Cognitive rehabilitation helps to treat chemical dependents

The topic was covered during the World Congress on Brain, Behavior and Emotions, in São Paulo.

By Karina Toledo

Agência FAPESP – The effects of marijuana, cocaine and crack on the brain and the damage that these drugs cause to cognitive functions, such as memory, attention, planning capacity and decision-making, were the topics of a lecture presented by the neuropsychologist Paulo Jannuzzi Cunha, of the Psychiatry Institute at Universidade de São Paulo’s School of Medicine (FM-USP), at the World Congress on Brain, Behavior and Emotions.

During the event, which was held in São Paulo in late June, Cunha presented recent research data that show how cognitive rehabilitation – performed using a stimulus, such as a chess game – can help to recover part of the abilities lost by drug consumption and can be fundamental to preventing relapse among substance abusers in treatment.

Excerpts of Agência FAPESP’s interview with Cunha are as follows:

Agência FAPESP – How do marijuana, cocaine and crack affect the brain?
Paulo Jannuzzi Cunha – Each drug has its particular action mechanism, but all affect the cerebral reward system, which involves the prefrontal cortex; the ventral tegmental area, where there is a series of neurons responsible for releasing the neurotransmitter dopamine; and the nucleus accumbens. When we feel pleasure through either a physical stimulus, like food, or an emotional stimulus, the release of dopamine occurs in the synapse, which is the connecting point between one neuron and another. However, we are not happy all of the time. To return to a balanced situation, this dopamine must be recaptured by the neuron that released it initially. Drugs impede this process of recapture, so excess dopamine remains in the synaptic cleft, stimulating communication between the neurons of the reward system, which intensifies and prolongs the sensation of pleasure.

Agência FAPESP – How is this process prejudicial?
Cunha – As drugs stimulate the reward system in an artificial manner, the brain begins to get lazy about producing and releasing dopamine. As the use of drugs becomes chronic, people literally begin to lose the pleasures of life, and the sensation of well-being is increasingly restricted to the use of the drug.

Agência FAPESP – How does this change affect cognitive function?
Cunha – Everything that we do must involve a certain degree of pleasure and well-being; otherwise, we would not be able to maintain attention for much time in an activity. The reward system is thus somehow related to executive functions, memory, attention, planning and decision-making. Furthermore, in the acute use of cocaine and crack, there is vascular constriction and an increase in arterial pressure. These events increase the risk of a cerebral vascular accident and small blockages of blood vessels (ischemia). The chronic use of drugs leaves several regions of the brain poorly irrigated, which can affect the cognitive process. The damage is greater when cocaine is associated with alcohol consumption because the mixture of two drugs causes the formation of a metabolite called cocaethylene in the liver, which intoxicates the neurons and can damage the heart. Because it is absorbed more quickly, crack causes the same effects as cocaine but in a more intense form. In contrast, marijuana does not cause vascular constriction, but there are studies that show other vascular alterations; an increase in the risk of strokes; and a reduction in certain regions, such as the amygdala and the hippocampus, which are rich in tetrahydrocannabinol (THC) receptors. These events could directly affect memorization ability and the regulation of emotions like fear and aggressiveness.

Agência FAPESP – Is this why marijuana is considered a risk factor for the development of psychotic disorders?
Cunha – Marijuana increases the risk of developing psychotic symptoms, but the mechanisms related to this fact are still being studied. The susceptibility seems to be linked to both genetic characteristics and the life history of the marijuana users, including the way that their neuropsychological development occurred and their psychological state at the time of drug use. There are studies that indicate that carriers of a certain polymorphism in the gene that codifies catechol-O-methyltransferase (COMT) have a greater risk of developing psychotic symptoms if they consume marijuana. A study by our group reinforces the hypothesis that the brains of carriers of psychotic disturbances – including schizophrenia and bipolar disorder – who use marijuana are different from the brains of carriers of psychosis without a history of marijuana use.

Agência FAPESP – How was this study conducted?
Cunha – The data were collected during the doctoral studies of Maristela Schaufelberger, who is now a lecturer at USP Ribeirão Preto, at FMUSP, and part of the data was analyzed during my post-doctoral studies, which were partly funded by FAPESP. The results were released in the July edition of the magazine Schizophrenia Research. Through neuroimaging exams, we compared the volume of certain cerebral areas in 80 healthy volunteers who were not drug users with the volume in 78 individuals with psychotic disturbances who were not drug users and in 28 individuals with psychotic disorders and a history of marijuana use. We also compared the performance of each group in tests that gauge verbal fluency, operational memory and the length of attention.

Agência FAPESP – What were the results?
Cunha – It was expected that the psychotic marijuana users would be worse in evaluations, but curiously, they had the results closest to those of the control group. The psychotic non-drug users had a lower cerebral volume, particularly in the prefrontal cortex, which is linked to executive functions, and in the hippocampus areas, which are linked to memory. Other recent studies are also pointing to this relationship.

Agência FAPESP – Are there any benefits of marijuana use?
Cunha – That does not seem to be the case. From the point of view of cerebral effects, marijuana consumed through smoking is more potent and rich in THC, which is the main active ingredient of the drug and is strongly associated with cognitive and psychotic symptoms. However, certain researchers defend the hypothesis that cannabidiol (CBD), another substance found in marijuana, could have a neuroprotective effect. However, our data do not allow us to affirm this effect because we do not have information about the concentrations of CBD and THC in the marijuana that the patients smoked. Furthermore, marijuana smokers absorb not only CBD but also high doses of THC, which is known to cause damage to the brain. Our hypothesis is that the people who develop a certain type of psychotic disturbance, even without using any type of drug, have already experienced previous damage to their neurodevelopment, perhaps in their childhood. This prior damage makes the initial state and the cerebral abnormalities more severe. However, the psychotic patient with a history of marijuana use will initially have a better-preserved neuropsychological profile, but with functional destructuring due to the initial stages of psychosis. However, as the disease advances, the scenario becomes more severe in the two groups and worsens further if marijuana use persists. Marijuana users do not have a lighter psychosis than others.

Agência FAPESP – Why are certain people more susceptible to damage caused by drugs, whereas others are more resistant?
Cunha – There are genetic and environmental factors. All of the stimuli that we receive throughout life, the culture that one is exposed to, languages learned and new abilities make the brain form a greater number of synapses, which generates a cognitive reserve. The greater this reserve, the greater the resistance to the deficit caused by drugs or diseases, such as Alzheimer’s, on executive functions and on memory. We are now studying how cognitive rehabilitation, which is a form of cerebral bodybuilding, can help to offset the functional deficit caused by drugs. We have data that indicate that the greater the loss of executive functions, the greater the risk of a dependent in treatment experiencing relapse.

Agência FAPESP – What was the effect of this study?
Cunha – The participants were 32 patients diagnosed with cocaine or crack dependence between the ages of 18 and 45 and hospitalized at the Impulsive Behavior Infirmary at HC-FMUSP. After one week of detoxification, when the toxicological exam stopped detecting drug metabolites in the patients’ urine, they were submitted to several tests to evaluate executive functions, such as sustained attention (maintaining focus for prolonged periods), alternate attention (observing two stimuli, such as numbers and letters, at the same time), a capacity for abstractions, cognitive flexibility (adapting to new standards of reasoning), planning and decision-making focused on the future. After an approximately five-week hospital stay, follow-up was conducted by phone for one month. The patients who relapsed during this period of follow-up were those who presented the worst performance on the evaluations of executive functions at the beginning of the treatment. In this way, cognitive deficits can be interpreted as indicators of the probability of relapses among addicts. The study was developed during the master’s studies of the neuropsychologist Priscila Dib Gonçalves, a FAPESP fellow who was mentored by Arthur Guerra de Andrade. As part of her doctoral studies, she is now evaluating the impact of cognitive rehabilitation on treatment based on the new model of cognitive rehabilitation that we created, called “Motivational Chess.”

Agência FAPESP – How does this model work?
Cunha – We use the chess game along with scientific approaches known as Motivational Interviews, in which therapists help a dependent to understand the motivations that lead him or her to drugs and help to outline goals for the future and strategies to stay away from drugs. Through magnetic resonance exams, we are also investigating the brain regions activated during rehabilitation with the support of Geraldo Busatoo, who coordinates USP’s Neuroimaging Laboratory with the help of the National Council on Scientific and Technological Development (CNPq). We know that chemical dependents have generalized damage in several regions, but we believe that the prefrontal regions – which coordinate executive functions – are more related to relapses and difficulty in adhering to treatment. For this reason, we focus on the rehabilitation of these prefrontal areas. Our objective is to investigate whether the training in fact makes these cerebral regions work better.

Agência FAPESP – How does cognitive rehabilitation act on the brain?
Cunha – Bringing back neurons that have died is impossible, but we can stimulate the areas that are preserved and make these areas stronger to offset the cognitive deficit. This concept is so-called neuroplasticity. Preliminary data have proven cognitive improvements in these patients, but we need to go beyond this finding and understand how this change represents an improvement in daily life and long-term recovery.