A Single Dose Of Ayahuasca Modulates Salivary Cortisol In Treatment-Resistant Depression

ABSTRACTMajor depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized placebo-controlled trial supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients and in healthy volunteers. Subjects received a single dose of ayahuasca or placebo, and both plasma and awakening salivary cortisol response were measured at baseline (before dosing) and 48h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients (DM), both with respect to healthy controls group (C). Salivary cortisol also was measured during dosing session and we observed a large increased for both C and DM that ingested ayahuasca, than placebo groups. After 48h of the dosing session (D2) with ayahuasca, awakening salivary cortisol response (for both sexes) of treated patients became similar to levels detected in controls. This was not observed in patients that ingested placebo. No changes in plasma cortisol were observed after 48 hours of ayahuasca or placebo ingestion for both groups and sexes. Therefore, these findings point to new evidence of modulation of ayahuasca on salivary cortisol levels, as cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes related to etiology of depression, this modulation could be an important part of the antidepressant effects observed with ayahuasca. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.

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Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Psychological Medicine ◽

10.1017/s0033291718001356 ◽

2018 ◽

Vol 49 (4) ◽

pp. 655-663 ◽

Cited By ~ 92

Author(s):

Fernanda Palhano-Fontes ◽

Dayanna Barreto ◽

Heloisa Onias ◽

Katia C. Andrade ◽

Morgana M. Novaes ◽

...

Keyword(s):

Rating Scale ◽

Remission Rate ◽

Controlled Trial ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Open Label ◽

Double Blind ◽

Therapeutic Value ◽

Antidepressant Effects ◽

Resistant Depression

AbstractBackgroundRecent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.MethodsTo test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.ResultsWe observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p= 0.04), and at D7 (p< 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64%v.27%;p= 0.04). Remission rate showed a trend toward significance at D7 (36%v.7%,p= 0.054).ConclusionsTo our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered athttp://clinicaltrials.gov(NCT02914769).

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A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression

10.1101/103531 ◽

2017 ◽

Cited By ~ 7

Author(s):

Fernanda Palhano-Fontes ◽

Dayanna Barreto ◽

Heloisa Onias ◽

Katia C Andrade ◽

Morgana Novaes ◽

...

Keyword(s):

Rating Scale ◽

Remission Rate ◽

Controlled Trial ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Open Label ◽

Double Blind ◽

Therapeutic Value ◽

Antidepressant Effects ◽

Resistant Depression

AbstractRecent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. Changes in depression severity were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to placebo (at D1 and D2: p=0.04; and at D7: p<0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’ s d=0.84; D2: Cohen’ s d=0.84; D7: Cohen’ s d=1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.

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Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression

Journal of Affective Disorders ◽

10.1016/j.jad.2019.11.028 ◽

2020 ◽

Vol 263 ◽

pp. 568-575 ◽

Cited By ~ 15

Author(s):

Elia E. Acevedo-Diaz ◽

Grace W. Cavanaugh ◽

Dede Greenstein ◽

Christoph Kraus ◽

Bashkim Kadriu ◽

...

Keyword(s):

Single Dose ◽

Side Effects ◽

Comprehensive Assessment ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Resistant Depression

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Left prefrontal transcranial magnetic stimulation for treatment-resistant depression in adolescents: a double-blind, randomized, sham-controlled trial

Neuropsychopharmacology ◽

10.1038/s41386-020-00829-y ◽

2020 ◽

Vol 46 (2) ◽

pp. 462-469

Author(s):

Paul E. Croarkin ◽

Ahmed Z. Elmaadawi ◽

Scott T. Aaronson ◽

G. Randolph Schrodt ◽

Richard C. Holbert ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Controlled Trial ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Double Blind ◽

Resistant Depression

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Mindfulness-based cognitive therapy for patients with chronic, treatment-resistant depression: A pragmatic randomized controlled trial

Depression and Anxiety ◽

10.1002/da.22788 ◽

2018 ◽

Vol 35 (10) ◽

pp. 914-924 ◽

Cited By ~ 18

Author(s):

Mira B. Cladder-Micus ◽

Anne E.M. Speckens ◽

Janna N. Vrijsen ◽

A. Rogier T. Donders ◽

Eni S. Becker ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Cognitive Therapy ◽

Chronic Treatment ◽

Controlled Trial ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Pragmatic Randomized Controlled Trial ◽

Randomized Controlled ◽

Resistant Depression

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Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial

American Journal of Psychiatry ◽

10.1176/appi.ajp.2020.20010018 ◽

2021 ◽

pp. appi.ajp.2020.2

Author(s):

Jennifer B. Dwyer ◽

Angeli Landeros-Weisenberger ◽

Jessica A. Johnson ◽

Amalia Londono Tobon ◽

José M. Flores ◽

...

Keyword(s):

Controlled Trial ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Adolescent Treatment ◽

Resistant Depression ◽

Intravenous Ketamine

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Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

BMC Psychiatry ◽

10.1186/s12888-019-2359-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Sanne Y. Smith-Apeldoorn ◽

Jolien K. E. Veraart ◽

Jeanine Kamphuis ◽

Antoinette D. I. van Asselt ◽

Daan J. Touw ◽

...

Keyword(s):

Controlled Trial ◽

Treatment Strategies ◽

Repeated Administration ◽

Additional Treatment ◽

Racemic Mixture ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Routes Of Administration ◽

Antidepressant Efficacy ◽

Resistant Depression

Abstract Background There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine’s enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. Methods This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. Discussion This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. Trial registration Dutch Trial Register, NTR6161. Registered 21 October 2016.

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Sevoflurane augmentation in treatment-resistant depression: a clinical case study

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125320957126 ◽

2020 ◽

Vol 10 ◽

pp. 204512532095712

Author(s):

Shikai Wang ◽

Shanfei Cheng ◽

Min Feng ◽

Ping Guo ◽

Mincai Qian ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Case ◽

Efficacy And Safety ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Clinical Case Study ◽

Antidepressant Effects ◽

Mucous Membranes ◽

Resistant Depression

Compared with other inhaled anaesthetics, sevoflurane has a faster onset and offset, causes less irritation to the mucous membranes, and has a better safety profile. These characteristics warrant investigating the effect of sevoflurane in depression. In this Case Report, we describe that sevoflurane treatment was feasible and well tolerated by a patient with treatment-resistant depression (TRD). Sevoflurane had rapid and durable antidepressant effects, with few adverse effects. Moreover, the patient showed significant improvements in neurocognitive measurements. Our preliminary results suggest that further clinical trials are needed to determine the independent efficacy and safety of sevoflurane in patients with TRD.

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