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The Pharmacologic and Clinical Effects of Medical Cannabis
Abstract
Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.
... There is preliminary evidence that cannabis interferes with the anti-coagulant properties of prescribed drugs used for treating blood clot (Murmoin, 2015) [17] . The mechanism for the antiinflammatory and possible pain-relieving effects of hemp were not defined and there were no governmental regulatory approvals or clinical or active for use of them as a drug (Borgelt et al, 2013). Medically, hemp refers to the use of cannabis and its cannabinoids to treat disease or improve symptoms, however there is no single agreed upon definition (Murmoin, 2015) [17] . ...
... The rigorous scientific study of cannabis as medicine has been hampered by production restriction and by the fact that it's classified as an illegal drugs by many government. There is unlimited evidence suggesting cannabis can be used to reduced nausea and vomiting during chemotherapy, to improve the appetite in people with HIV/AIDS or to treat chronic pain and muscle spasms (Borgelt et al, 2013) [9] . So, the significant of the study is primarily aim at providing information about the nutritional evaluation of cannabis seed, and the importance of the seed. ...
... The rigorous scientific study of cannabis as medicine has been hampered by production restriction and by the fact that it's classified as an illegal drugs by many government. There is unlimited evidence suggesting cannabis can be used to reduced nausea and vomiting during chemotherapy, to improve the appetite in people with HIV/AIDS or to treat chronic pain and muscle spasms (Borgelt et al, 2013) [9] . So, the significant of the study is primarily aim at providing information about the nutritional evaluation of cannabis seed, and the importance of the seed. ...
The hemp (Cannabis sativa) used for this work were obtained in a farm at Ogbese in Owo Local Government of Ondo State Nigeria. They were prepared for use by decoating, sun drying and milling. The milled sample were subdivided into two portions, one portion was defatted and named as defatted sample using normal hexane while the other portion was left raw. The samples were powdered in willey mill 60 mesh sizes and stored in screw cap bottle at room temperature for further analysis. Proximate analysis, mineral, phytochemical and functional composition of hemp (Cannabis sativa) were examined. The mean values of various parameters for proximate composition, of both raw and defatted samples were moisture content (5.65+0.03) and (5.60+0.05), ash content (6.50+0.01) and (6.40+0.01), fiber content (18.85+0.20 and 16.05+0.12), fat content (30.43+0.03) and (15.60+0.15), crude protein (25.45+0.02) and (28.05+0.00) and finally carbohydrate (13.12+0.01) and (28.30+0.02) for both raw and defatted samples respectively. Mineral (mg/kg) includes Potassium (8.75+0,01), Calcium (18.60+0.35), Sodium (7.52+0.02), Magnesium (14.10+0.03), Zink (2.10+0,02), Lead (0.05+0,01). The macronutrients and micronutrients present in the study is required for optimal functioning of physiological and biochemical process in the body. The results of functional properties of Cannabis sativa seed flour with the mean value of the following parameters bulk density (20.05+0.01 g/ml), Water absorption capacity (35.15+0.12), Oil absorption capacity (25.01+0.12), Foaming capacity (5.05+0.01) and Emulsion capacity (20.00+0.01) respectively. The result of phytochemical screening revealed that Oxalate, saponin and alkaloid were moderately present in Cannabis sativa seed four, tannins was slightly present while phytate was highly present in Cannabis sativa seed flour suggesting that the Cannabis sativa is relatively save for consumption.
... • Bypasses first pass metabolism [16] • Difficult to determine the total amount of product inhaled or absorbed, leading to unintended bias • Difficult to reliably titrate dose when dose inhaled is uncertain [16] • May be less portable depending on device used to vaporize product • Bystanders exposed to inhaled product [16,19] • Longer duration to peak plasma concentration (120 minutes) [2,16,19] • Lower bioavailability [16,19] • Undergoes first-pass metabolism [16] • the active concentration of cannabinoids, enhancing the possibility of adverse effects, or they may decrease cannabinoid concentrations, compromising their physiologic effects [33]. The converse effect might be expected from the competing drug. ...
... • Bypasses first pass metabolism [16] • Difficult to determine the total amount of product inhaled or absorbed, leading to unintended bias • Difficult to reliably titrate dose when dose inhaled is uncertain [16] • May be less portable depending on device used to vaporize product • Bystanders exposed to inhaled product [16,19] • Longer duration to peak plasma concentration (120 minutes) [2,16,19] • Lower bioavailability [16,19] • Undergoes first-pass metabolism [16] • the active concentration of cannabinoids, enhancing the possibility of adverse effects, or they may decrease cannabinoid concentrations, compromising their physiologic effects [33]. The converse effect might be expected from the competing drug. ...
... • Bypasses first pass metabolism [16] • Difficult to determine the total amount of product inhaled or absorbed, leading to unintended bias • Difficult to reliably titrate dose when dose inhaled is uncertain [16] • May be less portable depending on device used to vaporize product • Bystanders exposed to inhaled product [16,19] • Longer duration to peak plasma concentration (120 minutes) [2,16,19] • Lower bioavailability [16,19] • Undergoes first-pass metabolism [16] • the active concentration of cannabinoids, enhancing the possibility of adverse effects, or they may decrease cannabinoid concentrations, compromising their physiologic effects [33]. The converse effect might be expected from the competing drug. ...
Cannabis medicines are in demand from the public for treating a range of diseases and symptoms; however, clinicians are reluctant to prescribe these products because of limited evidence and prescribing information. To generate this evidence , quality clinical trials of cannabis medicines must be undertaken, yet their design is a complex, often uncharted territory, and involves the cooperation and sharing of knowledge of multiple stakeholders. Before designing a clinical trial, researchers require a clear understanding of the potential therapeutic benefit cannabis medicines may have, the form and formulation of the product, and the dose to be investigated. Researchers must also be aware of the applicable pharmaceutical regulations in the country or jurisdiction where the research is to be undertaken, as well as manufacturing or licensing regulations that may be imposed at the source of the cannabis product. Importantly, collaborations with industry are a key to the successful outcome of cannabis medicines clinical trials. Without funding and sponsorship of clinical trials, the ability to generate quality data will be limited and the evidence for cannabis medicines to be registered as therapeutics lacking. Collaborations between researchers, industry, and regulators, working together in sharing knowledge, are therefore critical to generate high quality cannabis medicines research.
... Most studies where pediatric patients are given cannabis-based drugs involve oral administration, typically oil drops or oromucosal sprays (Tables 1 and 2). While obviously preferable to inhalation, given the age of the patients, this method typically has low bioavailability, typically between 5% and 20% [81]. While intravenously administered cannabis has similar bioavailability to inhaled cannabis [81], there have been no investigations into this method of administration in children. ...
... While obviously preferable to inhalation, given the age of the patients, this method typically has low bioavailability, typically between 5% and 20% [81]. While intravenously administered cannabis has similar bioavailability to inhaled cannabis [81], there have been no investigations into this method of administration in children. ...
... However, some patients did not respond to medical marijuana treatment. The authors attributed the lack of negative side effects (and possibly the lack of response) to the fact that most chose oil drops as the method of ingestion, which typically have very low bioavailability [81]. However, the study did not use validated methods of collecting information about patient response and acknowledges the possibility of a placebo effect [89]. ...
The antineoplastic effects of cannabis have been known since 1975. Since the identification of the components of the endogenous cannabinoid system (ECS) in the 1990s, research into the potential of cannabinoids as medicine has exploded, including in anti-cancer research. However, nearly all of this research has been on adults. Physicians and governing bodies remain cautious in recommending the use of cannabis in children, since the ECS develops early in life and data about cannabis exposure in utero show negative outcomes. However, there exist many published cases of use of cannabis in children to treat pediatric epilepsy and chemotherapy-induced nausea and vomiting (CINV) that show both the safety and efficacy of cannabis in pediatric populations. Additionally, promising preclinical evidence showing that cannabis has anti-cancer effects on pediatric cancer warrants further investigation of cannabis’ use in pediatric cancer patients, as well as other populations of pediatric patients. This review aims to examine the evidence regarding the potential clinical utility of cannabis as an anti-cancer treatment in children by summarizing what is currently known about uses of medical cannabis in children, particularly regarding its anti-cancer potential.
... THC is predominantly important for psychoactive effects, whereas CBD is often found in hemp-containing commercial commodities, such as paper, construction material, and textiles. [27][28][29][30][31][32] The dried leaves, flowers, and seeds of these plants are used as marijuana, which has both recreational and therapeutic effects. The varying content of THC and CBD are present in different strains of cannabis, altering their clinical effects. ...
... By seeing the rapidly increasing demand for research on marijuana, we have tried to gather the statistical information from publications on marijuana at science direct. Just by searching with a single keyword, "marijuana," we had got 37,119 results (dated October 12, 2020) [190] including review articles (3131), research articles (19,561), encyclopedia (610), conference abstracts (2728), book chapters (3925), book reviews (659), case reports (335), conference info (67), correspondence (556), discussion (375), data articles (4) editorials (383), errata (26), examinations (28), mini-reviews (189), news (240), practice guidelines (66), product reviews (9), short communications (2036), and other (2191). It indicates the focus of academicians, scientists, and other health professionals on marijuana research and its related products or phytoconstituents. ...
... After ingestion, absorption is slow and variable due to the degradation by gastric acid and hepatic first-pass metabolism. Bioavailability ranges from 10% to 20% and is lower than the inhaled route [14,15]. However, many edibles contain a much higher concentration of THC than smoked cannabis [15]. ...
... Bioavailability ranges from 10% to 20% and is lower than the inhaled route [14,15]. However, many edibles contain a much higher concentration of THC than smoked cannabis [15]. In addition, edibles are ingested by a greater number of children due to their palatability, interesting packaging, and delayed onset of symptoms [3,16,17]. ...
An increasing trend of cannabis use places children at risk for the detrimental effects of marijuana. Poison control centers in the United States have been experiencing an upsurge in calls involving marijuana ingestion among children in the past years, specifically in states where marijuana is legal. With marijuana ingestion, neurologic symptoms predominate but cardiovascular manifestations have also been observed. Bradycardia and bradyarrhythmia are both uncommon cardiac manifestations of cannabis ingestion in children. Here, we present the case of a previously healthy two-year-old male with sinus bradycardia and first-degree atrioventricular (AV) block following accidental ingestion of tetrahydrocannabinol-laced gummies. Although bradycardia and first-degree AV block are uncommon after cannabis ingestion in children, clinicians should be aware of these findings and must consider evaluating for marijuana toxicity whenever presented with these acute signs. Prevention is crucial and can be achieved through supervision, parental education, and support.
... [21] Both CB1 and MORs are present on the presynaptic membrane, in the different brain areas, and overlap in the reduction of the neurotransmitter release. [22] These receptors are involved in the primary rewarding effects of drugs. [23] The interaction between orexinergic and cannabinoid systems in some areas of reward circuits, in response to some addictive substances such as nicotine, has already been demonstrated. ...
... [47] Both CB1 and µ receptors are present on the presynaptic membrane and by inhibition of adenylate cyclase, a decrease of Ca 2+ conduction and an increase of K conduction reduce the release of neurotransmitters, such as acetylcholine, serotonin, and noradrenaline. [22,48] Furthermore, stimulation of CB1 can reduce the release of GABA on pyramidal neurons in the hippocampus. [48] Thus, blockade of this receptor in the basal state may have no effect on neuronal activity, but when an effective drug such as tramadol has affected this area, it can prevent the effects of tramadol by inhibiting GABA release. ...
Background:
CA1, as a major structure involved in learning and memory, has been shown to be affected by tramadol addiction. Both orexin and endocannabinoid receptors express in CA1 and play an important role in drug dependency. The aim of this study was to evaluate the modulatory effects of orexin-2 (OX2R) and endocannabinoid-1 (CB1R) receptors on neuronal activity in CA1, in response to tramadol in rats.
Materials and methods:
Male Wistar rats were divided into 8 groups (n = 6-7); saline-dimethyl sulfoxide (DMSO), tramadol-DMSO, saline-TCS-OX2-29, saline-AM251, tramadol-TCS-OX2-29, tramadol-AM251, saline-TCS-OX2-29-AM251, tramadol-TCS-OX2-29-AM251. Tramadol was injected intraperitoneally, and then, AM251 (1 nmol/0.3 μL), CB1R antagonist and TCS-OX2-29 (1 nmol/0.3 μL), OX2R antagonist, were microinjected individually or concurrently into the CA1. Using in vivo extracellular single-unit recording, the firing of CA1 pyramidal neurons was investigated.
Results:
Tramadol decreased neuronal activity in CA1 (P < 0.01) but increased it after micro-injection of DMSO. TCS-OX2-29 increased neuronal activity in saline group (P < 0.05) but decreased it in tramadol group. AM251 had no effect on saline group but decreased neuronal activity in tramadol group (P < 0.05). Concurrent micro-injection of TCS-OX2-29 and AM251 had no effect on saline group but decreased neuronal activity in tramadol group (P < 0.05).
Conclusions:
Our findings suggest that neural activity in CA1 is rapidly affected by acute use of tramadol, and some of these effects may be induced through the endocannabinoid and orexin systems. Thus, the function of endocannabinoid and orexin systems in CA1 may play a role in tramadol addiction.
... These edibles can correspond with candy bars, gummy bears, etc. that can contain 100 mg or less of THC (Light et al. 2014). However, the consumption of this type of product can be problematic due to the peak of THC serum concentration by orally absorbed not being reached until around between 1-3 hours elapsed (Borgelt et al. 2013;Hudak, Severn, and Nordstrom 2015). This period is in accordance with the experiments carried out by Cone et al. (1988) in a laboratory study where different participants received marijuana-laced brownies and experimented peak responses between 2.5 to 3.5 hours after ingestion (Cone et al. 1988).In addition, it is also necessary to take into account the bioavailability, in this case, and according to the reported literature by Borgelt et al. (2013), this can vary between 5 and 20% for THC and between 13 and 19% for cannabidiol. ...
... However, the consumption of this type of product can be problematic due to the peak of THC serum concentration by orally absorbed not being reached until around between 1-3 hours elapsed (Borgelt et al. 2013;Hudak, Severn, and Nordstrom 2015). This period is in accordance with the experiments carried out by Cone et al. (1988) in a laboratory study where different participants received marijuana-laced brownies and experimented peak responses between 2.5 to 3.5 hours after ingestion (Cone et al. 1988).In addition, it is also necessary to take into account the bioavailability, in this case, and according to the reported literature by Borgelt et al. (2013), this can vary between 5 and 20% for THC and between 13 and 19% for cannabidiol. The fact of this time-lapse has caused that some consumers ate the suggested serving size but due to that they "didn't feel anything" they continued eating and consumed over 100 mg of THC (Hudak, Severn, and Nordstrom 2015). ...
The commercialization of products with cannabidiol (CBD) has undergone a significant increase. These products can be presented in different forms such as baked goods, gummies or beverages (such as kombucha, beer or teas, among others) using wide concentrations ranges. The use of CBD in edibles favors its consumption, for medicinal users, during the work week, avoid its possible social stigma and facilitates its transport. These products can be purchased on store shelves and online. There is a large number of specialized studies, in which the possible advantages of CBD consumption are described in the preclinical and clinical trials. it is also necessary to recognize the existence of other works revealing that the excessive consumption of CBD could have some repercussions on health. in this review, it is analyzed the composition and properties of Cannabis sativa L., the health benefits of cannabinoids (focusing on CBD), its consumption, its possible toxicological effects, a brief exposition of the extraction process, and a collection of different products that contain CBD in its composition.
... Prvi se nahaja predvsem v predelih možganov (na primer v hipokampusu, malih možganih, bazalnih ganglijih in v kortikalnih področjih velikih možganov), kar se ujema z njegovim delovanjem na spomin, kognitivne sposobnosti in gibanje (Ferjan et al., 2015). Z vidika terapevtskega delovanja kanabinoidov so zanimivi predvsem receptorji CB 2 , ki so vključeni v proces delovanja imunskega sistema, v vnetne procese in procese zmanjševanja bolečine (Borgelt, Franson, Nussbaum, & Wang, 2013;Ferjan et al., 2015;Bellnier, Brown, & Ortega 2018). ...
... V zadnjih petih letih je prišlo do izrazitega povečanja publikacij o CBD-ju (Zuardi, 2008), ki ga spodbuja predvsem odkritje njegovih protivnetnih, antioksidativnih in nevroprotektivnih učinkov. V zadnjih 45 letih je bilo mogoče dokazati, da ima CBD širok spekter farmakoloških učinkov, ki imajo mnoge terapevtske koristi, vendar še vedno čakajo, da jih potrdijo klinične izkušnje (Abramovici, 2013;Borgelt et al., 2013;Ferjan et al., 2015). ...
Uvod: Slovenija je leta 2017 spremenila uredbo o razvrstitvi prepovedanih drog in omogočila uporabo konoplje v medicinske namene. Konoplja ima več kot 140 kanabinoidnih spojin, med katerimi sta najbolj izpostavljeni kanabidiol in tetrahidrokanabinol, saj imata potencial za zdravljenje bolezni. Namen pregleda je raziskati rabo konoplje v medicinske namene.
Metode: Izveden je bil integrativni pregled literature v digitalni zbirki podatkov PubMed, spletnem iskalniku Google učenjak in vzajemnemu bibliografskemu sistemu COBISS s pomočjo besednih zvez: »cannabis AND medical use«, »marihuana AND medical use« in »raba konoplje v medicinske namene«. Omejitve iskanja so bile: obdobje objave literature (2008–2019), prost dostop do recenziranih strokovnih in znanstvenih člankov ter literatura v angleškem ali slovenskem jeziku. Za pregled literature je bila uporabljena tematska analiza prebranega gradiva.
Rezultati: Za pregled literature je bilo za končno analizo primernih 29 člankov. Identificiranih je bilo 52 kod, združenih v štiri teme: (1) zdravljenje s konopljo, (2) lastnosti konoplje, (3) delovanje kanabidiola, (4) delovanje tetrahidrokanabinola.
Diskusija in zaključek: Konoplja se že tisočletja uporablja v medicinske namene. Danes jo v svetu uporabljajo predvsem za zdravljenje naslednjih bolezni: astme, diabetesa, epilepsije, raka, Parkinsonove bolezni, Alzheimerjeve demence, multiple skleroze. V Sloveniji je konoplja odstranjena s seznama najbolj nevarnih drog, a do njene rabe v medicinske namene je zahteven proces.
... Different cannabinoids play different physiological and psychological effects in various human body systems, creating unwanted side effects. The most reported change involves neurological system which dizziness is the most common side effect, nevertheless it is typically not very serious [116]. Cannabis can cause mood and perceptual changes, which can be stated as "being high" or euphoria. ...
... Cannabis can cause mood and perceptual changes, which can be stated as "being high" or euphoria. It can also produce dysphoric reactions, including severe anxiety, panic, depression, paranoid, and agitation [116,117]. Shortterm use may cause impaired short-term memory and impaired motor coordination [118]. On the other hand, long-term use of cannabis has been linked to a motivational syndrome, simulating depression with symptoms of apathy, dullness, lethargy, and impaired judgment [117]. ...
Objective: The purpose of this review was to present general data of cannabinoids, its function related to orofacial pain management, and its adverse effects.
Methods: The data was searched through PubMed database and Google Scholars by various keywords without time limits. Hand searching and citation mining were also applied. Unpublished, incomplete, non-English data were excluded.
Results: The presence of cannabinoids receptors throughout orofacial tissues has been reported, which could be a therapeutic site of action. Only in neuropathic pain, cannabinoids have been proven to be successful over conventional treatment. More clinical approvals of its analgesic effects are extremely required for pain originating from other tissues. When prescribing cannabis, dentists should be cautious about its adverse effects in many systems.
Conclusion: Currently, cannabinoids have not been officially endorsed for analgesic effects in orofacial area. It can be useful for neuropathic orofacial pain especially when the standard treatment was unsuccessful.
... 98 Therefore, this compound is responsible for the known psychoactive effects of Cannabis sativa, such as euphoria, sedation, and hallucination. 83,102 This agonist effect on CB1 explains the use of this substance for pain relief in several clinical conditions, 103 such as neuropathic pain, 104 for nausea and vomiting associated with chemotherapy, 103 and for the treatment of psychiatric diseases such as anxiety and depression. 105 However, this compound used alone can cause several side effects (Fig. 1). ...
... 98 Therefore, this compound is responsible for the known psychoactive effects of Cannabis sativa, such as euphoria, sedation, and hallucination. 83,102 This agonist effect on CB1 explains the use of this substance for pain relief in several clinical conditions, 103 such as neuropathic pain, 104 for nausea and vomiting associated with chemotherapy, 103 and for the treatment of psychiatric diseases such as anxiety and depression. 105 However, this compound used alone can cause several side effects (Fig. 1). ...
Introduction: Obesity is defined as an excess of accumulation of fat that can be harmful to health. Storage of excess fat in the adipose tissue triggers an inflammatory process, which makes obesity a low-grade chronic inflammatory disease. Obesity is considered a complex and multifactorial disease; hence, no intervention strategy appears to be an ideal treatment for all individuals. Therefore, new therapeutic alternatives are often studied for the treatment of this disease. Currently, herbal medicines are gaining ground in the treatment of obesity and its comorbidities. In this context, much attention is being paid to Cannabis sativa derivatives, and their therapeutic functions are being widely studied, including in treating obesity. Objective: Highlight the pharmacological properties of Δ9-tetrahydrocannabivarin (THCV), Δ9-tetrahydrocannabidinol (THC), and cannabidiol (CBD), the predominant isolated components of Cannabis sativa, as well as its therapeutic potential in the treatment of obesity. Methods: This is a narrative review that shows the existing scientific evidence on the clinical application of Cannabis sativa as a possible treatment for obesity. Data collection was performed in the PubMed electronic database. The following word combinations were used: Cannabis and obesity, Cannabis sativa and obesity, THCV and obesity, THC and obesity, CBD and obesity, and Cannabis sativa and inflammation. Results: Evidence shows that Cannabis sativa derivatives have therapeutic potential due to their anti-inflammatory properties. In addition, people who use cannabis have a lower body mass index than those who do not, making the plant an option to reduce and reverse inflammation and comorbidities in obesity. Conclusion: It is concluded that phytocannabinoids derived from Cannabis sativa have therapeutic potential due to its anti-inflammatory, antioxidant, and neuroprotective properties, making the plant a study option to reduce and reverse inflammation and comorbidities associated with obesity.
... Posteriormente, en 1992, esta droga fue aprobada como estimulante del apetito para evitar la pérdida de peso en pacientes con Síndrome de Inmunodeficiencia Adquirida (SIDA) en EE.UU., Nueva Zelanda y Alemania (Struwe et al., 1993). (Borgelt et al., 2013;Hazekamp et al., 2013;Whiting et al., 2015). Curiosamente, la inclusión del componente no psicoactivo cannabidiol (CBD) en Sativex® reduce muchos de los efectos adversos, como la disforia y la sedación, que se producen cuando los cannabinoides sintéticos de THC se administran solos (Russo & Guy, 2006). ...
... Since then, the use of cannabis-based medicines (CBMs) has dramatically increased [2]. CBMs are widely used in the treatment of several conditions and symptoms such as chronic pain, multiple sclerosis, epilepsy, nausea, vomiting and spasticity, to mention but a few [3,4]. Moreover, CBMs cover a wide number of substances ranging from recreational cannabis used in medical settings with a licence to plantbased cannabidiol (CBD); tetrahydrocannabinol (THC) and combinations thereof (CBD/THC), all prescribed in different doses and combinations. ...
Background
Cannabis-based medicines are widely used in the treatment of a number of medical conditions. Unfortunately, cognitive disturbances are often reported as adverse events, although conversely, cognitive improvements have been reported. Hence, the objective of the present study was to identify, critically appraise and synthesise research findings on the potential impact of cannabis-based medicines on cognitive functioning.
Methods
Four databases (EMBASE, PsycINFO, PubMed and Scopus) were systematically searched. Studies were included if they provided findings on the impact of cannabis-based medicines in controlled settings on cognitive functioning measured by recognised cognitive tests in human adults. Study participants were required to be their own case-control, and neither studies on abuse, abstinences, patients with severe neurodegenerative diseases nor cancer-related pain conditions were included. Screening, risk of bias assessment and data extraction were conducted independently by two researchers. Findings were tabulated and synthesised by outcome.
Findings
Twenty-three studies were included, comprising a total of N = 917. Eight studies used Sativex as the cannabis-based medicine two used Epidiolex, two other studies used sprays, three studies used gelatine capsules, five smoked cannabis, two other and finally one studied cannabis withdrawal. Fifteen studies reported non-significant findings; six reported cognitive impairments; one study found cognitive improvement and a single study found improvement following withdrawal. Thirteen studies had cognitive or neuropsychological functioning as the primary outcome.
Conclusions
Due to a large heterogeneity and methodological limitations across studies, it is not possible to make any definite conclusions about the impact of cannabis-based medicines on cognitive functioning. However, the majority of high-quality evidence points in the direction that the negative impact of cannabis-based medicines on cognitive functioning is minor, provided that the doses of THC are low to moderate. On the other hand, long-term use of cannabis based medicines may still adversely affect cognitive functioning. In the studies that found impaired cognitive functioning to be significant, all of the test scores were either within the normal range or below what would be characterised as a neuropsychologically cognitive impairment.
... After decades of legal restrictions and prohibitions, the use of Cannabis sativa L. (hereinafter, cannabis) for medical purposes has significantly increased in the past few years. Its clinical benefits include the symptomatic treatment of anorexia, pharmacological-induced nausea, multiple sclerosis, AIDS and many other conditions [1][2][3]. The pharmacological and psychoactive effects of cannabis are mostly attributed to the cannabinoids present in the plant, particularly delta-9 tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), which become active after decarboxylation to delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) [4]. ...
The therapeutic use of Cannabis oil extracts is constantly increasing. However, in Italy, they are allowed to be prepared with only a few methods and matrices. With this work, we aimed to assess how the different processes might affect the chemical composition of two different matrices (olive oils and medium chain triglycerides oils - MCT), accounting as variables for both the presence of Cannabis dried apices of the female flower and the adding of tocopherol acetate as an antioxidant. The macerated oils were prepared with four of the methods allowed according to the Italian legislation (Romano-Hazekamp, Cannazza-Citti, SIFAP and Calvi) and analyzed for normal and oxidized tocopherols, oxidized and conjugated fatty acids and volatile carbonyl compounds (VCCs), all using liquid chromatography coupled to UV or PDA detectors. According to our results, neither normal nor oxidized tocopherols are affected by the addition of antioxidants or Cannabis, while the oxidation state (according to the levels of oxidized and conjugated fatty acids) is often altered in either case. The VCCs concentrations, on the other hand, are never notably altered. These results suggest a worthless use of antioxidants in Cannabis macerated oils preparations, while the dried apices of female flowers might have a protective role in maintaining the oil oxidation state.
... Cannabinoids are a large group of compounds found in Cannabis sativa and Cannabis indica plants, whose two major constituents are tetrahydrocannabinol (THC) and cannabidiol (CBD). Different categories of cannabinoid medicines are currently used: cannabis-derived pharmaceuticals, including synthetics (e.g., nabilone and dronabinol) and botanical cannabinoids (e.g., nabiximols), and various phytocannabinoid plant-derived preparations (i.e., medical cannabis or marijuana) [3]. Cannabinoids can be administered orally (ingested, topically, or sublingually), smoked, inhaled, mixed with food, or assumed as a decoction [4]. ...
Introduction:
The IASP ICD-11 chronic primary pain (CPP) definition includes 19 different painful conditions. In recent years, interest in the potential role of cannabinoids in the management of CPP has increased, since they demonstrated a possible efficacy in treating pain, especially in secondary pain conditions. However, limited evidence is available for patients with CPP. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of cannabinoid administration in CPP.
Methods:
PubMed, EMBASE, and Cochrane Library were searched form the beginning up to 31 October 2021 to retrieve published articles of randomized controlled trials (RCTs) or observational, retrospective or prospective, studies, investigating cannabinoids in CPP. The study screening process was completed during November 2021. The primary outcome was pain reduction by means of the visual analogue scale (VAS). Secondary outcomes were quality of life by means of the fibromyalgia impact questionnaire (FIQ) or other available scales, appetite, anxiety, depression, and sleep by means of any available scales. Safety was assessed with the reporting of serious adverse events (SAE) and discontinuation due to adverse events. Risk of bias was assessed. The weighted generic inverse variance method and Mantel-Haenszel method were used to estimate the mean difference (MD) and odds ratios (OR) with 95% confidence intervals (CI) for continuous and dichotomous outcomes, respectively. For outcome measures reported with different scales (pain, anxiety, depression), we used the standardized MD (SMD) as the effect measure and then converted it into units of the VAS scale for pain, the Beck Anxiety Inventory (BAI) for anxiety, and the Beck Depression Inventory (BDI) for depression. Summary of findings was produced using GRADEproGDT.
Results:
From 3007 identified records, we included eight articles reporting the results of eight different RCTs (four parallel and four crossover studies; seven compared to placebo and one to amitriptyline), with a total population of 240 patients. VAS pain reduction was non-significant for cannabinoids against placebo (MD = - 0.64; 95% CI - 1.30 to 0.02) or amitriptyline (MD = - 0.19; 95% CI - 0.58 to 0.19). More than 4 weeks cannabinoid treatment significantly reduced pain compared to placebo in parallel studies with more than 4 weeks of treatment duration (MD = - 1.28; 95% CI - 2.33 to - 0.22). Differences for the FIQ (MD = - 21.69; 95% CI - 46.20 to 2.82), BAI (MD = - 2.32; 95% CI - 7.99 to 3.08), and BDI (MD = 2.32; 95% CI - 1.71 to 6.35) were non-significant, likewise for discontinuation due to adverse events (OR = 2.15; 95% CI 0.44-10.65), when comparing cannabinoids to placebo. The quality of the evidence was generally low mainly as a result of imprecision and risk of bias.
Conclusion:
Cannabinoid treatment in patients with CPP had limited benefit on pain relief; however, it might improve pain with long-term administration.
... The many bioactive compounds in cannabis are known as cannabinoids, which bind to cannabinoid receptors (CB1 and CB2) on cell membranes [28]. These cannabinoid receptors typically bind endogenous cannabinoids (anandamide and 2-arachidonoylglycerol) [29]. CB1 receptors are mainly found in the central and peripheral nervous systems; CB2 receptors are primarily found on immune cells [28]. ...
Background Spinal stenosis is a degenerative narrowing of the spinal canal with encroachment on the neural structures by surrounding bone and soft tissue. This chronic low back condition can cause restrictions in mobility, impairment of daily activities, opioid dependence, anxiety, depression, and reduced quality of life. Spinal stenosis can be treated through surgical and nonsurgical methods, but neither has proven consistently reliable. Cannabidiol (CBD) has also been observed to have anxiolytic, anti-inflammatory, antiemetic, and antipsychotic behaviors. CBD may provide greater nonsurgical treatment options for the pain associated with spinal stenosis while minimizing the need for opioids. An observational study was undertaken to assess the effects of CBD on patients suffering from chronic spinal stenosis. Methodology This observational study was investigator-initiated and designed to determine the effect of hemp-derived CBD gel caps for patients with spinal stenosis related to low back pain and leg pain relative to patient outcomes, medication utilization, and quality of life outcome measures. A total of six physician visits would be required where a set of surveys would be filled out each four weeks apart. Results The study population consisted of 48 patients. The patient population's age ranged from 63 to 95 years and was normally distributed, with a mean age of 75 ± 7.13 years. The sex distribution was 33% male and 67% female patients. The pain was broken down between the six visits for each of the following four questions: pain right now, usual pain level during the week, best pain level during the week, and worst pain level during the week. Usual pain levels (p < 0.001) and worst pain levels (p < 0.005) demonstrated statistically significant improvement over time, while pain right now (p > 0.05) and best pain level (p > 0.05) stayed consistent throughout without statistical significance. Conclusions This open-label, prospective, observational study found that treatment with hemp-derived CBD gel caps was associated with significant improvements in pain scores and several quality-of-life measures for patients with lumbar spinal stenosis.
... The lack of fluid in the intestine leads to constipation [17]. Cannabis is an alternative analgesic treatment with positive effects in pain alleviation for cancer patients [18]. Cannabinoids are chemical compounds that affect neurotransmitter release and could be helpful for patients with chronic pain from inflammatory or neuropathic conditions [19]. ...
Esophageal Cancer (EC) has the sixth-worst prognosis because of its aggressiveness and poor survival. Patients with EC are malnourished due to anorexia, dysphagia, pain, and hypercatabolic state, which results in cancer cachexia and high mortality rates. Oral feeding usually remains inadequate to cover nutritional needs, while Enteral Nutrition (EN) remains the recommended solution. Here, we report on a 78-year-old male diagnosed with tumor of the esophagus with dysphagia and cachexia under opioid therapy, who fed on Percutaneous Endoscopic Transgastric Jejunostomy (PEG-J) after undergoing surgery. In contrast with the usual clinical practice for semi-elemental formulas via jejunos-tomy, we fed with a polymeric solution to cause temporarily normal defecation in the presence of morphine-induced constipation. The family decided to administer hemp oil to the patient alternatively with morphine. Surprisingly, the polymeric formula was well tolerated, weight and muscle mass increased, and nutrition indices improved. In addition, the use of hemp oil contributed to pain alleviation. Following this experimental approach, the patient gained weight, sarcopenia was revoked in a short time, as depicted from the computed tomography, and tumor size was reduced by 30%. The clinical observation in this study poses questions about the potential benefits of hemp oil in cancer patients.
... The two main cannabinoids found in cannabis are ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) [33]. THC is considered a psychoactive component, while CBD lacks psychotropic activity [10]. ...
For centuries, the cannabis plant has been used as a source of food, fiber, and medicine. Recently, scientific interest in cannabis has increased considerably, as its bioactive compounds have shown promising potential in the treatment of numerous musculoskeletal and neurological diseases in humans. However, the mechanisms that underlie its possible effects on neurodevelopment and nervous-system functioning remain poorly understood and need to be further investigated. Although the bulk of research on cannabis and cannabinoids is based on in vitro or rodent models, the zebrafish has now emerged as a powerful in vivo model for drug-screening studies and translational research. We here review the available literature on the use of cannabis/cannabinoids in zebrafish, and particularly in zebrafish models of neurological disorders. A critical analysis suggests that zebrafish could serve as an experimental tool for testing the bioactivity of cannabinoids, and they could thus provide important insights into the safety and efficacy of different cannabis-extract-based products. The review showed that zebrafish exhibit similar behaviors to rodents following cannabinoid exposure. The authors stress the importance of analyzing the full spectrum of naturally occurring cannabinoids, rather than just the main ones, THC and CBD, and they offer some pointers on performing behavioral analysis in zebrafish.
... These compounds act on the cannabinoid receptors (CB1 and CB2) that normally bind endogenous cannabinoids (anandamide and 2-arachidonoylglycerol) to affect appetite, mood, and pain. 7 The CB1 receptors are mostly found in the central nervous system and peripheral nervous system, particularly in the nocicep-n Review Article tive centers of the dorsal root ganglion. 8 Conversely, CB2 receptors are located within immune and musculoskeletal cells and are important for the regulation of inflammatory processes. ...
Cannabinoid compounds are being increasingly used as an analgesic adjuvant in the orthopedic population, but little data exist to either support or oppose this practice pattern. A review of all contemporary (2000-2020) studies on the use of cannabinoids in orthopedics is presented. Physicians and patients are optimistic that cannabinoids can decrease pain scores and perhaps opioid use; however, their application in orthopedics is not well characterized. In addition to the social stigma regarding the use of cannabis, there is limited high-quality evidence of the efficacy of cannabinoids in treating orthopedic-related pain. As cannabis becomes more accessible, well-designed trials are needed to better understand cannabinoids and guide orthopedic practice. [Orthopedics. 202x;xx(x):xx-xx.].
... There are currently four cannabis-based pharmaceuticals (apart from the cannabis plant) that are approved by a major regulatory body, such as the Food and Drug Administration (United States) or the Medicines and Healthcare products Regulatory Agency (United Kingdom) (Advisory Council on the Misuse of Drugs (ACMD). 2020; Schlag et al. 2020;Borgelt et al. 2013): i. Dronabinol, synthetic delta-9-tetrahydrocannabinol (THC) administered as a per oral capsule for the treatment of anorexia and weight loss in patients with acquired immune deficiency syndrome; and chemotherapy-induced nausea and vomiting. ii. ...
Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.
... Moreover, there is a risk of developing addiction, although this risk may vary depending on routes of administration, doses, forms of cannabis and setting (13). Estimations indicate that 10-20 percent of those using cannabis on a daily basis develop addiction (14) and that a ∼10% of those who use cannabis even once develop an addiction (1). Prior research has repeatedly shown that low socioeconomic status is a risk factor for substance use and related problems (15,16). ...
Background
Cannabis use carries an increased risk of ill health and social problems, especially when initiated at a young age. Drug use is influenced by individual beliefs, knowledge, and attitudes, which are, in turn, governed by social and environmental factors. In recent years, a less restrictive attitude toward cannabis has been observed in many countries, with concerns about increased cannabis use among young people. The aim of the current study was to gain a deeper understanding of young adults' attitudes toward cannabis use and public prevention information about cannabis.MethodsA qualitative interview study was conducted among 32 anonymous informants aged 18–29 years in the Stockholm region. Participants were recruited through purposeful sampling, and semi-structured in-depth interviews were conducted using a digital video calling platform. A qualitative content analysis of the interviews was performed to generate categories and codes for cannabis use and attitudes toward prevention information.ResultsBoth cannabis users and abstainers perceived some risks with cannabis; however, for many users, the positive effects appeared to outweigh any expected harm. Furthermore, the existing public information was perceived as less credible because of an excessive focus on harm. The informants expressed a desire for neutral facts about the effects of cannabis, delivered by credible senders. Moreover, they felt that prevention information should be delivered by individuals whom young people look up to or with whom they can identify, for example, people with authority or famous people such as influencers. The informants also underlined the importance of dialogue with the target group and taking young people's experiences into account when providing information about cannabis.Conclusion
Current risk awareness associated with cannabis use among young adults is insufficient to prevent them from using cannabis. Public prevention information should preferably combine a fact-based focus on risks with recognition of cannabis' short-term desired effects, delivered by credible senders with authority or those with whom young people can identify.
... These steps in education will provide greater consumer safety and satisfaction and enhance the potential for efficacy for the patient. Oncologists may have broad utility for symptom management, and compared with other therapeutic agents, the side effect profile of cannabis is suitable (157,158). ...
Cannabis and cannabinoids are increasingly being accessed and used by patients with advanced cancer for various symptoms and general quality of life. Specific symptoms of pain, nausea and vomiting, loss of appetite and cachexia, anxiety, sleep disturbance, and medical trauma are among those that have prompted patients with cancer to use cannabis. This conference report from the National Cancer Institute’s “Cannabis, Cannabinoid and Cancer Research Symposium” on the topic of “Cancer Symptom/Treatment Side Effect Management” is an expert perspective of cannabis intervention for cancer and cancer treatment-related symptoms. The purpose of the symposium was to identify research gaps, describe the need for high-quality randomized prospective studies of medical cannabis for palliative care in patients with cancer, and evaluate the impact of medical cannabis on cancer survivors’ quality of life. Further, education of clinicians and affiliated health-care providers in guiding cancer patients in using cannabis for cancer care would benefit patients. Together, these steps will further aid in refining the use of cannabis and cannabinoids for symptom palliation and improve safety and efficacy for patients.
... It has pivotal psychotropic effects including exhilaration, hallucinations, delusions, blurred vision, poor coordination, stupor and coma [256]. There is also evidence that THC accumulates in the brain [257]. For these reasons, psychoactive cannabinoids at higher doses are not used for clinical applications. ...
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.
... CB1R has been implicated in various disorders. However, the direct modulation of CB1R by agonists or antagonists has been associated with adverse psychiatric effects, such as depression, anxiety and suicidal ideation, thus limiting the clinical development of such agents [21]. ...
Novel interest has arisen in recent years regarding bone, which is a very complex and dynamic tissue deputed to several functions ranging from mechanical and protective support to hematopoiesis and calcium homeostasis maintenance. In order to address these tasks, a very refined, continuous remodeling process needs to occur involving the coordinated action of different types of bone cells: osteoblasts (OBs), which have the capacity to produce newly formed bone, and osteoclasts (OCs), which can remove old bone. Bone remodeling is a highly regulated process that requires many hormones and messenger molecules, both at the systemic and the local level. The whole picture is still not fully understood, and the role of novel actors, such as the components of the endocannabinoids system (ECS), including endogenous cannabinoid ligands (ECs), cannabinoid receptors (CBRs), and the enzymes responsible for endogenous ligand synthesis and breakdown, is extremely intriguing. This article reviews the connection between the ECS and skeletal health, supporting the potential use of cannabinoid receptor ligands for the treatment of bone diseases associated with accelerated osteoclastic bone resorption, including osteoporosis and bone metastasis.
... Ancak elde edilen verilerde THC'nin endişe verici yan etkileri olduğu kaydedilmiştir[73][74][75].Kannabinoidlerin analjezik olarak kullanımı, daha çok opioid gibi diğer analjezik ilaçlara alternatif bulma hedefi dolayısıyla ortaya çıkmıştır. Hava yoluyla kenevirin kullanımınının ağrı üzerindeki etkisini araştıran bir çalışmada artan THC oranıyla birlikte katılımcıların hissettikleri ağrı derecesinin de azaldığını bildirdiği kaydedilmiştir[76]. Genel olarak kenevirin analjezik etkisinin hafif olduğu, özellikle bu amaçla reçete edilen GABA reseptör agonistleri gabapentin ve pregabalin gibi ilaçlar kadar etkili olmadığı ifade edilmektedir. ...
Objective: Cannabis sativa L. is a plant that has been used for therapeutic purposes since ancient times.
However, its use has been limited due to its content. Cannabis causes many changes at the gene level in the endocannabinoid system with the phytocannabinoids it contains. The aim of this study was to provide evidence that the endocannabinoid system could be a potential therapeutic target in many pathological conditions.
Result and Discussion: The change in the expression levels of receptors, endocannabinoids or enzymes in the endocannabinoid system may be associated with the pathologies of diseases such as Parkinson, Alzheimer, and Huntington. Besides, changes in the endocannabinoid system can affect the migration, proliferation of cancer cells. Also, cannabinoids, have been shown to play a role in the treatment of neuropathic
pain. Today, some cannabis-based treatment preparations such as dronabilon and nabilon capsules used in the treatment of chemotherapy-induced nausea and vomiting have been approved and available in many countries. Preparations such as Δ9 tetrahydrocannabinol /cannabidiol oromucosal spray are also among the preparations approved for use as analgesic in cancer patients or for the relief of muscle spasticity in multiple sclerosis
patients. However, standardized preparations of cannabis and further research are needed for many other medical conditions.
Keywords: Cancer, cannabinoid, cannabis, neurodegenerative diseases
... Ancak elde edilen verilerde THC'nin endişe verici yan etkileri olduğu kaydedilmiştir[73][74][75].Kannabinoidlerin analjezik olarak kullanımı, daha çok opioid gibi diğer analjezik ilaçlara alternatif bulma hedefi dolayısıyla ortaya çıkmıştır. Hava yoluyla kenevirin kullanımınının ağrı üzerindeki etkisini araştıran bir çalışmada artan THC oranıyla birlikte katılımcıların hissettikleri ağrı derecesinin de azaldığını bildirdiği kaydedilmiştir[76]. Genel olarak kenevirin analjezik etkisinin hafif olduğu, özellikle bu amaçla reçete edilen GABA reseptör agonistleri gabapentin ve pregabalin gibi ilaçlar kadar etkili olmadığı ifade edilmektedir. ...
... Medical research on Cannabis has primarily focused on isolated THC and CBD (Borgelt et al., 2013;Maa and Figi, 2014;Backes and Weil 2014;National Institute on Drug Abuse, 2016a, 2020Baron, 2018;Citti et al., 2018;Cousijn et al., 2018) but there are hundreds of other chemical constituents in Cannabis (ElSohly, 2007), including cannabinoids and terpenes (Baron, 2018). Recent research has documented that NIDAprovided Cannabis has distinctly different cannabinoid profiles than commercially available Cannabis (Vergara et al., 2017). ...
Currently in the United States, the sole licensed facility to cultivate Cannabis sativa L. for research purposes is the University of Mississippi, which is funded by the National Institute on Drug Abuse (NIDA). Studies researching Cannabis flower consumption rely on NIDA-supplied “research grade marijuana.” Previous research found that cannabinoid levels of NIDA-supplied Cannabis do not align with commercially available Cannabis. We sought to investigate the genetic identity of Cannabis supplied by NIDA relative to common categories within the species. This is the first genetic study to include “research grade marijuana” from NIDA. Samples (49) were assigned as Wild Hemp (feral; 6) and Cultivated Hemp (3), NIDA (2), CBD drug type (3), and high THC drug type subdivided into Sativa (11), Hybrid (14), and Indica (10). Ten microsatellites targeting neutral non-coding regions were used. Clustering and genetic distance analyses support a division between hemp and drug-type Cannabis. All hemp samples clustered genetically, but no clear distinction of Sativa, Hybrid, and Indica subcategories within retail marijuana samples was found. Interestingly, the two analyzed “research grade marijuana” samples obtained from NIDA were genetically distinct from most drug-type Cannabis available from retail dispensaries. Although the sample size was small, “research grade marijuana” provided for research is genetically distinct from most retail drug-type Cannabis that patients and patrons are consuming.
... Of course, high-THC cannabis species has proven medical benefits and they are prescribed by physicians for their patients, with different restrictions depending on each country (Murnion, 2015). Several are the medical uses, as chronic pain (Jensen et al., 2015), multiple sclerosis spasticityor spinal cord injury-associated symptoms (Borgelt et al., 2013), chemotherapy-induced nausea and vomiting or appetite stimulation for AIDS patients (Parolaro, 2021), glaucoma (Sachs et al., 2015), anxiety or depressive disorders, pediatric epilepsy (Gaston et al., 2017), among others. ...
Recently, the cultivation of light Cannabis, with a total THC content less than 0.6%, has been encouraged due to its industrial and therapeutic potential. This has increased the consumption of hemp for both smoking purposes and food preparation. Even so, Cannabis inflorescences are not subject to EU regulations and standards provided for food and tobacco products. A study was carried out on thirty-one inflorescences samples, collected in different Italian regions, in order to determine cannabinoids, pesticides and metals and to evaluate the exposure of consumers to contaminants and ensure a safe consumption. Contents of THC were always below 0.5%, while CBD ranged between 0.3 and 8.64%. The determination of 154 pesticides showed that 87% of the samples contained fungicides and insecticides in the range 0.01–185 μg/g. The most found are spynosad and cyprodinil. The concentration of metals ranged from 1 to more than 100 μg/g, and As, Cd, Co, Cr, Hg, Cu, Mo, Ni and V exceeded the regulatory US limits for inhaled Cannabis products, while Pb exceeded them for both oral and inhaled products. These contaminants are intrinsically toxic and may affect public health. Actions are needed to establish regulatory measures and reduce the adverse effects caused by contaminants in Cannabis.
... Δ9-tetrahydrocannabinol (THC) [1]. THC is best known for its psychotropic effect, but THC-containing products are also used to alleviate pain, spasticity, vomiting, nausea, and loss of appetite. ...
Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland. We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6–16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy. Improvements were reported in 59 (66%) study participants. The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).
Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young. What is Known:
• The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing.
• In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders.
What is New:
• This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting.
• The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions.
... Various pharmacotherapies, including benzodiazepines, capsaicin cream, haloperidol, and tricyclic antidepressants, have all been used with little evidence to suggest superiority of any one class in the treatment of CHS. 5,6 Although this study was undertaken at a single health care system and describes the economic impact at a single location, the results may be extrapolated to a national level. There is evidence to show that CHS incidence has been rising with legalization of cannabis and, thus, this has become a national public health issue. ...
Cannabis is the most commonly consumed recreational drug in the world. As more states legalize cannabis use in some form, the incidence of cannabinoid hyperemesis syndrome (CHS) is expected to rise. CHS is a constellation of symptoms including severe cyclical nausea and vomiting and epigastric or periumbilical abdominal pain as a result of long-term cannabis use. Recognizing the diagnosis and educating patients on the benefits of cessation is essential, as these patients often undergo extensive and repeated evaluations in the clinic, emergency department, and inpatient setting that could be avoided with extensive history taking and early recognition of the syndrome. In this study, we compared costs incurred by patients in various settings to determine if there is a difference between patients with and without CHS. Although there were not statistically significant cost differences between groups for all cost categories, it is clear that patients with CHS consume considerably more health care dollars than patients who deny cannabis use, and obtaining a detailed social history is imperative to prevent unnecessary workups and increased financial burden on the health care industry.
Cannabis plays a role in the legal, medical and dental fields. With more states passing medical marijuana laws, policymakers are concerned about possible cannabis use among nonpatients. Oral health effects include periodontitis, bone loss and gingival enlargement. Its Schedule I classification makes it difficult to run randomized controlled studies on its effects. However, further medical study will allow for better policy concerning marijuana that may affect the population as a whole.
Transtorno do Espectro do Autismo | Trauma na Infância | Adição
Transtorno Do Estresse Pós-Traumático (TEPT) | Depressão | Esquizofrenia |Epilepsia
Dor Crônica | Zumbido | Estado Vegetativo e Outros Distúrbios de Consciência
Demência Do Tipo Alzheimer | Doença De Parkinson
Aspectos Neuropsiquiátricos Da Infecção Pelo HIV
Cannabis Sativa e Seus Derivados Naturais e Sintéticos: uso Terapêutico e Recreativo
Elisabete Castelon
Transtorno do Espectro do Autismo | Trauma na Infância | Adição
Transtorno Do Estresse Pós-Traumático (TEPT) | Depressão | Esquizofrenia |Epilepsia
Dor Crônica | Zumbido | Estado Vegetativo e Outros Distúrbios de Consciência
Demência Do Tipo Alzheimer | Doença De Parkinson
Aspectos Neuropsiquiátricos Da Infecção Pelo HIV
Cannabis Sativa e Seus Derivados Naturais e Sintéticos: uso Terapêutico e Recreativo
We study whether the work capacity of the older working population responds to improved pain management therapy access. We use the adoption of state recreational marijuana laws (RMLs) as a large policy shock to access to a non‐pharmaceutical pain management option. We focus on workers’ compensation cash benefit receipt as a measure of work capacity, finding that receipt declines in response to RML adoption. Workers’ compensation cash benefits are awarded to workers who require time away from work to recover from an injury, which arguably captures a policy‐relevant aspect of work capacity. We observe similar shifts in complementary proxies for work capacity, including work‐limiting disability rates. After considering a range of alternative mechanisms, the evidence suggests that the primary driver of the reductions in workers’ compensation benefits is improvements in work capacity. This article is protected by copyright. All rights reserved
Shengjie Yang,1,* Weijuan Tan,1,* Xiao Ma,2 Lu Qi,1 Xinghe Wang1 1Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Surgery Medicine, Zhangqiu People’s Hospital, Jinan, 250200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinghe Wang, Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road Yangfangdian, Haidian District, Beijing, People’s Republic of China, Tel +86-15301378575, Email wangxh@bjsjth.cnAbstract: Cancer-related neuropathic pain is a common adverse effect in the process of cancer development and treatment and has gradually attracted the attention of researchers. The purpose of this article is to systematically review the articles on cancer-related neuropathic pain published between 2012 and 2021 and visualize the data through CiteSpace and R software. The results show that in the past 10 years, a total of 5715 articles have been published, involving 118 categories, of which the most is Clinical Neurology, followed by Neurosciences, Pharmacology Pharmacy. The country with the most published articles is the United States, followed by China and Italy. A total of 22,228 authors were involved in the study of cancer-related neuropathic pain. These historical opinions about cancer-related neuropathic pain could be an important practical basis for further research into potential development trends.Keywords: cancer, neuropathic pain, bibliometric, author, country, institution
Introduction
On the basis of both scientific progress and popular lore, there is growing optimism in the therapeutic potential of cannabis (marijuana) and cannabinoid-based chemicals for movement disorders. There is also notable skepticism regarding the scientific basis for this therapeutic optimism and significant concerns regarding the safety and regulation of cannabinoid products, particularly those available without prescription.
Methods
In recognition of the high interest and controversial nature of this subject, the meeting committee of the International Parkinson and Movement Disorders Society arranged for a talk on cannabis at the 2019 annual meeting's Controversies in Movement Disorders plenary session. This paper summarizes the highlights of this session.
Results
The endocannabinoid system is strongly tied to motor function and dysfunction, with basic research suggesting several promising therapeutic targets related to cannabinoids for movement disorders. Clinical research on cannabinoids for motor and nonmotor symptoms in Parkinson's disease, Huntington's disease, Tourette's syndrome, dystonia, and other movement disorders to date are promising at best and inconclusive or negative at worst. Research in other populations suggest efficacy for common symptoms like pain. While social campaigns against recreational cannabinoid use focus on cognitive changes in adolescents, the long-term sequelae of regulated medical use in older adults with movement disorders is unknown. The overall risks of cannabinoids may be similar to other commonly used medications and include falls and apathy.
Conclusion
Further research is greatly needed to better understand the actual clinical benefits and long-term side effects of medical cannabis products for movement disorders indications and populations.
Importance:
The cannabis industry has sought to normalize itself and expand its markets in the 21st century. One strategy used by companies to generate positive public relations is corporate social responsibility (CSR). It is critical to understand these efforts to influence the public and politicians given the risks of increased cannabis use.
Objectives:
To analyze cannabis industry CSR behaviors, determine their characteristics, and compare their practices with those of the tobacco industry.
Design, setting, and participants:
This qualitative study of CSR activities conducted between January 1, 2012, and December 31, 2021, evaluated 9 of the 10 largest publicly traded cannabis companies in the US and Canada. Data were collected from August 1 to December 31, 2021. The 10th company was excluded because it engaged in cannabis-based pharmaceutical sales but not CSR. A systematic review of corporate websites and Nexis Uni was performed, resulting in collection of 153 news articles, press releases, and Web pages. Charitable and philanthropic actions were included. Themes were identified and interpreted using modified grounded theory.
Main outcomes and measures:
CSR activities and spending.
Results:
Nine major cannabis companies in the US and Canada engaged in CSR activities that encouraged increased consumption and targeted marginalized communities. Companies claimed these activities would mitigate the harms of cannabis prohibition, promote diversity, expand access to medical cannabis, and support charitable causes. They developed educational programs, sustainability initiatives, and voluntary marketing codes and used strategies similar to those used by tobacco companies to recruit public interest organizations as allies.
Conclusions and relevance:
These findings suggest that cannabis companies developed CSR strategies comparable to those used by the tobacco industry to influence regulation, suggesting that cannabis companies should be included when addressing commercial determinants of health.
Background
Cannabis is frequently used recreationally and medicinally including for symptom management in patients with kidney disease.
Methods
We elicited the views of Canadian adults with kidney disease regarding their cannabis use. Participants were asked whether they would try cannabis for anxiety, depression, restless legs, itchiness, fatigue, chronic pain, decreased appetite, nausea/vomiting, sleep, cramps and other symptoms. The degree to which respondents considered cannabis for each symptom was assessed with a modified Likert scale ranging from 1–5 (anchored at 1 ‘definitely would not’ and 5 being ‘definitely would’). Multilevel multivariable linear regression was used to identify respondent characteristics associated with considering cannabis for symptom control.
Results
Of 320 respondents, 290 (90.6%) were from in-person recruitment (27.3% response rate) and 30 (9.4%) responses were from online recruitment. 160/320 respondents (50.2%) had previously used cannabis including smoking (140, 87.5%), oils (69, 43.1%) and edibles (92, 57.5%). The most common reasons for previous cannabis use were recreation (84/160, 52.5%), pain alleviation (63/160, 39.4%) and sleep enhancement (56/160, 35.0%). Only 33.8% of previous cannabis users thought their physicians were aware of their cannabis use. >50% of respondents probably would or definitely would try cannabis for symptom control for all 10 symptoms. Characteristics independently associated with interest in trying cannabis for symptom control included symptom type (pain, sleep, restless legs), online respondent (ß 0.7, 95% CI 0.1–1.4) and previous cannabis use (ß 1.2, 95% CI 0.9, 1.5).
Conclusions
Many patients with kidney disease use cannabis and there is interest in trying cannabis for symptom control.
There is widespread support of cannabis for therapeutic purposes (CTP) despite lack of federal oversight and inconsistencies in screening, consenting, and authorizing use. Young people may have increased vulnerability to adverse effects including psychosis, substance use disorder, reduced academic achievement or other symptoms. We describe a case of a 20 year old who was prescribed CTP in the context of an emerging psychotic illness. The student was hospitalized for a psychotic episode and CTP a risk factor that complicated care. Use of CTP in this patient was concerning for several reasons, including emergence of psychosis, escalating cannabis use, as well as the lack of coordination among health care providers. This case illustrates the complexity of evaluating and treating high-risk youth; every precaution should be taken to prevent harm, reduce pathology and improve functioning. Without federal regulation and oversight, variable guidance for screening, consenting, authorizing and procuring CTP will unfortunately continue.
Cannabidiol (CBD) has poor water solubility and is subjected to extensive first-pass metabolism. These absorption obstacles are responsible for low and variable oral bioavailability of CBD. This study endeavored to improve CBD bioavailability by intramuscular (IM) injection of CBD nanocrystals (CBD-NC). The nanocrystals were prepared by antisolvent precipitation method and were characterized in terms of the particle size, polydispersity index (PDI), zeta potential, morphology, and crystalline status. CBD-NC displayed a particle size of 141.7±1.5 nm, a PDI of 0.18±0.01, and a zeta potential of −25.73 mV. CBD-NC freeze-dried powder using bovine serum albumin (BSA) as cryoprotectant had good redispersibility, and the average particle size was 139.1±1.4 nm after reconstitution. Moreover, these freeze-dried powders were characterized for drug loading and pH and were evaluated for in vitro dissolution and in vivo studies in a rat model. The in vivo results showed that AUC0–24 h and Cmax of CBD by IM injection of CBD nanocrystals increased significantly compared with that of oral (P.O) administration of CBD nanocrystals and CBD oil solution. This underlines the nano-sized CBD could be suggested as a practical and simple nanosystem for IM delivery with improved bioavailability. More importantly, these results pave the way for future development of CBD-NC retentive dosage forms.
Graphical abstract
Public interest in the analgesic potential of cannabinoids has grown, but there is no consensus regarding orthopedic applications. Available evidence was identified for cannabinoid use in arthritis, neuropathic pain, fibromyalgia, multiple sclerosis, and postoperative pain. Extracted information included the risks of preoperative use, associations with opioid dependence, and surgical complications. There is limited evidence for therapeutic benefit of cannabinoids in rheumatoid arthritis and fibromyalgia. Cannabinoids are not indicated for postoperative pain. Preoperative unregulated use has been linked with postoperative opioid dependence. Cannabinoids may be considered a second- or third-line treatment for analgesia for some orthopedic pathologies. [Orthopedics. 202x;xx(x):xx-xx.].
Background: The current social and legal landscape is likely to foster the medicinal and recreational use of cannabis. Synthetic cannabinoid use is associated with acute kidney injury (AKI) in case reports; however, the association between natural cannabis use and AKI risk in patients with advanced chronic kidney disease (CKD) is unknown. Materials and Methods: From a nationally representative cohort of 102,477 U.S. veterans transitioning to dialysis between 2007 and 2015, we identified 2215 patients with advanced CKD who had undergone urine toxicology (UTOX) tests within a year before dialysis initiation and had inpatient serial serum creatinine levels measured within 7 days after their UTOX test. The exposure of interest was cannabis use compared with no use as ascertained by the UTOX test. We examined the association of this exposure with AKI using logistic regression and inverse probability of treatment weighting with extensive adjustment for potential confounders. Results: The mean age of the overall cohort was 61 years; 97% were males, 51% were African Americans, 97% had hypertension, 76% had hyperlipidemia, and 75% were diabetic. AKI occurred in 56% of the cohort, and in multivariable-adjusted analysis, cannabis use (when compared with no substance use) was not associated with significantly higher odds of AKI (odds ratio 0.85, 95% confidence interval 0.38-1.87; p=0.7). These results were robust to various sensitivity analyses. Conclusions: In this observational study examining patients with advanced CKD, cannabis use was not associated with AKI risk. Additional studies are needed to characterize the impact of cannabis use on risk of kidney disease and injury.
Background and objective:
Although cannabinoid-based medications are increasingly used by older adults, their safety and tolerability in this age group remain unclear. The purpose of this systematic review was to examine the safety and tolerability of cannabinoid-based medications by conducting a meta-analysis of open-label observational studies of cannabinoid-based medications for all indications in individuals with a mean age of ≥50 years.
Methods:
A systematic search was conducted on PubMed, PsycINFO, MEDLINE, EMBASE and CINHAL. Study quality was assessed using an adapted version of the Grading of Recommendations Assessment, Development and Evaluation criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. We included studies that (a) were published from 1990 onwards; (b) included older adults (mean age ≥50 years); and (c) provided data on the safety and tolerability of medical cannabinoids. Data were pooled using a random-effects approach. Risk of adverse events, serious adverse events and withdrawals was computed as the incidence rate (IR). Separate analyses were conducted by the cannabinoid-based medication used, for delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and a combination of THC and CBD (THC:CBD).
Results:
Thirty-eight studies were identified (THC = 23; CBD = 6; THC:CBD = 9; N = 2341, mean age: 63.19 ± 8.08 years, men: 53.86%). THC had a very low incidence of all-cause and treatment-related adverse events (IR: 122.18, 95% confidence interval [CI] 38.23-253.56; IR: 84.76, 95% CI 0.13-326.01, respectively) and negligible serious adverse events (IR = 0). Similar IRs for CBD (all cause, IR: 111.91, 95% CI 1.24-495.93; treatment related, IR: 1.76, 95% CI 4.63-23.05) and no serious adverse events (IR = 0). CBD was not associated with a risk of treatment-related withdrawals. THC had a low risk of all-cause and treatment-related withdrawals (IR: 25.18, 95% CI 12.35-42.52; IR: 7.83, 95% CI 3.26-14.38, respectively). The THC:CBD treatment had a low risk of all-cause and treatment-related adverse events (IR: 100.72, 95% CI 0.25-383.00; IR: 55.38, 95% CI 8.61-142.80, respectively), but reported a risk of all-cause and treatment-related serious adverse events (IR: 21.32, 95% CI 0.18-93.26; IR: 3.71, 95% CI 0.21-11.56, respectively), and all-cause and treatment-related withdrawals (IR: 78.63, 95% CI 17.43-183.90; IR: 34.31, 95% CI 6.09-85.52, respectively). Significant heterogeneity (I2 >55%) was present in most analyses.
Conclusions:
Although cannabinoid-based medications were generally safe and acceptable to adults aged over 50 years, these estimates are limited by the lack of a control condition and considerable heterogeneity. Nevertheless, they complement and are consistent with comparable evidence from randomised controlled trials.
Increasing patient interest in cannabinoid-based treatments is creating a significant demand for medical education. Without formalized access to such training, patients are often using cannabis or cannabis products without medical support or supervision. Additionally, regulatory restrictions have limited legal access to regulated cannabinoid-based treatments. Consequently, there is a growing need to develop clinical guidelines for cannabinoid safe and responsible prescription. Despite a paucity of high-quality evidence, pain management has been a common indication for the use of cannabis-based medicines. Most research has utilized prescription or pharmaceutical cannabinoids such as nabilone, dronabinol, and nabiximols, leaving the safety and efficacy of natural cannabis products to require further clinical research development. Healthcare practitioners (HCPs) seek opportunities to learn about the fundamentals of cannabis-based medicines, including available methods of administration, product formulations, and available evidence. HCPs should be able to recognize the main therapeutic properties and clinical differences between delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The proposed systematic approach for medical cannabis use is based on existing practical recommendations and clinical experience from countries where cannabis has been approved. Specific guidance will assist HCPs to decide whether a patient is a candidate or not for cannabinoid therapy. Finally, key steps and essential information will support chemotype selection, starting dose, titration regimen, cannabinoid method of administration, and treatment monitoring. HCPs should be aware of potential adverse effects associated with cannabinoid therapy and monitor patients in regular follow-up appointments. Patient education to address expectations and common misconceptions will be crucial to clarify treatment objectives and to support beneficial patient outcomes.
The use of cannabinoids has been on the rise for various indications among cancer patients. As cancer patients are commonly afflicted with the burden of pain, patients and providers are regularly seeking alternative therapies to improve their quality of life and lift the burden of pain. We explore the relevant mechanisms, state of the current literature, clinical considerations, and the future of cannabinoids in cancer pain.
Although cannabis has been used therapeutically to alleviate diverse clinical conditions and symptoms for several thousands of years, acceptance of medical cannabis or cannabinoid-based treatment in modern medicine has been hindered by several challenges. Misconceptions, social stigma, and political challenges resulting in restricted or complicated regulatory frameworks have limited access to cannabis products and to funding for research, further contributing to limited medical cannabis acceptance among society and the medical community. Lack of differentiation between medical and nonmedical cannabis use and general stigma of psychoactive substances has also contributed to these limitations. As a result, a paucity of high-quality clinical evidence and divergent conclusions of systematic reviews and meta-analyses have led to many physicians who are still reluctant to recommend cannabinoid-based medicines. However, due to many advancements in access during the last 20 years, continuous research development, and clinical experience from countries where medical cannabis has been underway, patients are now pursuing medical cannabis treatments for a multitude of different symptoms and conditions and are seeking advice from healthcare professionals. But limited or nonexistent academic training on cannabinoids and the endocannabinoid system remains one of the most significant barriers for healthcare professionals to communicate accurate information to patients and their families. The development of such curriculums within medical training, and especially continuing medical education programs, is crucial to meet the needs and prepare for the future. Deployment of funding and mechanisms to access regulated medical cannabis products for well-designed clinical trials is also key to understand the efficacy and safety of cannabinoid-based treatments.
Objective: To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study. Methods: In total, 630 patients with stable MS with muscle spasticity from 33 UK centres were randomised to receive oral D9-tetrahydrocannabinol (D9-THC), cannabis extract, or placebo in the main 15 week CAMS study. The primary outcome was change in the Ashworth spasticity scale. Secondary outcomes were the Rivermead Mobility Index, timed 10 metre walk, UK Neurological Disability Score, postal Barthel Index, General Health Questionnaire-30, and a series of nine category rating scales. Following the main study, patients were invited to continue medication, double blinded, for up to12 months in the follow up study reported here. Results: Intention to treat analysis of data from the 80% of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months (D9-THC mean reduction 1?82 (n=154, 95% confidence interval (CI) 0.53 to 3.12), cannabis extract 0.10 (n=172, 95% CI 20.99 to 1.19), placebo 20.23 (n=176, 95% CI 21.41 to 0.94); p=0.04 unadjusted for ambulatory status and centre, p=0.01 adjusted). There was suggestive evidence for treatment effects of D9-THC on some aspects of disability. There were no major safety concerns. Overall, patients felt that these drugs were helpful in treating their disease. Conclusions: These data provide limited evidence for a longer term treatment effect of cannabinoids. A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS.
Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo.
As the use of medical marijuana expands, it is important to consider its implications for the patient-physician relationship. In Colorado, a small cohort of physicians is recommending marijuana, with 15 physicians registering 49% of all medical marijuana patients and a single physician registering 10% of all patients. Together, they have registered more than 2% of the state to use medical marijuana in the last three years. We are concerned that this dramatic expansion is occurring in a setting rife with conflicts of interest despite insufficient scientific knowledge about marijuana. This system diminishes the patient-physician relationship to the recommendation of a single substance while unburdening physicians of their usual responsibilities to the welfare of their patients.
Marijuana is a currently illegal psychoactive drug that many physicians believe has substantial therapeutic uses. The medical literature contains a growing number of studies on cannabinoids as well as case studies and anecdotal reports suggesting therapeutic potential. Fifteen states have passed medical marijuana laws, but little is known about the growing population of patients who use marijuana medicinally. This article reports on a sample of 1,746 patients from a network of nine medical marijuana evaluation clinics in California. Patients completed a standardized medical history form; evaluating physicians completed standardized evaluation forms. From this data we describe patient characteristics, self-reported presenting symptoms, physician evaluations, other treatments tried, other drug use, and medical marijuana use practices. Pain, insomnia, and anxiety were the most common conditions for which evaluating physicians recommended medical marijuana. Shifts in the medical marijuana patient population over time, the need for further research, and the issue of diversion are discussed.
The associations between marijuana use and mental illness are numerous. In the United States, marijuana is the most frequently abused illicit substance, with over 16.7 million Americans reporting past-month use, and it is identified as the primary substance of abuse in 17.1% of substance treatment admissions. A growing body of evidence associates marijuana use with an earlier onset and more adverse course of psychotic disorders. What is less well known is that longitudinal studies associate marijuana use with depression. While infrequent marijuana use does not appear to be associated with depressive disorders, the medicalization of marijuana encourages regular use, and regular use has a modest but significant association with depression that endures even after controlling for possible confounders. Language: en
Use of cannabis is often an under-reported activity in our society. Despite legal restriction, cannabis is often used to relieve chronic and neuropathic pain, and it carries psychotropic and physical adverse effects with a propensity for addiction. This article aims to update the current knowledge and evidence of using cannabis and its derivatives with a view to the sociolegal context and perspectives for future research.
Cannabis use can be traced back to ancient cultures and still continues in our present society despite legal curtailment. The active ingredient, Δ9-tetrahydrocannabinol, accounts for both the physical and psychotropic effects of cannabis. Though clinical trials demonstrate benefits in alleviating chronic and neuropathic pain, there is also significant potential physical and psychotropic side-effects of cannabis. Recent laboratory data highlight synergistic interactions between cannabinoid and opioid receptors, with potential reduction of drug-seeking behavior and opiate sparing effects. Legal rulings also have changed in certain American states, which may lead to wider use of cannabis among eligible persons.
Family physicians need to be cognizant of such changing landscapes with a practical knowledge on the pros and cons of medical marijuana, the legal implications of its use, and possible developments in the future.
Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human brain.
To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor-rich regions of the brain, the hippocampus and the amygdala.
Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging.
Participants were recruited from the general community and underwent imaging at a hospital research facility.
Fifteen carefully selected long-term (>10 years) and heavy (>5 joints daily) cannabis-using men (mean age, 39.8 years; mean duration of regular use, 19.7 years) with no history of polydrug abuse or neurologic/mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years).
Volumetric measures of the hippocampus and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured.
Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P = .001), with a relatively (and significantly [P = .02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippocampal volume was inversely associated with cumulative exposure to cannabis during the previous 10 years (P = .01) and subthreshold positive psychotic symptoms (P < .001). Positive symptom scores were also associated with cumulative exposure to cannabis (P = .048). Although cannabis users performed significantly worse than controls on verbal learning (P < .001), this did not correlate with regional brain volumes in either group.
These results provide new evidence of exposure-related structural abnormalities in the hippocampus and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.
Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to 'schizophrenia-like' cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter:total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.
The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users.
Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36).
Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI.
The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.
Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design.
A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4weeks, after which those achieving an improvement in spasticity of ≥20% progressed to a 12-week randomized, placebo-controlled phase.
Of the 572 subjects enrolled, 272 achieved a ≥20% improvement after 4weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of nabiximols (P=0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of nabiximols.
The enriched study design provides a method of determining the efficacy and safety of nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment.
Background:
Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition.
Method and findings:
Objective:
To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN.
Design:
Systematic review and meta-analysis.
Data sources:
Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles.
Selection criteria:
Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method.
Review methods:
Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥ 30% and ≥ 50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values.
Results:
Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4 g/day), pregabalin (1200 mg/day), prosaptide (16 mg/day), peptide-T (6 mg/day), acetyl-L-carnitine (1g/day), mexilitine (600 mg/day), lamotrigine (600 mg/day) and topical capsaicin (0.075% q.d.s.).
Conclusions:
Evidence of efficacy exists only for capsaicin 8%, smoked cannabis and rhNGF. However,rhNGF is clinically unavailable and smoked cannabis cannot be recommended as routine therapy. Evaluation of novel management strategies for painful HIV-SN is urgently needed.
There are at least two types of cannabinoid receptors (CB(1) and CB(2)). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ(9)-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB(1), non-CB(2) established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB(1) and/or CB(2) receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel "CB(3)" cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB(1), non-CB(2) pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB(3) receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB(1) receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB(1)/CB(2) receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB(1), non-CB(2) cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.
Background:
Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.
Methods:
Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events.
Results:
We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough.
Conclusion:
A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).
Cannabis is one of the most widely used illicit drugs among adolescents, and most users first experiment with it in adolescence. Adolescence is a critical phase for brain development, characterized by neuronal maturation and rearrangement processes, such as myelination, synaptic pruning and dendritic plasticity. The endocannabinoid system plays an important role in fundamental brain developmental processes such as neuronal cell proliferation, migration and differentiation. Therefore changes in endocannabinoid activity during this specific developmental phase, induced by the psychoactive component of marijuana, Delta(9)-tetrahydrocannabinol, might lead to subtle but lasting neurobiological changes that can affect brain functions and behaviour. In this review, we outline recent research into the endocannabinoid system focusing on the relationships between adolescent exposure to cannabinoids and increased risk for certain neuropsychiatric diseases such as schizophrenia, as highlighted by both human and animal studies. Particular emphasis will be given to the possible mechanisms by which adolescent cannabis consumption could render a person more susceptible to developing psychoses such as schizophrenia.
To determine the efficacy of Sativex (USAN: nabiximols) in the alleviation of spasticity in people with multiple sclerosis.
The results from three randomized, placebo-controlled, double-blind parallel group studies were combined for analysis.
666 patients with multiple sclerosis and spasticity.
A 0-100 mm Visual Analogue Scale (VAS, transformed to a 0-10 scale) or a 0-10 Numerical Rating Scale (0-10 NRS) was used to measure spasticity. Patients achieving a > or =30% improvement from baseline in their spasticity score were defined as 'responders'. Global impression of change (GIC) at the end of treatment was also recorded.
The patient populations were similar. The adjusted mean change of the numerical rating scale from baseline in the treated group was -1.30 compared with -0.97 for placebo. Using a linear model, the treatment difference was -0.32 (95% CI -0.61, -0.04, p = 0.026). A statistically significant greater proportion of treated patients were responders (odds ratio (OR) = 1.62, 95% CI 1.15, 2.28; p = 0.0073) and treated patients also reported greater improvement: odds ratio 1.67 (95% CI 1.05, 2.65; p = 0.030). High numbers of subjects experienced at least one adverse event, but most were mild to moderate in severity and all drug-related serious adverse events resolved.
The meta-analysis demonstrates that nabiximols is well tolerated and reduces spasticity.
Cannabis (marijuana) has been used for medicinal purposes for millennia, said to be first noted by the Chinese in c. 2737 BCE. Medicinal cannabis arrived in the United States much later, burdened with a remarkably checkered, yet colorful, history. Despite early robust use, after the advent of opioids and aspirin, medicinal cannabis use faded. Cannabis was criminalized in the United States in 1937, against the advice of the American Medical Association submitted on record to Congress. The past few decades have seen renewed interest in medicinal cannabis, with the National Institutes of Health, the Institute of Medicine, and the American College of Physicians, all issuing statements of support for further research and development. The recently discovered endocannabinoid system has greatly increased our understanding of the actions of exogenous cannabis. Endocannabinoids appear to control pain, muscle tone, mood state, appetite, and inflammation, among other effects. Cannabis contains more than 100 different cannabinoids and has the capacity for analgesia through neuromodulation in ascending and descending pain pathways, neuroprotection, and anti-inflammatory mechanisms. This article reviews the current and emerging research on the physiological mechanisms of cannabinoids and their applications in managing chronic pain, muscle spasticity, cachexia, and other debilitating problems.
Recent increases in marijuana smoking among the young adult population have been accompanied by the popularization of smoking marijuana as blunts instead of as joints. Blunts consist of marijuana wrapped in tobacco leaves, whereas joints consist of marijuana wrapped in cigarette paper. To date, the effects of marijuana smoked as joints and blunts have not been systematically compared. The current within-subject, randomized, double-blind, placebo-controlled study sought to directly compare the subjective, physiological, and pharmacokinetic effects of marijuana smoked by these two methods. Marijuana blunt smokers (12 women and 12 men) were recruited and participated in a 6-session outpatient study. Participants were blindfolded and smoked three puffs from either a blunt or a joint containing marijuana with varying Delta(9)-tetrahydrocannabinol (THC) concentrations (0.0, 1.8, and 3.6%). Subjective, physiological (heart rate, blood pressure, and carbon monoxide levels) and pharmacokinetic effects (plasma THC concentration) were monitored before and at specified time points for 3h after smoking. Joints produced greater increases in plasma THC and subjective ratings of marijuana intoxication, strength, and quality compared to blunts, and these effects were more pronounced in women compared to men. However, blunts produced equivalent increases in heart rate and higher carbon monoxide levels than joints, despite producing lower levels of plasma THC. These findings demonstrate that smoking marijuana in a tobacco leaf may increase the risks of marijuana use by enhancing carbon monoxide exposure and increasing heart rate compared to joints.
Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Delta-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size = 0.60; p = 0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95% CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally
Previous reports of accidental ingestion of cannabis by children are rare. None has reported coma, although one described a stuporous state that required assisted ventilation. Over the past four years, the staff of British Columbia's Children's Hospital has managed six children with cannabis toxicity, three of whom presented in coma, including one with airway obstruction. Recurring diagnostic features included rapid onset of drowsiness, moderate pupil dilation, hypotonia, lid lag, and the presence of small granules or leaves in the mouth. Confirmation was obtained by positive urine screening for cannabinoids. The six cases described emphasize the need for emergency physician awareness of possible diagnostic criteria, the potential severity of intoxication, and the need for prevention through parent education.
A comparative study was done in women and men of the effects of 9-tetrahydrocannabinol (9-THC), intravenously or orally, on dynamic activity, metabolism, excretion, and kinetics. In general no differences between the two sexes were observed. 9-THC is converted by microsomal hydroxylation to 11-hydroxy-9-THC (11-OH-9-THC), which is both a key intermediate for further metabolism to 11-nor-9-THC-9-carboxylic acid (11-nor-acid) by liver alcohol-dehydrogenase enzymes and a potent psychoactive metabolite. Major differences in the ratio of the concentration of 11-OH-9-THC to that of 9-THC in plasma were found after intravenous dosing (ratio 1:10 to 20) compared with oral administration (ratio 0.5 to 1:1). The final metabolic products are the 11-nor-acids and the related, more polar acids. Urinary excretion of 9-THC is restricted to acidic nonconjugated and conjugated metabolites. After 72 hr mean cumulative urinary excretion, noted for both routes and for both sexes, ranged from 13% to 17% of the total dose. After 72 hr the cumulative fecal excretion for both sexes after intravenous administration ranged from 25% to 30%; after oral administration the range was 48% to 53%. Metabolites were found in the feces in large concentration in the nonconjugated form; concentrations of 11-OH-9-THC were particularly noteworthy. Kinetics of 9-THC and metabolites were much the same for female and male subjects. For 9-THC, terminal-phase t½s for both sexes, irrespective of the route, ranged from 25 to 36 hr. A comparison of the results for AU C i dose (9-THC) after oral dosing with comparable data from intravenous administration indicated bioavailability of the order of 10% to 20% for both sexes. After intravenous 9-THC, large apparent volumes of distribution were noted (about 10 l/kg for both sexes).
This fifth edition is a timely and welcome one because of recent management changes in the treatment of acute poisoning. The routine use of syrup of ipecac as the primary household emetic has been supplanted by immediately calling the Poison Control Center, which may then recommend ipecac or, more likely, other measures and actions.
General management of poisoning and overdoses is more important than the use of specific antidotes. Nevertheless, important antidotes or antagonists are still useful and recommended for special situations. Each chapter ends with an in-depth discussion of the relevant antidotes for the particular type of poison.
I particularly enjoyed the historical account of the "birth" of the Poison Control Center concept and movement, since I was a member of the first Accident Prevention Committee of the American Academy of Pediatrics when it made the survey of its 3000 members in 1952 seeking the most prevalent childhood accident.
This current study assessed neurocognitive functioning in a carefully selected sample of schizophrenia patients with and without heavy cannabis use and healthy controls. All subjects were negative for any other substance use. Schizophrenia subjects had impaired neurocognitive functions across a wide range of tasks compared to healthy controls. Cannabis using schizophrenia patients had focused impairments on tasks of attention, and the findings suggest an impulsive pattern of response among these patients.
In the last 15 years there has been a major shift in the laws governing medical use of cannabis in the United States. Corresponding with this change there has been escalating interest in the role that cannabis, commonly referred to as marijuana, and cannabinoids play in the care of patients with cancer. This review will examine cannabis' and cannabinoids' current and potential roles in cancer care. Specifically, we will examine five areas of cannabis medicine: (1) pharmacologic properties of cannabis; (2) its potential role in the development of human cancers, particularly smoking-related malignancies; (3) cannabinoids' potential as anti-cancer therapies; (4) cannabis and cannabinoids in the palliation of common cancer-associated symptoms; (5) current legal status of cannabis for medical purposes in the United States.
This current study assessed neurocognitive functioning in a carefully selected sample of schizophrenia patients with and without heavy cannabis use and healthy controls. All subjects were negative for any other substance use. Schizophrenia subjects had impaired neurocognitive functions across a wide range of tasks compared to healthy controls. Cannabis using schizophrenia patients had focused impairments on tasks of attention, and the findings suggest an impulsive pattern of response among these patients.
Cannabis is associated with psychotic outcomes in numerous studies, an effect that is commonly attributed to Δ (9)-tetrahydrocannabinol (Δ 9-THC). An increasing number of authors identify cannabidiol, another component of the cannabis plant, as an antipsychotic agent. The objective of the current study is to investigate the role of cannabidiol content in the association between cannabis use and psychiatric symptoms in a large non-clinical population of cannabis users.
In a web-based cross-sectional study we obtained detailed information about cannabis use and subclinical psychiatric experiences using the Community Assessment of Psychic Experiences (CAPE). Different types of cannabis (i.e. marijuana, hashish etc.) have distinctive proportions of Δ 9-THC and cannabidiol. Since average concentrations of Δ 9-THC and cannabidiol in the most popular types of cannabis sold on the Dutch market are annually measured, we were able to estimate exposure to Δ 9-THC and cannabidiol.
We included 1877 subjects (mean age 23, SD 6.0) who used the same type of cannabis in the majority of the occasions (in >60% of occasions). We found a significant inverse relationship (F(1,1877): 14.577, p<0.001) between cannabidiol content and self-reported positive symptoms, but not with negative symptoms or depression. The estimated effect size of cannabidiol content was small.
Although the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol.
While neuropsychological deficits have been reported in healthy individuals who use street cannabis, data in patients with multiple sclerosis (MS) are lacking. Given that MS is associated with cognitive deterioration, the aim of this study was to determine the neuropsychological effects of cannabis use in this population.
Two groups, each of 25 patients with MS (cannabis users and nonusers), were administered the Minimal Assessment of Cognitive Function in MS battery of neuropsychological tests, the Hospital Anxiety and Depression Scale (HADS), and the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I). Group-matching and regression analysis were used to control for the effects of age, sex, education, premorbid intelligence, disability, and disease course and duration on cognitive function.
Cannabis users performed significantly more poorly than nonusers on measures of information processing speed, working memory, executive functions, and visuospatial perception. They were also twice as likely as nonusers to be classified as globally cognitively impaired. There were no between-group differences on the HADS measures of depression and anxiety or lifetime SCID-I psychiatric diagnoses.
This cross-sectional study provides empirical evidence that prolonged use of inhaled or ingested street cannabis in patients with MS is associated with poorer performance on cognitive domains commonly affected in this population. Whatever subjective benefits patients may derive from using street cannabis (e.g., pain and spasticity relief) should be weighed against the associated cognitive side effects.
Converging lines of evidence suggest an adverse effect of heavy cannabis use on adolescent brain development, particularly on the hippocampus. In this preliminary study, we compared hippocampal morphology in 14 "treatment-seeking" adolescents (aged 18-20) with a history of prior heavy cannabis use (5.8 joints/day) after an average of 6.7 months of drug abstinence, and 14 demographically matched normal controls. Participants underwent a high-resolution 3D MRI as well as cognitive testing including the California Verbal Learning Test (CVLT). Heavy-cannabis users showed significantly smaller volumes of the right (p < 0.04) and left (p < 0.02) hippocampus, but no significant differences in the amygdala region compared to controls. In controls, larger hippocampus volumes were observed to be significantly correlated with higher CVLT verbal learning and memory scores, but these relationships were not observed in cannabis users. In cannabis users, a smaller right hippocampus volume was correlated with a higher amount of cannabis use (r = -0.57, p < 0.03). These data support a hypothesis that heavy cannabis use may have an adverse effect on hippocampus development. These findings, after an average 6.7 month of supervised abstinence, lend support to a theory that cannabis use may impart long-term structural and functional damage. Alternatively, the observed hippocampal volumetric abnormalities may represent a risk factor for cannabis dependence. These data have potential significance for understanding the observed relationship between early cannabis exposure during adolescence and subsequent development of adult psychopathology reported in the literature for schizophrenia and related psychotic disorders.
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