C&P#31: your genes & your pain + cannabis & memory + dentists say stop showing up stoned
C&P#31: your genes & your pain + cannabis & memory + dentists say stop showing up stoned
Big votes today on cannabis legalization + abhorrent immigration decision because of cannabis use
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. Writing, science archives, newsletter content & if you need a podcast, I’m the host for you.
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Editor’s note:
Sorry to be a day late on this one. The kids have been on school vacation for two weeks & it puts me underwater with work – but we do hit those playgrounds hard.
Livestream paused + new EU correspondent for Weed Talk News
I’ve decided to pause the YouTube livestreams. It doesn’t feel like the best use of my time when the gathering of science is what you’re here for. Instead, I’m the new European correspondent for Weed Talk News by Pro Cannabis Media. You can see my latest dispatch here. Subscribe to see their weekly update every Friday.
For video presentations about the new cannabis science each week, I’m looking for the right company to work with. If you know of a cannabis or CBD company who wants to up their short-form & long-form video content, forward this to them or reply & let me know about them. I know how to increase a company’s online presence & engagement with education.
This week…
Your genes alter how well cannabis works for your pain
So much info on cannabinoids & memory & why you can’t remember that movie as well stoned
Cannabis probably not great for your teeth & gums – and dentists ask you to stop showing up high
Eat hemp seeds! An ideal mix of fatty acids…
Responses to CBD differ by gender
A rich week for studies on CBD & seizures
Lots on microdosing psychedelics
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Popular Science
On CBD oil for menopause by Ruby Deevoy
https://www.womanandhome.com/health-wellbeing/benefits-of-cbd-oil-for-menopause
Martin Torgoff on Jazz, Race, The Beats & Drugs: an interview by Ethan Nadelmann on his podcast Psychoactive
Torgoff authored the excellent drug history book, ‘Can't Find My Way Home: America in the Great Stoned Age, 1945-2000’.
Marijuana, Cognition, Psychosis & Addiction with Amir Englund on Nick Jikome’s Mind & Matter podcast
Best of cannabinoid science...
In people with moderate to severe anxiety, a sublingual CBD solution for four weeks improved anxiety, mood, sleep, quality of life & cognition (hattip to Col. Dr. Michael Lewis)
Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628346
And in a mouse model of stress & depression caused by trauma, cannabis oil improved their symptoms related to anxiety & depression
Broad-Spectrum Cannabis Oil Alleviates Behavioral Symptoms Associated with Stress-Related Anxiety and Depression in Mice
https://ps.tbzmed.ac.ir/Article/ps-34488
A great study about your genetic variants for the ECS affects how effective cannabis is for treating your pain
The Pharmacogenetics of Cannabis in the Treatment of Chronic Pain
https://pubmed.ncbi.nlm.nih.gov/36292717
In COVID patients, their smell & taste dysfunctions may be linked to a dysregulation of their endocannabinoid system
Possible Role of Endocannabinoids in Olfactory and Taste Dysfunctions in COVID-19 Patients and Volumetric Changes in the Brain
https://pubmed.ncbi.nlm.nih.gov/36247977
A review of using cannabinoids against microbes
Antimicrobial and Cytotoxic Effects of Cannabinoids: An Updated Review with Future Perspectives and Current Challenges
https://pubmed.ncbi.nlm.nih.gov/36297340
Using cannabinoids against our bacterial adversaries is one of the most important & under-utilized aspects of their nature!
2020: A review of CBD & other non-psychoactive cannabinoids for GI tract disorders
Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?
https://pubmed.ncbi.nlm.nih.gov/32357565
A big review of the gender differences in response to CBD
Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review
https://pubmed.ncbi.nlm.nih.gov/36291671
Yes, gender is a social construct. But male & female matters for how the body processes the cannabinoids.
“Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ⁹-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD).”
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 questions.
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Book a session here:
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the Headlines & Fav Articles
An analysis of what Biden’s cannabis rescheduling might look like by Shane Pennington of On Drugs
Here’s the states voting on legalizing cannabis today:
Arkansas, Maryland, Missouri, North Dakota & South Dakota
https://www.linkedin.com/pulse/midterm-elections-see-five-states-voting-adult-use-cannabis-/
2021: In an analysis of worker’s compensation insurance, 6 states allowed for cannabis reimbursement, 14 did not require it & 6 prohibited it
Review of cannabis reimbursement by workers' compensation insurance in the U.S. and Canada
https://pubmed.ncbi.nlm.nih.gov/34532872
A federal judge agreed with the US Citizenship and Immigration Services to block the citizenship of a Swiss woman because her use of cannabis did not constitute “good moral character”
https://www.coloradopolitics.com/news/premium/feds-properly-denied-colorado-womans-citizenship-request-for-marijuana-use-judge-says/article_9e83588a-5570-11ed-b5c2-cb07f84192ae.html
Fuck this.
The Economist on how a global revolution in attitudes towards cannabis is underway
https://www.economist.com/international/2019/08/29/a-global-revolution-in-attitudes-towards-cannabis-is-under-way
In New York, the leaders of the largest cannabis business association say that the testing requirements for mold & yeast are unnecessarily strict & pose an existential threat to the industry
https://www.newyorkupstate.com/cannabis-insider/2022/10/yeast-and-mold-limits-posing-existential-threat-to-nys-marijuana-growers.html
A Leafly report puts cannabis as the 6th most valuable crop in the US
https://www.marijuanamoment.net/marijuana-is-a-more-valuable-crop-than-potatoes-or-rice-new-leafly-report-on-adult-use-market-finds
A Nevada judge told the Board of Pharmacy that exceeded their authority by keeping cannabis as a Schedule 1 Drug
https://www.marijuanamoment.net/nevada-judge-orders-board-of-pharmacy-to-remove-marijuana-from-schedule-i-under-agencys-unconstitutional-code
In the UK, a little boy named Alfie is coming up on 1,000 days without a seizure – but he is one of only 3 kids in the country with an NHS-funded-prescription for his whole-plant cannabis treatment
https://metro.co.uk/2022/10/28/cbd-has-saved-my-son-from-daily-seizures-the-nhs-needs-to-be-prescribing-it-17555355
And a survey highlights the broad range of issues facing UK cannabis patients
https://cannabishealthnews.co.uk/2022/11/01/survey-reveals-broad-spectrum-of-issues-facing-uk-cannabis-patients
- 62% report ‘unreasonable delays’ to their prescription
- 31% have had quality control issues
- Over 35% spend over £350 a month
- Only 50% allowed to consume at work
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]
Half of all psychedelic companies at risk of running out of cash this year
MAPS prepares for trial in wrongful death lawsuit stemming from the 2017 death of a Lightning in a Bottle participant who attended the Zendo
https://www.lucid.news/maps-trial-wrongful-death-lawsuit
The use of psychedelics is linked to a greater knowledge about climate change via the person’s increase in nature relatedness
Psychedelic use predicts objective knowledge about climate change via increases in nature relatedness
https://journals.sagepub.com/doi/full/10.1177/20503245221129803
The potency of psilocybin mushrooms ranked… by Maria Holyanova
https://psychedelicspotlight.com/the-strongest-magic-mushroom-species-ranked-by-potency
On DiPT, the auditory psychedelic by Ruby Deevoy
https://psychedelicspotlight.com/dipt-is-the-psychedelic-for-your-ears
This is one of Shulgin’s more entertaining entries in TIHKAL.
A cool review of that old standard of high school: DXM, aka robotripping by Matt Sutton of OnDrugs
On the new club drug 3-MMC by gonzo journalist by Michelle Lhooq
https://doubleblindmag.com/3-mmc
Why can flickering lights induce psychedelic experiences?
https://theconversation.com/manipulating-light-can-induce-psychedelic-experiences-and-scientists-arent-quite-sure-why-192885
In a study following people taking ayahuasca saw “wide-ranging improvements in mental health, relationships, personality structure, and alcohol use”
Changes in mental health, wellbeing and personality following ayahuasca consumption: Results of a naturalistic longitudinal study
https://www.frontiersin.org/articles/10.3389/fphar.2022.884703/full
On how LSD causes both an afterglow & a hangover: the next morning: better spatial memory & verbal fluency but impaired cognitive flexibility
LSD, afterglow and hangover: Increased episodic memory and verbal fluency, decreased cognitive flexibility
https://pubmed.ncbi.nlm.nih.gov/35158230
It could also be that they just had a lousy night of sleep. People are often wired & have trouble getting a full night’s rest after a trip.
A survey of psychedelic users finds belief changes induced for dualism, paranormal/spirituality, non-mammal consciousness, mammal consciousness & non-physicalist beliefs plus a big increase in the belief in a Higher Power
Belief changes associated with psychedelic use
https://pubmed.ncbi.nlm.nih.gov/36317643
A survey of microdosers for their mental disorders found that they reported it more helpful than conventional treatments
Self-Rated Effectiveness of Microdosing With Psychedelics for Mental and Physical Health Problems Among Microdosers
https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00672/full
And my buddy Ido on why set & setting matter for microdosing too
Set and setting in microdosing: an oft-overlooked principle
https://pubmed.ncbi.nlm.nih.gov/36289109
And a study of tolerance in microdosers suggests that those using LSD may need to take a break & that psilocybin may be better for microdosing
Evidence for tolerance in psychedelic microdosing from the self-blinding microdose trial
https://psyarxiv.com/s4qhf
A review of how psychedelics work in the brain
The neural basis of psychedelic action
https://pubmed.ncbi.nlm.nih.gov/36280799
And why they’re worth considering for treating schizophrenia
Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation
https://pubmed.ncbi.nlm.nih.gov/36280752
A review of how ayahuasca works in the brain
Molecular Pathways of the Therapeutic Effects of Ayahuasca, a Botanical Psychedelic and Potential Rapid-Acting Antidepressant
https://www.mdpi.com/2218-273X/12/11/1618
COMPASS Pathways announce their phase 2B study results of psilocybin for depression
https://ir.compasspathways.com/news-releases/news-release-details/compass-pathways-announces-publication-phase-2b-study-comp360
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
https://www.nejm.org/doi/full/10.1056/NEJMoa2206443
Another salvo on the ongoing debate about endogenous DMT
Significance of mammalian N,N-dimethyltryptamine (DMT): a 60-year-old debate
https://www.iceers.org/significance-mammalian-dimethyltryptamine
The Plant & the History
In the US, this year’s hemp harvest down by half
https://mjbizdaily.com/2022-us-hemp-harvest-projected-to-shrink-by-nearly-half-of-2021
The National Hemp Council of America wants the FDA to approve hemp seed meal for animal feed
https://www.ganjapreneur.com/national-hemp-council-of-america-urges-fda-to-approve-hemp-seed-meal-as-animal-feed
The fatty acids & other ingredients that make hemp seeds so good,
Fatty acids and minor functional compounds of hemp (Cannabis sativa L.) seeds and other Cannabaceae species
https://www.sciencedirect.com/science/article/abs/pii/S0889157522005804
their nutrient power
Nuts of Fibrous Hemp Cannabis sativa L. - Concentrated Power of Nutrients
https://www.tandfonline.com/doi/abs/10.1080/15440478.2022.2128967
And its source as an underutilized source of protein & fat
Nutritional qualities of hemp seed (Cannabis sativa L.): An underutilized source of protein and fat
https://www.researchgate.net/publication/364225028_Nutritional_qualities_of_hemp_seed_Cannabis_sativa_L_An_underutilized_source_of_protein_and_fat
There’s a reason that in China, formerly known as the Land of Mulberry & Hemp, hemp seeds are still a widely loved & nutritious snack.
A review of the techniques for clearing mold off your medical cannabis & the effects on cannabinoid content
Evaluation of Different Techniques to Decontaminate Medical Cannabis and Their Effect on Cannabinoid Content
https://pubs.acs.org/doi/full/10.1021/acsagscitech.2c00231
On using biotech to take cannabis to the next level
Releasing the Full Potential of Cannabis through Biotechnology
https://www.mdpi.com/2073-4395/12/10/2439
2021: A review of hemp as an industrial crop
Evaluation of hemp (Cannabis sativa L.) as an industrial crop: a review
https://pubmed.ncbi.nlm.nih.gov/34476693
Cannabis had a greater yield with increased light intensity but not UV radiation
Indoor grown cannabis yield increased proportionally with light intensity, but ultraviolet radiation did not affect yield or cannabinoid content
https://pubmed.ncbi.nlm.nih.gov/36237501
2021: The shape of the cannabis plant alters its cannabinoid production & this study looks at the best ways to manipulate the plant’s architecture for the highest yield
Shape Matters: Plant Architecture Affects Chemical Uniformity in Large-Size Medical Cannabis Plants
https://pubmed.ncbi.nlm.nih.gov/34579367
2021: For hemp plants, the use of urea & urea inhibitors yielded more height, more seeds & more CBD content
Effect of Fertilization with Urea and Inhibitors on Growth, Yield and CBD Concentration of Hemp (Cannabis sativa L.)
https://www.mdpi.com/2071-1050/13/4/2157
2021: And while pinching did not alter CBD content in hemp plants, greater plant density seemed like it could increase economic returns depending on how its done
How do pinching and plant density affect industrial hemp produced for cannabinoids in open field conditions?
https://acsess.onlinelibrary.wiley.com/doi/abs/10.1002/agj2.20882
2021: An analysis of the CBC synthesis pathway in the plant & how that might contribute to final cannabinoid levels
Analysis of Sequence Variability and Transcriptional Profile of Cannabinoid synthase Genes in Cannabis sativa L. Chemotypes with a Focus on Cannabichromenic acid synthase
https://pubmed.ncbi.nlm.nih.gov/34579390
2021: A deep computer analysis of the genetic variants in the cannabis plant
In silico analysis enabling informed design for genome editing in medicinal cannabis; gene families and variant characterization
https://pubmed.ncbi.nlm.nih.gov/34551006
2021: In Croatia, hemp was being grown in the Late Middle Ages
Food and agriculture in Slavonia, Croatia, during the Late Middle Ages: the archaeobotanical evidence
https://link.springer.com/article/10.1007/s00334-021-00857-8
Using sediments in a lake to measure the historical levels of hemp retting
Bacterial phylogenetic markers in lake sediments provide direct evidence for historical hemp retting
https://www.sciencedirect.com/science/article/pii/S0277379122004346
Hemp is hard to break down & humans often left it in lakes to break the hurds. That leaves bacterial evidence in the lakes that can be measured to find out how much hemp was being retted.
Cannabinoid Science
2021: A nice personal history piece on Dr. Viswanathan Natarajan who helped to discover one of the lipid synthesis pathways that lead to endocannabinoids
Discovering a New Metabolic Pathway. Early Work with My Friend, Viswanathan Natarajan
https://pubmed.ncbi.nlm.nih.gov/34510384
Clinical Studies & Surveys
Ha. In a double-blind study, 13% of the participants unblinded themselves by testing their cannabis to see if it had THC
Implications for blinding in clinical trials with THC-containing cannabinoids based on the CANNA-TICS trial
https://pubmed.ncbi.nlm.nih.gov/36213751
“Life finds a way.”
What do young people know about CBD & where did they hear about it from
Young adults' knowledge, perceptions and use of cannabidiol products: a mixed-methods study
https://pubmed.ncbi.nlm.nih.gov/36217613
A survey of problem gambling & cannabis use
Problem gambling severity, gambling behavior, substance use, and mental health in gamblers who do and do not use cannabis: Evidence from a Canadian national sample
https://pubmed.ncbi.nlm.nih.gov/36257248
Mental Health, Addiction & Mental Effects
In people who experienced maltreatment as a child, their resilience to developing substance use disorders may relate to their endocannabinoid tone
Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation
https://assets.researchsquare.com/files/rs-2119392/v1/426b82d9-b3a7-4cfc-a07e-7830ce99b94b.pdf
In people with their first episode of psychosis, they realize that giving up cannabis might be a good thing – but they’re not going to do it, especially when there’s no good replacement to help with social interactions & improved enjoyment of life
Young adults with psychosis: Intentions for cannabis reduction and cessation based on theory of planned behavior
https://pubmed.ncbi.nlm.nih.gov/36201809
In humans, nabilone (a pharmaceutical THC derivative) impaired spatial & verbal memory
Nabilone Impairs Spatial and Verbal Working Memory in Healthy Volunteers
https://pubmed.ncbi.nlm.nih.gov/36201240
And chronic cannabis use caused a worse performance on a spatial rotating task
Chronic cannabis use affects cerebellum dependent visuomotor adaptation
https://pubmed.ncbi.nlm.nih.gov/36219905
And in monkeys, a drug that activates the CB1 receptor caused worse performance on a memory test but tolerance developed to the effects – and the performance problems disappeared with the stopping of the drug
Effects of cannabinoid exposure on short-term memory and medial orbitofrontal cortex function and chemistry in adolescent female rhesus macaques
https://pubmed.ncbi.nlm.nih.gov/36248648
And finally a review looking at the complexity of cannabinoids in the hippocampus (memory center of the brain)
Cannabinoid control of hippocampal functions: the where matters
https://pubmed.ncbi.nlm.nih.gov/33977665
https://addi.ehu.es/bitstream/handle/10810/57949/The%20FEBS%20Journal%20-%202021%20-%20Robledo%E2%80%90Menendez%20-%20Cannabinoid%20control%20of%20hippocampal%20functions%20the%20where%20matters.pdf?sequence=1&isAllowed=y
A look at how anandamide & 2-AG cause long-term potentiation (a persistent increase in synaptic strength) in the hippocampus (memory center of the brain) via inhibition of the neurons using GABA
2-AG and anandamide enhance hippocampal long-term potentiation via suppression of inhibition
https://pubmed.ncbi.nlm.nih.gov/36212685
2021: In regular cannabis users, they performed similarly on behavioral tasks but their brains displayed different dynamics when reorienting their attention
Regular recreational Cannabis users exhibit altered neural oscillatory dynamics during attention reorientation
https://pubmed.ncbi.nlm.nih.gov/34889178
2021: A review of fMRI studies on how brains respond to the sight of cannabis
Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users: a systematic review of fMRI studies
https://pubmed.ncbi.nlm.nih.gov/34505940
“The literature consistently reported greater brain activity in cannabis users while exposed to cannabis vs neutral stimuli in three key brain areas: the striatum, the prefrontal (anterior cingulate, middle frontal) and the parietal cortex (posterior cingulate/precuneus) and additional brain regions (hippocampus, amygdala, thalamus, occipital cortex). Preliminary correlations emerged between cannabis craving and the function of partially overlapping regions (amygdala, striatum, orbitofrontal cortex ).”
2021: A review of how cannabis affects reward processing
The acute and non-acute effects of cannabis on reward processing: A systematic review
https://pubmed.ncbi.nlm.nih.gov/34509513
Harms, Cannabis Use Disorder & Street Synthetics
On the rise of toddlers accidentally exposed to cannabis edibles
The Continued Rise of Unintentional Ingestion of Edible Cannabis in Toddlers-A Growing Public Health Concern
https://pubmed.ncbi.nlm.nih.gov/36215048
A comparison of the withdrawal effects between strong cannabis & synthetic cannabinoids
Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis
https://pubmed.ncbi.nlm.nih.gov/34533608
“Compared to high-potency herbal cannabis, SCRAs [synthetic cannabinoid receptor agonists] were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal.”
A study of using nabiximols (1:1 THC:CBD sprays) to treat cannabis use disorder combined with counseling showed an increased chance of abstinence or reduction of use
Correlates of treatment engagement and client outcomes: results of a randomised controlled trial of nabiximols for the treatment of cannabis use disorder
https://pubmed.ncbi.nlm.nih.gov/36209081
2021: In a cohort that followed adolescents, frequent cannabis use in their teens was “associated with problematic substance use, more delinquency, and poorer functional well-being at age 20”
Frequent teenage cannabis use: Prevalence across adolescence and associations with young adult psychopathology and functional well-being in an urban cohort
https://pubmed.ncbi.nlm.nih.gov/34601277
A systematic review & two case reports of heart problems in heavy cannabis users
MARIJUANA USE AND CARDIAC ARREST/VENTRICULAR TACHYARRHYTHMIAS: A SYSTEMATIC REVIEW OF PUBLISHED CASE REPORTS
https://journal.chestnet.org/article/S0012-3692(22)01523-9/fulltext
MARIJUANA-INDUCED VASOSPASTIC ANGINA
https://journal.chestnet.org/article/S0012-3692(22)01557-4/fulltext
Nobody likes to hear it, but cannabis is a small but real drag to your heart health.
In a cohort of patients with a synthetic cannabinoid overdose, over 30% had acute respiratory failure
Respiratory failure in confirmed synthetic cannabinoid overdose
https://pubmed.ncbi.nlm.nih.gov/34499005
2021: A young man who seemed to commit suicide by vaping 4F-MDMB-BINACA
Suicide by vaping the synthetic cannabinoid 4F-MDMB-BINACA: cannabinoid receptors and fluoride at the crossroads of toxicity?
https://pubmed.ncbi.nlm.nih.gov/34542803
The mystery in Brazil of why people are taking BZO-HEXOXIZID (MDA-19) when it doesn’t activate the CB1 receptor
The mystery behind the apprehensions of the selective cannabinoid receptor type-2 agonist BZO-HEXOXIZID (MDA-19) as a drug of abuse
https://link.springer.com/article/10.1007/s11419-022-00646-6
2021: In rats, how 5F-MDMB-PICA moves through the body
Pharmacokinetics and pharmacodynamics of the synthetic cannabinoid, 5F-MDMB-PICA, in male rats
https://pubmed.ncbi.nlm.nih.gov/34547333
A book chapter on the synthetic cannabinoids
Chapter15 - Synthetic cannabinoids (SC)
https://www.sciencedirect.com/science/article/pii/B9780128187883000127
Neurodegenerative & Brain Diseases
How the cannabinoids treat diseases of the central nervous system
The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review
https://www.sciencedirect.com/science/article/pii/S2225411022000761
And how the endocannabinoids interact with the microglia (guardian immune cells of the brain)
Endocannabinoid signaling in microglia
https://pubmed.ncbi.nlm.nih.gov/36222019
A study of how CBD works for complex adult seizures
Efficacy of the FDA-approved cannabidiol on the development and persistence of temporal lobe epilepsy and complex focal onset seizures
https://pubmed.ncbi.nlm.nih.gov/36216124
And for early-life seizures
Preclinical efficacy of cannabidiol for the treatment of early-life seizures
https://pubmed.ncbi.nlm.nih.gov/36220975
And in canine epilepsy
Cannabidiol in canine epilepsy
https://pubmed.ncbi.nlm.nih.gov/36209995
And in a hippocampus model of seizures, CBD lowered activation of the microglia (immune cells of the brain) & lessened neuronal damages
Cannabidiol inhibits microglia activation and mitigates neuronal damage induced by kainate in an in-vitro seizure model
https://pubmed.ncbi.nlm.nih.gov/36240948
In a mouse model of spinal cord injury, activating the CB2 receptor lowered inflammation, reduced loss of the myelin sheaths, increased autophagy (recycling of damaged cellular components), caused less neuronal apoptosis (cellular suicide) & improved functionality of the hind legs
Cannabinoid receptor-2 attenuates neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome post spinal cord injury
https://pubmed.ncbi.nlm.nih.gov/36238284
How beta-caryophyllene (one of the most common terpenes in cannabis) functions as a brain anti-inflammatory via several different pathways
Anti-Inflammatory Effect of Beta-Caryophyllene Mediated by the Involvement of TRPV1, BDNF and trkB in the Rat Cerebral Cortex after Hypoperfusion/Reperfusion
https://pubmed.ncbi.nlm.nih.gov/35408995
Pain & Inflammation
A cohort study of kids & teens using nabilone (a pharmaceutical THC derivative) against their chronic pain
Synthetic Cannabinoid for the Treatment of Severe Chronic Noncancer Pain in Children and Adolescents
https://www.tandfonline.com/doi/pdf/10.1080/24740527.2022.2132138
2021: In chronic pain patients, medical cannabis prescriptions caused a small but significant drop in the use of opioid prescription medication
Opioid and healthcare service use in medical cannabis patients with chronic pain: a prospective study
https://pubmed.ncbi.nlm.nih.gov/34521640
In a rat model of neuropathic pain, THC worked the best for reducing pain – but high-CBD cannabis extracts was more effective than CBD alone
Combinations of Cannabidiol and Δ9-Tetrahydrocannabinol in Reducing Chemotherapeutic Induced Neuropathic Pain
https://pubmed.ncbi.nlm.nih.gov/36289810
In a rat model of neuropathic pain, a synthetic cannabinoid combined well with the painkiller tramadol
Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats
https://hrcak.srce.hr/file/402756
In mice, PEA combined well with melatonin & paracetamol to reduce pain
Melatonin synergizes with the antinociceptive effect of N-palmitoylethanolamide and paracetamol
https://pubmed.ncbi.nlm.nih.gov/36199181
The Skin
In humans, using the cannabinoids against hyperhidrosis (excessive sweating)
Cannabinoids in hyperhidrosis
https://pubmed.ncbi.nlm.nih.gov/36200741
“In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids. We found a remarkable reduction in the volume of sweat and an improvement to the patient's quality of life using this novel low-cost and low-impact approach.”
2021: In patients with epidermolysis bullosa (a rare genetic skin fragility disorder), a survey found that topical & oral cannabinoid use helped with pain, itchiness & wound healing
Cannabinoid use and effects in patients with epidermolysis bullosa: an international cross-sectional survey study
https://pubmed.ncbi.nlm.nih.gov/34488820
A study on how to make topical CBD more skin permeable
Evaluations of Skin Permeability of Cannabidiol and Its Topical Formulations by Skin Membrane-Based Parallel Artificial Membrane Permeability Assay and Franz Cell Diffusion Assay
https://www.karger.com/Article/FullText/526769
The Immune System
A test of the major cannabinoids & terpenes on altering the immune parameters of white blood cells
Evaluation of the anti-inflammatory effects of selected cannabinoids and terpenes from Cannabis Sativa employing human primary leukocytes
https://pubmed.ncbi.nlm.nih.gov/36228902
“Delta-9-tetrahydrocannabinol possessed the greatest activity affecting 11 immune parameters followed by cannabidivarin, cannabigerol, cannabichromene, cannabinol and cannabidiol. α-Pinene showed the greatest immune modulating activity from the selected group of terpenes, followed by linalool, phytol, trans-nerolidol. Limonene had no effect on any of the parameters tested.”
In kidney transplant patients, CBD oil caused three of them to have increased tacrolimus levels (not a good thing) & they had to stop using it - while another patient had decreased levels
Cannabidiol (CBD) Oil and Tacrolimus: The Unexpected High in Renal Transplant Recipients – Case Series and Review
https://journals.lww.com/transplantjournal/Fulltext/2022/09001/P8_057__Cannabidiol__CBD__Oil_and_Tacrolimus__The.862.aspx
The Guts & Oral Health
The American Dental Association asks patients to stop showing up high to dentist visits, especially because it can mean needing more anesthesia – but the whole press release is kind of funny
https://www.ada.org/about/press-releases/half-of-dentists-say-patients-are-high-at-dental-appointments
A review of why cannabis may be linked to the loss of gum & bone tissue in the mouth
Potential Mechanisms Underlying Marijuana-Associated Periodontal Tissue Destruction
https://pubmed.ncbi.nlm.nih.gov/34515556
2021: And a survey finds that cannabis use is associated with worse oral health
Cannabis Use and Oral Health in a National Cohort of Adults
https://pubmed.ncbi.nlm.nih.gov/34483631
2021: In patients with an inflammatory bowel diseases, treatment with cannabis seemed to improve endocannabinoid tone
Endocannabinoid Levels in Ulcerative Colitis Patients Correlate With Clinical Parameters and Are Affected by Cannabis Consumption
https://pubmed.ncbi.nlm.nih.gov/34531823
“In UC [ulcerative colitis] patients treated with placebo, but not in those treated with cannabis, the levels of PEA, AEA, and AA decreased significantly. The percent reduction in bowel movements was negatively correlated with changes observed in the circulating AEA and OEA, whereas improvement in quality of life was positively correlated with the levels of 2-AG. In the biopsies from UC patients, FAAH levels increased over the study period.”
The Liver
2021: In a rat model of liver ischemia (loss of blood flow), blocking the CB1 receptor reduced liver injury, inflammation, scar formation, oxidative stress & pathological damage partially via autophagy (cellular recycling)
Rimonabant ameliorates hepatic ischemia/reperfusion injury in rats: Involvement of autophagy via modulating ERK- and PI3K/AKT-mTOR pathways
https://pubmed.ncbi.nlm.nih.gov/34536742
The Lungs
In rats with lung injuries from sepsis, activating the CB2 receptor reduced inflammation, lowered water levels in the lungs, improved alveolar pathologies & protected against acute lung injury
Activation of cannabinoid receptor 2 alleviates acute lung injury in rats with lipopolysaccharide-induced sepsis
https://pubmed.ncbi.nlm.nih.gov/36210711
The Eyes
How the endocannabinoids in the eye’s photoreceptor cells interact with the TRP channels
Endocannabinoids produced in photoreceptor cells in response to light activate Drosophila TRP channels
https://pubmed.ncbi.nlm.nih.gov/36219683
Reproductive & Maternal Effects
A review of targeting the endocannabinoid system for endometriosis
Role of the endocannabinoid system in the pathophysiology of endometriosis and therapeutic implications
https://pubmed.ncbi.nlm.nih.gov/36207747
And a study of how patients are interested & what are their barriers to use
“A glimmer of hope” - Perceptions, barriers, and drivers for medicinal cannabis use amongst Australian and New Zealand people with endometriosis: A qualitative study
https://assets.researchsquare.com/files/rs-2140485/v1/04f41d14-0d17-4112-b91c-036f23f3564c.pdf
In mothers who used cannabis throughout their pregnancy, they had worse pregnancy outcomes than those who just used at the beginning of the prenatal care
Effect of maternal adverse childhood experiences (ACE) and cannabis use on pregnancy outcomes
https://pubmed.ncbi.nlm.nih.gov/36203114
2021: A cohort study finds that cannabis use did not alter IVF success
The relationship between cannabis use and IVF outcome-a cohort study
https://pubmed.ncbi.nlm.nih.gov/34493346
The protein kisspeptin regulate sperm development via the CB1 receptor
Kisspeptin regulates sperm differentiation by affecting cannabinoid receptors expression and distribution in vivo
https://www.proquest.com/openview/6173f6d389dae2a8c08aeac75d245621/1
& CB1 may regulate their maturation
Endocannabinoid system functions in spermatozoa: potential role of the CB1 receptor during epidydimal maturation
https://www.proquest.com/openview/765c817c82f4e100d9ecebe70a2c3f52/1
Thus it makes sense that cannabis slightly messes with your sperm.
2021: CB1 helps to direct the formation of the placenta
Cannabinoid and planar cell polarity signaling converges to direct placentation
https://pubmed.ncbi.nlm.nih.gov/34521753
A prenatal exposure to alcohol causes anxiety & alters the endocannabinoid & nitric oxide signaling (your brain’s only two systems for retrograde transmission – the ability to cause the upstream neuron to calm down their firing)
Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats
https://pubmed.ncbi.nlm.nih.gov/36216807
Cancer & Chemo
A review of using oleamide to treat cancer (plus an overview of how it affects ion channels)
Oleamide, a Sleep-Inducing Compound: Effects on Ion Channels and Cancer
https://www.liebertpub.com/doi/abs/10.1089/bioe.2022.0010
In cancer cells, CBDA activates the PPARβ/δ receptors that alter genetic transcription
Cannabidiolic acid activates the expression of the PPARβ/δ target genes in MDA-MB-231 cells
https://pubmed.ncbi.nlm.nih.gov/36228705
Thanks.
- lex
PS: For today’s sweet Hawaiian slack key guitar, Gabby Pahinui’s 1946 album ‘Gabby’. Known for his mastery of this traditional Hawaiian guitar & for his beautiful expressive vocals, Gabby might have been the first person who ever recorded a Hawaiian song with a slack-key guitar. Here’s an interview with Gabby to learn more about the guitar & how he learned it. He played with many of the great musicians of his time & was later influential in the Hawaiian Renaissance of the 1970s. Check out the album he did with Atta Isaacs called ‘Two Slack Key Guitars’.
The Living Glossary
This is a running glossary of the basic cannabinoid terms. It will also function as the legend for the ‘neural ocean’ metaphor that I’m using in my graphic novel series on the endocannabinoid system based on Moby-Dick. You can watch a lecture laying out the full idea here - but the basics are that we treat the human brain like the ocean: deep, mysterious & chockablock with fish, molecules & feedback systems that we don’t understand.
Endocannabinoids are whales. Phytocannabinoids are elephants (because what is an elephant but a whale of the land?) and neurons are complex underwater cities where hundreds of fish interact.
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]
CBG (cannabigerol)
Known as the “mother cannabinoid”, CBG is the chemical precursor to THC, CBD, and the other cannabinoids in the plant. CBG occurs only at low levels in cannabis because it tends to be quickly converted to other cannabinoids. Binding slightly to the CB1 and CB2 receptor, it also inhibits the enzymes that break down anandamide and 2-AG, hence raising the levels of those endocannabinoids. CBG interacts with an adrenaline receptor (α-2 adrenoceptor) & a serotonin receptor (5-HT1A Receptor) as well as modulating the expression of glutamate, GABA, and dopamine via the PPAR receptors on the nucleus, controllers of genetic transcription. CBG is also active at the TRP channels involved in the sensations of temperature, pressure, pH, smell, taste, vision, and pain perception whose dysfunction are linked to neuropathic pain, inflammation, and respiratory disorders.
Surveys show patients reporting help for anxiety, chronic pain, depression, and disturbed sleep. In preclinical trials, it's been studied for eye pressure, gut problems, appetite modulation, blood pressure lowering, bladder control, oral care, muscle spasms, airway inflammation, arthritis, painkilling, and most notably for brain health and neuroinflammation. In adult neural stem cells, CBG increased their viability. The breakdown products of CBG have been shown to reduce inflammation via the brain’s immune cells.
[since it’s the first cannabinoid produced, it must be the wooly mammoth
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.