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"Cannabis is the single most versatile herbal remedy, and the most useful plant on earth. No other single plant contains a wide range of active herbal constituents"

       - Dr. Ethan Russo, Cannabinoid Research Institute

Getting started

Cannabis is an annual flowering herb-plant that can grow up to a height of 13 feet. It belongs to the family Cannabaceae and has two main species, namely Cannabis Sativa and Cannabis Indica. Another type of Cannabis plant; the Hemp is grown industrially using a special cannabis variety which has all the active components but has very low <0.3% Tetrahydrocannabinol (THC) the psychoactive component of the cannabis plant.

The history of use of medical cannabis is very ancient and can be traced back to South-East Asia. Indian Mythology talks about Lord Shiva whose nectar (elixir) is cannabis. Even today, it is a religious tradition in India to consume Bhaang (cannabis leaves) on Holi (onset of spring). In ayurvedic texts, it is said that cannabis (vijaya) extract has the ability to balance all the three “Doshas” (Vatta, pitta and Kapha).

 

The oldest written description of medical cannabis can be dated back to 2350 BC on a stone from the Pyramids Texts from the Old Kingdom in memphis, Egypt. In China, emperor Shen-Nung allegedly prescribed this for treating ailments in the 28th century BC.

It has been used in the past to treat a range of ailments including mood disorders, seizures, muscle spasms, chronic pain etc.

The advancement in science and technology has allowed us to better elucidate the function of these cannabis derivatives as pharmacological options in several conditions, such as pain treatment, skin pathologies, anticonvulsant therapy, neurodegenerative and infectious diseases. This potential has been a revolutionary factor worldwide concerning the production, use and sale of cannabis, and has even led to legislative changes in some countries.

Reference:

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology. Physiol Rev. 2016 Oct;96(4):1593-659. doi: 10.1152/physrev.00002.2016.

https://www.institut-icanna.com/en/blog/23/Cannabis-from-the-perspective-of-Indian-Traditional-Medicine-Ayurveda

 

Robert Svoboda: "Ayurveda, Life, Health, and Longevity"

History of Cannabis

It is an entire science of treatment based on our Endocannabinoid system (ECS). ECS is one of the most conserved systems through evolution and can be seen even in the lowest life forms. All vertebrates and invertebrates have been shown to have functional ECS. ECS plays a crucial role even before our birth. It is required for the implantation and embryo development and the programming of neural cells and development of the brain.

ECS is a response system. It responds to various internal and external stimuli. For example, when we are faced with danger, our body releases adrenaline which initiates a cascade of changes in the body which enables us to face this danger. Similarly, in response to internal/ external stimuli, the body generates its own endocannabinoids to bring out functional changes. One of the major areas where ECS functions is stress response.

 

Our body produces certain molecules called as Endocannabinoids (EC) that fir into certain designated receptors (like a lock and key mechanism) to trigger a desired response. These receptors are called as Cannabinoid receptors (CB). These are two types of these receptors can CB-1 and CB-2.

 

The two main endocannabinoids that we produce are 2-AG and Anandamide which act on CB-1 and CB-2 receptors. Cannabinoids from cannabis also act on these receptors thus modifying the tone of the ECS.

Location of CB1 receptors:

It is highly expressed in the brain (especially cortex, substantia niagra, hippocampus, cerebellum and brain stem). It modulates various brain functions like motor activity, mood, learning, appetite, pain perception and memory.

 

Location of CB2 receptors:

Mainly on inflammatory (white blood) cells and so activation of CB2 receptors can cause reduction in inflammatory response (Anti-inflammatory action). It is also present in the gut, kidneys, pancreas, adipose tissue (fat tissue), skeletal muscle, bone, eye, tumours, reproductive system, immune system, respiratory tract, skin, cardio-vascular system and liver.

Effects of ECS in our body

“Modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans.” Kunos and Pacher of NIH.

 

ECS is responsible for the homeostasis or fine-tuning of all bodily functions. It is the master system which regulates all other systems in the body. Importantly, it regulates energy balance and food intake.

Clinical Endocannabinoid deficiency (CED)

This theory was first published in 2001 and has gained momentum since then. Medically, we have identified diseases which occur due to deficiencies in certain neurotransmitters. For example Parkinson’s is dopamine deficiency or Acetylcholine deficiendcy in Alzheimer’s etc.

Migraines, fibromyalgia and IBS are one of the greatest candidates for CED because their diagnosis is usually based on exclusion of all other diagnoses and cannot be physiologically explained by any other body system. They also display an elevated level of anxiety or can be labelled as being “psychosomatic”.

An extensive list of other disorders previously cited that may fall under the CED rubric included

  • neonatal failure to thrive

  • cystic fibrosis,

  • causalgia,

  • brachial plexopathy,

  • phantom limb pain,

  • infantile colic,

  • glaucoma,

  • dysmenorrhea

  • hyperemesis gravidarum,

  • post-traumatic stress disorder (PTSD),

  • bipolar disease,

  • unexplained fetal wastage (repetitive miscarriages),

ECS modulation and thereby Cannabis can be useful in the above conditions

 

References:

Stress Regulates Endocannabinoid-CB1 Receptor Signaling. Cecilia J. Hillard. Semin Immunol. 2014 Oct; 26(5): 380–388. Published online 2014 May 29. doi: 10.1016/j.smim.2014.04.001

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology. Physiol Rev. 2016 Oct;96(4):1593-659. doi: 10.1152/physrev.00002.2016.

https://www.youtube.com/watch?v=8GsmTFytBYI&t=907s

Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Ethan B Russo. Cannabis and Cannabinoid Research. Volume 1.1, 2016    DOI: 10.1089/can.2016.0009.

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Cannabinoid medicine and ECS (Endo-cannabinoid system)

Cnnaboid medicine

How to Stimulate the ECS naturally ???

Even without cannabis, it is possible to naturally stimulate the body to generate its own cannabinoids where by balance can be restored.

 

1. Essential fatty acids

Fats (Arachidonic acid) form the basic molecule from which endocannabinoids are made. Lack of EFA in the diet can lead to lowered tone of ECS and cause many vague symptoms. EFA can come from

seed oils (hemp seed, chia seeds, flax seeds),

ghee (clarified butter),

Fatty fish (salmon, sardine, anchovies),

Eggs,

Nuts (walnuts, almonds, groundnuts)

Bone broth

 

2. Cocoa powder

Studies have shown that Cocoa has 3 different molecules (phytocannabinoids) which act on endocannabinoid receptors. Darker the chocolate, more concentration of phytocannabinoids in them.

3. Stress reduction

Chronic stress has been shown to downregulate CB1 receptors in the brain there by reducing the ECs tone in the body. Hence, stress reduction methods have shown to improve the ECS

  • Exercises

  • Lifestyle change (changing stressful job, toxic home or work enviroment)

  • Massage or Osteopathic manupulation

  • Hugging and physical touch

  • Breathing exercises

  • Dancing and singing. Interestingly, even hearing to someone sing can release ECs in the body. Hence, these recreational activities become extremely essential to maintain the health of the ECS.

4. No Alcohol

Alcohol has been shown to depress the ECS and also reduce the CB1 receptor density in the brain. Reducing drinking or even stopping in altogether can definitely help is improving the ECS.

 

5. Probiotics

Probiotics are beneficial bacteria that help rebalance the gut microbiome and also have an effect of CB2 expression in the intestines. Fermented foods such as kimchi, sauerkraut, yogurt also do the same. Lactobacillus acidophilus and bifidobacterium strain specifically are highly beneficial.

 

6. Avoiding endocrine disruptors

Plastics (especially containing phthalates) and  pesticides (such as DDT, chlorpyrifos and diazinon) are known to disrupt the ECS by having an antagonistic effect on CB1 receptors.

7. Herbs

 

Some herbs are known to elevate ECs levels by various mechanisms. Some directly stimulate the CB1 receptor, some increase the EC production and some reduce the breakdown of the already produced ECs in the brain. Besides cannabis, some common herbs which can help stimulate the ECS are black pepper, curcumin (haldi), Boswellia, Artemisia etc.

Caryophyllene is a “terpene,” which is another term for an aromatic compound. This unique terpene is prevalent in herbs and spices such as cloves, rosemary, basil, oregano, black pepper, and cannabis! It’s actually the only known terpene to stimulate endocannabinoid receptors by binding to them. The properties of caryophyllene are found to be neuroprotective, preventing stress and anxiety. Perhaps this explains the urban legend that chewing on a black peppercorn can help alleviate the paranoia and anxiety from consuming too much cannabis and getting too high… (paraphrase and put reference).

References:

https://www.leafly.com/news/health/how-to-stimulate-the-endocannabinoid-system-without-cannabis#_edn2

di Tomaso, Emmanuelle. “Brain cannabinoids in chocolate.” Nature 382 (1996): 677-678.

McPartland JM, Guy GW, Di Marzo V. Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System. Romanovsky AA, ed. PLoS ONE. 2014;9(3):e89566.

Certain specific chemical compounds found in the cannabis plant are called “Cannabinoids". The two main pharmacologically active cannabinoids are Cannabidiol (CBD) and Tetrahydrocannabinol (THC). The other compounds include Cannabigerol (CBG), CBC, CBGV, THCV, CBDV and THCV. These compounds are not directly produced by the plant, but as the plant is heated, they are formed as a result of decarboxylation. Except THC, none of the others have psychoactive properties (So they cannot get you high). Other than psychoactive effects, THC works as a potent pain-killer and hence has a crucial role to play in pain relief and various chronic ailments.

The cannabinoids obtained from plants are called as phytocannabinoids. They have similar structure to the ECs that we produce and hence they affect the CB receptors. The role of phytocannabinoids from cannabis are complex. THC is a agonist (stimulates positively) at the CB1 receptor. The functional role of CBD is much more complex and we are still identifying the various pathways though which it brings about homeostasis.

 

Apart from these 2 main pharmacologically active components, there are many more pharmacologically active components present in the cannabis plant. The number and concentration of the chemically active compounds found in the Cannabis plant varies with genotype, climate, type of soil, mode of preparation, as well as the different cultivation types. It can be cultivated in gardens and pots (natural or artificial light) or using hydroponic techniques. Below are some of the chemically active compounds that are found in the cannabis plant. They are individually well studied but their effect in synergy with the cannabinoids is something that is not talked about sufficiently enough.

 

Flavonoids:

These are not specific to cannabis but are abundantly found in the cannabis plant. Flavonoids are made up of groups of polyphenolic secondary metabolites with a wide range of functions.

Cannaflavin A:

Cannaflavin A is a pharmacologically active compound found in the cannabis plant.   There are studies that show that its anti-inflammatory properties might be stronger than those found in Aspirin. Cannaflavin B and C are still being studied for their medical effects. Other highly active flavonoids found in cannabis include Orientin, Quercetin, Silymarin, and Kaempferol, all with anti-inflammatory, anti-fungal, anti-microbial, antioxidant, and anti-cancer potential. Silymarin is also found in Milk-thistle and has liver protective properties.

 

Terpenes:

 

These are aromatic compounds that are commonly associated with cannabis as they are found in high concentrations in the cannabis plant. The characteristic scent and aroma of many plants are attributed to the presence of terpenes in them. It is the combination of various terpenes that gives the plants their unique fragrance. Some examples of such unique scents are rosemary, lavender, pine as well as fresh orange peel. The production of these secondary metabolites is nature’s way to attract pollinators, repel predators or protect the plants from infectious diseases or physical damage. The process of purification of the chemically active compounds from the cannabis plant is optimized to extract and exploit these compounds for bio-pharmaceutical purposes.

 

Scientists have discovered over 200 varieties of terpenes in cannabis alone. Of these, some which are most commonly found here in India are Limonene, beta-caryophylline, beta-myrcene and alpha-pinene.

 

Limonene, found in lemon peels, has been studied for its use in relieving anxiety, and activity against acne bacteria.

Beta-caryophyllene, found in black pepper and cinnamon, has been studied for its use as an antimalarial and for protecting stomach cells.

Beta-myrcene, also found in hops, has been studied for its use in relieving pain, relaxing muscles, and as a sedative.

Alpha-pinene, also found in pine trees, has been studied for its use as an anti-inflammatory and for opening up lung passages.

Role of cannabis in ECS

The effect these compounds have on our body is very famously coined as “The Entourage Effect”. This is a term given to the synergistic action produced by the various cannabinoids, flavonoids and terpenes in the body. This means that flavonoids and terpenes will affect or enhance the effect cannabinoids (mainly CBD and THC) have on our body. An example of this “entourage effect” was put together as a literature review in the Frontiers in Neurology. It describes an experimental study carried out on patients with epilepsy. These patients were divided into two groups and one group was treated with CBD rich extract while the other group was treated with pure isolated CBD. The results clearly indicated that patients treated with the CBD rich extract had improved symptoms and lesser side effects as compared to the pure CBD. This entourage effect is the deciding factor in treating patients with full spectrum oils rather than just pure isolates.

The Entourage effect

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