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Mean plasma concentrations of ∆ 9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) of six cancer patients after ingestion of one oral dose of THC 15mg (estimated from single graphs for each patient of Frytak et al., [46] with permission). The plasma courses of THC showed considerable interindividual variation (see figure 8 for the individual courses of THC plasma concentrations of three patients).

Mean plasma concentrations of ∆ 9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) of six cancer patients after ingestion of one oral dose of THC 15mg (estimated from single graphs for each patient of Frytak et al., [46] with permission). The plasma courses of THC showed considerable interindividual variation (see figure 8 for the individual courses of THC plasma concentrations of three patients).

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Delta(9)-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endog...

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... In several clinical studies, [44,46] 11-OH-THC concen- trations even exceeded THC concentrations. In a figure 6 after ingestion of one oral dose of THC 15mg (estimated from graphs of figure 2 of Frytak et al., [46] with permission). ...

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... There are four different stereoisomers, but only the (-)-trans form exists naturally [1]. Its metabolism takes place mostly in the liver [3] but also in other tissues such as the brain, small intestine, heart, and lungs [1,4,5]. The main pathway involves hydroxylation of THC into the phase I active metabolite 1-hydroxy-∆ 9tetrahydrocannabinol (THC-OH), which is then oxidized into the phase I inactive metabolite 11-nor-9-carboxy-∆ 9 -tetrahydrocannabinol (THC-COOH) [3,6,7]. ...
... There are four different stereoisomers, but only the (-)-trans form exists naturally [1]. Its metabolism takes place mostly in the liver [3] but also in other tissues such as the brain, small intestine, heart, and lungs [1,4,5]. The main pathway involves hydroxylation of THC into the phase I active metabolite 1-hydroxy-Δ 9 -tetrahydrocannabinol (THC-OH), which is then oxidized into the phase I inactive metabolite 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THC-COOH) [3,6,7]. ...
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Cannabinoids are still the most consumed drugs of abuse worldwide. Despite being considered less harmful to human health, particularly if compared with opiates or cocaine, cannabis consumption has important medico-legal and public health consequences. For this reason, the development and optimization of sensitive analytical methods that allow the determination of these compounds in different biological specimens is important, involving relevant efforts from laboratories. This paper will discuss cannabis consumption; toxicokinetics, the most detected compounds in biological samples; and characteristics of the latter. In addition, a comprehensive review of extraction methods and analytical tools available for cannabinoid detection in selected biological specimens will be reviewed. Important issues such as pitfalls and cut-off values will be considered.
... Although it possesses psychoactive activity, this phytocannabinoid extracted from Cannabis sativa does not provoke any intoxicating effects, unlike its counterpart Δ9-tetrahydrocannabinol (THC) [5]. Through decarboxylation reactions that occur upon heating, tetrahydrocannabinolic acid-A (THCA-A) and cannabidiolic acid (CBDA) are converted into THC and CBD, respectively [6]. Chemically, CBD is a terpenophenol molecule containing a cyclohexene ring, a phenolic ring, and a pentyl side chain, as shown in Figure 1 [1]. ...
... SR144528 is also a CB2 receptor-selective antagonist/inverse agonist which is widely used in cannabinoid research [102]. Currently, there are more options on the market to mimic THC than CBD, including nabilone, HU-210, and dexanabinol [6,103]. Nabilone is used as an antiemetic and for chronic pain management, and dexanabinol has been associated with neuroprotective effects [104,105]. ...
... Nabilone is used as an antiemetic and for chronic pain management, and dexanabinol has been associated with neuroprotective effects [104,105]. These molecules retain THC's ring structures and oxygen atoms [6]. ...
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... The pharmacokinetics of cannabinoids can vary greatly on the basis of route of administration, with inhalation being significantly faster than oral ingestion, with peak plasma levels within 3-10 min [84]. The active ingredients THC and CBD are primarily metabolized in the liver by the cytochrome P450 (CYP)3A4 and CYP2C9 enzymes [85]. ...
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IntroductionPain is a global phenomenon encompassing many subtypes that include neuropathic, musculoskeletal, acute postoperative, cancer, and geriatric pain. Traditionally, opioids have been a mainstay pharmacological agent for managing many types of pain. However, opioids have been a subject of controversy with increased addiction, fatality rates, and cost burden on the US healthcare system. Cannabinoids have emerged as a potentially favorable alternative or adjunctive treatment for various types of acute and chronic pain. This narrative review seeks to describe the efficacy, risks, and benefits of cannabinoids as an adjunct or even potential replacement for opioids in the treatment of various subtypes of pain.Methods In June of 2022, we performed a comprehensive search across multiple databases for English-language studies related to the use of cannabinoids in the treatment of various types pain: neuropathic pain, musculoskeletal pain, acute postoperative pain, cancer pain, and geriatric pain. Data from meta-analyses, systematic reviews, and randomized control trials (RCTs) were prioritized for reporting. We sought to focus our reported analysis on more recent literature as well as include older relevant studies with particularly notable findings.ResultsThere is conflicting evidence for the use of cannabinoids in the management of pain. While cannabinoids have shown efficacy in treating specific chronic pain subtypes such as neuropathic pain, fibromyalgia pain, and geriatric pain, they do not show as clear benefit in acute postoperative and the majority of musculoskeletal pain syndromes. Data trends towards cannabinoids having a positive effect in treating cancer pain, but results are not as conclusive. To date, there is a paucity of data comparing cannabinoids directly to opioids for pain relief. Overall, the side effects of cannabinoids appear to be relatively mild. However, there is still potential for addiction, altered brain development, psychiatric comorbidities, and drug–drug interactions.Conclusion Cannabinoids may be effective in specific subtypes of pain, but current evidence and guidelines do not yet support its use as the first-line treatment for any type of acute or chronic pain. Rather, it may be considered a good adjunct or alternative for patients who have failed more typical or conservative measures. Additional studies are needed with standardized forms of cannabinoids, route of delivery, and dosing for greater-powered analysis. Providers must weigh the individualized patient risks, benefits, and concurrent medication list in order to determine whether cannabinoids are appropriate for a patient’s pain treatment plan.
... Interestingly, in the Barnard et al. (2022) study, plasma THC concentrations were higher at the time of testing (124 ng/ml, 30 min post-IP injection) compared with the present study (40.7 ng/ml, 90 min postoral gavage). This highlights differences in pharmacokinetics and pharmacodynamics based on the route of administration (Baglot et al., 2021), as well as the commonly observed lack of correlation between THC blood levels and behavior (Ginsburg et al., 2014;Grotenhermen, 2003;Hollister et al., 1981). ...
... Following THC or THC + CBD administration, levels of THC and metabolites, 11-OH-THC and THC-COOH observed in the present study were comparable to other preclinical studies (Baglot et al., 2021;Moore, Davis, Harvey, et al., 2021), and these levels are similar to those observed in clinical studies following THC administration (Grotenhermen, 2003). The levels of THC and metabolites This document is copyrighted by the American Psychological Association or one of its allied publishers. ...
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A well-documented side effect of cannabis and Δ9-tetrahydrocannabinol (THC) acute administration is deficits in cognition and attention. Cannabidiol (CBD), a nonintoxicating constituent of cannabis, may modulate THC's impairing effects. A goal of this study was to determine the effects of THC and CBD, alone and in combination, on performance in the rodent Psychomotor Vigilance Test (rPVT), a translational paradigm used to quantify sustained attention. Outcome measures in the rPVT include motor speed, premature responding, and lapses in attention. Sprague Dawley rats were trained to perform the rPVT to the acquisition criteria and then received oral doses (mg/kg) of THC (1-17.6), CBD (1-100), and combinations of THC + CBD in sesame oil prior to rPVT sessions, administered in a within-subject randomized design. Blood was collected from rats receiving selected doses of THC alone or THC + CBD for analysis of THC and its metabolites. THC alone produced significant decreases in accuracy and increases in lapses in attention at higher doses (10 mg/kg; ps < .05). The coadministration of CBD (10 mg/kg) with THC (3 or 10 mg/kg) caused greater impairments to sustained attention compared with administration of THC alone (ps < .05). The rPVT is a translational platform sensitive to detect impairments in attention associated with THC and other cannabis constituents. Further work is necessary to determine the mechanism of THC and CBD interactions on impairments in sustained attention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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The use of cannabinoids in both veterinary and human medicine is controversial for legal and ethical reasons. Nonetheless, the availability and therapeutic use of naturally occurring or synthetic phytocannabinoids, such as Δ ⁹ -tetrahydrocannabidiol and cannabidiol, have been the focus of attention in studies regarding their medical uses. This review aims to examine the role of cannabinoids in pain modulation by analyzing scientific findings regarding the signaling pathways of the endocannabinoid system and discussing the analgesic effects of synthetic cannabinoids compared to cannabinoid extracts and the extent and involvement of their receptors. In animals, studies have shown the analgesic properties of these substances and the role of the cannabinoid binding −1 (CB1) and cannabinoid binding −2 (CB2) receptors in the endocannabinoid system to modulate acute, chronic and neuropathic pain. This system consists of three main components: endogenous ligands (anandamide and 2-arachidonoylglycerol), G protein-coupled receptors and enzymes that degrade and recycle the ligands. Evidence suggests that their interaction with CB1 receptors inhibits signaling in pain pathways and causes psychoactive effects. On the other hand, CB2 receptors are associated with anti-inflammatory and analgesic reactions and effects on the immune system. Cannabis extracts and their synthetic derivatives are an effective therapeutic tool that contributes to compassionate pain care and participates in its multimodal management. However, the endocannabinoid system interacts with different endogenous ligands and neurotransmitters, thus offering other therapeutic possibilities in dogs and cats, such is the case of those patients who suffer from seizures or epilepsy, contact and atopic dermatitis, degenerative myelopathies, asthma, diabetes and glaucoma, among other inflammatory diseases. Moreover, these compounds have been shown to possess antineoplastic, appetite-stimulating, and antiemetic properties. Ultimately, the study of the endocannabinoid system, its ligands, receptors, mechanism of action, and signaling, has contributed to the development of research that shows that hemp-derived and their synthetic derivatives are an effective therapeutic alternative in the multimodal management of pain in dogs and cats due to their ability to prevent peripheral and central sensitization.
... [24][25][26][27] Absorption and bioavailability of THC depends on the type of smoking device, the depth of inhalation, puff duration, smoking habits (breath-holding), and the composition of cigarettes. 28 Vaporization offers a potential risk-reduction tool with a similar pharmacological profile as smoking. 29 In contrast to smoking as a method of delivery, oral absorption of cannabis is slow, variable, and highly dependent on the fat content of associated food ingestion. ...
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... The method of administration of CBPMs, oral versus inhaled, can impact clinical outcomes-including the onset of action and duration of action of the drug. See Table 1 for an appropriate summary of oral versus inhaled administration of CBPMs [36,37]. Oral preparations have delayed onset but act over a longer period compared to inhaled preparations, which act much faster but in conjunction dissipate faster, hence resulting in shorter-term effects. ...
... There are public health concerns regarding the addictive potential of cannabis, particularly with greater concentrations of THC and its withdrawal potential [106]. There is little information on the lethal doses of CBPM in adults unless triggering myocardial infarction leading to death, and it is generally considered that a lethal overdose of CBPM is an unlikely event; note that monkeys can tolerate 9000 mg/kg THC without fatal consequences [37]. However, there are concerns regarding neurotoxicity in paediatric cases of acute toxicity with once case of a fatal outcome [107]. ...
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Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.
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Background Urine drug screening is a frequently used method to detect the abuse of psychoactive substances. Daily heavy cannabis users can have positive urinary cannabinoid metabolites up to 30 days following abstinence. Case presentation Consumer is a 29-year-old male with BMI of 54.64 Kg/m2 and a history of long-term cannabis dependence. He was diagnosed to have co morbid mental illness of schizophrenia. His urinary drug screen was positive for cannabinoid metabolites 102 days following abstinence. He had neither access nor other objective evidence of cannabis use during that period. Confirmatory testing using GC/MS method confirmed the dropping concentration of cannabinoid metabolites over 102 days and confirmed the same with cannabinoid creatinine ratio. Conclusion This is the longest detection period of urinary cannabinoid metabolites following abstinence of cannabis use. Differentiating active recent cannabis use from long term excretion of previously used cannabis is vital in making legal and treatment decisions.
... Out of these cannabinoids, Δ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) are the most significant Page 2 of 7 Amini et al. Journal of Cannabis Research (2022) 4:12 ones (Grotenhermen 2003). THC is responsible for the psychoactive property of cannabis and causes euphoria, drowsiness, hallucinations, and temporal distortions (Ashton 2001). ...
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Background Δ ⁹ -tetrahydrocannabinol (THC) is the main psychoactive component and one of the most important medicinal compounds in cannabis. Whether in human body fluids and breath or in laboratory and field samples, rapid and easy detection of THC is crucial. It provides insights into the impact of THC on human organism and its medicinal benefits, it guides the cannabis growers to determine different stages of the growth of the plant in the field, and eventually it helps scientists in the laboratory to assure the quality of the products and determine their potency or better understand the product development procedures. The significance of fast THC detection in forensic analysis also cannot be overlooked. Electrochemical sensor technologies are currently in the focus of attention for fast, easy, and low-cost detection of THC. Method In this work, we review the recent advances in sensor technologies developed for the purpose of fast and accurate THC detection. The research works performed mostly in the past decade and those detecting THC directly without any derivatization were the main target of this review. The scope of this narrative review was the reports on detecting THC in synthetic samples and plants as well as oral fluid. Results Electrochemical sensor technologies are sensitive enough and have the potential for fast, easy, and low-cost detection of THC for roadside testing, THC trending in growing cannabis plants, THC product development and formulation for medical purposes, etc., and they can provide an alternative for costly chromatography and mass spectrometry-based methods. Conclusion The main challenges facing these sensors, however, are nonspecific interaction and the interference of compounds and species from the matrix. Special requirement for storing sensors modified with antibodies or proteins is another challenge in this field. Preparing long-lasting and reusable sensors is a field worthy of attention.
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