Dorian:
Judging from the study whose abstract I paste below, it looks as though supplementing with SAM-e might make it more difficult to shake a pre-existing addiction, but the study doesn't speak to the question of whether taking SAM-e could contribute to developing an addiction in the first place. It's also a rat study, not a human study.
J Neurosci. 2015 May 27;35(21):8042-58. doi: 10.1523/JNEUROSCI.3053-14.2015.
Role of DNA methylation in the nucleus accumbens in incubation of
cocaine craving.
Author information
1
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
2
Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 52900, Israel, Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
3
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada, McGill Centre for Bioinformatics, McGill University, Montreal, Quebec H3G 0B1, Canada.
4
McGill Centre for Bioinformatics, McGill University, Montreal, Quebec H3G 0B1, Canada.
5
Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, and.
6
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada, Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec H3G 0B1, Canada moshe.szyf@mcgill.ca yadidg@gmail.comgmail.com.
7
Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 52900, Israel, Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel, moshe.szyf@mcgill.ca yadidg@gmail.comgmail.com.
Abstract
One of the major challenges of cocaine addiction is the high rate of relapse to drug use after periods of withdrawal. During the first few weeks of withdrawal, cue-induced cocaine craving intensifies, or "incubates," and persists over extended periods of time. Although several brain regions and molecular mechanisms were found to be involved in this process, the underlying epigenetic mechanisms are still unknown. Herein, we used a rat model of incubation of cocaine craving, in which rats were trained to self-administer cocaine (0.75 mg/kg, 6 h/d, 10 d), and cue-induced cocaine-seeking was examined in an extinction test after 1 or 30 d of withdrawal. We show that the withdrawal periods, as well as cue-induced cocaine seeking, are associated with broad, time-dependent enhancement of DNA methylation alterations in the nucleus accumbens (NAc). These gene methylation alterations were partly negatively correlated with gene expression changes. Furthermore, intra-NAc injections of a DNA methyltransferase inhibitor (RG108, 100 μm) abolished cue-induced cocaine seeking on day 30, an effect that persisted 1 month, whereas the methyl donor S-adenosylmethionine (500 μm) had an opposite effect on cocaine seeking. We then targeted two proteins whose genes were demethylated by RG108-estrogen receptor 1 (ESR1) and cyclin-dependent kinase 5 (CDK5). Treatment with an intra-NAc injection of the ESR1 agonist propyl pyrazole triol (10 nm) or the CDK5 inhibitor roscovitine (28 μm) on day 30 of withdrawal significantly decreased cue-induced cocaine seeking. These results demonstrate a role for NAc DNA methylation, and downstream targets of DNA demethylation, in incubation of cocaine craving.
Copyright © 2015 the authors 0270-6474/15/358042-17$15.00/0.
A couple of key excerpts (from the full text):
…In contrast to the effect of RG108, treatment with SAM caused a significant increase in active lever pressing during the extinction test (day 30) compared with aCSF-treated rats; this effect remained up to 1 month after the single SAM treatment (day 60) (one-way ANOVA main effect of group: F(2,19) = 9.37; p = 0.0005, Student-Newman-Keuls' test; p < 0.001 for day 30 and p < 0.05 for day 60; Fig. 5F).
…In the present study, we show broad, dynamic, and time-dependent increases in DNA methylation alterations in the NAc after cocaine withdrawal and cue-induced cocaine seeking. These methylation changes occurred in gene promoters at the whole-genome level and in selected candidate genes related to drug addiction and were partly negatively correlated to gene expression changes. DNMT inhibition by intra-NAc injection of RG108 significantly attenuated cue-induced cocaine seeking after prolonged withdrawal and up to 1 month after treatment, whereas the methyl donor SAM had the opposite effect, inducing a long-term increase in cue-induced cocaine seeking.
