Pregabalin
(3S)-3-(aminomethyl)-5-methylhexanoic acid
Overview
Pregabalin belongs to Depressants.
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology,
mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or
desirable outcomes.
- At therapeutic doses: reduced neuropathic pain, seizure frequency and anxiety, commonly with drowsiness, dizziness, unsteadiness and sometimes peripheral oedema or weight gain.
- At higher or recreational doses: alcohol- or opioid-like relaxation, disinhibition, sociability and mild euphoria, sometimes with a 'floaty' or mildly dissociative quality. Effects and misuse potential are more pronounced in people with a history of substance use and in opioid users.
- Onset is roughly 30–45 minutes and effects are long (about 9–17 hours). Tolerance develops with repeated use, and dependence with a distinct withdrawal syndrome can follow regular use.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a
“safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start
low, go slow, wait for full effects before redosing, and never assume an unknown product matches these
figures. Missing data is not evidence of safety.
Oral (capsules, tablets or solution). Non-medical use is usually oral, occasionally rectal or insufflated.. The figures below are commonly cited reference ranges, not a recommendation or a 'safe' dose, and the recreational single-dose ranges shown exceed the licensed clinical maximum of 600 mg per DAY (taken in divided doses). The critical harm-reduction point is combination: pregabalin taken with opioids, benzodiazepines, gabapentin or alcohol markedly increases the risk of sedation, respiratory depression and death: a combination repeatedly implicated in overdose fatalities and the reason the UK made it a controlled drug in 2019. Regular use causes tolerance and dependence, and abrupt cessation can trigger a withdrawal syndrome (including seizures): taper, do not stop suddenly. Pregabalin accumulates in renal impairment.
Dose ranges
Threshold
50 mg
Light
50–225 mg
Common
225–600 mg
Strong
600–900 mg
Heavy
900 mg +
Duration
onset
30–45 minutes
total
9–17 hours
after effects
4–10 hours, with regular use, tolerance, dependence and a withdrawal syndrome (seizure risk on abrupt cessation)
Chemical & Physical Properties
| Formula | C8H17NO2 |
| Molar mass | 159.23 g/mol |
| State | Solid (white to off-white crystalline) |
| Melting point | 176–188 °C (reported range) |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | pKa1 = 4.2 (carboxyl), pKa2 = 10.6 (amine): zwitterionic |
| LogP | 1.3 (LogP), −1.35 (logD at pH 7.4, experimental) |
| Solubility | Freely soluble in water (~11.3 g/L), Freely soluble in acidic and basic solutions |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 148553-50-8 |
| CAS (enantiomer) | |
| PubChem CID | 5486971 |
| InChIKey | AYXYPKUFHZROOJ-ZETCQYMHSA-N |
| InChI | InChI=1S/C8H17NO2/c1-6(2)3-7(5-9)4-8(10)11/h6-7H,3-5,9H2,1-2H3,(H,10,11)/t7-/m0/s1 |
| SMILES | CC(C)C[C@@H](CC(=O)O)CN |
Synonyms
- Lyrica
- (S)-3-(aminomethyl)-5-methylhexanoic acid
Pharmacodynamics & Biochemistry
Pregabalin is a lipophilic analogue of the neurotransmitter GABA and a close relative of gabapentin, but, despite the GABA-mimetic design, it does not bind GABA receptors, is not converted to GABA, and does not affect GABA uptake or metabolism. It is used for neuropathic pain, focal (partial) epilepsy and, in Europe, generalised anxiety disorder. Its established mechanism is high-affinity binding to the α2δ auxiliary subunit of voltage-gated calcium channels (principally α2δ-1). This reduces depolarisation-evoked calcium influx at nerve terminals and dampens the release of excitatory neurotransmitters such as glutamate, noradrenaline and substance P, producing analgesic, anticonvulsant and anxiolytic effects. Pregabalin binds α2δ with higher affinity and is roughly six times more potent than gabapentin. Reported binding affinity is high: a dissociation constant (Kd) of about 19 nM has been measured at the α2δ subunit in pig-brain membranes. The IUPHAR/BPS Guide to PHARMACOLOGY notes that it has been unable to find publicly available human α2δ bioactivity data, so the quantitative figure shown below is from animal tissue. Pregabalin differs pharmacokinetically from gabapentin in a clinically important way: whereas gabapentin is absorbed by a saturable transporter (giving non-linear, dose-limited absorption), pregabalin shows linear, dose-proportional absorption and near-complete bioavailability. Like gabapentin it is essentially not metabolised and is eliminated unchanged by the kidneys, so doses must be reduced in renal impairment.
Biological targets
- VGCC α2δ
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| VGCC α2δ | pKd 7.72 | Pig (brain membranes) |
Pharmacokinetics
| Bioavailability | Oral ≥90% (linear, dose-proportional, unlike gabapentin's saturable absorption) |
| Tmax | ≈1 h |
| Half-life | ≈6.3 h |
| Vd | Not reported |
| Protein binding | Negligible (not plasma-protein bound) |
| Metabolism | Essentially not metabolised (<2%) |
| Excretion | Renal, almost entirely unchanged (dose adjustment in renal impairment) |
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual
health factors. Missing harms should never be interpreted as evidence of safety.
Not reported
Pregabalin is an effective medicine for neuropathic pain, focal epilepsy and anxiety, but it carries a genuine and growing misuse and dependence risk. On its own it is relatively safe in overdose, but combined with opioids, benzodiazepines, gabapentin or alcohol it markedly increases the risk of sedation, respiratory depression and death: a pattern repeatedly seen in overdose fatalities and the reason it (with gabapentin) became a controlled drug in the UK in 2019. Regular use produces tolerance and physical dependence, and abrupt discontinuation can cause a withdrawal syndrome including anxiety, insomnia, sweating and seizures, so it must be tapered rather than stopped suddenly. Misuse is especially common in people with opioid or other substance-use histories. Common effects include dizziness, drowsiness, unsteadiness, weight gain and peripheral oedema. Pregabalin accumulates in renal impairment and needs dose reduction.[10][8][6]
Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status,
prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
US: Schedule V. UK: Class C. DE: Prescription only (Rx)
Interactions & Contraindications
Drug interactions
Contraindications
Known hypersensitivity to the drug hypersensitivity to pregabalin.[8]
Kidney or liver impairment dose reduction required in renal impairment (renally cleared unchanged, accumulates otherwise).[6]
Combining with alcohol or other CNS depressants concomitant opioids or other CNS depressants (respiratory-depression and overdose-death risk).[10]
History of stimulant or substance use disorder history of substance-use disorder (genuine misuse and dependence potential).[11]
Abrupt discontinuation after regular use (withdrawal and seizure risk) avoid abrupt withdrawal (withdrawal syndrome, seizure risk), tapering on discontinuation.[8]
No interactions or contraindications listed.
Usage & Context
- A widely prescribed medicine (Lyrica and generics) for neuropathic pain, as an adjunct for focal (partial) seizures, and, in Europe, for generalised anxiety disorder. Also used for fibromyalgia (notably in the US) and off-label for other conditions.
- Increasingly misused recreationally for a relaxing, alcohol- or opioid-like effect, often alongside opioids, the most dangerous pattern, and commonly diverted in prison and opioid-using populations, which drove its control in several countries.
Sources & Evidence
- PubChem: Pregabalin (CID 5486971) — identifiers & experimental properties
- IUPHAR/BPS Guide to PHARMACOLOGY: pregabalin (ligand 5484) — α2δ VGCC ligand, Kd ≈19 nM (pig brain) CC BY-SA 4.0
- Field MJ, Cox PJ, Stott E, et al. (2006). Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A 103:17537-42.
PMID 17088553 · doi:10.1073/pnas.0409066103
- Schwarz JB, Colbry NL, Zhu Z, et al. (2006). Carboxylate bioisosteres of pregabalin. Bioorg Med Chem Lett 16:3559-63.
PMID 16621528 · doi:10.1016/j.bmcl.2006.03.083
- Schwarz JB, Gibbons SE, Graham SR, et al. (2005). Novel cyclopropyl beta-amino acid analogues of pregabalin and gabapentin that target the alpha2-delta protein. J Med Chem 48:3026-35.
PMID 15828841 · doi:10.1021/jm0491086
- Bockbrader HN, Wesche D, Miller R, et al. (2010). A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet 49:661-9.
PMID 20818832 · doi:10.2165/11536200-000000000-00000
- Bockbrader HN, Radulovic LL, Posvar EL, et al. (2010). Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol 50:941-50.
PMID 20147618 · doi:10.1177/0091270009352087
- FDA / DailyMed: Pregabalin prescribing information — pharmacokinetics & metabolism
- DEA Diversion Control Division: Controlled Substance Schedules — pregabalin is Schedule V
- GOV.UK: Controlled drugs list (Misuse of Drugs legislation) — pregabalin is Class C / Schedule 3 (April 2019) OGL v3.0
- Wikipedia: Pregabalin (pharmacology, pharmacokinetics, misuse & legal status) CC BY-SA 4.0
- PsychonautWiki: Pregabalin (dosage & duration) CC BY-SA 4.0