Relapse and The Persistence of Memory

peristence of memory(Salvador Dali:  The Persistence of Memory)

“But the thing about remembering is that you don’t forget.”

― Tim O’Brien, The Things They Carried

While addiction is viewed in most corners of the treatment and recovery communities (including the American Society of Addiction Medicine)  as a chronic and relapsing brain disease,  as I have pointed out in previous posts, this is usually a  difficult idea for families and friend of addicts to accept.  It is particularly hard when relapse occurs after a long period of sobriety.  Loved ones wonder how   a loss of control can  occur when life has been normal and predictable   for an extended period of time.  It seems as though the addict made a terrible choice, with no thought at all about the impact such an eventful decision would have on everyone else.  Is that the case?   Yet another complicated question, but it is important to understand that, even after extended periods of sobriety and stability,  brain structure and brain chemistry still matter.

Animal studies and imaging studies of the human brain have taught us that all natural reinforcers such as food and sex, and all psychoactive drugs  increase the production of dopamine in the nucleus accumbens, which is a structure in the basal forebrain sometimes referred to as the brain’s “pleasure center”.  When this part of the brain receives  a massive  hit of dopamine from the ingestion of a drug, the user feels high, and the experience of this huge reward constitutes  a powerful learning experience. Repeated experiences of intense reward eventually make other parts of life far less interesting and important to the brain than the pursuit and use of addictive substances and activities. Moreover  and very importantly, the flow of dopamine to the nucleus accumbens  increases not only when the addict is using a drug, but when the addict’s brain anticipates receiving it because it is coming into contact with cues that are associated with use.  This is why 12-step programs remind people in recovery to avoid “slippery people places and things”. Those slippery entities are paving the way to relapse by priming the brain with a dopamine rush.

But a publication by Harvard Health makes the important point that changes in the brain’s reward circuitry don’t make addiction inevitable. Rather:

What makes permanent recovery difficult is drug-induced change that creates lasting memories.

What are these changes?  

The Role of  Delta FosB  in addiction and relapse

The article, Addiction and the Problem of Relapse, explains that addiction involves many of the same brain circuits that control learning and memory  and that, “Long-term memories are formed by the activity of transcription factors.”  A transcription factor   is a protein that binds to specific DNA sequences and controls “the flow (or transcription) of genetic information from DNA to messenger RNA”. In this manner it establishes new neural connections and strengthens old ones. The Harvard report  notes that:

All rewards increase the concentration of the transcription factor delta FosB in the nucleus accumbens. An excess of this transcription factor can heighten the risk of relapse in addicts long after they have stopped taking the drug. Even after levels (of the factor) return to normal, addicts may remain hypersensitive to the drug and the cues that predict its presence. *

Again, all rewards induce delta FosB in the nucleus accumbens, including drugs of abuse such as cocaine,  amphetamines, morphine, nicotine and phencyclidine.  Another article, a piece in  Scientific American  about The Addicted Brain , explains that delta FosB is an extraordinarily stable protein.  It accumulates and  remains active in nerve cells for weeks to months after someone ingests a drug.  It is believed that the lingering presence of delta FosB in the nucleus accumbens and other brain regions enables it to  “maintain changes in gene expression long after drug taking ceases”.  It may do so by causing neurons to induce the dendrites, or signal-receiving branches of the nucleus accumbens, to grow additional buds (dendritic spines) that heighten the ability of these cells to communicate with other neurons.  This sprouting of additional buds has been seen in rodents for months after the animals stop receiving drugs.  Authors Eric Nestler and Robert Malenka note that while extrapolation from animal studies is speculative, this finding nontheless,

raises the possibility that the extra connections generated by delta FosB activity amplify signaling between the linked cells for years and that such heightened signaling might cause the brain to overreact to drug-related cues. The dendritic changes may, in the end, be the key adaptation that accounts for the intransigence of addiction.

In sum, neuroscientists seem to be coming to the conclusion that changes to the reward circuitry induced by repeated drug use are important factors that compel addicts while they are actively using drugs, and that they continue to be key  for some time after  people stop using.   However,  after people abstain from drug use for longer periods,  other drug-induced changes in brain activity may become bigger players in making them vulnerable to relapse. The action of delta FosB may be a change that is of particular importance, making addicts more sensitive to a drug’s effects when it is used again after a long break and creating extremely powerful responses to “memories of past highs and to cues that bring those memories to mind”.

What is the takeaway for family members and friends of addicts, and for addicts themselves? As Tim O’Brien notes in The Things They Carried, “…you don’t forget”.  Not only that, but in some important respects, even when addicts stop using, they still have the brain they had when they were active in their addictions.  Slippery entities remain slippery entities even after long periods of sobriety because the brain responds to them in the same way it responded to them during active addiction.  This at least reduces the capacity for choice.   There may one day be medicines that block such responses.  In the meantime, addicts can make the choice to avoid the slippery entities and to  strengthen their resistance to relapse by engaging in  activities that strengthen the part of the brain that exercises executive control over powerful and primal responses.  “Push-ups” for the pre-frontal cortex, that is,  activities that increase focus and the ability to regulate strong feelings include regular 12-step attendance, psychotherapy, meditation and exercise.  Neuroscience is teaching us that the need for some combination of  these interventions is ongoing.  Even a sober  brain is busy remembering the rewards of drug and alcohol use for a very long time.  So it is necessary for most people in recovery to be equally busy remembering and addressing the “cunning, powerful and baffling” impact of psychoactive substances for a very long time as well.

 *In another article, Dr. Nestler notes that “drug induction of ΔFosB in … is more dramatic in adolescent animals, a time of greater addiction vulnerability”.

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