Advanced Psychopharmacology

Impulsivity, Compulsivity, and Addiction, Lecture 2 Video Transcript

This is lecture two of a series on impulsivity and addiction. Hallucinogens are a group of agents that act at serotonin synapses in the reward system. The experiences of a hallucinogen can be broken down in either psychedelic or psychotomimetic.

The primary action of hallucinogenic drugs are shown here, namely agonism of 5HT2A receptors. Hallucinogens may have additional actions at other serotonin receptors.

Although food addiction is not yet accepted as a formal diagnosis, it does appear that when external stimuli are triggers for maladaptive eating habits that are performed despite apparent satiety and adverse health consequences, this does define a compulsion and a habit with the formation of aberrant eating behaviors in a manner that parallels drug addiction.

Appetite is regulated by the balance between an appetite-stimulating pathway and an appetite-suppressing pathway. The appetite-suppressing neurons make the precursor POMC, which is broken down into alpha-MSH, which, in turn, binds to melanocortin for receptors to suppress appetite.

Phentermine increases dopamine and norepinephrine in the hypothalamus by blocking both the norepinephrine and dopamine reuptake transporters. Topiramate hypothetically inhibits the appetite-stimulating pathway on the left by reducing excitatory glutamatergic input and by increasing inhibitory GABAergic input. Combining this with phentermine actions on the right that stimulate the appetite-suppressing pathway, this results in a synergistic and enhanced effect on appetite and on weight loss.

The antidepressant and smoking cessation aid bupropion is thought to have effects in the appetite center of the hypothalamus as well. Bupropion increases dopamine and norepinephrine in the hypothalamus by blocking both the norepinephrine and dopamine reuptake transporters. Both naltrexone and bupropion alone can lead to some weight loss by themselves. However, the combination of naltrexone and bupropion have a synergistic effect on weight losses or passes monotherapy with either agent by dual pharmacologic actions on the appetite-suppressing pathway.

The 5HT2C agonist lorcaserin has recently been approved for treatment of obesity. This hypothetically binds to 5HT2C receptors on POMC neurons in the appetite-suppressing pathway, activating POMC neurons and leading to the release of alpha-MSH, which binds to melanocortin-4 receptors to robustly suppress appetite.

The anticonvulsant zonisamide has actions in the appetite center of the hypothalamus that are similar to those of topiramate. Zonisamide hypothetically both reduces excitatory glutamatergic input and increases inhibitory GABAergic input onto neurons in the appetite-stimulating pathway, leading to less output of neuropeptide Y and AgRP and decreased appetite stimulation.

The combination of histamine 1 antagonism and serotonin 5HT2C antagonism present in many atypical antipsychotics may lead to enhanced appetite and consequential weight gain. Conversely, the actions of a 5HT2C agonist, such as lorcaserin, may lead to appetite suppression and weight loss.

Many impulses can become an impulsive-compulsive disorder when done to excess, and several of these examples are listed in this table. Some experts believe gambling disorder should be classified along with drug addiction as the only nod substance disorder in that category. Many disorders considered to be neurodevelopmental have impulsivity or compulsivity as a symptom dimension. This includes notably ADHD, discussed in chapter 12.

Aggression and violence have long been controversial issues in psychiatry. When violence is premeditated, callous, and calculated, it may be criminal, psychopathic, and predatory, and this type of violence would neither be impulsive nor compulsive. However, aggression and violence, both to others and to oneself, are associated with many psychiatric disorders, seen here in table 14.7.

Obsessive Compulsive Disorder or OCD in many ways is the prototypical impulsive-compulsive disorder, although it's been considered to be an anxiety disorder as well. In OCD, many patients experience an intense urge to perform stereotypic, ritualistic acts despite having full insight into how senseless and excessive those behaviors are and having no real desire for the outcome of these actions.

The most common types of compulsions are checking and cleaning. Seen here in this table are some of the other impulsive-compulsive related disorders, such as skin picking, trichotillomania, which is hair pulling.