The effect of DHEA complementary treatment on heroin addicts participating in a rehabilitation program: A preliminary study

Maayan, Rachel; Touati-Werner, Dafna; Shamir, D.; Yadid, Gal; Friedman, Alexander; Eisner, Dana; Weizman, Abraham; Herman, Issaschar

doi:10.1016/j.euroneuro.2007.12.003

Cited by 10 publications

(10 citation statements)

References 40 publications

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“…There may also be a role for DHEA and its sulfate ester DHEAS in regulation of stress-associated drug seeking. Promisingly, DHEA administration has been shown to suppress relapse to heroin seeking in humans ( Maayan et al, 2008 ) and cocaine reinstatement in rodents ( Doron et al, 2006 ) in the absence of a stressor. As DHEA has been shown to promote adaptive responding to stressful stimuli ( Shields et al, 2016 ), it presents a promising target for pharmacotherapeutic investigation in stress-induced drug-seeking.…”

Section: Neuroactive Steroidal Targetsmentioning

confidence: 99%

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

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Reichel

McRae‐Clark

2021

Neurobiology of Stress

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Stress is a frequent precipitant of relapse to drug use. Pharmacotherapies targeting a diverse array of neural systems have been assayed for efficacy in attenuating stress-induced drug-seeking in both rodents and in humans, but none have shown enough evidence of utility to warrant routine use in the clinic. We posit that a critical barrier in effective translation is inattention to sex as a biological variable at all phases of the research process. In this review, we detail the neurobiological systems implicated in stress-induced relapse to cocaine, opioids, methamphetamine, and cannabis, as well as the pharmacotherapies that have been used to target these systems in rodent models, the human laboratory, and in clinical trials. In each of these areas we additionally describe the potential influences of biological sex on outcomes, and how inattention to fundamental sex differences can lead to biases during drug development that contribute to the limited success of large clinical trials. Based on these observations, we determine that of the pharmacotherapies discussed only α 2 -adrenergic receptor agonists and oxytocin have a body of research with sufficient consideration of biological sex to warrant further clinical evaluation. Pharmacotherapies that target β-adrenergic receptors, other neuroactive peptides, the hypothalamic-pituitary-adrenal axis, neuroactive steroids, and the endogenous opioid and cannabinoid systems require further assessment in females at the preclinical and human laboratory levels before progression to clinical trials can be recommended.

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Section: Neuroactive Steroidal Targetsmentioning

confidence: 99%

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

Doncheck

Reichel

McRae‐Clark

2021

Neurobiology of Stress

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“…Most recently, a randomized, double‐blind controlled study evaluated the effect of DHEA in human opiate addicts as an add‐on to a detoxification and maintenance treatment with buprenorphine (Maayan et al . ). The results of this study showed a biphasic effect: 34 out of 49 patients showed a significant improvement in withdrawal symptoms and depression and anxiety scores, whereas 15 out of 49 patients demonstrated deterioration in all these measures.…”

Section: Introductionmentioning

confidence: 97%

Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users

et al. 2015

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A major problem in the treatment of addiction is predicting and preventing relapse following a rehabilitation program. Recently, in preclinical rodent studies dehydroepiandrosterone (DHEA) was found to markedly improve the resistance to drug reuse. In a double-blind, placebo-controlled study, we examined the effect of DHEA on relapse rates in adult polydrug users taking part in a detoxification program enriched with intensive psychosocial interventions and aftercare. During treatment, participants (79 percent males, mean age 28) consumed DHEA (100 mg/day) or placebo daily for at least 30 days. Of the 121 initial volunteers, 64 participated for at least 1 month. While in treatment, DHEA reduced negative affect on the Positive and Negative Affect Scale (F = 4.25, P = 0.04). Furthermore, in a 16-month follow-up, we found that reuse rates in the DHEA condition were about a third compared with placebo (12 versus 38 percent; χ(2) = 5.03, P = 0.02). DHEA treatment also resulted in an increase in DHEA sulfate (DHEA-S) 1 month following treatment, and the level of DHEA-S predicted relapse in the follow-up assessment.

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“…9,10 These studies further revealed that DHEA treatment led to an increase in circulatory DHEA-S levels 1 month after treatment and that circulatory DHEA-S levels at treatment initiation predicted relapse rates at 16 months. 9,10 The mechanisms through which DHEA may act to aid SUD remission and reduce relapse rates in pSUD are not yet clear. One potential mechanism may relate to a recent finding in rodents that DHEA administration led to an increase in white matter (WM) integrity, which in turn was associated with long-term reduction in craving behavior.…”

mentioning

confidence: 92%

The Effect of Dehydroepiandrosterone Administration during Rehabilitation on White Matter Integrity Among Individuals With Polysubstance Use Disorder

Bilaus,

Turchinski,

Ahdoot

et al. 2023

J Addict Med

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Objectives: Individuals with polysubstance use disorder (pSUD) exhibit vulnerability to relapse even after prolonged abstinence, with rehabilitation efforts achieving limited success. Previous studies highlighted dehydroepiandrosterone (DHEA) as a putative therapeutic agent that may aid rehabilitation, potentially by impacting white matter (WM) properties. The current study tested, for the first time, the effect of DHEA administration during rehabilitation on WM integrity among pSUD individuals, while assessing its putative association with long-term relapse rates. Methods: Immediately after admission to rehabilitation, 30 pSUD individuals were assigned to receive either placebo or DHEA (100 mg) daily for 3 months, via a randomized double-blind counterbalanced design. Participants also provided blood samples to assess circulating DHEA levels at treatment initiation and completed a diffusion tensor imaging (DTI) scan approximately 1 month after treatment initiation. Clinical status was evaluated 16 months after treatment initiation. Thirty matched healthy controls also underwent a DTI scan without any intervention.Results: DHEA administration was not associated with reduced relapse rates compared with placebo. Nevertheless, exploratory analysis revealed that DHEA was associated with successful rehabilitation among pSUD individuals with low circulating DHEA levels at treatment initiation. White matter integrity in the splenium corpus callosum (CC) was reduced in pSUD individuals compared with healthy controls, yet pSUD individuals receiving DHEA exhibited recovery of splenium CC WM integrity. Conclusions: DHEA administration during rehabilitation may restore WM integrity in the CC among pSUD individuals. Although DHEA was not associated with reduced relapse rates in here, its therapeutic efficacy may depend on circulating DHEA levels at treatment initiation.

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The effect of DHEA complementary treatment on heroin addicts participating in a rehabilitation program: A preliminary study

Cited by 10 publications

References 40 publications

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users

The Effect of Dehydroepiandrosterone Administration during Rehabilitation on White Matter Integrity Among Individuals With Polysubstance Use Disorder

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