The Positive And Negative Health Effects Of Cannabis, The Relationship Between Cannabis And Various Diseases Part 1

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Abstract: Hemp (Cannabis sativa L.)is a herbaceous-anemophilous plant that belongs to the Cannabis-Linaceae family. The cannabis seed (hemp)has long been utilized as a food source and is commercially important as an edible oil source. In this review, the positive and negative health effects of cannabis, the relationship between cannabis and various diseases, and the use of cannabis in various food products have been discussed. In addition, the scientific literature on the potential use of cannabis and its derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic degenerative diseases in animals and humans has been reviewed. Cannabis is being developed as a key ingredient in a variety of food items, including bakery, confectionery, beverages, dairy, fruits, vegetables, and meat. Hemp seeds are high in readily digestible proteins, lipids, polyunsaturated fatty acids (PUFA), insoluble fiber, carbs, and favorable omega-6 PUFA acid to omega-3 PUFA ratio and have high nutritional value. The antioxidants of cannabis, such as polyphenols, help with anxiety, oxidative stress, and the risk of chronic illnesses, including cancer, neurological disorders, digestive problems, and skin diseases. Cannabis has been shown to have negative health impacts on the respiratory system, driving, psychomotor functions, and the reproductive system. Overall, the purpose of this research is to stimulate more in-depth research on cannabis's adaptation to various foods and for the treatment of chronic illnesses.

Keywords: cannabis; hemp; tetrahydrocannabinol;life extension cistanche; cannabidiol; cannabis-infused foods; maca ginseng cistanche seahorse;cannabis products

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1. Introduction

Cannabis sativa L., commonly called hemp (cannabis seed) or cannabis, is the herbaceous anemophilous plant in the Cannabaceae family. Cannabis is a general word that refers to all plants that belong to the Cannabis genus. Most researchers are of the opinion that this plant originated in Asia and was transported to Europe as a domesticated and cultivated crop during the Bronze Age (22nd to the 16th century BC), as observed from molecular analysis, polygenetic studies, and DNA extraction from modern and archaeobotanical samples. Regardless of where it originated, C. Sativa is widely grown and cultivated not only in Asian countries but also in Africa, Canada, Europe, and the United States [1].

Cannabis contains over 100 active chemical compounds known as cannabinoids[2]The plant contains a huge number of cannabinoids, the most psychoactive of which is delta-9-tetrahydrocannabinol (THC).THC also has appetite stimulant, anti-inflammatory, analgesic, and anti-emetic qualities, making it a very promising medication for medicinal applications [3]. Cannabis is used for textile and food uses since it is high in cannabidiol (CBD) or similar chemicals and is practically devoid of delta-9-THC[4]. In drug-type plants, the most abundant cannabinoids are delta-9-tetrahydrocannabinol acid (THCA)and THC, whereas fiber-type plants are known to contain primarily cannabinoid acids, such as cannabigerol acid (CBGA) and cannabidiol acid (CBDA), followed by their decarboxylated forms, namely cannabigerol (CBG) cannabidiol(CBD)[5].

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There are three major species of cannabis that have been identified (Sativa, Indica, and ruderalis). The strength of the two main active chemicals in cannabis, THC, and CBD, varies between strains, with Sativa carrying the most THC and the least CBD [6]. The euphoric and psychotropic effects of cannabis are due to THC. Synthetic versions of THC, such as dronabinol and nabilone, are used to relieve nausea and improve appetite, in addition to their recreational effects. CBD, a non-psychoactive component, may be able to offset these effects. Furthermore, the Food and Drug Administration recently approved an oral CBD solution for the treatment of two uncommon, severe kinds of epilepsy as an "orphan drug."It is frequently recommended for use in chronic pain and inflammation due to its anti-inflammatory properties [7].

Cannabis has a high nutritional content, which is why all parts of the plant, including the stem, seeds, roots, and flowers, have been used for food, feed, and therapeutic purposes for a long time. Hemp seed has been utilized as a food source since ancient times, particularly in Asian civilizations, and is commercially significant as a source of edible oil [1]. It consists of 30% oil and 25% protein, both of which are rich in nutritional value, as well as 10-15% insoluble fiber. Seeds can be used in cosmetics, different food products, and animal feed [8]. Seeds are subjected to a cold press to extract good-quality oil. Polyunsaturated fatty acids (PUFA) abound in the oil, with an optional ratio of -linolenic acid (w-6) to linoleic acid (w-3)for nutritional science(2.5-3:1). The oil is high in linoleic acid, oleic acid, stearidonic acid, and a-linolenic acid, with saturated fatty acids accounting for just approximately 10% of the total [9]. Hemp seed contains powerful antioxidants, such as polyphenols, that can help to treat many diseases, such as anxiety, oxidant stress, and the risk of chronic illnesses, including cancer, neurological disorders, digestive problems, and skin diseases In comparison to other flowering species, the root system of hemp is well developed, which makes it ideal for the phytoremediation of heavy metal-contaminated soil [10]. Fiber residue is collected from the stem of cannabis. Hemp fiber is a highly valuable raw resource for the production of long-lasting textiles and specialized papers [1]. Hemp is composed of chemical compounds, such as linoleic acid, alpha-Linolenic acid, tocopherol, cannabidiol cannabis in A, and caffeoyltyramine (Figure 1)[11-14]. ALA (alpha-linolenic acid) is an n-3(-3)fatty acid found mostly in plant foods like flaxseed, walnuts, and vegetable oils such as canola and soybean oils. Clinical experiments have demonstrated that substituting saturated fat with linoleic acid lowers total and LDL cholesterol, indicating that ALA has a cardioprotective effect [12]. micronized purified flavonoid fraction tablet uses.Cannabidiol, a non-psychoactive cannabinoid mole, is a promising therapy option for both illnesses. Cannabinoids are involved in the pathophysiology of both psychotic and substance-abusing diseases (SUDs) [13]. Caffeoyltyramine and its phenolic amides, including cis-N-caffeoyltyramine and trans-N-caffeoyltyramine, are known to have anti-fungal and antioxidant effects [14].

2. Potential Health Benefits of Cannabis

Hemp seed is associated with a variety of health effects and possible treatments. Hemp seeds are high in antioxidants, which may help to prevent chronic diseases such as cancer, neurological diseases, immunomodulatory effects, gastrointestinal disorders, lipid metabolism, dermatological diseases, and cardiovascular health [15]. 2.1.Cardiovascular Health Cardiovascular disease refers to any illness that affects the heart or blood vessels. It is generally linked to the deposition of fats in the arteries (atherosclerosis) and an elevated chance of thrombosis. Cardiovascular diseases (CVDs) are the most common cause of mortality across the world.oteflavonoid.By 2030, cardiovascular disease is predicted to kill 25 million people worldwide [16].

THC was discovered to be the primary active ingredient in cannabis, which led to the discovery of specific THC receptors in the human body, known as cannabinoid receptors type1(CB-1)and type2(CB-2)(CB-2).CB-1 receptors are found in the liver, fat, muscles, and brain, whereas CB-2 receptors are found in great quantities in the immune cells, spleen, and peripheral organs, though at lower doses [17]. These findings triggered a wave of research that ultimately led to the development of endocannabinoids (ECS). ECS has been detected in cardiac tissues, and new research reveals that it is implicated in blood pressure and heart rate (HR) regulation, as well as other hereditary illnesses. In the presence of sick situations, experimental research has demonstrated redundancy in endocannabinoid signaling and endocannabinoid substrates, with dual participation of CB-1 and CB-2 receptors [18].

Steffens and Pacher [19] examined the recent literature on the cannabinoid receptor CB-2in cardiac diseases and stated that CB-2 receptor expression in cardiac cell components, as well as attempting to penetrate immune cells, such as leukocytes and macrophages, was apparently involved in attempting to control the severity of tissue inflammation and injury occurring in different cardiovascular conditions, implying that all these receptors could play a role in controlling the severity of tissue inflammation and damage occurring in different cardiovascular disorders. The use of CB-2 receptor agonists and antagonists to pharmaceutically control CB-2 receptors seems to be a potential treatment option for conditions, such as stroke, heart failure, atherosclerosis, and restenosis. Identification of molecules with therapeutic qualities similar to cannabis and cannabinoids but with fewer adverse effects will necessitate a thorough understanding of the human endocannabinoid receptor system.

According to a recent mice study that examined three THC administration methods, pre-treatment with an ultra-low dosage of THC provided considerable protection against cellular damage to the heart, as demonstrated by reduced infarct size and low troponin levels[20]. As a result, there is data suggesting that cannabis use is linked with an increased risk of acute cardiovascular problems in both patients with atrial fibrillation and those who do not have any substantial atherosclerotic risk factors. However, some researchers feel that cannabis usage is only connected with minimal and temporary risk of cardiovascular events, given the rarity of reports of mortality among medical cannabis users owing to the drug [21]. Some cannabis enrichment studies related to cancer are shown in Table 1.

2.2.Cancer

Cancer is the second biggest cause of mortality worldwide, accounting for around 8.8 million fatalities in 2015 (GHO 2018 estimates); cancer accounts for nearly one in every six deaths. Cancer is a multiphase disease that begins with the creation of a paraneoplastic lesion (initiation process) and develops into a malignant tumor over time. Cancer develops when the cellular reproduction mechanism becomes uncontrollable. It is a condition marked by uncontrolled, disorganized, and unwanted cell division. Cancer cells, unlike normal cells, continue to divide and develop throughout their lifetimes, thus generating harmful cells [11].

Cannabinoids have been shown to decrease tumor cell proliferation while sparing normal tissue. Glioma cells exposed to cannabis, for example, die from ceramide-induced cell death, but astrocytes are protected from oxidative stress in the same way [27]. Cannabidiol enhances THC's anti-tumor action on glioma cells[28]. Finally, in certain cancers, the expression of CBT and/or CB2 receptors has been linked to prognosis. Increased expression of CBT and CB2 receptors has been associated with enhanced prognosis in hepatocellular carcinomas, while higher expression of CB2 receptors has been linked to higher tumor grades in gliomas [29]. Glioblastoma multiform, prostate, breast thyroid, colon, colon, pancreatic, leukemia, and lymphoma models have all shown tumor growth inhibition in vitro and in vivo. Reduction of proliferating cell signaling pathways, blockage of cell migration and angiogenesis, encouragement of apoptosis, and/or regulation of autophagy could all contribute to this anti-tumor effect [30].

THC's safety and effectiveness in patients with refractory glioblastoma multiform were investigated in a study. Nine patients had a tumor debulking operation followed by the insertion of an infusion catheter into the resection cavity. THC was injected into the cavities every day for 10-64 days at doses ranging from 0.80 to 3.29mg total. The drug produced a slight psychoactive effect on one patient, but it was otherwise well tolerated. THC inhibited tumor growth on MRI, as well as tumor ki-67 immunostaining and angiogenesis in tissues taken after treatment [31]. To properly identify cannabis's potential as an anti-cancer drug, more preclinical and clinical research is needed.

2.3.Disorders of the Central Nervous System

Central nervous system (CNS)illness is a wide term for a group of diseases in which impaired brain function restricts one's health and capacity to operate. Every year, approximately 6.8 million individuals eventually die from neurological disorders[32]. Some of the symptoms linked with neurological illnesses, such as multiple sclerosis (MS) and chronic pain, have been shown to be relieved by cannabis. MS is an autoimmune neurodegenerative disease characterized by demyelinating CNS pathology. Symptoms of this condition include spasticity, tremors, chronic pain, muscle cramps, and vesicle and intestinal dysfunctions, all of which are thought to be caused by the demyelinating process. In individuals with MS and central pain, cannabis-based medicines decreased subjective measures of MS symptoms and improved appetite [3].

Epilepsy is a neurological illness that frequently results in seizures, which are electrical discharges between brain cells that cause uncontrollable muscular activity and can also result in death. Epilepsy affects around 50 million people globally, according to the World Health Organization; the Centers for Disease Control and Prevention reports epilepsy affects 3.4 million people in the United States [34].

In 2015, the American Academy of Neurology presented a three-month clinical research study involving 137 children and young adults with various kinds of epilepsy who were treated with the CBD medication Epidiolex. Dravet syndrome (16%), Lennox-Gastaut syndrome (16%), and ten additional types of epilepsy were present in the individuals (some among them were very rare conditions). Nearly half of the individuals in this trial reported a decrease in seizure frequency. Tiredness, diarrhea, and a loss of appetite were all reported as adverse effects by 21%,17%, and 16%, respectively. Severe side effects have been reported in a few cases, but it is unclear: if these were caused by Epidiolex. There were ten cases of status epilepticus, three cases of diarrhea, two cases of weight loss, and one instance of liver injury [35].

Bergamaschi et al. [36] described long-term research in which an adolescent with significant antipsychotic side effects was given up to 1500 mg of CBD per day for four weeks. Her symptoms improved, and there were no side effects. Bergamaschi et al. reported a similar beneficial effect in another trial, in which three patients were given a starting dose of CBD of 40 mg, which was gradually increased to 1280mg/day for four weeks.

Lorenzetti and his associates compared the neuroanatomical correlates of regular cannabis use to non-use in a meta-analysis [37]. Cannabis usage was linked to smaller brain sizes in areas involved in learning, reward, and addiction (i.e, hippocampus and orbitofrontal cortex). Neuroscientific theories of addiction have identified these pathways, and their modification has been demonstrated in substance use disorders other than cannabis. More research is needed to determine who is most prone to these brain changes, the role of vulnerability factors (such as age and sex, cannabis dependency and potency, and comorbid mental health and drug use), and how brain changes translate to cannabis-related disorders.

2.4.Rheumatoid Arthritis

Rheumatoid arthritis (RA)is a long-term autoimmune disorder that leads to inflammation of the joints and surrounding tissues. RA primarily affects the joints, which are generally attacked at the same time. In the years 2007-2009, about 50million(22.2 percent)adult Americans over the age of 18 were diagnosed with arthritis, the most common of which were osteoarthritis and the autoimmune disease rheumatoid arthritis. By 2030, the initiative is expected to grow to 67 million people [38].

After employing Freund's adjuvant to induce arthritis in rats, several CBD doses (0.6,3.1,6.2, or 62.3 mg/day)were given daily in a gel for transdermal administration for four days. CBD has been shown to lessen joint swelling and immune cell infiltration. After four days of CBD administration, the synovial membrane thickened and nociceptive sensitization/spontaneous pain increased in a daily dosage manner. In the dorsal root ganglia (TNF alpha) and spinal cord, pro-inflammatory indicators were similarly decreased in a dose-dependent manner (CGRP, OX42). There were no side effects, and exploratory behavior was unaffected (unlike 9-THC, which produced hypo locomotion) [38]. A cannabis enrichment study related to arthritis is shown in Table 1.

2.5.Dermatitis and Skin Disorders

Dermatitis is a term that refers to a group of skin conditions that cause inflammation. These skin ailments include atopic dermatitis (eczema), seborrheic dermatitis (dandruff), and contact dermatitis. Red rashes, dry skin, and itching are some of the symptoms of these diseases. Eczema (atopic dermatitis) is a skin disorder that causes redness and itching. It is most prevalent among children, although it can affect anyone at any age. Atopic dermatitis is a long-term (chronic) condition that flares up from time to time. It is possible that it will be linked with asthma or seasonal allergies. Eczema is a skin ailment that affects up to 10%to 20% of the world's population [39].

Hempseed oil is a good source of w-6 and w-3 PUFAs. In a 20-week controlled, single-blind randomized trial with atopic sufferers, dietary hempseed oil and olive oil were compared. In this research, fatty acid profiles in plasma triglycerides, cholesterol, and phospholipid components were investigated. Further information about skin dryness, irritation, and the use of dermatological medicines was obtained using a patient survey. TEWL (Trans Epidermal Water Loss) was also quantified on the skin. Both essential fatty acids (EFAs), ALA(18:3n3), and linoleic acid (18:2n6), as well as gamma-linolenic acid (GLA; 18:3n6), were enhanced in all lipid components after hempseed oil, but not arachidonic acid (20:4n6). After hempseed oil treatment, intra-group TEWL values reduced (p50.074), skin roughness and itchiness improved (p50.027), and topical medicine use was reduced (p50.024). Hempseed oil consumption led to a significant alteration in plasma lipid content, as well as a decrease in clinical signs of dermatitis. polyphenols benefits, These advantages are thought to be attributable to hempseed oil's well-balanced and plentiful supply of PUFAs [26]. A cannabis enrichment study related to skin diseases is shown in Table 1. 2.6.Sleep Disorders and Mental Health

Sleep is a vital physiological activity that contributes to the restoration of processes that are necessary for proper everyday function [40]. Appropriate sleep health is influenced by a number of factors, including duration, timing, efficiency, and a sense of restorative sleep that keeps a person alert and productive throughout the day [41]. Insufficient sleep is reported by 30-35 percent of the general population[42].

Cannabinoids (nabilone) were tested especially for the treatment of sleep difficulties in two studies (5 reports; 54 participants). The first was a high-risk-of-bias parallel-group trial. This study found that nabilone had a larger benefit on the sleep apnea/hypopnea index than placebo (mean difference from baseline,19.64;p value=0.02). The other was a minimal crossover experiment in fibromyalgia patients that compared nabilone to amitriptyline. This indicated that nabilone was linked to decreased insomnia (mean difference from baseline,3.25 percent CI,5.26 to 1.24) and increased sleep restfulness (mean difference from baseline,0.48(95 percent CI,0.01 to 0.95). Sleep was also investigated as an endpoint in 19 placebo-controlled studies for additional purposes (chronic pain and MS). Thirteen studies looked at nabiximols, one looked at nabilone, one looked at dronabinol, two looked at THC/CBD capsules, and two looked at smoked THC (one at various doses). Two of the trials that looked at nabiximols also looked at oral THC, and the dronabinol trial looked at oral THC/CBD. There was some indication that cannabinoids could help these patients sleep better. Cannabinoids (mostly nabiximols) were linked to a higher average improvement in sleep quality (WMD,0.58,95 percent CI,0.87 to 0.29;8 trials) and sleep disturbance (WMD, 0.26, 95 percent CI,0.52 to 0.00; 3 trials). THC/CBD was tested in one experiment, while nabiximols were tested in the others; the results were comparable for both cannabinoids [33].

Hoch and colleagues looked at randomized clinical trials that looked at the efficacy and safety of cannabis-based medicine in the treatment of mental illnesses. In dementia, cannabis and opioid dependence, schizophrenia, general social anxiety, post-traumatic stress disorder, anorexia nervosa, attention-deficit/hyperactivity disorder, and Tourette's disorder, their systematic review found some evidence that THCor CBD given as adjunctive treatment to other pharmacotherapies and psychotherapy improved specific symptoms of some disorders (e.g, in dementia, schizophrenia, cannabis and opioid dependence, general social anxiety, anorexia nervosa, post-traumatic stress disorder, and Tourette's disorder). There were some negative effects mentioned, but they were rarely serious[43].

This article is extracted from Molecules 2021, 26, 7699