C&P#90: Migraines, depression & canine autoimmune skin conditions + car crashes & gendered differences

Germany legalizes!

Feb 27, 2024

Why does cannabis cause healthy young people to have heart attacks?
7 papers on gendered differences in cannabinoid effects
Cannabis users have less car crashes? + some people with Tourette syndrome drive better with THC & CBD
The old puzzle: why does smoking cannabis increase lung capacity?
PEA for migraines & glaucoma
Two on the antidiabetic effects of CBD & the terpenes
Endocannabinoids in the cervical remodeling of labor & in breast milk
Two variants of the CB1 receptor associated with schizophrenia
Margaret Mead & the psychedelic ‘50s + potential negatives of psychedelics for the human heart

Hello everyone,

Welcome to the 90^th edition of Cannabinoids & the People, Lex Pelger’s free weekly digest of all the new cannabinoid science + assorted canna-news & psychedelic updates.

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Analyzing the best papers of the week, sponsored by CV Sciences

#PEA!

In people with migraines, 600 mg of PEA resolved headaches, lowered pain & reduced rescue medication significantly more than a placebo with no adverse events
Effectiveness of Palmitoylethanolamide (Levagen+) Compared to a Placebo for Reducing Pain, Duration, and Medication Use during Migraines in Otherwise Healthy Participants—A Double-Blind Randomised Controlled Study
https://www.mdpi.com/1424-8247/17/2/145
And a review of how PEA reduced the eye’s intraocular pressure for glaucoma
Evaluation of the nutraceutical Palmitoylethanolamide in reducing intraocular pressure (IOP) in patients with glaucoma or ocular hypertension: a systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/38269580/

You almost couldn't pay for a better study to illustrate the power of our Relief softgels. In this double-blind, randomized control study, 64 participants with migraines took either 600 mg of PEA (from Levagen+) or a placebo (maltodextrin). If the migraine hadn't resolved by hour two, the participants were instructed to take a second dose (the researchers had “previously shown that Levagen+ appears in the blood within 30 min of consumption and peaks within 2 h of consumption”).
With this regimen, the people taking PEA had more of their migraines resolve, had lower pain scores, and used significantly less rescue medication, with no adverse effects reported. This agrees with a previous study that showed 90 days of PEA to provide pain relief for people suffering from migraines with auras as well as a study showing PEA reducing the intensity and number of migraines in children.
In other PEA news this week, a meta-analysis showed the ability of PEA to lower the intraocular pressure of the eye for treating glaucoma. For a complete list of PEA studies, see the PEA page of CVResearch.info.

#DEPRESSION

In a naturalistic study of patients with depression, cannabis caused a clinically significant reduction of depression severity & was found to be well tolerated with a dropout rate comparable to those in clinical trials of antidepressant medication
Effectiveness of Medical Cannabis for the Treatment of Depression: A Naturalistic Outpatient Study
https://pubmed.ncbi.nlm.nih.gov/38211630/
And a review of how antidepressant drugs alter the endocannabinoid system
How depression and antidepressant drugs affect endocannabinoid system?-review of clinical and preclinical studies
https://pubmed.ncbi.nlm.nih.gov/38280009/
And a study of the role of the endocannabinoids & PEA on depression severity
Dysfunction in endocannabinoids, palmitoylethanolamide, and degradation of tryptophan into kynurenine in individuals with depressive symptoms
https://pubmed.ncbi.nlm.nih.gov/38273283/

In 59 patients with major depressive disorder treated with medical cannabis via a telemedicine platform, half of them reported more than a 50% reduction in symptom severity after three weeks of treatment. While a third of the patients mentioned side effects, none were considered severe and the dropout rate was comparable to the clinical trials of other antidepressant medications. This trial dovetails with new research that came out this week showing that a dysregulation of the endocannabinoid system in humans is associated with depressive symptoms.
Unfortunately, this article is behind a paywall - because it would be nice to know the dosage - but it speaks to the power of our Reserve products. For depression, people often find microdoses of ~1 mg to be helpful, while for others it may take anywhere from 5 to 50 mg to make a difference. But one key is to keep using the THC consistently. We are not sure of the mechanisms cannabinoids use to alleviate depression, but one hypothesis is that it’s via neurogenesis (the growth of new brain cells) and that takes time. For depression, the best bet would be to use high levels of CBD and moderate levels of THC for a month to allow the effects to start working. After that, start trying to incorporate PEA as well. See our Anxiety, Stress & Depression page on CVResearch.info for more studies on the antidepressant effects of the cannabinoids.

#DOGS

A case report of a dog using CBD-rich full spectrum oil to treat the common autoimmune skin disease discoid lupus erythematosus
Case report: Cannabinoid therapy for discoid lupus erythematosus in a dog
https://www.frontiersin.org/articles/10.3389/fvets.2024.1309167/full

Discoid lupus erythematosus is an autoimmune skin disease that affects both canines and humans. It’s the cause of the lesions on the face of Seal – but if he can marry Heidi Klum, your dog too can have a rich and fulfilling life (but perhaps not 4 Grammys). The cause of discoid lupus erythematosus is the production of antibodies that target healthy skin cells. This leads to hair loss, depigmentation, and lesions that can be inflamed and painful. The most common treatment is corticosteroids, but these can cause an array of side effects in dogs. The ability of the cannabinoids to both lower inflammation as well as to calm overreactive autoimmune conditions suggests them as a potential treatment. Plus, THC seems to act via the CB1 receptors in the sensory neurons of the skin to lower the transmission of itch signals.
This 2-year-old dog had scaling across their nose and inside their nostrils. Treatments with tacrolimus, vitamin E, and a hydration lotion caused no improvement. Treatment with the corticosteroid prednisolone led to a worsening of the lesions as well as weight gain, increased irritability, and signs of liver damage. The owner, concerned with these side effects, explored alternative treatments and found a vet specialized in cannabinoid therapy. They prescribed a full-spectrum oil with 2:1 THC:CBD (40 mg /mL) to be taken orally. But giving 8 drops of that twice a day (1.28 mg/kg – quite low) showed no improvement. But when they switched to 10 drops of CBD-rich oil and three drops of the THC-rich oil, the dog exhibited significant improvements after a few weeks. Increasing the CBD dosage to 15 drops a day led to further improvements as well as weight loss and a return to normal, playful behavior. After a year, all of the lesions had disappeared and a full blood workup found everything in a clinically stable range.
As these rather poetic researchers stated, “Discoid lupus erythematosus (DLE) remains a mysterious foe in dogs. Its origins are shrouded in a mix of genetics, infections, hormones, and sun exposure.” But “cannabis derivatives, beyond their pain-relieving prowess, are emerging as potential knights in shining armor against inflammation and immune system overwork in the veterinary world. Unlike traditional drugs, these compounds dance with the body’s own endocannabinoid system (ECS), a master conductor of cellular harmony, homeostasis and diverse functions. By influencing the immune response’s orchestra, they can silence the pro-inflammatory drums and amplify the anti-inflammatory melodies.” <swoon>
To see all of the pet research that’s ever been done, check out our collection on the Dogs & Cats page at CVResearch.info.

Best Of Cannabinoid Science...

A secret buyer survey out of Hungary finds only half the CBD products analyzed to be correctly labeled for their CBD concentration
Safety and risks of CBD oils purchased online: unveiling uncertain quality and vague health claims
https://pubmed.ncbi.nlm.nih.gov/38192407/

Finally, a development of a new scale for the positive consequences of cannabis (PCOC)
Development and preliminary validation of the positive consequences of cannabis (PCOC) scale
https://pubmed.ncbi.nlm.nih.gov/38295608/

Clinical

From a pediatric palliative care clinic, a case report of the benefits of medical cannabis for spasticity, seizures & cancer symptoms
Experience With Medical Marijuana in a Pediatric Palliative Care Clinic: Case Report
https://pubmed.ncbi.nlm.nih.gov/38278190/

A pushback against the data analysis in two recent Israeli studies on cannabis interfering with immunotherapies
Immunotherapy and Cannabis: A Harmful Drug Interaction of Reefer Madness?
https://www.medrxiv.org/content/10.1101/2024.01.26.24301817v2.full.pdf
I get out the popcorn for scientific fights. P-values! Unverifiable information! Numerous discrepancies! 🍿 🍿 🍿

Driving

Justice Department researchers questions ‘per se’ THC limits for driving
https://www.marijuanamoment.net/justice-department-researcher-says-we-may-need-better-tests-for-marijuana-impairment-questioning-per-se-thc-limits-for-driving
“A Justice Department research says states may need to “get away from that idea” that marijuana impairment can be tested based on the concentration of THC in a person’s system.”
And it’s true, these tests – whether saliva, blood or urine – are not accurate enough to correlate to impairment for driving, especially when the penalties are so high & so racistly applied.

In an analysis of driving accidents among emergency department patients, cannabis use was associated with lower odds of a crash - but alcohol or combined alcohol & cannabis use was associated with a higher risk
Risk of motor vehicle collision associated with cannabis and alcohol use among patients presenting for emergency care
https://pubmed.ncbi.nlm.nih.gov/38277855/

In a double-blind driving study of people with Tourette syndrome & tic disorders, treatment with nabiximols (1:1 THC:CBD) did not impair their driving skills & even improved fitness to drive in a subset of patients who were unfit to drive before treatment
The Effect of Nabiximols on Driving Ability in Adults with Chronic Tic Disorders: Results of a Substudy Analysis of the Double-Blind, Randomized, Placebo-Controlled CANNA-TICS Trial
https://pubmed.ncbi.nlm.nih.gov/38265476/

In Jamaica, on the demographics of driving after cannabis use showed that ~40% of cannabis users drive under the influence (~10% of total population)
Drug driving: a secondary analysis of factors associated with driving under the influence of cannabis in Jamaica
https://pubmed.ncbi.nlm.nih.gov/38262644/

Harms

A review of why cannabis & synthetic cannabinoids seem to cause heart attacks in healthy young people (great charts!)
Why Do Marijuana and Synthetic Cannabimimetics Induce Acute Myocardial Infarction in Healthy Young People?
https://pubmed.ncbi.nlm.nih.gov/35406706/

In a meta-analysis of 33k+ adolescents, cannabis use was linked with the subsequent development of an anxiety disorder
Cannabis use in adolescents and anxiety symptoms and disorders: a systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/38285048/
Of course, the egg could have come before the chicken. These kids might have been self-medicating before their anxiety diagnosis. Though my bet is that sometimes it brings it out & sometimes it keeps it at bay.

A case report of inhaled cannabis potentially causing bilateral optic neuropathy (damage to the optic nerve that impairs vision)
Bilateral Optic Neuropathy Associated with Acute Inhaled Marijuana Use: Case Report and Review of the Literature
https://www.tandfonline.com/doi/abs/10.1080/01658107.2023.2290755

A review of studying the potential liver toxicity of high levels of CBD
Advances and Challenges in Modeling Cannabidiol Pharmacokinetics and Hepatotoxicity
https://pubmed.ncbi.nlm.nih.gov/38286636/
“During clinical trials, CBD caused dose-dependent hepatocellular toxicity at therapeutic doses. The risk for toxicity was increased in patients taking valproate (VPA), another hepatotoxic antiepileptic drug, through an unknown mechanism.”

Reviews

A review of the puzzle on why smoking cannabis increases lung capacity
The Puzzle of Marijuana Use and Forced Vital Capacity
https://pubmed.ncbi.nlm.nih.gov/38271695/

Grom the Irish Health Research Board, a giant 200+ page review on the efficacy of cannabis in adults (though somehow they only looked at 47 papers)
The efficacy and safety of medicinal cannabis in adult populations: An evidence review
https://www.hrb.ie/fileadmin/2._Plugin_related_files/Publications/2024_Publications/Evidence_Centre/HRB_Medicinal_cannabis_Final_Report.pdf
“While some evidence was found to support the use of medicinal cannabis for some indications for which it has traditionally been recommended, such as nausea and vomiting in cancer and spasticity in multiple sclerosis, findings for most other outcomes were inconsistent at best, including for anxiety and pain in conditions such as cancer, rheumatic diseases and fibromyalgia, and multiple sclerosis. The evidence for neuropathic pain was promising: moderate- to high-certainty evidence indicated a significant benefit of cannabis, mixed cannabinoids, and THC:CBD, although some moderate-certainty evidence indicated no significant benefit of THC.”
Sometimes these reviews are better for giving a sense of how disconnected the scientific literature can be from the real world.

A review of the biphasic effects of cannabinoids (a little bit helps, a lot makes it worse) in the domains of pain, anxiety & sleep
Biphasic effects of cannabis and cannabinoid therapy on pain severity, anxiety and sleep disturbance: A scoping review
https://pubmed.ncbi.nlm.nih.gov/38268491/

An overview of cannabis-based medicines for chronic pain
Overview: Chronic Pain and Cannabis-Based Medicines
https://pubmed.ncbi.nlm.nih.gov/38198809/
And for pain, an updated review of THC & CBD
Tetrahydrocannabinol and Cannabidiol for Pain Treatment—An Update on the Evidence
https://www.mdpi.com/2227-9059/12/2/307
“Cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain. Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly.”

In palliative care, a review of the challenges of using cannabinoids
Challenges of the greater use of cannabinoids in palliative care
https://www.incbac.org/pdf/UNIGOU%20Training%20-%20Publication%202023%20-%20Ricardo%20Manoel%20de%20Armada%20Maturana.pdf

Gender Differences

A study of how high levels of CBD move through the system finds females to have quite higher levels
Pharmacokinetic Variability of Oral Cannabidiol and Its Major Metabolites after Short-Term High-Dose Exposure in Healthy Subjects
https://pubmed.ncbi.nlm.nih.gov/38292071/

For cannabis use disorder treatments, the different mechanisms of behavior change
Differential Mechanisms of Behavior Change in Cannabis Use Disorder Treatments: Functional Improvements and Clinical Implications
https://link.springer.com/article/10.1007/s11469-023-01231-7
“We found that craving reduction may be a MOBC [mechanisms of behavior change] for the full and men samples. However, for women, depression functioned concurrently as an immediate outcome and a MOBC for follow-up quality-of-life challenges. Additionally, we observed gender differences in treatment progressions; for men, the MOBC was craving reduction, while for women, it was reducing cannabis use.”

In a mouse model of pain, a drug that inhibits the MAGL enzyme (which breaks down 2-AG) caused a weak sustained painkilling effect in males while in females, a tolerance to the pain-killing effects emerged after a week
Effects of Repeated Treatment with the Monoacylglycerol Lipase Inhibitor MJN110 on Pain-Related Depression of Nesting and Cannabinoid 1 Receptor Function in Male and Female Mice
https://pubmed.ncbi.nlm.nih.gov/38262742/

In mice without DAGL (an enzyme that synthesizes 2-AG) in their astrocytes (brain support cells), the females had a reduced hedonic appetite for food while the males did not
Astrocytic Dagla Deletion Decreases Hedonic Feeding in Female Mice
https://pubmed.ncbi.nlm.nih.gov/38265773/

In a rat model of opioid use disorder, CBD lowered the withdrawal signs of males but not females
Morphine-induced side effects can be differentially modulated by cannabidiol in male and female rats
https://www.biorxiv.org/content/10.1101/2024.01.22.576721v1.full.pdf

In a mouse model of fentanyl withdrawal, the endocannabinoid 2-AG decreased sleep more in females than in males
Sex-specific Effects of the Endocannabinoid Agonist 2-Arachidonoylglycerol on Sleep and Circadian Disruptions during Fentanyl Withdrawal
https://pubmed.ncbi.nlm.nih.gov/38187736/

In a rat model of neonatal loss of blood to the brain, a drug that blocks the CB1 receptor but activates the CB2 receptor protected from brain damage in both genders & in females, enhanced neurogenesis
URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia-Ischemia and Enhances Neurogenesis in Females
https://pubmed.ncbi.nlm.nih.gov/38338884/

Pregnancy & Delivery

During pregnancy, a review of how the hormone shifts alter how THC moves through the system
The impact of pregnancy and associated hormones on the pharmacokinetics of Δ9-tetrahydrocannabinol
https://pubmed.ncbi.nlm.nih.gov/38258511/

In a meta-analysis covering 14 studies & 200k+ participants, prenatal cannabis exposure was associated with a higher risk of ADHD & autism symptoms in the offspring
Prenatal cannabis use and the risk of attention deficit hyperactivity disorder and autism spectrum disorder in offspring: A systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/38281464/

An analysis of the endocannabinoids found in human breast milk
Lipids and lipid signaling molecules in human milk and infant formula, a chemical characterization of relevant biochemical components
https://pubmed.ncbi.nlm.nih.gov/38272323/

In a mouse model of labor, the role of the endocannabinoids in cervical remodeling & the dysregulation that may play a role in premature delivery
Endocannabinoid regulation in the cervix during pregnancy: insights into molecular mechanisms of premature labor
https://rep.bioscientifica.com/view/journals/rep/aop/rep-23-0383/rep-23-0383.xml
“Using mass spectrometric analysis, we found an increase in anandamide and 2-arachidonoylglycerol in the cervix of pregnant mice when compared to non-pregnant mice. We have also found a reduction in FAAH protein expression in these tissues. Furthermore, when treated with LPS, we observed a reduction in the cervical immunostaining with anti-CB1, and anti-CB2 antibodies. Likewise, using cervix explants from pregnant mice, we found that LPS significantly increased cervical metalloprotease activity and cyclooxygenase 2, which were subsequently modulated by cannabinoid receptor antagonists.
Collectively, our findings suggest that an LPS-induced imbalance of cervix endocannabinoidome likely contributes to premature cervical remodeling, which is part of the key components that contribute to premature delivery.”

A thesis project seeking to quantify human fetal exposure to THC & its metabolites
Quantification and Prediction of Human Fetal (-)-Δ9-Tetrahydrocannabinol (THC)/11-OH-THC Exposure to Inform Neurodevelopmental Toxicity of Cannabis
https://www.proquest.com/openview/63fee5424f54987c5d4c9bebeb36f3c8/1?pq-origsite=gscholar&cbl=18750&diss=y

Preclinical

On the antihyperglycemic properties of cannabis seed extracts
Chemical Analysis of the Antihyperglycemic, and Pancreatic α-Amylase, Lipase, and Intestinal α-Glucosidase Inhibitory Activities of Cannabis sativa L. Seed Extracts
https://pubmed.ncbi.nlm.nih.gov/38202676/

In a rat model of juvenile diabetes, CBD helped to control blood glycemia, body weight & to improve insulin levels to close to normal values
Efficacy And Safety of Cannabidiol on Juvenile Diabetes Outcomes in Male Rats
https://laur.lau.edu.lb:8443/xmlui/handle/10725/15294
And in a rabbit model of diabetes, a number of the cannabis terpenes derived from leaves caused antidiabetic effects including a decrease in liver & fasting blood glucose levels
Assessment of the Antidiabetic Properties of Essential Oil from Cannabis sativa
https://anst.scione.com/newfiles/anst.scione.com/41/ANST-18-23.pdf

In a mouse model epilepsy, CBD protected against neuronal death from overreactive astrocytes (brain support cells)
Cannabidiol protects against neurotoxic reactive astrocytes-induced neuronal death in mouse models of epilepsy
https://assets.researchsquare.com/files/rs-3878760/v1/430ab5fc-22e8-44e3-9292-8c8c005cd6d0.pdf?c=1706123264

In dorsal root ganglion (sensory) neurons, CBN inhibited sodium currents & neuronal excitability
Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol
https://pubmed.ncbi.nlm.nih.gov/38263462/

An evergreen note on reading restricted papers:
First stop for seeing if there’s a free version of a paper, use the Google Scholar Chrome extension (Mac version), Google Scholar itself or try ResearchGate.
Three 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.
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.

the Headlines & Fav Articles

For your best daily cannabis news source: Marijuana Moment

The Job Corps (a national job training program) of the US Dept. of Labor will no longer penalize youth for past cannabis use & will lower penalties for positive cannabis tests during the program
https://www.marijuanamoment.net/job-corps-loosens-marijuana-testing-rules-for-federal-youth-workforce-training-program/

The FDA analyzes social media posts to find therapeutic evidence for several diseases
https://www.marijuanamoment.net/new-fda-report-highlights-how-marijuana-rescheduling-review-analyzed-cannabis-users-social-media-posts
“This six-month study involved manually analyzing hundreds of posts on publicly available online/social media platforms to provide context directly from users regarding marijuana, including its effectiveness for several therapeutic purposes such as anorexia, anxiety, nausea, and pain; nonmedical purposes; benefits and negative effects, experiences with access.”

A new set of cannabis security standards released by the American National Standards Institute (ANSI)
https://www.asisonline.org/publications--resources/news/press-releases/cannabis-security-standard

New York expands their rule for homegrown cannabis
https://www.wshu.org/long-island-news/2024-02-19/ny-pot-rules-homegrown-cultivation
And also in New York, almost none of the $25M in fines against unlicensed cannabis shops have been collected
https://www.marijuanamoment.net/new-york-state-has-collected-almost-none-of-its-25-million-in-fines-against-illicit-marijuana-stores/
https://www.thecity.nyc/2024/02/22/new-york-state-hochul-fines-illegal-cannabis-shops/

On the Medgar Evers College program for improving black entrepreneurship through cannabis education
Improving Black Entrepreneurship through Cannabis-Related Education
https://www.mdpi.com/2227-7102/14/2/135

Whew. Gene Simmons says he only got high once - but it was by accidentally eating 6 cannabis brownies
https://people.com/gene-simmons-recalls-mistakenly-eating-weed-brownies-8594113

International

Germany legalizes cannabis!
https://internationalcbc.com/germany-votes-to-legalize-cannabis-for-adults/
“According to the recently passed bill, adults in Germany will be able to cultivate up to three plants in private for personal use… In addition to being able to cultivate cannabis, adults in Germany will be able to possess a personal amount of cannabis. The possession limit will reportedly be set at 25 grams for adults when they are away from their private residence, and 50 grams at their private residence. In addition to the expressed legal possession limit, penalties for possessing slightly more than the legal threshold will be considered an ‘administrative violation’ rather than a criminal offense yielding jail time…

Noncommercial cannabis clubs are expected to launch as early as July 1, 2024, as part of the measure… Consumers will also be able to purchase seeds and clones from noncommercial clubs.”

Australian Senate holds first hearing on legalizing cannabis
https://cannabiswire.com/2024/02/22/australian-lawmakers-host-daylong-cannabis-legalization-hearing/

The Dutch cannabis company Bedrocan opens a clinical cannabis research unit
https://businessofcannabis.com/bedrocan-opens-its-own-cannabis-clinical-research-unit

In Peru a study of the therapeutic potential of their cannabis cultivars
Therapeutic Potential of Cannabinoid Profiles Identified in Cannabis L. Crops in Peru
https://www.mdpi.com/2227-9059/12/2/306
“This study analyzed the chemotypes of eight samples of dried inflorescences from cannabis cultivars in four different regions of Peru, and based on the significant variation in the cannabinoid profiles, we suggest their therapeutic potential. The most important medical areas in which they could be used include the following: they can help manage chronic pain, they have antiemetic, anti-inflammatory, and antipruritic properties, are beneficial in treating duodenal ulcers, can be used in bronchodilators, in muscle relaxants, and in treating refractory epilepsy, have anxiolytic properties, reduce sebum, are effective on Methicillin-resistant Staphylococcus aureus, are proapoptotic in breast cancer, can be used to treat addiction and psychosis, and are effective on MRSA, in controlling psoriasis, and in treating glioblastoma, according to the properties of their concentrations of cannabidiol, cannabigerol, and Δ9-tetrahydrocannabinol, as reviewed in the literature.”

In Morocco, an ethnobotanical survey on the therapeutic use of cannabis
An ethnobotanical survey on the therapeutic use of Cannabis sativa L. in the province of Taounate, Morocco.
https://ethnobotanyjournal.org/index.php/era/article/view/5687

The Laws, The War on Drugs & the End of Prohibition

A DEA agent on trial for taking $250k in bribes from the Buffalo Mafia
https://apnews.com/article/dea-corruption-mafia-mob-buffalo-bribery-drugs-bfa546895215ba235a770b17af9e6256
As the excellent writer/researcher Douglas Valentine made clear in his two books, this is the norm. You can’t catch people engaged in crimes that nobody reports without getting dirty yourself.
All the shenanigans of small-town cops gets repeated at the city level & the federal level & finally by the CIA at the international level. Who do you think was one of the major traffickers of heroin out of the Golden Triangle during the Vietnam War?

In Washington state, an analysis of the cannabis industry’s rhetoric to stop regulations of high THC products: threat, distract & discredit
Threat, Distract, and Discredit: cannabis industry rhetoric to defeat regulation of high THC cannabis products in Washington State, USA
https://pubmed.ncbi.nlm.nih.gov/38270913/

Psychedelics, Plant Medicines & Other Psychoactives

For my favorite newsletter on this topic, Psychedelic Alpha.

An excellent essay reviewing Breen’s new book about the psychedelic ‘50s with a focus on Margaret Mead (by the excellent Margaret Talbot)
When America First Dropped Acid
https://www.newyorker.com/magazine/2024/01/29/tripping-on-utopia-margaret-mead-the-cold-war-and-the-troubled-birth-of-psychedelic-science-benjamin-breen-book-review

Psilocybin mushrooms probably evolved 67 MYA & began producing their psilocybin 9 MYA to 40 MYA
Phylogenomics of the psychoactive mushroom genus Psilocybe and evolution of the psilocybin biosynthetic gene cluster
https://pubmed.ncbi.nlm.nih.gov/38194448/

The Psychoactive Research

[This isn’t a deep dive into the science of psychedelics & other psychoactives like I do for the cannabinoids. If your organization would be interested in a breakdown of all the new psychedelic science, reach out to me]

In California, the last eight years saw an increase in emergency department visits associated with hallucinogens
Trends in hallucinogen-associated emergency department visits and hospitalizations in California, USA, from 2016 to 2022
https://pubmed.ncbi.nlm.nih.gov/38213013/

A review of the potential negatives of hallucinogens on the human heart
Effects of hallucinogenic drugs on the human heart
https://pubmed.ncbi.nlm.nih.gov/38370480/

An analysis of psychedelic use on what predicts beneficial outcomes
What Predicts Beneficial Outcomes in Psychedelic Use? A Quantitative Content Analysis of Psychedelic Health Outcomes
https://pubmed.ncbi.nlm.nih.gov/38341606/
“Path analysis using structural equation modeling showed that psychological insight, not metaphysical beliefs, uniquely predicted beneficial outcomes. Moreover, beneficial outcomes' positive relation to ego dissolution and therapeutic intent was fully mediated by psychological insight.”

Similarly for MDMA, how the different settings & intentions alter the long term emotional & social effects
Subjective long-term emotional and social effects of recreational MDMA use: the role of setting and intentions
https://pubmed.ncbi.nlm.nih.gov/38341455/
“Members of the self-insight and mixed intentions clusters reported considerably more long-term socio-emotional benefits than members of the euphoria and energy cluster.”

In people with treatment-resistant depression, a double-blind trial of oral psilocybin revealed several themes to their experience
Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study
https://pubmed.ncbi.nlm.nih.gov/38316896/
“After qualitative analysis, three major themes were identified: (1) challenges with trust-building and expectation management; (2) navigating the experience; and (3) the need for a more comprehensive treatment. Subthemes of the first theme include a general distrust in mental healthcare, trust in study therapists, limited time for preparation, and managing expectations. The second theme included the following subthemes: trusting to surrender, profound and overwhelming experiences, and music as a guide. The third theme addressed a desire for multiple psilocybin sessions, and challenges with sensemaking. Patients' perspectives provided important insights into potential optimization of psilocybin treatment of TRD, including individualized preparation, investment in trust-building, offering additional psilocybin sessions, providing access to sustained (psycho)therapy with trusted therapists, and personalizing treatment approaches, which may also enhance real-world adaption of these treatments.”

In a naturalistic study, ayahuasca ceremonies caused a significant increase in gratitude, nature relatedness & nature appreciation
Effects of Ayahuasca on Gratitude and Relationships with Nature: A Prospective, Naturalistic Study
https://pubmed.ncbi.nlm.nih.gov/38310541/
“Ratings of mystical-type experiences and awe, but not ego dissolution, during participants' ayahuasca sessions were weakly-to-moderately correlated with these increases. The number of ayahuasca ceremonies attended at the retreat was not related to change in outcomes, underscoring the importance of the quality rather than the quantity of the experiences in post-acute change. Lastly, participant age was negatively related to the occurrence of mystical-type experiences and awe, supporting literature indicating blunted psychedelic effects with increased age.”

In healthy humans, DMT improved measures of depression
Effects of DMT on mental health outcomes in healthy volunteers
https://pubmed.ncbi.nlm.nih.gov/38326357/

In healthy humans, low doses of LSD increased neural complexity but moderate to high doses of oral THC or methamphetamine did not
Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine
https://www.nature.com/articles/s41386-024-01809-2
And brain scans of humans microdosing found changes in the plasticity of their long-term potentiation (a strengthening of synapses related to learning & neuroplasticity)
Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
https://pubmed.ncbi.nlm.nih.gov/38317077/

A case report of an adolescent on low doses of lithium using LSD & developing seizures
New-Onset Seizures in an Adolescent Following Use of LSD while on Low-Dose Lithium Therapy: A Case Study.
https://openurl.ebsco.com/EPDB%3Agcd%3A5%3A20899717/detailv2?sid=ebsco%3Aplink%3Ascholar&id=ebsco%3Agcd%3A174853355&crl=c

In a mouse model of depression, methylone (the cathinone version of MDMA) showed potential for treating depression & anxiety
Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity
https://pubmed.ncbi.nlm.nih.gov/36704743/

The Plant & the History

Growing & Farming

A very positivistic take on the U.S. Hemp Market (belied by the fact that acres planted have been plummeting these last years)
Legalization of Hemp Production and its Impacts on the US Hemp Export Competitiveness
https://www.researchgate.net/publication/377658062_Legalization_of_Hemp_Production_and_its_Impacts_on_the_US_Hemp_Export_Competitiveness
And an analysis of why farmers were growing hemp
Motivations for Growing Hemp: Insights from Hemp Production, Disposition, and Income Survey
https://www.researchgate.net/publication/377696622_Motivations_for_Growing_Hemp_Insights_from_Hemp_Production_Disposition_and_Income_Survey

A history of cannabis virome research
EXPLORING AND EXPLOITING THE CANNABIS VIROME FOR ADVANCING BIOTECHNOLOGICAL TOOLS IN HEMP RESEARCH
https://air.unimi.it/handle/2434/1023670

A genetic analysis of the flower development of cannabis
Morphological and genetic analysis of inflorescence and flower development in hemp (Cannabis sativa L.)
https://www.biorxiv.org/content/10.1101/2024.01.25.577276v1.full.pdf
“We define eight landmark events in male and female flower development and show that developmental differences between male and female plants extend beyond floral morphology, additionally comprising inflorescence structure as well as flowering time. Further, we demonstrate that the time of activation of key reproductive developmental regulators is significantly different in male and female hemp plants.”

A handbook on growing & processing hemp
Handbook fibre hemp cultivation, processing and applications
https://library.wur.nl/WebQuery/wurpubs/625352

On how to better isolate & propagate protoplasts for tissue cultures
Enhancing Protoplast Isolation and Early Cell Division from Cannabis sativa Callus Cultures via Phenylpropanoid Inhibition
https://pubmed.ncbi.nlm.nih.gov/38202437/

For southern blight in hemp, analysis of the efficacy of various biocontrols
Biocontrol Evaluation and Benefits in Controlling Southern Blight in Pepper and Hemp
https://www.proquest.com/openview/957490713b2d03a007197058900097e2/1?pq-origsite=gscholar&cbl=18750&diss=y

In Georgia hemp, a survey of the fungus Fusarium oxysporum
A SURVEY OF FUSARIUM OXYSPORUM IN GEORGIA HEMP FARMS AND VEGETABLE GARDENS
https://digitalcommons.gaacademy.org/cgi/viewcontent.cgi?article=2594&context=gjs

On using hemp to clean up soil contaminated with copper & how this actually produces more CBD
Phytoremediation & Valorization of Cu-contaminated Soils Through Cannabis sativa (L.) Cultivation: A Smart Way to Produce Cannabidiol (CBD) in Mediterranean Soils
https://link.springer.com/article/10.1007/s12649-023-02388-x

Hemp as food

On a hyperspectral imaging system to determine the macronutrient concentrations in cannabis
A non-destructive method to quantify the nutritional status of Cannabis sativa L. using in situ hyperspectral imaging in combination with chemometrics
https://www.sciencedirect.com/science/article/pii/S0168169924000474

In goats, partially substituting hemp for alfalfa feed improved their feed efficiency, fermentation & gut microbiome
Partially substituting alfalfa hay with hemp forage in the diet of goats improved feed efficiency, ruminal fermentation pattern and microbial profiles
https://www.sciencedirect.com/science/article/pii/S2405654524000052

In sunflower oil, how hemp extract acted as an antioxidant to help with storage
New insights on phytocannabinoids role in antioxidant activity of hemp inflorescences extract in high-oleic sunflower oil
https://www.sciencedirect.com/science/article/pii/S0023643824000860

A chapter on the proteins of hemp seeds
Hempseed (Cannabis sativa L.) Proteins: Composition, Structure, Enzymatic Modification, and Functional or Bioactive Properties
https://www.sciencedirect.com/science/article/abs/pii/B9780323916523000356

Industrial Use

On making particle boards out of hemp & recycled materials
Particleboards with Recycled Material from Hemp-Based Panels
https://pubmed.ncbi.nlm.nih.gov/38203991/

CANNABINOID SCIENCE

Public Health

How do older Canadians access cannabis as well as information about it?
How older Canadians access medical cannabis and information about it: A descriptive survey
https://www.tandfonline.com/doi/pdf/10.1080/28324897.2024.2303502
“A total of 107 older adults participated in the study. Most sought information from healthcare professionals (HCP) (49.5%) or cannabis retail stores (40.2%) and accessed cannabis via retail stores (56.1%). High cost, judgement from others, and HCP reluctance to prescribe were reported as the common barriers to access. Participants most often sought information related to benefits, safety, and dosage of medical cannabis. Many older adults relied on medically unauthorized sources such as retail stores to access medical cannabis and information related to it.”

On how stigma alters a patient's disclosure of cannabis use
The role of stigma in cannabis use disclosure: an exploratory study
https://pubmed.ncbi.nlm.nih.gov/38273362/

Adolescents & Young Adults

In sexual minority undergrad students, microaggressions related to their sexual orientation were associated with negative cannabis outcomes
Sexual orientation-based microaggressions and cannabis use outcomes among sexual minority individuals: The impact of negative affect and coping-motivated cannabis use
https://pubmed.ncbi.nlm.nih.gov/38272122/

A survey of why Canadian youth enjoy vaping cannabis
Perceptions and Use of Cannabis Vaping Products Amongst Youth: A Cross-Sectional Analysis of 1100 Cannabis Consumers
https://link.springer.com/article/10.1007/s11469-024-01246-8
The reasons include: easy to conceal, faster onset time & lack of odor.

A survey of why German young people use cannabis
Profiling Cannabis Consumption Motivation and Situations as Casual Leisure
https://ideas.repec.org/p/fau/wpaper/wp2024_04.html
“The primary reason for using cannabis is for hedonic pleasure, relaxation, and enhancing social experiences. Male respondents tend to be more motivated by conformity, while millennials and more educated cannabis users prioritize hedonic pleasure, relaxation, and sociable conversation.”

A review of the complicated studies on the consequences of simultaneous alcohol & cannabis use by college students
Assessment of simultaneous alcohol and cannabis use and its related consequences and cognitions in college students: A narrative review
https://pubmed.ncbi.nlm.nih.gov/38212143/

On the demographics of youth cannabis use over the last 10 years
Evolving Disparities in Cannabis Use Among Youth by Demographics and Tobacco and Alcohol Use in the U.S.: 2013-2021
https://pubmed.ncbi.nlm.nih.gov/38272242/

The Brain & Neurological Disorders

In a tissue model of the blood brain barrier, lowering 2-AG synthesis led to a loss of barrier integrity via altered expression of VE-cadherin
Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome
https://pubmed.ncbi.nlm.nih.gov/38203706/

Mental Health & Substance Use Disorders

For schizophrenia, 2 polymorphisms (variants) of the CB1 receptor were associated with a risk of developing a schizophrenia-spectrum disorder
Genetic and neurodevelopmental markers in schizophrenia-spectrum disorders: analysis of the 2 combined role of the Cannabinoid Receptor 1 gene (CNR1) and dermatoglyphics.
https://www.medrxiv.org/content/10.1101/2024.01.23.24301648v1.full.pdf

In a veteran cohort with PTSD, cannabis use disorder was associated with two genes being methylated (turned off)
Genome-wide DNA methylation analysis of cannabis use disorder in a veteran cohort enriched for posttraumatic stress disorder
https://pubmed.ncbi.nlm.nih.gov/38309009/

In a comparison of male patients with cannabis dependence or synthetic cannabinoid dependence versus matched controls, those using the cannabinoids were associated with higher sexual depression & lower sexual esteem, erectile function, sexual desire, intercourse satisfaction & overall satisfaction & for the synthetic cannabinoids, lower orgasmic function & a higher negative impact on male sexual function
Psychosexual dysfunction in male patients with cannabis dependence and synthetic cannabinoid dependence
https://pubmed.ncbi.nlm.nih.gov/38282460/

A small trial of treating cannabis use disorder with relaxation training or a substance-free activity session
A pilot trial of a brief intervention for cannabis use supplemented with a substance-free activity session or relaxation training
https://pubmed.ncbi.nlm.nih.gov/38271079/

In a mouse model of THC withdrawal, the effects on their attentional & motivational processes
Differential disruption of response alternation by precipitated Δ9-THC withdrawal and subsequent Δ9-THC abstinence in mice
https://pubmed.ncbi.nlm.nih.gov/38272272/

In a mouse model of fear, inhibiting the DAGL enzyme (an enzyme that synthesizes 2-AG) helped to suppress contextual fear learning as well as the expression of contextual fear memories
Pharmacological diacylglycerol lipase inhibition impairs contextual fear extinction in mice
https://pubmed.ncbi.nlm.nih.gov/38182791/

Reproduction & Hormones

In an Aboriginal Australian cohort, the women who used cannabis during pregnancy tended to have higher levels of psychological stress, depression & anxiety in the postpartum period
Understanding cannabis use and mental health difficulties in context with women's experiences of stressful events and social health issues in pregnancy: The Aboriginal Families Study
https://pubmed.ncbi.nlm.nih.gov/38340534/

In a survey of pregnant mothers or women with young children, ~70% reported cannabis products were allowed in their home & 42% reported smoking cannabis was permitted in one or more rooms
Cannabis Smoking and Storage within the Home: A Cross-Sectional Survey of Pregnant Women and Women with Young Children
https://pubmed.ncbi.nlm.nih.gov/38270715/

From the American Society for Reproductive Medicine, a review of the murky data on the effects of cannabis on fertility & reproduction
Tobacco or marijuana use and infertility: a committee opinion
https://pubmed.ncbi.nlm.nih.gov/38284953/

In zebrafish embryos, the negatives of CBD & THC on development
THE EFFECT OF CANNABINOIDS ON THE DEVELOPMENTAL MORPHOLOGY OF ZEBRAFISH
https://digitalcommons.gaacademy.org/gjs/vol82/iss1/60/

Pain & Surgeries

In people undergoing elective surgery, cannabis users tended to have higher postoperative opioid use & pain scores
Association Between Cannabis Use and Opioid Consumption, Pain, and Respiratory Complications After Surgery: A Retrospective Cohort Analysis
https://pubmed.ncbi.nlm.nih.gov/38190341/

In people getting shoulder surgery, those using cannabis had the greatest risk for both superficial & deep infections
Elevated risk of prosthetic infections in cannabis users after shoulder arthroplasty
https://pubmed.ncbi.nlm.nih.gov/38183443/

The Guts, Metabolism, Oral Health & CHS

In mice, disrupting neurons in their hypothalamus (a center of feeding) led to problems regulating their satiety response & disruptions in their endocannabinoid system that made them more prone to obesity & glucose tolerance
DEFICIENCY OF THE NUTRIENT SENSOR CPT1c IN SF1 NEURONS DISRUPTS THE ENDOCANNABINOID SYSTEM RESULTING IN COMPROMISED SATIETY AND FUEL SELECTION UPON FAT INTAKE
https://www.biorxiv.org/content/biorxiv/early/2024/01/23/2024.01.23.576690.full.pdf

The Lungs

A case report of someone using cannabis & amphetamines who suffered from acute respiratory distress syndrome
A Case Report of Acute Respiratory Distress Syndrome From Cannabis and Amphetamine Use
https://pubmed.ncbi.nlm.nih.gov/38186429/

The Genitourinary System

In a rat model of acute kidney injury, blocking the CB2 receptor improved kidney function while blocking the CB1 receptor caused negative results
Protective Effect of Cannabinoid Receptor-2 Blockage in Experimental Myoglobinuric Acute Kidney Injury
https://www.medigraphic.com/pdfs/revnefdia/rnd-2023/rnd234b.pdf

The Skin

In human keratinocytes (skin stem cells), peptides from cannabis seeds caused antioxidant effects via the Nrf2 signaling pathway
Cannabis sativa (Hemp) seed-derived peptides WVYY and PSLPA modulate the Nrf2 signaling pathway in human keratinocytes
https://www.biorxiv.org/content/10.1101/2024.01.26.577509v1

Cancer & Chemotherapy

For glioblastomas (the most aggressive brain cancer), a review of targeting the endocannabinoids in the tumor microenvironment
Targeting the Endocannabinoid System Present in the Glioblastoma Tumour Microenvironment as a Potential Anti-Cancer Strategy
https://pubmed.ncbi.nlm.nih.gov/38338649/

Cool Chemistry & Tools

Using mutagenesis to find CB1’s positive allosteric binding site
Determination of the Cannabinoid CB1 Receptor’s Positive Allosteric Modulator Binding Site through Mutagenesis Studies
https://www.mdpi.com/1424-8247/17/2/154

Improving the stability of cannabis oil against UV radiation by putting it in a chitosan matrix
Photochemical stability of chitosan films doped with cannabis oil
https://pubmed.ncbi.nlm.nih.gov/38277961/

Thanks.
- lex

PS: For this week’s vocalese, Annie Ross ‘Sings a Song with Mulligan’. One of the elite jazz singers of the ‘50s, she came from a Scottish family of vaudevillians & performers in South London. At the age of four, they took her to New York where she won a child's radio contest & a contract with MGM. She moved with her aunt to LA while her parents returned to Scotland & she didn't see them again for 14 years. By the age of twelve, she was playing Judy Garland's sister in the movie ‘Presenting Lily Mars’. By the end of 10th grade, she dropped out of school & moved to Europe to establish a singing career. It was there that she began to craft the new vocal style that would be known as vocalese, a way to use the voice & lyrics to create a jazz solo similar to what instruments do.
By 1957, she teamed up with Dave Lambert & Jon Hendricks to create the jazz trio Lambert, Hendricks & Ross, one of the most important jazz groups of the century. The group created a string of hit records but during this time she started dating Lenny Bruce & joined him in his heroin habit. By 1963, she had moved back to London, kicked her habit & married the English actor Sean Lynch. She started to appear in television shows but by the mid-70s her voice was no longer in demand and she had fallen on hard times, bankrupt & divorced. In the ‘80s, she returned to the stage & an appearance in Superman III led to more film roles & jazz singing gigs. Still recording into her eighties, the National Endowment for the Arts named her a Jazz Master, the documentary ‘No One But Me’ highlighted her virtuosic voice for a new generation & then she passed into that good night just 4 days shy of her 90^th birthday.

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Cannabinoids & the People