Short Term Effects on Tolerance

Anecdotally, Memantine has possibly immediete effects on opiate and amphetamine tolerance.

In these mice, the co-administration of memantine and MRZ 2/579, but not dextromethorphan, resulted in the reversal of morphine tolerance. In experiment 3, memantine and MRZ 2/579 (10 mg/kg) inhibited the acute antinociceptive effect of morphine, but dextromethorphan did not. These data indicate that low-affinity, clinically available and/or therapeutically promising NMDA receptor antagonists may be used to inhibit ongoing morphine tolerance.

Naunyn Schmiedebergs Arch Pharmacol. 2000 Apr;361(4):425-32.
Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice.
Popik P1, Kozela E, Danysz W.

There is no need for long term intake if one is using Memantine to reduce drug tolerance intermitently, though there are of course those who with to reduce tolerance in the long term, or try to get the D2 nootropic effects of Memantine, this would require consideration of long term usage.

Long Term Titration for Nootropics Effects and ADHD

Rats were trained on the Morris water maze, a spatial memory task in which rats swim in a pool of murky water until they locate the platform hidden beneath its surface. During this exercise, normal rats are expected to associate the location of the hidden platform with salient cues placed at specific positions around the circumference of the maze. After training, one group of rats had their hippocampi bathed in the NMDA receptor blocker APV, while the other group served as the control. Both groups were then subjected to the water maze spatial memory task. Rats in the control group were able to locate the platform and escape from the pool, while the performance of APV-treated rats was significantly impaired. Moreover, when slices of the hippocampus were taken from both groups, LTP was easily induced in controls, but could not be induced in the brains of APV-treated rats. This provided early evidence that the NMDA receptor — and by extension, LTP — was required for at least some types of learning and memory.

The NDMA receptors are incredibly important in cognition, which is why Memantine is being researched and tested for ADHD and nootropic applications, as we already know – modulation of the the NDMA receptors also reduces drug tolerance, prominently mostly researched for opiates.

At week 12, AISRS data showed reduction in total symptoms (-17.5, P < 0.001), inattentive symptoms (-10.6, P < 0.001), and hyperactive symptoms (-6.9, P < 0.01). A total of 44% of subjects had CGI ratings of much or very much improved. Cognitive performance improved in measures of attention, working memory, and other selected executive domains by weeks 6 and 12 (each P < 0.05); simple reaction time declined by week 12 (P < 0.05). There were no severe adverse events, but mild adverse events were common and six subjects discontinued due to adverse effects.

Memantine was largely well-tolerated and associated with improvement in ADHD symptoms and neuropsychological performance. Randomized studies are indicated to confirm whether memantine is a novel therapy for ADHD across the lifespan.

A pilot open label prospective study of memantine monotherapy in adults with ADHD.
Surman CB1, Hammerness PG, Petty C, Spencer T, Doyle R, Napolean S, Chu N, Yorks D, Biederman J.
Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital

However, we know the nootropic effects of nootropics take a while to occur, also there is a possibility of “tip of the tongue” phenomenon where it feels like the person can’t think and talk as fluidly as before, this tends to happen when high dosages like 20mg are immedietely used without titration and is highly uncomfortable for some.

In boring medicine, Memantine is titrated for parkinson patients – so it makes little sense for people using it off label to think they can take large doses suddenly and get away with it without side effects. Of course Memantine is safe and any cognitive side effect will go away upon cesssation of intake. Still a lot of people get put off by this, however in reality the side effects of Memantine goes away with continued use.

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Therefore for long term use of Memantine we are going to suggest a titration regime, this is the best way to avoid the cognitive deficits that seem to occur in some when doing so without titration.


Memantine Titration Regiment Explained for Once

So if you are trying to take Memantine for ADHD or long term drug tolerance reduction, you are going to have to admit you are either really in need of divine intervention (since you have already asked your doctor, and he or she can’t help you) – or you are a masochist.

For those who don’t know what titration means – it simply means starting your dosages low and slowly increasing it as your body adjusts instead of suddenly taking a large dosage, this reduces the apperance of side effects.

Memantine has a rocky startup period, the longer the titration period the better, 8 months is the most comfortable, 4 months is the norm. It’s a long term thing, if you are doing it for opiate tolerance etc, its recommended you try it out for its immediate effects first. For nootropics effects, we think long term titration is the only way. So ADHD people who have no options left, strap your seat-belts on.

Note: Titration is not necessary for everyone, some people get no side effects (cognitive issues) from sudden high dosage use.

So we start at 5mg a day.

A fair few people will experience cognitive decline. I know exactly what you’re talking about when you say it makes you feel dumber. Everything is going through a on-the-tip-of-your-tongue kinda phenomenon,. Even thoughts seem to be going through that same filter.

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The jump from 5mg to 5mg 2x a day is the worst titration in the entire adjusting period, it can be very discouraging at this point, because not only are you taking more, but  you have 2 separate administrations.

There is a light at the end of the tunnel. starting week 4, you’ll begin to notice your senses coming back to you. you’ll find that “thought that’s on the verge of being thought” actually comes out and for a while, you begin to think Memantine isn’t so bad.

At week 5 we increase dosage to 15mg a day, 5mg in the morning and 10mg at night, so you can sleep through the 8 hours of side effects. Oh dear, now the side effects are bad, but this time you are prepared and you learn to adjust.

At week 6, you start to feel kinda good, your senses are coming back.

Week 7. Final increase to 20mg. This is the easiest one. You’ve already gotten used to twice daily administrations and bumping up one dose is no new thing, by the end of week 7 you are fine.

Week 8, Memantine seems like its in the background, you stop noticing it and it means you’ve won.

Now at 20mg (2x 10mg a day) you still need to wait for a while for the nootropic effects to come online. Fast forward another 6 weeks, and you start noticing something about yourself. Answers come faster, thoughts seem less distracting and you seem to about things with a much more level out. In the months to come it kicks the ass of any other nootropic or amphetamine. There is some serious stuff happening in your brain. As a bonus is also negates drug tolerance.

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However like I said, its not for the faint hearted, those who want something fast acting for ADHD should look into Armodafinil.