Nicotinamide: A New Form of Rehab?

By Diana Chapman

Photo by Marco Verch [CC-BY 2.0]

The number of drug disorders and deaths is continu- eral animal forms of neurodegenerative disorders, such ing to skyrocket, with more than 70,000 Americans as Parkinson’s and Alzheimer’s diseases (Figure 2).3 One of dying from drug overdose in 2019 alone, but unfor- the ways NAM is thought to improve the effects of these tunately the majority of people who do seek help before disorders is through inhibition of an enzyme called PARP, it is too late often fall back into the cycle of relapse fol- or poly(adp-ribose)polymerase.⁴ Interestingly, researchlowing treatment.1 Rehabilitation can help many patients ers have also seen the activation of this enzyme in those maintain abstinence from substances, but not all people suffering from addiction, prompting some to anecdotcan afford or access treatment options; the lengthy, daunt- ally indicate NAM as a possible avenue of addiction treating, and emotional process of rehab can also frighten some ment.⁵ These arguments pointed at the conclusion that people with addiction away altogether. Furthermore, many NAM could possibly be used to prevent drug relapse, but people who have been treated for drug addiction still have Witt and Dr. Kathryn Reissner, a UNC psychology professor, lingering effects that can lead to relapse later on in life. The wanted to give a firmer conclusion to the rumors floating effects include psychological and physiological cues that around the scientific community. researchers have discovered can tap a part of a former or The pair set out to create an experiment to see if current patient’s brain and drive them to relapse.2 These NAM specifically diminished the responses caused by a cues may come from work stress or even something as cue. To do so, they first induced an association between simple as walking down a street where one bought or took cocaine and an environmental stimulus in an animal moddrugs before. This part of recovery is extremely difficult for el. 225 male and 175 female Sprague-Dawley rats were many people to get through, but Emily Witt, a neurosci- trained to press a lever for cocaine self-administration, ence graduate researcher at UNC-Chapel Hill, is working to causing a presentation of a tone and light illumination for see how a form of Vitamin B3 five seconds.3 Over time, Pavlovian conditioning occurred, may help prevent the notion in which the light and tone presentation induced the beof needing to respond to havioral response even in the absence of cocaine adminthese pervasive cues using istration. Then, following the 12-day conditioning period animal research. and a 15-day abstinence period, the rats individually went Nicotinamide, or NAM, through a process of receiving the light stimulus in order a pharmaceutical used most- for researchers to see if the rats pressed the lever. Half of ly for acne and dermatologi- the rats were given NAM injections prior to this process; in cal treatments, has recently the first two sessions of the process, the response of the leFigure 1. Chemical structure come into light as a possible ver press from the rats resulted in the concurrent light and of nicotinamide [PubChem] aid in the treatment of sev- tone presentation, and, in the last sessions, the lever press

resulted in a dose of cocaine instead.3 This way, the researchers could look at not only cocaine use as a response but also take into account general conditioning caused by the cue. “Both [cocaine and cue-primed reinstatement] relate to the reasons why humans relapse…. an individual may be able to maintain [sobriety] until they see some environmental cue that they associate with the drug… [or] they take the drug again,” Witt explained.⁶ Without the NAM, the rats would generally respond to the cue of the light or cocaine and continually press the lever throughout the entire session. The end goal was for the researchers to see if a decrease occurred in lever presses in rats that were administered NAM, as that would show a correlation between taking the therapeutic and not responding to the stimulus.

The study eventually ended with inconclusive but helpful evidence toward the use of NAM. While the female rats showed almost no difference in number of responses between NAM administration and no NAM administration, the male rats did show a difference in lever presses when administered NAM daily (Figure 3,4).3 This evidence is interesting, as it possibly leads the way into looking at how biological differences in the brain can further variation in how men and women become addicted and get treated for addiction. Witt also took particular interest in the gender disparity, stating, “I find any difference between males and females to be fascinating. History shows that research is mainly performed in male individuals, including in the animal research world. These days the scientific world has recognized this issue and the differences people are discovering are amazing.”⁶ Reissner and Witt concluded their study saying the next step from the evidence they collected would be to see why there is this difference in response in males and females. Witt herself explained, “I always like to keep in mind just how little we know about the brain! … Because I’m always keeping in mind the fact that my hypothesis could be wrong, I’m always thinking of what the next step could be to develop or test a new hypothesis.”⁶ This study is promising in showing what experiments to begin in the future and what to look at next in the realm of relapse preventative medicine. The relevance of this work could not be any greater. Cases of drug disorders and abuse are continuing to rise in America; drug use and misuse cost Americans more than $700 billion a year in healthcare costs, crime, and lost productivity.1 In light of these statistics, drug rehabilitation has not changed in years, and many of the programs created around rehab are solely behavioral. Witt affirmed, “A single treatment that prevents drug relapse for all drugs is ‘the dream’ but, I predict, a highly unlikely outcome…. Behavioral therapy in addition to a pharmacological treatment will, I think, always be a part of overcoming addiction. Medication is fine, therapy is fine, but the two together likely produce the best outcomes for individuals.”⁶ While there is no one-size-fit-all solution to addiction and recovery, with Witt’s research, there is hope for a guaranteed and more accessible way to help put an end to one’s drug addiction and the drug pandemic around the world.

Figure 2. Results of female rats’ lever presses. Figure provided by Emily Witt.

Figure 3. Results of male rats’ lever presses. Figure provided by Emily Witt.

References

1. National Institute on Drug Abuse. Overdose Death Rates. https://www.drugabuse.gov/drug-topics/trends-statistics/ overdose-death-rates [accessed 2021 Feb 27]. 2. Fricker RA, Green EL, Jenkins SI, Griffin SM. The Influence of Nicotinamide on Health and Disease in the Central Nervous System. International Journal of Tryp. 2018;11. https://pubmed.ncbi.nlm.nih.gov/29844677/. doi:10.1177/1178646918776658 3. Reissner, K.J.; Witt, E.A. Psychopharmacology. 2020, 237 (3), 669-680 4. Scobie KN, Damez-Werno D, Sun H, Shao N, Gancarz A, Panganiban CH, Dias C, Koo J, Caiafa P, Kaufman L, Neve RL, Dietz DM, Shen L, Nestler EJ. Essential role of poly(ADP-ribosyl)ation in cocaine action. PNAS. 2014 Feb 4. https://www.pnas.org/content/111/5/2005. doi:10.1073/ pnas.1319703111 5. Namazi MR. Nicotinamide: a potential anti-addiction weapon. Med Hypotheses. 2004;62(5):844-5. doi: 10.1016/j. mehy.2004.01.020. PMID: 15082118. 6. Interview with Emily Witt. 2/20/21.