What Makes Pregabalin Addictive
Pregabalin produces euphoria and "liking" effects similar to benzodiazepines through its CNS activity, with recreational users rating its subjective effects comparable to diazepam, making it particularly addictive in patients with substance abuse history. 1
Neurobiological Mechanisms of Addiction
Pregabalin's addictive potential stems from its ability to produce pleasurable subjective effects through central nervous system activity, though the exact receptor mechanisms differ from classic drugs of abuse:
Euphoric effects: In controlled clinical studies, 4% of pregabalin-treated patients reported euphoria as an adverse reaction, with rates ranging from 1-12% in certain patient populations. 1
Subjective reward: In recreational drug users, pregabalin 450 mg produced subjective ratings of "good drug effect," "high," and "liking" that were similar in magnitude to diazepam 30 mg. 1
Physical dependence development: Abrupt discontinuation produces withdrawal symptoms including insomnia, nausea, headache, diarrhea, anxiety, and hyperhidrosis, reinforcing continued use to avoid these unpleasant effects. 1
High-Risk Patient Populations
Patients with prior substance abuse history face dramatically elevated risk for developing pregabalin addiction:
Polydrug abuse history: Among 118 published cases of pregabalin abuse or dependence, current or past polydrug abuse was present in the majority of cases, with a mean daily dose of 2.9 grams (nearly 10 times the typical therapeutic dose). 2
Male sex and psychiatric comorbidity: Male patients (67% of cases), those with psychiatric diagnoses beyond substance use disorders, and patients with opioid addiction history represent key risk factors for developing addictive behaviors with pregabalin. 2
Dangerous combinations: Pregabalin taken with opioids can cause dangerous respiratory depression, increasing both the euphoric effects and overdose risk. 3
Physical Dependence vs. Addiction
It is critical to distinguish physical dependence from true addiction, as this confusion leads to both over- and under-recognition of the problem:
Physical dependence is common: Withdrawal symptoms can occur even with regular therapeutic doses (150-600 mg/day) after as little as 2 months of use, and does not constitute addiction. 4
True addiction is characterized by: Development of tolerance, dose escalation, drug-seeking behavior, inability to control use despite harm, and obsessive preoccupation with obtaining the drug—not merely experiencing withdrawal symptoms. 1, 2
Clinical Risk Factors and Warning Signs
Monitor for these specific addiction indicators rather than confusing normal physical dependence with addiction:
Dose escalation: Patients taking progressively higher doses beyond prescribed amounts, with some cases reporting doses up to 2,900 mg daily. 2
Unauthorized routes: Reports of crushing, snorting, or injecting pregabalin indicate severe addiction. 5
Drug-seeking behaviors: Requests for early refills, "lost" prescriptions, multiple prescribers, or combining with other substances of abuse. 2, 5
Psychiatric symptoms on discontinuation: Nearly all patients with pregabalin dependence experienced withdrawal symptoms when the drug was discontinued. 2
Critical Clinical Caveat
Pregabalin carries sedation, dizziness, confusion, edema, euphoria, and weight gain as adverse effects, with particular caution needed in patients with psychiatric disease or addiction history due to euphoria risk. 6 The drug is classified as Schedule V controlled substance, reflecting recognized but lower abuse potential compared to opioids or benzodiazepines. 1
Importantly, some patients develop dependence without any prior substance abuse history, though this is less common—approximately half of reported cases had no known history of substance abuse. 5 This means clinicians cannot rely solely on substance abuse history to predict risk, though it remains the strongest predictor.