GABA, benzodiazepines and the brain

My husband sent this email in response to doing a bit of research regarding my general state of being lately.

Gianna,
I can’t give a particularly technical description, but it’s clear that many (and maybe most) of the symptoms you are experiencing – feelings relating to balance and general weirdness – are the result of changes taking place inside your cerebellum — see wikipedia entry here.

This deals with spacial relations, fine motor coordination and regulating fear and the most important neurotransmitter in this part of the brain is, of course, GABA. The most important type of cells in the cerebellum are Purkinje cells. There are about 20 million such cells. Each cell has up to 200,000 synapses and each synapse will have multiple GABA receptors. I would conservatively estimate that we’re talking about 40,000,000,000,000 GABA receptors. That’s 40 trillion!

The way benzos work (now I understand it a bit more clearly) is that they potentiate the effectiveness of GABA – they don’t substitute the GABA but mean that you need less of it. That means your body adjusts by producing less GABA because it doesn’t need as much.

Now that you don’t have benzos in your bloodstream your body needs to start producing more GABA and since this is an inhibitory neurotransmitter, it’s production is only going to be elevated when your environment is signalling that you don’t need to be in a state of arousal. The more stimulation you have, the more your body is getting the message: no more GABA required.

J (my kitty) helps boost your GABA production.

Yes, my animals are the most soothing thing in my existence these days.

After writing this post I found a quotation by Heather Ashton, the woman who has done all the research on benzo withdrawal in the UK. Her manual is the most comprehensive tool we have for information on what is going on with those of us who have nasty withdrawals.

This is an excerpt that is similar to what my husband writes above:

Some brain GABA receptors (which are large proteins) have a number of specific subunits which combine with benzodiazepines. When benzos combine with these subunits (of which there are several different types), GABA activity in the brain is enhanced, resulting in the typical benzo effects (sedative/hypnotic, anxiolytic, muscle relaxant, amnesic, and anti convulsant – each involving different receptor subtypes). Meanwhile, with chronic use of benzos and adaptive (homeostatic) response occurs in which many of the benzo subunits ‘down-regulate’. These subunits actually become engulfed within the neurons so that GABA activity is no longer enchanced, the benzo effects wear off, and the subject becomes tolerant.

When the benzos are stopped after these adaptive changes have occurred the brain is left in a state of GABA-underactivity and therefore in a hyperexcitable state. This accounts for the withdrawal symptoms which are largely the opposite of the original benzo effects (e.g insomnia instead of hypnosis, anxiety instead of anxiolysis, muscle tension instead of relaxation etc).

To restore normality the various subunits which have been down-regulated have to be resynthesised and re-externalised onto the GABA receptor assembly. This is a slow process involving much energy, enzymatic activity and protein synthesis. It takes place over many weeks or months, long after the drugs has left the body. It also occurs at different rates in different parts of the brain and in different subunits mediating different functions – probably accounting for the variable time of emergence, duration and resolution of individual withdrawal symptoms and sometimes the protracted benzo withdrawal. In addition, recovery may require the growth and establishment of new brain synapses as the subject learns drug-free ways to cope with stress.

For more info on benzos see here.