OPEN Foundation

A. Newberg

Of Roots and Fruits A Comparison of Psychedelic and Nonpsychedelic Mystical Experiences


Experiences of profound existential or spiritual significance can be triggered reliably through psychopharmacological means using psychedelic substances. However, little is known about the benefits of religious, spiritual, or mystical experiences (RSMEs) prompted by psychedelic substances, as compared with those that occur through other means. In this study, 739 self-selected participants reported the psychological impact of their RSMEs and indicated whether they were induced by a psychedelic substance. Experiences induced by psychedelic substances were rated as more intensely mystical (d = .75, p < .001), resulted in a reduced fear of death (d = .21, p < .01), increased sense of purpose (d = .18, p < .05), and increased spirituality (d = .28, p < .001) as compared with nonpsychedelically triggered RSMEs. These results remained significant in an expanded model controlling for gender, education, socioeconomic status, and religious affiliation. These findings lend support to the growing consensus that RSMEs induced with psychedelic substances are genuinely mystical and generally positive in outcome.

Yaden, D. B., Le Nguyen, K. D., Kern, M. L., Belser, A. B., Eichstaedt, J. C., Iwry, J., … & Newberg, A. B. (2016). Of Roots and Fruits A Comparison of Psychedelic and Nonpsychedelic Mystical Experiences. Journal of Humanistic Psychology, 0022167816674625.
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A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression


Context: Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health.

Objective: To determine whether an N-methyl-Daspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression.

Design: A randomized, placebo-controlled, doubleblind, crossover, add-on study conducted from October 2006 to June 2009.

Setting: Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland.

Patients: Eighteen subjects with DSM-IV bipolar depression (treatment-resistant).

Interventions: Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery- Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion.

Results: Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d=0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d=0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point.

Diazgranados, N.,  Ibrahim, L. Brutsche, N. E., Newberg, A., Kronstein, P.,  Khalife, S., … Zarate Jr., Z. A. (2010). A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression. Archives of General Psychiatry, 67(8).
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4 October - Online psychedelic Q&A with Rick Doblin (founder and president of MAPS)