Addiction is a Treatable Disease
Let me congratulate you on receiving the title of “Honorary Doctor and Professor” conferred upon you by the Senate of ELTE University. You have developed a strong collaboration with the Faculty of Education and Psychology of our university since the early 2000s. Can you talk about your experiences in regard to this collaboration and the students you hosted from Hungary?
Thank you! I first met professor Zsolt Demetrovics at a meeting of the European Association on Substance Abuse Research and we have been in collaboration ever since. I am amazed by his work power. He has become a central figure in addiction sciences. We have been writing papers together and I visited Budapest a few times and built a good partnership with him.
Your main area of research is related to the neurobiology of drug addiction. There are competing definitions of addiction. How would you define it?
The concept of addiction has been changing over time. In the 19th century people viewed addiction as a moral weakness and a lack of willpower that should be punished. Later this view was replaced by the pharmacological approach that blamed the substance for making people addicted. This view led to alcohol prohibition and is still in place when it comes to the “war on drugs”. But this concept has proven to be false. Now we know that many people are able to control their drug use and don’t become addicts. Later new biological and psychological models of addiction were developed. Sociologists say it is a normal behaviour in abnormal circumstances.
I think it is a bio-psycho-social condition with the brain as the target organ.
Like diabetes is a bio-psycho-social determined disease with the pancreas as the target organ. It is definitely a disease. It has all the characteristics of a disease. It is a brain disorder or brain disease. And it is a treatable disease.
In my carrier I was mainly looking at the biological aspects of this disease, at some of the psychological aspects, and the combination of the two. For example, craving was previously not seen as a central part of addiction but it is now. Craving is a problem of a hyperactive motivational brain system. The other key element of addiction is the lack of cognitive control (impulsivity). This problem is mainly located in the prefrontal cortex while the problem of motivation is located in the lower parts of our brain. If we look at the late consequences of the disease, it is not so much craving or impulsivity anymore but it becomes a habit and compulsivity becomes the main problem.
These are only models, attempts to grasp reality but they don’t claim to include the full truth. Addiction has a strong genetic component and it translates itself in biological abnormalities. Neuroimaging studies prove that. Consequently, medical-biological interventions can be effective to treat and prevent addiction. One of our most important findings is that if we treat kids with ADHD with stimulant medication at an early age, we can prevent the development of addiction. I think the biological model is not a full model that can explain everything in addiction, but it is a useful model to develop new treatments.
There is a growing body of literature on the role of early childhood trauma in the later development of addictions, which was often overlooked in previous decades. What do we know about this phenomenon from scientific studies?
Who are those kids who will develop addiction at later age? This is an important question. If you look at addiction from a biological perspective, it has three main components: cognitive control deficits, hyperactive motivational system and hyperactive stress system. We know that ADHD is an important risk factor. The lack of cognitive control is present in kids with ADHD and we see biochemical processes in their brains that are very similar to those in the brains of adults with addiction. This means that
kids struggling with problems with attention and impulsivity have a greater chance to develop addiction.
They may start to use drugs as a form of self-medication or as an expression of their biochemical vulnerability. Another important risk factor is what you mentioned: early childhood traumatisation.
We see that many people who are addicted live with a hyperactive stress system. And we see the same with many people who suffer the consequences of traumatisation without addiction. This means that early childhood trauma and neglect is an important risk factor in developing addiction. It also means that we should pay attention to trauma and stress pathology in the treatment of people with an addiction.
A major challenge of any addiction treatment is relapse prevention. You have studied methods of relapse prevention for a long time. I saw one of your papers a few years ago that claimed that modafinil can be a promising medication to reduce craving among cocaine addicts. Please tell me more about this subject!
You are right to bring up the issue of relapse because it is much more important than detoxification, which is the easier part of treatment. We studied several different methods of relapse prevention, cognitive-behavioural methods and pharmacological models. We did one of the first studies about acamprosate as a medication to treat alcohol dependence. We also studied other substances in treating alcohol dependence, such as modafinil and baclofen. We used very different ways all directed to cure a person from the risk of relapse. If relapse prevention does not work, we can do substitution treatment with long acting medications. The best-known example is opiate substitution treatment with methadone and suboxone.
We looked at neuromodulation as well – putting some stimulation of the brain with external equipment, stimulating the impulse regulation areas of the brain with electrodes: transcranial magnetic stimulation (TMS). I must say I am a little disappointed in this regard. Unlike with depression, we did not see very good results with it in treating addiction. We also tried a more invasive form of neuromodulation: deep brain stimulation (DBS). Again, we were not as successful as our colleagues in the department with treatment-resistant obsessive-compulsive disorder. Moreover, it was too difficult to attract patients for this intervention. Only two patients finally started brain surgery from the 150 who initially applied. Others were too afraid and found drug use a better alternative.
Not every patient has the same path to addiction, and we start to think about how to select the best medication to different patients: personalized treatment. For example, there are different forms of craving with their own neurotransmitter system: reward craving (opioid system), relief craving (GABA-glutamate system), and obsessive craving (serotonin system). Based on this three-pathway model, we did one of the first studies where we randomized alcohol dependent patients to naltrexone and acamprosate groups and measures neurotransmitter-related genes (opioid, glutamate, and GABA) and we tried to predict which patients (with what kind of neurotransmitter genes) would respond best to which treatment. We had clear indications that patients with certain opioid-receptor variants responded better to naltrexone. This was a small study and many more studies have been conducted since then and
now we can say quite a lot about how different patients will respond to different treatments.
You have been among those who pioneered heroin-assisted treatment (HAT) in the Netherlands. For many people, this form of treatment is still controversial because at the first sight, it seems counterintuitive. Can you explain what this treatment is about?
I don’t like HAT myself. People have to come to 2-3 times a day to the treatment center which is a big burden on their lives. This is not a first line treatment. It is only for those who did not respond to other treatments. You have to see this in the medical model of what works for different patients. It was professor Ambros Uchtenhagen in Switzerland who started to use supervised heroin treatment to those patients who did not do well with methadone. But this was an open label trial with no control group. We decided in 1996 to do a randomised controlled trial, comparing methadone and heroin. We did two big studies, total with 600 patients, one with injecting and one with smoking/inhaling heroin users. HAT has proven to be safe and very effective. Although it is expensive it is cost-effective too.
Several randomised controlled trials have been conducted since then and even a Cochrane Review confirmed the effectiveness of HAT. Nobody criticises it in the scientific literature anymore. Some people think it is counterintuitive to give (pharmaceutical) heroin to heroin addicted patients, but the same can be said about methadone, which is now an essential treatment.
The incentive is the same: we should remove people from the criminal system.
But before introducing HAT, I recommend countries to develop a good opiate substitution treatment with methadone and/or buprenorphine first. HAT is a very valuable contribution to the treatment of 5-10% of the patients, i.e. patients not responding to methadone or buprenorphine. But this small minority is very important because they experience the most social and health problems. Similar to methadone for heroine dependent patients, in the last few years we used long acting dexamphetamine for treatment-resistant cocaine dependent patients with similarly good results.
We see a terrible opioid overdose epidemic in North America in recent years, driven by illicit synthetic opiates like fentanyl, killing more young people than car accidents. We see a growing number of ODs in the UK as well. Do you think there is a risk that Europe will face a similar epidemic?
This crisis started among poor black people but only received a great public attention after it also started to affect wealthy white people. There is always politics when it comes to addiction. The pharmacological industry had a great responsibility in starting the opioid overdose epidemic by aggressively promoting oxycodone as an effective and non-addictive pain medication. The epidemic started with a huge increase in the prescription of these new opioid painkillers. But the market of prescription drugs dried up and people turned to illegal heroin. And in the next wave of the epidemic, synthetic opioids imported from China took over the market.
We just wrote a new paper on the risk of an opioid epidemic in Europe, which is still under review in World Psychiatry. It concludes that
there is no opioid crisis in Europe but we see some outbreaks of opioid overdoses in some countries.
We have seen one spike in Estonia, with a quick increase of fentanyl overdose deaths and a short spike in Bavaria. But the real exception in Europe is the UK, especially in Scotland, where there is a real opioid crisis with more hospital visits and overdose deaths than in the US. It is mainly driven by heroin and methadone, together with benzodiazepines. We must be vigilant and should constantly monitor the market. But the second warning is not to be too careful: we should not cause shortage in the access to pain medication among those who need it.
What do you recommend to those young psychologists who would like to study addictions, what are the most exciting new areas of research?
Aetiology – the causes of addiction – is an exciting subject. We know that young people with ADHD or anxiety disorder have a greater risk to develop addiction. But what is not studied well is the role of the reward system in that. In addition, some interesting new research should be done in the area of the psychological treatment of addictions as well. For example, there are new forms of therapy treating craving with acceptance and commitment therapy.
Maybe the most promising new area of research is the use of psychedelics in the treatment of psychiatric disorders, including addiction. In the late 1950s and 1960s, there were studies with very good results in treating alcohol dependence with LSD. Even a meta-analysis was conducted suggesting that studies with LSD showed bigger effect sizes than those with other medical treatments (naltrexone, acamprosate, disulfiram). Psylocibin should be studied in this regard too. To study what really happens in the brain and how psychedelics work in treating dependence is a really important area. Is this psychological-supported pharmacotherapy or a pharmacological-supported psychotherapy?
And finally, the study of behavioural addictions, such as gaming disorder, is very important too. Zsolt Demetrovics has been very important and influential in putting this issue on the clinical and research map. This is very interesting for all researchers of addiction because you can study addiction separately from the confounding effects of substance use.