A proof-of-principle study of the short-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus and neural connectivity.

G D Searchfield; T N E R Poppe; M Durai; M Jensen; M A Kennedy; S Maggo; A L Miller; J Park; B R Russell; G S Shekhawat; D Spiegel; F Sundram; K Wise

doi:10.1080/00207454.2019.1702544

A proof-of-principle study of the short-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus and neural connectivity.

G D Searchfield, T N E R Poppe, M Durai, M Jensen, M A Kennedy, S Maggo, A L Miller, J Park, B R Russell, G S Shekhawat, D Spiegel, F Sundram, K Wise

International Journal of Neuroscience July 2020 DOI: 10.1080/00207454.2019.1702544 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Double-blind randomized controlled cross-over trial Peer reviewed
Sample size	8
Population	Adults with tinnitus
Intervention	MDMA
Dose	30 mg, 70 mg
Topics	MDMA
Keywords	3,4-methylenedioxymethamphetamine Tinnitus Rs-MRI Treatment
Key findings	At 70 mg, MDMA significantly reduced tinnitus annoyance and ignore ratings after four hours, though a placebo effect was also observed; at 30 mg results were similar to placebo. Resting-state fMRI showed decreased connectivity between amygdala, hippocampal, and parahippocampal regions and increased connectivity in temporal and frontoparietal networks. The authors argue there is sufficient proof of concept to support further investigation of MDMA for tinnitus.

Abstract

Background: This study was conducted to investigate the short-term behavioural and neurophysiological effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus perception.Methods: A double-blind randomized controlled cross-over design. Part 1. Behavioural measures of tinnitus following 30 mg MDMA or placebo administration (N = 5 participants) and Part 2. Behavioural measures of tinnitus and correlations between pairs of apriori regions of interest (ROI) using resting-state functional magnetic resonance imaging (rs-fMRI) before and after 70 mg of MDMA or placebo (N = 8 participants).Results: The results to MDMA were similar to placebo. For the 70 mg dose, there was a significant reduction after 4 h in annoyance and ignore ratings. RsMRI showed decreased connectivity compared with placebo administration between the left hippocampal, right hippocampal, left amygdala and right amygdala regions, and between the right posterior parahippocampal cortex and the left amygdala after two hours of 70 mg MDMA administration. Increased connectivity compared to placebo administration was found post MDMA between the right post-central gyrus and right posterior and superior temporal gyrus, and between the thalamus and frontoparietal network.Conclusions: Following 70 mg of MDMA two tinnitus rating scales significantly improved. There was, however, a placebo effect. Compared with placebo the rsMRI following the MDMA showed reductions in connectivity between the amygdala, hippocampus and parahippocampal gyrus. There is sufficient proof of concept to support future investigation of MDMA as a treatment for tinnitus.

Comparable studies

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Study	Year	Design	Participants
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Patients with severe PTSD, including those with comorbidities such as dissociation,...	2021	Randomized controlled trial	n = 90
The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Patients with chronic post-traumatic stress disorder refractory to both psychotherapy...	2010	Randomized controlled trial	n = 20
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Military veterans and first responders aged 18 or older with chronic PTSD lasting 6...	2018	Randomized, double-blind, dose-response, phase 2 clinical trial	n = 26
A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) Patients with treatment-resistant PTSD	2012	Randomized controlled trial	n = 12
MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Adults with moderate to severe post-traumatic stress disorder	2023	Randomized controlled trial	n = 104

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