Addressing issues related to addictive behaviors and diagnoses
Euphoric or pleasurable responses occur in response to a variety of behaviors and experiences or artificial substances, and are the result of stimulating opioid receptors. Endogenous or natural opioids are substances that bind with opioid receptors in the brain and comprise four classes: endorphins, enkephalins, dynorphins, and endomorphins (Koneru, Satyanarayana, & Rizwan, 2009). Activation of opioid receptors in the brain can occur from natural opioids or artificially from substances such as heroin, prescription opioid drugs, alcohol, amphetamine agents, and cannabis. Natural and artificial stimulation of opioid receptors increases dopamine levels by decreasing inhibition of the dopamine pathways, which creates a feeling of pleasure (Koneru et al., 2009). Dopamine is a complex neurotransmitter that can create a variety of health problems if levels are either too high or too low. Some of the vital functions that dopamine plays a role in include movement, memory, pleasure, attention, mood, sleep, behavior, and cognition, as well as regulation of prolactin levels (Mandal, 2015).
There are five subtypes of dopamine (i.e., D1 to D5) and two receptor pathways on which they play a role in neurobiology, which are divided into two major subclasses: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptors (Panesar & Guzman, 2017). There are four dopamine pathways in the brain: nigro-striatal, associated with movement; mesolimbic, associated with pleasure; mesocortical, associated with cognition, emotional behavior, and memory; and tuberoinfundibular, associated with regulating prolactin as well as sexual arousal (Ayano, 2016; Richard, 2016). Both subclasses play a role in mental health disorders (e.g., high levels of dopamine are associated with schizophrenia and low dopamine levels are associated with attention-deficit/ hyperactivity disorder [Ayano, 2016]).
Once dopamine is triggered and a higher level is present, a lasting memory of the feeling of pleasure is created, which can be triggered to varying degrees in the form of cravings. Pleasurable activities associated with an increase in dopamine include natural (e.g., sex, eating) and artificial (e.g., substance use) sources (Volkow, Koob, & McLellan, 2016). With normal natural source stimulation through endogenous or natural opioids, dopamine is increased, but the cells stop firing after repeated consumption, which normally satisfies the drive for further consumption (Volkow et al., 2016). Artificial substances taken for pleasure circumvent satiation, resulting in prolonged and increased elevated dopamine levels (Volkow et al., 2016). Repeated activation of the brain reward system and higher dopamine production results in dysfunction or desensitization of the reward system, causing a decrease in dopamine levels that leads to craving the substance to maintain normal dopamine levels as well as other negative emotions and behaviors, including a decreased feeling of well-being and ability to respond to stress (Volkow et al., 2016).
Although it is widely known that substance use disorders (SUDs) occur in conjunction with cravings for substances, many other mental health disorders are known to have an addictive component that includes cravings. The physiological response of increased dopamine triggered by a compulsive behavior, which then leads to chronic decreased dopamine levels, is also thought to occur in association with other disorders (e.g., eating disorders, gambling, internet gaming, self-injury, compulsive sexual behaviors) (Volkow et al., 2016).
Role of Pleasure in Eating Disorders
Food consumption is a pleasurable activity stimulated by the smell, sight, and taste of food that activates the brain reward systems (Frank, 2013). The neurobiology of anorexia nervosa and binge eating disorder is still not completely understood; however, dopamine is thought to play a role when levels are increased as a result of the stress associated with restricting calories and over-exercising or binging and purging. The elevated dopamine response associated with eating disorder behaviors becomes rewarding or pleasurable either consciously or subconsciously—not unlike that which occurs in SUDs (Södersten, Berg, Leon, & Zandian, 2016). Low levels of dopamine in patients with eating disorders have been linked to anhedonia (Monteleone et al., 2017). These low levels could result from initial surges similar to the down regulation that occurs with SUDs. For example, in binge eating disorders, stimulation of the dopamine system from binging has been shown to result in progressive impairment of dopamine signaling (Bello & Hajnal, 2010).
Role of Pleasure in Non-Suicidal Self-Injury
Neurobiology is thought to play a significant role in non-suicidal self-injury (NSSI). Although the disorder is not fully understood, patients who engage in NSSI are thought to do so for reasons that include ending a negative emotional state or numb feeling (Bresin & Gordon, 2013). Individuals with a history of NSSI have been found to have low levels of endogenous opioids (Groschwitz & Plener, 2012). Pain activates opioid receptors; therefore, an increase in endogenous opioids occurs when engaging in NSSI behaviors (Bresin & Gordon, 2013). Low endogenous opioid levels in NSSI are proposed to be a result of chronic stress or exposure to past trauma (Stanley et al., 2010). It is also thought that pain leading to increased endogenous opioids serves as a function to regulate negative affect (Bresin & Gordon, 2013).
Role of Pleasure in Compulsive Sex Behaviors
Although no formal diagnosis exists for sex addiction in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association [APA], 2013), hypersexual disorder was considered in a DSM work group (Kafka, 2010). Compulsive or hypersexual behaviors include those that interfere with functioning, such as pornography dependence; excessive, impulsive, or compulsive sexual activity; and an inability to stop the behavior (Bostwick, Hecksel, Stevens, Bower, & Ahlskog, 2009). Abnormal dopamine levels have been proposed as an underlying cause or contributing factor of excessive sexual behaviors (Rosenberg, Carnes, & O'Connor, 2014). Studies show that patients treated with dopamine for Parkinson's disease have a higher incidence of developing new onset sexual compulsivity (Bostwick et al., 2009). Sex hormones (e.g., testosterone) trigger endorphin release and dopamine activation, which reinforces pleasure, the expectation of reward, and the desire to repeat it (Reynaud, Karila, Blecha, & Benyamina, 2010). The high dopamine release seen in compulsive sexual behaviors (e.g., cybersex) can result in the same dopamine down regulations seen in other addictive disorders, which can lead to heightened risk and intrigue to sustain the pleasure (Riemersma & Sytsma, 2013).
Role of Pleasure in Internet Gaming and Gambling Disorders
Internet gaming disorder is proposed as a condition for further study in the DSM-5. Criteria include persistent engagement or preoccupation with gaming that leads to significant impairment or distress, withdrawal, tolerance, and unsuccessful attempts to control the behavior (APA, 2013). Gambling disorder is listed in the DSM-5 as a non-substance–related disorder and criteria include persistent problematic gambling that leads to significant impairment or distress, impacted relationships, lies to conceal, preoccupation, and gambling when distressed (APA, 2013).
Gaming and gambling share neurocircuitry and neurochemical changes with other SUDs, including that the behavior triggers increased dopamine levels which then lead to down regulation and low dopamine levels further resulting in a desire to continue the behavior despite negative consequences (Kuss, 2013; Potenza, 2014).
Naltrexone is an opioid antagonist approved in the 1960s for opioid use disorder and was later approved for alcohol use disorder in 1994 (Substance Abuse and Mental Health Services Administration [SAMHSA], 2009). It is available in a daily oral dose or a monthly injectable form (SAMHSA, 2016). It is also available in time-release form as a combination medication with bupropion, approved for obesity (Ornellas & Chavez, 2011). Naltrexone's mechanism of action as an antagonist is that it attaches to opioid receptors in the brain, which block the effect of opioid agents and alcohol and reduce cravings (Ornellas & Chavez, 2011; SAMHSA, 2016). Off-label naltrexone has been extensively studied in randomized controlled trials and systematic reviews for treatment of a variety of mental health disorders associated with an addictive component and other substances, including methamphetamine (Grant, Odlaug, & Kim, 2010), cannabis (Haney et al., 2015), and cocaine (Ling et al., 2016). Because naltrexone is generic, it is less likely approval will be sought for new indications unless a change in the chemical structure or drug combination is formulated. However, off-label use is not precluded, particularly when evidence based.
Naltrexone has been shown to reduce symptoms in eating disorders (Blasio, Steardo, Sabino, & Cottone, 2014; Mitchell, Roerig, & Steffen, 2013; Murray et al., 2014). In 2014, the U.S. Food and Drug Administration (FDA) approved the combination medication Contrave®, which comprises time release naltrexone and time release bupropion for obesity (Takeda Pharmaceuticals America, 2014). Studies have also shown that naltrexone can reduce symptoms of self-injury (Guerdjikova, Gwizdowski, McElroy, McCullumsmith, & Suppes, 2014; Meiser, Dupper, Wedekind, & Bandelow, 2015; Turner, Austin, & Chapman, 2014), compulsive or hypersexual behaviors (Capurso, 2017; Derbyshire & Grant, 2015; Kraus, Meshberg-Cohen, Martino, Quinones, & Potenza, 2015), gaming disorders (Griffiths, Kuss, & Pontes, 2016;), and gambling disorders (Grant, Odlaug, & Schreiber, 2014; Yip & Potenza, 2014; Yoon & Kim, 2013).
Evidence shows SUDs as diseases involving neurocircuit and neurochemistry disruption. The neurotransmitters and circuits involved are those involving the pleasure response from endogenous and artificial opioid agents' effect on dopamine pathways. With continuous activation of the dopamine pathway, down regulation of dopamine occurs. This imbalance of dopamine is thought to be responsible for cravings and continued use of substances regardless of negative consequences. Understanding of the role of the pleasure response and subsequent effect on dopamine levels in other mental health disorders thought to have an addictive component involving cravings is also being gained. When certain behaviors (e.g., binge eating or purging, restrictive calorie intake, NSSI, compulsive sex, gaming and gambling disorders) are understood to result in activation of endogenous opioid agents and dopamine that leads to decreased dopamine levels similar to SUDs, these conditions can begin to be accepted as diseases of chemical and neurocircuitry dysfunction. Without normal dopamine levels, a person will likely exhibit behaviors and characteristics including cognitive inflexibility, negativity, and impulsivity; low energy and mood; problems with cooperation; obsessions; negative thinking and behavior; and lack of enjoyment (Volkow, Wang, Tomasi, & Baler, 2013). This understanding can help demonstrate that a chemical or physical cause is underlying the behavior and associated symptoms rather than a choice. This knowledge can help relieve patients of guilt and also help health care providers have increased compassion for patients when they realize that the symptoms are similar to those common in other diseases from chemical imbalances, such as high blood pressure and blood glucose. A mind shift is required to understand and accept that behaviors seen as negative are related to pleasure centers in the brain and that resulting chemical imbalances drive the disorder.
Naltrexone shows promise in treating a variety of SUDs and mental health disorders that may involve chemicals and brain regions associated with pleasure. This medication is often underused, likely due to the lack of FDA approval for these disorders stemming from generic availability and lack of incentive from pharmaceutical manufacturers. However, ample evidence exists that may justify benefit versus risk. Mental health disorders associated with an addictive or craving component have the potential to be devastating to the individual; therefore, a consideration of alternative approaches may be warranted.
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