Psychological dependence explained
Psychological dependence is a cognitive disorder and a form of dependence that is characterized by emotional–motivational withdrawal symptoms upon cessation of prolonged drug use or certain repetitive behaviors.[1] Consistent and frequent exposure to particular substances or behaviors is responsible for inducing psychological dependence, requiring ongoing engagement to prevent the onset of an unpleasant withdrawal syndrome driven by negative reinforcement.[2] Neuronal counter-adaptation is believed to contribute to the generation of withdrawal symptoms through changes in neurotransmitter activity or altered receptor expression.[3] Environmental enrichment and physical activity have been shown to attenuate withdrawal symptoms.
Symptoms
Psychological withdrawal symptoms include:
Development
Psychological dependence develops through consistent and frequent exposure to a stimulus. After sufficient exposure to a stimulus capable of inducing psychological dependence (e.g., drug use), an adaptive state develops that results in the onset of withdrawal symptoms that negatively affect psychological function upon cessation of exposure.
Psychostimulants, such as amphetamine and cocaine, exemplify a drug class that induces psychological withdrawal symptoms, rather than the somatic symptoms typical of physical dependence. Whilst psychological dependence is commonly associated with prolonged drug use, a behavioral dependence-withdrawal syndrome can also manifest through certain behaviors. For instance, exercise dependence can develop in amateur and professional athletes whereby cognitive withdrawal symptoms (e.g., anxiety and irritability) arise during periods of abstinence, with symptom severity often correlating with the duration of abstinence.[4] Other behaviors that can produce observable psychological withdrawal symptoms (i.e., cause psychological dependence) include shopping, sex and self-stimulation using pornography, and eating food with high sugar or fat content, among others.[5]
The process responsible for the induction of psychological dependence is a negative feedback mechanism that involves neuronal-counter adaptation, leading to tolerance to the desirable effects of certain drugs or stimuli and a subsequent withdrawal syndrome upon abrupt cessation of exposure. While psychological dependence and addiction are distinct disease states mediated by opposite modes of reinforcement, they arise through partially overlapping biological processes. In the nucleus accumbens, both conditions involve overlapping signaling cascades that diverge at the CREB transcription factor. Upregulation of CREB expression in the nucleus accumbens plays a major role in mediating psychological dependence by inhibiting reward-related motivational salience, which mediates the onset of emotional-motivational withdrawal symptoms. Evidence indicates that the unpleasant nature of these withdrawal symptoms intensifies the desire to resume the associated drug or behavior.
Biomolecular mechanisms
Methods for reducing dependence
A study examined how rats experienced morphine withdrawal in different surroundings. The rats were either placed in a standard environment (SE) or in an enriched environment (EE). The study concluded that EE reduced depression and anxiety withdrawal symptoms.[6]
Another study tested whether swimming exercises affected the intensity of perceivable psychological symptoms in rodents during morphine withdrawal. It concluded that the anxious and depressive states of the withdrawal were reduced in rats from the exercise group.[7]
Distinction between psychological and physical dependence
The defining contrast between psychological dependence and physical dependence syndromes lies in the nature of the withdrawal symptoms experienced from removal of a particular stimulus following the development of tolerance. Psychological dependence is characterized by symptoms that are cognitive in nature and may include anxiety, dysphoria, exhaustion, hyperphagia, or irritability, among other symptoms. Conversely, physical dependence involves entirely somatic symptoms, such as diarrhea, myalgia, nausea, sweating, tremors, and other symptoms that are readily observable.[9] Substance dependence is a general term that can refer to either psychological or physical dependence, or both, depending on the specific substance involved.
Notes and References
- Book: Molecular Neuropharmacology: A Foundation for Clinical Neuroscience . Malenka RC, Nestler EJ, Hyman SE, Holtzman DM . McGraw-Hill Medical . 2015 . 9780071827706 . 3rd . New York . Chapter 16: Reinforcement and Addictive Disorders . Dependence is defined as an adaptive state that develops in response to repeated drug administration, and is unmasked during withdrawal, which occurs when drug taking stops. Dependence resulting from long-term drug use may have both a somatic component, manifested by physical symptoms, and an emotional–motivational component, manifested by dysphoria and anhedonic symptoms, that occur when a drug is discontinued. While physical dependence and withdrawal occur dramatically with some drugs of abuse (opiates, ethanol), these phenomena are not useful in the diagnosis of an addiction because they do not occur as robustly with other drugs of abuse (cocaine, amphetamine) and can occur with many drugs that are not abused (propranolol, clonidine). The official diagnosis of drug addiction by the Diagnostic and Statistical Manual of Mental Disorders (2013), which uses the term substance use disorder, is flawed. Criteria used to make the diagnosis of substance use disorders include tolerance and somatic dependence/withdrawal, even though these processes are not integral to addiction as noted. ...
As previously discussed, cessation of cocaine use and the use of other psychostimulants in dependent individuals does not produce a physical withdrawal syndrome but may produce dysphoria, anhedonia, and an intense desire to reinitiate drug use. ...
Long-term caffeine use can lead to mild physical dependence..
- Nestler EJ . 2013 . Cellular basis of memory for addiction . Dialogues in Clinical Neuroscience . 15 . 4 . 431–443 . 10.31887/DCNS.2013.15.4/enestler . 3898681 . 24459410 . Stimulant and opiate drugs of abuse activate CREB in several brain regions important for addiction, including prominently in the NAc. ...
Drug activation of CREB in NAc has been shown to represent a classic negative feedback mechanism, whereby CREB serves to reduce an animal's sensitivity to the rewarding effects of these drugs (tolerance) and to mediate a negative emotional state during drug withdrawal (dependence). These effects have been shown recently to drive increased drug self-administration and relapse, presumably through a process of negative reinforcement..
- Koob . George F. . Le Moal . Michel . 2008 . Addiction and the brain antireward system . . 59 . 29–53 . 10.1146/annurev.psych.59.103006.093548 . 0066-4308 . 18154498.
- Weinstein AA, Koehmstedt C, Kop WJ . November 2017 . Mental health consequences of exercise withdrawal: A systematic review . General Hospital Psychiatry . 49 . 11–18 . 10.1016/j.genhosppsych.2017.06.001 . 1873-7714 . 28625704 . Results showed a consistent pattern for adverse effects of exercise withdrawal on these mental health measures, particularly depressive symptoms and anxiety. For the studies reviewed, depressive symptoms consistently occurred following the cessation of exercise. Depressive symptoms includes a variety of complaints, including fatigue, tension, confusion, lower self-esteem, insomnia, and irritability. However, the severity of these symptoms did not reach the level of a clinical diagnosis. Exercise deprivation also consistently resulted in an increase in general anxiety (state anxiety), but no information was provided regarding anxiety disorders based on clinical diagnostic criteria. Regarding general mood symptoms and general well-being, results indicated consistent negative changes in both general mood and wellbeing. The most frequently reported feelings were guilt, irritability, anger, confusion, restlessness, tension, frustration, stress, and sluggishness (loss of vigor)..
- Olsen CM . Natural rewards, neuroplasticity, and non-drug addictions . Neuropharmacology . 61 . 7 . 1109–1122 . December 2011 . 21459101 . 3139704 . 10.1016/j.neuropharm.2011.03.010.
- Hammami-Abrand Abadi. Arezoo. Miladi-Gorji. Hossein. Bigdeli. Imanollah. April 2016. Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats. Behavioural Pharmacology. 27. 2 and 3 - Special Issue. 270–278. 10.1097/fbp.0000000000000197. 26397757. 11212134. 0955-8810.
- Fadaei. Atefeh. Gorji. Hossein Miladi. Hosseini. Shahrokh Makvand. 2015-01-15. Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats. European Journal of Pharmacology. 747. 88–95. 10.1016/j.ejphar.2014.11.042. 1879-0712. 25498794.
- Fornaro M, Cattaneo CI, De Berardis D, Ressico FV, Martinotti G, Vieta E . 2023 . Antidepressant discontinuation syndrome: A state-of-the-art clinical review . European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology . 66 . 1–10 . 10.1016/j.euroneuro.2022.10.005 . 36345093 . free. 2445/208551 . free .
- Volkow ND, Bianco C . 2020-01-02 . Medications for opioid use disorders: clinical and pharmacological considerations . The Journal of Clinical Investigation . 130 . 1 . 10.1172/JCI134708 . 6934219 . 31763992.
