Alzheimer’s Sex Differences May Not Be What They Appear
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Alzheimer’s Sex Differences May Not Be What They Appear
Women get Alzheimer’s at nearly twice the rate than men do, and deteriorate more rapidly after onset, too.
So… Why?
There are many potential things to look at, but four stand out for quick analysis:
- Chromosomes: women usually have XX chromosomes, to men’s usual XY. There are outliers to both groups, people with non-standard combinations of chromosomes, but not commonly enough to throw out the stats.
- Hormones: women usually have high estrogen and low testosterone, compared to men. Again there are outliers and this is a huge oversimplification that doesn’t even look at other sex hormones, but broadly speaking (which sounds vague, but is actually what is represented in epidemiological studies), it will be so.
- Anatomy: humans have some obvious sexual dimorphism (again, there are outliers, but again, not enough to throw out the stats); this seems least likely to be relevant (Alzheimer’s is probably not stored in the breasts, for examples), though average body composition (per muscle:fat ratio) could admittedly be a factor.
- Social/lifestyle: once again, #NotAllWomen etc, but broadly speaking, women and men often tend towards different social roles in some ways, and as we know, of course lifestyle can play a part in disease pathogenesis.
As a quick aside before we continue, if you’re curious about those outliers, then a wiki-walk into the fascinating world of intersex conditions, for example, could start here. But by and large, this won’t affect most people.
So… Which parts matter?
Back in 2018, Dr. Maria Teresa Ferretti et al. kicked up some rocks in this regard, looking not just at genes (as much research has focussed on) or amyloid-β (again, well-studied) but also at phenotypes and metabolic and social factors—bearing in mind that all three of those are heavily influenced by hormones. Noting, for example, that (we’ll quote directly here):
- Men and women with Alzheimer disease (AD) exhibit different cognitive and psychiatric symptoms, and women show faster cognitive decline after diagnosis of mild cognitive impairment (MCI) or AD dementia.
- Brain atrophy rates and patterns differ along the AD continuum between the sexes; in MCI, brain atrophy is faster in women than in men.
- The prevalence and effects of cerebrovascular, metabolic and socio-economic risk factors for AD are different between men and women.
See: Sex differences in Alzheimer disease—the gateway to precision medicine
So, have scientists controlled for each of those factors?
Mostly not! But they have found clues, anyway, while noting the limitations of the previous way of conducting studies. For example:
❝Women are more likely to develop Alzheimer’s disease and experience faster cognitive decline compared to their male counterparts. These sex differences should be accounted for when designing medications and conducting clinical trials❞
~ Dr. Feixiong Cheng
Read: Research finds sex differences in immune response and metabolism drive Alzheimer’s disease
Did you spot the clue?
It was “differences in immune response and metabolism”. These things are both influenced by (not outright regulated by, but strongly influenced by) sex hormones.
❝As [hormonal] sex influences both the immune system and metabolic process, our study aimed to identify how all of these individual factors influence one another to contribute to Alzheimer’s disease❞
~ Dr. Justin Lathia
Ignoring for a moment progesterone’s role in metabolism, estrogen is an immunostimulant and testosterone is an immunosuppressant. These thus both also have an effect in inflammation, which yes, includes neuroinflammation.
But wait a minute, shouldn’t that mean that women are more protected, not less?
It should! Except… Alzheimer’s is an age-related disease, and in the age-bracket that generally gets Alzheimer’s (again, there are outliers), menopause has been done and dusted for quite a while.
Which means, and this is critical: post-menopausal women not on HRT are essentially left without the immune boost usually directed by estrogen, while men of the same age will be ticking over with their physiology that (unlike that of the aforementioned women) was already adapted to function with negligible estrogen.
Specifically:
❝The metabolic consequences of estrogen decline during menopause accelerate neuropathology in women❞
~ Dr. Rasha Saleh
Critical idea to take away from all this:
Alzheimer’s research is going to be misleading if it doesn’t take into account sex differences, and not just that, but also specifically age-relevant sex differences—because that can flip the narrative. If we don’t take age into account, we could be left thinking estrogen is to blame, when in fact, it appears to be the opposite.
In the meantime, if you’re a woman of a certain age, you might talk with a doctor about whether HRT could be beneficial for you, if you haven’t already:
❝Women at genetic risk for AD (carrying at least one APOE e4 allele) seem to be particularly benefiting from MHT❞
(MHT = Menopausal Hormone Therapy; also commonly called HRT, which is the umbrella term for Hormone Replacement Therapies in general)
~ Dr. Herman Depypere
Source study: Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer’s disease
Pop-sci press release version: HRT could ward off Alzheimer’s among at-risk women
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We don’t all need regular skin cancer screening – but you can know your risk and check yourself
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Australia has one of the highest skin cancer rates globally, with nearly 19,000 Australians diagnosed with invasive melanoma – the most lethal type of skin cancer – each year.
While advanced melanoma can be fatal, it is highly treatable when detected early.
But Australian clinical practice guidelines and health authorities do not recommend screening for melanoma in the general population.
Given our reputation as the skin cancer capital of the world, why isn’t there a national screening program? Australia currently screens for breast, cervical and bowel cancer and will begin lung cancer screening in 2025.
It turns out the question of whether to screen everyone for melanoma and other skin cancers is complex. Here’s why.
Pixel-Shot/Shutterstock The current approach
On top of the 19,000 invasive melanoma diagnoses each year, around 28,000 people are diagnosed with in-situ melanoma.
In-situ melanoma refers to a very early stage melanoma where the cancerous cells are confined to the outer layer of the skin (the epidermis).
Instead of a blanket screening program, Australia promotes skin protection, skin awareness and regular skin checks (at least annually) for those at high risk.
About one in three Australian adults have had a clinical skin check within the past year.
Those with fairer skin or a family history may be at greater risk of skin cancer. Halfpoint/Shutterstock Why not just do skin checks for everyone?
The goal of screening is to find disease early, before symptoms appear, which helps save lives and reduce morbidity.
But there are a couple of reasons a national screening program is not yet in place.
We need to ask:
1. Does it save lives?
Many researchers would argue this is the goal of universal screening. But while universal skin cancer screening would likely lead to more melanoma diagnoses, this might not necessarily save lives. It could result in indolent (slow-growing) cancers being diagnosed that might have never caused harm. This is known as “overdiagnosis”.
Screening will pick up some cancers people could have safely lived with, if they didn’t know about them. The difficulty is in recognising which cancers are slow-growing and can be safely left alone.
Receiving a diagnosis causes stress and is more likely to lead to additional medical procedures (such as surgeries), which carry their own risks.
2. Is it value for money?
Implementing a nationwide screening program involves significant investment and resources. Its value to the health system would need to be calculated, to ensure this is the best use of resources.
Narrower targets for better results
Instead of screening everyone, targeting high-risk groups has shown better results. This focuses efforts where they’re needed most. Risk factors for skin cancer include fair skin, red hair, a history of sunburns, many moles and/or a family history.
Research has shown the public would be mostly accepting of a risk-tailored approach to screening for melanoma.
There are moves underway to establish a national targeted skin cancer screening program in Australia, with the government recently pledging $10.3 million to help tackle “the most common cancer in our sunburnt country, skin cancer” by focusing on those at greater risk.
Currently, Australian clinical practice guidelines recommend doctors properly evaluate all patients for their future risk of melanoma.
Looking with new technological eyes
Technological advances are improving the accuracy of skin cancer diagnosis and risk assessment.
For example, researchers are investigating 3D total body skin imaging to monitor changes to spots and moles over time.
Artificial intelligence (AI) algorithms can analyse images of skin lesions, and support doctors’ decision making.
Genetic testing can now identify risk markers for more personalised screening.
And telehealth has made remote consultations possible, increasing access to specialists, particularly in rural areas.
Check yourself – 4 things to look for
Skin cancer can affect all skin types, so it’s a good idea to become familiar with your own skin. The Skin Cancer College Australasia has introduced a guide called SCAN your skin, which tells people to look for skin spots or areas that are:
1. sore (scaly, itchy, bleeding, tender) and don’t heal within six weeks
2. changing in size, shape, colour or texture
3. abnormal for you and look different or feel different, or stand out when compared to your other spots and moles
4. new and have appeared on your skin recently. Any new moles or spots should be checked, especially if you are over 40.
If something seems different, make an appointment with your doctor.
You can self-assess your melanoma risk online via the Melanoma Institute Australia or QIMR Berghofer Medical Research Institute.
H. Peter Soyer, Professor of Dermatology, The University of Queensland; Anne Cust, Professor of Cancer Epidemiology, The Daffodil Centre and Melanoma Institute Australia, University of Sydney; Caitlin Horsham, Research Manager, The University of Queensland, and Monika Janda, Professor in Behavioural Science, The University of Queensland
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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20 Easy Ways To Lose Belly Fat (Things To *Not* Do)
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Waist circumference (and hip to waist ratio) has been found to be a much better indicator of metabolic health than BMI. So, while at 10almonds we generally advocate for not worrying too much about one’s BMI, there are good reasons why it can be good to trim up specifically the visceral belly fat. But how?
What not to do…
Autumn Bates is a nutritionist, and her tips include nutrition and other lifestyle factors; here are some that we agree with:
- Do less cardio! Unless it’s High-Intensity Interval Training, cardio will cause a metabolic slow-down to compensate afterwards.
- Stop adding sugar to coffee, or anything else, really!
- Stop buying smoothies; they spike blood sugars; eat fresh fruit instead
- Stop eating bread; a drastic move, but as a general rule of thumb, it helps a lot of people
- Stop having more than 2 cups of coffee (this is actually about the caffeine, not the coffee; caffeine spikes cortisol in most people, and chronically high cortisol can cause fat to be redistributed to the belly and face)
- Stop sitting for more than an hour; spend more time on your feet
- Stop having more than 1 alcoholic drink per day (we’d advise stop having more than zero alcoholic drinks per day, but that may be a difficult immediate change for some)
- Stop eating “protein” bars; the rest of their contents are usually not good, to say the least.
For more, including to learn what she has against peanut butter, enjoy her video:
Click Here If The Embedded Video Doesn’t Load Automatically
Want to know more?
Check out our previous main feature:
Visceral Belly Fat & How To Lose It
Take care!
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How Old Is Too Old For HRT?
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It’s Q&A Day at 10almonds!
Have a question or a request? We love to hear from you!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small 😎
❝I think you guys do a great job. Wondering if I can suggest a topic? Older women who were not offered hormone replacement therepy because of a long term study that was misread. Now, we need science to tell us if we are too old to benefit from begininng to take HRT. Not sure how old your readers are on average but it would be a great topic for older woman. Thanks❞
Thank you for the kind words, and the topic suggestion!
About the menopause and older age thereafter
We’ve talked a bit before about the menopause, for example:
What You Should Have Been Told About The Menopause Beforehand
And we’ve even discussed the unfortunate social phenomenon of post-menopausal women thinking “well, that’s over and done with now, time to forget about that”, because spoiler, it will never be over and done with—your body is always changing every day, and will continue to do so until you no longer have a body to change.
This means, therefore, that since changes are going to happen no matter what, the onus is on us to make the changes as positive (rather than negative) as possible:
Menopause, & When Not To Let Your Guard Down
About cancer risk
It sounds like you know this one, but for any who were unaware: indeed, there was an incredibly overblown and misrepresented study, and even that was about older forms of HRT (being conjugated equine estrogens, instead of bioidentical estradiol):
As for those who have previously had breast cancer or similar, there is also:
The Hormone Therapy That Reduces Breast Cancer Risk & More
Is it too late?
Fortunately, there is a quick and easy test to know whether you are too old to benefit:
First, find your pulse, by touching the first two fingers of one hand, against the wrist of the other. If you’re unfamiliar with where to find the pulse at the wrist, here’s a quick explainer.
Or if you prefer a video:
Click Here If The Embedded Video Doesn’t Load Automatically!
Did you find it?
Good; in that case, it’s not too late!
Scientists have tackled this question, looking at women of various ages, and finding that when comparing age groups taking HRT, disease risk changes do not generally vary much by age i.e., someone at 80 gets the same relative benefit from HRT as someone at 50, with no extra risks from the HRT. For example, if taking HRT at 50 reduces a risk by n% compared to an otherwise similar 50-year-old not on HRT, then doing so at 80 reduces the same risk by approximately the same percentage, compared to an otherwise similar 80-year-old not on HRT.
There are a couple of exceptions, such as in the case of already having advanced atherosclerotic lesions (in which specific case HRT could increase inflammation; not something it usually does), or in the case of using conjugated equine estrogens instead of modern bioidentical estradiol (as we talked about before).
Thus, for the most part, HRT is considered safe and effective regardless of age:
How old is too old for hormone therapy?
👆 that’s from 2015 though, so how about a new study, from 2024?
❝Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%).❞
❝Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with estradiol rather than conjugated estrogen.❞
Read in full: Use of menopausal hormone therapy beyond age 65 years and its effects on women’s health outcomes by types, routes, and doses
As for more immediately-enjoyable benefits (improved mood, healthier skin, better sexual function, etc), yes, those also are benefits that people enjoy at least into their eighth decade:
See: Use of hormone therapy in Swedish women aged 80 years or older
What about…
Statistically speaking, most people who take HRT have a great time with it and consider it life-changing in a good way. However, nothing is perfect; sometimes going on HRT can have a shaky start, and for those people, there may be some things that need addressing. So for that, check out:
HRT Side Effects & Troubleshooting
And also, while estrogen monotherapy is very common, it is absolutely worthwhile to consider also taking progesterone alongside it:
Progesterone Menopausal HRT: When, Why, And How To Benefit
Enjoy!
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Oral retinoids can harm unborn babies. But many women taking them for acne may not be using contraception
10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.
Oral retinoids are a type of medicine used to treat severe acne. They’re sold under the brand name Roaccutane, among others.
While oral retinoids are very effective, they can have harmful effects if taken during pregnancy. These medicines can cause miscarriages and major congenital abnormalities (harm to unborn babies) including in the brain, heart and face. At least 30% of children exposed to oral retinoids in pregnancy have severe congenital abnormalities.
Neurodevelopmental problems (in learning, reading, social skills, memory and attention) are also common.
Because of these risks, the Australasian College of Dermatologists advises oral retinoids should not be prescribed a month before or during pregnancy under any circumstances. Dermatologists are instructed to make sure a woman isn’t pregnant before starting this treatment, and discuss the risks with women of childbearing age.
But despite this, and warnings on the medicines’ packaging, pregnancies exposed to oral retinoids continue to be reported in Australia and around the world.
In a study published this month, we wanted to find out what proportion of Australian women of reproductive age were taking oral retinoids, and how many of these women were using contraception.
Our results suggest a high proportion of women are not using effective contraception while on these drugs, indicating Australia needs a strategy to reduce the risk oral retinoids pose to unborn babies.
Contraception options
Using birth control to avoid pregnancy during oral retinoid treatment is essential for women who are sexually active. Some contraception methods, however, are more reliable than others.
Long-acting-reversible contraceptives include intrauterine devices (IUDs) inserted into the womb (such as Mirena, Kyleena, or copper devices) and implants under the skin (such as Implanon). These “set and forget” methods are more than 99% effective.
Oral retinoids taken during pregnancy can cause complications in babies. Gorodenkoff/Shutterstock The effectiveness of oral contraceptive pills among “perfect” users (following the directions, with no missed or late pills) is similarly more than 99%. But in typical users, this can fall as low as 91%.
Condoms, when used as the sole method of contraception, have higher failure rates. Their effectiveness can be as low as 82% in typical users.
Oral retinoid use over time
For our study, we analysed medicine dispensing data among women aged 15–44 from Australia’s Pharmaceutical Benefit Scheme (PBS) between 2013 and 2021.
We found the dispensing rate for oral retinoids doubled from one in every 71 women in 2013, to one in every 36 in 2021. The increase occurred across all ages but was most notable in young women.
Most women were not dispensed contraception at the same time they were using the oral retinoids. To be sure we weren’t missing any contraception that was supplied before the oral retinoids, we looked back in the data. For example, for an IUD that lasts five years, we looked back five years before the oral retinoid prescription.
Our analysis showed only one in four women provided oral retinoids were dispensed contraception simultaneously. This was even lower for 15- to 19-year-olds, where only about one in eight women who filled a prescription for oral retinoids were dispensed contraception.
A recent study found 43% of Australian year 10 and 69% of year 12 students are sexually active, so we can’t assume this younger age group largely had no need for contraception.
One limitation of our study is that it may underestimate contraception coverage, because not all contraceptive options are listed on the PBS. Those options not listed include male and female sterilisation, contraceptive rings, condoms, copper IUDs, and certain oral contraceptive pills.
But even if we presume some of the women in our study were using forms of contraception not listed on the PBS, we’re still left with a significant portion without evidence of contraception.
What are the solutions?
Other countries such as the United States and countries in Europe have pregnancy prevention programs for women taking oral retinoids. These programs include contraception requirements, risk acknowledgement forms and regular pregnancy tests. Despite these programs, unintended pregnancies among women using oral retinoids still occur in these countries.
But Australia has no official strategy for preventing pregnancies exposed to oral retinoids. Currently oral retinoids are prescribed by dermatologists, and most contraception is prescribed by GPs. Women therefore need to see two different doctors, which adds costs and burden.
Preventing pregnancy during oral retinoid treatment is essential. Krakenimages.com/Shutterstock Rather than a single fix, there are likely to be multiple solutions to this problem. Some dermatologists may not feel confident discussing sex or contraception with patients, so educating dermatologists about contraception is important. Education for women is equally important.
A clinical pathway is needed for reproductive-aged women to obtain both oral retinoids and effective contraception. Options may include GPs prescribing both medications, or dermatologists only prescribing oral retinoids when there’s a contraception plan already in place.
Some women may initially not be sexually active, but change their sexual behaviour while taking oral retinoids, so constant reminders and education are likely to be required.
Further, contraception access needs to be improved in Australia. Teenagers and young women in particular face barriers to accessing contraception, including costs, stigma and lack of knowledge.
Many doctors and women are doing the right thing. But every woman should have an effective contraception plan in place well before starting oral retinoids. Only if this happens can we reduce unintended pregnancies among women taking these medicines, and thereby reduce the risk of harm to unborn babies.
Dr Laura Gerhardy from NSW Health contributed to this article.
Antonia Shand, Research Fellow, Obstetrician, University of Sydney and Natasha Nassar, Professor of Paediatric and Perinatal Epidemiology and Chair in Translational Childhood Medicine, University of Sydney
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Can You Step Backwards Without Your Foot Or Torso Turning Out?
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Walking backwards is often overlooked, but research shows it can enhance forward walking, especially in stroke patients; it has other benefits for everyone else, too. The physiotherapists at Fitness4Life Physical Therapy explain:
…and one step back
How it works: walking backwards heightens proprioception and stimulates muscles, improving balance and posture. Additionally, our daily lives tend to involve forward-leaning postures, causing upper back bending, and walking backwards helps counterbalance this.
Extra benefits: training to walk backwards can reduce the risk of falls, as stepping back is a common movement that is often untrained.
Exercise: try doing backwards lunges, to assess your skill and balance while moving backward. If foot rotation or torso rotation occurs during the exercise, then there’s room for improvement. Correcting these movements is then simply a matter of practicing backward lunges without turning.
10almonds tip: any exercise is only as good as your will to actually do it. For this reason, dancing is a great exercise in this case, as almost all forms of dance involve stepping backwards (in order to have steps without travelling somewhere, forwards steps are usually balanced with backwards ones)
For more on all this, plus a visual demonstration of the exercise, enjoy:
Click Here If The Embedded Video Doesn’t Load Automatically!
Want to learn more?
You might also like to read:
Fall Special ← About how to avoid falling, and how to avoid (and failing that, at least minimize) injury if you do fall. If you think this only happens to other/older people, remember, there’s a first time for everything, so it is better to be prepared in advance!
Take care!
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Sweet Dreams Are Made of THC (Or Are They?)
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It’s Q&A Day at 10almonds!
Have a question or a request? We love to hear from you!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small 😎
❝I’m one of those older folks that have a hard time getting 7 hrs. I know a lot of it my fault…like a few beers at nite…🥰am now trying THC gummies for anxiety, instead of alcohol……less calories 😁how does THC affect our sleep,? Safer than alcohol…..I know your next article 😊😊😊😊❣️😊alot of us older kids do take gummies 😲😲😲thank you❞
Great question! We wrote a little about CBD gummies (not THC) before:
…and went on to explore THC’s health benefits and risks here:
For starters, let’s go ahead and say: you’re right that it’s safer (for most people) than alcohol—but that’s not a strong claim, because alcohol is very bad for pretty much everything, including sleep.
So how does THC measure up when it comes to sleep quality?
Good news: it affects the architecture of sleep in such a way that you will spend longer in deep sleep (delta wave activity), which means you get more restorative and restful sleep!
See also: Alpha, beta, theta: what are brain states and brain waves? And can we control them?
Bad news: it does so at the cost of reducing your REM sleep, which is also necessary for good brain health, and will cause cognitive impairment if you skip too much. Normally, if you are sleep-deprived, the brain will prioritize REM sleep at the cost of other kinds of sleep; it’s that important. However, if you are chemically impaired from getting healthy REM sleep, there’s not much your brain can do to save you from the effects of REM sleep loss.
See: Cannabis, Cannabinoids, and Sleep: a Review of the Literature
This is, by the way, a reason that THC gets prescribed for some sleep disorders, in cases where the initial sleep disruption was because of nightmares, as it will reduce those (along with any other dreams, as collateral damage):
One thing to be careful of if using THC as a sleep aid is that withdrawal may make your symptoms worse than they were to start with:
Updates in the use of cannabis for insomnia
With all that in mind, you might consider (if you haven’t already tried it) seeing whether CBD alone improves your sleep, as while it does also extend time in deep sleep, it doesn’t reduce REM nearly as much as THC does:
👆 this study was paid for by the brand being tested, so do be aware of potential publication bias. That’s not to say the study is necessarily corrupt, and indeed it probably wasn’t, but rather, the publication of the results was dependent on the company paying for them (so hypothetically they could have pulled funding from any number of other research groups that didn’t get the results they wanted, leaving this one to be the only one published). That being said, the study is interesting, which is why we’ve linked it, and it’s a good jumping-off-point for finding a lot of related papers, which you can see listed beneath it.
CBD also has other benefits of its own, even without THC:
CBD Oil: What Does The Science Say?
Take care!
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