Medicinal Cannabis: History, Pharmacology, And Implications
There has been a surge in interest in medical marijuana, also known as medicinal cannabis, in recent years. Legal, ethical, and sociological issues surrounding marijuana usage, as well as concerns about its effects on health and safety (including overdoses and fatalities) and therapeutic potential (based on little clinical evidence) are just a few of the many thorny issues surrounding this therapy. Schedule I controlled substances are defined by the Controlled Substances Act of 1970 as having a high potential for abuse, no currently accepted medicinal use in the United States, and no accepted safety data to support use of the treatment under medical supervision.
Around 147 million people or 2.5% of the global population use marijuana every year, according to WHO statistics. Cannabis is the most widely grown, trafficked and misused illegal narcotic in the world today.
As of 2014, roughly 22.2 million adults in the United States aged 12 or older admitted to regular cannabis usage, with 8.4% having done so in the month before their admission. 3,4 A Gallup poll in October 2016 found that 60 percent of Americans support the legalization of marijuana for recreational and medicinal purposes. This is consistent with legislative actions, ballot measures, and public opinion surveys, which show increasing support for the use of marijuana for both recreational and medicinal purposes. 5 Extra research shows that 54% of American people support legalizing marijuana without additional restrictions, while 81% of those polled prefer legalizing it for medical reasons. 6 Despite the lack of evidence, it’s possible that medical professionals may look at this treatment option. 7–9 Medical marijuana has been legalized in 28 states, the District of Columbia, Guam and Puerto Rico since the beginning of 2017.
There has been a steady rise in the number of states that allow medicinal marijuana usage for specified medical conditions. To ensure that medical cannabis claims are backed by solid science, the FDA is now reviewing public data to determine the drug’s safety and misuse potential. 11,12 Here, we will cover the history of medicinal cannabis, analyze its pharmacology, and evaluate select data on therapeutic benefits, as well as the consequences of increasing medical cannabis rules on the acute care hospital environment.
MERIT OF IMPORTANCE
Ancient civilizations have used cannabis, a plant-based, or botanical, substance. Extensive research suggests it was in use in what is now Romania more than 5,000 years ago. 13 Using 6-tetrahydrocannabinol [6-THC] in ashes is the sole direct proof that cannabis was initially used medicinally approximately 400 AD. 14 As a patent medication in the United States in the 19th and early 20th centuries, cannabis was described in the United States Pharmacopeia in 1850. The Marihuana Tax Act of 1937 was the first federal law to regulate the use and selling of cannabis. 15,16 Legal penalties for marijuana possession increased in 1951 and 1956, respectively, when the Boggs and Narcotic Control Acts were enacted. In 1970, federal law prohibited the possession of marijuana at all levels of government. 1,17,18 Legislation such as these not only criminalized cannabis, but it also restricted academics’ ability to get the drug for research reasons.
Medical cannabis was legalized for medicinal use under physician supervision in California in 1996 with the passage of the Compassionate Use Act. On January 1, 2017, there will be 28 states and the District of Columbia that will have enacted legislation that governs the sale and distribution of medicinal cannabis; 21 states and the District of Columbia will have decriminalized marijuana and eliminated prohibition for possession of small amounts; while eight states, including Alaska and the District of Columbia, will have decriminalized and eliminated prohibition for the possession of small amounts of marijuana.
DEBATE OVER MEDICAL CANNABIS
With no accepted medicinal use and high abuse potential, concerns for dependence, and lack of accepted safety for use under medical supervision — as well as a national stigma surrounding the potential harms and implications of cannabis use as a gateway drug — transitioning from a vilified substance to one with therapeutic merits has been contested. There are multiple molecules and intricate interactions between substances in this plant-based medicine, and the US Pharmacopeia and the FDA have explored how this product may be regulated in the United States and how it would fit into the present regulatory framework for medications.
Many believe that the rise of interest in botanical medicinal cannabis is a byproduct of the opioid abuse epidemic; public perception of medicinal cannabis suggests that this plant-based therapy is not much different from a botanical drug product or supplement used for health or relief of symptoms if the disease persists. It is possible, however, that medical cannabis has comparable health hazards, such as psychotropic, intoxicating, and impairing effects that have yet to be fully investigated in clinical studies, as with other herbal preparations or supplements. A number of conditions can be treated with botanical medicinal cannabis, particularly when symptoms are refractory to other therapies; there is evidence that beneficial cannabinoids exist, as evidenced by single-entity agents derived from cannabis containing the compounds THC and cannabidiol (CBD); cannabis is relatively safe, with few deaths reported from use; therapy is self-titratable by the patient; and therapy is reliant on the patient. 20–22 It is argued by critics of medicinal cannabis use that there are no well-designed randomized trials to confirm the benefits and harms; that there is no standardization in potency or quantity of pharmacologically active constituents; that adverse health effects are not only related to smoking cannabis but also to unmasking mental health disorders; that standardization is lacking; and that the adverse health effects are not only related to smoking cannabis but also to impairing coordination and affecting judgment.
It is irresponsible for clinicians to deny or ignore the implications of this substance’s use on patient health and the health care system’s infrastructure, regardless of personal views and perceptions. Clinicians should be aware of these implications and informed about how this therapy may influence practice in various health care settings, including acute care.
PHARMACOLOGY
The neurological system, internal organs, connective tissues, glands, and immunological cells all contain endocannabinoids (eCBs) and receptors for these compounds. A homeostatic function is played by the eCB system, which has been referred to as a system of “eat, sleep, relax, forget, and protect.” 26 Although their involvement in pathology is well-established, it is also clear that eCBs have a protective effect in a number of medical illnesses. 27 Clinical eCB deficient symptoms have been suggested to include migraine, fibromyalgia, and irritable bowel syndrome (CEDS). It’s possible that depression is caused by a deficiency in eCB signaling. eCB system deficits have been linked to schizophrenia, multiple sclerosis (MS), Huntington’s illness, Parkinson’s disease, anorexia, persistent motion sickness, and failure to thrive in babies in human studies.
The eCB system is a microcosm of psycho-neuroimmunology, or “mind–body” medicine, as it is often called. Enzymes and receptors are the building blocks of the eCB system. When cannabinoid receptors are activated, a wide range of physiological events take place. Among G-protein–coupled receptors, cannabinoid receptor type 1 (CB1) is the most prevalent. The substantia nigra, globus pallidus, hippocampus, cerebral cortex, putamen, caudate, cerebellum, and amygdala are some of the areas where it is most prominently expressed in the central nervous system (in that order). Additionally, CB1 is expressed in non-neuronal cells, such as hepatocytes, connective and musculoskeletal tissues, and the gonads. However, CB2 may also be expressed in the central nervous system, which is primarily responsible for immunological function. To get 420 evaluations virginia 2022 follow the link.
There are a number of eCB agonists, including anandamide (AEA) and sn-2-arachidonoyl-glycerol (sn-2AG) (2-AG). The phospholipid precursors of cell membranes release AEA and 2-AG on demand. As new ligands, secondary receptors, and enzymes involved in ligand metabolism have been discovered, the “classic” eCB system has grown in complexity. The phytocannabinoids 9-THC and CBD, for example, may behave similarly to capsaicin by acting as ligands for GPR55, GPR18, GPR119, and many transient receptor potential ion channels (e.g. TRPV1, TRPV2, TRPA1, TRPM8). 28 Through substrate competition, “entourage compounds” may help extend the effects of AEA and 2-AG by increasing their synergy and augmenting them. Accompanying cannabinoid molecules include N-palmitylethanolamide (PEA), SEA, and oleamide, which may constitute a whole new method for controlling the activation of endogenous cannabinoid receptors.
In addition to cannabinoid receptors, cannabis is connected to a number of other targets. Norepinephrine, dopamine, and serotonin receptors are all inhibited noncompetitively by G-protein–coupled receptors. Ligand-gated ion channels cause allosteric antagonism at serotonin and nicotinic receptors and increase glycine receptor activity. Noncompetitive antagonism inhibits calcium, potassium, and sodium channels at nonspecific ion channels, and AEA influences activation of PPAR and PPAR at peroxisome proliferator-activated receptors.
The central nervous system’s CB1 receptors mediate THC’s euphoric effects, but this mechanism also restricts the drug’s usage because of its potentially harmful side effects. These additional phytocannabinoids, which have little or no psychoactive effects, are now widely recognised as medicinal medicines for humans. CBD has received the greatest attention as a non-psychoactive cannabinoid. 31 When compared to THC, CBD doesn’t seem to have any impact on CB1 or CB2 receptors in the body. Its antiepileptic, anxiolytic, antipsychotic and neuroprotective properties are only a few of the many activities that make CBD an attractive therapeutic candidate. There have been regulatory authorization in various European nations for the use of CBD in conjunction with THC. Some states, however, have established laws allowing the use of CBD-rich cannabis products for specific pathological disorders, despite the lack of standardization of CBD concentration and the best method of delivery. 32 Specific uses for CBD have recently developed in the treatment of pain (both chronic and neuropathic) as well as in the treatment of diabetes, cancer, and illnesses of the nervous system, including Huntington’s disease. In animal experiments, large levels of CBD seem to have an antidote to the effects of lower THC dosages. Furthermore, clinical investigations have shown that CBD may extend and/or enhance the effects of THC when taken orally or orally. The earliest clinical studies show that high-dose CBD (150–600 mg per day) may have a therapeutic impact on epilepsy, sleeplessness and social anxiety disorder. CBD has also been demonstrated to induce drowsiness at high dosages.
administration and pharmacokinetics
Among the most prevalent routes of administration include smoking, vaporization, and the consumption of edible goods. The mode of administration may affect the onset, intensity, and duration of psychoactive effects; the effects on organ systems; and the addictive potential and negative repercussions of usage.
To understand how cannabinoids interact with the body and how they are metabolized, pharmacokinetic research has proven difficult due to low analyte concentration, fast metabolism, and physicochemical properties. As a result of the adsorption of molecules of interest to various surfaces, the overall consequence is a decreased drug recovery. 35 9-THC, marijuana’s principal mind-altering ingredient, is quickly transported from the lungs to the bloodstream when being smoked. THC was discovered in plasma soon after the first inhalation of marijuana smoke in a randomized controlled study done by Huestis and colleagues. This indicates that the lungs are able to efficiently absorb THC from marijuana smoke. THC levels spiked quickly and peaked just before the user stopped puffing. 36 Vaporization is quickly overtaking smoking as the preferred method of consuming cannabis. Smoking-like effects are achieved by vaporization, but there is less exposure to combustion byproducts and potential carcinogens, and there are less severe respiratory symptoms. THC is extremely lipophilic, spreading quickly to tissues with strong blood flow and then to fat. 37 Testing on 11 healthy volunteers who were given 9-THC by smoking, injecting it intravenously orally showed that the plasma profiles of THC after these methods were similar, but the plasma levels after oral administration were low and irregular, indicating that the drug was absorbed slowly and irregularly during the testing period. During the four-hour period, plasma concentrations and the clinical “high” from intravenous injection and smoking had similar temporal courses, with rapid start and consistent decrease. The clinical effects of oral THC were delayed and persisted longer, although they occurred at lower plasma concentrations than those of the other two routes of administration.
There have only been a few trials using other delivery methods for cannabinoids, such as the rectal route, sublingual administration, transdermal distribution, ocular drops, and aerosols, therefore they are of limited utility in everyday life. THC’s pharmacokinetics differ depending on how it is administered. Within minutes after inhaling THC, the plasma concentration reaches a maximum and the psychoactive effects begin to take effect. After 15 to 30 minutes, the effects begin to diminish and last for two to three hours. It takes between 30 and 90 minutes after oral administration for psychoactive effects to appear, for them to reach their peak impact after around two to three hours, and for the effects to persist anywhere from four to twelve hours, depending on the dosage.
Different methods of cannabis administration have substantial public health consequences in the ever-changing legal environment of medicinal cannabis. Qualtrics and Facebook data showed that people in states with medical marijuana laws had a significantly higher likelihood of ever using the substance with a history of vaporizing marijuana (OR, 2.04; 99 percent confidence interval [CI], 1.62–2.58) and a history of oral administration of edible marijuana than those in states without such laws. Higher dispensary densities and longer periods of medicinal cannabis status were also shown to be strongly linked with the use of vaporized and edible marijuana. There is a correlation between state-level trends of cannabis use and medical marijuana regulations.
INTERACTIONS BETWEEN DRUGS
Medical marijuana and other medications may interact metabolically and pharmacodynamically in certain cases. Exogenous cannabinoids, such as THC, CBD, and cannabinol (CBN), were studied for their in vitro metabolism and the hepatic cytochrome 450 (CYP450) isoenzymes 2C9 and 3A4 were found to be important in the primary metabolism of THC and CBN, while 2C19 and 3A4 were found to be responsible for CBD metabolism. 40 Exogenous cannabinoids have been shown to interact with various drugs in clinical studies, however the prescription information from cannabinoid-derived pharmaceutical products such as Sativex (GW Pharmaceuticals, United Kingdom) and dronabinol may provide information on drug interactions (Marinol, AbbVie [United States]). 41,42 THC and CBD concentrations increased by 1.2 to 1.8 times and twice, respectively, when ketoconazole and oromucosal cannabis extract containing THC and CBD were administered together. Rifampin coadministration is linked to a decrease in THC and CBD concentrations. Drug interactions between dronabinol and other medicines with comparable physiological effects have not been found in clinical studies, however this does not rule out the possibility of additive pharmacodynamic effects (e.g., sedatives, alcohol, and antihistamines may increase sedation; tricyclic antidepressants, stimulants, and sympathomimetics may increase tachycardia). 41 Theophylline metabolism may also be increased after smoking cannabis, as it is after smoking tobacco.
POSSIBLE RESULTS
Studies on recreational marijuana users have revealed a great deal about the dangers of medical cannabis.
If you’ve been using marijuana for a short period of time and haven’t seen any of the side effects mentioned above, you may want to avoid it.
Addiction, abnormal brain development, cognitive impairment, poor educational results (e.g., dropping out of school), and decreased life satisfaction have all been linked to long-term or heavy cannabis use, particularly among teens. 45 Chronic bronchitis and an increased risk of chronic psychosis-related health problems, such as schizophrenia and variations of depression, are also connected with long-term or heavy cannabis use among those with a predisposition to such illnesses. 46–48 Medical disorders such as myocardial infarction and stroke have also been linked to cannabis usage. 49–51 Using cannabis to treat symptoms of neurodegenerative disorders including Parkinson’s, Alzheimer’s, and MS has yielded information on reduced cognition in these patients.
Medical cannabis have been studied extensively over the last 40 years in order to determine the potential side effects of this treatment.
Medicinal cannabis was the subject of 31 investigations, including 23 randomized controlled trials and 8 non-randomized studies. Cannabinoid exposures in the randomized studies ranged from eight hours to 12 months in length, with a median of two weeks. Of the 4,779 adverse effects reported in these studies, 96.6 percent (4,615) were rated not severe by the authors of the papers. SEVERE ADVERSE EFFECTS: Relapsing MS, vomiting, and urinary tract infections were the three most prevalent significant side effects (9.1 percent ; 15 events). Patients who received medicinal cannabis had neither higher or lower incidence of major adverse events than controls (relative risk:1.04; 95% CI: 0.78–1.39). People exposed to marijuana reported dizziness as the most prevalent non-serious adverse event, with an incidence rate of 15.5% (714 occurrences).
There have also been reports of adverse effects associated with chronic cannabis use, including anxiety, suicidal ideation or tendencies, and psychotic symptoms, in addition to the hyperemesis syndrome and impaired coordination and performance associated with acute cannabis use. Other chronic side effects include mood disturbances, the worsening of psychotic disorders, cannabis use disorders and withdrawal syndrome.
Research on the long-term consequences of chronic medical cannabis usage must be carried out in order to determine the hazards of long-term use.
THE MEDICAL USE OF
As a result, the effectiveness of cannabis and cannabinoid medicines to relieve symptoms or cure illness is not well established. The analgesic impact on chronic pain is still uncertain. Research on cannabinoids for the treatment of chronic non-cancer pain, including smoked marijuana, oromucosal extracts of cannabinoid-based therapy, nabilone, dronabinol, and an entirely new THC analogue, has been thoroughly reviewed using randomised controlled trials. 55 Fibromyalgia, arthritis, and other types of chronic pain are all included in this category of neuropathic pain. Analgesic effects of cannabis were shown in 15 of the 18 studies that included them when compared to a placebo. Overall, the usage of cannabinoids was well tolerated, with the most often reported side effects being mild to moderate in intensity. Overall, data shows that cannabinoids are safe and modestly helpful in neuropathic pain, with tentative evidence for effectiveness in fibromyalgia and rheumatoid arthritis.
While national and international cancer societies do not have enough evidence to support the routine use of medicinal cannabis to alleviate chemotherapy-related nausea and vomiting, therapeutic agents based on THC (e.g. dronabinol) have been approved for use as an antiemetic in the United States for a number of years. When it comes to addressing chemotherapy-induced nausea and vomiting, cannabis-based drugs have just lately been tested for their effectiveness and side effects. Patients who received cannabis-based products suffered less nausea and vomiting than those who got placebo in a study of 23 randomized, controlled studies. 56 The percentage of patients who got cannabis-based medications for nausea and vomiting was comparable to the percentage of those who received traditional antiemetics. There were more withdrawals from trials including cannabis-based drugs than placebo or traditional antiemetics owing to undesirable effects such as “feeling high,” dizziness, drowsiness and dysphoria. Patients preferred cannabis-based antiemetics in crossover studies including patients who were given both cannabis-based and conventional antiemetics. Conventional antiemetics fail to control chemotherapy-induced nausea and vomiting, while cannabis-based drugs may help. However, the studies yielded low- to moderate-quality data and were based on chemotherapeutic drugs and antiemetics that were available in the 1980s and ‘90s.
A Cochrane review of four clinical trials that included 48 epileptic patients using CBD as an adjunct treatment to other antiepileptic medications concluded that there were no serious adverse effects associated with CBD use but that no reliable conclusions on the efficacy and safety of the therapy could be drawn from this limited evidence.
According to the American Academy of Neurology (AAN), oral cannabis extract is beneficial in lowering MS patient-reported symptoms of spasticity and central discomfort or painful spasms. 58 There is insufficient evidence to support the use of cannabis extracts for the treatment of Huntington’s disease, levodopa-induced dyskinesias in individuals with Parkinson’s disease, or lowering tic intensity in Tourette’s, according to the American Academy of Neurology.
Dyskinesia, dyspnea, and chemotherapy-induced nausea and vomiting have not been alleviated by medicinal marijuana in elderly individuals. Patients with dementia and anorexia may benefit from THC therapy, according to preliminary research. Sedation-like feelings were the most often reported side effects of cannabis therapy in older persons.
