Effect of DHEA on Drug Abuse Treatment

Preclinical rodent studies have shown that DHEA markedly improves resistance to cocaine’s initial effects, and prevents relapse to its use (1,2).

In addition, DHEA increases neurogenesis and neuronal survival in human neural stem cells cultures (3); this is important because high dosage cocaine decreases neurogenesis in the brain, and impairs working memory in rats (4).

DHEA also appeared to contribute to the success of outcomes in addiction treatment of humans:

DHEA complementary treatment was effective in heroin addicts, showing significant improvement in the severity of withdrawal symptoms, depression and anxiety scores (providing subjects had not previously used cocaine or benzodiazepines, and had experienced few withdrawal programs) (5).

Moreover, a double-blind, placebo-controlled study in adult polydrug users in a detoxification program showed the efficacy of DHEA treatment combined with psychosocial enrichment and after-care. DHEA administration positively affected decision-making, mood and well-being as early as one month into treatment, and had a long-lasting preventive effect on relapse to drug use. The DHEA treated subjects reported fewer negative emotions, and showed more advantageous choosing in a decision-making task (Figure 1). Furthermore, in a 16-month follow-up, relapse rates of DHEA-treated subjects were only 11.5% (Figure 2). No adverse symptoms were found. These findings demonstrate the long-term effect of DHEA on drug relapse.


Supporting Research

  1. Maayan R, Lotan S, Doron R, Shabat-Simon M, Gispan-Herman I, Weizman A, Yadid G. Dehydroepiandrosterone (DHEA) attenuates cocaine-seeking behavior in the self-administration model in rats. Eur Neuropsychopharmacol. 2006 Jul;16(5):329-39.

  2. Doron R, Fridman L, Gispan-Herman I, Maayan R, Weizman A, Yadid G. DHEA, a neurosteroid, decreases cocaine self-administration and reinstatement of cocaine-seeking behavior in rats. Neuropsychopharmacology. 2006 Oct;31(10):2231-6.

  3. Suzuki, M., Wright, L.S., Marwah, P., Lardy, H.A., Svendsen, C.N., 2004. Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex. Proc. Natl. Acad. Sci. U.S.A. 101, 3202–3207.

  4. Sudai E, Croitoru O, Shaldubina A, Abraham L, Gispan I, Flaumenhaft Y, Roth-Deri I, Kinor N, Aharoni S, Ben-Tzion M, Yadid G. High cocaine dosage decreases neurogenesis in the hippocampus and impairs working memory. Addict Biol. 2011 Apr;16(2):251-60.

  5.  Maayan R, Touati-Werner D, Shamir D, Yadid G, Friedman A, Eisner D, Weizman A, Herman I. The effect of DHEA complementary treatment on heroin addicts participating in a rehabilitation program: a preliminary study. Eur Neuropsychopharmacol. 2008 Jun;18(6):406-13

  6. Ohana D, Maayan R, Delayahu Y, Roska P, Ponizovsky AM, Weizman A, Yadid G, Yechiam E. Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users. Addict Biol. 2015 Mar 26.

DHEA Program

Our program revealed that for optimal efficacy and outcome, DHEA must be taken at adequate, individually tailored doses. Therefore, we developed a novel algorithm, which takes into account personal data (age, gender, ethnicity, previous drug consumption, diseases, etc.) and various physical and psychological parameters, and calculates the optimal dose of DHEA and length of treatment required. Our software also provides a personal profile for each patient, through which the caregiver can monitor the patient’s progress, manage the course of treatment, and even predict the length of treatment needed and probability to relapse. Our treatment program is an add-on treatment that can be easily integrated into existing rehab programs and enhance the various therapies given. Our group of skilled specialists will be at your service throughout the treatment process, and will promptly respond to every question or concern. 

DHEA in Humans

DHEA is a steroidal pro-hormone, naturally produced from cholesterol. DHEA synthesised in the brain functions as a neurosteroid. DHEA is the most abundant circulating steroid hormone in humans, although its secretion changes across the lifespan. Its natural production in the body begins at the age of 7 and peaks at the age of 25, followed by a steady decline in production; by the age of 75, it is at ~20% of its peak amount. DHEA is essential for the immunological system and was shown to help prevent various diseases, including high blood pressure, diabetes, and autoimmune disorders. DHEA was also found to boost energy, improve mood and well-being, decrease depression and anxiety, and also have an anti-aging effect [1, 2]. DHEA may have weak side effects, e.g., transient increase in hepatic enzymes, increased perspiration, oily facial skin or increased facial hair, abdominal pain, sleep disturbances, rash, or breast sensitivity. These transient effects were seen mostly at higher doses of 100-200 mg per day given for 12-24 weeks [3, 4]; as for longer periods of 10-12 months (at 50 mg DHEA), either slight or no serious adverse events were reported [5, 6]. For treatment of addiction, DHEA is generally taken at the higher doses, and therefore patients require tight supervision, including weekly data collection and analysis, and possible alterations of DHEA dosage accordingly.

Supporting Research

  1.  Yadid G, Sudai E, Maayan R, Gispan I, Weizman A. The role of dehydroepiandrosterone (DHEA) in drug-seeking behavior. Neurosci Biobehav Rev. 2010 Nov;35(2):303-14.

  2. Vinson GP, Brennan CH. Addiction and the adrenal cortex. Endocr Connect. 2013 May 31.

  3. Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002. 46 (11): 2924–2927.  

  4. Flynn MA, Weaver-Osterholtz D, Sharpe-Timms KL, Allen S, Krause G. Dehydroepiandrosterone replacement in aging humans. J Clin Endocrinol Metab. 1999. 84(5):1527-33.

  5. Brooke AM, Kalingag LA, Miraki-Moud F, Camacho-Hübner C, Maher KT, Walker DM, Hinson JP, Monson JP. Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement. J Clin Endocrinol Metab 2006. 91 (10): 3773–3779.

  6. Villareal DT, Holloszy JO. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am J Physiol Endocrinol Metab 291. 2006 (5): E1003–1008.

A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention

In the recent published paper, it was demonstrated, that intervention with DHEA, that has a long-term therapeutic effect on human addicts resulted in reversal of DNA methylation changes in genes related to pathways associated with the addictive state.

Supporting Research

  1.  Lax EWarhaftig GOhana DMaayan RDelayahu YRoska PPonizovsky AMWeizman AYadid GSzyf MA DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention. Front. Mol. Neurosci., 10 September 2018