C&P#57: CBD for alcohol use disorder + yin & yang for heart health + gender weirdness
Patrick Henry & taxes
[Editor’s note: the newsletter will be off next week. Going in for a minor surgery under general anesthesia. Snip snip. Prayers appreciated]
Welcome to the 57th edition of Cannabinoids & the People, a weekly newsletter where I collect all the new cannabinoid science. You can check out last week’s issue here & if you haven’t subscribed yet, please do.
As always, here’s the Living Glossary of Cannabinoid Terms & at the bottom is the album of the week.
Thanks to Kelly Ebbert of Tree of Life PR for taking advantage of the Venmo donation option (@Lex-Pelger) to support this newsletter.
Searching for sources for an article on doctors, addiction & cannabis:
I’m writing an article for the American Journal of Endocannabinoid Medicine about substance abuse disorders among doctors & the potential of using cannabis to help. If you or someone you know has experience with this & would be willing to share, please reach out.
(anonymity available upon request, but on the record preferred)
Cannabinoids for chronic neuropathic pain & MS
CBD for alcohol use disorder, but also reproductive toxicity
The goods & the bads of cannabis for heart health (so much info that we broke it out as a top section)
Gender weirdness: CBD vapes only help males with inflammatory pain but vaped CBD only helped males & in another study, effects all depended on the estrous cycle
CBD & THC for the pain of your cat’s osteoarthritis
Cannabis as a promoter of cervical cancer according to UK public health data as well as cannabinoids potentially lowering the power of anti-cancer drugs
For ketamine, activating your CB1 receptor may lower the anxiety
Nerd alert! Hemopressin may activate the CB1 receptor!
More links between the earlier the consumption of cannabis, the more likelihood of schizophrenia (listen, I don’t like it either, but I don’t trust any activist who denies it)
“Cannabis involved pregnancies”
A number of negative or null trial results #honestdata
Hemp seed protein to keep your carbon steel from rusting
Cannabinoids found in wooly umbrellas! … (sounds like Dr. Seuss, but it isn’t)
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3 very special formulations with other ingredients:
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(No videos this week. Recovering from a week of solo-papaing)
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Anandamide; or, the People: my graphic novel series on cannabis, the endocannabinoid system & the War on Drugs based on Moby-Dick
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Best Of Cannabinoid Science...
Great piece of science writing on how transcranial magnetic stimulation benefits severe depression by reversing brain signal flow in the brain
I include this because one of the wildest & most underreported (but not understudied) aspects of the endocannabinoid system is that it causes retrograde transmission.
(I’m too tired to explain retrograde transmission tonight. I think I’ll make a video on it this week…)
The title says it all…
In patients with chronic neuropathic pain, cannabinoids improve sleep and reduce pain vs. placebo
A survey of how adults with multiple sclerosis used cannabis for pain management
Characterizing cannabis use in a sample of adults with multiple sclerosis and chronic pain: An observational study
On using CBD patches to help with drug-resistant epilepsy in children
Adjunctive Use of Cannabidiol: A Joint Action to Patch Up Drug-Resistant Epilepsy
From the UK Biobank’s public health data, cannabis was a significant promoting factor for cervical cancer & potentially for laryngeal cancer & breast cancer
Causal relationship between cannabis use and cancer: a genetically informed perspective
And two researchers posit that the rise in pancreatic cancer rates among women may be because of rising levels of cannabis use
Cannabis Could Be the Missing Environmental Carcinogen Hiding in Plain View
The first finding is more solid & the second more speculative, but both point to a signal I’ve noticed over the past years.
In Swedish young people, those with a history of cannabis use had an earlier age of onset for schizophrenia, a higher number of hospital admissions & a higher total number of hospital days
Does a history of cannabis use influence onset and course of schizophrenia?
What do medical cannabis patients do when they are in the hospital?
How Are Patients Who Legally Use Medical Marijuana Treated When Hospitalized?
“Among those respondents, only a small percentage reported that inpatients had some access to their medical marijuana: 5.8% reported that the drug was kept in the pharmacy and dispensed like other prescriptions; another 3.4% indicated that patients kept the medical marijuana in their rooms and took it, as needed. Most respondents (55.6%) reported that patients were switched to an alternative medication during their inpatient hospital stays. Almost half (49.4%) of the nurse leaders who reported that alternative medications were used, reported that opioids were substituted, and the majority reported that the marijuana was safer than the opioids.”
In a study of people using take home opioids (buprenorphine/naloxone or methadone) to treat opioid use disorder, cannabis did not have a significant effect on the outcomes
Differential effect of cannabis use on opioid agonist treatment outcomes: Exploratory analyses from the OPTIMA study
A case study of a cat with osteoarthritis where full spectrum cannabis oil for 30 days helped with the pain
A case report of CBD and THC as analgesic therapy in a cat with chronic osteoarthritic pain
On the ways to beat a hair drug test…
Advances in testing for sample manipulation in clinical and forensic toxicology-part B: hair samples
The most important part is that it's impossible to differentiate between regular hair treatments & purposeful manipulation. So try all the tricks to get the levels in your hair down for these dastardly tests…
From 1996 to 2019, the use of cannabis in the US increased five-fold
Age, period and cohort effects on time trends in monthly cannabis use in adult population: 1996-2019
I was 13 at the start of this data & while I can't take all the credit, I hope I had a little bit to do with this.
A review of using CBD for the cognitive impairment arising from psychiatric & neurological illnesses
Use of cannabidiol (CBD) for the treatment of cognitive impairment in psychiatric and neurological illness: A narrative review
On older people using cannabis to protect their axonal myelination (the protective sheaths around their axons that allow for electrical signaling)
Enhancing axonal myelination in seniors: A review exploring the potential impact cannabis has on myelination in the aged brain
The loss of myelin around axons is linked to the cognitive declines of aging & is accelerated in many of the most common neurodegenerative disorders.
A review of using cannabis for acute pain
Medicinal cannabis products for the treatment of acute pain
A review of how the endocannabinoid system interacts with the dopamine system across the midbrain
Crosstalk between the endocannabinoid and mid-brain dopaminergic systems: Implication in dopamine dysregulation
In patients with hypertension, a single dose of either CBD or a novel CBD capsule reduced diastolic blood pressure & mean arterial pressure
Trial of a Novel Oral Cannabinoid Formulation in Patients with Hypertension: A Double-Blind, Placebo-Controlled Pharmacogenetic Study
A review of cannabis & cardiovascular health finds no significant increase for heart attacks & strokes from cannabis use
Cannabis and adverse cardiovascular events: A systematic review and meta-analysis of observational studies
Another review shows how the endocannabinoid system can help repair the damage after heart attacks
The Endocannabinoid System and Myocardial Ischemia-Reperfusion Injury
But a case study of cannabis causing arteritis (damage to the small arteries that blocks blood flow to the organs & limbs)
Cannabis arteritis presenting with Raynaud's and digital ulcerations: a case-based review of a controversial thromboangiitis obliterans-like condition
And a case report of a congenital heart defect potentially being worsened by cannabis use
Sudden Cardiac Arrest in Patient With Ventricular Septal Defect and Marijuana Consumption: A Case Report and Review of Literature
Cannabinoid drugs may lower the efficacy of cancer drugs based on platinum
Cannabis-derived products antagonize platinum drugs by altered cellular transport
“Our study raises the possibility that the desirable effect of counteracting adverse effects of chemotherapy might, at least for some cannabinoids, reflect impaired cellular availability, and consequently attenuation of the anticancer effects of platinum drugs.”
In rats, a test of CBD's reproductive & developmental toxicity
Reproductive and developmental toxicity evaluation of cannabidiol
In a rat model of alcohol use disorder, CBD inhibited the development of tolerance to alcohol, perhaps via changes to CB2 receptors in the striatum & dopamine receptors in the hippocampus
Cannabidiol as a Modulator of the Development of Alcohol Tolerance in Rats
In mice, CBD increased good bacteria in the gut as well as displaying potential benefits for cardiovascular protection
Multi-Omics Reveals the Effects of Cannabidiol on Gut Microbiota and Metabolic Phenotypes
In mice, the anxiety-increasing effects of ketamine are inhibited by the activation of CB1 receptors in the hippocampus
Activation of ventral hippocampal CB1 receptors inhibits ketamine-induced anxiogenic-like behavior: Alteration of BDNF/c-Fos levels in the mouse hippocampus
In a rat model of persistent inflammatory pain, vaporized THC-rich extract helped both male & female rats (though tolerance developed) but the CBD dominant extract was only effective in male rats
Vaporized cannabis extract-induced antinociception in male vs female rats with persistent inflammatory pain
In mice, the inhibition of their FAAH (breaking down anandamide) reduced anxiety in males all the time but in females, it changed with their estrous cycle while inhibition of their MAGL enzyme (breaking down of 2-AG) increased anxiety in males but decreased it in females depending on their cycle
The Estrous Cycle Influences the Effects of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Inhibition in the Anxiety-Like Behavior in Rats
In a rat model of epilepsy, activating the CB1 receptor lowered convulsions & blocking the CB1 receptor increased convulsions, giving hemopressin lowered convulsions, but blocking the CB1 receptor while giving hemopressin lowered convulsions
The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats
But the star finding may be that hemopressin is activating the CB1 receptor. If you glance at the literature, hemopressin has been speculated to be an antagonist at CB1, an inverse agonist & “just friends”.
In a rat model of fear, this in-depth study looks at how that emotion involves complex interactions in the prefrontal cortex between the cholinergic, glutamatergic, nitrergic & cannabinergic signaling systems
Contextual fear expression engages a complex set of interactions between ventromedial prefrontal cortex cholinergic, glutamatergic, nitrergic and cannabinergic signaling
Cannabinoid biosynthesis found in a woolly umbrella plant (Helichrysum umbraculigerum)
Parallel evolution of cannabinoid biosynthesis
Turning a new leaf on cannabinoids
Using computers to predict binding between 55 cannabinoids & 4,799 targets
Predicting binding between 55 cannabinoids and 4,799 biological targets by in silico methods
“From this screening, 827 cannabinoid-target binding pairs were predicted, which included 143 unique targets. Many cannabinoids sharing core structures (cannabinoid "types") had similar binding profiles, whereas most cannabinoids containing carboxylic acid groups were similar without regards to their core structure. For some of the binding predictions (43), in vitro binding data were available, and they agreed well with in silico binding data (median fourfold difference in binding concentrations). Finally, clinical adverse effects associated with 22 predicted targets were identified from an online database.”
We haven’t even started getting to the base of this plant or this system.
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.
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.
the Headlines & Fav Articles
The list of orgs calling for the Senate to pass a cannabis banking bill:
American Bankers Association & all 50 of its state affiliates
the Independent Community Bankers of America
9 insurance groups
And rejected by 5 former directors of the White House Office of National Drug Control Policy (drug czars)
The Cato Institute agrees: Unlock the Cannabis Industry for Financial Institutions
Cannabis Industry Paid $1.8 Billion in Excess Taxes in 2022
And they wonder why it’s a bloodbath out there…
If the big companies are losing millions to tens of millions each quarter, how are we supposed to enjoy a land of mom & pop pot shops under these brutal taxation regimes?
It’s a damn shame.
A survey finds that 30% of young people didn’t apply for government jobs or withdrew their applications because of the strict cannabis policies
I, for one, would like to see more stoners in public service. And if my government called on me to serve, I’d probably wag my tail in the mud.
On making weed wine
Amsterdam Bans Outdoor Cannabis Smoking in Red Light District
Singapore hangs the second person for cannabis trafficking in three weeks
The War on Drugs & Prohibition
A new Congressional bill introduced to end the lifetime ban on SNAP benefits for those with felony drug convictions
I don’t usually post about proposed legislation because it rarely becomes law, but this one is important. This unending punishment for those with drug convictions or the black letter F stamped on their chest is unconscionable.
A review of studies finds mixed evidence on the effects of cannabis legalization on cannabis use among youth with most studies finding no significant association
Effects of cannabis legalization on the use of cannabis and other substances
Nice dissection of Kevin Sabet
Psychedelics, Plant Medicines & Other Psychoactives
When I started microdosing psychedelics, I experimented with wearing my girlfriend's clothes and makeup. It helped me explore my gender expression.
Psychedelic churches in Phoenix record court wins over legal status
NIDA will give $1.5M to research psychedelics for substance use disorders
The DEA gave the first licenses for growing whole psilocybin mushrooms to Ohio State University & Inner State Inc
Andrew Gallimore on the tricky subject of how to define a psychedelic
‘Psychedelic workers of the world, unite!’ & a collection of wisdom for guides by Jules Evan
Arizona Veteran Faces Prison Time for Treating Cluster Headaches with DMT
On how certain light patterns can induce psychedelic experiences
On the animals that can get you high
I mean, like, ingesting them or their fluids can get you high. They won’t physically smoke you up themselves.
Except for the bears, watch out for the bears.
The Psychoactive Research
[This isn’t a deep dive into all of the science of psychedelics & other psychoactives like I do for the cannabinoids. If a newsletter with all that new science would be of interest to your company or organization, reach out to me]
LSD helped humans with learning
Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans
A study of LSD suggests 100 mics as the sweet spot
Dose-response relationships of LSD-induced subjective experiences in humans
For amyotrophic lateral sclerosis (ALS – Lou Gehrig’s disease), a narrative review of using psychedelics for the psychiatric & psychospiritual distress
Exploring the Potential Utility of Psychedelic Therapy for Patients With Amyotrophic Lateral Sclerosis
On the regulatory challenges for psychedelic medicine
Pressing regulatory challenges for psychedelic medicine
A survey of what methods people trust for learning about psychedelics starts with self-experimentation & ends with government agencies & pharma companies
"How Do I Learn More About this?": Utilization and Trust of Psychedelic Information Sources Among People Naturalistically Using Psychedelics
“The most common source of participants' information on psychedelics was their own experimentation and experiences (79.52%). Most also sought information from Internet websites (61.67%), friends (61.02%), Internet discussion forums (57.08%), books (57%), and articles in peer-reviewed scientific journals (54.55%). Few sought information from their primary health care provider (4.83%). Articles published in scientific journals, psychedelic nonprofits, and researchers based in colleges or universities were the most trusted sources of psychedelic information. Government agencies and pharmaceutical companies were the least trusted.”
The Plant & the History
A genomic analysis of the enzymes for creating oxylipins, the primary family of precursors to the cannabinoids
Oxylipin biosynthetic gene families of Cannabis sativa
Growing & Farming
New York’s cannabis production manual
New York State Cannabis sativa L. Production Manual
On the advantages of a monoecious cannabis plant (one that contains both sex organs)
Monoecious Cannabis sativa L. discloses the organ-specific variation in glandular trichomes, cannabinoids content and antioxidant potential
“In conclusion, the CH-1 accession is superior to the other in terms of morphological characters, phytocannabinoids synthesizing glands and cannabinoids content.”
An analysis of how methyl jasmonate doubles the plant’s cannabinoid production
Metabolomic analysis of methyl jasmonate treatment on phytocannabinoid production in Cannabis sativa
On using metabolic analysis to better assess the health of your plants
Beyond cannabinoids: Application of NMR-based metabolomics for the assessment of Cannabis sativa L. crop health
On the best ways to freeze dry your cannabis
Freeze-drying Cannabis sativa L. using real-time relative humidity monitoring and mathematical modeling for the cannabis industry
On how to find the best drying method for your flowers
TECHNOLOGICAL APPROACH IN CHOOSING THE CORRECT AND APPROPRIATE DRYING METHOD IN THE PRODUCTION OF DRIED CANNABIS FLOWERS FOR MEDICINAL PURPOSES
Rotating a field’s crops between hemp & chili lowers the disease levels in the chili
Hemp (Cannabis sativa L.) Interruption Cultivation Evidently Decreases the Anthracnose in the Succeeding Crop Chilli (Capsicum annuum L.)
Different extraction methods for cannabis & the evaluation of their antimicrobial activities
Isolation of Biologically Active Compounds from Cannabis sativa L. Inflorescences by Using Different Extraction Solvents and Evaluation of Antimicrobial Activity
On how hemp-based tea can exceed THC limits
Hemp-based tea - Impact of preparation technique on major cannabinoids content and consumers' exposure and health risk
How to modify hemp proteins to make them easier to work with in food products
Structural and Functional Characteristics of Hemp Protein Isolate-Pullulan Polysaccharide Glycosylation Conjugate in an Aqueous Model System
Turning hemp stems & waste plastics into biochar briquettes
Co-pyrolysis of industrial hemp stems and waste plastics into biochar-based briquette: Product characteristics and reaction mechanisms
On learning how to make long hemp fibers by studying how we process flax
Production of Long Hemp Fibers Using the Flax Value Chain
Hemp seed protein powder for a green & highly effective corrosion inhibitor in carbon steel
Fructus cannabis protein extract powder as a green and high effective corrosion inhibitor for Q235 carbon steel in 1 M HCl solution
Using hemp in a reinforced vinyl ester hybrid for aerospace, vehicles & athletic gear applications
Investigations on physical, mechanical, morphological and water absorption properties of ramie/hemp/kevlar reinforced vinyl ester hybrid composites
A review of GPR18 & GPR55, two orphaned receptors closely linked to the endocannabinoid system
GPR18 and GPR55-related Ligands Serving as Antagonists or Agonists: Current Situation, Challenges and Perspectives
A Nature profile of a scientist growing research cannabis in the shadow of a volcano
Cultivating cannabis in the shadow of a volcano
Clinical Use & Ingestion Methods
A survey of doctors at a university hospital finds that most of them don't know enough to prescribe it & they focus mostly on the risks rather than dosages or harm reduction
Physicians' Attitudes and Practices Regarding Cannabis and Recommending Medical Cannabis Use
In adolescents, having a friend who consumes cannabis did not increase the chances of a person using cannabis but their romantic partners consuming cannabis did increase their chances of using it as well
Investigating the Relative Influence of Romantic Sex Partners and Close Friends on Adolescent Alcohol and Marijuana Use
In female rats, a study of how vaporized THC moved through the body
Vaporized Delta-9-tetrahydrocannabinol Inhalation in Female Sprague Dawley Rats: A Pharmacokinetic and Behavioral Assessment
The Brain & its Diseases
I can’t even see the abstract of this intriguing study
Cannabinoids for painful dystonia in corticobasal syndrome: a report of three patients
In a mouse model of Alzheimer's disease, a new drug that activates the CB2 receptor & inhibits butyrylcholinesterase helped with brain immune cells as well as short & long- term memory
Dual-Acting Small Molecules: Subtype-Selective Cannabinoid Receptor 2 Agonist/Butyrylcholinesterase Inhibitor Hybrids Show Neuroprotection in an Alzheimer's Disease Mouse Model
Harms, Cannabis Use Disorder & Street Synthetics
A review of 13 studies on how increased cannabis availability led to increase your visits for vomiting, psychosis or cannabis-involved pregnancies
The impact of legal cannabis availability on cannabis use and health outcomes: A systematic review
I think that last one happened to me. Twice.
In young sexual & gender minorities, problematic cannabis use was associated with decreased gut microbial community richness
Problematic Cannabis Use Is Associated with Reduced Rectal Microbial Species Richness and Diversity Among a Pilot Sample of Young Sexual and Gender Minorities
Using avatars to treat cannabis use disorder
Avatar Intervention for Cannabis Use Disorder in Individuals with Severe Mental Disorders: A Pilot Study
A review of interventions for those who use both tobacco & cannabis
Interventions for dual users of tobacco and marijuana: A literature review
Creating a mouse model of cannabinoid use disorder using the synthetic cannabinoid WIN 55,212-2
A male mouse model of WIN 55,212-2 self-administration to study cannabinoid addiction
In a mouse model of vulnerability to the abuse potential of drugs (their Cryab gene is deleted), they were more likely to show addiction symptoms to a synthetic cannabinoid as well as experiencing more neuroinflammation, possibly via upregulated NF-κB
Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression
Pain, Inflammation & Surgeries
In facial fracture surgeries, cannabis (& tobacco) are associated with an increased risk of post-operative infection & nonunions (failure for bones to heal together)
Patterns of Postoperative Complications Related to Cannabis and Tobacco Usage in Patients Undergoing Facial Fracture Surgeries
Making a product out of cannabis leaves that has antioxidant activity
Formulation and Phytochemical Profile of a Product Prototype Infused with Cannabis sativa Leaves
Immune System & Microbials
In blood stem cells, activating the CB1 receptor made them less responsive to inflammatory stimuli, induced functional regulatory T cells & rescued macrophages (immune cells) from death via mTORC1 signaling, glycolysis & histone modulation
Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation
In mast cells (immune cells of allergic response, inflammation & pathogen defense), the little studied endocannabinoid LPI (lysophosphatidylinositol) caused changes to the cellular skeleton & movement as well as an increased production of cytokines via the CB2 & GPR55 receptors
Lysophosphatidylinositol Promotes Chemotaxis and Cytokine Synthesis in Mast Cells with Differential Participation of GPR55 and CB2 Receptors
In a mouse model of psoriasis, activating the CB2 receptors reduced skin lesions, plaque thickness, inflammation & the levels of iNOS & CB2 expression, possibly via the Keap1/Nrf2 signaling pathway
Specific Activation of CB2R Ameliorates Psoriasis-Like Skin Lesions by Inhibiting Inflammation and Oxidative Stress
The Guts & Metabolism
In mice, a certain variant of their FAAH enzyme caused them to be more prone to overeating & weight gain, perhaps via an increased response to ghrelin by orexin
A genetic variant of fatty acid amide hydrolase (FAAH) exacerbates hormone-mediated orexigenic feeding in mice
The Musculoskeletal System
In patients with systemic sclerosis (a hardening of the skin & organs), an activator of the CB2 receptor did not display benefits on the endpoints measured
Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis
The Genitourinary System
In patients with urinary stents, CBD oil showed no difference from placebo on pain scores or opioid usage
Effect of Cannabidiol Oil on Post-ureteroscopy Pain for Urinary Calculi: A Randomized, Double-blind, Placebo-controlled Trial
Cancer & Chemotherapy
Among survivors of cancer, less of them used cannabis then non-cancer survivors, but more of them used it for medical purposes
Cannabis use among cancer survivors in 22 states: Results from the Behavioral Risk Factor Surveillance System, 2020
A review of cannabinoids & terpenes for colorectal cancer
Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis
The anti-cancer properties of CBD, CBG, CBC & CBN
Cannabidiol and Minor Phytocannabinoids: A Preliminary Study to Assess Their Anti-Melanoma, Anti-Melanogenic, and Anti-Tyrosinase Properties
In a rat model of neuropathic pain from chemotherapy, the painkiller tramadol combined well with an activator of the CB1 receptor to lower pain with a lower risk of hypothermia
Interaction of the synthetic cannabinoid WIN55212 with tramadol on nociceptive thresholds and core body temperature in a chemotherapy-induced peripheral neuropathy pain model
The common CBD oxidation product CBD-hydroxyquinone (HU-331) that occurs as a contaminant in CBD isolates can get changed by light to produce a highly reactive intermediate
CBD hydroxyquinone photo-isomerises to a highly reactive intermediate
PS: This week’s album, ‘Railroad Bill’, comes from the incomparable guitar picker & blues master Etta Baker.