New Insights into Cannabis Consumption; Abuses and Possible Therapeutic Effects

Cannabis is one of the oldest psychotropic drugs known to humanity. The paper assesses the current knowledge on the cannabis, including the mechanisms of action and the therapeutic potential of cannabinoids. Three varieties of Cannabis plant are recognised: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The variety indica is used predominantly to obtain the drugs. Cannabis herb is usually named marijuana, while the cannabis oleoresin secreted by the glandular hairs found mainly on the flowering or fruiting tops of the plant is known as hashish. More than 400 known chemicals are present in cannabis, at least 70 of which are called cannabinoids. The major psychoactive constituent in cannabis is delta-9-tetrahydrocannabinol (Δ9-THC). It is now recognized that there are three types of cannabinoids: natural (phytocannabinoids), endogenous cannabinoids, and synthetic cannabioids. 2 (CB2) receptors, found predominantly in peripheral tissues with immune functions have been cloned. Therefore, the concept of endogenous cannabinoid system (endocannabinoid system, SEC) has been developed. Based on the current scientific evidence, there are several effects of cannabinoids with potential therapeutic use: antiemetic, analgesic in cancerous pains, and chronic neuropathic pain, in multiple sclerosis or spinal cord injuries. Cannabis consume can result in a state of drug dependency and cannabis withdrawal has been included in DSM-V. Cannabis plant remains controversial in the twenty-first century and the potential therapeutic of specific cannabinoid compounds and medical marijuana remains under active medical research

Comparative cytotoxicity study of nicotine and cotinine on MRC-5 cell line

Nicotine has several health hazards regarding carcinogenic potential. It also imparts increased risk for respiratory, cardiovascular, and gastrointestinal disorders. Several mechanisms have been proposed for the carcinogenic potential, including effects on cell proliferation, inducing oxidative stress, DNA mutation, or inhibition of apoptosis. The cotinine metabolite is generally thought to have effects similar to nicotine in some experimental systems. The purpose of this study was to assess the nicotine and cotinine cytotoxicity on MRC-5 lung fibroblasts. The pulmonary fibroblasts were treated with various concentrations of nicotine or cotinine (in the range 1 µM – 2 mM) for 24 or 48 h and analyzed for cell viability by MTT test. The results indicated that high nicotine concentrations (2 mM) induced marked cell death (about 50%) in MRC-5 cell line. Cotinine showed lower toxicity than nicotine on the MRC-5 cells. In contrast to nicotine treatment, cells treated with cotinine continued to proliferate after the 48h incubation period

Toxicological Analysis of Some Drugs of Abuse in Biological Samples

Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their consequences are one of the major current problems of European society because of the significant repercussions in individual, family, social and economic level. In this context, toxicological analysis of the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an auto-response, mandatory screening in some treatment programs, identification of a substance in the case of an overdose, determining compliance of the treatment. The present paper aims to address the needs of healthcare professionals involved in drugs addiction treatment through systematic presentation of information regarding their toxicological analysis. Basically, it is a tool that help you to select the suitable biological sample and the right collecting time, as well as the proper analysis technique, depending on the purpose of analysis, pharmacokinetic characteristics of the drugs of abuse, available equipment and staff expertise

Determination of Tramadol in human plasma by HPLC with fluorescence detection

Tramadol is a centrally acting analgesic, atypical opioid, and although it is generally considered as a medicinal drug with a low potential for dependence, there is growing evidence of tramadol abuse in some countries. The ultraviolet detection is not suitable for analysis of tramadol in plasma, due to the lack of sensitivity and selectivity. However, it was shown that tramadol has a weak fluorescence, and the latest techniques for determination of tramadol in plasma include liquid chromatographic methods with fluorescence detection (FL). The objective of the paper was to develop a HPLC-FL method applicable for quantification of tramadol in human plasma.The separation was achieved by reverse phase HPLC method, using as stationary phase C18 – Kromasil® column and a mobile phase consisted of acetonitrile:0.1% formic acid (20:80). The fluorescence detection has been applied with λex/em= 280/310 nm. A solid phase extraction procedure using C18 cartridge was carried out. The linearity of the method has been demonstrated in the range of both therapeutic and toxic plasma tramadol levels (concentrations of 0.100 – 1µg/mL). The selectivity, precision, and accuracy of the method have been demonstrated. The limit of detection (LOD= 0.010 µg/mL) and the limit of quantification (LOQ = 0.100 µg/mL) have been established.The proposed method can be used to assess tramadol levels in human plasma in pharmacokinetic studies, as well as in overdose cases. The utility of the method for the quantification of therapeutic levels of tramadol has been shown on the plasma samples from the patients with tramadol treatment as analgesic (doses ranging from 100 mg to 400 mg/day).The developed method is rapid, using simple experimental conditions and an accurate and short extraction procedure

Current Concepts on Drug Abuse and Dependence

Drug addiction is a complex disease characterized by compulsive and uncontrollable desire to seek and consume the drug. In time, drug-related terminology has undergone many changes, arising from the deepening of the mechanisms of action, but also about the need for a greater precision in the definition. Drug dependence can be assigned not only to pharmacological effects of the drugs of abuse, but also to their interaction with each particular neurological and psychological constitution. The research on the neurobiological mechanisms of addiction processes allows both a better understanding of current pharmacotherapy and the development of new treatment strategies in drug abuse and dependence. In this review we intend to present the current concepts related to drug abuse and dependence

Comparative cytotoxicity study of nicotine and cotinine on MRC-5 cell line

Nicotine has several health hazards regarding carcinogenic potential. It also imparts increased risk for respiratory, cardiovascular, and gastrointestinal disorders. Several mechanisms have been proposed for the carcinogenic potential, including effects on cell proliferation, inducing oxidative stress, DNA mutation, or inhibition of apoptosis. The cotinine metabolite is generally thought to have effects similar to nicotine in some experimental systems. The purpose of this study was to assess the nicotine and cotinine cytotoxicity on MRC-5 lung fibroblasts. The pulmonary fibroblasts were treated with various concentrations of nicotine or cotinine (in the range 1 µM – 2 mM) for 24 or 48 h and analyzed for cell viability by MTT test. The results indicated that high nicotine concentrations (2 mM) induced marked cell death (about 50%) in MRC-5 cell line. Cotinine showed lower toxicity than nicotine on the MRC-5 cells. In contrast to nicotine treatment, cells treated with cotinine continued to proliferate after the 48h incubation period

HPTLC assay of nicotine and cotinine in biological samples

This study presents the development of a simple high-performance thin layer chromatography (HPTLC) method for the determination of nicotine and its metabolite cotinine in human plasma and urine. The following mobile phases: methanol: ammonia (100:1.5, v:v), chloroform: acetone: ammonia (48.75: 48.75: 2.5, v:v:v), methanol: chloroform: ammonia (48.75: 48.75: 0.5, v:v:v) and glass plates precoated with silicagel 60 F254 (20x20) as a stationary phase were used. Densitometric scanning was performed at 263 nm. Two different extraction procedures have been applied: liquid-liquid extraction using dichloromethane at alkaline pH and solid-phase extraction using C18 cartridges. Preliminary tests in order to establish the system of solvents for development, as well as the range of linearity, were conducted. The best separation of nicotine and cotinine was obtained by using methanol: chloroform: ammonia (48.75: 48.75: 0.5, v:v:v) as the mobile phase. The liquid-liquid extraction technique led to better results than solid phase extraction. The regression curves were linear (with a corresponding correlation coefficient higher than 0.99) in the quantities range of 200 ng–1000 ng/spot for both nicotine and cotinine. The UV spectra confirm the identification of nicotine and cotinine both in the standards and in the extracts after liquid-liquid extraction. The proposed method can be applied for the simultaneous evaluation of nicotine and cotinine in biological samples at toxic/lethal levels. Thus, the method may be applicable in lethal nicotine intoxication cases in forensic toxicological analysis

Methotrexate Liposomes - A Reliable Therapeutic Option

Liposomes were proposed as drug vector systems in the treatment of many diseases. The following characteristics recommend the liposomes as attractive candidates for drug transportation: solubilisation, duration of action, targeting potential and internalisation. Methotrexate, a folate antagonist, was originally developed as an antineoplastic agent and subsequently used in inflammatory and/or immunosuppressive diseases. Its side effects have led researchers to direct their efforts to reduce toxicity, while maintaining efficacy of methotrexate. Liposomes with methotrexate as such, as well as its disodium salt, were prepared using two methods. The liposomes were characterized in terms of structure, size, degree of poly‐dispersion and encapsulation efficiency. The effect of methotrexate incorporated in liposomes has been investigated in vitro on human lymphoblastic cell line K562. Methotrexate incorporated into liposomes moderately reduces the proliferation of K562 cells, but significantly inhibits RNA synthesis. The cellular activation is probably the main target of the drug and not the neoplastic proliferation of cells. The methotrexate liposomes exhibited significant anti‐inflammatory activity and showed reduced toxicity. Given that the encapsulating of the drug in vector systems may result in the increasing concentration at the site of action, the methotrexate liposomes represent a targeted therapy with an optimized therapeutic efficacy—risk toxicity ratio

Psychological and psychiatric characterization of various groups of drugs users

Aim. We aimed to assess the differences among various groups of drugs users, especially in the psychiatric and psychological domains. Materials and Methods. A retrospective study was carried out in collaboration with C.E.T.T.T `St. Stelian` Institute from Bucharest. There were analyzed the medical records of 604 hospitalized patients with heroin or polydrug addiction. Results. Significant differences in diagnosis at submission among groups were outlined (personality and behavior disorders, p-value = .04298, psychotic disorders, p-value = .004274, schizophrenia, p-value = .000141) as well as significant differences among psychiatric parameters: perception (legal highs, opiates), attention (cannabis), consciousness (legal highs), thinking (legal highs), and, instinctive life (legal highs). Conclusions. Personality and behavioral disorders have been particularly linked to opiate use, the psychotic disorder was related to cannabis and legal highs intake, while schizophrenia was related to legal highs intake

Analysis of potentially toxic contaminants in milk powder

The aim of this study was to identify potentially toxic contaminants in milk powder. Powdered milk contains a range of toxic and non-toxic substances that are present in a wide variety, also having very different origins. A number of seven milk powder samples from different producers sold on the Romanian market were analyzed, the samples that were collected from the original packaging: P1, P 2, P3, P4, P5, P6 and P7. The concentration of the following elements was analyzed using the X-ray (XRF) fluorescence method: potassium (K), chlorine (Cl), calcium (Ca), phosphorus (P) and aluminum (Al). The vast majority of the samples showed the levels of elements K, Ca, Cl, Al, P well above the maximum allowable limit (AML). In a single test, the elements potassium, calcium, chlorine, phosphorus showed levels below the maximum allowable limit, but the level of aluminum was much above. The experimental results showed that the market sells assortments of milk powder that exceed concentrations above the maximum limits established by the legislation in force for some constituent elements. Concentrations of constituent elements are not always specified on food labels, and if this information appears, they are not always the correct values