HOLISTIC AYURVEDIC MEDICINE Medical cannabis, a potential panacea for holistic healing, is now backed by innumerable studies and research, reinforcing its therapeutic benefits. Therefore, the acceptance and consumption of medicinal cannabis in India are also progressing rapidly.

“The endocannabinoid system is very important. Almost all illnesses we have are linked to it in some way or another. And that is very strange.” – Dr. Raphael Mechoulam, known as “the father of cannabis research.”

The ECS is identified in early 1900s and is a collection of neuromodulators (endocannabinoids), their receptors and signaling pathways in our body. It is a self-regulating biological system in the human body.

Endocannabinoids are endogenously produced compounds that bind with specific receptors throughout our bodies, including the central nervous system, peripheral nervous system, and immune system. Our bodies consist of receptors that have an affinity to bind with cannabinoids like CBD (Cannabidiol), THC (Delta-9-tetrahydrocannabinol), CBN, CBC, CBG, etc.

When a patient takes exogenous cannabinoids, they interact with our already existing ECS. The fact is that these compounds are already a part of us, and although these cannabinoids are supplemented by plants, they are quite similar to the ones that exist in our bodies.

Cannabis works in two ways, one by maintaining the ECS tone and secondly by complementing if there is a deficiency. Low Cannabinoid tone indicates an imbalance. It is believed by Dr Ethan Russo that the root cause of most of all modern ailments, there is a clinical endocannabinoid deficiency (CEBD).

Cannabinoid receptors are the most abundant GPCRs distributed throughout the body. Other than cannabinoid receptors there are some no-cannabinoid receptors are also functioning in endocannabinoid system. CB1, CB2, TRVP1, TRVP2, GPR18, GPR55 and GPR119 are considered as endocannabinoid receptors. CB1 and CB2 are the cannabinoid receptors. CB1 is known to be psychoactive, neuromodulatory, and a pain receptor found in the brain, fat, liver, skeletal, and muscular tissues. Whereas, CB2 is responsible for the anti-inflammatory functions located in cells that are responsible for immune function and may also be found in the CNS.

There is substantial evidence² that cannabinoid acts as adjuvant analgesic in management of all type of pain including chronic pain. The analgesic effect of cannabinoids especially THC mediate by induction of antinociception via supraspinal mechanisms and peripheral CB2 receptors³. The consequent events are inhibition of the release of neurotransmitters and neuropeptides from presynaptic nerve endings, modulation of postsynaptic neuron excitability, activation of descending inhibitory pain pathways, and reduction of neural inflammation.

Neuropathic pain is a type of chronic pain resulting from peripheral nerve injury, toxic insults, and disease states such as diabetes, cancer, HIV, nerve disorder, MS and herpes infection. More recently, CBD is shown to be effective in well-established experimental models of neuropathic pain. It is believed that the analgesic effect of CBD is mediated, at least in part, by TRPV1 receptor⁴. CBD binds to non-cannabinoid receptor TRPV1 receptor and prolonged activation of TRPV1 receptor desensitize and inhibits activation of other intermediary molecules of signaling pathway and thus alleviates pain.

FM is a pain syndrome with multiple etiologies, central sensitization, altered stress response, pro-inflammatory state, abnormal activity of neurotransmitters, small-fiber peripheral neuropathy, and genetic predisposition. Research⁵ suggests that cannabis can reduce these symptoms in different ways with its anti-epileptic, analgesic, anxiolytic, and sedative effects.

The ability of Cannabis to promote eating has been already documented in ayurveda. Cannabis has potent anti-inflammatory, antiemetic, appetite-stimulating, and antidiarrheal effects.

The ECS regulates energy intake and appetite through central and peripheral metabolic pathways. ECS affects homeostatic pathways in the hypothalamus and brainstem through supression of leptin hormone and release of ghrelin hormone. The CNS also affects energy intake occurs through behavior–reward pathways. Cannabinoids through the ECS inhibit GABAergic neurons, leading to disinhibition of dopamine and activation of the hedonic drive toward further food consumption. Researchers¹² have also found that cannabis intake can stimulate appetite.

In additional tot that ECS is also took a major role in maintaining gastrointestinal homeostasis, thus helps manage liver and pancreatic disorders, insulin secretion etc.

Cannabis has also been used to treat abdominal pain, anorexia, Crohn’s disease, ulcerative colitis, emesis, gastroenteritis, diarrhea, intestinal inflammation, and diabetic gastroparesis. A recent survey¹³ supports the traditional view that cannabis provides benefits in disturbances of the gastrointestinal tract.

Cannabis affects the release of cortisol and acts as a sedative. Patients treated with CBD had a prompt and substantial reduction in the frequency of RBD-related events without side effects, as suggested by research¹⁴.

Studies¹⁵ suggest that cannabis exerts a tissue-sparing effect during chronic myocardial ischemia and acute reperfusion (I/R).

Myocardial ischemia occurs when blood flow to the heart muscle (myocardium) is obstructed by a partial or complete blockage of coronary arteries by the build-up of plaques (atherosclerosis). CBD acts as a cardioprotective drug.

Cannabis has been demonstrated to be effective in alleviating impaired bladder control, muscle spasms, and spasticity. Studies¹⁶ found that cannabinoids such as THC bind with cannabinoid receptors of the human body to reduce the levels of inflammatory proteins and suppress the spasm response. Different THC/CBD combination therapies decrease muscle spasticity and suppress neuroinflammation.

Most common respiratory disorders are chronic obstructive pulmonary disease (COPD), asthma, acute lower respiratory tract infections, tuberculosis, and lung cancer. It has been found that cannabinoid receptors, specifically CB1 receptors are abundantly found in bronchi, pulmonary artery, lung tissues such as alveolar type II cells, respiratory epithelium, fibroblast, dendritic cell and pulmonary macrophages. Overstimulation of peripheral CB1 receptors is linked to several pathological processes such as fibrosis (lung, liver, heart, kidney, and skin), inflammation, oxidative/nitrosative stress. Likewise, activation of peripheral CB2 receptors produces anti-inflammatory, immunosuppressive, and anti-fibrotic effects.

Cannabidiol (CBD) and D9-tetrahydrocannabivarin (THCV) are non-intoxicating phyto-cannabinoids affecting lipid and glucose metabolism. Studies¹⁷ suggest that THCV and CBD decreased blood glucose levels and increased insulin production in people with type 2 diabetes.

Coronavirus impacts the respiratory system much deeper and causes coagulation. Cannabis has anti-inflammatory properties and can act as a vasorelaxant. Clinical trials¹⁸suggest that whole-plant cannabis extracts high in CBD can reduce blood coagulation and can be used to counter SARS-CoV-2 infections by quelling the cytokine storm. In addition to the above-mentioned diseases, cannabis medicines have also been proven effective for diseases like seizures, wasting syndrome (cachexia), mood disorders, such as ADD or ADHD, allergies, immunity, psoriasis, autism, Tourette’s, PTSD disorders, and migraine.

Since 1970, cannabis has been known to exert palliative effects in cancer patients. Along with its palliative effects, it has antiproliferative, antitumoral, and pro-apoptotic effects that inhibit cancer cell migration, adhesion, and invasion. Studies suggest¹⁹ that cannabinoids inhibit tumor progression at multiple levels. Their most prevalent antitumor effect is the induction of cancer cell death by apoptosis and the inhibition of cancer cell proliferation. Additionally, Cannabinoids has been shown to impair tumor angiogenesis and block invasion and metastasis.

Studies²⁰ also found the co-administration of cannabis medicines with chemotherapy drugs improved the potency of its antitumor effects. These synergistic effects can prove beneficial, especially in cancers that are refractory to chemotherapy. However, these effects depend on the cancer type, dosage of medicine, and abundance of receptor targets.

Growing evidence²¹ demonstrates cannabinoids are effective inhibitors of multiple types of cancer.

Chemotherapy-induced nausea and vomiting (CINV) remains significant cause of morbidity in oncology patients. The mechanism of delayed nausea and vomiting is incompletely understood, but may involve non-serotonergic receptors including the cannabinoid CB1 receptor, with a potential role for cannabis products in its amelioration.

Cannabinoids exert their anti-emetic properties through interactions with the centrally located CB1 receptors and 5-HT3 receptors in the dorsal vagal complex (DVC), which mediates emesis. The activation of the 5-HT1A receptor ultimately reduces the amount of serotonin released, and thus a lower potential to trigger emesis. CBD is also thought to activate the CB1 receptors in the gastrointestinal tract through their GPCR (G-protein-coupled receptor) inhibitory effect, leading to decreased gastrointestinal motility. Phyto-cannabinoids such as THC and CBD also inhibit fatty acid amide hydrolase (FAAH), leading to an increased concentration of anandamide that could exert its anti-emetic properties at a higher intensity.

Cannabis has the potential of becoming a useful treatment for glaucoma, as they seem to have neuroprotective properties and effectively reduce intraocular pressure. Cannabinoid receptors are found in the trabecular meshwork, non-pigmented ciliary epithelium, and ciliary muscle of human eyes.

Research²² suggests that Cannabis with THC can lower IOP in 60% to 65% of both normal individuals and patients with glaucoma. Intraocular pressure (IOP) is the fluid pressure inside the eye, which is an important aspect in the evaluation of patients at risk of glaucoma.

Medical cannabis products available in India are in capsule, oil and gummy dose form. So it can be consumed orally. Best practice of taking oil is to keep for sometimes under the tongue for a better absorption.

Dosage is the vital factor to reap maximum benefits with minimal side effects of cannabis medicines. HempCann Solutions, the parent company of brand Vedi, invests a lot in researching cannabis and improving awareness around it to make it a more safe, versatile, and effective drug.

It is advisable to start with a low dose, as body’s tolerance to dose varies with person to person, and there are other factors involved too, such as the state of disease, age, etc. It is best to follow a physician’s advice to find the correct dose and treatment protocol.

Cannabis medicines are likely safe and can be taken with most drugs. However, it is best to consult your doctor before starting and sharing the list of all medications to learn more about drug interactions.

Cannabis can accelerate or inhibit the effects of other drugs, especially the ones that cause drowsiness, including antidepressants, antihistamines, sedatives, seizure medicines, pain relievers, anxiety medicines, muscle relaxants, and alcohol.

The risk/benefit ratio of cannabis should be carefully and individually evaluated, especially for people who:

• Are under 18
• Have hypersensitivity to any cannabinoid
• Have severe cardio-pulmonary disease with hypotension/ hypertension/ syncope or tachycardia
• Have a family history of schizophrenia
• Have severe respiratory diseases such as chronic obstructive pulmonary disease (COPD)
• Women who are planning pregnancy, or are pregnant, or breastfeeding.