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Neuropharmacology Jan 2022Because of increased opioid misuse, there is a need to identify new targets for minimizing opioid tolerance, and physical and psychological dependence. Previous studies...
Because of increased opioid misuse, there is a need to identify new targets for minimizing opioid tolerance, and physical and psychological dependence. Previous studies showed that fibroblast growth factor 21 (FGF21) decreased alcohol and sweet preference in mice. In this study, FGF21-transgenic (FGF21-Tg) mice, expressing high FGF21 serum levels, and wildtype (WT) C57BL/6J littermates were treated with morphine and saline to determine if differences exist in their physiological and behavioral responses to opioids. FGF21-Tg mice displayed reduced preference for morphine in the conditioned place preference assay compared to WT littermates. Similarly, FGF21-Tg mice had an attenuation of the magnitude and rate of acute morphine antinociceptive tolerance development, and acute and chronic morphine physical dependence, but exhibited no change in chronic morphine antinociceptive tolerance. The ED50 values for morphine-induced antinociception in the 55 °C hot plate and the 55 °C warm-water tail withdrawal assays were similar in both strains of mice. Likewise, FGF21-Tg and WT littermates had comparable responses to morphine-induced respiratory depression. Overall, FGF21-Tg mice had a decrease in the development of acute analgesic tolerance, and the development of physical dependence, and morphine preference. FGF21 and its receptor have therapeutic potential for reducing opioid withdrawal symptoms and craving, and augmenting opioid therapeutics for acute pain patients to minimize tolerance development.
Topics: Animals; Behavior, Animal; Drug Tolerance; Fibroblast Growth Factors; Mice, Inbred C57BL; Mice, Transgenic; Morphine; Morphine Dependence; Nociception; Respiratory Insufficiency; Substance Withdrawal Syndrome; Mice
PubMed: 34715121
DOI: 10.1016/j.neuropharm.2021.108858 -
Frontiers in Behavioral Neuroscience 2016
PubMed: 27147999
DOI: 10.3389/fnbeh.2016.00078 -
Medicina (Kaunas, Lithuania) Mar 2024Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older... (Review)
Review
Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older generations of these compounds, new formulations appeared on the drug market. One of them is metaphedrone (3-methylmethcathinone, 3-MMC), a structural isomer of 4-methylmethcathinone and a psychostimulant drug. Metaphedrone became popular in a large number of countries in a short period of time. The collection, analysis, and review of relevant research on the subject of metaphedrone in order to present information about the pharmacological, clinical, and toxicological profile of this compound. An assessment of the significance and role of metaphedrone in consumption patterns of novel psychoactive substances among recreational drug users. By using search engines like Google Scholar and PubMed, the relevant literature on metaphedrone was looked for and analyzed. The search was not limited to a specific period of time. All information regarding the compound of interest was analyzed and presented. All novel psychoactive substances are abused due to their pronounced stimulatory, hallucinogenic, dissociative, and euphoric and/or relaxing characteristics. Users of 3-methylmethcathinone usually opt for this substance for recreational purposes and/or sexual stimulation. Metaphedrone has the potential to cause a psychological dependence to the users. It was determined in relevant studies that most users are from 17 to 50 years of age. Older users usually administer metaphedrone intravenously, while younger ones usually choose snorting and oral ingestion of the drug. In Serbia, metaphedrone is a legally controlled substance. The pharmacodynamic properties make metaphedrone similar to classical recreational drugs. The method of administration, mainly repeated administration in a single session, could be explained using the pharmacokinetic profile of the drug. The most reported symptoms of intoxication were those of a sympathomimetic nature, such as tachycardia, chest pain, hypertension, diaphoresis, and agitation. Most intoxications and fatal outcomes occurred to users who combined several psychoactive substances. The correlation between measured blood concentrations of the drug and outcomes of intoxication was not found. The mechanisms of metaphedrone's toxicity are not fully understood. There is an increasing trend of abuse of metaphedrone among recreational drugs users. Future studies should focus on pharmacological and toxicological effects of metaphedrone on animals and humans.
Topics: Humans; Animals; Illicit Drugs; Hypertension; Serbia; Methamphetamine
PubMed: 38541192
DOI: 10.3390/medicina60030466 -
Journal of Pain and Symptom Management Nov 1994There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful... (Review)
Review
There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful review of the literature reveals insufficient evidence to support the contention that the benzodiazepines have meaningful analgesic properties in most clinical circumstances. Treatment with the benzodiazepines may reduce complaints of pain, but this seems to be an indirect effect related to their psychotropic properties, such as alleviation of anxiety and, in selected cases, depression. In the absence of definitive data, clinical experience suggests a potential role for treatment with benzodiazepines for acute muscle spasm, concomitant chronic pain and anxiety, and lancinating neropathic pain, in which case clonazepam and alprazolam may be the agents of choice. They should probably not be considered as first-line choices even for the above indications, since potential benefits must be considered in the context of potential for the development of cognitive impairment, physical and psychological dependence, worsening depression, overdose, and other side effects.
Topics: Adjuvants, Pharmaceutic; Analgesics; Benzodiazepines; Clinical Trials as Topic; Humans; Palliative Care
PubMed: 7531735
DOI: 10.1016/0885-3924(94)90112-0 -
Basic and Clinical Neuroscience 2021Previous studies have shown that physical and psychological dependence and the vulnerability to relapse are still present during MMT. Thus, this study examined whether...
Environmental Enrichment Ameliorates Psychological Dependence Symptoms and Voluntary Morphine Consumption in Morphine Withdrawn Rats Under Methadone Maintenance Treatment.
INTRODUCTION
Previous studies have shown that physical and psychological dependence and the vulnerability to relapse are still present during MMT. Thus, this study examined whether Enriched Environment (EE) would attenuate anxiety, depressive, and obsessive-compulsive-like behaviors, as well as voluntary morphine consumption following Methadone Maintenance Treatment (MMT) in morphine withdrawn rats.
METHODS
The rats were injected bi-daily doses (10 mg/kg, 12-h interval) of morphine for 14 days. Then, the rats were reared in a Standard Environment (SE) or EE for 30 more days during morphine withdrawal, simultaneous with receiving MMT. The rats were tested for anxiety (the Elevated Plus Maze [EPM]) and depression (Sucrose Preference Test [SPT]), Obsessive-Compulsive Disorder (OCD) as grooming behavior, and voluntary morphine consumption using a Two-Bottle Choice (TBC) paradigm.
RESULTS
The findings revealed that EE experience in morphine withdrawn rats under MMT significantly increased the EPM open-arm time and higher sucrose preference than SE rats. Also, we found that the EE decreased the self-grooming behavior and morphine preference ratio in morphine withdrawn rats receiving MMT compared to the SE group.
CONCLUSION
We conclude that exposure to EE decreased methadone-induced anxiety, depressive and OCD-like behaviors, and voluntary morphine consumption in morphine withdrawn rats under MMT. Thus, the EE seems to be one of the strategies for reducing MMT-induced behavioral dysfunction and the risk of relapse induced by morphine withdrawal.
PubMed: 35173915
DOI: 10.32598/bcn.12.5.886.3 -
Tidsskrift For Den Norske Laegeforening... Jan 2009The aim of this paper is to assess the substance pregabaline's potential for abuse. Little information is available on the subject and that retrieved is in part... (Review)
Review
The aim of this paper is to assess the substance pregabaline's potential for abuse. Little information is available on the subject and that retrieved is in part conflicting. Pregabaline is likely to be abused for its positive psychological effects, e.g. euphoria. However, these effects are weak and not sustained during long-term use. Pregabaline is therefore likely to have a lower potential for abuse than benzodiazepines. In clinical studies, symptoms suggestive of physical dependence (e.g. insomnia, nausea, headache, diarrhoea) have been observed in some patients after abrupt discontinuation of pregabaline. However, available documentation indicates that pregabaline is associated with less physical and psychological dependence than benzodiazepines.
Topics: Analgesics; Humans; Pregabalin; Risk Factors; Substance-Related Disorders; gamma-Aminobutyric Acid
PubMed: 19180163
DOI: 10.4045/tidsskr.08.0047 -
British Journal of Clinical Pharmacology Dec 2020Glucocorticoids are highly effective medicines in the treatment of inflammatory disorders. However they cause severe adverse reactions, particularly where taken at high... (Review)
Review
Glucocorticoids are highly effective medicines in the treatment of inflammatory disorders. However they cause severe adverse reactions, particularly where taken at high doses systemically for prolonged periods. Systemic glucocorticoids are therefore given at dosage sufficient to control the disease, then withdrawn as fast as is possible to minimise dose- and time-related adverse drug reactions without losing disease control. Adverse withdrawal reactions present a major challenge in the withdrawal of long term glucocorticoids. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis causes adrenal insufficiency, which is potentially life threatening and can become symptomatic as treatment is withdrawn. Adrenal insufficiency can be extremely difficult to differentiate from 'glucocorticoid withdrawal syndrome', where patients experience symptoms despite adequate adrenal function, and from psychological dependence. Long term systemic glucocorticoids should therefore be withdrawn slowly. The rate at which the dose is tapered should initially be determined by treatment requirements of the underlying disease. Once 'physiological' doses are reached, the rate of reduction is determined by rate of HPA recovery and need for exogenous glucocorticoid cover while endogenous secretion recovers. If symptoms prevent treatment withdrawal, HPA testing should be used to look for adrenal insufficiency. Patients with adrenal insufficiency require 'physiological' doses of glucocorticoids for adrenal replacement, which may be lifelong if the HPA axis fails to recover.
PubMed: 33289121
DOI: 10.1111/bcp.14679 -
Pharmacy (Basel, Switzerland) Nov 2022Over-the-counter (OTC) drugs, such as codeine, are available as an OTC drug at common drugstores and major e-commerce platforms, despite their known propensity for...
Over-the-counter (OTC) drugs, such as codeine, are available as an OTC drug at common drugstores and major e-commerce platforms, despite their known propensity for causing psychological dependence and harm from overuse. Misuse of and dependence on over-the-counter drugs are serious public health issues. Possible measures include stricter regulation and control, as well as regulation of access to information and awareness activities, but their effectiveness is limited. Up-scheduling, in which OTC drugs are placed under prescription or full regulation, is expected to have a definite effect. However, up-scheduling poses public health ethical challenges. Up-scheduling restricts the freedom of consumers to purchase OTC drugs, and the economic right of manufacturers and sellers. Up-scheduling may also interfere with people's right to seek self-care through the proper use of OTC drugs. Limited up-scheduling with respect to age may be an effective way to implement up-scheduling while avoiding ethical issues. However, from a public health perspective, it is necessary to improve the information infrastructure so that prescription drug information can be shared electronically, and to strengthen measures to prevent mental health problems among young people that lead to OTC drug misuse, even after up-scheduling.
PubMed: 36412831
DOI: 10.3390/pharmacy10060155 -
CNS Spectrums Jun 2014Distinguishing dependent from recreational drug use can be a surprisingly difficult task, and the current means for identifying substance abuse can be inadequate or even... (Review)
Review
Distinguishing dependent from recreational drug use can be a surprisingly difficult task, and the current means for identifying substance abuse can be inadequate or even misleading. In subjective self-reports, those who are most at risk may down play their consumption, not admitting to the full extent of their habit, and measures purely of quantity of use rarely capture the true nature of an individual's relationship to the drug, such as a psychological dependence on the substance. This trend is particularly true for heavy stimulant use, which is absent of the physical withdrawal symptoms that can help identify opiate or alcohol dependence. As such, a simple objective measure to help identify substance abuse, particularly in individuals who might not otherwise raise suspicion, would be a valuable tool in both clinical and experimental settings. We propose that the drug-word Stroop task, an objective assessment of attentional bias and distraction to salient drug-related stimuli, would be a valuable tool in helping to make these categorizations. This measure has been shown to correlate with drug craving, as well as to successfully distinguish dependent from recreational stimulant users and to help to predict outcomes in treatment-seeking individuals. Here, we survey prior literature on the drug-word Stroop task and provide a perspective on using the assessment as a potential diagnostic for drug use severity.
Topics: Attention; Bias; Cognition Disorders; Cues; Humans; Illicit Drugs; Stroop Test; Substance-Related Disorders; Word Association Tests
PubMed: 24625759
DOI: 10.1017/S1092852914000133