Following My Bliss – All about Anandamide and How to Make It Yourself

I’m not exactly the curmudgeonly sort; in fact I’m pretty amiable and forward-thinking most of the time.  But when I heard about a body-produced substance that mimics THC – so much so that it was named after the blissful effects it purportedly produces – well, I wanted more of that.   Perhaps there is a way to turn on the spout that releases the happy stuff called Anandamide, aka “the molecule of wonder.”

For cannabis-science neophytes, Anandamide is classified as an endocannabinoid, your body’s own version of cannabis.  The irony about Anandamide (and other endocannabinoids) is that researchers really didn’t go fishing for these molecules until the late 1980s when they observed that THC fit like a glove into special receptors in the brain and central nervous system.  So they set about to examine the theory that if we have this complex network of receptors, we must produce some kind of endogenous substances as keys to the receptor locks.  Finally, in 1992, anandamide was discovered and promptly named it after the Sanskrit word for divine joy.  (Also, the chemical name for anandamide is Arachidonoylethanolamide and who wants to try tripping all over those syllables?  )

 Eureka!

Producing Anandamide and Breaking it Back Down

Anandamide is a fragile molecule produced upon demand in the brain by a synthesis process within neurons called a condensation reaction (the combination of two molecules to become a single molecule).  Once produced, it’s quickly broken down into other compounds by a degrading enzyme called fatty acid amide hydrolase (FAAH).  Wash, rinse, repeat.

Now if FAAH doesn’t work too fast, anandamide will hang around longer in the body and promote the beneficial effects that the bliss molecule is known for.  Some people, by virtue of genetic mutation, have the ability to block FAAH from degrading anandamide.  In turn, these fortunate few maintain higher levels of anandamide and they enjoy less anxiety and fearfulness than the rest of us.  And that’s because anandamide, as the namesake for “joy”, is linked to an elevation in mood and happiness.

But the potential for anandamide goes beyond having a happy day.

Health Benefits of the Joy Molecule

Since anandamide synthesizes in areas of the brain where memory, motivation, cognitive processes and movement control are managed, it can influence physiological systems such as pain, appetite regulation, pleasure and reward.  Additionally, anandamide has been shown to promote neurogenesis (1), the formation of new nerve cells, and to slow cancer cell proliferation (2). 


.

Brain Research, Mice and Men – Who Moved My Cheese?

  Research suggests that anandamide can remodel the process of brain reward circuitry.  For example, a study on mice from 2017 (3) tested its effects on motivation and reward. With different possibilities of choice and after receiving an injection of anandamide, the mice were able to choose more quickly and to choose the best solution.  

Anandamide is also known as a molecule that helps you to forget – but in a good way.  One study (4) at the University of Calgary compared a group of genetically happy humans with rodents that had been injected with the same rogue gene, finding that had higher levels of anandamide led to a greater ability to erase fear- based memories.  The reason underlying this strategic forgetfulness is that higher levels of anandamide allow for greater connectivity between the prefrontal cortex (the brain’s highest-level center of cognitive processing) and the amygdala, the part of the brain responsible for recalling painful, often tragic memories.   The amygdala’s stubborn retention of bad experiences gets in the way of cognitive performance and emotional health in huge ways throughout a lifetime – just ask any PTSD survivor.

Boosting Anandamide Yourself

Besides choosing our own parents to inherit a lucky genetic mutation, how can we boost our levels of anandamide naturally? 

Take CBD

CBD plays an interesting and complex role in the brain.   As mentioned earlier in this blog, THC fits perfectly into the endocannabinoid receptors found throughout the brain and central nervous system, releasing the psychoactive properties it’s known for. But CBD (Cannabidiol), the non-psychoactive and second most abundant cannabinoid, has very little binding compatibility with the endocannabinoid receptors.  

However, CBD is now known to increase levels of anandamide in the body.  CBD inhibits the FAAH enzyme responsible for breaking down the endocannabinoid.  In turn – voila! – anandamide stays onboard in higher levels to release its positive mood enhancing effects.

Exercise

As far as exercise goes, I must confess that I’m one of the afflicted; I love distance running (although my gait is more like a shuffle these days.)   I am hooked on the after-affects that exercise conveys, the pleasant buzz that has long been termed an “endorphin rush.”

But the endorphin theory is losing ground as researchers have discovered that exercise (of at least 30 minutes duration) facilitates the production of anandamide.  Endorphin molecules, it turns out, are too large to cross the blood brain barrier to enter the brain.  So the whole “runners high” attributed to endorphins may in fact be unfounded and we need to adjust our vocabulary to credit anandamide instead.  Who knew?



Chocolate!

Ok, if you weren’t too keen on that last section on exercise, here’s some terrific news.  Eating chocolate boosts anandamide in two ways - by stimulating the endocannabinoid receptors and by blocking anandamide’s breakdown. In fact, some researchers say that the simplest way to increase anandamide levels is by eating dark chocolate. 

Chocolate has over 300 known chemical compounds including a significant amount of a substance called theobromine which not only boosts anandamide levels but has evidence of both calming the brain and increasing neural activity.  Sweet!

To be clear, the chocolate best for healthy consumption is high quality dark chocolate with higher percentages of cocoa, not the cheap, highly sugared chocolate products that are pushed on kids at Halloween.  If you really want to be a purist, the effects are supposedly even greater if you chew cocoa husks. 

Little wonder why chocolate is the number one food craving.

Truffles

Truffle-rooting anyone?

Certain animals, namely dogs and pigs, go wild when they sniff out a fungus delicacy called truffles.   Scientists have discovered that anandamide can be found in black truffles (Tuber melanosporum). Interestingly, truffles produce anandamide, but they don’t contain any accompanying internal receptors that would trigger a biological effect.  Perhaps, researchers think, truffles develop anandamide as a means to attract animals to eat it, a process that releases their spores and allows them to propagate.  

If you haven’t had a personal culinary experience with truffles, it’s probably because they are difficult to cultivate, and most are found in the wild by truffle hunters and truffle-hunting dogs.  So – ouch! -  they are expensive $50-$125 per ounce.  On my budget, I’ll stick with chocolate, thank you.

In the Zone

When I’m doing something that I really love – like journaling or playing Chopin - I get lost in it and time fades away.  It’s a state of heightened concentration, performance and focus called “flow “or of being “in the zone.”   If you haven’t heard of flow, you’re not watching enough Oprah.  In such a state, the brain releases an abundance of chemicals like serotonin, dopamine, endorphins, and our friend anandamide. 

 No wonder we’re advised to follow our bliss – it’s because bliss begets itself.

References:

  1. https://www.ncbi.nlm.nih.gov/pubmed/16224541

  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20983/

  3. https://www.kalapa-clinic.com/en/what-is-anandamide/#_ftn4

  4. https://www.nature.com/articles/ncomms7395

CBG – The Mother of All Cannabinoids: Part Two

CBG, aka “the mother cannabinoid”, shows great promise for potential medical uses as researchers take a closer under- the –microscope look at prospective clinical applications.  Since CBG works by turning on and off important brain/body receptors (see Part 1 of this blog), it has enormous versatility as a helper-agent for many common conditions which we’ll explore here.

 Cancer and Chemotherapy Patients

CBG shows promise in lowering cancer cell growth in animal studies by blocking the receptors that cause growth. In a study using mice, for instance, CBG was shown to inhibit growth of colorectal cells, in turn slowing colon cancer growth.

Like THC, CBG can be used to treat appetite loss commonly seen in patients undergoing chemotherapy. In research using rodents, rats who were given CBG ate more frequently than those without the CBG dosing. If a similar effect is found for humans, it would be a boon for patients on chemotherapy who have a very hard time tolerating food due to nausea.  And the task is accomplished without imposing an unwanted THC-induced psychoactive effect.

Packing a Power Punch to Pain

 CBG is considered a powerful pain reliever – mostly because of its ability to push and pull on the alpha-2 and 5HT1A receptors that we discussed in part one of this blog.  When CBG stimulates alpha-2 and inhibits 5HT1A, it creates a synergistic effect that yields both physical and emotional effects.  Ask anyone who has suffered with chronic pain and they will tell you that it hurts both physically and, worse, psychologically especially with a long-term affliction.  I think of CBG as a double-whammy attacker for pain.

Curbing Depression Without a Prescription

CBG works in a similar fashion (stimulating alpha-2 receptors and blocking 5-HT1A receptors) on depression. In fact, the lab tests involving rodents likened CBG to an old-school antidepressant called imipramine. Known as Tofranil, imipramine is a” tricyclic” pharmaceutical antidepressant, mainly used in the treatment of major depression and enuresis (bed-wetting).   The problem is (no surprise here!) Tofranil has a boatload of potential side effects including weight gain, vomiting, weakness, appetite loss and impotence.  By the way, those are only a few of the common, “less serious” side effects.

So Much More

I’ve only scratched the surface of the potential health benefits that CBG has been suggested for in the infancy of its research days.  The list includes intraocular pressure (glaucoma), muscle spasms, and Inflammatory Bowel Disease (IBD). It’s supposed to have anti-bacterial and antifungal properties, help stimulate bone growth and serve as a neuroprotectant.  

 I could go on until the cows come home about CBG’s outstanding safety profile, its non-toxicity, lack of psychoactive effects, no withdrawal nor addiction to worry about.  At this point, the research on this compound is scant in comparison with the dominant cannabis compounds, THC and CBD.   But with what we’ve seen so far, other cannabinoids may need to share the limelight with their quiet but powerful working mother.

The Mother of All Cannabinoids: Health Benefits of CBG : Part One

As I become better acquainted with cannabinoids, I find myself revisiting the marvels of homeostasis, the body’s self-regulatory automatic mechanism of running checks and balances to ensure equilibrium.  Homeostasis is a tremendous thing – imagine having to think about initiating perspiration every time you exercise vigorously, or ask your blood to coagulate after a cut. The human endocannabinoid system helps regulate homeostasis—so when homeostasis goes haywire, adding plant-derived cannabinoids can help right the ship. Today, we’ll look at the grand matriarch of the cannabis family and its role in human health.Cannabinoids – we’ve met your mother, and her name is Cannabigerol.

All cannabinoids start off as CBG

Cannabigerol (CBG) is a non-psychoactive cannabinoid that acts as a chemical precursor to other cannabinoids, including THC and CBD. CBG is considered to be the ‘mother’ of the other cannabinoids because it is the first cannabinoid produced by the cannabis plant. CBG starts off as CBGA (the raw or “acidic” form version of the compound).  CBGA then combines with enzymes to render THC, CBD and CBC (also from their acidic forms) later in the flowering cycle.

Let’s rewind just a bit to explain what is meant by acidic forms of cannabis compounds. In the young days of the plant’s growth cycle, cannabis compounds have a different molecular design. When heat is applied in processing the plant (as in drying, smoking or cooking), the end-result compounds we are so familiar with are produced.  Such is the process known as decarboxylation, well known to growers and breeders. 

But alas, as the conversion from CBG to THC and CBD takes place in the cycle of flower growth, CBG loses its influence and is present only in trace amounts in most cannabis strains (isn’t that just like kids to take over their mother’s lives?)  Indeed, some breeders are looking to block the conversion to render higher percentages of CBG for its potential health benefits, which we’ll explore later in this article.

How CBG works on receptors

In an earlier blog, I described the various cell receptors throughout the brain and body as parts of a giant switchboard, switching various body processes on and off.  Like other cannabinoids, CBG interacts with a few key receptors that modulate important body and brain responses.

One such receptor, found in the brain stem and the peripheral nerves, is called the alpha-2 receptor. On its own, this receptor is heavily involved with the regulation of the parasympathetic (calming) and sympathetic (excitable) nervous systems as well as blood vessel dilatation or constriction. Think of how the body and mind spring to action when faced with a “flight or fight” situation – jumping up excitedly, heart pounding and mind racing, followed by a quick return-to-normal state after the threat has passed.  When CBG binds to alpha -2 it mimics the parasympathetic system, lowering blood pressure, decreasing stress and anxiety.  

CBG also blocks a brain-based receptor called 5HT1A receptor which is involved with the regulation of serotonin.  Serotonin is an especially important neurotransmitter in mental health because it is our “feel good” mood neurotransmitter, heavily associated with the chemistry underlying depression. Aside from being a stress-buster, blocking the 5HT1A receptor has been shown to improve learning and memory in animal studies.   

And finally, CBG inhibits the reuptake of anandamide. In case you’ve forgotten, anandamide is one of our own endocannabinoids, known by its street moniker, the “bliss hormone”.  CBG allows the effect of anandamide to last longer.  And as far as I know there’s no such thing as too much bliss! 

I’ll continue the conversation about cannabinoids in my next blog post. More to come!

The Rules of Cannabis Consumption: Take with Food

As a nurse who also teaches, I spend a lot of my time talking about medications and how to take them – as pills or capsules, crushed into applesauce or mixed into syrup for easier swallowing, sometimes as droplets sprinkled under the tongue.  Medicine – and the regime of taking daily medicine – is at the front of the mind for many people when asked about their health.  “What meds are you on?” is part of every patient interview.  My personal translation of that question is “what do you put into your mouth when you start your day”?

Medication administration has its own code of rules.  Some meds don’t mix well with others.  Some have to be taken with other drugs to augment the desired effect or to offset a side- effect.  When a nurse prepares medication for administration, she “pours them up” into tiny paper cups (charmingly called soufflé cups) and proffers them to her patients along with a glass of water.  In a healthcare facility, this is called a “med pass.”

The busiest med pass at any facility is in the morning, right after breakfast.  This is because medications are commonly prescribed once a day and morning is generally convenient.  The other reason is that many medications, unless instructed otherwise, are best taken with food because it makes the medicine work better - and without the side effect of an upset stomach.  

Oral cannabis medications – be it a gummy candy, tincture, or oral spray - follow the same rule.  Look on any cannabis consumer website and you’re given fair warning.  Do not take on an empty stomach or be prepared for possible unpleasant side effects like a racing heart, feeling of paranoia, or nausea.    The experience may be intense but in a bad way (especially if THC is involved).

 To top it off, if you’re using cannabis for strictly medicinal purposes and are more interested in non-psychoactive results from a compound like CBD, the desired absorption of cannabinoids is worse if you take it without eating first.

 Surprised?  To understand how all this works, grab a snack and let’s talk about organs and intestines, large and small.


Down the Hatch:  How Medicine (and Cannabinoids) are Absorbed

To understand the absorption of cannabinoids from cannabis edibles, we first must understand a few basic concepts of drug absorption and the effect of food. 

 While your stomach is certainly teeming with digestive activity, you may be interested to find out that virtually nothing (except alcohol) is absorbed there. Your small intestine, the next stop, is the site of virtually all absorption, be it from a food, supplement or a prescription drug. Think of your stomach as a sort of holding tank that partially digests whatever you’ve consumed and then releases it into the small intestine at a steady rate. 

 I should mention that the liver is also involved as it is your body’s processor/filter and it’s where the absorbed compounds are metabolized. For example, THC is metabolized in the liver and transforms into a compound called 11-hydroxy-THC. This compound is stronger than THC, keeps its potency for a longer time and can be very sedating. This mechanism in the liver is responsible for why edibles have such variation in effect from one person to another. But that’s a story for another day.

When you eat a meal and then consume a drug, the result a slowing of this gastric emptying so that the passage to the small intestine is more limited.  In other words, a full stomach avoids dumping a substance too quickly into your system and circumventing effective absorption.

Oil and Water Don’t Mix – Drugs, Cannabis and Solubility

For a drug to work when taken orally, it must be able to have some form of solubility which means that it happily mixes with a fluid solution.   Think of grains of salt being mixed into water.  A low -solubility drug will typically take a longer time to be absorbed. Some cannabinoids, including THC, have very low solubility in water since they prefer dissolving into lipids or fats.  But when the cannabis consumer eats a meal, the food causes the gallbladder to release bile acids, which help to solubilize lipid-loving molecules like THC. This generally increases the rate and extent of absorption.

Time Factors – Slower but Longer-Lasting Effects

Consuming cannabis-infused edibles means the effects take a longer time to take place and the potency of effects gradually increases. The effects may be noticed at 45 minutes or can take up to 3 hours for full onset. Duration can last between 4 and 6 hours. 

Looking at Research

A European study published in 2013 tested the effect of food on absorption of an oral cannabis spray called Sativex which is an extract containing a 1:1 ratio of THC and CBD. Although it’s in spray form, most of it ends up getting swallowed so the test results should translate to other cannabis edibles.

 In this study, subjects were divided into two groups:  a fasting group who had no food for 10 hours before or 4 hours after dosing and a “fed” group who ate a high-fat meal within 30 minutes of dosing. Subjects were each administered 4 sprays.

The results? THC and CBD were rapidly absorbed in the fasted condition, reaching their peak plasma concentrations at 1.5 hours. For participants who had eaten a meal, these cannabinoids took much longer to absorb, with peak plasma concentrations not occurring until 4 hours after dosing.  

But the more interesting part of this study unfolded when researchers looked at bioavailability (a measurement of the extent of absorption) of the cannabinoids.  Subjects who ate a meal before dosing had significantly more cannabinoids absorbed - 2.8-fold higher for THC and 4.1-fold higher for CBD – compared to the fasting group subjects.


Some Take-Aways Before You Order Take-Out

Eat before you eat:  When taking cannabis in edible form, eat a solid meal beforehand, preferably one with some fat to stimulate that helpful bile acid release.  Keep in mind that peak concentration effects will take longer, although the time varies for each person, so you might need to plan ahead to create the timing you desire.

Absorption considerations: If you are taking an edible mainly for CBD – even if it’s a combination product with THC, definitely eat a meal first since the boost in absorption, according to this study, is four times higher.  For THC alone, it’s your call as an empty stomach isn’t such an important factor as long as you get the dose right.    

Follow the Low and Slow Mantra

Remember – the effect from edible cannabis is going to last longer so if a product is new for you, start with a tiny microdose (no more than half of a full dose).  

Off the Clock, Off the Streets

For novice users, take precautions and stay home when dosing cannabis.  Psychoactive effects are variable, and you don’t want be navigating the freeways or answering to your boss if such effects kick in.  For most people, this means dosing at home, in the evening.


Read the Packaging!

The potency of an edible product is indicated by the milligram (mg) amount of cannabinoids contained in the product. An edibles package should state both the milligrams per serving and the milligrams in the entire package.  It’s much like reading the number of calories per serving in a packaged food item. So, if an entire candy bar has 20 mg of a particular cannabinoid, a quarter of it would contain 5 mg.   Knowing the accurate dosage of an edible product and consuming at a measured pace is extremely important due to the delayed onset time and variable dosage options. 

 Are Edibles Blazing a New Trail? 

 You bet.  The Specialty Foods Association named cannabis edibles as one of the top 10 food trends of 2018 right up there with broccoli -stem slaw, cardamom and grilled haloumi.  Browse through a well-stocked cannabis dispensary and try not to drool over the chai teas, savory nut mixes, ranch tortilla chips, buttery popcorn, gum drops, extra-virgin olive oils, gourmet coffees, cacao, crackers, miso, and mint chocolate bars.  I feel like I’m in the buffet line on a cruise ship.

As the trend continues, the producers who create cannabis-infused edibles will continue to offer something for every appetite.  Just be sure to eat before you swallow.