Drug Abuse: Gabapentinoids

Gabapentinoids

• Gabapentinoids (pregabalin and gabapentin) are a class of prescribed agents with a high risk for misuse, abuse, and dependency.
• They are used to treat epilepsy, neuropathic pains, generalized anxiety disorder, and fibromyalgia.
• Off-label uses include treatment of bipolar disorder, alcoholic/narcotic withdrawal state, ADHD, and migraine.

Pregabalin

• Pregabalin is an analog of γ-aminobutyric acid (GABA) but does not bind directly to GABA or benzodiazepine receptors.
• Total sales of pregabalin worldwide reached $5 billion in 2013.
• Pregabalin is 6 times more potent than gabapentin and has higher binding affinity at their receptors.
• Oral pregabalin has rapid absorption and higher bioavailability.

Pharmacology of Pregabalin

• Pregabalin binds to and blocks α2-δ subunit of voltage-gated calcium channels on neurons, decreasing excitatory neurotransmitters (e.g., glutamate, noradrenaline, and substance P).
• Pregabalin has GABA-mimetic activity, inhibiting GABA metabolism and altering neuronal GABA transporters.
• Gabapentin administration increases GABA concentration by about 50%.

Psychotropic Effects of Pregabalin

• Pregabalin is considered an ideal psychotropic drug for recreational purposes, producing sedation, euphoria, improved sociability, marijuana-like high/relaxant effect, opioid-like sedative effects, and dissociative/psychedelic effects.

Pregabalin Overdose and Withdrawal

• High doses of pregabalin cause sedation, suicidal ideation, dizziness and somnolence, impaired driving, respiratory depression, and death.
• Withdrawal symptoms include anxiety, depression, agitation, nausea, palpitations, insomnia, hyperhidrosis, and diarrhea.

Pregabalin in Addiction Treatment

• Pregabalin has beneficial effects in managing addiction to various drugs, including alcohol, benzodiazepines, opioids, and cannabis.
• Treatment of pregabalin dependence involves discontinuation by tapering the dose and administration of CNS depressants to control withdrawal symptoms.