MEDICAL CANNABIS
In this module, we will comprehensively explore the topic of medical cannabis, examining its potential applications in various medical conditions. We will analyze the available evidence supporting its use, as well as examine the current status of medical cannabis across different countries and regions around the world.
Cannabis has potential to be used as a medicine because it interacts with the endocannabinoid system, which plays a role in various bodily functions such as pain relief, immune system regulation, appetite, cognitive processes, and motor control. The biological plausibility of cannabis as medicine is based on this interaction.
In 2737 BC, Chinese Emperor Shen-Nung was the first to describe the medicinal value of cannabis.
In modern times, the discovery of the therapeutic potential of cannabis can be attributed to the discovery of the endocannabinoid system (ECS) in the 1990s.
The ECS is a complex system of neurotransmitters and receptors that regulate various physiological processes, including pain, appetite, mood, and immune function. It was discovered that the cannabinoids found in the cannabis plant can interact with the ECS to produce a variety of effects.
As a result of these discoveries, research into the medical properties of cannabis has increased, leading to the development of cannabis-based medicines such as Dronabinol, Nabilone, Nabiximols, and Epidiolex.
These medications have been shown to be effective in treating a variety of medical conditions and symptoms, including chronic pain, nausea and vomiting associated with chemotherapy, muscle spasticity associated with multiple sclerosis, and seizures associated with certain forms of epilepsy.
NABILONE | - Nabilone is a synthetic cannabinoid that is structurally similar to delta-9-tetrahydrocannabinol (THC), acts on the endocannabinoid system in the body, which includes the CB1 and CB2 receptors.
- It is metabolized in the liver and converted into its active metabolite, which binds to CB1 receptors in the brain and other parts of the body.
- It is marketed under the brand name Cesamet and is used to treat nausea and vomiting caused by chemotherapy, as well as neuropathic pain.
- Nabilone is typically administered orally and is available in capsule form. Its effects can take up to 1-2 hours to onset and can last for several hours.
- Dosage- 1-6 mg/day, varies as per patient’s condition.
- Common side effects of dronabinol include dizziness, drowsiness, headache, dry mouth, nausea, vomiting, and abdominal pain.
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DRONABINOL | - Property is similar to Nabilone
- When dronabinol is ingested, it is metabolized in the liver and converted into its active metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC), which binds to CB1 receptors in the brain and other parts of the body.
- This activation of the CB1 receptors results in various effects, including pain relief, appetite stimulation, and relaxation.
- It is marketed under the brand name Marinol and is used to treat nausea and vomiting caused by chemotherapy, as well as appetite loss and weight loss in people with HIV/AIDS.
- Dronabinol is typically administered orally and is available in capsule form.
- Its effects can take up to 1-2 hours to onset and can last for several hours.
- Dosage- 5-20 mg/day, varies as per patient’s condition.
- Similar side effects as Nabilone.
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NABIXIMOLS | - Nabiximols is a medication that contains a combination of two cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
- THC is the primary psychoactive component of cannabis, while CBD is a non-psychoactive component that may have potential therapeutic effects.
- It is administered orally as an oral-mucosal spray and acts on the endocannabinoid system in the body.
- Nabiximols has multiple potential effects on the body, including pain relief, muscle relaxation, and reduction of spasticity.
- The effects of nabiximols can start within minutes and can last for several hours.
- The usual starting dose for nabiximols is one spray into the mouth, either onto the inside of the cheek or under the tongue, up to a maximum of 12 sprays per day.
- Dosage- 10-120 mg/day in divided dosages.
- The drug is legally available in Canada and most of Europe and is undergoing phase III clinical trials in the United States.
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EPIDIOLEX | Epidiolex (cannabidiol) is a medication that is derived from the cannabis plant and is approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures associated with two rare forms of epilepsy: Lennox-Gastaut syndrome and Dravet syndrome. The pharmacology of Epidiolex involves its effects on the endocannabinoid system, which plays a role in regulating the central nervous system. Specifically, Epidiolex acts as a partial agonist at the CB1 and CB2 receptors in the brain, which are part of the endocannabinoid system. For the treatment of Lennox-Gastaut syndrome and Dravet syndrome, the starting dose is usually 2.5 mg/kg twice daily, with gradual increases to a maintenance dose of 10 mg/kg twice daily over a period of several weeks. The most common side effects include sleepiness, decreased appetite, diarrhea, and elevated liver enzymes. More serious side effects, such as suicidal thoughts and behavior, have also been reported in a small number of patients. |
- The issue of cannabis as medicine is not only a scientific question but also, a matter of public policy.
- It is important to weigh the risks versus benefits of cannabis use, especially in children.
- Until we have more robust evidence supporting the benefits of medicinal cannabis, it will be difficult and challenging to recommend its use for any day-to-day therapeutic benefit.
| USE IN SPECIFIC MEDICAL CONDITION | CURRENT EVIDENCE |
1. | Nausea and vomiting in chemotherapy | The systematic review by Lesley A. Smith et al, 2015 found that people had: more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I2 = 0%; very low-quality evidence) less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). Cannabis‐based medications may be useful for treating refractory chemotherapy‐induced nausea and vomiting. |
2. | AIDS – Cachexia | Dronabinol has been registered for the treatment of AIDS-associated anorexia in some countries. However, the evidence for positive effects in patients with HIV/AIDS is limited, and some of that which exists may be subject to the effects of bias. Those studies that have been performed have included small numbers of participants and have focused on short-term effects. Longer-term data, and data showing a benefit in terms of survival, are lacking (Lutgee AT, 2013) |
3. | Multiple sclerosis | Compared with placebo, nabiximols probably reduce the severity of spasticity in the short term in people with MS. Cannabinoids may increase treatment discontinuation slightly due to AEs, nervous system and psychiatric disorders compared with placebo. The overall certainty of evidence is limited by short-term duration of the included studies (Filippini G, 2022) |
4. | Chronic neuropathic pain | The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/ oromucosal routes than by inhalation. |
5. | Fibromyalgia | Nabilone did not convincingly relieve fibromyalgia symptoms (pain, sleep, fatigue) better than placebo or amitriptyline (very low-quality evidence). Compared with placebo and amitriptyline, more people experienced side effects and left the study due to side effects (very low-quality evidence). No serious side effects were reported (Brian Walitt, 2016). |
ADVERSE EFFECTS OF CANNABIS
- The most commonly reported AEs were fr the central nervous system (CNS) and the gastro-intestinal system (GI).
- Other AEs were divided into groups by psychological, musculoskeletal, cardiac, vision, and hearing AEs.
SIDE- EFFECTS | |
Central nervous system (CNS) | Most common- Dizziness, drowsiness Ataxia, confusion, disassociation, disconnected thought, disorientation, disturbance in attention, dreaminess etc. |
Gastro-intestinal system (GI) | Most common- Nausea, Vomiting Abdominal discomfort, abdominal pain, anorexia, bad taste, constipation, decreased appetite, loss of appetite, increased appetite, diarrhoea, dry mouth, dyspepsia, epigastric distress, gastric acid, glossodynia. |
Psychological | Depressed mood/ euphoria/ dysphoria, disinterest in surroundings, dissociation, feeling high, feeling abnormal, fidgety fingers, foggy mental state, forgetfulness, hallucinations e.t.c |
Musculoskeletal | arthritic pain, contracted jaw muscles, decreased motor skill, distortion of wrist, left back shoulder bruise, limb heaviness, limb weakness etc. |
Cardiac | Abnormal heart rate, cardiac disorders, hypotension, orthostatic hypotension, palpitations, and tachycardia. |
Vision, and hearing | Blurred vision, diplopia, and change in vision; tinnitus, loud noise, ringing in the ears, vertigo, and ear buzzing |
- Physician should consider CBMs treatment after a complete discussion about the possible AEs that can appear.
- Additionally, due to the high rates of CNS-related AEs, specifically dizziness, drowsiness, and cannabinoid-related vision impairments, the patient needs to be warned not to drive a vehicle or operate heavy machinery
STATUS IN WORLD
- The status of medical cannabis varies widely around the world. While some countries have legalized medical cannabis and established regulations for its use, others have strict laws prohibiting its use, possession, and cultivation.
In some countries, such as the United Kingdom, medical cannabis is legal, but access to it is limited and heavily regulated.
The World Health Organization (WHO) has recognized the potential therapeutic benefits of cannabis and its components, such as cannabidiol (CBD) and tetrahydrocannabinol (THC), and has recommended that cannabis and its components be removed from Schedule IV of the Single Convention on Narcotic Drugs. The WHO has also recommended that countries consider rescheduling cannabis and its derivatives to make them more accessible for medical and scientific purposes.
Overall, the status of medical cannabis around the world is evolving, with more countries considering legalization or expanding access to medical cannabis for patients in need. However, the regulatory landscape remains complex and varies widely between countries.
STATUS IN INDIA
The use of cannabis for medical purposes is highly restricted and controversial in India. Cannabis is listed as a Schedule I substance under the Narcotic Drugs and Psychotropic Substances (NDPS) Act, 1985, which means that it is classified as a substance with a high potential for abuse and no recognized medical use.
Under the provisions of the Narcotics Drugs and Psychotropic Substances Act 1985, a person possessing a small amount of marijuana (1kg) will be imprisoned for six months or have to pay a fine of Rs 10,000. Punishment for commercial quantity– Rigorous imprisonment from 10 years (min) to 20 years (max) and a fine from Rs 1 lakh to 2 lakhs. Punishment for quantity greater than small but lesser than commercial (Intermediate)- Rigorous imprisonment that may extend to 10 years & fine that may extend to Rs 1 lakh.
At the same time, the use of bhang which is a liquid form of cannabis is excluded from Section 2 (iii) of the said act.
Section 10 of the NDPS Act empowers the State Governments to permit and regulate possession and inter-state movement of opium, poppy straw, the manufacture of medicinal opium and the cultivation of cannabis.
In 2020, the Central Drugs Standard Control Organization (CDSCO) approved two cannabis-based medicines, namely, Sativex and Epidiolex, for the treatment of spasticity and seizures associated with certain conditions, respectively. These medicines are available only through prescription from authorized medical practitioners and are subject to strict regulations.
It is important to note that the use of cannabis and cannabis-based medicines in India is still highly restricted and controversial, and patients who require such medicines for medical purposes are advised to consult with their doctors and seek legal advice before using them.
NOTE– American society of addiction medicine (ASAM) recommends that physicians should assess the patients, in which they recommend medical marijuana for potential problems, such as pre-existing addiction to marijuana, addiction to other substances like opioids, and signs of substance use disorder related to marijuana.
It is also important to consider whether marijuana use is negatively impacting the patient’s life.
The use of cannabis as medicine is not only a scientific question, but also a policy issue that requires careful consideration.
Please take notes and you can refer later
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