Cannabis sativa L., the most crucial source of phytocannabinoids, has been used as a herbal remedy for centuries. The endocannabinoid system (ECS) is made up of receptors, endogenous ligands (endocannabinoids), and metabolising enzymes and is involved in various physiological and pathological processes. Phytocannabinoids and synthetic cannabinoids can interact with components of the ECS or other cellular pathways, influencing disease development/progression, including cancer. Cannabinoids have primarily been used in cancer patients as part of palliative care to relieve pain, nausea and stimulate appetite. Medical Cannabis refers to the flowers or extracts of the flowers and preparations made from the ingredients of the female cannabis plant Cannabis sativa L. (hemp) that are intended for medical use. This hemp family (Cannabaceae) plant species is best known for its long-stemmed, finger-shaped split leaves, also used as intoxicants. Cannabinoids, which are found in hemp, are responsible for the pharmacological effects. Neurogenic spasticity, chemotherapy-induced nausea and vomiting, anorexia, and chronic pain are typical medical cannabis applications.
This hemp family (Cannabaceae) plant species is best known for its long-stemmed, finger-shaped split leaves, also used as intoxicants. Cannabis spread throughout the world as a plant cultivated for fibre production, originating in Central Asia. However, hemp as a crop is distinguished by a low content of psychoactive substances compared to hemp for medical purposes; Cannabis is also used colloquially to refer to the narcotic drugs derived from hemp. While marijuana (also known as Mary Jane, grass, or weed) is derived from dried leaves and flowers, hashish (also known as dope or shit) is derived from the resin of inflorescences. Different marijuana compounds have other effects on the human body. Delta-9-tetrahydrocannabinol (THC), for example, appears to cause the “high” experienced by marijuana users and can also help relieve nausea and pain, reduce inflammation, and act as an antioxidant. Cannabidiol (CBD) has been shown to help treat seizures, reduce anxiety and paranoia, and counteract the “high” caused by THC.
Ingredients and Quality requirements
Approximately 560 different substances have been identified in Cannabis sativa so far. Around 120 of these are cannabinoids, which are unique to this plant genus and are responsible for its pharmacological effects. Cannabinoids are a heterogeneous group of substances. They include phytocannabinoids and synthetic cannabinoids found in plants and endocannabinoids, which are messenger substances produced naturally in the body.Delta-9-tetrahydrocannabinol (THC) is the most psychoactive of the plant’s 100 or so cannabinoids, 21-carbon–containing terpene phenolic compounds. Several other cannabinoids are also thought to be medicinally beneficial. Cannabidiol (CBD), for example, is believed to be analgesic and anti-inflammatory while being non-psychoactive. The most critical phytocannabinoids are delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their inactive precursors delta-9-tetrahydrocannabinol acid (THC-A) and cannabidiolic acid (CBD-A). The concentration of cannabinoids varies depending on the plant drug (flowers or leaves) and the method of preparation. Most are found in essential oil, which is obtained by distilling flowers or resin.
This essential oil should not be confused with hemp oil, derived from cannabis seeds and does not contain significant amounts of cannabinoids as edible oil. Marijuana’s effects also differ depending on how marijuana compounds enter the body. Marijuana is most commonly used in food (edible marijuana) and by smoking or vaping it (inhaled marijuana): When marijuana is consumed orally, such as in drinks,cooking oils (beer, soda, vodka), baked goods (cookies, brownies,), and candy, the THC is poorly absorbed and can take hours to be interested. Once absorbed, the liver processes it, producing a second psychoactive compound (a substance that acts on the brain and changes mood or consciousness) that has a different effect on the brain than THC.. It’s critical to understand that THC amounts in marijuana-infused foods are frequently unknown, and consuming too much THC may result in overdose symptoms.THC enters the bloodstream and quickly travels to the brain when marijuana is smoked or vaporised. Because the second psychoactive compound is produced in small quantities, it has a minor effect. Marijuana inhaled has a shorter duration of action than marijuana taken orally.
Does the mode of administration (inhalation vs. oral consumption) make a difference?
When Cannabis is inhaled, whether as combusted or vaporised plant matter, the peak THC concentration occurs in 2 to 5 minutes, followed by a rapid drop-off. The kinetics of inhaled oils, such as those found in portable electric devices, may not yet be fully understood. The oral bioavailability is low and variable when taken orally, ranging from 5% to 20% of the ingested dose. In studies, the peak plasma concentration of THC taken orally reached 2.5 hours and declined much more slowly. Orally ingested THC has a terminal half-life of 25 to 30 hours, and when delta-9-THC passes through the liver, it is metabolised into a psychoactive 11-hydroxy-THC, which may be even more psychoactive than delta-9-THC.
Mechanism of action
The endocannabinoid system and its receptors mediate many of the effects of herbal and synthetic cannabinoids in the human body. So far, cannabinoid receptors refer to two types of cell membrane receptors: CB1 and C2. Both CBS are inhibitory G-protein-coupled receptors that inhibit adenylate cyclase, resulting in decreased intracellular second messenger substances. CB1 receptors are abundant in the cortex and hippocampus, as well as the basal ganglia and cerebellum. They are thus found in areas related to mental performance and motivation and movement coordination, spatial orientation, and sensory perception. CB1s protect the central nervous system through presynaptic inhibition by compensating for the over-or under-activity of many transmitter systems.CB2s are found on nearly all immune system cells and microglial cells in the central nervous system. They have a mild anti-inflammatory effect, modulating both acute and chronic inflammatory processes. Anandamides, which are arachidonic acid derivatives and are referred to as endocannabinoids, are natural ligands for both receptor types. Tetrahydrocannabinol is a cannabinoid receptor partial agonist at both cannabinoid receptors. Its psychotropic effects are primarily due to CB1 activation.
This applies to both therapeutically desirable effects on pain, nausea, and appetite, as well as motor function, and therapeutically undesirable effects such as dysphoria, hallucinations, reduced thinking and memory capacity, dizziness, and vegetative symptoms.CBD, in contrast to THC, only weakly binds to cannabinoid receptors. CBD, as an allosteric modulator of CB1, reduces THC binding and activation (25). CBD is thought to have anti-epileptic properties because it inhibits anandamide degradation by the fatty acid amide hydrolase (FAAH.
Cancer symptoms are influenced by marijuana.?
Several small studies on smoked marijuana discovered that it could help treat nausea and vomiting caused by cancer chemotherapy. A few studies have found that marijuana inhaled (smoked or vaporised) can help treat neuropathic pain (pain caused by damaged nerves).. Certain cannabinoids have also been shown in animal studies to slow the growth and spread of certain cancers. There have been some preliminary clinical trials of cannabinoids in cancer treatment in humans, and more research is being planned. While research has shown that cannabinoids are safe for use in cancer treatment, there is no evidence that they help control or cure the disease. Relying solely on marijuana as a treatment for cancer while avoiding or delaying conventional medical care may have serious health consequences(Dariš et al., 2019).
Cannabinoid drugs
In the United States, two chemically pure drugs based on marijuana compounds have been approved for medical use.
1.Dronabinol (Marinol®) is a gelatin capsule containing delta-9-tetrahydrocannabinol (THC) that has been approved by the US Food and Drug Administration (FDA) for the treatment of vomitting and nausea caused by cancer chemotherapy, as well as weight loss and poor appetite in AIDS patients.
2.Nabilone (Cesamet®) is a synthetic cannabinoid that functions similarly to THC. It can be taken orally to treat vomitting and nauea caused by cancer chemotherapy when other medications have failed.
CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
When one of several sensory centres in the brain or the digestive tract is stimulated, nausea and vomiting occur. It is possible to feel nauseous without vomiting or to vomit without feeling sick. Vomiting (also known as emesis) requires the digestive tract, respiratory muscles, and posture to work together(Mack & Joy, 2000). Scientists have reconstructed the chain of physiological events that lead to vomiting because all of these chemotherapy can be easily measured.n contrast, little is known about the actual mechanisms that cause nausea, which appears to be driven solely by brain activity. Because sickness has no discernible action, researchers studying its causes rely on patients’ subjective descriptions of their feelings. Although researchers are unsure exactly how chemotherapy agents cause vomiting, they believe the drugs or their digestive byproducts stimulate receptors in critical sensory cells. Some agents, such as cisplatin, cause nearly every patient to vomit multiple times; others, such as methotrexate, cause this effect in only a small percentage of chemotherapy patients. Vomiting can begin as soon as a few minutes after treatment, as with the drug mustine, or as late as an hour after chemotherapy, as with cisplatin. Most clinical trials of antiemetics (medicines that prevent vomiting) are usually conducted on cisplatin-treated patients because drugs that reduce vomiting after Several cannabinoids, including two types of THC, have been tested for their ability to suppress vomiting by researchers (delta-9 and the less abundant delta-8-THC). As potential antiemetics, two synthetic cannabinoids (nabilone and levonantradol) that activate the same receptors as THC have also been investigated.
Cisplatin treatment is likely to work at least as well as other chemotherapy agents. As will be discussed, all four compounds have shown to be mildly effective in preventing vomiting after cancer chemotherapy. In clinical trials, THC was found to be more effective than a placebo at reducing chemotherapy-induced vomiting.
However, few trials have used the same chemotherapy agent on all patients, and some have significant flaws. One study, for example, looked at THC’s efficacy in patients who were taking methotrexate, a drug that only rarely causes vomiting(Chang et al., 1979).THC’s effectiveness was found to be comparable to prochlorperazine (Compazine), one of the most effective antiemetics available in the 1980s, in some studies. With the development of more effective medications, such as ondansetron (Zofran) and granisetron (Kytril), which are serotonin antagonists, these findings have little significance. Researchers compared THC to metoclopramide (sold under a variety of brand names in the United States, including Clopra, Maxolon, Octamide PFS, Reclomide, and Reglan), an effective and widely used antiemetic. Due to the fact that none of the patients in this study had previously received chemotherapy, there was no risk that they would vomit because they had become conditioned to do so—a common reaction in people who have had multiple rounds of chemotherapy. Every patient in this study received the same cisplatin dose; participants were randomly assigned to either THC or metoclopramide. Seventy-three per cent of THC-treated patients vomited at least twice after chemotherapy, compared to only 27 per cent of metoclopramide-treated patients(Cancer Treatment Reports – Google Books, n.d.).
Side effects
Marijuana can also be harmful to users. While the most common effect of marijuana is euphoria (“high”), it can also impair movement control, cause disorientation, and occasionally cause unpleasant thoughts or feelings of anxiety and paranoia.THC and other cannabinoids are delivered to the body through smoking marijuana. Still, it also provides harmful substances to users and those nearby, including many of the same substances found in tobacco smoke. Because marijuana plants come in various strains with varying active compounds, each user’s experience can be challenging to predict. The effects can also vary depending on how deeply and for how long the user inhales. Similarly, the results of ingesting marijuana orally can differ from person to person. In addition, some long-term marijuana users may develop an unhealthy dependence on the drug.
Conclusion:
Cannabinoids are a diverse and significant class of complex compounds. with promising therapeutic potential for a wide range of diseases, including cancer. Cannabinoids have been shown to effectively modulate tumour growth in various in vivo and in vitro cancer models; however, these anticancer effects appear to be cancer type and drug dose-dependent. Understanding how cannabinoids can modulate essential cellular processes involved in tumorigeneses, such as cell cycle progression, cell death, and cell proliferation, as well as interactions between cannabinoids and the immune system, is critical for improving existing medications and developing new therapeutic approaches. Several experimental studies have been conducted using cancer cell lines and genetically engineered mouse models.have shown that plant-derived and synthetic cannabinoids have the ability to control cancer cell growth, invasion, and death. Furthermore, different cannabinoids may have different modes of action.
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