An interesting read on nitrous oxide and GABA

I've always wondered if Nitrous would be safe to do while in withdrawal. I've even heard some positive stories about nitrous in withdrawal. I will be needing some dental work done soon, and have been reading some on it, and came across this wiki and thought I'd share.

 

 

Neuropharmacology

 

The pharmacological mechanism of action of N2O in medicine is not fully known. However, it has been shown to directly modulate a broad range of ligand-gated ion channels, and this likely plays a major role in many of its effects. It moderately blocks NMDA and β2-subunit-containing nACh channels, weakly inhibits AMPA, kainate, GABAC, and 5-HT3 receptors, and slightly potentiates GABAA and glycine receptors.[40][41] It has also been shown to activate two-pore-domain K+ channels.[42] While N2O affects quite a few ion channels, its anesthetic, hallucinogenic, and euphoriant effects are likely caused predominantly or fully via inhibition of NMDAR-mediated currents.[40][43] In addition to its effects on ion channels, N2O may act to imitate nitric oxide (NO) in the central nervous system as well, and this may be related to its analgesic and anxiolytic properties.[43]

 

 

Anxiolytic effect

 

In behavioral tests of anxiety, a low dose of N2O is an effective anxiolytic, and this anti-anxiety effect is associated with enhanced activity of GABAA receptors, as it is partially reversed by benzodiazepine receptor antagonists. Mirroring this, animals which have developed tolerance to the anxiolytic effects of benzodiazepines are partially tolerant to N2O.[44] Indeed, in humans given 30% N2O, benzodiazepine receptor antagonists reduced the subjective reports of feeling "high", but did not alter psycho-motor performance, in human clinical studies.[45]

 

 

Analgesic effect

 

The analgesic effects of N2O are linked to the interaction between the endogenous opioid system and the descending noradrenergic system. When animals are given morphine chronically they develop tolerance to its pain-killing effects, and this also renders the animals tolerant to the analgesic effects of N2O.[46] Administration of antibodies which bind and block the activity of some endogenous opioids (not β-endorphin) also block the antinociceptive effects of N2O.[47] Drugs which inhibit the breakdown of endogenous opioids also potentiate the antinociceptive effects of N2O.[47] Several experiments have shown that opioid receptor antagonists applied directly to the brain block the antinociceptive effects of N2O, but these drugs have no effect when injected into the spinal cord.

Conversely, α2-adrenoceptor antagonists block the antinociceptive effects of N2O when given directly to the spinal cord, but not when applied directly to the brain.[48] Indeed, α2B-adrenoceptor knockout mice or animals depleted in norepinephrine are nearly completely resistant to the antinociceptive effects of N2O.[49] It seems N2O-induced release of endogenous opioids causes disinhibition of brain stem noradrenergic neurons, which release norepinephrine into the spinal cord and inhibit pain signaling.[50] Exactly how N2O causes the release of endogenous opioid peptides is still uncertain.

 

 

Euphoric effect

 

In rats, N2O stimulates the mesolimbic reward pathway via inducing dopamine release and activating dopaminergic neurons in the ventral tegmental area and nucleus accumbens, presumably through antagonization of NMDA receptors localized in the system.[51][52][53][54] This action has been implicated in its euphoric effects, and notably, appears to augment its analgesic properties as well.[51][52][53][54]

However, it is remarkable that in mice, N2O blocks amphetamine-induced carrier-mediated dopamine release in the nucleus accumbens and behavioral sensitization, abolishes the conditioned place preference (CPP) of cocaine and morphine, and does not produce reinforcing (or aversive) effects of its own.[55][56] Studies on CPP of N2O in rats is mixed, consisting of reinforcement, aversion, and no change.[57] In contrast, it is a positive reinforcer in squirrel monkeys,[58] and is well known as a drug of abuse in humans.[59] These discrepancies in response to N2O may reflect species variation or methodological differences.[56] Though, it is noteworthy that in human clinical studies, N2O was found to produce mixed responses similarly to rats, reflecting high subjective individual variability.[60][61]

 

 

Link for reference:  http://en.wikipedia.org/wiki/Nitrous_oxide

 

 

I'm having work on Friday [scared] and am wondering about n2o too

 

This made me concerned...

"In behavioral tests of anxiety, a low dose of N2O is an effective anxiolytic, and this anti-anxiety effect is associated with enhanced activity of GABAA receptors"

 

But I searched nitrous oxide in benzobuddies and read through other's experiences.  Seems pretty positive overall i'd say.

 

Good luck on YOUR work...

Nitrous oxide can cause a paradoxical reaction in those who are tapering or recently stopped withdrawing. Its effects on GABA-A, AMPA, and NMDA can cause a panic reaction, albeit short-lived.

Thanks EtherealRemnant,

 

"Short-lived" sounds good for any bad reaction.

 

I'm most concerned that the n2o is not GABAergic, does not kickout the benzo, like quinolone antibiotics do.