Jst Gain Reduction Crack Cocaine
Everardo Laboy
The scientists found that cocaine use may cause profound metabolic changes which can result in dramatic weight gain during recovery, a distressing phenomenon that can lead to relapse. It was previously widely believed that cocaine suppresses the appetite and that the problematic weight gain during rehabilitation was a result of patients substituting food for drugs.
Dr Karen Ersche, from the Behavioural and Clinical Neuroscience Institute at the University of Cambridge, said: Our findings challenge the widely held assumptions that cocaine use leads to weight loss through appetite suppression. Rather, they suggest a profound metabolic alteration that needs to be taken into account during treatment.
The results suggest that overeating in regular users of cocaine pre-dates the recovery process, this effect being disguised by a lack of weight gain. As a result, when cocaine users in recovery discontinue using cocaine but continue consuming their high fat diets - now without the effects of cocaine on their metabolism - they gain weight.
Dr Ersche said: We were surprised how little body fat the cocaine users had in light of their reported consumption of fatty food. It seems that regular cocaine abuse directly interferes with metabolic processes and thereby reduces body fat. This imbalance between fat intake and fat storage may also explain why these individuals gain so much weight when they stop using cocaine.
Dr Ersche and her team will next investigate more closely the underlying factors contributing to the marked weight gain in abstinent cocaine-dependent individuals to develop interventions to better support drug users in recovery.
All drug users satisfied the DSM-IV-TR (American Psychiatric Association, 2000) criteria for cocaine dependence. They were non-treatment seeking and actively using cocaine either in powdered (40%) or in freebase form (60%). They had been using cocaine for an average of 15.3 years (9.0 SD), starting at the age of 19.2 years (5.5 SD). On the testing day, urine samples tested positive for stimulants in all except four users, indicating that they consumed either cocaine or amphetamines within the detection window of 72 h (Preston et al., 2002). On the Obsessive-Compulsive Drug Use Scale (OCDUS, Franken, Hendriks, & Van Den Brink, 2002) they indicated moderate levels of cocaine-related compulsivity (mean score = 23.8 10.7 SD). The majority of the drug user sample also met criteria for dependence on another substance (91% nicotine, 43% opiates, 29% alcohol, 20% cannabis, 3% amphetamines) and used other drugs sporadically (68% cannabis, 20% sedatives, 15% opiates, 14% ecstasy, 3% hallucinogens). Participants with co-morbid opiate dependence were either prescribed methadone (31%, mean dose: 55 mg 16.2SD) or buprenorphine (9%, mean dose: 3 mg 2.6SD), or were using street heroin on a daily basis (3%). A quarter of cocaine users reported taking prescribed medication, including narcotic-like pain relief (11%), antidepressants (9%), benzodiazepines (9%), and d-amphetamine (3%).
The specific reduction in body fat in the cocaine group is striking, given that the majority of the cocaine-dependent individuals have been long-term tobacco smokers, and chronic cigarette smoking has been associated with increased visceral fat in spite of relatively low body weight (Chiolero, Faeh, Paccaud, & Cornuz, 2008). This observation further strengthens our hypothesis that chronic cocaine use selectively reduces body fat deposition. We also investigated possible effects of the higher rate of past tobacco smoking in the control group by including smoking status as a covariate in the model. Cessation of tobacco smoking has been associated with weight gain (Filozof, Fernandez Pinilla, & Fernandez-Cruz, 2004), but we did not find evidence that the higher number of former smokers in the control group confounded the results.
The CD4/CD8 lymphocyte ratio in peripheral blood is used in the diagnosis of HIV infection, autoimmune disorders or susceptibility to infections. The present experiment aimed to evaluate the lymphocyte subsets, their distribution and CD4/CD8 ratio in blood after repeated, intravenous administration of cocaine. Adult male Wistar rats received three daily, in 30 min intervals, intravenous infusions of cocaine hydrochloride (5 mg/kg) or saline for 14 consecutive days. After each infusion the locomotor-activating effects of cocaine were assessed. Blood samples were collected 30 min after the last daily infusion on the 1st, 7th and 14th day of treatment. Total leukocyte numbers, percentages of leukocyte subpopulations, and T, B, NK, T CD4+, and T CD8+ lymphocyte subsets, IFN-γ, and plasma corticosterone were determined. Repeated cocaine treatment resulted in an increase in neutrophil numbers and a significant decrease in total leukocyte and lymphocyte numbers involving a significant reduction in numbers of T, B, and NK lymphocyte subsets. T CD4+ and T CD8+ lymphocyte numbers were reduced but with a considerably smaller decrease in T CD4+ number. Cocaine treatment altered proportions between the lymphocyte subsets by decreasing the percentages of T CD8+, B, and NK cells but increasing a percentage of T CD4+ cells. Destabilization in proportions between T CD4+ and T CD8+ was manifested as an elevated CD4/CD8 ratio that occurred despite increased plasma corticosterone and the lymphocytopenia. Cocaine did not affect the concentration of IFN-γ. The results suggest that although cocaine induced lymphopenia, it did not suppress the overall immune activity in terms of the CD4/CD8 ratio.
Pregnant Long-Evans rats were administered cocaine orally (60 mg/kg) on gestational days 14-21, or subcutaneously (40 mg/kg) on gestational days 8-21. The oral dosage of cocaine produced some maternal lethality and reduced maternal weight gain throughout the pregnancy by approximately 12%. The subcutaneous dosage regimen reduced the lethality but still caused a decrease in maternal weight gain. Neither dosing regimen affected the number of pups in the litter, their weight, or growth. The offspring of dams that received the oral dosage were examined as adults in an automated holeboard apparatus and were also tested at postnatal day 21 and as adults in an open field. Adult animals exposed prenatally to cocaine did not differ from untreated controls in any of the automated measures of the holeboard apparatus or in the various behaviors, including nosepokes, recorded in the open field. Animals in the vehicle control group did make fewer nosepokes in the open field than the cocaine group, which did not differ from untreated animals. The offspring of dams given the subcutaneous dosage regimen were observed in the open field at day 21. In this case, the prenatal cocaine group had a tendency to make fewer crosses into adjacent quadrants, to rear less often, and to make fewer nosepokes than the control groups. Based on these and other data from our lab, it does not appear that in the rat, prenatal cocaine exposure has pronounced effects on subsequent exploratory behavior and activity in weanling or adult animals.
Weight gain or body fat redistribution are common side effects of many widely used drugs. Weight gain amounts varying between a few kg to an increase of 10% or more of initial body weight have been described. Often accompanying this weight gain are worsened health risks, including an increased incidence of the metabolic syndrome, type 2 diabetes, and other cardiovascular risk factors. With many drug classes, such as β-receptor antagonists, anti-psychotic drugs, corticosteroids, neurotropic drugs, and those used in the therapy of HIV, both significant weight gain and metabolic disturbances occur in susceptible patients. In this review, we provide an overview of drugs that affect body weight, fat distribution, and metabolism. Attention is given to the possible pathogenic mechanisms underlying these effects and their metabolic consequences. Potential preventive, alternative, or therapeutic measures are suggested where applicable. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
Weight gain is consistently associated with many older agents for the treatment of diabetes and with neuropsychotropic medications, including atypical antipsychotics, antidepressants, and antiepileptic drugs (1). For other drug classes, e.g. β-blocking agents, data are less consistent or well-studied. Glucocorticoids are associated with weight gain and lipodystrophy, as are retroviral agents used in the therapy of human immunodeficiency virus (HIV). Also, drugs used to manage lipid disorders, such as MTTP inhibitors and anti-sense apo-B oligonucleotides, are associated with changes in body fat distribution, especially liver lipid accumulation. Unfortunately, the mechanisms behind these effects on body weight and fat distribution are often poorly understood, which hampers identification of high-risk patients for prevention, development of lower risk-drugs, and possible treatments (2).
In this chapter, drugs affecting body weight, fat distribution, and glucometabolic outcomes will be reviewed, as well as the possible mechanisms contributing to these side effects. Recent studies will be highlighted that have been undertaken to identify predictors of weight gain and metabolic complications, and where possible, options for prevention and therapy will be discussed.
Insulin, sulfonylurea (SU), and thiazolidinediones (TZD) are medications used in the management of diabetes that may cause substantial weight gain when compared to placebo (1). Metformin and Dipeptidyl Peptidase-4 (DPP-4) inhibitors are considered to be weight neutral, whereas sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor analogues (GLP1RA) are associated with weight loss on average (3).
Insulin causes weight gain by multiple mechanisms (4). Sulfonylureas cause weight gain by increasing endogenous insulin levels. Appetite stimulation, sometimes triggered by hypoglycemia and fluctuating glycemia, is probably the most important factor in body fat increase. Defensive snacking in order to prevent hypoglycemia or compensate for it, can be observed in some patients. Poor glycemic control increases metabolic rate and consequently, improving glycemic control decreases metabolism. Improving metabolic control also reduces glycosuria and retention of otherwise lost calories. Finally, the anabolic effects of insulin can increase protein synthesis and inhibit lipolysis and proteolysis, resulting in a gain of lean body mass (3,4).
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