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People, places, and things - How important are drug-related triggers for relapse?

Drug associated triggers are powerful re-activators of addictive behavior

In cognitive behavioral therapy they're a big part of the "Five W's" = When, Where, Why, With, and What. In the various 12-step programs they're simply referred to as "People, places, and things." But no matter how you refer to them, drug-associated cues, or "triggers" as they are more commonly known, obviously play a big role in reminding addicted individuals about their drug-seeking behavior, and they are often enough to restart old behavior, even among those who have been absent for a while and especially for those unprepared for their effect.

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Different triggers to reactivate old behavior

Research on relapse (what researchers call reinstatement) has long shown that there are a number of things that can return a person, or an animal, to drug seeking after they have been absent for a while. Stress, small drug doses, and the presentation of triggers are all very capable of doing this, even after months of abstinence and likely even years. It's probably not surprising that giving drugs to an abstinent person can make them want the drug again. In fact, I would venture to guess that most readers believe that this is the most powerful way to induce a relapse (assuming the initial exposure was out of a person's control and doesn't count).

Well, recent research suggests that in actuality, triggers, or those people, places, and things, might be more powerful or at least longer lasting relapse risks than even taking drugs!

Triggers, not drugs, shown to be longest lasting relapse risk

Researchers in Japan trained mice to press a lever for meth, getting them to poke their nose into a hole 60 times for a total of 30 meth administration per three hour session. Every time they poked their nose in the right hole they got a shot of meth and a little light above their nose-poke hole went on (this will become the trigger in the end). Once they were doing this reliably the researchers took away the meth and the animals learned, within 10-20 days, that pressing the lever no longer got them a drug and reduced their number of presses to less than 15 presses per session.

After all this the researchers gave the mice an injection of meth 30 minutes before putting them back in the box - leading the mice to start pressing again for the drug even though in the previous session they has pretty much stopped pressing knowing that no drug was coming. Obviously, the drug injection caused the mice to relapse back into their drug seeking. But, as you can see from the figure below (on the left side, the right side shows that the mice didn't poke their nose into a hole that did nothing as a control), this little trick only worked once, and the next time the mice were given a shot of meth before being put in the box (after once again being taken through extinction training teaching them that pressing the lever did nothing), they didn't press the lever any more and just around not doing much.

For the following part of the study the researchers once again took the animals through extinction training (and once again the mice stopped pressing the lever for meth) and then in a following session reintroduced the little light that used to go on every time the mice originally got meth. Just like they did with the meth the animals immediately went back to pressing the lever like crazy, hoping that now that the light was back, so was their meth. Just like with the drug relapse experiment above, the researchers repeated this whole process over two months later, only this time, the little light managed to re-trigger the lever pressing again, unlike the one-trick-pony meth. Seeing this, the researchers went for broke and tried another run of this with the same animals, now following up five months after the last time the animals received meth when they pressed the lever. Again the little light got the animals to increase their pressing, only this time it was a little less impressive than the first two tries (but still significantly higher). All in all, the little light managed to restart the lever pressing by the mice three times and a full five month after the meth-relapse experiment had failed!!!

Conclusions, thoughts, and implications about triggers, relapse, and addiction

In a completely different article I'd written that researchers found a number of different patterns of relapse among alcoholics who went to rehab and that in fact, the vast majority of those who did relapse never went back to the kind of heavy drinking that characterized their earlier problem (see here for One is too many, a thousand not enough). While this research touches on a different aspect of relapse, it once again challenges our thinking about the crucial factors in relapse prevention among addicts. Everyone knows that triggers are important, but the fact that they are at least as powerful and apparently longer lasting dangers than even being re-exposed to the addictive drug is a novel one. Still, this isn't very surprising given the very long-lasting impact of drugs of abuse (especially stimulants like crystal meth) on learning mechanisms. In my opinion, and based on my own experience, those changes are essentially permanent and the only thing that makes an ex-user less likely to run back to pressing that drug lever when being re-triggered 10 years later is the life they've built, the experience they have, and the training they've undergone in reacting to those triggers. As you can see from the graph above, if a person runs back to the drugs and actually starts using again on that first, second, or third exposure to a trigger they are likely to start the whole cycle again, possibly making it ever more difficult to escape the next time.

Obviously preventing trigger-induced relapse should be a major strategy of addiction treatment and indeed, from CBT relapse prevention strategies to groundbreaking medications that have been shown to be effective for relapse rate reduction (like Vivitrol, Buprenorphine, Bupropion, and more), there is quite a bit of effort going exactly that way.

Citation:

Yijin Yan, Kiyofumi Yamada, Atsumi Nitta  and Toshitaka Nabeshima (2007). Transient drug-primed but persistent cue-induced reinstatement of extinguished methamphetamine-seeking behavior in mice. Behavioral Brain Research, 177, 261-268.

 

© 2010 Adi Jaffe, All Rights Reserved

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Adi Jaffe, Ph.D., is the executive director of Alternatives Behavioral Health and a lecturer at UCLA and California State University Long Beach.

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