Health - Perpetual high without addiction/tolerance?

[darawk]

I've been thinking for a little while now about the possibility of alternating pharmacologically different downers over a potentially infinite period of time.

We have three main classes of euphoric downers that I can think of which should have little to no cross-tolerance with one another(AFAIK, that is):

- Benzodiazepines (GABA-A)
- GHB & Analogs (GABA-B and GHB-specific receptors)
- Opiates (Opioid receptors)

For opiates, it is possible to reverse tolerance to them using a substance called 'proglumide'. It would also be possible to quickly reverse tolerance to opiates on days in which they aren't being used, using something like naloxone or naltrexone.

Opiate tolerance can also be reversed using NMDA antagonists, such as DXM, Ketamine, and PCP. This could imply that throwing in a dissociative trip on the weekends could significantly lower tolerance to opiates as well.


According to this study:

http://jpet.aspetjournals.org/cgi/co...full/291/3/932

GABA-A antagonists can at least partially reduce tolerance to benzodiazepines. However, i'm not sure how a GABA antagonist would feel subjectively...it might be unpleasant.

http://www.ionchannels.org/showabstr...p?pmid=7637878

The above study seems to say that in rats(And it's important to remember that this result is for rats, not people), tolerance to flurazepam(a benzodiazepine) obtained from 1 week of oral administration disappears to undetectable levels after 7 days of abstinence, but not after 2. This only applies to the one specific area of the brain that they examined, however.

Anyone else have any thoughts on this subject? Approximate estimates of how long it might take to completely reverse tolerance after a single dose of any of these substances? Etc..?


Another interesting, though mostly unrelated, study that I found in my searches shows that GABAA antagonists can increase the reward response for small doses of cocaine:

http://www.ionchannels.org/showabstr...?pmid=15820531

This might imply that benzo's blunt the euphoria produced by cocaine?