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The human endocannabinoid system. 

The human endocannabinoid system. 

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The efforts to understand the nature of how the consumption of cannabis affects the human body are ongoing, complex, and multifaceted. Documentation on the use of cannabis dates back thousands of years; however, it is only now with the recent softening of legal restrictions that modern research approaches have been able to initiate an appropriate l...

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Cannabinoids, produced only in Cannabis sativa, are meroterpenoid secondary metabolites composed of monoterpene and polyketide moieties. Numerous cannabinoids have been isolated, and their pharmacological studies and clinical trials have been extensively conducted. Consequently, in recent years, certain formulations containing ∆⁹-tetrahydrocannabin...

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... Since the turn of the century, the potential of medicinal cannabis has been scientifically reacknowledged through a large number of studies (Nahtigal et al., 2016). These have suggested that cannabis-based remedies can alleviate and treat a wide range of medical disorders (Cascio et al., 2017) such as nausea (Parker et al., 2002), psychotic symptoms of schizophrenia (Leweke et al., 2012), pediatric epilepsy (Goldstein, 2015) and pain (Baron, 2018). ...
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In recent decades with the reacknowledgment of the medicinal properties of Cannabis sativa L. (cannabis) plants, there is an increased demand for high performing cultivars that can deliver quality products for various applications. However, scientific knowledge that can facilitate the generation of advanced cannabis cultivars is scarce. In order to improve cannabis breeding and optimize cultivation techniques, the current study aimed to examine the morphological attributes of cannabis inflorescences using novel image analysis practices. The investigated plant population comprises 478 plants ascribed to 119 genotypes of high−THC or blended THC−CBD ratio that was cultivated under a controlled environment facility. Following harvest, all plants were manually processed and an image of the trimmed and refined inflorescences extracted from each plant was captured. Image analysis was then performed using in-house custom-made software which extracted 8 morphological features (such as size, shape and perimeter) for each of the 127,000 extracted inflorescences. Our findings suggest that environmental factors play an important role in the determination of inflorescences’ morphology. Therefore, further studies that focus on genotype X environment interactions are required in order to generate inflorescences with desired characteristics. An examination of the intra-plant inflorescences weight distribution revealed that processing 75% of the plant’s largest inflorescences will gain 90% of its overall yield weight. Therefore, for the optimization of post-harvest tasks, it is suggested to evaluate if the benefits from extracting and processing the plant’s smaller inflorescences outweigh its operational costs. To advance selection efficacy for breeding purposes, a prediction equation for forecasting the plant’s production biomass through width measurements of specific inflorescences, formed under the current experimental methodology, was generated. Thus, it is anticipated that findings from the current study will contribute to the field of medicinal cannabis by improving targeted breeding programs, advancing crop productivity and enhancing the efficacy of post-harvest procedures.
... After all, the individual compounds have their own pharmacology, too [250]. They can either increase therapeutic activity or decrease toxicity by interacting with many cellular and physiological systems in the body [249,254]. The main controversy arises regarding medicinal use of cannabis due to toxicity of some cannabinoids, especially THC, which is found in dried inflorescences from female plants known as marijuana [249] and is a widely abused recreational drug [255]. ...
... The overall structural properties, physicochemical properties, biochemical properties, pharmacokinetics and safety profile with regard to the pharmacology of individual antimicrobial compounds and mixtures need to be critically analyzed [252,267]. Cannabinoids have challenging pharmacological properties, and their pharmacokinetics depend on the route of administration, dosing, formulation and preparation of a certain product [254,268]. There is evidence that the onset, rate of absorption and bioavailability of CBD and THC are significantly lower after ingestion or oral administration than after inhalation [254]. ...
... Cannabinoids have challenging pharmacological properties, and their pharmacokinetics depend on the route of administration, dosing, formulation and preparation of a certain product [254,268]. There is evidence that the onset, rate of absorption and bioavailability of CBD and THC are significantly lower after ingestion or oral administration than after inhalation [254]. The activity of THC and CBD against GPB in media containing 5% horse blood and 4% serum was recorded to be very poor: likely, binding protein in the media and quickly disappearing from the blood [115]. ...
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Abstract: Antimicrobial resistance has emerged as a global health crisis and, therefore, new drug discovery is a paramount need. Cannabis sativa contains hundreds of chemical constituents produced by secondary metabolism, exerting outstanding antimicrobial, antiviral, and therapeutic properties. This paper comprehensively reviews the antimicrobial and antiviral (particularly against SARS-CoV-2) properties of C. sativa with the potential for new antibiotic drug and/or natural antimicrobial agents for industrial or agricultural use, and their therapeutic potential against the newly emerged coron-avirus disease (COVID-19). Cannabis compounds have good potential as drug candidates for new antibiotics, even for some of the WHO's current priority list of resistant pathogens. Recent studies revealed that cannabinoids seem to have stable conformations with the binding pocket of the M pro enzyme of SARS-CoV-2, which has a pivotal role in viral replication and transcription. They are found to be suppressive of viral entry and viral activation by downregulating the ACE2 receptor and TMPRSS2 enzymes in the host cellular system. The therapeutic potential of cannabinoids as anti-inflammatory compounds is hypothesized for the treatment of COVID-19. However, more systemic investigations are warranted to establish the best efficacy and their toxic effects, followed by preclinical trials on a large number of participants.
... These cannabinoids are terpenophenolic compounds which are prevalently synthesised and stored in a resinous form over inflorescences and bracts of pistillate plants [14][15][16]. To date, ~ 120 cannabinoids have been scientifically recognized [17] and a number of them have been specifically linked with the treatment of particular medical disorders [18] such as Epilepsy and Parkinson's disease [19,20], as well as for cancer pain management [21] and as an appetite stimulant [22]. However, regardless of its popular historical medicinal application, due to its inebriant effect and drug-type classification, cannabis has been prohibited in most countries during the last century [23]. ...
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Background For millennia, drug-type cannabis strains were extensively used for various medicinal, ritual, and inebriant applications. However, cannabis prohibition during the last century led to cultivation and breeding activities being conducted under clandestine conditions, while scientific development of the crop ceased. Recently, the potential of medicinal cannabis has been reacknowledged and the now expanding industry requires optimal and scientifically characterized varieties. However, scientific knowledge that can propel this advancement is sorely lacking. To address this issue, the current study aims to provide a better understanding of key physiological and phenological traits that can facilitate the breeding of advanced cultivars. Results A diverse population of 121 genotypes of high-THC or balanced THC-CBD ratio was cultivated under a controlled environment facility and 13 plant parameters were measured. No physiological association across genotypes attributed to the same vernacular classification was observed. Floral bud dry weight was found to be positively associated with plant height and stem diameter but not with days to maturation. Furthermore, the heritability of both plant height and days to maturation was relatively high, but for plant height it decreased during the vegetative growth phase. To advance breeding efficacy, a prediction equation for forecasting floral bud dry weight was generated, driven by parameters that can be detected during the vegetative growth phase solely. Conclusions Our findings suggest that selection for taller and fast-growing genotypes is likely to lead to an increase in floral bud productivity. It was also found that the final plant height and stem diameter are determined by 5 independent factors that can be used to maximize productivity through cultivation adjustments. The proposed prediction equation can facilitate the selection of prolific genotypes without the completion of a full cultivation cycle. Future studies that will associate genome-wide variation with plants morphological traits and cannabinoid profile will enable precise and accelerated breeding through genomic selection approaches.
... These properties will permit the passive migration across biological membranes and entrance into the blood stream. The migration will be an influencing factor for activities in brain, heart, and other vital organs (Nahtigal et al. 2016). ...
... In human, free radicals are associated with the neurodegeneration, cardiovascular deterioration, diabetis and cardiovascular disease. The antioxidants are acting by delaying or inhibiting the oxidation from lipid and facilitating the repairing of damage cells (Nahtigal et al. 2016).A study by Nafis et al. (2019) was conducted to determine the antioxidant activity of C. sativa from Morocco. The Moroccan C. sativa consist of terpenoids compound such as (E)caryophyllene (35.0%), α-humulene (12.8%) and caryophyllene oxide (10.6%). ...
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Terpenoids, also referred as terpenes have been used extensively in drug related industry due to pharmaceutical properties. These have driven the emergence of studies on terpenoid from plant. Cannabis sativa plant is one of the common natural sources of terpenoids and cannabinoids. The cannabis produces and accumulates terpenoids in grandular trichomes. The grandular trichomes are abundant on the surface of female inflorescence. About 140 terpenoids are known in cannabis and some of them have medicinal potential in treatment of pain, inflammatory, cognition, epilepsy and immune functioning. The biological effect of terpenoid from cannabis is mainly attributed to limonene, myrcene, pinene, linalool, ß-caryophyllene, caryophyllene oxide, nerolidol and phytol. The different composition of terpenoids are responsible in exhibit the unique organoleptic properties and influence the medicinal qualities of difference cannabis strains and varieties. This article aims to review the cannabis plant for terpenoid, terpenoid biosynthesis and its pharmacological activities. The terpenoids from cannabis could be valuable natural resources for drug development.
... But it would be too early to predict anything about CBD for treating cancer. But it is sure that it is helpful in dealing with the symptoms of cancer and also the effects of treatment therapies used for cancer (Nahtigal et al., 2016). The majority of evidence shows that cannabis can prove helpful in complementing the treatment of cancer. ...
... Because of prolonged gut absorption, orally ingested products can exhibit a slower peak onset of 1 hour or more, with effects that can last 5 or 6 hours. 10,16 Because of delayed onset of a perceived effect, individuals may ingest additional cannabis product, potentially leading to intoxication through what can be described as stacking of dosage, a term used to define the perils of selfadministering without waiting for the onset of effects. Oral cannabis products undergo extensive first-pass metabolism via liver enzymes, notably cytochrome (CYP) P450, producing active metabolites that can have more pronounced effects than the parent compound, THC. 10 Many of these metabolites play a substantial role in the physiologic activity expressed by the drug consumed. ...
... Hypotension as a result of vasodilation may respond to fluid resuscitation or vasopressor therapy. 16 Conversely, if parasympathetic activity prevails because of higher dose ingestion, bradycardia may require pharmacologic management. 14 ...
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Cannabis is now legalized, for medical and/or recreational use, in numerous states. Although the cultural shift in acceptance of cannabis is apparent in the public, that sentiment has not necessarily translated to healthcare professionals. As anesthesia providers, we must understand the pharmacology of cannabis and its effects on physiology to provide safe anesthetic care to patients who consume it. The purpose of this article is to describe cannabis and its pharmacologic and physiologic effects and to review the anesthetic implications of its short-term and long-term use.
... [6] An important consideration is that the affinity and potency of the different cannabinoids for CB 1 and CB 2 receptors differ such that efficacy and safety of one cannabinoid cannot be applied to another. [11,12] Phytocannabinoids are isolated from the Cannabis sativa and Cannabis indica plants. THC and CBD are the most widely researched phytocannabinoids. ...
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The South African (SA) Constitutional Court recently decriminalised the private cultivation, possession and use of cannabis by adults. Cannabis contains varying amounts of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), depending on various cultivation factors. No commercial plant-derived cannabis products are currently registered by the SA Health Products Regulatory Authority (SAHPRA) for medical use. Such products are therefore unregulated, but are freely available in SA, and may be of inadequate quality and unverified composition, and not guaranteed to be safe or effective. SAHPRA has to date approved only one synthetic medical cannabis product, dronabinol. Evidence supporting benefit from medical cannabis exists for two drug-resistant childhood forms of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome. Adjuvant therapy with medical cannabis can reduce seizure frequency for Lennox-Gastaut syndrome and Dravet syndrome by 18.8% and 22.8%, respectively, and may be beneficial for other rare forms of epilepsy. There is moderate evidence for chemotherapy-induced nausea and vomiting with the synthetic cannabinoids. Multiple sclerosis-associated spasticity showed a small clinical improvement in self-reported spasticity when a purified form of THC/CBD was added to existing therapy. Currently, low-level or no convincing evidence exists for the use of medical cannabis for chronic pain, sleep and weight disorders, and neuropsychiatric disorders. Cannabis is associated with a greater risk of adverse effects than active and placebo controls, and may be involved in clinically significant drug-drug interactions. The evolving regulatory and legal landscape on the use of medical cannabis will guide prescription and recreational use in the coming years. (PDF) Medical cannabis: What practitioners need to know. Available from: https://www.researchgate.net/publication/339543908_Medical_cannabis_What_practitioners_need_to_know [accessed Feb 28 2020].
... The overlap between the opioid and cannabinoid receptor systems and the interactions between the two is believed to also be involved in the analgesic effect of cannabinoids [36]. Furthermore, the effect is also enhanced by the important anti-inflammatory role through the reduction of proinflammatory markers (TNF-α, iNOS and COX-2), increasing at the same time the anti-inflammatory effects of adenosine agonists by inhibiting A2A receptors [40], exerted most likely through CB2 receptor activation. ...
... Both absorption and bioavailability differ in inhalatory, oral ingestion or transdermal delivery, especially due to CYP450 metabolism in the firstpass hepatic metabolism and due to their lipophilic proprieties, regards of crossing the blood-brain barrier. Thus, inhaled CBD has a bioavailability of 2-56% and achieves peak plasma concentration in 5-10 min, as compared to oral administration, which reaches its highest concentration in up to six hours and has a bioavailability of under 20% [40]. In preclinical neuropathic pain models, even the administration of effective CB1 agonist doses leads quickly to tolerance. ...
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Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography–mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.
... is not psychoactive but has recently been shown to block the effect of THC in the nervous system. [34] Non-cannabinoid constituents isolated from various parts of plant include a range of nitrogenous compounds (including alkaloids), sugars, sugar polymers, cyclitols, fatty acids, amino acids, proteins, glycoproteins, enzymes, hydrocarbon, simple alcohols, flavonoids, acids, aldehydes and ketones, steroids, terpenes, vitamins and pigments. [13] ...
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The drug Qinnab (Cannabis sativa L.) or Indian hemp plant of cannabinaceae family, consists of dried leaves and seeds and commonly known as Bhang. It is an important drug used in Unani System of Medicine for the treatment of various ailments. The plant is an annual dioecious herb, indigenous to Central and Western Asia, but largely cultivated in temperate and tropical countries. The parts of the plant widely used are Bhang (dried leaves), Tukhm Bhang (seeds) Charas (resin), Ganja (flowering heads). It is chiefly used for Muqawwi-i-bah (aphrodisiac), Mumsik (retentive), Musakkin (sedative), and Munawwim (hypnotic) properties. Its widely used phytochemicals are cannabidiol, tetrahydrocannabinol, cannabinol etc. Though the main psychoactive constituent of cannabis is tetrahydrocannabinol (THC). The plant is known to contain more than 500 compounds, among them at least 113 cannabinoids. However most of these minor cannabinoids only produced in trace amounts. Besides THC another cannabinoid produced in high concentration by some plant is cannabidiol. Its important Unani compound formulations are Ma‘jun Falaksair, Ma‘jun Muqawwi wa Mumsik, Ma‘jun Masihi, Ma‘jun Murawwahul Arwah etc. and used effectively for the treatment of diseases related to nerve and brain and also for sexual diseases such as spermatorrhoea, premature ejaculation, general body pain etc. This review compiled with special emphasis on single use and compound formulations and its pharmacological studies relevant to Unani System of Medicine.
... However, the concentrations of these CBs may reach significant levels in special cultivated strains. Additive or synergistic interactions between CBD, THC with minor phyto-CBs, or non-CBs, such as terpenes, in the extracts may increase the therapeutic efficiency of the extract for the treatment of inflammation and cancer [12,33]. ...
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Cannabinoids (CBs) from Cannabis sativa provide relief for tumor-associated symptoms (including nausea, anorexia, and neuropathic pain) in the palliative treatment of cancer patients. Additionally, they may decelerate tumor progression in breast cancer patients. Indeed, the psychoactive delta-9-tetrahydrocannabinol (THC), non-psychoactive cannabidiol (CBD) and other CBs inhibited disease progression in breast cancer models. The effects of CBs on signaling pathways in cancer cells are conferred via G-protein coupled CB-receptors (CB-Rs), CB1-R and CB2-R, but also via other receptors, and in a receptor-independent way. THC is a partial agonist for CB1-R and CB2-R; CBD is an inverse agonist for both. In breast cancer, CB1-R expression is moderate, but CB2-R expression is high, which is related to tumor aggressiveness. CBs block cell cycle progression and cell growth and induce cancer cell apoptosis by inhibiting constitutive active pro-oncogenic signaling pathways, such as the extracellular-signal-regulated kinase pathway. They reduce angiogenesis and tumor metastasis in animal breast cancer models. CBs are not only active against estrogen receptor-positive, but also against estrogen-resistant breast cancer cells. In human epidermal growth factor receptor 2-positive and triple-negative breast cancer cells, blocking protein kinase Band cyclooxygenase-2 signaling via CB2-R prevents tumor progression and metastasis. Furthermore, selective estrogen receptor modulators (SERMs), including tamoxifen, bind to CB-Rs; this process may contribute to the growth inhibitory effect of SERMs in cancer cells lacking the estrogen receptor. In summary, CBs are already administered to breast cancer patients at advanced stages of the disease, but they might also be effective at earlier stages to decelerate tumor progression.