Participants Receiving Dehydroepiandrosterone During Treatment for Cocaine Dependence Show High Rates of Cocaine Use in a Placebo-Controlled Pilot Study.
Friends Research Institute, Los Angeles, CA, USA.Experimental and Clinical Psychopharmacology (Impact Factor: 2.71). 06/2004; 12(2):126-35. DOI: 10.1037/1064-12220.127.116.11
Twenty-three cocaine-dependent participants were randomly assigned to receive either dehydroepiandrosterone (DHEA; n = 11; 100 mg/day) or placebo (n = 12) in the context of 12 weeks of thrice weekly cognitive-behavioral group counseling. Outcomes were retention, urine drug screening, cocaine craving, adverse experiences, and medication compliance. DHEA-treated participants averaged 45.8 (SD = 28.8) days in treatment, compared with 70.7 (SD = 20.6) days for placebo, r(21) = -2.4, p =.03, and provided 26.8% (SD = 29.3) of urine samples free of cocaine metabolite compared with 70.6% (SD = 39.9) for the placebo condition, r(21) = -3.0, p =.01. No differences were detected between conditions for cocaine craving or adverse experiences. High levels of medication compliance were documented. Results argue against using high doses of DHEA as a pharmacotherapy for cocaine dependence.
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- "Several animal studies demonstrated involvement of neurosteroids in drug addictions (Budziszewska et al. 1996, Reddy and Kulkarni 1997, Yadid et al. 2010). Previous clinical studies documented an ambiguous involvement of DHEA(S) in psychostimulant addiction (Shoptaw et al. 2004, Wilkins et al. 2005), where high endogenous levels of this steroid in blood correlated with protection of cocaine addicts from relapse (Wilkins et al. 2005), but treatment of addicts with high dose of DHEA seemed to augment the rewarding effect of cocaine (Shoptaw et al. 2004). Because DHEA(S) can be metabolized to androsterone, which has opposite neuronal activity, we were interested in comparing the direct effects of both these steroids on psycho-behaviors intrinsically linked with addiction processes such as locomotor activity, reward and anxiety . "
ABSTRACT: The neurosteroids, dehydroepiandrosterone sulfate (DHEAS) and androsterone, are implicated in drug addictions. We examined their influence on locomotor activity and reward in male Wistar rats, and on steroid and monoamine metabolism in the hippocampus and striatum. In the open field test, DHEAS injections (10, 40, 80 mg/kg, i.p.) 30 min prior the test had no significant effect on ambulation, but androsterone (10 mg/kg) increased general locomotion and at doses 1-10 mg/kg, increased central field activity, suggestive of an anxiolytic action. In the conditioned place preference test, both steroids had a biphasic effect: DHEAS was rewarding at doses of 10 and 40 mg/kg, but not at 80 mg/kg, while androsterone was rewarding at doses of 1 and 10 mg/kg, but aversive at 40 mg/kg. Monoamine and steroid concentrations were analyzed in homogenates from the hippocampus and striatum of DHEAS and androsterone injected rats. DHEAS reduced the hippocampal dopamine level, increased striatal homovanilic acid (HVA) and decreased the striatal serotonin concentrations. Androsterone did not affect dopamine levels or turnover, but increased noradrenaline concentration and serotonin turnover in the hippocampus. DHEAS administration augmented concentrations of DHEA, pregnenolone, androstendiol and androstentriol in both brain structures, while androsterone injections increased brain levels of androsterone, epiandrosterone, 5α-dihydrotestosterone, and androstandiol. Present data document that although psychobehavioral and neurochemical effects of DHEAS and androsterone differ in several aspects; both neurosteroids have rewarding properties at certain dose ranges, suggesting their likely involvement in addictions, which entail different mechanisms.
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- "In this regard we have shown that cocaine addicts, who had higher concentrations of endogenous DHEAS in blood during therapy for drug dependence, were more likely to succeed in maintaining prolonged abstinence after the therapy than those, who had lower levels of this hormone (Wilkins et al. 2005). However, treatment of cocaine addicts with high pharmacological doses of DHEA was not therapeutic and even resulted in increased cocaine use (Shoptaw et al. 2004). These apparently discordant results suggest the existence of a complex relationship between the levels of different neuroactive steroids in the blood (and presumably in the CSF) and intricate mental phenomena such as drug dependence, craving and use. "
ABSTRACT: Ion channels are vital components of plasma membranes. This article presents an evolutionary view of the biochemical mechanism of controlling activity of ion channels by rigid lipids, such as steroids or biophysically similar molecules, which were instrumental in formation and control of ion channels in cell membranes at the very origin of life. Such regulatory mechanisms exist in all cellular forms of life from ancient bacteria to humans and participate in a diversity of biological functions, from the most basic, such as maintenance of cell shape, homeostasis, feeding, cell fusion, and reproduction to the most intricate, such as the mind. Learning about the regulation of membrane ion channels by steroids and like molecules is important for understanding the evolution of life and various aspects of cell and organism physiology, for unraveling the mysteries of mind, and for practical purposes such as developing new pharmacotherapies.
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- "Only patients in which a spontaneous increase in DHEA-S levels was observed were identified as being successful at abstaining from cocaine usage over time (Wilkins et al, 2005). Although a connection between DHEA/DHEA-S, low distressed mood levels, and enhanced CNS resiliency during withdrawal was suggested (Wilkins et al, 2005), it seems that selecting their exogenous dose is critical to avoid relapse (Shoptaw et al, 2004). "
ABSTRACT: Dehydroepiandrosterone (DHEA), which can act as a potential antidepressant in both animals and humans, appears to lower distress involved with cocaine withdrawal. In fact, a role for neurosteroids in modulation of substance-seeking behavior is becoming increasingly clear. Therefore, we tested the effects of DHEA on the self-administration of cocaine (1 mg/kg/infusion) by rats. At maintenance, a relatively low dose of exogenous DHEA (2 mg/kg; i.p.) attenuated cocaine self-administration after several days of chronic treatment. More than 2 weeks (19 days) of daily DHEA injections were required to decrease the cocaine-seeking behavior of rats to less than 20% of their maintenance levels. DHEA does not seem to decrease cocaine self-administration by increasing the reinforcing properties of the drug, as indicated by a cocaine dose-response determination. After being subjected to extinction conditions in the presence of DHEA, rats demonstrated a minimal response to acute exposure to cocaine (10 mg/kg), which indicated a protective effect of DHEA on relapse to cocaine usage. Our results suggest a potential role for the neurosteroid DHEA in controlling cocaine-seeking behavior, by reducing both the desire for cocaine usage and the incidence of relapse.
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