Is pregabalin psychoactive? Understanding its effects and risks

October 9, 2025 •

2 min read

Reports from clinical trials dating back to 2005 indicated that pregabalin produced acute euphoric effects in an unusually high percentage of individuals, leading to its classification as a controlled substance. The question, is pregabalin psychoactive, is thus answered with a definitive 'yes,' which is a key reason for its regulatory control.

Quick Summary

Pregabalin is a psychoactive medication with central nervous system depressant and euphoric effects, leading to its controlled substance classification. It works by binding to calcium channels to reduce neurotransmitter release, posing risks of misuse, dependence, and dangerous interactions with other depressants.

Key Points

Definitively Psychoactive: Yes, pregabalin is psychoactive, causing central nervous system effects like euphoria and sedation, especially at higher-than-prescribed doses.
Controlled Substance Classification: Due to its abuse potential, pregabalin is a Schedule V controlled substance in the U.S. and a Class C controlled drug in the U.K..
Mechanism of Action: It binds to the $\alpha_2$-$\delta$ subunit of voltage-gated calcium channels, reducing the release of excitatory neurotransmitters like glutamate.
Risk of Respiratory Depression: Combining pregabalin with other CNS depressants, such as opioids, greatly increases the risk of severe and potentially fatal respiratory depression.
Higher Potency than Gabapentin: Pregabalin is significantly more potent and has faster absorption than its analogue, gabapentin, which contributes to a higher abuse potential.
Abuse Risk in Vulnerable Populations: Individuals with a history of substance use disorder are at a higher risk of misusing pregabalin for its euphoric or sedative effects.
Withdrawal Symptoms: Discontinuing pregabalin, particularly abruptly, can trigger withdrawal symptoms, including anxiety, insomnia, and headache, necessitating careful tapering.

What Makes Pregabalin Psychoactive?

Pregabalin (Lyrica) is psychoactive due to its action on the central nervous system (CNS). It is structurally similar to GABA but doesn't bind directly to GABA receptors. Instead, pregabalin binds to the $\alpha_2$-$\delta$ subunit of voltage-gated calcium channels. This action reduces calcium influx and decreases the release of excitatory neurotransmitters like glutamate, noradrenaline, and substance P. This calms overactive nerves, providing therapeutic effects for pain, seizures, and anxiety, but can also cause dose-dependent psychoactive effects, including relaxation and euphoria.

The Spectrum of Pregabalin's Psychoactive Effects

Pregabalin's effects on the CNS can alter brain function and mood. While therapeutic doses can induce calm, higher doses or misuse can lead to more significant effects:

Euphoria: Frequently reported at higher doses.
Sedation: Causes drowsiness, adding to relaxation.
Anxiolysis: Can induce relaxation and reduce inhibitions.
Dissociation and Hallucinations: Reported by recreational users at high doses.
Cognitive and Motor Impairment: Can cause clumsiness, poor concentration, slurred speech, and unsteadiness.

Why is Pregabalin a Controlled Substance?

The potential for abuse and psychoactive effects are the main reasons for pregabalin's controlled status.

United States: Classified as a Schedule V controlled substance in 2005 due to euphoric effects similar to benzodiazepines.
United Kingdom: Reclassified as a Class C controlled substance in 2019 due to increased misuse and deaths.

Pregabalin vs. Gabapentin: Psychoactive Differences

Both are gabapentinoids but differ in psychoactive properties.


Feature	Pregabalin	Gabapentin
Potency	Higher binding affinity to $\alpha_2$-$\delta$ subunit.	Lower binding affinity.
Absorption	Rapid, linear absorption.	Slower, saturable absorption.
Abuse Potential	Higher potential, especially in those with substance use history.	Lower risk.
Controlled Status	Schedule V in the U.S., Class C in the UK.	Not federally controlled in the U.S. (some states), Class C in the UK.

Risks Associated with Pregabalin's Psychoactive Properties

Non-medical use or high doses carry significant risks:

Dependence and Withdrawal: Can lead to dependence; withdrawal symptoms include insomnia, nausea, and anxiety.
Respiratory Depression: Increased risk when combined with other CNS depressants like opioids. This risk is higher with polysubstance use.
Addiction Vulnerability: Higher risk for individuals with a history of substance abuse; can potentiate other drugs like opioids.
Poly-drug Use: Using pregabalin with other drugs increases overdose risk.

Conclusion: A Balancing Act

Pregabalin is psychoactive, providing therapeutic benefits but also posing risks of misuse and addiction. Its controlled substance classification reflects these risks. Prescribers must carefully consider risks, especially in patients with substance abuse history, and monitor for misuse. Its potency and absorption profile contribute to a higher abuse potential than gabapentin. Patient education and clinical supervision are vital for safe use. More information on addiction potential is available from sources like the National Institutes of Health.

Frequently Asked Questions

The primary psychoactive effect of pregabalin is a feeling of euphoria, which is a key reason for its controlled substance classification. It also causes sedation, relaxation, and anxiolysis.

Pregabalin was classified as a controlled substance because clinical trials showed it produced acute euphoric effects in a significant number of individuals, similar to controlled benzodiazepines.

Pregabalin has a higher binding affinity to its target site in the brain and faster absorption than gabapentin, leading to a quicker and more potent euphoric effect. This gives pregabalin a higher potential for misuse and dependence.

Yes. Abrupt discontinuation of pregabalin can lead to withdrawal symptoms, including insomnia, nausea, headache, anxiety, and irritability, which is why a gradual tapering of the dose is recommended.

Combining pregabalin with other central nervous system depressants, such as opioids, benzodiazepines, or alcohol, can cause severe and potentially fatal respiratory depression.

Pregabalin binds to the $\alpha_2$-$\delta$ subunit of voltage-gated calcium channels, which reduces the release of excitatory neurotransmitters in the central nervous system and can increase extracellular GABA levels, contributing to its mood-altering effects.

Yes. Due to its potential to cause euphoria and other pleasant effects, pregabalin carries a risk of misuse, dependence, and addiction, especially in individuals with a history of substance use disorders.

Common psychoactive-related side effects include dizziness, somnolence (sleepiness), confusion, and difficulty with concentration. Euphoric mood is also reported as a side effect.