C&P#7: THC for PTSD + cannabis for anxiety + the Living Glossary expands...

VA doctors & cannabis, positive drug tests for blue collar workers & FDA warning letters

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Hello everyone,

Congress might force the VA docs to talk about cannabis (but probably won’t), a positive drug test from a hemp extract continues to ruin a life, lots on the notorious Δ8-THC & the FDA issues a new warning letter about making medical claims for CBD.

In science news, there was so much work on PTSD that I broke it out into its own section. And apparently, this is the week of the minor cannabinoids. So if you’re into the cannabinoids like a hipster with their music, there are a couple of little-known cannabinoids that you might get into before they get cool:
cannabichromanon & cannabicyclolic acid for COVID-19 as well as cannabielsoin, dehydrocannabielsoin, cannabimovone & 3'-epicannabimovone for inflammation.
(no, I didn’t add these to the Living Glossary yet. There’s too little known & I wouldn’t know what the hell kind of elephant to make them)

But in the Living Glossary at the bottom, I did add new sections on the approved cannabinoid pharmaceutical formulations, the fatty acid-binding proteins (whale cars), Δ8-THC & the pygmy sperm whale oleoylethanolamide.

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My ad: Cannabis counseling sessions for the brave of heart

My cannabis counseling sessions are not for those afraid to do the hard work of experimenting on themselves & figuring out what works. The cannabinoids can be powerful medicine – but everyone’s endocannabinoid system is different. We have many tools – CBD, THC, PEA, OEA & CBDA – but finding the solution that helps for serious conditions like pain, insomnia, autoimmune disorders & neurodegenerative diseases is not easy. So if you know anyone ready to do the hard work to find health - especially folks dealing with aging, send them here: Cannabinoid Education Sessions.

This newsletter is a free offering from my company White Whale Creations.
I produce educational content for cannabis & psychedelic companies & have sponsorship opportunities for The Lex Files podcast.
#lookingtowork

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Best of cannabinoid science...

A review of medical cannabis in Canada found that it helped patients with anxiety & depression
Medical cannabis use in Canada and its impact on anxiety and depression: a retrospective study
https://www.sciencedirect.com/science/article/abs/pii/S0165178122001834
Here’s my advice for those looking to use the cannabinoids for anxiety & depression.

In sexual & gender minorities who experienced discrimination, they felt less stressed after using cannabis
Real-time associations between discrimination, cannabis use, and mood among sexual and gender minority individuals
https://pubmed.ncbi.nlm.nih.gov/35467899/

This review about using cannabis for rheumatic diseases (joint pain & inflammation) says that the number of positive observational & survey studies points to the need for controlled clinical trials
Cannabis for Rheumatic Disease Pain: a Review of Current Literature
https://pubmed.ncbi.nlm.nih.gov/35486218/
Over & over again you see the same phrase in the cannabinoid literature, “more clinical trials needed.” Despite all the surveys collected by caretakers, all the observational studies carried out by local research centers, despite all the glowing reports that you can read on Reddit & patient forums, the next step of clinical trials to determine the best practices of dosing, ingestion methods & potential side effects do not materialize. We have this incredible medical tool – and for the most part, we just leave it there lying on the ground - occasionally poking it with a stick.
For the FAQs of using cannabinoids for pain, see my advice here. Or for more detailed guidance, book a session with me here.

In cervical cancer, a review of enhancing conventional treatment with CBD
Enhancement of Conventional and Photodynamic Therapy for Treatment of Cervical Cancer with Cannabidiol
https://pubmed.ncbi.nlm.nih.gov/35481367/

In mice with heart failure, CBD “significantly prevented cardiac dysfunction and the development of fibrosis”
Cannabidiol Therapy For Chronic Heart Failure Prevents Cardiac Hypertrophy And Contractile Dysfunction By Reducing Mitochondrial Ros Generation In A Murine Model
https://www.sciencedirect.com/science/article/abs/pii/S1071916422003669

In rat hearts & human heart cells simulating bypass surgery, THC protected the cardiac function, decreased the number of dead cells & reactive oxygen species as well as improved their metabolic function
Δ 9-Tetrahydrocannabinol (Δ 9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment
https://pubmed.ncbi.nlm.nih.gov/35468673/
They propose THC as a pre-treatment before heart surgery.

In a mouse model of oral mucositis (mouth ulcers from chemotherapy), nano-CBD balls accelerated healing & decreased inflammation
Inflammation-targeted cannabidiol-loaded nanomicelles for enhanced oral mucositis treatment
https://pubmed.ncbi.nlm.nih.gov/35467472/

In mice, PEA helps with inflammation in a variety of situations via Toll receptors
Comprehensive lipidomics of lupus-prone mice using LC-MS/MS identifies the reduction of palmitoylethanolamide that suppresses TLR9-mediated inflammation
https://pubmed.ncbi.nlm.nih.gov/35485445/

A study of the minor cannabinoids find anti-inflammatory activities for cannabielsoin, dehydrocannabielsoin, cannabimovone & 3'-epicannabimovone
Synthesis of the Cannabimovone and Cannabifuran Class of Minor Phytocannabinoids and Their Anti-inflammatory Activity
https://pubmed.ncbi.nlm.nih.gov/35476908/
There’s 120+ cannabinoids discovered – and not even the most basic work has been done on any of them. So it’s heartening to see the anti-inflammatory activities of these little known cannabinoids mapped out.

In a computer analysis of cannabinoids against the COVID-19 virus, they found the strongest to be CBN, CBNA, cannabichromanon & cannabicyclolic acid
The Role of Cannabis sativa L. as a Source of Cannabinoids against Coronavirus 2 (SARS-CoV-2): An In Silico Study to Evaluate Their Activities and ADMET Properties
https://www.mdpi.com/1420-3049/27/9/2797

Popular articles & videos

By David Alm, this is one of the best pieces of cannabis journalism I’ve seen in quite a long time: NYC, cannabis, exercise & Black entrepreneurship – an inspiring story (hattip to Ned Pelger)
https://www.runnersworld.com/runners-stories/a38911565/thai-richards-running-cannabis/

ProjectCBD on CBD for traumatic brain injuries
https://www.projectcbd.org/cbd-thc-traumatic-brain-injury

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the Headlines & Fav Articles

A US House bill that encourages medical cannabis discussions by the doctors of the Department of Veterans Affairs got 2 new cosponsors - for a total of 2
https://www.congress.gov/bill/117th-congress/house-bill/6991/cosponsors?loclr=cga-bill&pageSort=lastToFirst
What a depressingly low number. And what’s even worse that it will take a Congressional Act to force the VA to do the obvious right thing.
Meanwhile, the US Navy continues to prohibit sailors from drinking energy drinks with hemp seed oil 🙄
https://twitter.com/navy_reserve/status/1520707356216205313
Ironic for anyone up on their cannabis military history because one of the first ever US governmental reports on cannabis was a 1925 US military study on marijuana smoking in the Panama Canal. Despite several attempts to find a reason to ban marijuana use by US soldiers, the Panama Canal Zone Report issued by the US Army found cannabis to not be addictive or harmful and recommended no stricter controls be taken.
(of course, they eventually banned it because they just didn’t like it. science be damned…)

After a 2-year legal battle, a West Virginia judge upheld the 6-month suspension of a coal miner from his work after a positive drug test caused by a CBD sleep aid (at the time, the miner had two young kids & another one on the way. whew)
https://www.tri-cityherald.com/news/nation-world/national/article260826812.html
A lousy part of this is that pharmacist who suggested a CBD hemp extract said it wouldn’t give a positive drug test. Which is bullshit. When I answered the phones at a CBD company, the number of times that I heard about lives ruined because of a positive drug tests from hemp extracts was far too high. They don’t happen often – but they happen often enough & anyone who says otherwise is selling something.
What needs to change is the drug testing regime. How in the great freedom loving nation of America do we have the right to force so many people to piss into a cup is unbelievable.

The CDC lists Cannabis Use Disorder as its disease of the week
https://www.cdc.gov/dotw/marijuana-use/index.html
And there’s a quiz!

Germany will share a cannabis legalization plan this autumn:
“Cannabis-Legalisierung kommt im Herbst”
https://t3n.de/news/lauterbach-herbst-1470551/
History fakt:
In 1160, Hildegard of Bingen, an abbess considered the founder of scientific natural history in Germany, writes of the medicinal uses of Cannabis in her ‘Physica’.

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Law & Business

Donnell Alexander on ‘The Rocky Road for Black Cannabis Entrepreneurs, Past and Present’
https://capitalandmain.com/the-rocky-road-for-black-cannabis-entrepreneurs-past-and-present

The FDA issued a CBD warning letter to Rena’s Organics for saying things about CBD’s “Cancer-Fighting Capabilities”, “Potential for Neurodegenerative Disorders and Brain Injury”, & “Can It Treat Opioid Dependency?”
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/renas-organic-613036-02112022
Just because all of these things are true does not at all mean that you can say them out loud.

First warning letters from the FDA targeting Δ8-THC products
https://www.marijuanamoment.net/fda-issues-first-warning-letters-targeting-delta-8-thc-products-it-says-are-being-illegally-marketed/
THC8 is the new bath salts.

Schwazze’s Star Buds becomes the first cannabis brand to sponsor a professional sports team: the Colorado Summit, an American Ultimate Disc League franchise
https://www.ganjapreneur.com/colorado-pro-ultimate-frisbee-team-sponsored-by-star-buds-dispensary-chain/
Of course it was an ultimate frisbee team…

The DEA publishes a video about the Pablo Escobar death mask that they have in their collection
https://museum.dea.gov/video-archive/stories-from-the-collection-pablo-escobar-mask
This is gross. Yet it’s an excellent portrait of what happens when you collaborate with the US government. They work with you while you’re useful, and then when you aren’t, they jail you or assassinate you. Escobar was a CIA agent & what happened to him is what happens when you dance with US intelligence. I’ve spent 15 years reading about the US-led Drug War & it still makes me sick to my stomach.
For today’s recommended reading, check out Gary Webb’s ‘Dark Alliance’ about the CIA as the source of the crack/cocaine epidemic. After publication, Webb was found dead by suicide with two shots in the back of the head.

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Medical Cannabis & Culture

On the great Harvey Milk & what he did for cannabis in San Francisco
https://weedmaps.com/news/2022/04/harvey-milk-cannabis-legalization/

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The Plant & the History

In hemp plants, pollination lowered the levels of cannabinoids
Does pollination alter the cannabinoid composition and yield of extracts from hemp (Cannabis sativa L. cv. Finola) flowers?
https://www.sciencedirect.com/science/article/abs/pii/S0926669022004721
In the underground cannabis world, there’s a horror of your female plants getting pollinated. Then they no longer need to produce those sticky resins to attract pollen & the cannabinoid levels drop. But in hemp production, pollination might be a good thing to make sure your crop stays below the (artificially stupid) level of 0.3% THC.

Hemp proteins to make fake meat?
Hemp (Cannabis sativa L.) protein concentrates from wet and dry industrial fractionation: Molecular properties, nutritional composition, and anisotropic structuring
https://www.sciencedirect.com/science/article/pii/S0268005X22002752

On using hemp hurds (inner core fibers) for their antimicrobial properties
Evidence for antimicrobial activity in hemp hurds and lignin-containing nanofibrillated cellulose materials
https://link.springer.com/article/10.1007/s10570-022-04583-w
We know that the refined cannabinoids have antimicrobial properties – but it turns out that you can just the inner stalks themselves for this as well.

On using two aphid predators on medical cannabis as a biological pest control
Glandular trichomes affect mobility and predatory behavior of two aphid predators on medicinal cannabis
https://www.sciencedirect.com/science/article/pii/S1049964422000974

A new handbook on how to produce cannabis indoors
Handbook of Cannabis Production in Controlled Environments
https://www.taylorfrancis.com/books/edit/10.1201/9781003150442/handbook-cannabis-production-controlled-environments-youbin-zheng

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Science

Clinical Studies & Surveys

In patients with severe neuropathic back pain, this industry study found that nabiximols (ie Sativex – a pharmaceutical 1:1 CBD:THC spray) was superior to a long-acting opioid analgesics in terms of pain control & side effects
Effectiveness, Safety, and Tolerability of Nabiximols Oromucosal Spray vs Typical Oral Long-Acting Opioid Analgesics in Patients with Severe Neuropathic Back Pain: Analysis of 6-Month Real-World Data from the German Pain e-Registry
https://pubmed.ncbi.nlm.nih.gov/34480564/
I added nabiximols to the Living Glossary below.

In cannabis dependent patients, nabiximols might help with sleep, mood & pain problems – but honestly, I can’t figure out what these researchers are trying to say (but I suspect they just wanted to milk their large study for another paper)
Mood, sleep and pain comorbidity outcomes in cannabis dependent patients: Findings from a nabiximols versus placebo randomised controlled trial
https://pubmed.ncbi.nlm.nih.gov/35316689/

In a double-blind human study of the skin disease dermatomyositis (muscle weakness & skin rash), activating the CB2 receptor with 20 mg of lenabasum decreased the severity of the condition with no adverse effects
Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Dermatomyositis Patients with Refractory Skin Disease A Randomized Clinical Trial
https://pubmed.ncbi.nlm.nih.gov/35490744/

A survey on the effects of Δ8-THC versus Δ9-THC & CBD
A crowdsourcing survey study on the subjective effects of delta-8-tetrahydrocannabinol relative to delta-9-tetrahydrocannabinol and cannabidiol
https://pubmed.ncbi.nlm.nih.gov/35467921/
Unsurprisingly, they reported it has less of the negative effects of Δ9-THC (probably due to lower potency) & more fun effects than CBD (which is not fun).
See the new entry on Δ8-THC in the Living Glossary below.

Data from the app StrainPrint showed people perceived the help of cannabis for depression, anxiety & insomnia
An investigation of cannabis use for insomnia in depression and anxiety in a naturalistic sample
https://pubmed.ncbi.nlm.nih.gov/35484520

This rather tame safety study of Spectrum Yellow oil (20:1 CBD:THC oil) found only mild or moderate side effects & that by day 7, CBD levels in the blood reached a steady level
Safety, Pharmacokinetics and Pharmacodynamics of Spectrum Yellow Oil in Healthy Participant
https://pubmed.ncbi.nlm.nih.gov/33710277/

A survey of pharmacy students found reasonable attitudes towards cannabis
Pharmacy Students' Knowledge, Attitudes, and Awareness Toward Marijuana Use
https://pubmed.ncbi.nlm.nih.gov/35475401/

An editorial on how the future of studying cannabis & brain health with cohort studies
Cannabis and Brain Health: What Is Next for Developmental Cohort Studies?
https://pubmed.ncbi.nlm.nih.gov/35491566/
A cohort study is following a large group of people for a long period of time & using the data collected to look for associations. They can be quite powerful – especially for the very moderate harms of cannabis that can be harder to detect with small sample sizes.

A reply to a commentary on a review of using CBD for tuberous sclerosis (uncontrolled tumor growth)
Reply to comments on "A scoping review on cannabidiol therapy in tuberous sclerosis: Current evidence and perspectives for future development"
https://pubmed.ncbi.nlm.nih.gov/35500511/
I love replies in the literature. It’s the scientific equivalent of spilling the tea. I wish I could get access to all of this one because the gentle language usually conceals the pointed daggers.

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PTSD

In humans with PTSD, 10 mg of THC helped with problems in the limbic (emotional) system while 5 mg decreased activation of the amygdala (fear center)
Varying Doses of THC Rescue Neural Fear Circuitry Dysfunction in Trauma-Exposed Adults
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)00978-7/fulltext
The researchers suggest treatment with FAAH inhibitors – which is exactly what CBD does. Here’s my advice on using cannabinoids for PTSD.

In humans, a PET scan shows that lower levels of FAAH in the brain are associated with a decreased threat response to threatening social cues
Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation
https://www.sciencedirect.com/science/article/pii/S2666956022000186
One activity of CBD is to lower the activity of FAAH (the enzyme that breaks down anandamide). So this study makes sense of the fact that using CBD helps with social anxiety.
#CBDToHelpYouNotHateParties!

In humans with PTSD whose genes create a slightly different type of FAAH enzyme, their amygdala (brain’s fear center) reacted more strongly to angry faces
Fatty Acid Amide Hydrolase and Threat Related Amygdala Activity in Individuals With PTSD
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)00972-6/fulltext

In children exposed to trauma, they had more anxiety & higher levels of FAAH in their brain’s white matter
Trauma Exposure, Endocannabinoid Signaling, and Variation in Frontolimbic White Matter Pathways in Children
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)00457-7/fulltext

In humans with PTSD, 6 months after the trauma their brains showed higher levels of cortisol, AEA & 2-AG in their blood
Preliminary Results on the Combined Role of Endocannabinoids and Cortisol in the Development of Post-Traumatic Stress and Dysphoria
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)00968-4/fulltext

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Harms & No Help

In those going through cannabis withdrawal, lowered levels of glutamate (the most common excitatory neurotransmitter) in the dorsal anterior cingulate cortex (brain region of cognition & motor controls) is associated with the symptoms of withdrawal
Lower dACC glutamate in cannabis users during early phase abstinence
https://pubmed.ncbi.nlm.nih.gov/35484401/
Look for my upcoming article about glutamate & the cannabinoids at ProjectCBD.

In Black cannabis users, cannabis abstinence phobia (the worry about increased anxiety when quitting) was associated with greater severity of cannabis use problems & more severe withdrawal symptoms
Abstinence Phobia among Adult African American/Black Cannabis Users
https://www.sciencedirect.com/science/article/abs/pii/S0306460322001101

A survey of cannabis users found an association between harmful cannabis use & anxious-depressive symptoms
The relationship between anxious-depressive symptoms and harmful cannabis use: Multiple mediation models via rumination, negative urgency, protective behavioral strategies and refusal self-efficacy
https://www.sciencedirect.com/science/article/pii/S0010440X22000268

A model to predict cannabis use disorder based on 7 factors: biological sex; scores on personality traits of neuroticism, openness & conscientiousness; and measures of adverse childhood experiences, delinquency & peer cannabis use
A Bayesian Learning Model to Predict the Risk for Cannabis Use Disorder
https://www.sciencedirect.com/science/article/abs/pii/S0376871622002137

Combining multiple studies, these researchers found that consuming cannabis with alcohol tended to increase the negative effects of the alcohol
Cannabis use and subjective response to alcohol in the human laboratory
https://pubmed.ncbi.nlm.nih.gov/35523112/
Plus, you might get the spins. Ugh.

The COVID lockdowns led to increased accidental cannabis exposure in young children
Changes in unintentional cannabis exposures in children 6 months to 5 years reported to United States poison centers during the first nine months of the coronavirus-19 pandemic
https://pubmed.ncbi.nlm.nih.gov/35471155/

In Israeli combat vets, those who screened positive for cannabis dependence were more likely to screen positive for depression (but not PTSD)
Sociodemographic and clinical correlates of cannabis dependence among Israeli combat veterans
https://www.sciencedirect.com/science/article/abs/pii/S074054722200068X

Two case studies of young people with heart problems from cannabis
Marijuana: cardiovascular effects and legal considerations. A clinical case-based review
https://bjcardio.co.uk/2022/04/marijuana-cardiovascular-effects-and-legal-considerations-a-clinical-case-based-review/

A case study of a man with seizures from synthetic cannabinoid withdrawal
Chronic Synthetic Marijuana Use: A Case of First-Onset Seizures as a Withdrawal Symptom
https://healthpsychologyresearch.openmedicalpublishing.org/article/34617

In mice going through THC abstinence, they had disturbed sleep patterns, maladaptive behavior & alterations to the release of dopamine in their striatum (a brain center of motor & reward systems)
Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice
https://pubmed.ncbi.nlm.nih.gov/35478010/

A book chapter on the toxicity of CBD
Cannabidiol (CBD) and Its Biological Toxicity
https://link.springer.com/referenceworkentry/10.1007/978-3-030-67928-6_69-1
I can’t get access to this one – but as a professional devil’s advocate, I’m quite curious what it might say.

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Cancer

In cancer survivors, almost 10% responding to this survey said that they used cannabis
Marijuana use among US adults with cancer: findings from the 2018-2019 Behavioral Risk Factor Surveillance System
https://pubmed.ncbi.nlm.nih.gov/35397761/

A look at two hemp varieties found a number of ingredients with activities against cancer
Phytochemical and pharmacological profiles of the essential oil from the inflorescences of the Cannabis sativa L.
https://www.sciencedirect.com/science/article/abs/pii/S0926669022004630

In glioma cells (the most aggressive brain tumor), CB1 levels were lower
Immunohistochemical assessment of cannabinoid type-1 receptor (CB1R) and its correlation with clinicopathological parameters in glioma
https://pubmed.ncbi.nlm.nih.gov/35481563/

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Recent Reviews

An excellent review of CBD’s effect on the TRP ion channels & how this might relate to its effects on seizure, inflammation, cancer, pain, acne, and vasorelaxation
Pharmacological effects of cannabidiol by transient receptor potential channels
https://pubmed.ncbi.nlm.nih.gov/35483477/

And a related paper on CBD & TRPV2
Cannabidiol preferentially binds TRPV2
https://journals.lww.com/nrronline/Fulltext/2022/12000/Cannabidiol_preferentially_binds_TRPV2__a_novel.33.aspx

A review of the effects of CBD on locomotor activity
Effects of Cannabidiol on Locomotor Activity
https://www.mdpi.com/2075-1729/12/5/652

On the other hand, this review of cannabinoids & rheumatology finds that while they might help patients, because of drug interactions & adverse effects, they decided that cannabinoids are a foe
Cannabinoids in rheumatology: Friend, foe or a bystander?
https://pubmed.ncbi.nlm.nih.gov/35476898/

A book chapter on using PEA & polydatin for bladder pain & cystitis
Treatment of Interstitial Cystitis/Bladder Pain Syndrome with Palmitoylethanolamide/Polydatin
https://link.springer.com/chapter/10.1007/978-3-030-94174-1_23

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Preclinical Research

In a number of different animals, CBD demonstrated a “very low abuse potential and [that it] is unlikely to produce physical dependence”
Preclinical assessment of the abuse potential of purified botanical cannabidiol: self-administration, drug discrimination, and physical dependence
https://pubmed.ncbi.nlm.nih.gov/35489780/

In mice with chronic unpredictable stress, those without two of the major fatty acid-binding proteins (FABPs – chaperones that move endocannabinoids around the cell) showed less stress effects in their brains
Unpredictable chronic mild stress differentially impacts resting brain glucose metabolism in fatty acid-binding protein 7 deficient mice
https://www.sciencedirect.com/science/article/abs/pii/S0925492722000476
I added fatty acid-binding proteins to the Living Glossary.

In adults rats exposed to alcohol as teens, oleoylethanolamide (an endocannabinoid-like molecule that alters genetic transcription) caused them to drink less via the CB1 receptor
Attenuation of oleoylethanolamide-induced reduction of alcohol consumption in adult rats exposed intermittently to alcohol during adolescence
https://pubmed.ncbi.nlm.nih.gov/35500667/
I added oleoylethanolamide to the Living Glossary. Confusingly, both this one & oleamide tend to be abbreviated with OEA.

In a rat model of heart injury from the anticancer drug cyclophosphamide, β-caryophyllene treatment improved cardiac markers, increased antioxidant capacity & lessened inflammation & apoptosis (cellular suicide)
β-Caryophyllene Ameliorates Cyclophosphamide Induced Cardiac Injury: The Association of TLR4/NFκB and Nrf2/HO1/NQO1 Pathways
https://www.mdpi.com/2308-3425/9/5/133

In kidney cells, treatment with cannabis leaf extract protected them against iron injuries
Cannabis sativa L. protects against oxidative injury in kidney (vero) cells by mitigating perturbed metabolic activities linked to chronic kidney diseases
https://pubmed.ncbi.nlm.nih.gov/35476933/

In rats with arthritis, aerobic exercise combined with ozone treatment helped to improve their anandamide levels & disease symptoms
The effect of aerobic exercise with ozone and stem cell on anandamide concentration in desert rat with osteoarthritis
http://feyz.kaums.ac.ir/article-1-4424-en.html

In rats with spinal cord injuries, the increased expression of CB2 receptors helped to reduce neuropathic pain by lowering the transmission of pain signals into the spinal cord
Cannabinoid CB2 receptors are upregulated via bivalent histone modifications and control primary afferent input to the spinal cord in neuropathic pain
https://pubmed.ncbi.nlm.nih.gov/35500651/

In a mouse model of colitis/IBD, activating the CB2 receptor improved their immune response & lowered inflammatory mediators
Cannabinoid Receptor 2 (CB2) Inverse Agonist SMM-189 Induces Expression of Endogenous CB2 and Protein Kinase A That Differentially Modulates the Immune Response and Suppresses Experimental Colitis
https://www.mdpi.com/1999-4923/14/5/936/htm

In bone cells of patients with inflammatory bowel disease, stimulating the CB2 & TRPV1 receptors reduces the osteoporosis caused by the abundance of iron in the system
Effects of CB2 and TRPV1 Stimulation on Osteoclast Overactivity Induced by Iron in Pediatric Inflammatory Bowel Disease
https://pubmed.ncbi.nlm.nih.gov/35472140/

In injured airway cells, they had increased levels of the vanilloid receptor TRPV1 – but we still don’t know why
Investigating potential TRPV1 positive feedback to explain TRPV1 upregulation in airway disease states
https://pubmed.ncbi.nlm.nih.gov/35473456/
Remember, anandamide is not only an endocannabinoid, it’s also an endovanilloid & acts upon this receptor.

In bull sperm, there’s a delicate dance between progesterone & endocannabinoid receptors to regulate sperm capacitation (the changes necessary after ejaculation to penetrate the egg)
Interplay mechanisms between progesterone and endocannabinoid receptors in regulating bull sperm capacitation and acrosome reaction
https://pubmed.ncbi.nlm.nih.gov/35476800/

In rabbits, the ability of nicotine to cause artery relaxation may be via the CB2 receptor
Effects of cannabinoid and vanilloid receptor antagonists on nicotine induced relaxation response enhancement in rabbit corpus cavernosum
https://ijbms.mums.ac.ir/article_20103.html

In a rat model of anxiety, exposure to tobacco smoke & ceftriaxone (an up regulator of glutamate – the brain’s most common excitatory neurotransmitter) found that the tobacco smoke dysregulated the endocannabinoid system & increased anxiety while the ceftriaxone reversed the effects
Effects of waterpipe tobacco smoke and ceftriaxone treatment on the expression of endocannabinoid receptors in mesocorticolimbic brain regions
https://pubmed.ncbi.nlm.nih.gov/35490908/

In rats, being fed a diet rich in lipids helped to improve the endocannabinoid levels in their saliva & might be a treatment for salivary dysfunctions
Dietary fatty acids modulate the endocannabinoid system in rat submandibular gland
https://europepmc.org/article/ppr/ppr486458

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Cannabinoid Chemistry

The design of FAAH & MGL inhibitors for treating the eyes
Design and synthesis of endocannabinoid enzyme inhibitors for ocular indications
https://pubmed.ncbi.nlm.nih.gov/35500728/
There’s so much potential for treating the eyes with cannabinoids - but we haven’t quite hit any home runs there yet.

In cells, the drug WOBE437 increased anandamide levels by inhibiting its reuptake into cells – but it had off-target effects on a number of other proteins
Chemical Proteomics Reveals Off-Targets of the Anandamide Reuptake Inhibitor WOBE437
https://pubmed.ncbi.nlm.nih.gov/35482948/

Using wiped-film molecular distillation for refining CBD from hemp
Refining Cannabidiol Using Wiped-Film Molecular Distillation: Experimentation, Process Modeling, and Prediction
https://pubs.acs.org/doi/abs/10.1021/acs.iecr.2c00290

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Plant Medicines, Harm Reduction & Psychoactives

The always engaging Dr. Mariavittoria Mangini on hidden history of women & psychedelics
https://maps.org/news/bulletin/a-hidden-history-of-women-and-psychedelics-spring-2019/
To dive deep on this subject, check out the unparalleled ‘Sisters of the Extreme: Women Writing on the Drug Experience’. It’s not a history but a well-curated anthology of the women themselves describing a wide range of psychoactive experiences. A particular favorite of mine is Louisa May Alcott’s ‘Perilous Play’ & her hashish bonbons.

NIDA Director Nora Volkow (<swoon>) with another breath of fresh air: forcing people into addiction treatment fails
https://www.nytimes.com/2022/04/30/opinion/forced-addiction-treatment.html

The NIH hosted a meeting on the therapeutic potential of kratom – the popular painkiller from SE Asia that has a huge underground network of supporters fighting the DEA's attempts to ban it
https://www.marijuanamoment.net/federal-agency-explores-benefits-of-the-controversial-tree-kratom/
It’s foolhardy to say that kratom isn’t addictive – but the number of people using it to control their pain is huge & a large number of people use it to get off of opioids. It’s the last legal safe-ish plant for painkilling.

A well-written article on ketamine therapy going mainstream by Emily Witt
https://www.newyorker.com/culture/annals-of-inquiry/ketamine-therapy-is-going-mainstream-are-we-ready

NYTimes on the unhealthy demand for natural 5-MeO-DMT sourced from the desert toad
https://www.nytimes.com/2022/03/20/us/toad-venom-psychedelic.html

Even National Geographic is covering magic mushrooms these days… by Daniel Merino
https://www.nationalgeographic.com/science/article/a-psychedelic-surprise-may-be-thriving-in-your-local-garden
Now you know it’s going mainstream.

A law professor looks at the reform of cannabis laws & the implications for the psychedelic renaissance
Observations on 25 Years of Cannabis Law Reforms and Their Implications for the Psychedelic Renaissance in the United States
https://www.annualreviews.org/doi/abs/10.1146/annurev-lawsocsci-120621-012645

In humans with depression, this review of neuroimaging literature shows that psilocybin changes activity in the amygdala (fear center), may decrease depressive symptoms & that it changes functional connectivity in both healthy & depressed people
The Effects of Psilocybin in Adults with Major Depressive Disorder and The General Population
https://www.sciencedirect.com/science/article/abs/pii/S0165178122001871

A pilot study finds psilocybin helpful for anorexia nervosa
Pilot Study Evaluation of Psilocybin Therapy for Anorexia Nervosa: Safety, Acceptability, and Preliminary Efficacy
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)00773-9/fulltext

PsychedelicAlpha with a summary of the new research in March
https://psychedelicalpha.com/news/psychedelic-research-bulletin-march-2022
A MAPS trial found MDMA helpful for eating disorders & a trial with 330 new mothers found low doses of ketamine after a C-section helpful for pain scores but not for depression

A review of the potential reproduction harms of nitrous oxide
Nitrous oxide-induced reproductive risks: Should recreational nitrous oxide users worry?
https://pubmed.ncbi.nlm.nih.gov/35510635/
In general, nitrous is considered a very safe drug. The main physical risk from a long-term habit is a Vitamin B12 deficiency (though with its ability to escape reality, it can be quite psychologically addicting as well). This work on the potential reproductive harm is news to me.

From a national drug survey,

·         LSD use linked to increased depression & suicidal thinking

·         Salvia linked to increased suicidal thinking

·         DMT & AMT & Foxy to increased suicidal planning

·         MDMA linked to decreased psychological distress, depression & suicidal thinking
Past-year hallucinogen use in relation to psychological distress, depression, and suicidality among US adults
https://www.sciencedirect.com/science/article/abs/pii/S0306460322001095

Thanks.
 - lex

PS: With lovely piano work, here’s Laraaji’s ‘Sun Piano’. A master of many instruments born in Philadelphia, he grew up studying violin, piano, trombone & voice. By the early ‘70s, he was studying Eastern mysticism & had acquired his first zither from a local pawn shop. He converted it to be electronic & then took to busking on the northeast corner of Washington Square Park where he would improvise for hours on end with his eyes closed. It’s here that Brian Eno found him & opened doors for him onto the international stage, setting off decades of experimental albums & collaborations around the world, including his Laughter Meditation Workshops.

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The Living Glossary

Here’s a running glossary of the basic cannabinoid terms. This 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 basically, we treat the human brain like the ocean: both deep, mysterious & chockablock with fish & 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]

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]

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]

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

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 squid that eats blue whales]

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]

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…]

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)
[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).
[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]

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 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.