medieval-to-the-Early-Modern-Periods.pdf

The optimal storage conditions for cannabis crops
Optimal Storage Conditions of Commercial Cannabis Crops
https://pubs.acs.org/doi/abs/10.1021/acs.iecr.2c02071

Looking at the transcription pathways in cannabis that lead to the production of cannabinoids
Comparative Transcriptome Analysis Reveals Coordinated Transcriptional Regulation of Central and Secondary Metabolism in the Trichomes of Cannabis Cultivars
https://pubmed.ncbi.nlm.nih.gov/35955443

Hermaphrodites got you down? Try this handheld inelastic photon scanner to find your intersex plants today!
Non-Invasive and Confirmatory Differentiation of Hermaphrodite from Both Male and Female Cannabis Plants Using a Hand-Held Raman Spectrometer
https://pubmed.ncbi.nlm.nih.gov/35956927
(I just wish scientists needed me to write copy for them)

A handheld infrared scanner for identifying high-THC plants
Use of near-infrared spectroscopy for the classification of medicinal cannabis cultivars and the prediction of their cannabinoid and terpene contents
https://pubmed.ncbi.nlm.nih.gov/36165867
The cops want this so badly. They hate this whole, “it might be legal hemp” thing.

Using fungi fertilizer to increase your cannabis yield
Enhancement of growth and Cannabinoids content of hemp ( Cannabis sativa) using arbuscular mycorrhizal fungi
https://pubmed.ncbi.nlm.nih.gov/35958223

Hempseeds as a functional food
Hempseeds (Cannabis spp.) as a source of functional food ingredients, prebiotics and phytosterols
https://9pdf.co/document/qo5gjvxj-view-hempseeds-cannabis-source-functional-ingredients-prebiotics-phytosterols.html

The best method for drying hemp seeds
CFD SIMULATION OF AN INNOVATIVE SYSTEM FOR HEMP SEEDS DRYING
https://acta.fih.upt.ro/pdf/2022-3/ACTA-2022-3-05.pdf

In Romania, the present & future of hemp cultivation
HEMP CULTIVATION IN ROMANIA. PRESENT AND FUTURE
https://acta.fih.upt.ro/pdf/2022-3/ACTA-2022-3-20.pdf

On feeding hemp proteins to fish
Biochemical Characterization and In Vitro Digestibility of Protein Isolates from Hemp ( Cannabis sativa L.) By-Products for Salmonid Feed Applications
https://pubmed.ncbi.nlm.nih.gov/35956747
I think it’s only a matter of time until a Los Angeles restaurant is boasting of only serving fish fed on marijuana, wine & the finest of squid.

Cannabinoid Science

Clinical Studies & Surveys

A look at the risks & benefits of cannabis for older adults
Cannabis Use and Misuse in Older Adults
https://pubmed.ncbi.nlm.nih.gov/34794704

Recommended for You

In a big review of 90 brain imaging studies in adolescents, cannabis use saw “preliminary evidence for functional and structural alterations in frontoparietal, frontolimbic, frontostriatal, and cerebellar regions”
Systematic review of structural and functional neuroimaging studies of cannabis use in adolescence and emerging adulthood: evidence from 90 studies and 9441 participants
https://pubmed.ncbi.nlm.nih.gov/34839363

A meta-analysis of fMRI scans of youths using cannabis found differences in reward processing, executive control & emotional/social processing across a number of brain regions
A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth
https://www.mdpi.com/2076-3425/12/10/1281

In an adolescent twin study, cannabis use was associated with less exercise (but this was explained by family factors) as well as a lower resting heart rate
The effects of cannabis use on physical health: A co-twin control study
https://pubmed.ncbi.nlm.nih.gov/34871975
“These results do not support a causal association between cannabis use once a week and poorer physical health effects among adults aged 25-35.”

A narrative review of using cannabis in the clinic
Clinical Approaches to Cannabis: A Narrative Review
https://pubmed.ncbi.nlm.nih.gov/34823727

A new protocol for administering cannabis for tests: have people smoke at home in front of their computer
The Naturalistic Cannabis Administration Protocol (NCAP): A Proof-of-Concept Study
https://pubmed.ncbi.nlm.nih.gov/36130915
Sign me up.

On using CBD/CBDA paste to treat seizures in dogs
Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs
https://pubmed.ncbi.nlm.nih.gov/35967998
“Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other [anti-seizure medications].”

Mental Health, Addiction & Mental Effects

A big review of 34 studies of using CBD (& equal levels of THC) for insomnia
Use of Cannabidiol in the Management of Insomnia: A Systematic Review
https://pubmed.ncbi.nlm.nih.gov/36149724
& a review of CBD for sleep disorders caused by other illnesses
Cannabidiol in the context of sleeping disorders-induced oxidative stress
https://ojs.actamedicamarisiensis.ro/index.php/amm/article/view/182

In psychiatric patient populations, cannabis use cannot be used as a predictor of aggression or violence
Does cannabis use predict aggressive or violent behavior in psychiatric populations? A systematic review
https://pubmed.ncbi.nlm.nih.gov/36137273

In college students, social anxiety as a cue for craving cannabis
The Relationship Between Social Anxiety and Marijuana Craving in Canadian College Students: Social Anxiety as The Predictor of Marijuana Craving
https://drpress.org/ojs/index.php/ijeh/article/view/1653
I mean, yeah. Despite the fact that cannabis makes me terribly anxious & awkward around people, it’s still the first thing I want to do when I know people are about to arrive.

Activating the GPR55 receptor to help with nicotine addiction
Central GPR55 may prevent nicotine reinforcing actions: a preliminary study
https://ane.pl/pdf/mpXJvKSFCxhnrePT.pdf
GPR55 may one day be known as CB3 & a number of the cannabinoids interact with it.

2021: In mice, the ability of CB1 to mediate the Pavlovian stimulus they receive seems to be mediated by the COX2 signaling pathway of the CB1 receptors in the astroglia (important support cells of the brain)
Astroglial CB1 Cannabinoid Receptors Mediate CP 55,940-Induced Conditioned Place Aversion Through Cyclooxygenase-2 Signaling in Mice
https://pubmed.ncbi.nlm.nih.gov/34887729

Neurodegenerative & Brain Diseases

Individualized (magistral) cannabis formulations helpful for adults with drug-resistant focal epilepsy
Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study
https://pubmed.ncbi.nlm.nih.gov/36129615

On using CBD to treat Parkinson’s disease (Portuguese & English)
Uso de Canabidiol como tratamento para a Doença de Parkinson
https://brazilianjournals.com/ojs/index.php/BJHR/article/view/52267

A review with a negative slant on how the cannabinoids change the activation of genes in your brain
Neurogenetic and Epigenetic Aspects of Cannabinoids
https://pubmed.ncbi.nlm.nih.gov/36135314

In a mouse model of temporal lobe epilepsy, activating the CB1 receptor lowered convulsions
Behavioral and Molecular Responses to Exogenous Cannabinoids During Pentylenetetrazol-Induced Convulsions in Male and Female Rats
https://pubmed.ncbi.nlm.nih.gov/36147210
Temporal lobe epilepsies can cause fascinating effects in the human brain - including religious epiphanies. See this essay by Oliver Sacks.

In a mouse model of poor muscle control (ataxia) caused by damage to the cerebellum, activating the CB1 receptor improved their locomotor activity & almost completely protected their cerebellum neurons from degradation
The cannabinoid antagonist, AM251 attenuates ataxia related deficiencies in a cerebellar ataxic model
https://pubmed.ncbi.nlm.nih.gov/36120979

In a mouse model of neuroinflammation, inhibiting the MAGL enzyme (which breaks down 2-AG) completely reversed their thermal & mechanical pressure sensitivities as well as reducing motor impairment, depressive behaviors & memory loss
Inhibition of Monoacylglycerol Lipase by NSD1819 as an Effective Strategy for the Endocannabinoid System Modulation against Neuroinflammation-Related Disorders
https://pubmed.ncbi.nlm.nih.gov/35955562

In α-synucleinopathy (the buildup of α-synuclein in neurodegenerative diseases like Parkinson’s & dementia with Lewy bodies), the CB2 receptor is critical for the necessary synaptic pruning by the microglia (guardian cells of the brain)
Loss of cannabinoid receptor 2 promotes α-Synuclein-induced microglial synaptic pruning in nucleus accumbens by modulating the pCREB-c-Fos signaling pathway and complement system
https://pubmed.ncbi.nlm.nih.gov/36162511

The creation of lipid nano-balls for carrying cannabis extracts for treating epilepsy
Lipid nano-carriers loaded with Cannabis sativa extract for epilepsy treatment - in vitro characterization and in vivo efficacy studies
https://pubmed.ncbi.nlm.nih.gov/36189477

Computer modeling on why CBD helps with seizures
Investigation of cannabidiol's potential targets in limbic seizures. In-silico approach
https://pubmed.ncbi.nlm.nih.gov/36129109

Harms, Synthetic Cannabinoids & Cannabis Use Disorder

In a pilot sample of older adults, long term cannabis use associated with lower executive functioning & processing speed
Long-Term Recreational Cannabis Use Is Associated With Lower Executive Function and Processing Speed in a Pilot Sample of Older Adults
https://pubmed.ncbi.nlm.nih.gov/34583547
I would bet that this is a real signal - but would you rather be fast or happy?

Should allergists focus more on cannabis?
Should cannabis be a higher priority for allergists?: A history and look down the pipe
https://pubmed.ncbi.nlm.nih.gov/36155693

A clinical guide to managing cannabis withdrawal
Clinical management of cannabis withdrawal
https://pubmed.ncbi.nlm.nih.gov/34791767
Cannabis is most certainly mildly physically addicting & can be quite mentally addicting. Here’s a guide for practitioners who want to help their patients lower or stop their cannabis use.

In brain scans of people with schizophrenia versus cannabis induced psychosis, the people with schizophrenia had the lowest cortical thickness but with differences across different brain areas
Surface-based brain morphometry in schizophrenia vs. cannabis-induced psychosis: A controlled comparison
https://pubmed.ncbi.nlm.nih.gov/36170756

2021: In chronic cannabis smokers, the microbiome of their mouth had increased bad bacteria which may be causing negative brain effects
Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases β-amyloid protein production in the brain
https://pubmed.ncbi.nlm.nih.gov/34826801

A big analysis looks at the factors associated with cannabis use disorder
Cannabis use disorder in relation to socioeconomic factors and psychiatric comorbidity: A cluster analysis of three million individuals born in 1970-2000
https://pubmed.ncbi.nlm.nih.gov/36120841
“Individuals with CUD were more often male, from younger birth cohorts, with lower education and income than those without CUD. Men and women with CUD exhibited differences in education, income and psychiatric comorbidity.”

2021: In people with alcohol use disorder & cannabis use disorder, only the alcohol caused problems in the brain’s oscillation activities
Occipital neural dynamics in cannabis and alcohol use: independent effects of addiction
https://pubmed.ncbi.nlm.nih.gov/34782632

2021: A review of the brain studies on the co-use of alcohol & cannabis
The Effects of Alcohol and Cannabis Co-use on Neurocognitive Function, Brain Structure, and Brain Function
https://link.springer.com/article/10.1007/s40473-021-00243-8

Cannabis use linked to overactive bladder
Relationship between marijuana use and Overactive Bladder (OAB): a cross-sectional research of National Health and Nutrition Examination Survey (NHANES) 2005 to 2018
https://pubmed.ncbi.nlm.nih.gov/36150516

Here's some kind of study on cannabis causing brain blood disorders - but it’s buried so deep behind a paywall that I can’t even read the abstract
Reversible cerebral venous dilatation syndrome associated to cannabis consumption: Expanding the spectrum of cerebrovascular dysregulation disorders?
https://link.springer.com/article/10.1007/s10072-022-06412-1
#FuckTheScientificPublishingModel

In mice, looking at the abuse potential of THC8
Assessment of dependence potential and abuse liability of Δ8-tetrahydrocannabinol in mice
https://pubmed.ncbi.nlm.nih.gov/36179506

Pain & Inflammation

2 reviews on using cannabis for chronic pain
Cannabis for Treatment of Chronic Pain
https://pubmed.ncbi.nlm.nih.gov/35977124
Medical Cannabis or Cannabinoids for Chronic Pain: BMJ Rapid Recommendation
https://pubmed.ncbi.nlm.nih.gov/35977118
& a review with a more negative slant
Systematic Review and Meta-analysis Seem to Indicate that Cannabinoids for Chronic Primary Pain Treatment Have Limited Benefit
https://pubmed.ncbi.nlm.nih.gov/36129666

In pain patients, a topical gel with cannabis oil & a whole bunch of other plant extracts & ingredients caused significant pain reduction
Evaluation of the Analgesic Effect of a New Topical Composition based on Cannabis sativa Oil Enriched in Cannabidiol, Escin, Bromelain, Boswellia Extract, lucosamine sulphate, Methylsulfonylmethane and Methylsalicylate
https://www.cibides.it/wp-content/uploads/2022/07/Favara-et-al.-OMCR-2022-Vol-11-Iss-6.pdf

In a mouse model of fibromyalgia, cannabis oil with low THC levels helped with pain & touch sensitivities as well as lessening depressive behaviors
Broad-spectrum cannabis oil ameliorates reserpine-induced fibromyalgia model in mice
https://pubmed.ncbi.nlm.nih.gov/35988425

In the sodium channels of neurons, an analog of anandamide lowered the transmission of pain signals
Inhibition of the human neuronal sodium channel Nav1.9 by ACEA (arachidonyl-2-chloroethylamide), an analogue of anandamide in a hNav1.9/rNav1.4 chimera, an experimental and in silico study
https://pubmed.ncbi.nlm.nih.gov/36156289

Extracts from hemp seed oil lowered inflammation in human white blood cells
Acyclic Diterpene Phytol from Hemp Seed Oil ( Cannabis sativa L.) Exerts Anti-Inflammatory Activity on Primary Human Monocytes-Macrophages
https://pubmed.ncbi.nlm.nih.gov/35954130

The Guts

In people with gastroparesis (problems with stomach emptying), females had lower levels of anandamide & 2-AG while the men had no differences in these levels
Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in gastroparesis: A sex- and subtype-dependent observation
https://pubmed.ncbi.nlm.nih.gov/32779297

& according to this large analysis, cannabis users “had better hospitalization outcomes, including decreased length of stay and improved in-hospital mortality”
Trends and Socioeconomic Health Outcomes of Cannabis Use Among Patients With Gastroparesis: A United States Nationwide Inpatient Sample Analysis
https://pubmed.ncbi.nlm.nih.gov/33780213
& most of all, cannabis & synthetic THC led to significant improvements for abdominal pain
Cannabinoids Lead to Significant Improvement in Gastroparesis—Related Abdominal Pain
https://journals.lww.com/ajg/fulltext/2018/10001/cannabinoids_lead_to_significant_improvement_in.1204.asp

Reproductive & Maternal Effects

2021: In adolescent rats, chronic exposure to THC led to decreased time in social play
Chronic exposure to ∆ 9-tetrahydrocannabinol in adolescence decreases social play behaviours
https://pubmed.ncbi.nlm.nih.gov/34987774
That being said, social play is measured by the number of attacks, defenses & pins. Maybe instead of wrestling, these mice were in art class making clay “vases” with a long neck & one hole at the bottom.

2021: Maternal cannabis use linked to suppression of certain immune system genes as well as increased anxiety in the offspring
Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring
https://pubmed.ncbi.nlm.nih.gov/34782458

Animal evidence on the link of cannabis smoke to reproductive toxicity
Animal evidence considered in determination of cannabis smoke and Δ9 -tetrahydrocannabinol as causing reproductive toxicity (developmental endpoint): Part III. Proposed neurodevelopmental mechanisms of action
https://pubmed.ncbi.nlm.nih.gov/36125082

2021: In zebrafish (a common model organism for reproduction), cannabis extracts caused “the absence of toxicity, and no significant differences were observed between treatments for both embryo hatching and survival rate” as well as increased locomotion
In Vivo Evaluation of Cannabis sativa Full Extract on Zebrafish Larvae Development, Locomotion Behavior and Gene Expression
https://pubmed.ncbi.nlm.nih.gov/34959625

Cancer

A review of cannabis & cannabinoids for treating children’s cancer
The Use of Cannabis Derived Medical Products in the Treatment of Children’s Cancer: A Systematic Review
https://www.authorea.com/doi/full/10.22541/au.166372385.55043721

In the most common type of pediatric leukemia, activation of the CB2 receptor reduced the expression of several genes related to tumor growth & progression
Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets
https://pubmed.ncbi.nlm.nih.gov/35955786

In animal models, the anti-cancer power of cannabinoids against mesothelioma (a cancer in the thin layer of tissue covering most of your organs)
An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma
https://pubmed.ncbi.nlm.nih.gov/35954477

In breast cancer cells, inhibiting the CB1 receptors made them more liable to cell death by ferroptosis (death by iron! (also the name of our new Viking death metal band))
Inhibition of cannabinoid receptor type 1 sensitizes triple-negative breast cancer cells to ferroptosis via regulating fatty acid metabolism
https://pubmed.ncbi.nlm.nih.gov/36130940

In melanoma & colon cancer cells, a drug that activates the CB2 receptor & blocks the CB1 receptor caused cell death, arrested cell cycles & decreased cell migration
The Synthetic Cannabinoid URB447 Exerts Antitumor and Antimetastatic Effect in Melanoma and Colon Cancer
https://www.mdpi.com/1424-8247/15/10/1166

2021: In mice with colon cancer, a drug that blocks the CB1 receptor & activates the CB2 receptor reduced cell viability, lowered cell migration & increased apoptosis (programmed cellular suicide)
The synthetic cannabinoid URB447 exerts antitumor effect in colon carcinoma and reduces liver metastasis in mice
https://sciforum.net/paper/view/11513

Preclinical Research & Cool Chemistry

Structure-activity relationships for some new cannabinoids
Structure-activity relationships for 5F-MDMB-PICA and its 5F-pentylindole analogs to induce cannabinoid-like effects in mice
https://pubmed.ncbi.nlm.nih.gov/34802041
Structure-activity relationships are a pretty fun part of chemistry. You slightly tweak a molecule’s structure & then see how that alters the molecule’s activity. Sometimes moving just one carbon makes a molecule impotent or supercharges its psychoactivity.

A look at 9 novel synthetic cannabinoids
In vitro and in vivo pharmacology of nine novel synthetic cannabinoid receptor agonists
https://pubmed.ncbi.nlm.nih.gov/36154844

Looking for the best lipid carriers to keep your THC stable
Effect of Lipid Vehicles on Solubility, Stability, and Topical Permeation of Delta-9-Tetrahydrocannabinol
https://pubmed.ncbi.nlm.nih.gov/35962264
Has it tried meditating?

Thanks.

- lex

PS: For this week’s topical music, let’s start with S.E. Rogie’s last album, ‘Dead Men Don’t Smoke Marijuana’. A native of Sierra Leone, Rogie grew up in the highlife & palm wine music style (a West African musical genre of the Kru people playing Portuguese guitars & combining local rhythms with Trinidadian calypso, a "light, easy, lilting style" for enjoying while drinking your palm wine). A master of the guitar & a baritone singer in 4 languages, Rogie incorporated western pop & folk into his repertoire as well as his love of the country music yodelings of Jimmie Rodgers. With this warm & loving musical style, he traveled the US & the UK as a cultural ambassador, often playing his two most famous songs, ‘Please Go Easy with Me’ & ‘My Lovely Elisabeth’. After a heart bypass surgery, he went against his doctor’s advice to travel & play a show in Russia. He collapsed on stage & passed away shortly thereafter, a performer to the very last minute.

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.