Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor

Institute of Neurology and Institute of Psychiatry, Catholic University, Rome, Italy.
Journal of Psychopharmacology (Impact Factor: 3.59). 12/2007; 21(8):820-5. DOI: 10.1177/0269881107078491
Source: PubMed


Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs may alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons. In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers. Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users. BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users. These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users.

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    • "The significance of changes in the levels of BDNF in substance users is still controversial. In patients using alcohol, marijuana, methamphetamine, and heroin, BDNF levels do not seem to be different when compared with controls, but some studies show either decrease or elevation of BDNF levels (Kim et al. 2005; Angelucci et al. 2007, 2010; Huang et al. 2008; Heberlein et al. 2010, 2011; Costa et al. 2011; D'Sa et al. 2012). In ecstasy (MDMA) users, BDNF levels appear to be elevated (Angelucci et al. 2010). "
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    ABSTRACT: An important goal of addiction research is to discover neurobiological markers that could predict the severity of addiction and help to determine appropriate treatment. Brain-derived neurotrophic factor (BDNF) and thiobarbituric acid reactive substances (TBARS) are being related to cerebral plasticity and impairment caused by substance abuse. This study aims to evaluate alteration of TBARS and BDNF levels among crack cocaine users during early drug withdrawal and its relationship to severity of drug use. Forty-nine adults crack cocaine users were recruited at a public psychiatric hospital with a specialized addiction treatment unit. Blood sample was collected at intake and discharge for the analysis of TBARS and BDNF measures. Information about drug use was assessed by the Addiction Severity Index 6th Version (ASI-6). Detailed information about crack cocaine use was obtained through the "Profile of the crack cocaine user." Severity of crack use was estimated using information from age of first crack use, years of crack use, and crack rocks used in the previous 30 days. There is a positive correlation between TBARS levels and severity of crack cocaine use (R = 0.304, p = 0.04) and a negative correlation between BDNF and severity of crack cocaine use (R = -0.359, p = 0.01) at discharge. Also, we found an inverse correlation between TBARS and BDNF levels (R = -0.294, p = 0.004) at discharge. Our findings suggest that BDNF and TBARS could be possible markers for the severity of drug use. Further studies may show how those markers could be related to staging, prognosis, and treatment in crack cocaine dependence.
    Psychopharmacology 03/2014; 231(20). DOI:10.1007/s00213-014-3542-1 · 3.88 Impact Factor
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    • "BDNF levels were found to be reduced in patients at the time of admission vs. discharge and vs. controls. This finding is in disagreement with a report describing similar BDNF levels between injecting cocaine users and control subjects (Angelucci et al., 2007), but is similar to the results reported by Corominas-Roso et al. (2012). Among methamphetamine abusers abstinent for a minimum of 30 d, one report found increased BDNF levels (Kim et al., 2005), whereas another study found a reduction (Chen et al., 2012). "
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    ABSTRACT: Recent reports suggest that brain-derived neurotrophic factor (BDNF) could be a biomarker for relapse, drug craving and withdrawal severity. In particular, elevated BDNF levels among former cocaine users have been associated with higher rates of relapse in 90 d. However, no data are available on BDNF levels at baseline and during crack cocaine withdrawal. This study evaluated BDNF among crack cocaine users during inpatient treatment, before and after withdrawal, vs. healthy controls. Clinical correlates with changes in BDNF levels were also assessed. Serum BDNF was evaluated in 49 male crack users on the first and last days of hospitalization and in 97 healthy controls. Serum BDNF was assayed using a sandwich ELISA kit. BDNF levels were significantly lower upon admission when compared to controls, even after adjustment for age, length of inpatient treatment, number of crack rocks used in the last 30 d, years of crack use and interaction between the latter two variables. At discharge, BDNF levels between patients and controls were similar. Number of crack rocks used in the last 30 d and years of crack use were inversely correlated with the outcome. Our findings show that BDNF levels increase during early crack cocaine withdrawal, at an inverse correlation with number of crack rocks used in the last 30 d and years of crack use.
    The International Journal of Neuropsychopharmacology 09/2013; 17(01):1-8. DOI:10.1017/S146114571300103X · 4.01 Impact Factor
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    • "Since BDNF crosses the blood–brain barrier in both directions (Pan et al., 1998) and can be measured in serum and plasma (Fujimura et al., 2002), serum BDNF levels may reflect brain BDNF levels (Klein et al., 2011). The first study assessing BDNF in cocaine addicts found no difference in BDNF serum levels in 15 cocaine addicts and a group of healthy controls (Angelucci et al., 2007). However, a recent cross-sectional study of 22 cocaine-dependent individuals reported a significant correlation between serum BDNF and number of abstinence days (Hilburn et al., 2011) and recently, BDNF was reported to be increased after 3 weeks of withdrawal (D'Sa et al., 2011). "
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    ABSTRACT: Preclinical studies indicate that brain-derived neurotrophic factor (BDNF) is involved in neuroplastic changes underlying enduring cocaine-seeking following withdrawal. However, little is known about temporal changes in serum BDNF levels or the involvement of BDNF in craving and abstinence in early-abstinent cocaine-dependent patients. Twenty-three cocaine-dependent individuals (aged 33.65±6.85 years) completed a two-week detoxification program at an inpatient facility. Two serum samples were collected for each patient at baseline and at the end of the protocol. Serum samples were also collected for 46 healthy controls (aged 35.52±9.37 years). Demographic, consumption and clinical data were recorded for all patients. Significantly lower serum BDNF levels (p<.0001) were observed for cocaine-dependent patients at baseline compared to healthy controls. Serum BDNF levels increased significantly across 12 days of early abstinence (p=.030). Baseline BDNF levels correlated with craving (p=.034). Post-detoxification BDNF levels correlated with craving (p=.018), loss of control (p<.000), abstinence measures (p=0.031), depression (p=0.036), and anxiety (p=0.036). Post-detoxification BDNF levels also had predictive value for the loss of control measure of craving. Chronic cocaine use is associated with decreased serum BDNF. A progressive increase in serum BDNF levels during early abstinence correlates with cocaine craving and abstinence symptoms and may reflect increasing BDNF levels in different brain regions. These findings suggest that serum BDNF may be a biomarker for cocaine addiction.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 09/2012; 23(12). DOI:10.1016/j.euroneuro.2012.08.016 · 4.37 Impact Factor
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