Practitioner Series

Index

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Lessons From Research

View of a microscope with a slide underneath

I bet you’ve heard audacious claims about CBD being the closest thing to a silver bullet in the health supplement space. Whilst I don’t believe in silver bullets, I think CBD (and cannabinoids) come pretty close, and I’ll tell you why.

My review of the evidence in T2D revealed that cannabinoids were able push a lot of buttons that attenuated diabetes progression.

!Disclaimer! Much research is still based in mechanistic sciences and may not necessarily translate into clinical outcomes. I’m waiting in anticipation for more clinical trials until something more concrete emerges.

You’d usually have a patient take a statin to reduce their blood lipids, Metformin to restore insulin sensitivity and Sulfonylureas to support insulin secretion from beta-cells. This is the essence of polyphamacy, one drug for one mechanism.

What astounded me was that certain cannabinoids were able to work on these mechanisms as well. Not only did cannabinoids work on the same mechanisms as some of the traditionally prescribed drugs, they also attenuated other mechanisms of pathophysiology in T2D. In addition to supporting lipid and glucose metabolism, they appeared to also work to reduce inflammation and oxidative stress.

The critical difference here is that cannabinoids co-exist in full/broad spectrum extracts from Cannabis, potentially reducing the need to take a polyphamacy approach. So there’s more to Cannabis than just CBD.

I’m not slating Polyphamacy; it can be useful, but its often complicated by side effects, drug interactions, increased expenses (for the NHS) and poorer adherence to interventions.

So when I discovered that the constituents of one plant, Cannabis, could potentially attenuate many aspects of diabetes progression, naturally I was intrigued.

What I realised was that specially bred strains of cannabis, fostering various cannabinoids could work on diabetes as a symphony rather than just a soloist. This may all sound too good to be true, but when you actually look at the mechanisms it all makes sense.

The mechanisms of lipid and glucose metabolism, inflammation and oxidative stress were all modulated by the activity at cannabinoid receptors. These receptors are the locks that form the signalling system of the endocannabinoid system (ECS).

If you’ve read the practitioners guide to CBD, then you’ll remember that we talked about the ECS being the master regulator of homeostasis in the body. So, it’s no surprise that when cannabinoids act on cannabinoid receptors, many aspects of human physiology are affected in diabetes; lipid and glucose (metabolic) homeostasis, mitochondrial function and oxidative stress, inflammation and immune function.

Cannabinoids all work on cannabinoid receptors in different ways. They can either activate, block or modify the receptors downstream signalling pathways. Thats why its important to use the whole plant, because it provides a complex means of bringing balance to the ECS.

The way whole plant extracts work on the ECS is not exclusive to diabetes, but is relevant to many diseases and imbalances. As you know many conditions result from multiple imbalances, and something that can potentially act to correct these imbalances would be quite significant.

My research into the evidence has piqued an interest as to which other diseases could be similarly affected by cannabinoids, and I look forward to sharing my insights with you going forward.

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CBD: Where to begin in clinical practice

Clear vase full with bamboo shoots in the foreground of a clinical room

1. UNDERSTAND CBD mg’s

CBD packaging can seem confusing with various percentages and total mg’s… The key is to know how many mg of CBD are in each drop so you can be very precise.

Here’s a summary of our 10ml oils which contain a total of 200 drops per bottle:
– 2% 200mg equates to 1mg CBD per drop
– 5% 500mg equates to 2.5mg CBD per drop
– 10% 1000mg equates to 5mg CBD per drop
– 20% 2000mg equates to 10mg CBD per drop

Our most popular starter oil is 2% with culinary sweet orange extract.

2. HOW TO TAKE CBD
CBD is best consumed sub-lingually. Encourage clients to hold the oil there as long as they can.

3. START LOW AND GO SLOW
We want to slowly activate the EndoCannabinoid System. Unsure what the ECS is? Read our blog.
Some people may notice improvements immediately, others may take 10 days for the ECS to ‘wake up’.

DAYS 1-5
5mg CBD in the morning
5mg CBD in the evening (especially if there are any sleep issues)

Days 6-10 (increase the dose if not noticed an improvement in symptoms)
10mg CBD in the morning
10mg CBD in the evening

After Day 10
The ECS should be activated. The client can continue with morning and evening dosages, or dose in response to symptoms (eg pain).

A standard dose could even go up to 20mg in the morning and 20mg in the evening.

Some clients may require higher doses based on their individual needs, which brings us to point 4:

4. USE THE MIGHTY GREEN DOSAGE/SYMPTOM TRACKER. Click here to view. Some people may want to increase the dose in response to symptoms. Encourage your clients to use the tracker to help them understand how CBD is helping them.

5. REACH OUT Rory and I are here to help. Send your questions to support@mightygreen.co.uk

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Does CBD help a Migraine?

Long haired brunette women covering face with hands in pain

Migraines are a form of primary headache disorder, characterised by recurrent headaches that are moderate to severe. The pain of a migraine can last from anywhere between a few hours to 3 days, and can be debilitating.

The addition of nausea, vomiting and sensitivity to light, sound and smell makes migraine attacks a significant burden on quality of life.

Typically, migraines are managed both acutely and preventatively.

Preventative drugs are taken daily to reduce the severity and frequency of migraines.

Pain relieving drugs are taken during a migraine attack, in an attempt to remove symptoms.

A side effect of using medication is the occurrence of an ‘overuse headache’ after regular and long term use of migraine medication.

Some individuals who can’t find relief, or have adverse side effects with conventional treatments have turned to using cannabinoids.

A study recently (2019) conducted by Washington State University used data from a symptom tracking app, Strainprint to assess the effectiveness of using smoked cannabis for migraines.

1,300 patients logged 12,000 sessions to track changes to their headaches after having used cannabis. Another 653 used the app to record 7,400 sessions tracking changes to their migraine severity.

There was no evidence of overuse headaches, however the doses did increase overtime suggesting the development of tolerance to cannabis effects.

Interestingly, cannabis concentrates were reported to produce a greater reduction in headache severity than cannabis flowers.

Using inhaled cannabis reduced headache severity by 47.3% and migraine severity by 49.6%, which is a significant reduction (Cuttler et al., 2019).

Although this is obviously limited by the fact it is self reported data, the dataset is a big one and is encouraging for the use of reducing headache and migraine severity.

Cannabis is also used prophylactically, to prevent the occurrence of migraines.

In 2016, a retrospective chart review was conducted across two speciality clinics in Colorado. Migraine headache frequency decreased from 10.4 to 4.6 headaches per month with use of medical cannabis. ~ 40% of patients said they experienced a positive effect, and ~ 20% said it reduced the frequency of migraine headaches (Rhyne et al., 2016).

Again, the data is limited by self reports. But there’s some evidence that backs this up in a clinical setting.

48 patients with chronic migraine were given Amytriptamine or 200mg of a 0.4% THC: 9% CBD cannabis preparation for 3 months. As a prophylactic, THC:CBD resulted in a 40.4% reduction in attacks compared to 40.1% who were using Amytriptamine. Acute dosing of THC:CBD for migraine abortion reduced pain intensity by 43.5%. However, THC:CBD was not an effective prophylactic for those with cluster headaches, only as an acute treatment for patents who’ve had cluster headaches since childhood (Baron et al., 2018).

Although cannabis is not CBD per se, this trial used a ratio of THC:CBD that favoured CBD. No trials have been conducted with CBD alone. Although, user reports with CBD report significant improvements in their migraine symptoms (Reddit, 2019).

Mechanistically speaking, CBD could help resolve a migraine. The endocannabinoid system is involved in the resolution of stress and pain, typically in response to an environmental trigger.

However, there’s evidence that migraine patients exhibit a deficiency in endocannabinoids, and therefore are unable to properly resolve a response to an environmental trigger, which leads to pain (Russo, 2016).

CBD is known to augment the levels of endocannabinoids in the brain, by inhibiting their degradation and re-uptake (Leweke et al., 2012). Increased levels of the endocannainoid Anandamide may produce the analgesia seen in migraine patients, via activation of the CB1 receptor in the nervous system (Manzanares, Julian and Carrascosa, 2006).

What;s also important to bear in mind as well, though is that THC is also analgesic, and almost certainly plays a role in reducing pain in migraines.

It’ll be interesting to see how clinical trials with CBD alone play out, but for now the best we can do is go by under reports, and extrapolate results from mixed THC and CBD studies.

References

Baron, E. P. et al. (2018) ‘Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort’, Journal of Headache and Pain. Springer-Verlag Italia s.r.l., 19(1). doi: 10.1186/s10194-018-0862-2.
Cuttler, C. et al. (2019) ‘Short- and Long-Term Effects of Cannabis on Headache and Migraine’, Journal of Pain. doi: 10.1016/j.jpain.2019.11.001.
Leweke, F. M. et al. (2012) ‘Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia’, Translational Psychiatry, 2. doi: 10.1038/tp.2012.15.
Manzanares, J., Julian, M. and Carrascosa, A. (2006) ‘Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes’, Current Neuropharmacology. Bentham Science Publishers Ltd., 4(3), pp. 239–257. doi: 10.2174/157015906778019527.
Reddit.com. (2019). Official Migraine / Headache Dosage Thread : CBD. [online] Available at: https://www.reddit.com/r/CBD/comments/74p67j/official_migraine_headache_dosage_thread/ [Accessed 17 Dec. 2019].
Rhyne, D. N. et al. (2016) ‘Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population’, Pharmacotherapy. Pharmacotherapy Publications Inc., 36(5), pp. 505–510. doi: 10.1002/phar.1673.
Russo, E. B. (2016) ‘Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes’, Cannabis and Cannabinoid Research. Mary Ann Liebert Inc., pp. 154–165. doi: 10.1089/can.2016.0009.

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Does CBD help with IBS?

If you’ve been getting stuck into the practitioners guide to CBD, then you’ll have an idea about what the endocannabinoid system (ECS) is and what it does.

The reason I bring this up with relation to IBS, is because its a perfect example of how widespread the effects of the ECS are.

As you’ll know very well, there’s imbalances across various functional systems in IBS, which present themselves as a variety of symptoms.

Anxiety, motility disruption like constipation and/or diarrhoea, insomnia and pain are usually the key players.

There’s good reason to believe that all these symptoms are underpinned by dysregulation of the universal conductor of the body – the ECS.

Ethan Russo is one of the most prolific cannabinoid researchers, and he has posited that IBS is a condition which is underpinned, in part by an Endocannabinoid deficiency (Russo 2016).

This makes sense, if you look at the mechanisms by which the ECS operates with relation to IBS:

Endocannabinoids regulate intestinal inflammation
Endocannabinoids control intestinal permeability
There’s cross talk between endocannabinoids and the intestinal microbiome
Endocannabinoids initiate and sustain sleep
Endocannabinoids put the brakes on the HPA axis, as part of a negative feedback loop to resolve stress
Endocannabinoids are involved in pain signalling
Endocannabinoids regulate GI motility

Surveys of CBD users report significant improvements with relation to IBS (projectCBD.org), which I believe is due to the fact that CBD is a tonic regulator of the ECS.

CBD has been found to act as both an intestinal anti pro-kinetic (Abalo et al.,2012) and pro-kinetic (Izzo et al.,2009). I suspect that whether CBD acts in one direction or the other depends upon the activity of an individuals own ECS.
CBD is an antibacterial and antifungal agent (Van Klingeren and Ham 1976), so using it internally could help arrest microbial imbalances such as SIBO and dysbiosis.
CBD can reduce intestinal permeability, reducing the impact of a leaky gut (Gigli et al. 2017).
CBD can modulate the HPA axis, and may help resolve stress (Viudez-Martínez et al,, 2018).
CBD can increase the time spent in deep, restorative REM sleep (when appropriately dosed) (Babson et al., 2017).
CBD is able to modulate sensitivity to pain

Dosing will be an important consideration with your IBS patients, since the ECS can be tonically regulated and may vary for constipation vs diarrhoea predominant IBS. Use ascending doses and start low, and go slow. Get your clients to use the dose and symptom tracker to find where they’ve had the best results.

References

Abalo, R. et al. (2012) ‘The Gastrointestinal Pharmacology of Cannabinoids: Focus on Motility’, Pharmacology, 90(1–2), pp. 1–10. doi: 10.1159/000339072.

Babson, K. A., Sottile, J. and Morabito, D. (2017) ‘Cannabis, Cannabinoids, and Sleep: a Review of the Literature’, Current Psychiatry Reports. Current Medicine Group LLC 1. doi: 10.1007/s11920-017-0775-9.

Gigli, S. et al. (2017) ‘Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells’, United European Gastroenterology Journal. SAGE Publications Ltd, 5(8), pp. 1108–1115. doi: 10.1177/2050640617698622.

Izzo, A. A. et al. (2009) ‘Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb’, Trends in Pharmacological Sciences. Elsevier Ltd, pp. 515–527. doi: 10.1016/j.tips.2009.07.006.

van Klingeren, B. and ten Ham, M. (1976) ‘Antibacterial activity of Δ9-tetrahydrocannabinol and cannabidiol’, Antonie van Leeuwenhoek. Kluwer Academic Publishers, 42(1–2), pp. 9–12. doi: 10.1007/BF00399444.

Russo, E. B. (2016) ‘Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes’, Cannabis and Cannabinoid Research. Mary Ann Liebert Inc., pp. 154–165. doi: 10.1089/can.2016.0009.

projectCBD.org

Viudez-Martínez, A., García-Gutiérrez, M. S. and Manzanares, J. (2018) ‘Cannabidiol regulates the expression of hypothalamus-pituitary-adrenal axis-related genes in response to acute restraint stress.’, Journal of psychopharmacology (Oxford, England), 32(12), pp. 1379–1384. doi: 10.1177/0269881118805495.

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Could CBD help with Obesity?

I think we need to tread carefully here. The world is saturated with weight loss gimmicks, and there are goodness knows how many weight loss supplements out there, herbal or otherwise.

I’m not saying CBD necessarily falls into this category, but its still early days to be making any concrete statements.

What I’m going to walk you through is how CBD may lend itself to helping Obesity, and share some of the research so far.

Some cross sectional studies have found that people with obesity have significantly elevated levels of endocannabinods in their blood.

Blood levels of endocannabinoids are suggested to represent the ‘spillover’ of excessive endocannabinoids produced by metabolic tissues such as skeletal muscle, the liver and adipose tissue , to name a few.

We know these tissues are dysregulated in obesity, and that’s partly because of the excessive levels of endocannabinoids they express.

Basically, people with Obesity have hyperactive endocannabinoid systems. Whats still uncertain is whether the ECS is hyperactive as a result of obesity, or if its driving it. Although I would suggest its the later based on what I’ve read.

Anyway, let’s continue. The ECS uses cannabinoid receptor 1 (CB1) to regulate all sorts of metabolic processes (Horn et al., 2018). Activation of CB1:

Reduces fatty acid oxidation
Increases lipogenesis
Reduces mitochondrial biogenesis
Reduces TCA cycle activity
Reduces Insulin sensitivity
Increases Insulin secretion
Increases appetite and food intake
Increases sweet taste perception
Reduces leptin sensitivity

So basically, most of the complications in Obesity can be partly attributed to ECS (mal)function.

The high level of endocannabinoids mean that the CB1 receptor is overstimulated and chronically activated, leading to a energy conserving, lipogenic phenotype.

Where CBD has been suggested to play a role is in the modulation of the CB1 receptor, and its sensitivity to activation by endocannabinoids. CBD has been found to block the CB1 receptor in the presence of CB1 agonists, like the endocannabinoid 2-Arachidonoylglycerol. (Remember: CBD has an adaptogenic effect on the ECS)

Its suggested to work as an antagonist at CB1, but the consensus is that it acts as a negative allosteric modifier, to dampen signalling elicited by an agonist.

What you’d expect to see from this effect is a reduction in appetite, fat mass, blood sugar and insulin levels, in addition to blood lipids. However, the only trial to look at these outcomes found no effect of CBD on these parameters, although it did reduce the levels of resistin, a hormone that raises LDL cholesterol (Jadoon et al., 2016).

The important thing to bear in mind here, though is that:

The trial used a very low dose (for research) of 200mg / day.
It was pure CBD (isolate), and any effect from entourage cannabinoids would have been missed.

CBD is also a powerful anti-inflammatory and antioxidant, so you’d expect that to negate the negative impact of inflammation and oxidative stress on insulin signalling.

Side effects reported from using CBD were associated with reduced appetite (Thiele et al., 2018), (Devinsky et al., 2016). CBD has also been found to reduce appetite and food intake in rats (Farrimond et al., 2012).

CBD also reduced body weight gain in rats when they were continuously given it for 14 days (Ignatowska-Jankowska et al., 2011).

Epidemiological studies hint at a similar effect when looking at the paradoxical effects of cannabis on body weight.

Data was used rom the National Epidemiologic Survey of Alcohol and Related Conditions. Researchers looked at the Body Mass Index, or BMI, of 33,000 participants, ages 18 and older(Alshaarawy and Anthony 2019).

Lead author of the study, Omayma Alshaarawy comments that “Over a three-year period, all participants showed a weight increase, but interestingly, those who used marijuana had less of an increase compared to those that never used.” (Sciencedaily.com)

“We found that users, even those who just started, were more likely to be at a normal, healthier weight and stay at that weight. Only 15% of persistent users were considered obese compared to 20% of non-users.”

The weight difference between users and non-users was modest, at around 2 lbs. Alshaarawy clarifies “An average 2-pound difference doesn’t seem like much, but we found it in more than 30,000 people with all different kinds of behaviours and still got this result,”

Although cannabis is more than just CBD, its plausible that CBD is contributing in some way. It seems as though cannabis, whilst not wholly promoting weight loss, may inhibit the gaining of weight.

What will be interesting to study is the effect of a CBD rich whole plant extract low in THC, much like our Broad Spectrum Hemp oral drops, on body weight and composition.

References

Alshaarawy, O. and Anthony, J. C. (2019) ‘Are cannabis users less likely to gain weight? Results from a national 3-year prospective study’, International Journal of Epidemiology. Oxford University Press (OUP). doi: 10.1093/ije/dyz044.

Devinsky, O. et al. (2016) ‘Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial’, The Lancet Neurology. Lancet Publishing Group, 15(3), pp. 270–278. doi: 10.1016/S1474-4422(15)00379-8.

Farrimond, J. A., Whalley, B. J. and Williams, C. M. (2012) ‘Cannabinol and cannabidiol exert opposing effects on rat feeding patterns’, Psychopharmacology, 223(1), pp. 117–129. doi: 10.1007/s00213-012-2697-x.

Horn, H. et al. (2018) ‘Endocannabinoids in body weight control’, Pharmaceuticals. MDPI AG. doi: 10.3390/ph11020055.

Ignatowska-Jankowska, B., Jankowski, M. M. and Swiergiel, A. H. (2011) ‘Cannabidiol decreases body weight gain in rats: Involvement of CB2 receptors’, Neuroscience Letters, 490(1), pp. 82–84. doi: 10.1016/j.neulet.2010.12.031.

Jadoon, K. A. et al. (2016) ‘Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, parallel group pilot study’, Diabetes Care. American Diabetes Association Inc., 39(10), pp. 1777–1786. doi: 10.2337/dc16-0650.

Thiele, E. A. et al. (2018) ‘Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial’, The Lancet. Lancet Publishing Group, 391(10125), pp. 1085–1096. doi: 10.1016/S0140-6736(18)30136-3.

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The Endocannabinoid System & The Skin

Both the dermis and the epidermis are home to cannabinoid receptors (CB1 & CB2).

Typically, the body’s ECS naturally maintains skin health, inflammation, pain, sensitivity and blood flow through these receptors.

CBD is usually taken orally, but can also be applied to the skin, as a massage oil.

It doesn’t have the same widespread effects as when its taken orally, since it doesn’t enter the bloodstream.

The advantages

CBD is more bioavailable when applied through the skin. (bypasses liver)
The effects are highly concentrated to the area it is applied.

The disadvantages

The effects of CBD are localised to the area it is applied on the body.
It may not pose the same benefits on the brain and psychological conditions. At least not directly.

However, sometimes the ECS can become dysregulated and fail to arrest pain, inflammation and skin damage.

That’s where CBD comes in; it helps support an ECS thats dysregulated, by modifying the activity of CB receptors.

Benefits of External CBD

When CBD was applied externally it reduced pain, reduced skin blistering and accelerated wound healing (Chelliah et al., 2018).

There is little clinical research in humans using CBD externally. However, in animals external CBD use has shown promise for:

Arthritis (Hammell et al., 2016)
Swelling (Lodzki et al., 2003)
Psoriasis (Wilkinson and Williamson, 2007)
Dermatitis (Eagleston et al., 2018)

A survey in the USA reported the most common use for CBD was for pain, joint pain

& arthritis (Corroon and Phillips, 2018)

Users also claim that CBD may also help with muscle pain and recovery.

Studies have also shown that CBD:

Reduces inflammation (Pellati et al., 2018) and dilates blood vessels (Jadoon, Tan and O’Sullivan, 2017), which may aid muscle pain and recovery.
Reducing inflammation also alleviates joint pain.
Reduces pain originating from the nervous system (Whiting et al., 2015) (Chelliah et al., 2018).
Is a powerful antioxidant (Hacke et al., 2019), which may help with the general maintenance of healthy, vibrant skin in general.
Is an antibacterial (Andre, Hausman and Guerriero, 2016), which may help eliminate bad bacteria which underlie skin conditions.

Benefits of CBD Massage

The therapeutic effects of a massage may be compounded in the following ways by CBD:

May enhance muscular relaxation.
May increase the relief of pain.
May soothe damaged skin.
May speed muscle recovery and reduce soreness.

Cannablissful Massage Oils

Cannablissful massage oils combine broad spectrum CBD from hemp with a wide array of aromatic and therapeutic essential oils.

Together Cannablissful massage oils provide a powerful synergy in combination with massage to soothe, energise and relax.

Soothe: Bring your body into balance with laid back lavender, geranium, bergamot & broad spectrum hemp.

Energise: Naturally awaken your energy with lively lemon, peppermint, eucalyptus, lavender & broad spectrum hemp.

Relax: Restore and renew with kick back chamomile, lavender, jasmine & broad spectrum hemp.

Cannablissful products are tested to ensure they contain less than 0.2% THC.

They are also tested to ensure they contain the CBD they claim to.

A massage oil can either be used for a specific bodily part, or the whole body.

Whole body massages will require more oil, and may not provide the same degree of pain relief as the same dose applied to a specific area.

Shake well before use, apply 5ml to clean palms to warm and activate the oil.
Spread across the body, or to a specific area if desired.
Apply more if needed.
Wait 15-45 minutes for effects to sink in.

Cannablissful Massage Balm

Massage balms provide a stronger grip, and lower glide than massage oils. They are ideal for treating specific areas of the body, since they can be applied with more control and precision.

Cannablissful massage balm has been designed to provide concentrated CBD and essential oils for targeted massages.

External CBD Caveats

Some people have found that they can be allergic to the cannabis plant. It’s worth remembering this when you use topical formulations, just in case.

Although topical CBD may help with wound healing, there is a risk of infection if it is applied to open wounds. Avoid applying CBD until the wound has undergone some healing first.

References

Andre, C. M., Hausman, J.-F. and Guerriero, G. (2016) ‘Cannabis sativa: The Plant of the Thousand and One Molecules’, Frontiers in Plant Science. Frontiers Media SA, 7, p. 19. doi: 10.3389/FPLS.2016.00019.

Bíró, T., Tóth, B. I., Haskó, G., Paus, R., & Pacher, P. (2009). The endocannabinoid system

of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends in pharmacological sciences, 30(8), 411–420.

Chelliah, M. P. et al. (2018) ‘Self-initiated use of topical cannabidiol oil for epidermolysis bullosa’, Pediatric Dermatology, 35(4), pp. e224–e227. doi: 10.1111/pde.13545.

Corroon, J. and Phillips, J. A. (2018) ‘A Cross-Sectional Study of Cannabidiol Users.’, Cannabis and cannabinoid research. Mary Ann Liebert, Inc., 3(1), pp. 152–161. doi: 10.1089/can.2018.0006.

Eagleston, L. R. M. et al. (2018) ‘Cannabinoids in dermatology: a scoping review.’, Dermatology online journal, 24(6). Available at: http://www.ncbi.nlm.nih.gov/pubmed/30142706 (Accessed: 2 October 2019).

Hacke, A. C. M. et al. (2019) ‘Probing the antioxidant activity of Δ9-tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts.’, The Analyst, 144(16), pp. 4952–4961. doi: 10.1039/c9an00890j.

Hammell, D. C. et al. (2016) ‘Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis’, European journal of pain (London, England). NIH Public Access, 20(6), p. 936. doi: 10.1002/EJP.818.

Jadoon, K. A., Tan, G. D. and O’Sullivan, S. E. (2017) ‘A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study’, JCI Insight, 2(12). doi: 10.1172/jci.insight.93760.

Lodzki, M. et al. (2003) ‘Cannabidiol—transdermal delivery and anti-inflammatory effect in a murine model’, Journal of Controlled Release, 93(3), pp. 377–387. doi: 10.1016/j.jconrel.2003.09.001.

Pellati, F. et al. (2018) ‘Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer’, BioMed Research International, 2018, pp. 1–15. doi: 10.1155/2018/1691428.

Whiting, P. F. et al. (2015) ‘Cannabinoids for Medical Use’, JAMA, 313(24), p. 2456. doi: 10.1001/jama.2015.6358.

Wilkinson, J. D. and Williamson, E. M. (2007) ‘Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis’, Journal of Dermatological Science, 45(2), pp. 87–92. doi: 10.1016/j.jdermsci.2006.10.009.

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CBD and Pain

One of the most common uses for CBD is undoubtedly pain.

This is not new. Hua Tho, a second-century Chinese physician invented mafeisan, ‘hemp boiling powder’ which dissolved in wine. It was the first recorded general anaesthesia employed during a surgical procedure.

Back to the modern day, there’s a good body of emerging evidence suggesting that CBD may be useful for all kinds of pain. Pain is usually differentiated into:
– neuropathic (originating in nerves)
– visceral (originating in an organ eg. menstrual cramps)
– somatic (musculoskeletal or the skin)
– psychogenic (the experience of a panic attack or tension headache for example).

CBD is an incredible plant compound, because it can have many different effects in the body all at one time – its impact is ubiquitous. Mechanistically speaking, CBD pushes a lot of buttons that help reduce pain.

CBD increases Anandamide, which is anti-inflammatory and analgesic upon activation of the CB1 receptor within the nervous system (Huang et al., 2016)..
CBD turns down the volume at mu (μ) and delta (δ) opioid receptors to reduce pain signalling (Kathmann et al., 2006)
CBD turns down the volume at Glycine receptors to reduce pain signalling (Xiong et al., 2012)
CBD increases the signalling at GABA receptors to overcome the sensation of pain (Bakas., et al 2017)
CBD activates TRPV1 and TRPA1 receptors to reduce pain signalling (Muller et al., 2018)
CBD promotes adenosine A2A signalling which may reduce pain (Pandolfo et al., 2011)

Clinical trials with CBD have also found it to be effective for managing pain. CBD (2.5mg per actuation) have been shown to significantly reduce neuropathic pain compared to placebo (Wade et al., 2002), (Notcutt et al., 2004).

A survey also found that pain was amongst the most common use for CBD (Corroon , Phillips., 2018), so it’s good to see real world data supporting the (sparse) evidence for CBD’s effect on pain.

References

Bakas, T. et al. (2017) ‘The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABAA receptors’, Pharmacological Research. Academic Press, 119, pp. 358–370. doi: 10.1016/j.phrs.2017.02.022.

Huang, W. J., Chen, W. W. and Zhang, X. (2016) ‘Endocannabinoid system: Role in depression, reward and pain control (Review)’, Molecular Medicine Reports. Spandidos Publications, pp. 2899–2903. doi: 10.3892/mmr.2016.5585.

Kathmann, M. et al. (2006) ‘Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors’, Naunyn-Schmiedeberg’s Archives of Pharmacology, 372(5), pp. 354–361. doi: 10.1007/s00210-006-0033-x.

Muller, C., Morales, P. and Reggio, P. H. (2019) ‘Cannabinoid ligands targeting TRP channels’, Frontiers in Molecular Neuroscience. Frontiers Media S.A. doi: 10.3389/fnmol.2018.00487.

Notcutt, W. et al. (no date) Initial experiences with medicinal extracts of cannabis for chronic pain: Results from 34 ‘N of 1’ studies.

Pandolfo, P. et al. (2011) ‘Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum’, European Journal of Pharmacology. Elsevier B.V., 655(1–3), pp. 38–45. doi: 10.1016/j.ejphar.2011.01.013.

Wade, D. T. et al. (2003) ‘(No Title)’, Clinical Rehabilitation, 1, pp. 21–29. doi: 10.1191/0269215503cr581oa.

Xiong, W. et al. (2012) ‘Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors’, Journal of Experimental Medicine, 209(6), pp. 1121–1134. doi: 10.1084/jem.20120242.

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Disordered eating and the Endocannabinoid System

The ECS plays a leading role in controlling several aspects of how we eat; what we want to eat, how much food we eat, and how frequently we eat it. We know the ECS plays a leading role in governing appetite because of the effect cannabis and THC has on the desire to eat.

It’s also a key player in how much energy we burn off in response to the food we have eaten, and instructs changes in metabolic rate and thus weight gain and body composition.

The activity of our ECS are all different, and affects what foods we eat, how much of it and how much weight we will put on as a result. Its the middle man between the food we eat and how it affects our body composition.

The ECS influences our relationship with food, and how food is stored in our bodies in a few ways.

Food intake (how much we eat)
How rewarding a food seems
Energy expenditure (rate at which food is burnt off)

Mechanistically, these processes are controlled in various brain regions by the ECS. Specifically, its the cannabinoid receptors in the brain (mainly CB1) that act as switches to turn appetite, pleasure (in response to food), and metabolism up or down.

The level of endocannabinoids present in these brain areas influence to what degree these switches are turned on or off, and essentially how hungry, rewarded and efficient we are at burning off energy.

Everyone has a different ECS activity, so the number of CB1 receptors and levels of EC’s will vary in everyone’s brain, and thus affect their appetites and body composition differently.

Keep an eye out for future emails where we’ll explain more…

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CBD & Anxiety

Perhaps one of the most popular uses for CBD is for anxiety. Both anecdotally and clinically, CBD is quickly becoming the remedy of choice. From stressed out housewives to anxious university students, lots of people are jumping on board.

CBD is a promiscuous chemical in the body, it pushes a lot of different buttons all at the same time, which is how its able to have a profound impact on anxiety.

One way CBD helps to alleviate anxiety is by supporting serotonin signalling in various parts of the brain. Serotonin is needed to foster feelings of safety, security and stability. Some people may lack the ability to produce sufficient serotonin, either from a genetic standpoint or through their circumstances in life.

CBD is a serotonin receptor activator (5HT1A agonist). What that means is your brain thinks it has more serotonin than it does, as CBD mimics its activity.

If you’ve ever drunk too much coffee, then you’ll know about anxiety. In the brain, you’ll find receptors which recognise caffeine, called Adenosine receptors. Under normal circumstances, Adenosine receptors keep a grip on how stimulated and excited our minds are. When we drink caffeine however, that blocks Adenosine receptors to increase stimulation, sometimes too much so and we become anxious.

CBD activates one Adenosine receptor and also increases the concentration of Adenosine itself (Maroon and Bost 2018). Consequently, this reduces excessive stimulatory activity whether induced by caffeine or not, such as high heart rate, anxiety and blood pressure.

This is why CBD has become a popular additive to coffee, for its ability to reduce the negative aspects of caffeine whilst keeping part of the buzz.

Yet another way CBD reduces anxiety is encouraging the brain towards a calmer state as opposed to a more excited one. Two opposing brain chemicals control whether we are in a state of excitation and arousal, or a calm, relaxed state. Glutamate and GABA are the two opposing chemicals which control the balance between arousal and relaxation. Too much glutamate signalling produces anxiety, and other negative outcomes (long term). Lack of GABA signaling similarly perpetuates anxiety.

For anxiety to resolve, GABA signaling often needs a helping hand. This is how benzodiazepine drugs such as Valium work by increasing GABA in the CNS and brain. Relaxing herbal teas such as chamomile and valerian also do the same, although to a lesser extent. CBD also turns up the volume of GABA signalling, so that our brains tend towards a more calm and relaxed state.

Perhaps the most profound way CBD influences anxiety is through supporting the ECS. CBD increases the EC Anandamide, which has a profound effect on mood regulation. Anandamide activates CB1 receptors on neurons that control all sorts of brain chemical systems, including serotonin.

Anxiety has been suggested to be related to an EC deficiency, and increasing Anandamide with CBD has the potential to support a wide range of ‘happy chemical’ systems. For example, Anandamide also controls the balance between arousal and relaxation, by regulating glutamate and GABA signalling.

CBD also has been shown to alter blood flow to certain areas of the brain which are involved in mood regulation and emotional processing (De Souza-Crippa 2004).

CBD has powerful direct and indirect effects (through the ECS) that enable it to crush anxiety.

A few clinical trials have found CBD to be effective for social anxiety and general anxiety (De Souza-Crippa 2004), although these were only short term in nature but certainly attest to the mountains of anecdotes that CBD helps anxiety.

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CBD & Alzheimers

Although there’s a lot of mechanistic evidence to support a case for CBD in Alzheimer’s, there’s been no research conducted directly with it.

Nonetheless, the basic science research is enough to keep me eagerly awaiting trials with CBD and I am optimistic as to the outcomes, particularly with regards to those relating to quality of life.

So while we wait for the trails, lets take a look at the mechanisms to see what we might be working with.

Alzheimers is characterised by cluster of pathophysiological mechanisms:

Beta-amyloid plaque accumulation
Glial cell activation
Neurodegeneration
Neuroinflammation
Excitotoxicity
Oxidative stress
Blood brain barrier permeability (leakiness)
Lipid peroxidation

These all culminate to produce the cognitive deficits and associated alterations to mood and personality seen in Alzheimers.

Both the functional and structural homeostatic processes by which the brain operates, maintains and regenerates itself are derailed in Alzheimers. Whats interesting to note is that the endocannabinoid system, which is the conductor of homeostasis, is working out of tune. This implicates it in the improper regulation of neurohomeostatic processes which are meant to keep the brain healthy.

The ECS has been reported to be under active in Alzheimer’s (Toczek and Malinowska 2018). This is where CBD comes in, as an aid to restore the ECS grip on homeostasis.

There are several ways which CBD may arrest the progression of Alzheimers, although until trials investigate these, this is very much still conjecture.

CBD has several features that may be exploited for the treatment of Alzheimers, including the prevention of glutamate-induced excitotoxicity, reduction of proinflammatory mediators, and the ability to scavenge reactive oxygen species (ROS) and reduce lipid peroxidation (Maroon and Bost 2018).

Acetylcholine is a neurotransmitter required for attention, learning and memory. Degeneration of cholinergic neurones eventually produces deficits in the ability to learn and form short term memories.

There are two ways in which CBD may help here:

CBD is neuroprotective. Its immunomodulatory and anti-inflammatory properties lend well to protecting neurones from degeneration.

CBD does this by decreasing the production of inflammatory cytokines tumor necrosis factor (TNF), interleukin 1β (IL-1β), interleukin 6 (IL-6) and interferon γ (IFN-γ) and encouraging microglial cells to return to a deactivated state.

Aside from protecting the cholinergic neurones that carry acetylcholine, CBD has also been found to increase acetylcholine itself (possibly by inhibiting acetylcholinesterase) (Murillo Rodriguez et al., 2018). This may amplify the signalling of the cholinergic system to partially restore some aspects of learning, memory formation and other processes like sleep.

Sleep is also problematic for Alzheimers patients, and the support of the cholinergic system as well as the endocannabinoid system (which also regulates sleep) by CBD may prove useful.

The real ringer here though is CBD’s role in the neurogenesis; the formation fo new neurones, which could play a significant role in Alzheimers.

CBD increases the formation of new neurons in the memory centre of the brain, the hippocampus (Maroon and Bost 2018). This may be due to CBD’s ability to increase a growth factor called BDNF which helps neurons grow (Sales et al., 2019).

Another issue in Alzheimers is the excessive signalling within the excitatory glutaminergic neurotransmitter system. The ECS normally controls the balance between inhibitory and excitatory neuronal signalling, but may fail to maintain the balance between them (in favour of excitation) in Alzheimers. CBD may help to depress excessive glutamate signalling, via increasing activation of the CB2 and 5HT1A receptor (*).

CBD’s ability to activate 5HT1A (serotonin) receptors may also promote better cognition as well (Mandolini et al. 2018).

CBD is also known to exert vascular effects, producing vasodilation as well as hypotension that may hold promise as protection against cerebrovascular damage associated with stroke (Maroon and Bost 2018).

CBD may preserve brain blood circulation when it can become restricted, and reduce vascular changes and associated neuroinflammation (Maroon and Bost 2018).

CBD also increases brain adenosine levels by reducing adenosine reuptake. Increased adenosine is associated with neuroprotection and decreased inflammation after brain trauma (Maroon and Bost 2018).

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Corona Chaos: Take A Load Off

As half the world descends into panic mode, us lot at Mighty Green are cracking open a couple 20% oral drops to take a load off.

Amidst what’s going on at the moment, it may be hard to find the wherewithal to relax, which is totally understandable. But let me tell you why we’re getting by (not high) on our own supply.

Now is perhaps one of the best times to seek a little herbal help from hemp for some much needed respite from the anxiety.

But don’t just take it from us, there are many other credible sources of information which demonstrate how popular and effective CBD can be for anxiety.

A cross-sectional study was conducted in 2018, which looked at what people reported using their CBD for and how effective they found it. The study used an online survey to record the experiences of 2409 CBD users. The results showed that almost 62% of people used CBD to treat a medical condition, amongst the top 3 of which was anxiety.

Also, participants most frequently reported feeling that CBD treated their medical condition(s) “very well by itself” or “moderately well by itself” for anxiety (Corroon and Phillips 2018).

What’s great about this observational study, is that it reports real world data that ties in nicely to what’s been found in (pre)clinical settings with CBD.

Most studies use a simulated public speaking test to test CBD’s efficacy, because it’s a reliable way of inducing anxiety.

In a randomised controlled trial of 57 healthy male subjects, CBD was studied at various doses compared to placebo. Anxiety was measured by the Visual Analogue Mood Scale (VAMS) to evaluate state anxiety levels. Compared to placebo, 300mg CBD resulted in significantly lower VAMS scores than placebo.

Studies examining the physiological changes that occur in the brain with CBD confirm that the anxiolytic effects of CBD are a result of changes in amygdala, hippocampus, parahippocampal gyrus and cingulate cortex activity (Fusar-Poli et al., 2009), (Crippa et al., 2011). The metabolism of endocannabinoids such as Anandamide is also altered by CBD (Crippa et al., 2011), in a way which has been shown to improve mood and lessen anxiety in animal studies (Melo Schier et al., 2014).

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CBD & Sleep

Sleep is one of the most important recovery processes, and there’s no compromise on losing out on it. This is especially true for clients who are working to recover from chronic health conditions. Poor sleep or sleep deprivation is a stressor, and one that can be done without.

When we don’t get enough sleep, our hormonal equilibrium suffers as a result. I’m mainly referring to cortisol, which becomes elevated with chronically bad sleep. Elevated cortisol is a sign of stress, and can have negative effects on overall health and wellbeing.

Stress comes in many forms: financial, emotional, romantic and mental stress all pitch in to raise cortisol.

Elevated Cortisol is a problem for a few reasons:

Cortisol is catabolic and breaks down muscle tissue (Gore et al., 1993). Muscle mass is an important factor for supporting health and longevity.
Cortisol is important for regulating inflammation, chronic elevations reduce immunity (Hannibal, Bishop 2014).
Cortisol is antagonistic to insulin and testosterone, two hormones needed for mental & metabolic wellbeing.
Cortisol reduces insulin sensitivity, and inhibits glucose uptake into muscle which interferes with normal blood sugar regulation (Geer et al., 2015)
Cortisol spikes in the evening make it tough to get good sleep (Hirotsu et al., 2015)

Cortisol forms part of the Hypothalamic Pituitary Adrenal (HPA) axis, the hormonal network which regulates stress. The ECS is also involved in regulating the HPA axis, through CB1 receptors found on the hypothalamus and pituitary gland. This enables the ECS to put the brakes on the HPA axis to resolve stress.

Cannabinoids are also a way of reducing stress, and CBD has been shown to reduce corticosterone (cortisol) (Crippa et al., 2018) in animals. CBD has also been shown to influence cortisol release in humans (Zuardi, Moriera 1993), which may help resolve stress.

This may be due to CBD’s ability to increase the brains natural cannabinoid, Anandamide. Anandamide activates the CB1 receptor in the hypothalamus, which may cause a downstream reduction in cortisol secretion from the adrenals (Crippa et al., 2018).

In support of this, CBD has been shown to lessen anxiety (Zuardi et al., 1993), (Crippa et al., 2011), (Linares et al.,2019), (Bergamaschi et al., 2011) and improve sleep in people with sleep disorders (Chagas et al., 2014), (CARLINI and CUNHA, 1981), (Shannon et al., 2019. CBD’s ability to improve sleep has been partly attributed to its ability to lessen anxiety, and perhaps by reducing cortisol.

Another way CBD helps promote sleep is via modulation of the sleep cycle – the timing duration and architecture of sleep. It does this by modulating the ECS.

The ECS is tied to the rhythms of night and day, and its activity fluctuates in response to what time of day or night it is.

By adjusting its activity according to the time of day/night, the ECS helps keep our body clocks in sync with the natural rhythms of night and day. In other words, we sleep and wake up when we are supposed to.

It’s also responsive to environmental cues which affect our body clocks. Light exposure affects the ECS, and so does food intake. These are both called timekeepers, because they affect the body clock and whether we stay synchronised with the Earth’s 24 hour cycle.

Eating late at night throws the ECS off, and so does exposing oneself to light when it’s dark outside.

The ECS maintains the relationship between our body clocks and sleep cycles. Naturally, it keeps our bodies in sync with night and day, so that our sleep cycles are initiated and maintained every night.

The ECS is subject to imbalances from everyday stressors like psychological and environmental stress, poor diet, infections and a sedentary lifestyle. Sometimes, a disrupted ECS may lead to issues with sleep.

Conditions which involve sleep irregularities such as PTSD, Parkinsons and Sleep deprivation are also associated with ECS imbalances.

Here are a few studies where CBD has shown promise for sleep thus far.

In a large retrospective case series at a psychiatric clinic, 25 psychiatric patients with sleep disorders taking 25 – 75mg CBD /day improved subjective sleep scores by 28% after 3 months (Shannon et al., 2019). However, in the 47 other psychiatric patients without overt sleep disorders the same doses had less of an impact. This suggests CBD’s efficacy depends upon the existence of a sleep disorder.

Consistently, a double blind RCT giving 160mg CBD to 15 insomniacs improved sleep duration (> 7 hrs), reduced waking and improved subjective sleep quality compared to placebo (CARLINI and CUNHA, 1981). Lower doses of 40 & 80mg did not have this effect. CBD also had no effect on the time it takes to get to sleep.

4 Parkinson’s patients with REM sleep disorder were treated with 75 – 300mg / day CBD for 6 weeks. 3/4 patients completely eliminated frequency symptoms (1-7 x per week > 0 x per week). 1 Patient still experienced symptoms (1 x / week), but still improved from 4 x / week (Chagas et al., 2014).

18-24mg CBD reduced insomnia and PTSD symptoms in a case report (Shannon and Opila- Lehman, 2015).

Here are the mechanisms:

High doses of CBD have been shown to aid sleep. CBD boosts Anandamide levels, by inhibiting FAAH (the enzyme that breaks Anandamide down). Anandamide aids sleep and modulates sleep architecture by activating CB1 (Chagas et al., 2013).

High dose CBD increases total sleep time and slow wave sleep in rats (Chagas et al., 2013).

High doses of CBD also increased REM sleep (Babson et al., 2017), which may improve sleep quality.

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CBD & Friends: The Entourage Effect

One of the reasons we are so fervently passionate about broad spectrum CBD is in large part due to something very special known as the entourage effect.

CBD comes in many different forms and varieties, which affects its efficacy and tolerability. We’ve carefully studied each of these, and came to the conclusion that broad spectrum was the best choice; it has everything you’d want in a CBD extract and nothing you don’t.

Im sure you know by now that CBD comes from a variety of the Cannabis plant known as Hemp. You may have even heard hemp referred to as a ‘superfood’ because of its plethora of nutrients and bioactive compounds. Although CBD is great, let’s not forget about all the other mighty compounds that make a broad spectrum extract so great.

In case you haven’t heard about the entourage effect, I’ll walk you through it. This is where the compounds of hemp extracts work together in synergy. Im talking about not just the cannabinoids, but the flavonoids and terpenes as well.

Together they produce a greater therapeutic effect than they would when given alone. In other words, the whole is greater than the sum of its parts.

Researcher Ethan Russo is one of the leading experts in studying the entourage effect. A large part of his focus is examining just how the other cannabinoids may complement the effects of CBD.

Take for example the muscle relaxant properties of CBD (Nitecka-Buchta et al., 2019) via increasing inhibitory GABAergic signalling in the CNS. Another cannabinoid, cannabigerol (CBG) has also demonstrated uptake inhibition of the neurotransmitter GABA (Banerjee et al., 1975), which may potentiate the muscle relaxant properties of CBD when combined.

Its not just cannabinoids, the aromatic compounds of hemp, known as terpenes can also synergise with CBD.

One such example of a terpene ~ CBD synergy is in the Mighty Green Sweet Orange 2% oil.

Sweet orange contains large amounts of the terpene Limonene. Limonene has been shown to have antidepressant effects in animals via boosting serotonin levels in the prefrontal cortex, and dopamine in the hippocampus via 5HT1a receptors (Russo and Marcu., 2017).

Furthermore, in an aromatherapy study in humans exposed to citrus scent, 9/12 hospitalized patients discontinued their antidepressant medication and normalised their depression scores (Komori et al., 1995).

Numerous animal studies also show an antidepressant effect of CBD via 5HT1a receptors; a shared mechanism with limonene (Mello Schier et al., 2017). This has still yet to be clinically confirmed in humans. However, a survey of CBD users reported depression was the third most common use for CBD (Corroon and Phillips 2018).

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CBDA: A Little Extra Goodness

CBDA (Cannabidiolic acid) is the acidic precursor to CBD which is also found alongside CBD select extracts, including our broad spectrum one. CBDA is considered as the raw form of CBD, as most CBD exists as CBDA before it gets heated or ‘activated’. CBDA was traditionally thought to be pharmacologically inactive, but research is now painting a very different picture.

CBDA is transformed into CBD via a process known as decarboxylation, the removal of carbon, oxygen and hydrogen atoms. Decarboxylation slightly alters the chemical structure and pharmacological properties of CBDA when forming CBD.

Decarboxylation occurs as a result of exposure to heat, sunlight and air and also occurs naturally over time.

New research is highlighting some exciting use cases for CBDA, and it may be more useful than CBD in some specific cases.

CBDA demonstrates 100-fold greater affinity for the 5-HT1A receptor when compared to CBD (Russo 2018). This may mean CBDA is more effective for conditions which involve complications with serotonin signalling, such as in psychiatric cases like depression, neurological ones like parkinsons and cases of migraine, epilepsy, nausea and vomiting.

Just like CBD, CBDA has also demonstrated significant antidepressant and anti-anxiety activity in mice (Hen-Shoval et al., 2018), although studies in humans are still needed to confirm this.

CBDA can potently suppress signs of nausea in rats and potently inhibits toxin- and motion-induced vomiting in shrews. Whereas CBD only appears to inhibit toxin induced vomiting. CBDA may be a promising agent for motion sickness, unlike CBD (Bologniniet al., 2013).

CBDA (0.1 and 0.5 mg·kg) was also able to reduce vomiting at significantly lower doses than CBD (>40 mg·kg) (Bologniniet al., 2013).

CBDA may also display greater potency, efficacy or selectivity at ameliorating signs of cerebral infarction, pain, anxiety and depression than CBD (Bologniniet al., 2013) (yet to be clinically confirmed).

CBDA was also found to have an antiepileptic effect, which may be due to its interaction with the serotonin system (Russo 2018).

CBDA was found to have potent anti-inflammatory and pain relieving effects in rats. In comparison to CBDA, an equivalent low dose of CBD did not reduce pain, suggesting that CBDA is more potent than CBD for pain relief (Rock et al., 2018).

CBD has a notoriously low oral bioavailability. Bioavailability varies based on method of administration (vaping, oral drops or capsules), but tends to be lowest for capsules (4-20%).

CBDA shows significantly greater bioavailability and absorption compared to CBD. CBDA was shown shown to reach blood levels significantly greater than CBD (55.03 ng/ml vs 3.14 ng/ml) (Pellesi et al., 2018).

CBDA
Despite being contained in a quantity just under double that of CBD in a cannabis oil preparation, CBDA blood levels reached over 18 times that of CBD (4.4mg vs 2.4mg).

CBDA mg
Using CBDA may also boost the bioavailability of CBD; the use of unheated cannabis extract rich in acidic phytocannabinoids may beneficially affect the uptake and metabolism of CBD or other phytocannabinoids (Ujváry and Hanuš 2016).

CBDA may also potentiate the effects of other 5HT1A agonists (Bologniniet al., 2013), such as CBD which is another compelling reason to combine the two.

Having CBDA in an extract with CBD is another example of the entourage effect, where the two can be complementary to one another and act in synergy.

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The Entourage Effect: Why its Clinically Meaningful

I bet you’ve heard us mention our broad spectrum extract several times now. That’s not only because it’s one of the purest around, but also largely because of something called the entourage effect.

We gave a presentation to nutritional therapists at BCNH which touched on the entourage effect, and some of you who saw it may even be reading this now. So today, we’re going to take a dive into what it is and its clinical significance.

Hemp extracts contain more than just CBD. They are home to numerous other pharmacologically active constituents, both in the same family as CBD (other cannabinoids) and other closely related families.

Let’s start by getting something straight – its not all about CBD. Yes, CBD has some pretty remarkable effects on it’s own, but its also taken a lot of credit from other cannabinoids that accompany it.

CBD is considered a major cannabinoid, because it’s typically present in extracts at higher concentrations than its siblings. Other major cannabinoids include Δ9-tetrahydrocannabinol (THC), Cannabigerol (CBG), Cannabichromene (CBC), Tetrahydrocannabivarin (THCV) and Cannabidivarin (CBDV).

Just like CBD, these other cannabinoids have significant therapeutic value too. They are similar in chemical structure, with subtle variations which allows them to both have shared and unique therapeutic effects.

For example, just like CBD, THCV can potently reduce inflammation. But it’s also able to reduce blood sugar in diabetics, which was an effect that was not shared by CBD (1).

Similarly, CBD can kill pain on its own, but pain relief is greater with THC combined (2), (3).

This means that with other cannabinoids present:

There is a greater diversity of therapeutic effects
The shared effects of CBD are compounded

That’s just cannabinoids. There are other curious characters present in hemp, which you can think of as cousins to CBD and other cannabinoids.

These are called terpenes, which are aromatic compounds present in many strains of hemp, but also many other plants. These are what make lavender smell well, like lavender and pine smell like pine to give a couple of examples. Much like cannabinoids they have shared and unique therapeutic effects too.

For example, the terpene found in citrus fruits (and also hemp) Limonene is an agonist at Adenosine A2A receptors just like CBD, which may provide additive effects for managing anxiety and inflammation.

Whereas unlike CBD which tends to have an inhibitory effect on gastrointestinal motility (4), limonene may increase the resting tone of the intestines (5).

Here’s some intriguing clinical evidence to support our argument above.

Clinical trials with purified CBD show that it has clinically meaningful effects on its own, particularly for Epilepsy (ref). However, when purified CBD was compared to whole plant CBD-rich extracts, similar to that of our broad spectrum one, we see some very different outcomes.

A recent meta analysis highlighted the fundamental differences in efficacy between purified CBD and whole plant CBD-rich extracts in patients with Epilepsy.

Firstly, patients using purified CBD reported having to use higher doses (1125 – 1625mg) in order to achieve respite from seizures than those using whole plant CBD-rich extracts (270-390mg).

Secondly, only 46% of patients using purified CBD reported reductions in seizure frequency compared to 71% of patients using a whole plant CBD-rich extract.

Third, only 33% of patients using whole plant CBD-rich extracts experienced side effects, 7% of which were considered severe. Whereas a whopping 76% of patients using purified CBD experienced side effects, of which 26% were severe (6).

This highlights what we have discussed above nicely, and is testament to the powerful synergy that exists between constituents of hemp. It’s not just for epilepsy, but for a myriad of functional interactions that influence health and disease related outcomes.

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CBD as an Adaptogen

If you’re a regular with us at Mighty Green, then you’ll certainly be familiar with the endocannabinoid system and its role in human physiology.

Here’s a little refresher; the endocannabinoid system is the master of maintaining homeostasis and fundamental equilibrium in the body. It’s crucial for maintaining the balance between excitatory and inhibitory processes, such as sleep and awakeness, immune stimulation and suppression etc.

Therefore, health depends on its ability to maintain a physiological goldilocks zone that promotes healthy sleep and daytime energy, and appropriate immune protection and resolution for example.

Problems can be associated with the ECS if it is both underactive and overactive. For example, ECS hypofunction was associated with anorexia (more studies needed to be certain) (*), whereas as seen in obesity, the ECS is reported to be overactive (good evidence) (*).

Similar processes like gastrointestinal motility, which controls the balance between diarrhea and constipation may also be regulated by a spectrum of endocannabinoid system activity (*).

The core mechanisms which dictate ECS activity, which is also referred to as ‘endocannabinoid tone’ are the interplay between the components of the ECS.

The number of cannabinoid receptors (CB1 and 2)
The levels of the endocannabinoids themselves
The activity of the metabolic enzyme which make and break down endocannabinoids

Together these components manage the activity of the ECS, which can be micromanaged at the tissue specific level (the pancreas can have a particularly high ECS tone in diabetes for eg).

What the ECS tries to do is balance itself out, usually by decreasing the number of cannabinoid receptors in relation to levels of high endocannabinoids and vice versa to maintain equilibrium.

Evidence for dysfunction can be seen when receptors or endocannabinoids are high or low in disease cases with respect to healthy controls.

The really neat thing about how CBD fits in here is based on its two fundamental interactions with the ECS.

CBD can antagonise endocannabinoids (at high levels) at the level of CB receptors, which is particularly relevant in obesity for example, where chronic CB1 activation drives metabolic problems. Therefore, CBD can act as an inhibitory agent to dampen down (excessive) ECS signalling.
CBD can inhibit the degradation (via inhibition of degrading enzymes) of one of the primary endocannabinoids, Anandamide. This serves to amplify ECS signalling, which may be clinically useful in cases of PTSD for example.

The point here is that CBD has the innate intelligence to recognise in what way specifically someone’s ECS may need support, and acts accordingly based on these two mechanisms.

This is similar to how classic adaptogens operate, to meet the needs of each individual to enable them to maintain balance, despite allostatic challenges.

This diagram very nicely illustrates how CBD strive to maintain equilibrium across many physiological processes.

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CBD & Blood Sugar

Although you might not expect it, your blood sugar has a pretty strong effect on your mood, and mental state in general. We all know that excessive amounts of sugar isn’t good, but that’s usually in the context of obesity and diabetes.

What about depression, anxiety and cognitive impairment? These aren’t talked about nearly as much as the former two conditions are in relation to sugar. Additionally, obesity, diabetes, depression and neurodegenerative diseases often occur together, what does that tell you?

High blood sugar isn’t great news. It causes a myriad of damaging responses in the brain, both short and long term which serve to disrupt emotional and psychological health.

Oxidative Damage

High blood sugar can encourage the formation of nasty mutants called advanced glycation end products (AGES). Accumulation of these in the body has been associated with depression (Van Dooren et al., 2017).

AGES interfere with the process of neurogenesis, which is crucial to the preservation of key brain areas (like the hippocampus), and subsequently mood and cognition. AGES have been shown to reduce neurogenesis in the hippocampus of animals (Wang et al., 2009).

AGES also contribute to neurotoxicity and neurodegeneration seen in Alzhiemers disease. They increase the formation of Amyloid Precursor Protein and Amyloid β that drive the accumulation of plaques amongst neurons that eventually disrupt memory and cognition (Ko et al., 2015). This process is dependent on Reactive Oxygen Species (ROS), which increase in response to AGES.

This is where CBD can pitch in; it is a potent antioxidant (more than vitamin C) with the ability to mop up excessive amounts of ROS. Although no studies have been conducted on Alzhiemers patients directly, animal studies demonstrate that CBD effectively reduces ROS formation (Booz et al., 2012).

CBD also encourages neurogenesis, as previously discussed. So this may also help offset some of the negative consequences of high blood sugar.

Inflammation

Inflammation is another product of spikes in blood sugar, and is perhaps one of the leading causes of destruction associated with high sugar and simple carbohydrate intake.

Systemic inflammation, that is inflammation that’s widespread in the body, can drive neuroinflammation, that is inflammation in the brain.

The effects of neuroinflammation aren’t ideal, both from a short and long term perspective. Inflammation messes with sleep, cognition, mood and brain fog, too. Long term, structural adaptations occur in the brain which kill mood and memory centres, and reduces the integrity of the blood brain barrier, which is meant to protect the brain.

CBD can actually tighten a leaky blood brain barrier, which is just one way it can protect the brain (Hind and O’Sullivan 2013)..

CBD is also neuroprotective against sugar, because it can reduce inflammatory cytokines, and other inflammatory messengers. It also tells immune cells, the microglia to behave. This has a sparing effect on the brain’s structure and function.

Blood Sugar Balance

Although there is no evidence to suggest CBD has an effect on blood sugar directly, it may have a role to play in the overall process.

High blood sugar is accompanied by high amounts of insulin necessary for shunting the sugar from the blood into cells, before it becomes inflammatory and damages various tissues, including the brain.

CBD has been shown to reduce the amount of insulin needed to maintain blood sugar (Romero-Zerbo et al., 2020), which could be a result of both improved function of the pancreas and a greater sensitivity to insulin itself.

High insulin is bad news, because it triggers metabolic inflammation (Kumar et al., 2018), which is a core driver of the metabolic syndrome and its complications.

What this means is that as well as protecting against the negative effects of high blood sugar, CBD may also minimise their occurrence in the first place by managing blood sugar through insulin.

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CBD & PTSD

PTSD is a type of anxiety disorder, which is associated with the recall of traumatic memories and an inability to resolve stress. Nightmares and disrupted sleep are also common problems with PTSD.

You may be thinking already, since CBD can help with sleep and anxiety, then it may be the perfect for PTSD.

The truth is though, there just aren’t many robust studies out yet to confirm what we already know about CBD.

Everything else seems to add up though. If we take a look at the ECS of people with PTSD, we see it’s underactive. Individuals exposed to the World Trade Centre attack who had developed PTSD, had a reduced level of the endocannabinoid 2-AG compared to those without PTSD (Bassir et al. 2019). Other people with PTSD and a history of trauma also had reduced levels of the other endocannabinoid, Anandamide (Bassir et al. 2019).

It’s no wonder they have trouble sleeping, nightmares, anxiety and find it difficult to escape stress.

These are all symptoms that come with a low functioning ECS. Adulthood trauma has been shown to reduce the activity of the ECS (Bassir et al. 2019). It makes sense that CBD could pitch in here, since it can increase the activity of the ECS, by increasing anandamide (Papagianni and Stevenson 2019).

Now, I’m not going to suggest that CBD can ‘cure’ PTSD. The fact of the matter is each individual with PTSD has experienced a traumatic emotional event that has manifested in a biochemical change in their ECS. That doesn’t mean that propping up the ECS with CBD will get rid of the problem, it potentially offers an attractive means to help manage it.

Truly treating PTSD may involve some sort of special psychotherapy that addresses the root cause of the issue – the traumatic memory and the emotions attached to it.

Studies in PTSD

In a case series (low quality evidence), CBD has been shown to reduce the PCL-5 score in PTSD patients by 28% (rating of PTSD symptom severity) after 8 weeks of use. Although only 11 people were monitored in this case series, this still provides encouraging data. What’s also interesting is that a third (36%) of the patients had improvements with their nightmares, and 72% reported improved sleep quality (Elms et al., 2019).

CBD is known to improve sleep quality and alter the time spent in deep and restorative phases of sleep (Babson et al., 2017), so it’s encouraging to see that data replicated here, in PTSD patients.

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CBD, The ECS & Depression

The ECS and Depression

Just like in anxiety, the ECS controls the regulation of a healthy mood. Therefore the way the ECS is working has a real impact on someone’s ability to regulate their mood.

What’s interesting to note is that depressed patients typically have low levels of the two main endocannabinoids 2-AG and Anandamide (Micale et al., 2015). Other literature also supports the hypothesis that low ECS function contributes to depression.

Seeking out to increase ECS activity (pharmacologically) has been shown to have antidepressant effects, which supports the notion that the ECS is generally underactive.

However, there’s also evidence that the ECS is hyperfunctional in cases of depression as well. For example, depression is often a co-morbidity of obesity and diabetes, and the ECS is overactive in these cases, which is a fairly consistent finding across the literature.

What’s complicated about the ECS is how some parts of it compensate for others that are imbalanced. In this way, it can be hard to tell if it is truly under or overactive.

This highlights the complexity of the ECS, but it also makes sense that both a hyper or hypo functional ECS could contribute to depression, as it is the ECS’ job to keep physiology within a ‘goldilocks zone’ that’s just right.

It may be that some mechanisms in depression are shared between low and high ECS activity, such as neuroinflammation, whereas others are exclusive.

CBD and Depression

Whilst there are no clinical trials looking at CBD in depression, some cross-sectional studies (surveys) report improved mood when using CBD.

Studies conducting surveys of CBD users reported positive outcomes. Of a sample of 1,631 people using CBD for mood disorders, 58% used it for depression, of which half were moderate cases. On average about half of the total sample found CBD made them feel much better in relation to complications of depression, such as irritability, mood swings, sadness and difficulty concentrating (projectcbd.org, 2020).

In another sample of 2,049 CBD users, amongst the top 3 uses reported for it was depression. 35% of the sample said that CBD treated their medical condition well by itself, closely followed by 29% who said that it worked moderately well by itself and 30% who said it worked well in combination with other medication (Coroon and Phillips 2018).

CBD is currently being studied clinically for bi-polar depression

A few key mechanisms whereby CBD could help depression:

Reduction of oxidative stress
Reducing neuroinflammation
Promoting neurogenesis
Restoring homeostasis in neurotransmitter signalling
Dampening HPA axis hyperactivity

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The ECS & Human Psychology

The ECS can be found within the human brain, as well as many other tissues and organs in the body.

As we’ve outlined above, the ECS is a communication system which governs the brain’s physiology which therefore affects psychology.

But it’s not just any communication system, it’s one that lies at the very core of how the brain works.

Get this; the CB1 receptor is the most densely populated receptor in the brain. That’s right, there are more CB1 receptors in the human brain than for any other brain chemical (Tantamonico et al. 2014). More than for serotonin, dopamine, adrenaline etc. This speaks volumes as to the importance of the ECS in controlling brain function, and psychology.

Although there is much more to psychology than the biochemistry that underlies the brain’s function, it still plays a large role, which affects thinking and behaviour as a result.

Extensive research has been done in animals demonstrating how behaviour can be altered as a result of manipulating the ECS, either with cannabinoids, synthetic cannabinoids or mice lacking specific ECS genes (known as knock out models).

It has been possible to alter behaviour in significant ways in these animals, due to the extensive role that the ECS plays in neurochemical signalling.

ECS signalling has been identified as an integral part of:

Brain Development, Maintenance & Repair
Mood, Thought & Consciousness
Stress
Reward & Addiction
Cognition, Learning and Memory
Sleep
Appetite & Disordered Eating

Tinkering with the ECS pharmacologically and genetically in animals has shown that it plays a role in both the function and structural architecture of the brain. This is significant because many psychological conditions are underpinned by either functional and/or structural aberrations in the brain.

These are some which are often dysregulated in various neurological and psychiatric conditions:

Synaptic Plasticity
Neuroinflammation
Oxidative Stress
Blood Brain Barrier Permeability
Neurodegeneration and neurogenesis
Lipid peroxidation
Excitotoxicity (Excitatory vs inhibitory)
Plaque formation and clearance

What’s also interesting is that early evidence is suggesting that there’s an association between psychiatric and neurological diseases, and the activity of the endocannabinoid system in humans.

The ECS has been found to be overactive in cases of:

Obesity (Toczek and Malinowska 2018)
Alcoholism (Toczek and Malinowska 2018)
Schizophrenia (Toczek and Malinowska 2018)

It’s also been found to be underactive in cases of:

Depression
PTSD (Russo 2016)
Migraine (Russo 2016)
Alzhiemers (Toczek and Malinowska 2018)

What this evidence highlights is that the ECS must operate within a ‘goldilocks zone’ of physiology that’s just right, in order to maintain psychological equilibrium.

What’s interesting to consider is what actually goes wrong in neurological and psychiatric conditions. They often share similarities in dysfunction, albeit to different degrees of severity.

For example, mood imbalances, irritability, deficits in memory and sleep issues can be seen in both depression, Alzhiemers and PTSD. The research with the ECS is suggesting that these may share a common thread in so far as their core pathology is concerned.

Particularly considering that the ECS is a core regulator of many of the underlying mechanisms that can go awry in the brain that produce the psychological disturbances that we can observe in the behaviour of people with these conditions.

What I also found to be interesting is that things that can disrupt the way the ECS works are also well established risk factors for neuropsychiatric and neurological conditions:

Poor diet
Sedentary lifestyle
Emotional trauma
Stress
Infection
Sleep deprivation / circadian disruption

So, if we consider how significant the interaction between the ECS and healthy psychology is, then supporting or manipulating its function stands to play a powerful role in correcting disturbed psychology.

Given the fundamental interaction CBD has with the ECS, there is a strong case to be made for CBD to support core components of psychological function in the brain.

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CBD & Autism Spectrum Disorder

Although its not psychoactive, CBD has psychopharmacological effects which have been investigated in anxiety, schizophrenia and more recently depression.

Increasing attention is now being directed at the application of CBD for other conditions which have neuropsychiatric co-morbidities, such as Autism Spectrum Disorder (ASD).

Amongst the deficits in social communication, behaviour abnormalities and intellectual disabilities, sleep, attention, mood and epilepsy may also be present.

Whats interesting is that CBD may be of interest to both the core symptoms and the co-morbidities of ASD, because of its interaction with the endocannabinoid system (ECS).

The ECS and ASD

The ECS central role is to maintain balanced brain activity in a way that preserves healthy emotional responses, behavioural reactivity to context and social interaction. Its functioning is implicated in many of the symptoms seen in ASD, which are of neurological origin.

Healthy responses depend on this endogenous systems flexibility, and inherent activity. The ECS can be subject to imbalances, where environmental and genetic components interact in a negative synergy to disturb its very equilibrium.

Whats integrating to note is indeed that seizures, anxiety, cognitive impairments, and sleep issues are prevalent with ASD. These co-morbidities themselves have been associated with imbalances in the ECS. Whats now also interesting is that disturbed ECS function has also been noted in ASD.

It was recently found that levels of the endocannabinoid anandamide were lower in the plasma in ASD patents than in healthy controls (1). Given the central role of the ECS in modulating neurological and neuropsychiatric functions, one could argue that its dysregulation may underpin the core and co-morbid symptoms of ASD.

The role of anandamide is to maintain homeostatic neuronal communication in the brain, as well as neuroimmune modulation via CB1 and CB2 receptors. If indeed it is under expressed in ASD, then this may be part of the mechanism which leads to widespread disruption of the communication network which maintains neurological function.

CBD and ASD

One of the principal mechanisms of CBD is to enhance the activity of the ECS. CBD inhibits the enzyme FAAH that degrades anandamide, preserving its concentrations in synapses. This mechanism has been implicated in the anti-anxiety, anti-depressant, anti-insomnia, antipsychotic and anti-inflammatory properties of CBD. In addition, CBD has shown clinical efficacy in improving all of these, except depression where it has not yet been studied in humans.

Although CBD is a pleiotropic molecule with many different targets pharmacologically, its effect on anandamide and the ECS is central and significant.

This is perhaps why emerging studies in ASD specifically have found widespread effects with regards to core symptoms and co-morbidities.

A study looked at whole plant CBD (20:1 CBD:THC) in 53 children for an average of 66 days. They found that self injury and rage attacks improved in 67% of children, whereas it worsened them in 8%. Hyperactivity symptoms improved in 68%, did not change in 29% and worsened in 3%. Sleep problems improved in 71%, and anxiety improved in 47% and worsened in 23% (2).

Given the worsening of some children’s symptoms, it is possible CBD may overcompensate for a ‘sweet spot’ in endocannabinoid system function. Perhaps using different doses and/or cannabinoid ratios would help the children that saw worsening symptoms improve.

Another study looked at cannabinoid preparations at ratios ranging from 20:1 to 6:1 (CBD:THC) in 60 children with ASD retrospectively. Considerable improvement in behaviour problems was reported in 61% of the children, as well as 47% for anxiety. Scores for disruptive behaviour improved by 29 and 33% from baseline to end of the study (2).

Further studies are looking at the impact of cannabinoid medicines in ASD, which have yet to be completed (3), (4).

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CBD & Pregnancy (Why its NOT a good idea)

Many women report using CBD oil during pregnancy to reduce severe pregnancy-related nausea and vomiting (1).

Some symptoms of pregnancy, such as nausea and anxiety, may be lessened with CBD.

However, its unknown whether using CBD to reduce these symptoms comes at a cost to the child’s development.

Overall, the FDA suggests against the use of CBD in pregnancy due to the similarity of CBD.

Due to the lack of research its NOT recommended to use CBD during pregnancy or breastfeeding.

Why CBD is not safe during Pregnancy….

Almost all of the research with cannabinoids has focused on either whole pant cannabis or THC. Therefore, precautions against CBD are justified via studies on cannabis in general.

There are no studies in which CBD oil has been used in humans with regards to pregnancy. However, there are numerous studies demonstrating cannabis-related adverse fetal effects.

Cannabinoids have been shown to cross the blood-brain barrier and the placenta. They can also affect brain development, by influencing the rate of neuronal growth. This is how cannabis exposure is associated with neurological impairment, hyperactivity, poor cognitive function, and changes in dopamine receptors in children (2).

Other human studies have highlighted that cannabis usage during pregnancy leads to adverse outcomes such as anencephaly, hyperactivity, and anxiety in children.

Studies that actually look at CBD are limited to specific cells, rat and mice offspring.

A study in mice recently discovered that a single exposure to both THC and CBD (given at equivalent of week 3/4 of pregnancy in humans), caused clear disruptions in embryonic brain and facial developments in the mice (4). The effects were similar to those seen in alcohol exposure in pregnancy.

The study author comments : “We know that there is no safe period to drink alcohol during a pregnancy, and I think this research shows the same is likely true of marijuana use”.

However, this study still doesn’t tell us about CBD taken alone. But given its ability to modulate the ECS, caution is advised.

One study investigated the effect of CBD on gastroschisis (Gastroschisis is a congenital malformation of the wall of the abdomen) in rat fetuses, when administered to the mothers. The rate of gastroschisis was assessed by measuring markers of inflammation in the baby rats. CBD use was associated with lower levels of inflammation, suggesting a beneficial effect for gastroschisis.

What was more significant though, was the evidence that CBD use in a mother can be transmitted across the placenta and have an effect on the foetus. However, this study did not assess the effects of brain development, so no beneficial effect of CBD can be speculated (5).

Consensus from the (limited) Research

The FDA has stated that there are no comprehensive research studies available that explore the effects of CBD on the developing fetus, pregnant mother, or breastfed baby.

There is still a need for high-quality research studies to fully elucidate the risks and benefits of CBD usage by pregnant patients.

Overall, the FDA suggests against the use of CBD in pregnancy due to the similarity of CBD to THC (6).

It is possible that any modulation of the endocannabinoid system during pregnancy, whether it be by THC or CBD may be a risk to the foetus, since the two compounds are very similar.

Are there any risks of using CBD oil before pregnancy?

The cannabinoid system has been shown to play a significant role in all steps of pregnancy, from fertilization to implantation and parturition. However, little is known about the interaction of CBD with the ECS when it comes to conceiving.

All we have to go by here is extrapolation of studies simply looking at mechanisms that are correlated with fertility. For example, high levels of the endocannabinoid anandamide are found at ovulation, and have been associated with a successful pregnancy (7).

On the flip side, low levels of anandamide may be associated with problems getting pregnant by interfering with ovulation. CBD increases levels of anandamide by inhibiting its breakdown, so if we were to speculate there is a chance there may be an effect on fertility – but this is simply based on a mechanism, and is not backed up by any clinical evidence.

Plus the effect of CBD on fertility is likely to be affected by the activity of that persons own ECS.

Fertility is also affected by stress. Hormones necessary for a successful pregnancy can be thrown off by stress, since they share the same hormonal highway of communication with stress hormones. CBD can soothe this hormonal highway, and reduce levels of stress hormones (8).

So again, theoretically CBD may help support conception via reducing stress.

There is no evidence for or against the safe use of CBD in conceiving, and anyone using it does so at their own risk.

There’s evidence that THC can alter the way genes are expressed in parents before they have even conceived (9). Epigenetic (changes to how the genome is ‘read’) changes have been noted in offspring where the parents used cannabinoids before conceiving.

There’s evidence that also comes from fathers either using alcohol or cannabis, whose epigenetic ‘blueprints’ were passed through the sperm, which affected the offspring (10).

Why CBD should not be used whilst breastfeeding…..

Endocannabinoids (the bodies naturally produced cannabinoids) are actually crucial to the development of an infant. They are passed down from mother to infant through breastmilk.

Since CBD can alter the bodies endocannabinoid system, and levels of endocannabinoids, there is a risk that CBD may somehow alter the developmental instructions passed down through breast milk.

Cannabinoids themselves can also be detected in breast milk, so even after birth CBD taken by mothers may still pose a risk to influencing an infants development. Again the big questions here are whether they will alter neurological or immunological development (11).

One of the two main endocannabinoids, 2-AG plays an important role in the suckling response in an infants brain so that it will feed (13). In the case of 2-AG deficiency a child may not consume enough food to sustain itself.

Its a delicate balance, and we don’t yet know how CBD affects this balance.

Once we are able to pinpoint the activity of an individuals ECS, it may be that either CBD to THC could be given at certain time-points, to delicately compensate for an individuals ECS imbalance.

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CBD & Menopause

The menopause can be a challenging and confusing time, as the body goes through a series of chemical changes that come with emotional, physical and mental challenges. Amongst these changes, theres one that really stands out, and that is the drop in Estrogen levels.

As we will cover today, the ECS has an interesting part to play in regulating hormonal balance and the levels of Estrogen during menopause.

Studies show that fertility, reproduction, sexual appetite and menstrual cycles are all closely controlled by the ECS (1).

When taking a closer look, research has shown that the ECS actually acts as a gatekeeper controlling the secretion, sensitivity and degradation of hormones and hormonal responses including estrogen and progesterone (2).

Whats interesting is the link between the ECS and hormonal balance during menopause. If we take a close look, we can see that many of the symptoms of menopause are actually regulated by the ECS.

The ECS controls (4), (5), (6):

Bone modelling (Osteoperosis)
Mood swings (anxiety)
Aches and pains (Inflammation)
Thermoregulation (Hot Flashes)
Sleep (Insomnia)
Metabolism (body weight, energy)

You can actually find the ECS and cannabinoid receptors densely concentrated in areas that regulate the secretion of sex hormones like estrogen. The hypothalamic pituitary ovarian axis (HPO) is where the magic happens, and it all starts in the hypothalamus.

The easy way to think of the ECS is as a gatekeeper that controls the flow of hormones in an effort to maintain continual equilibrium. Depending on what time of the month it is, the ECS will either open the flood gates on hormonal release, or rain it in. Its this cyclical process that helps keep hormones on the clock.

A perfect example is by what happens before ovulation, when levels of Anandamide are low, but rapidly increase during and after ovulation, which ends up pushing the alterations in levels of Estrogen and progesterone (3).

Its actually levels of Anandamide that are acting on the HPO axis to control the release of the above sex hormones, keeping them in equilibrium.

However, research has shown that when the menopause hits the ECS can become imbalanced, and lets slip as a gatekeeper of homeostasis allowing hormonal imbalances to creep in. Studies have shown that levels of Anandamide and 2-AG fluctuate around menopause, which cause a change in regular cycles (7).

As women make their way through menopause, the ECS is working double-time to find a new sense of balance. However, as it tries to do this there can be some nasty symptoms to deal with.

But, as we will soon see, there is plenty that can be done to help support the ECS and its balance.

Progesterone

Levels of progesterone can have an influence on levels of inflammation, mood and sleep when imbalances crop up. This interaction is because progesterone actually influences levels of Anandamide, which is a mood boosting, pro-sleep and anti-inflammatory endocannabinoid.

Progesterone does this by communicating to the ECS in bodily areas such as the ovaries and hypothalamus.

One study found that progesterone levels can be altered when CB1 receptors are activated or blocked in the hypothalamus, and the result is a change in sexual appetite in women (3).

This is exciting, because it means that one may be able to use cannabinoid like CBD to modulate the ECS in order to improve sexual appetite, theoretically.

Estrogen

Like progesterone, estrogen can also tap into the way the ECS works. It actually forms a communication loop within the ECS that revs up or dampens down its activity.

Estrogen can actually change the levels of CB1 receptors either up or down, which is different based on which brain area it is working on. Another neat interaction is that estrogen can prevent the breakdown of the bodies natural bliss chemical Anandamide (3).

So, essentially this indicates that when the ECS is out of balance, so is estrogen. So it very well might be that its actually the ECS thats responsible for a lot of the menopause symptoms though to be related to low levels of estrogen.

Get this, the perks of estrogen as an anti-inflammatory are partly because of its influence of Anandamide levels, which reduce the activity on T cells (3). Its also a similar case for the mood boosting effects of estrogen, which may actually be a result of increased anandamide levels, as well as its effect on CB1 receptor levels.

So when estrogen levels start to fall, so might some of the effects of Anandamide (anti-inflammatory, mood boosting and sleep enhancing).

This is a which came first situation, as levels of both hormones and endocannabinoids are dependent on each other. But whats evident is there are some close interactions.

Take 2-AG for example, its an endocannabinoid that has been shown to dramatically increase as women journey through menopause (7). Excessive levels of 2-AG are actually seen in metabolic syndrome, diabetes and obesity, which is the underlying culprit in metabolic dysfunction. This could be related to the weight increase, and blood glucose and cholesterol increases in menopause.

Anandamide also controls the equilibrium between bone synthesis and breakdown, via CB1 receptors found on bone forming and bone degrading cells (8). Hence, changes in estrogen and therefore anandamide may be involved in bone loss during menopause.

Another example is the interaction between estrogen, mood and sleep. Anandamide controls the activity of GABA neurones, which acts to calm brain, helping reduce nervousness and support sleep. So when estrogen declines, so does anandamide which loses then struggles to promote GABA responses.

CBD to The Rescue

CBD is effectively a means to buffer against ECS imbalances, by restoring the communication loops between hormones and the ECS and hormonal equilibrium.

In theory based on mechanistic research, CBD may help bolster estrogen and progesterone function by intervening downstream, at the levels of the ECS. There has been no research to my knowledge that has shown CBD to increase the levels of these hormones.

However, there is a good case to argue that many of the beneficial effects of CBD are due to increased levels of Anandamide (9), (10):

Immune support
Bone support
Pain relief
Anti-inflammatory
Libido?
Balanced mood
Sleep support
Bone support

Many of the benefits of CBD are through its ability to regulate the ECS. There’s a good case to argue that since many of the complications of menopause are similar to those of ECS imbalance, that some sort of ECS disequilibrium is involved in menopause.

CBD is a great candidate because it acts as an adaptogen, supporting balance across the ECS in ways that meet individual needs.

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Can CBD help with Weight Loss?

With a global pandemic like COVID-19 still very much at large, there’s never been a better time to lose weight than right now.

Since carrying extra weight is a risk factor for all sorts of other diseases, naturally it also exposes many people to a greater risk of COVID-19 infections and complications.

The PM, Boris Johnson recently had a run in with COVID-19, mentioning that had his weight been in better order, he may not have had to fight quite as hard to come through the other side.

So now, supported by the UK government, Boris is encouraging people who are overweight and obese to double down on their exercise efforts, as well as fostering healthier food climate legislation.

If I’m being real, I don’t have the greatest confidence in state led programmes when it comes to weight and health. Obesity is a systemic issue, thats best addressed at an individual level.

Obviously working on the relationship with food is a key element of sustainable weight loss. But until more people have access to individualised support, using herbs and supplements to support a healthy body weight is good low hanging fruit to pick.

Although there’s very little research examining the direct relationship between CBD and body weight, there’s some evidence to suggest that it may be useful.

Based on how CBD affects bodily processes that influence body weight, we can start to lay the groundwork for studies examining a direct effect.

Appetite Management

Leptin, Ghrelin and insulin all work on neurones in the hypothalamus to control appetite, and there’s some crosstalk between these hormones and the ECS.

In cases of obesity, the ECS can be overactive in the hypothalamus driving excessive firing of pro-hunger neurones.

Whats neat here is that CBD can actually block the pro-appetite signals from an overactive ECS.

But, research in animals tells us that CBD will only reduce an excessive appetite, and not reduce an already healthy appetite (1), (2).

This is testament to CBD working to restore equilibrium within body processes, and not counter compensating for opposite imbalances.

So at best, It seems that CBD may prevent excessive eating to prevent further weight gain, not under eating to achieve weight loss.

Body Weight

Similarly, CBD does not result in weight loss in animal studies. Animals are usually fed a obesogenic diet which encourages weight gain.

Whats been found with CBD is that it actually results in less weight gain when given with an obesogenic diet. So animals that received CBD gained less weight than animals given the same diet that didn’t take CBD (3).

However, this is not a consistent finding (4).

In a human study of psychosis, CBD did not result in either weight loss or weight gain (5). Antipsychotic medications like amisulpride usually result in significant weight gain, so in this scenario CBD would be an obvious choice because it does not foster weight gain.

The pattern that is starting to emerge here is that CBD is not a weight loss solution (for most people). Unless someone is seriously overweight or overeating, then CBD is unlikely to result in significant changes to body weight.

CBD is essentially trying to restore the closest thing to equilibrium it can. So essentially the best thing it may do is slow the process of gaining more weight.

This is due to CBD’s mechanism of action, in only blocking high levels of ECS activation.

Looking for cannabinoid extracts high in other cannabinoids (as well as CBD) like THCV may actually promote weight loss, because THCV actively opposes the pro-weight gain effects of the ECS.

Summary

CBD may help with the more serious cases of obesity, but for most people it’s looking like its best use case is an insurance policy against more weight gain.

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CBD and Leaky Gut

As practitioners, you know how much of a role the gut plays in setting someone up for chronic disease.

It all starts in the gut, and finding ways to support good GI function is essential for helping someone recover from chronic health issues.

Leaky gut, or intestinal permeability is one of the leading reasons behind chronic health issues, which paves the way for downstream complications like chronic inflammation to take hold.

The ECS and the Gut

There are cannabinoid receptors found in abundance throughout the GI tract, from the stomach through the intestines. They endogenously control many aspects of digestion and immunity within the gut.

Using exogenous cannabinoids is a way of modulating the digestive and immune processes, especially when they are imbalanced.

Many cases of IBS, IBD and other gut disorders are related to the leakiness of the gut. They are also associated with a deficiency of endocannabinoids, which usually maintain the permeability of the gut, and healthy levels of inflammation within it.

Dysbiosis within the gut also disrupts microbial regulation of barrier function, and also disturbs the ECS and its ability to maintain a healthy barrier.

Barrier function is controlled by CB1 receptors, and there is crosstalk between microbes and the ECS which bridges the gap between gut infections, imbalances and gut leakiness.

Therefore, solutions lie in being able to directly modulate CB1, and also alter the composition of the microbiome to indirectly modulate CB1 and permeability.

Barrier function is also influenced by levels of inflammation in the gut. When the ECS loses its grip on immune cells within the gut, barrier permeability increases.

Image Source

Cannabis reduces intestinal permeability

How Can CBD Help?

CBD help the gut on many levels.

First off, it can directly control barrier permeability via the CB1 receptor and modulation of tight junction proteins (Zonulin).

CBD has been found to decrease intestinal permeability.

This has been shown in studies ranging from in vitro all the way through to human studies using the lactulose manitol test.

This is basically restoration of typical gut barrier function even under pathological conditions, which may help arrest the progression of certain conditions.

Secondly, CBD is a powerful antimicrobial, which may assist in the rebalancing of a dysbiotic microbial community within the gut. Healthy crosstalk may be encouraged between microbial communities and the ECS in the gut with the help of CBD, reducing permeability.

Lastly, CBD is immunoregulatory. It helps organise immune responses in much the same way an NFL team organises its defensive plays vs its offensive plays.

Its one of its major protective roles it plays in protecting the gut from physical damage, as well as the damage microbial toxins cause as a result of inflammation induced permeability.

Restoring inflammatory homeostasis is essential for good gut function, and CBD can help do this via CB1 and CB2 receptors on immune cells like mast cells and macrophages.

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CBD and Alcohol

CBD has become a popular choice in bars, with many people opting for a drop or two of oil to their drinks. But what does adding CBD to a drink really do?

Whilst there’s little research exploring the effects of CBD with alcohol. One could expect the anti-anxiety and calming effects of alcohol to be complimented by CBD, although studies are needed to clarify this.

It’s also tempting to speculate that CBD may also reduce some of the negative side effects of alcohol, such as the cognitive impairment. Sadly, the few existing studies found no effect of CBD on cognitive measures when taken with alcohol (1). It could be that 200mg of CBD is too low a dose to have any meaningful effect on cognition.

However, CBD has been found to reduce blood alcohol levels at this dose; humans taking 200mg CBD with alcohol had lower blood alcohol levels than those receiving just alcohol (2).

Perhaps higher doses could further reduce blood levels of alcohol to meaningfully reduce brain and motor function impairment seen with alcohol consumption.

Beyond the buzz, there’s a great case to be made for CBD use long term, which may offset some of the negative effects of drinking (excess) alcohol.

May help reduce inflammation and cellular damage after excessive alcohol consumption (3). This is protective for the brain and the liver.
May help prevent against development of alcohol induced fatty liver (4).

There are strong implications that CBD may be protective against steatosis of the liver and brain damage due to excessive alcohol consumption.

CBD, reduces lipid accumulation, inflammation and oxidative stress in the liver. It also reduces alcohol associated brain damage by preventing neuronal loss via antioxidant and immune neuroprotection (5).

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CBD and Heart Health

As a universal regulator of the body and its systems, it probably comes as no surprise that CBD may help support a health heart.

It’s main action, which could be beneficial for the prevention of heart attacks, is calming the nervous systems (1). Subsequently, this may dampen the effects that stress has on things like blood pressure and heart rate. We’re talking about work / life related stressors of course – those things we’d rather be non-reactive to.

Stress is the biggest killer, and it manifests itself in the heart a lot of the time – so reducing the effects of stress within the nervous system may help the old ticker.

Secondly, cannabinoids like CBD have been shown to alter the way the liver packages and makes lipids like cholesterol. There’s some exciting research which suggests CBD can improve the balance of HDL:LDL cholesterol as well as lowering triglycerides in the blood (2). We haven’t seen these results in humans yet, so we are still speculating a little.

However, if confirmed, this could be yet another benefit of CBD for the cardiovascular system, and heart disease. Reducing the amount fo LDL in the blood may reduce the chances of forming plaques and arterial blockages. Also, CBD may help prevent the oxidisation of LDL, which is part of the process by which plaques form (3). As a potent antioxidant, CBD could be a star player in reducing oxidative damage that surrounds many aspects of heart disease – not just plaque formation, but also damage to myocardial tissues and arterial walls.

CBD has also been found to reduce blood pressure in a small clinical trial of around 9 people (4). Through its effects on vessel elasticity, CBD may help maintain healthy and flexible arterial walls, as well as reducing the burden on the heart to pump blood through rigid blood vessels.

CBD is also broadly anti-inflammatory, and is largely immunosuppressive – these are excellent qualities when trying the preserve the structural and functional aspects of cardiovascular function. When immune cells are overactive, this can lead to cardiomyocyte damage and subsequent heart disease/failure. The immunoregulatory roles that CBD plays are hugely important for heart health in this regard (5).

As you can see, there are quite a few targets by which CBD operates. Whilst many different interventions are applied to these individual mechanisms (statins, beta blockers), CBD represents a single, yet very potent ploy-mechanistic medicine which could be of great therapeutic benefit in heart disease.

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Dealing with CBD Stigma

To handle objections from clients, simply state these myths and facts about CBD.

Facts

1) CBD is not a cure

Whilst CBD may lend a helping hand in supporting health, its another thing to suggest it can be a cure all.

To say that CBD cures anything is scientifically inaccurate, because there’s little evidence in human studies using CBD long term for specific diseases to suggest otherwise.

There’s also root causes that are driving disease in the first place, and although CBD can help a great deal in managing them, it often doesn’t address the root cause of why the body becomes imbalanced in the first place.

These kinds of claims can be misleading, because it also implies that just because one thing works for me, it’ll work for you too.

2) CBD won’t get you high, but can make you feel good

Although CBD isn’t fully non-psychoactive, it still wont get you high. Its all to do with the mechanism of action of CBD.

CBD doesn’t activate the CB1 receptor, like THC does. This means that CBD cannot produce a high like THC can. The activation of CB1 is the only established mechanism that tells the brain to become fully psychoactive.

CBD can make people feel good though. Thats because CBD boosts a natural feel good cannabinoid, anandamide. Anandamide activates CB1, but to a much lesser degree than THC. This alternative mechanism is what is thought to provide a sense of wellbeing from CBD, without the high.

3) CBD can produce side effects

It’s not all rainbows and lollipops, like a lot of people may make out. CBD has been known to produce some side effects, albeit relatively mild ones.

The side effects of CBD are considered pretty good compared to that of some conventional drugs (*). So for a few conditions, some people may find the experience with CBD preferable to conventional approaches.

4) CBD from hemp is legal

Most strains of hemp naturally contain no more than 0.2% THC. In the UK and EU, so long as CBD extracts from hemp don’t surpass this level of THC, it is legal.

Thats why you’d rarely see a cannabis derived CBD extract in the UK or EU, because it naturally contains more than 0.2% THC and is illegal.

5) It’s been used to support health for centuries

CBD is one of the key constituents of hemp and cannabis plants. They’ve been around for thousands of years, and have documented use across India, Egypt, Europe, China and Japan (Russo, 2007).

Traditionally, cannabis has been used for many of the ailments people use CBD for today; anxiety, insomnia, pain, menstrual cramps being just a few.

6) CBD is (sort of) classified as a medicine

Most CBD products you’d find online and in stores have been classed as food supplements in the UK. But, did you know that the Medicines and Healthcare products Regulatory Agency (MHRA) actually voiced another opinion on CBD in 2016.

They suggested it is a medicine, but only if it is marketed for medical purposes. AKA as a pharmaceutical preparation, like Epidiolex, which is a 99% pure CBD extract.

As you can probably tell its still a grey area as to what CBD actually is, but for most people in the UK, it remains a food supplement.

7) CBD can come from hemp and marijuana

CBD is not exclusively found in hemp. Its 1 of over 100 similar compounds called cannabinoids that are found in cannabis plants.

Although they both contain CBD, marijuana tends to be a richer source than hemp. The amount of hemp relative to cannabis needed to extract CBD tends to be greater, making cannabis the more economical (but not legal) option.

Myths

1) There’s no evidence that CBD supports health.

Although there’s not an awful lot of research out there on CBD, a few pre-clinical studies suggest that it may be helpful in the following cases:

Anxiety (Zuardi et al., 1993), (Bergamaschi et al., 2011), (Linares et al., 2019).
Pain (Whiting et al., 2015).
Insomnia (Shannon, 2019), (CARLINI and CUNHA, 1981).
Epilepsy (Szaflarski et al., 2018), (Cunha et al., 1980)
Psychosis (Zuardi et al., 2009)

2) CBD works for everyone

It depends on your state of health, and what you’re using it for.

Some people use CBD to manage symptoms of disease, whereas others use it to bring a little bit of happiness and ease back into their day. It may not necessarily have any noticeable effects for other people, who are healthy and happy anyway.

This depends on how much help someones endocannabinoid system needs from CBD.

CBD works to meet the needs of everyones ECS differently. Plants that do this are called adaptogens – they adapt to suit peoples needs differently.

In cases, some peoples endocannabinoid systems are doing just fine without CBD.

3) CBD is non-psycoactive

Although CBD doesn’t get you high, like THC; a lot of people say it boosts their mood and lessens anxiety. If CBD has these effects in the brain, then there’s clearly some sort of psychoactive element to it.

Interestingly, CBD may boost feelings of happiness via interaction with the bodies serotonin system. Serotonin is a chemical which affects happiness, mood and lessens anxiety.

4) All CBD is created equal

CBD is technically a singe molecule, which is universally the same. However, the packaging CBD comes in can be subject to variation.

In nature, CBD does not exist as a single molecule, but is found within plants with over a hundred other cannabinoids. When extracted, you not only get CBD, but all the other cannabinoids. These are called full spectrum extracts (which most people just call CBD extracts).

In contrast, CBD can be isolated from its original packaging, to exist as a single molecule. You guessed it; this is what CBD isolate is.

The benefits one may experience with CBD isolate is questionable compared to the complete packaging of a full spectrum CBD extract.

5) CBD is addictive

The world health organisation recently conducted a comprehensive review on CBD, which also included its potential for addiction.

They concluded that:

“In humans, CBD exhibits no effects indicative of any abuse or dependence potential.”

6) A little is enough

This again ties into everyones unique needs for CBD, and it depends on what you are using it for.

There’s a common phrase in the CBD industry which you may have heard….thats start low and go slow.

Whilst thats a useful and safe means of introducing CBD, a lot of folks may find that low doses just don’t cut it anymore. Especially someone with intense pain or severe anxiety, who is far more likely to require higher doses than usual.

7) CBD oil is the same as hemp oil

Although CBD does come from hemp, there is a key difference between hemp oil and CBD oil.

Hemp oil is made exclusively from the seeds of hemp plants. Whilst these contain beneficial nutrients like omega oils and fats, the seeds contain almost no CBD.

The leaves, stalks and flowers of hemp however, do contain CBD. Thats what you’d refer to as a CBD oil.

References

Bergamaschi, M. M. et al. (2011) ‘Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients’, Neuropsychopharmacology, 36(6), pp. 1219–1226. doi: 10.1038/npp.2011.6.

CARLINI, E. A. and CUNHA, J. M. (1981) ‘Hypnotic and Antiepileptic Effects of Cannabidiol’, The Journal of Clinical Pharmacology, 21(S1), p. 417S–427S. doi: 10.1002/j.1552-4604.1981.tb02622.x.

Cunha, J. M. et al. (1980) ‘Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients’, Pharmacology, 21(3), pp. 175–185. doi: 10.1159/000137430.

Linares, I. M. et al. (2019) ‘Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test’, Brazilian Journal of Psychiatry, 41(1), pp. 9–14. doi: 10.1590/1516-4446-2017-0015.

Russo, E. B. (2007) ‘History of Cannabis and Its Preparations in Saga, Science, and Sobriquet’, Chemistry & Biodiversity, 4(8), pp. 1614–1648. doi: 10.1002/cbdv.200790144.

Shannon, S. (2019) ‘Cannabidiol in Anxiety and Sleep: A Large Case Series’, The Permanente Journal. doi: 10.7812/TPP/18-041.

Szaflarski, J. P. et al. (2018) ‘Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study’, Epilepsy & Behavior, 87, pp. 131–136. doi: 10.1016/j.yebeh.2018.07.020.

Whiting, P. F. et al. (2015) ‘Cannabinoids for Medical Use’, JAMA, 313(24), p. 2456. doi: 10.1001/jama.2015.6358.

Zuardi, A. et al. (2009) ‘Cannabidiol for the treatment of psychosis in Parkinson’s disease’, Journal of Psychopharmacology, 23(8), pp. 979–983. doi: 10.1177/0269881108096519.

Zuardi, A. W. et al. (1993) ‘Effects of ipsapirone and cannabidiol on human experimental anxiety’, Journal of Psychopharmacology, 7(1_suppl), pp. 82–88. doi: 10.1177/026988119300700112.

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CBD & Crohn’s

There’s some interesting research with cannabinoids when it comes to Crohn’s disease. As a form of inflammatory bowel disease and autoimmune condition, Crohn’s requires powerful modulation of the immune system to spare further destruction of intestinal tissues and disruption of gut function.

Cannabinoids, including CBD have powerful immunomodulatory effects. This makes them suitable candidates for suppressing excessive immune system activity, and its deleterious downstream consequences.

Cannabinoids inhibit cytokine production in much the same way as traditional immunosuppressive drugs. TNF-α is an inflammatory cytokine which is released by overactive T cells, singling for the destruction of the intestinal mucosa. Anti-TNF therapy is one of the first line treatments for Crohn’s (1).

However, other cytokines such as IL-17 also play a role in the disease, so a broader immunoregulatory strategy is needed. There is excessive activity of both Th1 and Th17 immune cells, which overproduce their respective inflammatory messengers. Also in Crohn’s, Treg cells are lacking in their ability to suppress autoimmunity and excessive Th1, Th2 and Th17 responses.

The microenvironment in the gut is drastically altered from unrelenting inflammation, which causes structural damage to the intestinal lining, and disruption of gut motility towards diarrhoea. This also leads to the knock on effects on mental state, such as depression and anxiety, weight loss and malnutrition.

The inflammatory environment in the gut is accompanied by disruptions in gut microbiome, as well as gut permeability which may underlie and perpetuate the condition.

Attention has been focused on the endocannabinoid system as a central regulator of (gut) homeostasis. Most components of the gastrointestinal tract, as well as immune cells express cannabinoid receptors that are receptive to the bodies endogenous cannabinoids as well as phytocannabinoids.

Endocannabinoids are key regulators of GI inflammation, motility, permeability and visceral sensitivity, implicating them in a wide array of factors in Crohn’s. Perturbations in their levels has also been identified as a factor in the development of Crohn’s (2).

It is entirely possible that disruption of gut homeostasis as a whole is underpinned by imbalances in the endocannabinoid system.

CBD has attracted attention as an adaptogenic and pleiotropic compound capable of normalising imbalances in endocannabinoid system function. By acting on the endocannabinoid system indirectly, it has a powerful ability to normalise (gut) homeostasis on many different levels.

Mechanisms

CBD is a powerful anti-inflammatory and has been shown to reduce the levels of cytokines which are problematic in Crohn’s. TNF-α, Il-17 and other cytokines have been shown to decrease in response to CBD treatment (*).

CBD is an immunomodulator, and has been shown to increase the number of Treg cells helping to restore their immunosuppressive grip on Th cell responses (3).

In line with this, CBD has been shown to suppress Th cell activity (4).

CBD also reduces hyper motility (diarrhoea) due to its effects on the endocannabinoid system. CB1 receptors are found throughout the nervous system in the GI tract, which regulate motility. CBD increases Anandamide, which activates CB1 to slow motility (5).

CBD also reduces hyper motility by reducing inflammation, via CB2 activation on immune cells within the GI tract (6).

CBD reduces intestinal permeability (gut leakiness) and normalises Treg cell function (7). Gut leakiness is another factor driving immune cell activation, inflammation and fatigue in Crohn’s.

In terms of mechanistic data, there is a strong case to be made for CBD for Crohn’s. However, the clinical data is still as yet uncertain.

CBD & IBD

A randomised controlled trial failed to show any significant improvements in Crohn’s disease activity index relative to placebo with 20mg CBD / day after 8 weeks. There was however a modest improvement in CDAI, indicating a trend towards clinical improvement. There were also no differences in inflammatory markers. This study only featured 19 participants, and the dose is significantly lower than that of other studies (8).

However, this study only used 99% pure CBD at an extremely low dose (usually effective doses of 99% pure CBD are 200-600mg).

In ulcerative colitis, a CBD-rich whole pant extract resulted in the improvement of quality of life scores, which is encouraging for IBD as a whole (9).

Cannabis & IDB

A number of epidemiological studies report that a significant portion of patients with IBD are cannabis users, helping them to manage symptoms such as abdominal pain relief, diarrhea relief, weight gain and improved appetite (10).

Patients also believed that cannabis improved their general well-being, stress level, and sense of control over IBD. Many of them also preferred cannabis to corticosteroids, reporting less side effects.

A prospective placebo controlled study found that 10/11 patients using cannabis had an improvement in CDAI compared with 1/10 in placebo group. Complete remission was achieved by 5/11 cannabis patients. 24% THC and 0.5% CBD inhaled cannabis was used (11).

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CBD & ADHD

ADHD is often a co-morbid condition that crops up alongside depression, anxiety and other neurological conditions such as Autism. Inattention, hyperactivity and impulsiveness are the key characteristics of the condition.

Brain imaging studies show that neural networks behave differently in patients with ADHD, particularly in the frontal cortex and basal ganglia. Underlying neural networks are the neurotransmitters that deliver messages to control brain actives which modulate attention and behaviour.

Dopamine is one of the leading neurotransmitters involved in modulating ADHD symptoms, and is targeted by ADHD drugs as a main of intervention.

Beneath the modulation of dopamine circuitry is the endocannabinoid system, which acts as a gatekeeper controlling the flow of neurotransmitters via GABA and Glutamine.

CBD can ‘plug’ into the endocannabinoid system to influence its modulation of neurotransmitter flow, and therefore the behaviour mediated by neurotransmitter activity at any given time.

Studies in mice show that in addition to irregularities in dopamine signalling, the endocnanabinoid system is dramatically impaired. Specifically this relates to the control of GABA activity by the ECS in the striatum, where there is a deficit which may underlie some of the hallmark features of ADHD (1).

Additionally, genetic mutations of the CB1 receptor gene have been associated with symptoms of ADHD (2). CB1 is found on GABA and Glutamine neutrons controlling the flow of other neurotransmitters such as dopamine. Deficits in its expression may be related to a deficit in signalling with relation to attention, hyperactivity and impulsiveness.

Cannabinoids, as adaptogens seeking to restore balance within the ECS, are worthy candidates to intervene at a level which underpins global neurotransmitter flow.

Several studies have examined the effects of (mostly) CBD on symptoms of attention, hyperactivity and impulsiveness. There seems to be a good case to use CBD for these symptoms, at least going by the initial data.

A study looked at whole plant CBD (20:1 CBD:THC) in 53 children with Autism Spectrum Disorder for an average of 66 days. Hyperactivity symptoms improved in 68%, did not change in 29% and worsened in 3% (3).

Another study looked at cannabinoid preparations at ratios ranging from 20:1 to 6:1 (CBD:THC) in 60 children with ASD retrospectively. Considerable improvement in behaviour problems was reported in 61% of the children, as well as 47% for anxiety. Scores for disruptive behaviour improved by 29 and 33% from baseline to end of the study (4).

An observational study of 18 autistic patients undergoing treatment with a CBD extract (CBD to THC ratio of 75/1). After 6-9 months of treatment, most patients, including epileptic and non-epileptic, showed some level of improvement in more than one of the eight symptom categories evaluated: Attention Deficit/Hyperactivity Disorder; Behavioural Disorders; Motor Deficits; Autonomy Deficits; Communication and Social Interaction Deficits; Cognitive Deficits; Sleep Disorders and Seizures, with very infrequent and mild adverse effects. The strongest improvements were reported for Seizures, Attention Deficit/Hyperactivity Disorder, Sleep Disorders, and Communication and Social Interaction Deficits.

The average dose of CBD administered from then until the end of the study was 4.55 mg/kg/day, with a minimum of 3.75 and a maximum of 6.45 mg/kg/day (5).

30 adults with ADHD were randomised to placebo or Sativex Oromucosal Spray, a cannabinoid medication containing a 1:1 ratio of delta-9-tetrahydrocannabinol (D9- THC) to Cannabidiol (CBD). Significant improvement in hyperactivity/impulsivity and a trend for improvement in inattention. There were further indications for improvement in activity and cognitive performance, and emotional lability (6).

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CBD & SARS-CoV-2

We wanted to [tentatively] cover some exciting and emerging research around CBD and SARS-CoV2.

The fact that a plant that is still demonised as a drug of abuse with no medicinal value could hold the key to alleviating the impact of coronavirus is beyond ironic.

But before I get ahead of myself, I’d like to offer this disclaimer; the research is still concentrated in the mechanistic sciences, and population studies / empirical evidence is still yet to confirm (or refute) initial findings.

Prevention

One suggested mechanism of action for cannabinoids like CBD to reduce the infectious burden of SARS-CoV2 is how it enters a cell within a host.

SARS-CoV2 gains access to cells within various tissues throughout the body via the ACE2 receptor. The level of ACE2 receptors changes during the course of a SARS-CoV2 infection.

Whats interesting to note is that 13 high CBD strains of cannabis have actually been shown to down regulate expression of the ACE2 gene and subsequent levels of the protein.

Additionally, these strains have also been shown to down regulate other proteins which permit entry of SARS-CoV2 into target tissues, including GI, Nose and Lung models (*).

It is possible that such strains of high CBD cannabis could reduce the infectious burden and spread of SARS-CoV2 within tissues throughout the body.

Immunomodulation

CBD and other cannabinoids have become well known for their immunomodulatory capacity, especially with regard to chronic inflammatory and autoimmune diseases.

Although there is concern over a potential immunosuppressive impact of cannabinoids, this may only be the case where an individual has a particularly high inflammatory / immune ‘tone’.

In line with the adaptogenic properties of CBD, there is also evidence of an immunostimulatory impact of CBD. So it may depend on how the individuals immune system needs support.

CBD has been shown to effectively reduce the expression of inflammatory cytokines such as TNF-a and IL1B. Such cytokines are involved in the surge seen in the cytokine storm, whereby tissues such as those found within the lungs are severely and possibly damaged irreversibly as a result of excessive immune stimulation.

Indeed, a combination of cannabinoids and terpenes have actually been found to reduce the inflammation seen in SARS-CoV2 up to twice as effectively as corticosteroids such as dexamethasone (*).

Whats more, dexamethasone has been shown to save lives in the face of cytokine storms (*).

However, its also worth noting that there has been cases of increased incidence of infections in children receiving CBD for seizures (almost exclusively in those also receiving clobazam) (*).

It may be that a drug-CBD interaction may alter immunity in some way, or some individuals are susceptible to immunosuppression and/or an adaptogenic effect of CBD does not apply.

Summary

It is still early days for cannabinoid research when it comes to SARS-CoV2. Almost all research is preliminary, and until it is backed up by population data, we are left to speculate.

But the future is exciting, as we require strategies to more effectively prevent and manage this disease as it appears it is here to stay, at least for a while.

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CBD & Depression: Lessons From Cases

Today we’re going to take a look at a case study, which hints at an anti-depressant action for CBD.

Until recently, there has been very little evidence to suggest that CBD can act as an anti-depressant.

Its use as an anti-anxiety agent has received a lot of attention, and is well on its way to being established. However, there has not been as much interest in its actions as an anti-depressant.

The mechanisms for CBD are clear when it comes to anxiety. CBD enhances the function of the endocannabinoid system whilst at the same time acting on serotonin signalling.

Both are a way of modulating mood, in the direction of greater happiness, safety and contentment at least on a biochemical level.

Although CBD does not share the same mechanism as an SSRI, that is increasing the amount of available serotonin available in the synapse by preventing its re-uptake; CBD still enhances serotonin signalling by increasing the 5-HT1a serotonin receptor sensitivity to serotonin. This has been connected with reductions in feelings of anxiety, and perhaps in feelings of depression as well according to cross sections survey data of CBD users.

Going by the Neurotransmitter hypothesis of depression, a fundamental imbalance of neurotransmitter activity in the brain leads to depressive symptoms (likely as a result of life experiences pas and present).

So in the same was as an anti-depressant is used (to ‘balance’ brain chemistry), without addressing lifestyle circumstances, CBD can be used as a temporary treatment to ‘balance’ brain chemistry whilst lifestyle adjustments (therapy etc) are made to address the underlying mental, emotional and spiritual issues disrupting brain chemistry in the first place.

CBD acts as a pleiotropic molecule – it can have many different effects at once, acting on numerous neurotransmitter systems ubiquitously, such as dopamine, serotonin and GABA.

In this way, it can bring ‘balance’ to mood states, acting as a complex homeostatic device. Whereas in contrast SSRI’s and other antidepressant medications target single mechanisms, which over time can lead to serious imbalance, side effects and mood imbalance in the long term.

In a case study, a 25 year old patient with Neurofibromatosis type 1 exhibited significant symptoms of pain, depression and anxiety (as a co-morbidity to others).

At the three-month follow-up visit, the patient reported starting with 4 mg BID of cannabis oil with CBD to THC ratio concentrations of 20 mg/ml to 1 mg/ml (CBD: THC 20:1). This was gradually increased by the patient to 8 mg BID.

During this period, the patient reported that her pain was significantly reduced (from an average of 6/10 down to 1/10). She reported being less emotional and feeling calmer. She said that her anxiety dropped from 9/10 down to 3 to 4/10 and that her mood had stabilised (1).

Numerous other CBD users also report an improvement in mood and symptoms of depression (possible as a result of reduce pain and/or stress) (2).

It will be interesting to see what affect CBD has in further studies on depression, where the underlying cause may not be related to pain and/or stress.

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CBD & Recovery (HRV)

One of the most renowned effects of CBD is for stress. As we’ve mentioned in our CBD handbook, CBD has a profound effect within the nervous system, and can act on hormonal pathways to instruct equilibrium.

Whether your clients are athletes, have some form of PTSD or are under chronic lifestyle stress, CBD may be able to help.

One marker of stress has emerged as a useful biomarker for measuring levels of stress, recovery and resilience. That marker is Heart Rate Variability (HRV).

HRV is a measure of the variation in time between each heartbeat. The variation is controlled by the activity of the autonomic nervous system. A greater sympathetic activity results in a lower HRV reading (less variance), whereas a higher HRV (greater variance) shows more parasympathetic activity.

HRV can be easily measured by fitness devices, like Fitbit, Oura ring and Garmin watches. Its useful for almost anyone to track, especially for clients who may be struggling with chronic stress and burnout.

Aside from breathing techniques, meditation, yoga and other mind body practices, CBD may also be used to enhance HRV.

CBD is an important regulator of nervous system activity, especially as an activator of the vagus nerve, helping to promote vagal braking on heart rate and HRV. It ensures that the yin and yang of sympathetic and parasympathetic nervous activity are at one with each other.

Cannabis has been shown to increase HRV in healthy young men, significantly (1). However, cannabis users also reported lower psychological well-being than controls, which is a significant down side to the improved HRV.

This is where CBD really comes into its own, because it affords many of the benefits of cannabis, but with the less desirable ones.

In a randomised cross-over study, 15 healthy men and women (age 21-62) had a single dose of CBD at 30mg, which resulted in modest improvements in HRV (2).

Another RCT with 65 overweight individuals measured changes in HRV over the course of 6 weeks. Participants dosed at 15mg CBD/day, which did not result in changes in HRV but did improve psychometric measures of stress (3).

It is possible that larger doses are needed to produce significant improvements in HRV, even when CBD is being taken regularly. Also, the quality of CBD oil, and whether it is an isolate or full spectrum preparation rich in other cannabinoids and terpenes will determine the magnitude of effect as well.

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CBD & Cholesterol

Despite the ambiguity between the link of cholesterol and heart disease, its still not ideal to have high cholesterol.

The first line treatment for cholesterol, statins are in some cases necessary, but if we can avoid using them and seek natural interventions, then thats a bonus.

Amongst herbal and nutraceutical interventions like red yeast rice extract and berberine lies CBD, another candidate to contribute to healthy metabolism.

Several animal studies have shown that CBD, through the endocannabinoid system (ECS) may have a subtle effect on lipid production, such as cholesterol.

High fat diets coupled with high intakes of simple sugars cause an increase in endocannabinoid system activity. This leads to a greater production of lipids in the liver, and subsequently higher output of cholesterol (VLDL) and triglycerides.

Early studies with the synthetic cannabinoid (Rimonabant 20 mg/day) in overweight and obese individuals improved lipid profiles by increasing high-density lipoprotein cholesterol (HDL) and decreasing triglycerides. Rimonabant worked by blocking the CB1 receptor in the liver.

Other studies found that levels of HDL-c increased continuously throughout 2-year treatment with a Rimonabant, whereas body weight stabilised. Significantly, only a portion (approximately 50%) of the effect associated with Rimonabant treatment on HDL was attributed to weight loss.

Rimonabant was recalled from market in the early 2000’s due to adverse side effects. But CBD is emerging as a safe alternative to Rimonabant, as it shares a similar, but fundamentally different mechanism of action.

Whilst Rimonabant is a potent blocker of CB1 receptors, which proved to be useful for enhancing metabolism, this was disastrous at the central level for mood regulation with regards to depression and anxiety. CBD however is a negative allosteric modulator of CB1, so instead of completely blocking it, it effectively turns down the volume of excessive endocannabinoids in cases of obesity and diabetes.

CBD is thought of as a negative modulator of the endocannabinoid system, with regards to conditions to where the ECS is overactive (Obesity and Diabetes).

Interestingly one study in humans found that 200mg of CBD isolate/day for 13 weeks had no effect on any of the metabolic parameters measured in diabetic patients (1).

In contrast, a study using just 15mg of full spectrum CBD / day for 6 weeks in overweight, but otherwise healthy individuals saw a significant improvement in HDl-c levels compared to those receiving placebo (2).

A few considerations are with noting here;

CBD isolate is inferior to full spectrum CBD, and requires much higher doses to prove efficacious. CBD isolate is typically used in doses from 600 – 1000mg in other clinical trials, so it is not surprising that no effect was seen in the first trial.
In the second study, CBD was used at a dose of 15mg / day, which is as well a relatively small dose. The FSA recommends that CBD can be taken up to 70mg/day without complication. It is possible that higher doses may provide an effect on triglycerides and VLDL-c that was not seen in the later study.
CBD is an adaptogen that works to restore balance mostly where significant imbalance exists. For example, the appetite suppressing effects of CBD are only present in overweight mice with elevated ECS function, in contrast to producing no effect in lean mice. Since subjects in the later study were otherwise healthy, it may not be expected for CBD to have a significant effect on metabolic parameters.

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CBD & Medications

We have put together a quick guide for reference, as to what medications have been shown to interact with CBD. However, this list is not extensive and there may be other unknown interactions.

CYP1A1

CBD inhibits this enzyme, so theoretically using it alongside drugs like Chlorzoxazone (Lorzone) and theophylline (Theo-Dur, others) may slow the breakdown of these drugs, which may potentiate their effects.

CYP1A2

CBD inhibits this enzyme. Other drugs broken down by this enzyme include :

Amitriptyline (Elavil)
Aloperidol (Haldol)
Ondansetron (Zofran)
Propranolol (Inderal)
Theophylline (Theo-Dur, others)
Verapamil (Calan, Isoptin)

CYP1B1

CBD inhibits CYP1B1. Drugs that are broken down by this enzyme may be affected:

Theophylline (Theo-Dur, others),
omeprazole (Prilosec, Omesec),
clozapine (Clozaril, FazaClo),
progesterone (Prometrium, others),
lansoprazole (Prevacid),
utamide (Eulexin),
oxaliplatin (Eloxatin),
erlotinib (Tarceva),
caffeine

CYP2A6

CBD inhibits CYP2A6. Drugs that are broken down by this enzyme may be affected:

nicotine,
chlormethiazole (Heminevrin)
coumarin, methoxyurane (Penthrox)
halothane (Fluothane)
valproic acid (Depacon)
disulram (Antabuse)

In clinical research, concomitant administration of valproic acid and cannabidiol is associated with elevated liver transaminases and thrombocytopenia. Liver transaminase elevation appears to be mild in the majority of cases, however, severe elevations can occur. Liver transaminase levels should be monitored when cannabidiol and valproic acid are taken together

CYP2B6

CBD inhibits CYP2B6. Drugs that are broken down by this enzyme may be affected:

ketamine (Ketalar)
phenobarbital,
orphenadrine (Norex)
secobarbital (Seconal)
and dexamethasone (Decadron)

CYP2C19

In clinical studies, concomitant administration of cannabidiol and clobazam is associated with up to a 60% increase in serum levels of N-desmethylclobazam, the primary active metabolite of clobazam. This increased concentration is likely due to inhibition of cytochrome P450 2C19 (CYP2C19) by cannabidiol

CYP2C9

In clinical research, concomitant administration of cannabidiol and topiramate, a CYP2C9 and CYP2C19 substrate, is associated with a modest increase in plasma levels of topiramate

Nonsteroidal anti-inammatory drugs (NSAIDs) such as diclofenac (Cataam, Voltaren), ibuprofen (Motrin), meloxicam (Mobic), and piroxicam (Feldene); celecoxib (Celebrex); amitriptyline (Elavil); warfarin (Coumadin); glipizide (Glucotrol); losartan (Cozaar)

Pharmaceutical CBD (Epidiolex®) was found to potentiate the effects of warfarin, which may increase its blood thinning effect (*)

CYP2D6

CBD inhibits CYP2D6. Drugs that are broken down by this enzyme may be affected:

amitriptyline (Elavil)
codeine
desipramine (Norpramin)
ecainide (Tambocor)
haloperidol (Haldol)
imipramine (Tofranil)
metoprolol (Lopressor, Toprol XL)
ondansetron (Zofran)
paroxetine (Paxil)
risperidone (Risperdal)
tramadol (Ultram)
venlafaxine (Effexor)

CYP3A4

CBD inhibits CYP3A4. Drugs that are broken down by this enzyme may be affected:

alprazolam (Xanax)
amlodipine (Norvasc)
clarithromycin (Biaxin)
cyclosporine (Sandimmune)
erythromycin
lovastatin (Mevacor)
ketoconazole (Nizoral)
itraconazole (Sporanox)
fexofenadine (Allegra)
triazolam (Halcion)
verapamil (Calan, Isoptin)

In clinical research, concomitant administration of cannabidiol and zonisamide, a CYP3A4 substrate, is associated with a modest increase in plasma levels of zonisamide

CYP3A5

CBD inhibits CYP3A5. Drugs that are broken down by this enzyme may be affected:

testosterone
progesterone (Endometrin, Prometrium)
nifedipine (Adalat CC, Procardia XL
cyclosporine (Sandimmune)

CNS Depressants

The use of cannabidiol with drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects. CBD interacts with some of the same receptors (GABA) that drugs like benzodiazepines do to induce sedation, which may add to their effects.

Some CNS depressants include:

Benzodiazepines,
Pentobarbital (Nembutal)
Phenobarbital (Luminal),
secobarbital (Seconal),
thiopental (Pentothal),
fentanyl (Duragesic, Sublimaze),
morphine,
propofol (Diprivan)

Other Drugs

In clinical research, concomitant administration of cannabidiol and runamide is associated with a modest increase in plasma levels of runamide.

In clinical research, concomitant administration of cannabidiol and eslicarbazepine is associated with a modest increase in plasma levels of eslicarbazepine.

The effectiveness of chemotherapy drugs rely on a very specific dose and time course of activity. Adding CBD into the mix may reduce the efficacy of these drugs, or worse induce toxicity from them. Chemo drugs are often dosed very specifically within a narrow therapeutic window. If that window is exceeded, there may be a risk of toxicity.

It may be worth cycling the use of CBD, with a washout period of a few weeks.
Include other herbs that speed up CYP’s
Be sure to talk to a doctor about using CBD with other medications first. They may be able to advise on a cycling protocol which avoids crossover between drug metabolism.

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CBD & Substance Abuse

Substance abuse involves an area of the brain which processes how rewarding a substance is, and subsequently how addictive it is.

The ECS acts as a middle man in the brain’s reward centre. It influences the firing of (dopamine) neurons that process reward. When exposed to rewarding substances, the ECS drives the physical changes in the brain that eventually makes them irresistible.

Some people may be more predisposed to addictive tendencies than others, which is influenced by how their ECS is functioning. Many factors influence how someone’s ECS works, including their genetic predisposition, and what’s happened to them in their lives.

For example, some people may have been separated from their mothers, or experienced trauma as a child. Research shows that childhood traumas dysregulate the ECS from an early age, and may increase their likelihood of experiencing greater reward from drugs, driving addiction (Portero-Tresserra et al., 2018), (Bassir et al., 2019).

A common finding is that they are low in endocannabinoids, and experience mood disorders as a result. If they are exposed to drugs or palatable foods which activate their ECS, then this produces an intense mood lift and rush of reward not otherwise experienced in life.

Similarly, kids who experienced trauma and also had the genetic variation in the CB1 receptor that means they produce less receptors, and have an even more underactive ECS. They had a greater tendency towards depression (Agrawal et al., 2013) and alcohol and drug dependence (Lingjun et al., 2007).

They also have a greater risk for cannabis dependence (Agrawal et al., 2013), since THC activates CB1, and compensates for a low functioning ECS, they develop a dependence on the mood enhancing effects of THC that they would have otherwise experienced from a well functioning ECS.

CBD & Combating Addiction

Although there are emotional and lifestyle issues which contribute to addiction, CBD may be used as a useful adjunct to working through these issues.

Fortunately, CBD can support a badly functioning ECS in a way which is specific to each individual. Herbs that do this are known as adaptogens, and just like the name suggests, can adapt to meet an individuals needs.

CBD can both increase and decrease the activity of the ECS, and does so differently depending on the areas of the brain that are imbalanced.

CBD can increase and decrease CB1 receptors depending on what brain area is imbalanced
CBD can block the CB1 receptor in certain brain areas
CBD can indirectly activate the CB1 receptor (by increasing endocannabinoids) in other brain areas

CBD also acts on other brain signalling systems in a way which is specific to the drug being used.

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CBD, IBS and Diabetes

Just to share an update on a previous piece we wrote on CBD and diabetes. Recently, Claudia was invited to contribute her insights on the relationship between diabetes and IBS, and how CBD may help here.

You can find the article here.

On top of this article, we wanted to take this opportunity to expand on how CBD may be useful in case of IBS and diabetes.

Even though there is yet to be human data to confirm a blood glucose lowering effect of CBD (that has been shown in animals), there is good mechanistic grounds to reason that there could be a strong chance it could.

Its worth noting that the only human study using THCV and CBD DID NOT show an effect on blood sugar – only in the group using THCV alone, despite diabetes.co.uk claiming that CBD did in fact have an effect.

Nonetheless, we can speculate as to some of the effects until more clinical data emerges. As we we’re discussing in our clubhouse hangouts today, there may be a use case for CBD to intervene at various stages in the development of diabetes.

Although everyone responds differently to foods (due to unique microbiomes), junk foods high in sugar tend to spike blood sugar levels. This is yet to be confirmed, but CBD may help increase the cellular sensitivity to insulin (at least thats what animal studies have shown).
Even if point #1 does not apply in humans, the powerful antioxidant and anti-inflammatory properties of CBD are highly likely to alleviate the damaging and cytotoxic effects of elevated blood sugar and the downstream consequences and diabetes complications.
The destruction of the microbiome and the gut lining is a driving factor that eventually leads to aberrant blood sugar control in response to a diet high in sugar. CBD interacts with the microbiome in a way which seeks to preserve its composition, in addition to closing tight junctures in the gut wall – preventing gut leakiness.
The anti-inflammatory effects of CBD lend well to keeping a healthy gut ecosystem, and levels of inflammation in check, offsetting the effects of meta-inflammation and metabolic disruption that disrupts blood sugar levels.
Besides diet, stress also plays a major role in the regulation of blood sugar levels. Given CBD’s dampening effect on the nervous system and HPA axis, adrenaline and cortisol responses to release sugar into the blood may be reduced (speculative).
Sleep is also a major factor in keeping hormonal control of blood sugar under control. CBD may help achieve deeper, more restful and uninterrupted sleep, which in turn may help keep a healthy circadian rhythm and hormonal balance and control of blood sugar.

Nothing occurs separately in the body, and whats good for blood sugar is also likely good for gut health and vice versa.

The many applications of CBD lend well to keeping a healthy gut, and subsequently a healthy blood sugar response (with help from dietary and lifestyle modifications).

MY BAG

Index

Lessons From Research

CBD: Where to begin in clinical practice

Does CBD help a Migraine?

Does CBD help with IBS?

References

Could CBD help with Obesity?

References

The Endocannabinoid System & The Skin

CBD and Pain

References

Disordered eating and the Endocannabinoid System

CBD & Anxiety

CBD & Alzheimers

Corona Chaos: Take A Load Off

CBD & Sleep

CBD & Friends: The Entourage Effect

CBDA: A Little Extra Goodness

The Entourage Effect: Why its Clinically Meaningful

CBD as an Adaptogen

CBD & Blood Sugar

CBD & PTSD

CBD, The ECS & Depression

The ECS & Human Psychology

CBD & Autism Spectrum Disorder

The ECS and ASD

CBD and ASD

CBD & Pregnancy (Why its NOT a good idea)

However, its unknown whether using CBD to reduce these symptoms comes at a cost to the child’s development.

Why CBD is not safe during Pregnancy….

Consensus from the (limited) Research

Are there any risks of using CBD oil before pregnancy?

Why CBD should not be used whilst breastfeeding…..

CBD & Menopause

Progesterone

Estrogen

CBD to The Rescue

Can CBD help with Weight Loss?

Appetite Management

Body Weight

Summary

CBD and Leaky Gut

The ECS and the Gut

How Can CBD Help?

CBD and Alcohol

CBD and Heart Health

Dealing with CBD Stigma

Facts

1) CBD is not a cure

2) CBD won’t get you high, but can make you feel good

3) CBD can produce side effects

4) CBD from hemp is legal

5) It’s been used to support health for centuries

6) CBD is (sort of) classified as a medicine

7) CBD can come from hemp and marijuana

Myths

1) There’s no evidence that CBD supports health.

2) CBD works for everyone

3) CBD is non-psycoactive

4) All CBD is created equal

5) CBD is addictive

6) A little is enough

7) CBD oil is the same as hemp oil

References

CBD & Crohn’s

Mechanisms

CBD & IBD

Cannabis & IDB

CBD & ADHD

CBD & SARS-CoV-2

CBD & Depression: Lessons From Cases

CBD & Recovery (HRV)

CBD & Cholesterol

CBD & Medications

CBD & Substance Abuse

CBD & Combating Addiction

CBD, IBS and Diabetes

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