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. Furthermore, in a 16-month follow-up, relapse rates of DHEA-treated subjects were only 11.5%. No adverse symptoms were found. These findings demonstrate the long-term effect of DHEA on drug relapse.

DHEA reverses the altered DNA methylation as a results of addiction of several genes in pathways related to neurotransmission and corticotrophin release

In the recent published paper (7), we 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.

More scientific facts about DHEA

DHEA administration improves memory and cognitive processing, induces neurogenesis and neural survival, and attenuates levels of the stress hormone cortisol (Ulmann et al., 2009Yadid, Sudai, Maayan, Gispan, & Weizman, 2010). In healthy men and women, DHEA has been shown to induce relaxation and a higher capability of handling stressful situations.


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.

  7. 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