Synthetic nootropic shows evidence for age-related cognitive health and potential for brainpower.
Centrophenoxine is a psychostimulant synthetic compound that is popularly used as an “anti-aging” supplement. It appears to aid the nervous system through:
- Antioxidant activity. Centrophenoxine appears to help protect the brain from oxidative stress.
- Stimulation of brain cell metabolism. Centrophenoxine may support the uptake of glucose and oxygen by neurons.
- Potential increase of acetylcholine. Centrophenoxine helps maintain healthy levels of the neurotransmitter acetylcholine.
Centrophenoxine — also known as meclofenoxate, the brand name Lucidril, or simply CPH — is a compound believed to stimulate brain activity mainly through elevating levels of acetylcholine, a neurotransmitter strongly associated with memory function.
Centrophenoxine supplies the active nootropic compound dimethylaminoethanol (DMAE), and is used to help DMAE reach the brain more effectively. CPH is suggested to be an advanced form of DMAE, but no evidence to date backs this belief.
With its close relationship to DMAE, centrophenoxine is popularly used by healthy individuals as a nootropic aid.
Although it is only available by prescription in Germany, Austria, Hungary and Japan, in most countries centrophenoxine is available over the counter and classified as a dietary supplement. More on nootropic legality worldwide
Is CPH a longevity pill?
Centrophenoxine is popularly regarded as an anti-aging compound because of its ability to improve age-related cognitive decline and reduce levels of lipofuscin, a cellular waste product that is recognized as a hallmark of aging.
- A 1973 study reported that centrophenoxine and DMAE seemed to be associated with longer average lifespan and maximum lifespan in mice.1
How Centrophenoxine Might Help the Brain
Potential enhancement of acetylcholine levels
Centrophenoxine’s main biological activity is theorized to be the elevation of acetylcholine — the neurotransmitter particularly important for memory and learning. Although there doesn’t seem to be much direct evidence for this, research does show that centrophenoxine results in increased activity of acetylcholinesterase, an enzyme which breaks down acetylcholine. Some researchers interpret this as indirect evidence that centrophenoxine may indeed increase acetylcholine levels.2
Brain-protective antioxidant activity
Centrophenoxine has been shown to decrease the concentration of lipid peroxidation products in the hippocampus region of the rat brain, indicating a protective, antioxidant effect.3 In addition, centrophenoxine has been found to significantly reduce the effects of experimentally-induced oxidative stress in a rat model of Parkinson’s.4 Similarly, centrophenoxine also appears to increase the activity of major antioxidant enzymes and decrease the level of lipid peroxidation products in the brains of the aged rats.5
May help regulate lipofuscin
Centrophenoxine has been suggested in early research to slow the accumulation of lipofuscin (a marker of cell aging) in neurons and other cells throughout the body.6
Researchers have linked centrophenoxine’s apparent ability to slow lipofuscin formation to its antioxidant activity. This bio-activity seems to lend further support to centrophenoxine’s anecdotal use in anti-aging practices, including for age-related cognitive issues.
Stimulation of brain cell metabolism
Centrophenoxine may also stimulate the uptake of glucose and oxygen by neurons, enhancing their metabolism and function. For example, studies in animal and cell culture models have demonstrated that centrophenoxine affects the activity of enzymes involved in glucose oxidation.7 In addition, centrophenoxine supplementation appears to increase the rates of RNA synthesis, protein synthesis and glucose uptake in human glial cells, which function as support cells in the nervous system.8
Centrophenoxine’s Proposed Benefits
Centrophenoxine is advertised as a nootropic aid that enhances memory, focus, and other aspects of cognition. Thus far however, there is only evidence of such benefits in older individuals, in whom centrophenoxine has been used for over five decades to keep the mind sharp and stave off neurological disorders such as Alzheimer’s.
On the other hand, there is currently no research to back up its use as a nootropic in young adults, although its biological activities may still have some benefit.
Animal studies suggest that centrophenoxine may:
- Alleviate cognitive deficits and neuronal degeneration in rat models of chronic reduced cerebral blood flow9
- Protect the aging brain from oxidative stress10
- Attenuate motor dysfunction in a rat model of Parkinson’s11
Centrophenoxine was tested in a large number of clinical trials in the 1960s and 1970s with the purpose of determining its efficacy in the treatment of cognitive decline in the elderly.12 However in most cases the results of these early studies are not available, making it difficult to say anything conclusive about its effects in humans.
This randomized, double-blind study tested the effects of centrophenoxine (CPH) on memory in elderly subjects. Sixty-seven geriatric patients were split into two groups, one receiving CPH and the other placebo for 9 months, and had their memory function tested at 0, 3, 6, and 9 months. The CPH group saw improvements in long-term memory, and had better mental alertness.
- The authors concluded that “CPH potentiated the consolidation of new information into long-term memory, but did not affect other aspects of remembering”13
In this double-blind clinical trial, 50 elderly people (average age 77) suffering from dementia were treated first for the first 2 weeks with placebo to establish baseline cognitive performance. Next, they were treated with placebo or centrophenoxine tablets (2 g) daily for 8 weeks. The CPH-treated group demonstrated significantly better improvements in memory function.
- The researchers concluded that “The rehydration of the intracellular mass due to CPH treatment is consistent with the hydroxyl (OH) free radical scavenger properties of CPH“14.
Dosage for Brain Health
- Successful clinical trials employed centrophenoxine doses in the range of 200-2000 mg/day
- Retail supplements typically supply doses of 300-400 mg
- For healthy, younger individuals, 1-3 doses of 250 mg appears sufficient
Although information about the safety of centrophenoxine supplementation is limited, a study of its effects in healthy Chinese men did not report any adverse effects. In this study, capsule and tablet centrophenoxine formulations were well-tolerated at the dose of 200 mg daily.15In general, this drug is considered to be safe and having minimum side effects.
Supplements in Review Recommendation
- Centrophenoxine, 300 mg capsules taken 2-3 times daily.
Centrophenoxine helps the brain through multiple ways. Although research is lacking, it’s fair to say that centrophenoxine is effective for older adults seeking to improve age-related cognitive decline. The only question that remains is whether it can also have benefits for younger individuals.
300 mg taken multiple times should be sufficient to see centrophenoxine’s effects. Doses as high as 2 g do not appear to cause any adverse effects, so taking upwards of 900 mg is perfectly safe and should be enough to test whether you benefit from this supplement.
- Hochschild R. Effect of dimethylaminoethyl p-chlorophenoxyacetate on the life span of male Swiss Webster Albino mice. Exp Gerontol 1973, 8(4):177-183 ↩
- Nehru B et al. Evidence for centrophenoxine as a protective drug in aluminium induced behavioral and biochemical alteration in rat brain. Molecular and cellular biochemistry 2006, 290(1-2):33-42 ↩
- Sharma D et al. Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine. Neurobiology of aging 1993, 14(4):319-330 ↩
- Verma R and Nehru B. Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson’s disease. Neurochemistry International 2009, 55(6):369-375 ↩
- Bhalla P and Nehru B. Modulatory effects of centrophenoxine on different regions of ageing rat brain. Experimental Gerontology 2005, 40(10):801-806 ↩
- Terman A, Welander M. Centrophenoxine Slows Down, but Does Not Reverse, Lipofuscin Accumulation in Cultured Cells. Journal of Anti-Aging Medicine. January 2009, 2(3): 265-273. doi:10.1089/rej.1.1999.2.265. ↩
- Nandy K and Bourne GH. Histochemical study of the oxidative enzymes in the olfactory bulb of the rat. Acta histochemica 1966, 23(1):86-93 ↩
- Ludwig-Festl M et al. Increase in cell metabolism in normal, diploid human glial cells in stationary cell cultures induced by meclofenoxate. Arzneimittel-Forschung 1983, 33(4):495-501 ↩
- Liao Y et al. Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats. Acta pharmacologica Sinica 2004, 25(12):1590-1596 ↩
- al-Zuhair H et al. The effect of meclofenoxate with ginkgo biloba extract or zinc on lipid peroxide, some free radical scavengers and the cardiovascular system of aged rats. Pharmacol Res. 1998 Jul;38(1):65-72. ↩
- Nehru B et al. Behavioral alterations in rotenone model of Parkinson’s disease: attenuation by co-treatment of centrophenoxine. Brain research 2008, 1201:122-127 ↩
- Heyward H. et al. Trial of ANP-235 (lucidril) on 27 chronic psychotics.Annales medico-psychologiques 1960, 118(2):879-890 ↩
- Marcer D and Hopkins SM. The differential effects of meclofenoxate on memory loss in the elderly. Age and ageing 1977, 6(2):123-131 ↩
- Pék G et al. Gerontopsychological studies using NAI (‘Nürnberger Alters-Inventar’) on patients with organic psychosyndrome (DSM III, Category 1) treated with centrophenoxine in a double blind, comparative, randomized clinical trial. Archives of Gerontology and Geriatrics, 9(1):17-30 ↩
- Zou JJ et al. Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study. Clinical therapeutics 2008, 30(9):1651-1657 ↩