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Blocking Human Fear Memory With The Matrix Metalloproteinase Inhibitor Doxycycline

paymanz

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Jan 6, 2015
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Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline




Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline
Received:
05 January 2017
Revised:
21 February 2017
Accepted:
22 February 2017
Published online:
04 April 2017
Abstract


Learning to predict threat is a fundamental ability of many biological organisms, and a laboratory model for anxiety disorders. Interfering with such memories in humans would be of high clinical relevance. On the basis of studies in cell cultures and slice preparations, it is hypothesised that synaptic remodelling required for threat learning involves the extracellular enzyme matrix metalloproteinase (MMP) 9. However, in vivo evidence for this proposal is lacking. Here we investigate human Pavlovian fear conditioning under the blood–brain barrier crossing MMP inhibitor doxycyline in a pre-registered, randomised, double-blind, placebo-controlled trial. We find that recall of threat memory, measured with fear-potentiated startle 7 days after acquisition, is attenuated by ~60% in individuals who were under doxycycline during acquisition. This threat memory impairment is also reflected in increased behavioural surprise signals to the conditioned stimulus during subsequent re-learning, and already late during initial acquisition. Our findings support an emerging view that extracellular signalling pathways are crucially required for threat memory formation. Furthermore, they suggest novel pharmacological methods for primary prevention and treatment of posttraumatic stress disorder.

The study medication was doxycycline, brand name Vibramycin (Pfizer, Zurich, Switzerland). The study dose of 200 mg was based on the smallest antibiotic dose recommended by the manufacturer, in order to reduce side effects. Peak cerebrospinal fluid concentrations are reached at approximately 180 min after oral administration.19 The drug's half-life is ~16 h according to manufacturer's information; such the drug was cleared by more than 99.9% at the retention test 7 days after ingestion.
 

Vinero

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Non-reactiveness to certain bad situations and people is a huge social advantage.
Methylene blue also helps with this.
 

jyb

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I once took doxycycline over a long period of time. I never noticed any psychological changes (or any positive health benefit whatsoever), I for sure was not less fearful.
 

Vinero

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ive found the complete opposite to be true of MB :(
How much do you take?
5 mg two to three times a day is very effective for reducing fear and anxiety.
It erases fearful memories of past negative situations.
You have to work up to this dose though, if you just start methylene blue you can get increased serotonin in the beginning.
Start with a few mgs a day and work your way up.
 
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My anecdotal experience confirms 3 months of doxy and 2 weeks of mino greatly reduced spantaneous recall of traumatic episodes.
 

TMCMac

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Dec 28, 2020
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How much do you take?
5 mg two to three times a day is very effective for reducing fear and anxiety.
It erases fearful memories of past negative situations.
You have to work up to this dose though, if you just start methylene blue you can get increased serotonin in the beginning.
Start with a few mgs a day and work your way up.
Super interesting. What are the mechanisms behind this? Are there any other compounds that do similar things?
 

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