Every week I am posting about everything you need to know about hormones. This weeks topic is cannabis.
Did you know – cannabis
- Cannabis refers to a group of three plants with psychoactive properties, known as
- Cannabis sativa
- Cannabis indica
- Cannabis ruderalis
- These plants contains naturally-occurring, biologically active, chemicals called cannabinoids, known as exo-cannabinoids
- 100 cannabinoids, such as Cannabidiol aka CBD and Tetra-hydro-cannabinol aka THC
- The body makes its own cannabinoids – called Anandamide also called AEA – N-arachidonoyl-ethanol-amine and 2-AG – 2-arachidonoyl-glycerol which are endo-cannabinoids
- In other words it makes its own Cannabis
- Just like the body makes its own Opium aka Morphine – called Endorphins
- Both Opium and Cannabis have been used for thousands of years as part of TCM and Ayurvedic practises
- It wasn’t until the 70’s that it was discovered the body produced its own opium and the receptors by which it works
- Likewise it wasn’t until the 80’s and 90’s that it was discovered the body produced its own cannabis and the receptors by which it works
- Without the receptors, the therapeutic benefits, or the high that’s associated with them would not be possible.
- The body even has its own endo-cannabinoid system named after the Cannabis plant
- Female cannabis plants have the buds that are covered with the resin that contain the cannabinoids, such as THC
- Cannabis street names – Marijuana, Pot, Weed, Grass, 420, Ganga, Dope, Joint, Reefer, Mary Jane, Buds, Stinkweed, Nuggets, Hay, Rope, and many more.
Meet Sally and get to know all about cannabis
What increases endocannabinoids
Meet the cannabinoids
The Endocannabinoid System
- Named by the plant that led to its discovery.
- One of the most important physiologic systems involved in establishing and maintaining human health.
- Endocannabinoids and their receptors are found throughout the body, such as in the brain, organs, connective tissues, glands, and immune cells, etc.
- Are literally a bridge between body and mind.
- By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.
- But much research is still needed.
- Is composed of endo-cannabinoids, which are fatty, retrograde neurotransmitters possibly produced in every cell in the body, that bind to cannabinoid receptors expressed throughout the body and brain.
- Retrograde means that the message moves backwards or in the opposite direction to other neurotransmitters, acting as communications traffic cops inhibiting the release of many excitatory and inhibitory neurotransmitters.
- May be involved in regulating physiological and cognitive processes, including fertility, pregnancy, pre- and postnatal development, various activity of the immune system, appetite, pain-sensation, mood, and memory, and in mediating the effects of cannabis.
- Plays an important role in control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behaviour and pain modulation.
- The endocannabinoid system includes:
– Endo-cannabinoids Anandamide and 2-AG
– Enzymes that synthesize and metabolize the endo-cannabinoids.
Cannabinoid receptors CB1 and CB2
- 2 primary cannabinoid receptors have been identified:
– CB1 in 1990
– CB2 in 1993
- CB1 receptors are found predominantly in the brain and nervous system but also in peripheral organs and tissues, and are the main target of the endo-cannabinoid Anandamide and exo-cannabinoid THC, the most known active component of cannabis.
- CB2 are more abundant outside the brain and the endo-cannabinoid 2-AG, activates both CB2 and CB1 receptors.
- Cannabidiol (CBD) is an exo-cannabinoid that acts as a weak antagonist ie. blocking of both receptors.
- Tetra-hydro-cannabinol (THC) is an exo-cannabinoid acts as a agonist for and binding strongly to CB1 receptors in the brain.
Receptors are like keyholes enabling Cannabinoids, both endo and exo to enter the cell or nucleus of the cell, where they create changes in cell activity.
- are located in the brain and throughout the body
- found in particularly high levels in the neocortex, hippocampus, basal ganglia, cerebellum and brainstem
- also found on peripheral nerve terminals and some sites outside the nervous system, such as the testis, eye, vascular endothelium and spleen
- Anandamide and 2-AG and exogenous THC activate this receptor
- THC (the psychoactive component of cannabis) binds more closely to the CB1 receptor than the CB2 receptor
- The hormone pregnenolone can also modulate CB1 receptor signalling
- are found mostly in the immune and gut
- are also found in the brain, but not expressed as densely as CB1 receptors.
- are associated with inflammation
- have a regulatory effect.
New cannabinoid receptors
- The existence of additional cannabinoid receptors has long been suspected.
This is due to the actions of compounds that produce cannabinoid-like effects on blood pressure and inflammation, yet do not activate either CB1 or CB2 receptors.
- Anandamide is a neurotransmitter derived from arachidonic acid, a long-chain omega 6 essential fatty acid.
- The name Ananda, comes from the Sanskrit word for “happiness, pleasure, joy, and delight.”
- The first endo-cannabinoid to be discovered
- It is one of the most important endocannabinoids, that binds to CB1 receptors in the brain and elsewhere throughout the body.
- After the discovery of Anandamide in 1992, scientists searching for cannabinoid receptors found that the human body is brimming with them
- Its discovery traces back to the detection of receptors for THC (tetrahydrocannabinol) in 1988, the main psychoactive component in marijuana (Cannabis sativa).
- THC receptors were first found in rat brains and later were found in humans.
- Initially, scientists were puzzled as to why there were THC receptors in the brain.
- The reason for their existence remained a mystery until the discovery of Anandamide and the realization that it binds to these cannabinoid receptors producing many behavioural effects similar to those of THC
- Is tonically / continuously active during development.
- Seems to be a growth factor during development and a stress-responsive modulator during adult life.
- Research indicates that inhibiting the enzyme (FAAH) that breaks down Anandamide, may be a useful strategy for treating cognitive dysfunction, drug addiction, anxiety disorders, and traumatic stress.
- Agonist / stimulator of the CB1 receptors, the same receptors that the psychoactive compound THC in cannabis acts on.
- Anandamide does not create euphoria like THC as Anandamide is broken-down immediately after it activates the receptor ie. not around long enough to create the ‘high’
- THC binds more strongly to receptor and is first broken-down in the liver by another enzyme
- Anandamide also activates TRPV1 a non-cannabinoid receptor
- Besides residing in several regions of the brain, cannabinoid receptors are widespread throughout the body occurring in
- the central nervous system
- white blood cells
- reproductive organs
- the gut
- the urinary tracts
- Because these cannabinoid receptors are located in so many places, the effects of Anandamide are widespread.
- Anandamide plays a role in
- Pain relief
- May protect against stroke and neuroinflammation
- Encourages the formation of new brain cells
- Interferes with the formation of memories in young people
- Later in life it protects against age-related cognitive decline by reducing brain inflammation
- There’s also evidence that anandamide can inhibit the production of cancerous cells
- helps keep the brain and body in a state of balance, called homeostasis.
May be a root cause of many conditions, including
- Multiple sclerosis
- Irritable bowel syndrome
- Increase fear and anxiety levels
- Decrease the ability to cope with stress
The Happiness Gene
- Researchers have found a direct correlation between the presence of a gene variant (rs324420) that affects anandamide levels and the level of happiness.
- This gene variant decreases the FAAH enzyme thus keeping levels of anandamide high.
- Areas of the world with high instances of this gene include:
- Western Africa
- Northern Latin America
- Northern Europe.
- Areas with low levels instances of this gene include:
- Areas of the Middle East
- Eastern Asia.
Anandamide in Food
- contains anandamide and may even cause the brain to produce more
- Temporarily improve mood when eating chocolate.
- Most anandamide in the least adulterated chocolate aka cocoa powder or cacao nibs, which are used to create chocolate, which are significantly less processed, contain no sugar, and are a more concentrated source of all of chocolate’s beneficial compounds, such as
- Tuber melanosporum which are mushrooms native to Spain, France, and Italy that grow in forests under oaks and other deciduous trees.
- Truffle-hunting pigs and dogs have anandamide receptors which may explain why they seek out truffles with great enthusiasm.
- Truffles are among the most expensive culinary delicacies in the world running at $20 per ounce, but are a bargain compared to white truffles which cost ten times as much at a jaw-dropping $211 per ounce.
- contain the compound guineensine that increases Anandamide activity.
- A flavonoid inhibits the production of FAAH, the enzyme that breaks down anandamide.
- Foods containing kaempferol include apples, blackberries, grapes, peaches, raspberries, broccoli, Brussel sprouts, cucumbers, endives, green beans, potatoes, spinach, squash, tomatoes and green tea
Foods Containing the Essential Fatty Acid Omega 6 – Arachidonic acid, which Anandamide is made from
Arachidonic acid can also be synthesized from Linoleic acid
- Found in substantial amounts in many popular vegetable oils including safflower, sunflower, and canola, which are oxidised and highly pro-inflammatory and not recommended.
- Olive oil contains ample levels of linoleic acid – make sure it’s cold pressed
- a naturally occurring compound in the body enhances anandamide activity
- produced by the body to combat inflammation.
- also called the “love drug” because it mimics the brain chemistry of being in love.
- isolated from soybean lecithin, egg yolk, and peanut meal to create supplements.
- is considered very safe and has no known serious side effects or drug interactions.
Cannabis sativa – Marijuana plant
- contains over 110 bioactive compounds
- one present in particular abundance is cannabidiol or CBD.
- CBD is not psychoactive and can be purchased as a nutritional supplement.
- does not bind to cannabinoid receptors and will not get you high.
- works in part by inhibiting the action of the FAAH enzyme, resulting in a net increase in anandamide.
- contains cacao powder and a few herbs, but NO Anandamide (not recommended).
Anandamide boosting Activities
Get In “The Zone”
- a state of heightened focus and peak performance is called being in “the zone.”
- Whenever you’re in “the zone,” your brain is flooded with anandamide and other feel-good brain chemicals like serotonin, dopamine, norepinephrine, and endorphins.
- For a regular anandamide surge, find a healthy activity that puts you in the zone and do it frequently.
- The runners high, usually attributed to an increase in pain-killing endorphins but evidence suggest that endocannabinoids, including anandamide, are more likely the brain chemicals behind runner’s high.
- One reason for this change in theory is the discovery that endorphins are too large to cross into the brain, but anandamide is not.
- Exercise works on the endocannabinoid system in two ways.
- It increases blood levels of anandamide and improves the sensitivity of anandamide receptors.
- a neurochemical that acts as a hormone and neurotransmitter.
- stimulates the production of anandamide
- increase Oxytocin by
- physical touch — hugs, cuddles, massage, stroking a pet, or making love.
- Physical therapies – massage chiropractic, one study found that Anandamide levels increased by 168% after a manipulation
- yoga, meditation, listening to relaxing music.
2-AG / 2-Arachidonoyl-glycerol 101
- A fatty acid neurotransmitter or known as a signalling lipid in the CNS – central nervous system
- Agonist / activator of the CB1 and CB2 receptors
- A key regulator of neurotransmitter release
- 170-fold more abundant in the brain than Anandamide
- Is more tonically (continuously) active in the adult CNS
- Seems to act more as a neuromodulator
- 2-AG, unlike Anandamide is present at relatively high levels in the central nervous system
- It has also been found in human milk
- Activation of the CB1 and CB2 receptors by 2-AG is associated with many physiological processes much like Anandamide, including
– Food intake
– Learning and memory
– Pain sensation
– Stress and anxiety
- Was first discovered in 1995
- Is synthesized “on demand”
- Acts as a retrograde messenger that inhibits the release of excitatory and inhibitory neurotransmitter
- 2-AG increases GABA-A receptor function at low GABA concentrations, which leads to inhibition of motility
- In addition to classical CB1 and 2 receptors, 2-AG can also affect other receptors, including GABA-A, adenosine A3, TRPV1, PPARγ and GPR55 receptors.
- Is a precursor for the biosynthesis of eicosanoids (fats) in the brain
- Its involvement in major physiological processes makes modulation of 2-AG levels an interesting therapeutic strategy, such as
– Reducing 2-AG levels can be beneficial for treatment of the metabolic syndrome, addiction, and neuro-inflammatory disorders
– Elevating 2-AG levels reduces neuro-inflammation, anxiety-related behaviour, withdrawal symptoms and nociception.
- BUT, due to 2-AG’s role in multiple physiological pathways can modulation increase.
- Increases the production of endocannabinoids in the sympathetic nervous system and liver
- Which stimulate CB1 receptors in the brain to elevate mood and reduce anxiety, and increase food consumption
- Increases the production of endocannabinoids in visceral adipose tissue aka tummy fat
- Which stimulate CB1 receptors in adipose tissue and liver that promote lipogenesis / fat storing and inhibit fat burning
- Increases the production of endocannabinoids in the gut
- Which stimulate CB1 receptors in adipose tissue, liver and gut that promote lipogenesis / fat storing, inhibit fat burning and decrease satiety signals
- Probably increases the production of endocannabinoids in muscle
- Which stimulate CB1 receptors in the brain elevating mood – ‘ the runners high’
- Probably increases the production of endocannabinoids in muscle, joints, skin and connective tissue
- Which stimulate CB1 receptors in the brain elevating mood, reducing pain, possibly stimulate CB2 receptors in the immune system decreasing inflammation
- Increases the production of endocannabinoids in leucocytes / white blood cells and the spleen
- Which stimulate CB2 receptors in the immune system that decrease pro-inflammatory cytokines / hormones and T-cell migration
- Increases the production of endocannabinoids in leucocytes / white blood cells and the spleen
- Which stimulate CB2 receptors in that immune system that decrease pro-inflammatory cytokines / hormones and T-cell migration
Time of day
- Mid-day is the time of peak production of all endocannabinoids
- Which stimulate both CB1 and CB2 receptors all over the body.
Know your Cannabis
- Cannabis refers to a group of three plants with psychoactive properties, known as
– Cannabis sativa
– Cannabis indica
– Cannabis ruderalis
- The flowers of these plants are harvested and dried to create one of the most common drugs in the world. Some call it weed, some call it pot, and others call it marijuana.
- Cannabis resin is a light to dark brown, sticky substance found on the trichomes / fine hairs on the flowers and leaves of a female cannabis plant.
- Resin is considered the most valuable part of the plant and delivers the majority of the psychoactive compound THC.
- Products containing resin are called concentrates.
- Live resin is a concentrate which is high in terpenes and other cannabis material. Terpenes are what give cannabis its full-bodied aroma.
- Cannabis is made up of more than 100 components, known as cannabinoids.
- It is still not sure what each cannabinoid does, but two of them are best known – cannabidiol aka CBD and tetra-hydro-cannabinol aka THC.
– a psychoactive cannabinoid, non-intoxicating and non-euphoric, meaning it won’t get you “high.” Is thought to be a major anti-convulsant
– the main psychoactive compound in cannabis is intoxicating and euphoric, responsible for the “high” associated with cannabis.
- CBC – Cannabi-chromene
– an anti-inflammatory which may contribute to the pain-killing effect of cannabis
- THCV – Tetra-hydro-cannabi-varin
– only found in small amounts is a cannabinoid receptor antagonist / blocker, which may help decrease food intake and regulate body-weight gain.
THC – Tetra-hydro-cannabinol 101
- The main psychoactive compound in Cannabis
- Binds to the same receptors as the endo-cannabinoid Anandamide.
- Was first discovered in 1964.
- Fresh cannabis contains tetra-hydro-cannabinolic acid (THCA), which converts into THC after heating
- THC is metabolized in the liver by cytochrome P450-2C enzymes to 11-hydroxy-THC and 11-nor-9-carboxy-THC and mainly excreted into urine.
- When smoked, THC is absorbed into the bloodstream via the lungs quickly traveling to the brain, attaching itself to the CB1 receptors located in the cerebral cortex, cerebellum, and basal ganglia, parts of the brain responsible for thinking, memory, pleasure, coordination and movement
- When ingested THC is absorbed through the gut, slowly reaching the cells of the body and brain via the liver
- Some people are less inclined to enjoy or get an effect from cannabis possibly due to low levels of the enzyme FAAH.
- FAAH breaks down the endo-cannabinoid Anandamide which also attaches to the same CB1 receptors.
Approx. 20% of the population has a gene variation leading to less FAAH, ie. more Anandamide using the receptors
These people tend to be less anxious in general
- Dronabinol, approved by the FDA as an appetite stimulant for people with AIDS and an antiemetic ( prevent vomiting) for people receiving chemotherapy
Available by prescription in the United States, Canada, Germany, and New Zealand
- As a specific extract of Cannabis as a mouth spray approved as a botanical drug in the United Kingdom in 2010 for people with multiple sclerosis to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms.
It’s the Dose Makes the Medicine
- One puff may be enough to produce noticeable memory improvement in seniors.
CBD – Cannabidiol 101
- Is a exo-cannabinoid discovered in 1940.
- One of 113 identified cannabinoids in cannabis plants, and accounts for up to 40% of the plant’s extract.
- As of 2019, clinical research on CBD included studies related to anxiety, cognition, movement disorders, and pain, but it is considered that there is’ insufficient high-quality evidence’ that cannabidiol is effective for these conditions, but with that said there is evidence and many enjoy the effects of CBD
- Cannabidiol can be smoked or vapor, ingested, such as CBD oil and as an aerosol spray into the cheek
- CBD does not have the same psycho-activity as THC and may change the effects of THC on the body if both are present.
- The mechanism of action for its biological effects has not yet been determined.
- CBD prevents the FAAH enzyme from breaking down Anandamide in the brain, allowing it to have more of an impact.
- Epidiokex a cannabidiol drug was approved by the Food and Drug Administration in 2018 for the treatment of two epilepsy disorders.
BUT the marketing and sale of CBD formulations for medical use or as an ingredient in dietary supplements or manufactured foods remains illegal under FDA regulation
Epidiokex is also available in Europe.
Testing for Cannabis
- Various drug test methodologies for the use of cannabis in medicine, sport, and law.
- Cannabis use is highly detectable and can be detected by urinalysis, hair analysis, as well as saliva tests for days or weeks.
- As cannabinoids are fat soluble compounds they easily store in fat, and have a longer elimination half-life
- Metabolites of cannabis are usually detectable in urine drug tests from 3 days up to 10 days
- Heavy users can even produce positive tests for 30 days or longer after ceasing cannabis use
- The lack of suitable tests and agreed-upon intoxication levels is an issue in the legality of cannabis, especially regarding intoxicated driving.
- The Duquenois-Levine test is commonly used as a screening test in the field, but it cannot definitively confirm the presence of cannabis, as a large range of substances have been shown to give false positives.
Detected in body fluids
THC and its 11-OH-THC and THC-COOH metabolites can be detected and quantified in
- Blood – detectable for approximately 12–24 hours, with heavy/frequent use detectable in the blood for up to 7 days
- Urine – detectable up to 3–5 days after exposure for infrequent users, 1–15 days for heavy users, and 1–30 days for chronic users and/or users with high body fat. The United Nations Office on Drugs and Crime (UNODC) recommend Fast Blue B and Fast Blue BB testing (the urine goes blue) instead of the Duquenois-Levine test.
- Hair – takes the most recent 1.5 inches of growth for testing, which provides a detection period of approximately 90 days.
- Saliva and oral fluids – detectable for 2–24 hours in most cases
Detection in breath
- Breath sampling as a non-invasive, easy method is still in development