Improve your memory while at the same time …

Stop Smoking with Galantamine
… and help repair and prevent lung damage

By Will Block

Back in the summer of 2012 we published an article suggesting that galantamine could help prevent smoking resumption (see “Galantamine Prevents Smoking Resumption” in the August 2012 issue). However, the study on which the article was based was on research done with rats — not humans. In a recent follow-up report by the same researchers—all from departments at the University of Pennsylvania—better and more conclusive findings are shown.1 This time, in addition to rats, the researchers also used humans.

Worldwide, tobacco smoking remains the leading cause of preventable death, while current smoking cessation medications have limited efficacy. About 5.8 trillion (5,800,000,000,000) cigarettes were smoked worldwide in 2014. And cigarette consumption is still on the rise globally. However, there have been significant reductions in smoking rates in a number of countries that have implemented increasingly tight tobacco control laws. Nonetheless, these reductions have been offset by the growing cigarette consumption in a single nation: China. The Chinese market now consumes more cigarettes than all other low- and middle-income countries combined.*


Worldwide, tobacco smoking
remains the leading cause of
preventable death, while current
smoking cessation medications have
limited efficacy.


Use of Cigarettes Has Decreased in the U.S.

The United States is one of those countries where tobacco use has declined. As little as 50 years ago cigarettes used to be everywhere throughout America. It was even fashionable, so much so that few TV shows or movies were made without showing the smoking of cigarettes. It seemed that the American way of “life” involved smoking. The rate then was 42.4 percent of U.S. adults who smoked. But that figure has declined by more than half. In fact, as of 2014 that number has reached a record low —17.8 percent in 2014. And the trend continues downwards.


More than 16 million Americans live
with a smoking-related disease.


Nonetheless, the new low still means that an estimated 40 million adults in the United States currently smoke cigarettes. Indeed, cigarette smoking remains the leading cause of preventable disease and death in the United States, accounting for more than 480,000 deaths every year, or 1 of every 5 deaths. In fact, more than 16 million Americans live with a smoking-related disease. These include coronary artery disease, stroke, peripheral vascular disease and COPD.


LEM1602Trends274.jpg
(click on thumbnail for full sized image)

Translational Research Needed

Although there are FDA-approved drug therapies available for nicotine dependence—including nicotine replacement therapies, bupropion, and varenicline—relapse rates remain high. Approximately 75% of smokers relapse within 6 months. Thus, there is a clear need for translational research focused on identifying novel pharmaco­therapies for nicotine addiction. Translational research means extending the science from the laboratory to clinical use.


Research suggests that AChEIs
(especially galantamine) could be
repurposed for smoking cessation in
humans.


Addiction Withdrawal May Result from Improved Cognition

The University of Pennsylvania researchers’ previous studies demonstrated that acute administration of an acetylcholinesterase inhibitor (AChEI) lessens nicotine taking and seeking in rats, and suggests that AChEIs (especially galantamine) could be repurposed for smoking cessation in humans. Earlier work was based on the idea that increasing cognitive performance during withdrawal might help treat addictions.2,3 In other words, getting smarter could improve the likelihood of an easier withdrawal.

The same may be true for alcohol-dependent, methamphetamine-dependent and schizophrenic smokers, as preliminary results seem to indicate. Higher cognitive powers may make withdrawal easier.


Higher cognitive powers may make
withdrawal easier.


Expanding Upon Prior Findings

In the new report1 the Pennsylvania researchers expand upon their previous findings with experiments designed to determine the effects of repeated AChEI administration on voluntary nicotine taking in rats as well as well as the smoking behavior in human smokers.

The principal goal of this study was to determine the possible efficacy of repeated AChEI administration in rat and human models of nicotine addiction, to provide sufficient rationale for large-scale clinical trials of AChEIs in human smokers.

This goal was an extension of the researchers’ previous studies, which examined the effects of repetitive AChEI administration on nicotine self-administration in rats. What was different was the transposition of the findings in rats (preclinical) to humans (clinical research), enabling a better investigation of the effects of repeated galantamine on smoking behavior and the subjective effects of smoking in the treatment of human smokers.

AChEIs Reduce Self-Administration of Nicotine

Rats were trained to self-administer intravenous infusions of nicotine on a fixed-ratio-5 schedule of reinforcement. Once rats maintained stable nicotine-taking, galantamine or donepezil was administered before 10 consecutive daily nicotine self-administration sessions. Repeated administration of 5 mg/kg of galantamine and 3 mg/kg of donepezil reduced nicotine self-administration in rats. In other recent clinical trials, donepezil modestly improved cognition, but had no effect on smoking behavior in humans.


Donepezil modestly improved
cognition, but had no effect on
smoking behavior in humans.


These effects were reinforcer-specific, and not due to adverse malaise-like effects of drug treatment, as repeated galantamine and donepezil administration had no effects on sucrose self-administration, ad libitum food intake and pica. Pica is an animal model that is used to assess rodent consumption of non-nutritive materials (for example, kaolin clay) in response to nauseating agents.

The effects of repeated galantamine use (versus placebo) for cigarette smoking were also tested in human treatment-seeking smokers. Male and female treatment-seeking smokers, ages 18–60 years old who smoked at least 10 cigarettes per day for the previous 6 months were recruited from the community via advertisements.

Of 32 participants, 13 were female and 19 were male. Overall, 40% (n = 13) of participants were female and 60% (n = 20) were African-American. On average, participants were 43 years old, had a Shipley IQ score of 103, reported smoking 14.8 cigarettes per day for 25 years and were moderately nicotine-dependent. Procedures involved a randomized double-blind, between-subjects, placebo-controlled study comparing 3 weeks galantamine treatment to placebo.


Two weeks of daily galantamine
treatment (8 mg (week 1) and 16 mg
(week 2) significantly reduced
smoking rate as well as smoking
satisfaction and reward compared
with placebo.


Two weeks of daily galantamine treatment (8 mg (week 1) and 16 mg (week 2) significantly reduced smoking rate as well as smoking satisfaction and reward compared with placebo. The galantamine group exhibited a reduction of 2.3 cigarettes per day, whereas the placebo group only reduced by 1.3 cigarettes per day. This corresponds to a 12% reduction for the galantamine group and a 7% reduction for the placebo group.

This translational study indicates that repeated AChEI administration reduces nicotine reinforcement in rats and smoking behavior in humans at doses not associated with tolerance and/or adverse effects.

Galantamine Keeps Gathering Benefits

In addition to the cognition-enhancing effects of galantamine, this natural plant extract offers value for smokers and possibly other addictions. But there’s more. One of the major adverse effects of smoking is lung damage, and a recent study finds that galantamine may be helpful for that too (see sidebar, “Galantamine Protects Against Lung Injury.”)

References

  1. Ashare RL, Kimmey BA, Rupprecht LE, Bowers ME, Hayes MR, Schmidt HD. Repeated administration of an acetylcholinesterase inhibitor attenuates nicotine taking in rats and smoking behavior in human smokers. Transl Psychiatry. 2016 Jan 19;6:e713. doi: 10.1038/tp.2015.209. PubMed PMID: 26784967.
  2. Sofuoglu M, DeVito EE, Waters AJ, Carroll KM. Cognitive enhancement as a treatment for drug addictions. Neuropharmacology. 2013; 64: 452–463.
  3. Ashare RL, Schmidt HD. Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal. Expert Opin Drug Discov. 2014; 9: 579–594.
  4. Li G, Zhou C, Zhou Q, Zou H. Galantamine protects against lipopolysaccharide-induced acute lung injury in rats. Braz J Med Biol Res. 2016;49(2). pii: S0100-879X2016000200601. doi: 10.1590/1414-431X20155008. Epub 2015 Dec 4. PubMed PMID: 26648090.
  5. Yang SR, Chida AS, Bauter MR, Shafiq N, Seweryniak K, Maggirwar SB, Kilty I, Rahman I. Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages. Am J Physiol Lung Cell Mol Physiol. 2006 Jul;291(1):L46-57.

Adding to the benefits of memory enhancement and addiction relief …
Galantamine Protects Against Lung Injury

While considering the benefits of galantamine for smoking, a new Chinese study for the alleviation of lung damage by galantamine has come to our attention.4 This is a welcome extension of knowledge because it indicates that the same treatment that helps stop smoking may help heal some of the damage caused by smoking.

In the study, the researchers observed that lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines, which can cause acute lung injury (ALI). Other research has shown that cigarette smoke-mediated oxidative stress induces an inflammatory response in the lungs by stimulating the release of proinflammatory cytokines.5

This study evaluated the effects of galantamine by measuring levels of inflammatory mediators and observing histopathological (histopathology is the microscopic examination of tissue in order to study the manifestations of disease) features associated with LPS-induced ALI. Using 60 8-10 week old male rats (200-240 g) the animal subjects were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+Galantamine group (5 mg/kg GAL before LPS administration).

Histopathological measurements were taken, along with a variety of proinflammatory markers. Mortality in the three groups was recorded at 72 hours. LPS-induced ALI was characterized by distortion of pulmonary architecture, elevation of myeloperoxidase (MPO) activity, and levels of pro-inflammatory cytokines.


The Chinese researchers
demonstrated that galantamine
exerted a protective effect on LPS-
induced ALI in rats.


Lung Pathological Changes Prevented, and Mortality Decreased

Pretreatment with galantamine significantly reduced the LPS-induced lung pathological changes, and levels of proinflammatory cytokines and MPO activity. Galantamine treatment significantly decreased the mortality rate. In conclusion, the Chinese researchers demonstrated that galantamine exerted a protective effect on LPS-induced ALI in rats. By reducing pro-inflammatory cytokines, galantamine may be able to help reduce lung damage, including that caused by smoking.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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