Memantine - An Overview
Memantine is a synthetic compound that may have some nootropic benefits, including:
- Improving Symptoms of Alzheimer’s and Dementia
- Treating ADHD
- Lowering Anxiety
- Improving Memory
- Treating Addiction/Withdrawal
It was first synthesized in the 1960’s, and it works by blocking NMDA receptors in the brain.
This is a unique method of action, and memantine is the only current drug that metabolizes this way.
It is now prescribed for treating Alzheimer’s in America and elsewhere.29Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond, Nat Rev Drug Discov. 2006 30Lipton SA. Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation, Curr Drug Targets. 2007
However, recently memantine has gained a reputation as a performance-enhancing nootropic.
Otherwise healthy people report seeing some cognitive benefits by taking memantine off-label.
However, you should always check the laws in your country and consult with a physician before using a drug like memantine.
What Does Memantine Do?
The primary official use of memantine is for treating symptoms of Alzheimer’s Disease.
According to current studies, it may be most effective alleviating moderate-to-severe Alzheimer’s, rather than more mild cases. 1McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, Maayan N, Ware J, Debarros J. Memantine as a treatment for dementia, Dementia and Cognitive Improvement Group. 2019
One meta-analysis showed that there was a significant improvement in cognitive function in AD patients who took memantine.
The researchers concluded was memantine was “beneficial as a first line drug for the treatment of Alzheimer’s dementia.” It may be especially effective alongside acholinesterase therapy. 2Kishi T, et al. Memantine for Alzheimer’s Disease: An Updated Systematic Review and Meta-analysis., J Alzheimers Dis. 2017
Researchers believe memantine is effective for Alzheimer’s due to its selective action on NMDA receptors.
This can prevent unnecessary glutamate buildup in your synapses, which can be neurotoxic. It can also prevent 3Lipton SA. The molecular basis of memantine action in Alzheimer’s disease and other neurologic disorders: low-affinity, uncompetitive antagonism, Curr Alzheimer Res. 2005 4Nyakas C, Granic I, Halmy LG, Banerjee P, Luiten PG. The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine, Behav Brain Res. 2011 5Liu MY, et al. Memantine improves spatial learning and memory impairments by regulating NGF signaling in APP/PS1 transgenic mice, Neuroscience. 2014
Memory and Learning
Studies show that memantine may also be effective for improving memory and learning in people without cognitive degradation.
The same mechanisms that make memantine effective for reversing signs of dementia may also give healthy people a boost as well.
There are a few animal studies that indicate memantine can improve overall cognitive function in mice, even those with healthy brains.
It seems that by modulating the brain’s NMDA receptors, memantine can improve neural plasticity, potentially improving recall, memory encoding, and general mental function.6Minkeviciene R, Banerjee P, Tanila H. Cognition-enhancing and anxiolytic effects of memantine, Neuropharmacology. 2008 7Danysz W, Parsons CG. Alzheimer’s disease, β-amyloid, glutamate, NMDA receptors and memantine–searching for the connections, Br J Pharmacol. 2012 8Scholtzova H, et al. Memantine leads to behavioral improvement and amyloid reduction in Alzheimer’s-disease-model transgenic mice shown as by micromagnetic resonance imaging, J Neurosci Res. 2008
There is some preliminary evidence that memantine could improve focus and concentration for people suffering from attention disorders.
One study saw that “the ADHD symptoms were improved in the subjects” that took memantine vs placebo.
They also noted that the “side effects are mild and tolerable” especially compared to traditional stimulant medications, like Adderall. 9Soleiman Mohammadzadeh, Tina Kaveh Ahangari, Fayegh Yousefi. The effect of memantine in adult patients with attention deficit hyperactivity disorder, Humaqn Psychopharmacology. 2019
Another study confirms that although “memantine was less effective than methylphenidate [Ritalin] in the treatment of attention deficit hyperactivity disorder, it may be considered as an alternative treatment.” 10Mohammad Reza Mohammadi, et al. Memantine versus Methylphenidate in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Double-Blind, Randomized Clinical Trial, Iran J Psychiatry. 2015
But memantine is not just useful as a replacement for these drugs. Another study found that memantine “may amplify the effects” of amphetamines and methylphenidate.
This could mean additional benefits for patients that take both medications. 11Joeseph Biederman, et al. Memantine in the Treatment of Executive Function Deficits in Adults With ADHD: A Pilot-Randomized Double-Blind Controlled Clinical Trial, Journal of Attention Disorders. 2014
Although more research needs to be done on memantine and ADHD, the initial findings are promising.
Hopefully, we will see more high-quality studies in the future. In the meantime, there is evidence that this drug can have at least some nootropic effects on attention.
Memantine may be useful for treating substance abuse and dependence. There is some clinical evidence that it can help people recover from stimulant and opioid addictions.
Multiple trials have found that memantine can attenuate some of the side-effects of cocaine abuse.
This is most likely because memantine works on the glutamate system, which is also involved in cocaine addiction.
Manipulating this neurotransmitter system by means of glutamate receptor antagonists can alter many of the effects of cocaine. 12Adam Bisaga, et al. A PLACEBO CONTROLLED TRIAL OF MEMANTINE FOR COCAINE DEPENDENCE WITH HIGH-VALUE VOUCHER INCENTIVES DURING A PRE-RANDOMIZATION LEAD-IN PERIOD, Drug Alcohol Depend. 2011
Memantine can modulate cocaine-conditioned motor activity in rats.
Theoretically, this effect may help addicts change habits and mental associations they picked up while using.13Bespalov AY, Dravolina OA, Zvartau EE, Beardsley PM, Balster RL. Effects of NMDA receptor antagonists on cocaine-conditioned motor activity in rats, Eur J Pharmacol. 2000 14Maldonado C, Rodríguez-Arias M, Castillo A, Aguilar MA, Miñarro J. Effect of memantine and CNQX in the acquisition, expression and reinstatement of cocaine-induced conditioned place preference, Prog Neuropsychopharmacol Biol Psychiatry. 2007
The glutamate system is part of the “reverse tolerance” mechanism to the effects of cocaine and amphetamine.
By selectively inhibiting the flow of glutamate, memantine can reverse some of the effects of habitual stimulant use and potentially help your brain revert to its baseline after stimulant abuse.15Karler R, Calder LD, Chaudhry IA, Turkanis SA. Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801, Life Sci. 1989
There’s also significant evidence that memantine can help recovering opioid addicts kick their habit.
In human and animal studies, memantine reduced cravings, decreased the probability of relapse, and reduced opioid tolerance.
The positive effects were most evident when memantine was combined with other addiction therapies and medications.16Gonzalez G, et al. Memantine improves buprenorphine/naloxone treatment for opioid dependent young adults, Drug Alcohol Depend. 2015 17H S Chen, S A Lipton. Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism, J Physiol. 1997 18Popik P, Kozela E, Danysz W. Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice, Naunyn Schmiedebergs Arch Pharmacol. 200019Semenova S1, Danysz W, Bespalov A. Low-affinity NMDA receptor channel blockers inhibit acquisition of intravenous morphine self-administration in naive mice, Eur J Pharmacol. 1999
According to current research, NMDA receptors and the glutamate system may play a key role in opiate dependence.
Inhibiting these systems makes memantine a useful adjunct tool for treating some of the withdrawal symptoms.20Harris AC, Rothwell PE, Gewirtz JC. Effects of the NMDA receptor antagonist memantine on the expression and development of acute opiate dependence as assessed by withdrawal-potentiated startle and hyperalgesia, Psychopharmacology (Berl). 2008 21Bisaga A, et al. The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans, Psychopharmacology. 2001
How Memantine Works In The Brain
Memantine is an NMDA receptor antagonist. The NMDA receptors are extremely pervasive in the brain and critical for memory formation, learning, and neurogenesis.
Like other NMDA receptor antagonists, memantine can enhance neuronal synaptic plasticity in the brain, improve memory, and act as a neuroprotectant against the destruction of neurons caused by too much glutamate.
Glutamate is an excitatory transmitter that is necessary for cognition, but in excessive levels, it can destroy neurons.22Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer’s disease, CNS Drug Rev. 2003
Some research suggests that memantine is unique because it “only interacts with the channel when it is pathologically activated under an excessive glutamate concentration in the synaptic cleft.”
In other words, it only kicks in when glutamate levels get too high. It will not lower glutamate levels below a certain threshold, which might be why memantine’s side-effect profile is fairly low.23Aracava Y, Pereira EF, Maelicke A, Albuquerque EX. Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons, J Pharmacol Exp Ther. 2005 24Léveillé F, et al. Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors, FASEB J. 2008
Memantine can also upregulate Nerve Growth Factor and Brain Derived Neurotrophic Factor, two important aspects of brain health and regeneration.
This may help prevent or treat neurodegenerative diseases such as Alzheimer’s.25Ito K, et al. Memantine reduces the production of amyloid-β peptides through modulation of amyloid precursor protein trafficking, Eur J Pharmacol. 2017 26Liu MY, et al. Memantine improves spatial learning and memory impairments by regulating NGF signaling in APP/PS1 transgenic mice, Neuroscience. 2014 27Meisner F, et al. Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine, Neuropsychopharmacology. 2008
This nootropic can also prevent the formation of amyloid-β plaques, which are heavily linked to Alzheimer’s Disease.28Bordji K, Becerril-Ortega J, Buisson A. Synapses, NMDA receptor activity and neuronal Aβ production in Alzheimer’s disease, Rev Neurosci. 2011
Memantine Potential Side Effects
Memantine has a fairly low side-effects profile, but some people do complain about:
- Body aches
- Joint pain
- Nausea/Gastrointestinal issues
We strive to bring you the most up to date, research-based information about Memantine and other nootropics.
Something we missed? Do you use Memantine? Share your thoughts and experiences in the comments below.
About the author:
Erik Levi is a co-founder of HolisticNootropics.com and a certified holistic nutritional therapy practitioner.
As an NTP Erik takes a nutrition first approach to health. He has worked with many different people to help them use nutrition to optimize their quality of life.
Erik believes that mental health is a physiological process and cognitive enhancement is not something that can be achieved by just taking some pills with good Amazon reviews.
Instead, true cognitive enhancement comes with the right balance of nutrients, movement, and gratitude. Erik continues to stay up to date with the most current nootropic and holistic health research and promises to deliver the best solutions possible.
You can check out his personal health blog/podcast/YouTube Channel all under the name Holistic A-Hole.