Pregabalin

Pregabalin
Chemical Nomenclature
Common names	Pregabalin, Lyrica, Nervalin
Substitutive name	3-Isobutyl GABA
Systematic name	(S)-3-(Aminomethyl)-5-methylhexanoic acid
Class Membership
Psychoactive class	Depressant
Chemical class	Gabapentinoid
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Bioavailability ~90% Threshold 50 mg Light 50 - 225 mg Common 225 - 600 mg Strong 600 - 900 mg Heavy 900 mg + Duration Total 9 - 17 hours Onset 30 - 45 minutes Come up 1 - 2 hours Peak 4 - 6 hours Offset 4 - 8 hours After effects 4 - 10 hours ⇣ Rectal Dosage Bioavailability ~99% Threshold < 40 mg Light 40 - 200 mg Common 200 - 450 mg Strong 450 - 600 mg Heavy 600 mg+ Duration Total 5 - 8 hours Onset 15 - 30 minutes Come up 30 - 120 minutes Peak 2 - 3 hours Offset 3 - 5 hours After effects 6 - 12 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions
Oxycodone
SSRI
MDMA

Pregabalin, marketed as Lyrica by Pfizer, is a central nervous system depressant drug. It is used to treat neuropathic pain, anxiety, restless legs syndrome, and as an adjunct drug in the treatment of seizures.

The pharmacological action of pregabalin is mediated by binding to the α2δ-1 site of voltage-gated calcium channels.. This site has also been referred to as the gabapentin receptor, as it is the target of the related drug gabapentin, also developed by Pfizer. Advantages to Lyrica over gabapentin include higher bioavailability and potency.

Chemistry

This chemistry section is incomplete. You can help by adding to it.

Pharmacology

Although pregabalin is a chemical derivative of GABA, it displays no activity at any GABA receptors, including GABA-A, GABA-B and the benzodiazepine site. Pregabalin, despite its GABA backbone, does not appear to alter GABA levels in the brain, so its pharmacological activity is presumed to be unrelated to GABA. Instead, it is its binding to the α2δ-1 site of voltage-gated calcium channels that appears to be the source of its subjective effects. By binding to this site, pregabalin reduces the release of several excitatory neurotransmitters, including glutamate, Substance P, acetylcholine and norepinephrine. Pregabalin and gabapentin form a new class of drugs with high affinity for the α2δ-1 or gabapentin site, and reduces brain overexcitability not like other depressants, by enhancing inhibitory neurotransmission (as in the case of benzodiazepines), but rather by decreasing excitatory neurotransmission.

One study has also shown that pregabalin promotes deep sleep, thus enhancing sleep quality. This may be important because reductions in slow-wave sleep have been associated with anxiety and fibromyalgia.

In addition, an independent action of the gabapentin site on the neurogenesis of excitatory synapses has been discovered. The endogenous neurochemical thrombospondin also binds to this site and is important for the generation of new excitatory synapses. Gabapentin and pregabalin, having a high affinity for this site, block this action and result in lower levels of excitatory synapses in animal models. This may form part of the therapeutic action of these drugs, as they treat conditions associated with overexcitability of the brain (anxiety, epilepsy, neuropathic pain).

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely if ever occur all at once but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical Effects

• Sedation - Pregabalin produces modest sedation, and improves sleep onset latency modestly, while sleep quality is also improved. However, it is not an overly sedating drug when taken in the day-time.
• Respiratory depression
• Pain relief - Pregabalin is effective against certain types of chronic pain, but not against acute pain.
• Muscle spasms - Somewhat paradoxically, since pregabalin is used as an adjunct treatment for epilepsy, pregabalin, especially in higher doses, can produce muscle spasms. Anecdotally, seizures have been reported in overdose.
• Dizziness
• Motor control loss

Cognitive Effects

Pregabalin's headspace is comparable to a more clear-headed alcohol or benzodiazepine buzz, although it can take a more dissociative turn at very high dosages.

• Amnesia - Compared to benzodiazepines, pregabalin is only mildly amnestic if not combined with other depressants. With chronic usage or high dosages, expect more "tip of the tongue" moments, and impaired short-term memory (e.g., walking into a room and forgetting what you were supposed to do there). Total blackouts do not seem to occur except in combination with other drugs.
• Anxiety suppression
• Thought deceleration
• Disinhibition
• Information processing suppression
• Motivation enhancement - Like kratom, pregabalin can be mildly sedative yet increase motivation in a stimulant-like fashion.
• Euphoria

Visual effects

• Internal hallucinations - At high dosages, one may experience dream-like states and hypnagogia, or "nodding", which can generate up to level 3 imagery.

Toxicity and harm potential

Pregabalin not co-ingested with other substances has a low acute toxicity. There exists a case report of a man who ingested 8,400 mg pregabalin and eventually fell into a coma, but was managed with supportive care alone until he regained consciousness. For comparison, the maximum recommended therapeutic dose of pregabalin is 300mg twice per day. Another case report details a man's suicide attempt with the co-ingestion of an estimated 11.5 grams of pregabalin and 32 grams of lamotrigine, another anti-epileptic agent which, by blocking sodium channels, lowers glutamate levels, similar to pregabalin. He presented with a lowered level of consciousness and an aggressive demeanor when not sedated. Eventually, he suffered respiratory problems that required intubation and ventilation. After 28 days in the hospital, 19 of which where in the intensive care unit, the man was discharged from the hospital. The man suffered seizures which were attributed to his underlying epilepsy. Pfizer's official package insert for Lyrica states that the highest accidental ingestion of pregabalin during clinical trials was 8 g, with no significant consequences.

As seen in these case reports, Lyrica appears to have a large therapeutic window, and to be relatively benign in overdose compared to other depressants. Combinations with other central nervous system depressants, however, will increase its effects, including respiratory depression and amnesia.

Finally, anecdotal reports of muscle spasms and seizure activity following Lyrica overdoses must be mentioned, although they are not attested in the medical literature. In the literature, seizure activity associated with pregabalin overdoses has been attributed to underlying epilepsy, as that is one of Lyrica's medical indications; however, anecdotal reports insist that high doses can lower the seizure threshold, paradoxically, since low doses are used to raise it.

Lethal dosage

Both rat and mouse oral acute LD50 has been established to be greater than 5000mg/kg. Rat IV LD50 was also established to be greater than 300mg/kg.

Tolerance and addiction potential

Lyrica was initially thought to be non-addictive, with a low abuse potential and low tolerance development. However, recreational use effects of the drug has caused a reevaluation of this assessment. The euphoric effects of the drug and the development of tolerance can lead to tolerance and use of dosages far above the therapeutic range. Pregabalin is indubitably both recreational and addictive.

The withdrawal effects of abrupt cessation of chronic usage include anxiety, insomnia, sweating, muscle spasms, gastrointestinal problems, hot and cold flashes, nausea, a flu-like feeling. There exist reports of patients with history of opioid and/or benzodiazepine abuse who considered pregabalin withdrawal to be worse than benzo or heroin withdrawal.

Legal issues

Pregabalin is regulated as a prescription drug in most countries.

• US: Pregabalin is in Schedule V, the lowest drug schedule. For comparison, benzodiazepines are in schedule IV.
• Norway: Pregabalin is in prescription schedule C, the lowest schedule, although it has been suggested that it be moved to schedule B alongside benzodiazepines.

See also

• Specific Substances
• Gabapentin
• 4-methylpregabalin