generation run 2026-04-21
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21 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | WebSearch/DEA | methamphetamine Schedule II DEA legal status US UK Class A Australia | 10 | 3 | Legal scheduling information |
| 2 | PubMed | methamphetamine TAAR1 trace amine receptor agonist | 8 | 3 | Primary structural biology of METH-TAAR1 interaction and TAAR1 functional studies |
| 3 | PubMed | methamphetamine neurotoxicity dopaminergic serotonergic brain damage oxidative stress | 5 | 3 | Reviews of molecular mechanisms of METH-induced neurotoxicity |
| 4 | PubMed | methamphetamine receptor binding affinity dopamine norepinephrine serotonin transporter Ki | 2 | 0 | Not directly measuring METH binding affinities at primary targets |
| 5 | WebSearch | methamphetamine history synthesis 1893 Nagayoshi Nagai 1919 Akira Ogata | 10 | 1 | Historical data not available in PubMed |
| 6 | PubMed | methamphetamine pharmacokinetics human bioavailability half-life metabolism | 8 | 4 | Primary PK data directly for methamphetamine in human subjects |
| 7 | PMC | methamphetamine binding affinity Ki DAT NET SERT | — | 1 | Primary source for human transporter binding affinities of methamphetamine |
| 8 | PubChem | methamphetamine by name | 1 | 1 | Primary chemical identity data for d-methamphetamine (active enantiomer) |
| 9 | PubMed | methamphetamine tolerance sensitization dopamine receptor downregulation | 3 | 2 | Documents METH sensitization and lasting vulnerability to relapse psychosis |
| 10 | OpenAlex | methamphetamine mechanism of action dopamine neurotoxicity | 10 | 1 | High-citation comprehensive methamphetamine review |
| 11 | ClinicalTrials.gov | methamphetamine treatment use disorder | 10 | 4 | Active and completed clinical trials for METH use disorder treatment |
| 12 | StatPearls/NCBI Bookshelf | methamphetamine pharmacology metabolism interactions | — | 3 | Clinical reference for FDA-approved therapeutic use and drug interaction data |
| 13 | PubMed | methamphetamine monoamine transporter inhibition dopamine norepinephrine serotonin release substrate | 7 | 2 | Foundational mechanism papers on amphetamine/METH reverse transport |
| 14 | WebSearch | methamphetamine UN 1971 Convention Psychotropic Substances Schedule II EU legal | 9 | 1 | — |
| 15 | PMC/OpenAlex | methamphetamine dopamine transporter PET imaging abstinent users | — | 1 | — |
| 16 | WebSearch | methamphetamine Canada CDSA Schedule I | 10 | 1 | — |
| 17 | PubMed | methamphetamine MAOI interaction fatal serotonin toxicity | 1 | 1 | — |
| 18 | PubMed | methamphetamine MAO inhibitor monoamine oxidase weak activity | 2 | 1 | — |
| 19 | PubMed | methamphetamine controlled dose human subjective effects cardiovascular dose response | 8 | 3 | — |
| 20 | PubMed | methamphetamine hemorrhagic stroke intracerebral hemorrhage young adult | 2 | 2 | — |
| 21 | PMC/OpenAlex | methamphetamine brain structural abnormalities MRI neuroimaging | — | 1 | — |
83 claims by section — every cited sentence, checked against its source
safety29 · 25 ok
Methamphetamine is a significant cause of stroke in adults under 45partially supported
Methamphetamine is a putative cause of strokes in younger people (below age 45). Review of epidemiology, mechanisms and case reports. jnnp-2017-316071
In one emergency department series, methamphetamine was implicated in 72% of agitated patient presentationssupported
202 agitated ED patients. METH toxicity in 146 (72%), cocaine 14%, psychiatric illness 10%. pmid:9696171
Droperidol demonstrated superiority to lorazepam in a randomized comparison for methamphetamine-induced agitationsupported
Droperidol superior to lorazepam for chemical restraint in METH-induced agitation. pmid:9696171
Serotonin syndrome triggered by methamphetamine combined with serotonergic agents requires discontinuation of offending drugs and administration of cyproheptadine or chlorpromazine; benzodiazepines for supportive care.supported
Treatment: discontinue agent, cyproheptadine, chlorpromazine, or benzodiazepine. pmid:16227063
Cardiovascular complications are the second leading cause of death in methamphetamine users:supported
Cardiovascular complications are the second leading cause of death in methamphetamine abusers. j.hlc.2015.10.019
Claim in safety — inconclusiveinconclusiveworking →
Pulmonary arterial hypertension (PAH): Documented epidemiological association with hemodynamic severity comparable to idiopathic PAH; reduced carboxylesterase 1 (CES1) activity may contribute to endothelial apoptosis via oxidative stresssupported
94.4% of METH-PAH patients had CES1 variant (rs115629050). Reduced CES1 promotes endothelial apoptosis. ajplung.00453.2016
Yen et al. documented 7 consecutive cases of stroke following methamphetamine inhalation (mean age 32 years): 5 hemorrhagic (lobar, caudate, and putaminal intracerebral hemorrhage) and 2 ischemic, all occurring within 3 days of drug usesupported
7 patients with stroke following methamphetamine inhalation. Mean age 32 years. 5 hemorrhagic, 2 ischemic strokes. Strokes occurred within 3 days after drug use. Lobar, caudate or putaminal intracerebral hemorrhage. pmid:8137834
Chronic methamphetamine use produces persistent reductions in striatal dopamine transporter density (23–25% in caudate and putamen by PET), gray-matter deficits in cingulate and limbic cortex (11.3%), hippocampal volume reduction (7.8%), and white-matter hypertrophy (7.0%)supported
PET showed DAT density reductions of 23-25% in caudate/putamen of abstinent METH users after ~3 years abstinence vs controls. pmid:9763484
Chronic methamphetamine use produces persistent reductions in striatal dopamine transporter density (23–25% in caudate and putamen by PET), gray-matter deficits in cingulate and limbic cortex (11.3%), hippocampal volume reduction (7.8%), and white-matter hypertrophy (7.0%)supported
MRI showed 11.3% gray-matter deficit in cingulate/limbic/paralimbic cortex, 7.8% smaller hippocampal volumes, 7.0% white-matter hypertrophy in chronic MA users vs controls. pmid:15229250
Pflügner et al. documented adverse neonatal outcomes in 102 neonates born to methamphetamine-using mothers at a single center in Germany.supported
102 neonates from mothers with antenatal METH consumption admitted to University Hospital Leipzig 2004-2015. Documents neonatal outcomes from prenatal METH exposure. s-0043-121991
Claim in safety — inconclusiveinconclusiveworking →
Sato demonstrated that chronic methamphetamine use produces a lasting vulnerability: even after prolonged abstinence, administration of small methamphetamine doses — or non-drug stressors including sleep deprivation and psychological stress — reliably triggered acute psychotic recurrence indistinguishable from the initial episodesupported
Chronic MAP abuse produces a lasting vulnerability to paranoid delusional psychosis with hallucinations similar to schizophrenia. Reuse of MAP, alcohol, and nonspecific stressors can trigger acute recurrence. pmid:1632581
Sato demonstrated that chronic methamphetamine use produces a lasting vulnerability: even after prolonged abstinence, administration of small methamphetamine doses — or non-drug stressors including sleep deprivation and psychological stress — reliably triggered acute psychotic recurrence indistinguishable from the initial episodepartially supported
16/21 experienced relapse with small METH doses. Haloperidol (3 mg/day) prevented acute provocation. pmid:6860719
Haloperidol (3 mg/day) prevented provocation in experimental challenge paradigms, confirming the dopaminergic mechanism.supported
Haloperidol (3 mg/day) prevented acute provocation. Suggests dopaminergic supersensitivity mechanism. pmid:6860719
Persistent psychosis is associated with more severe cognitive impairment in methamphetamine users, suggesting that psychosis vulnerability may serve as a clinical marker for underlying neurotoxic damage.supported
Persistent psychosis indicates more severe cognitive impairment. j.drugalcdep.2014.12.035
Claim in safety — inconclusiveinconclusiveworking →
Neuroimaging confirms persistent DAT reductions of 23–25% after years of abstinence — a finding that reflects structural terminal loss rather than reversible pharmacological tolerancesupported
PET showed DAT density reductions of 23-25% in caudate/putamen of abstinent METH users after ~3 years abstinence vs controls. Raises possibility of increased risk for parkinsonism. pmid:9763484
The evidence base for pharmacological treatment of methamphetamine withdrawal remains poorsupported
Insufficient knowledge regarding the withdrawal syndrome of methamphetamine and appropriate management may contribute to low treatment attendance. j.1465-3362.2010.00240.x
Mirtazapine, naltrexone, and bupropion show potential efficacy signals across acute and protracted withdrawal phasessupported
Potential efficacy for MA withdrawal noted for mirtazapine, naltrexone, bupropion and repetitive transcranial magnetic stimulation during acute, early protracted and late protracted withdrawal phases. add.16093
No FDA-approved medication exists for methamphetamine use disordersupported
No established pharmacotherapy for AMPH/MA dependence. s40263-020-00711-x
No FDA-approved medication exists for methamphetamine use disordersupported
No established pharmacotherapy for METH dependence. dar.12048
Claim in safety — inconclusiveinconclusiveworking →
Mechanisms include fatal hypertensive crisis from massive norepinephrine accumulation, serotonin toxicity from combined monoamine release and degradation blockade, and secondary intracranial hemorrhagesupported
Fatalities reported for MAOIs + methamphetamine. Hypertensive urgency/emergency and intracranial hemorrhage documented. Serotonin toxicity suspected with MAOI + methamphetamine. s40263-025-01256-7
The additive serotonergic burden creates risk for serotonin syndrome — a potentially fatal condition presenting as hyperthermia, rigidity, clonus, and autonomic instabilitysupported
Serotonin syndrome typically occurs within hours of addition of new serotonergic agent or abuse of stimulants such as MDMA or methamphetamine. pmid:16227063
Concurrent MAOI use: Fatal hypertensive crisis, serotonin toxicity, and intracranial hemorrhage are documented consequencessupported
Fatalities reported for MAOIs + methamphetamine. Hypertensive urgency/emergency and intracranial hemorrhage documented. Serotonin toxicity suspected with MAOI + methamphetamine. s40263-025-01256-7
History of drug-induced psychosis: Sensitization produces lasting vulnerability to psychotic recurrencesupported
Chronic MAP abuse produces a lasting vulnerability to paranoid delusional psychosis with hallucinations similar to schizophrenia. pmid:1632581
Concurrent serotonergic medications: SSRIs, SNRIs, tramadol — serotonin syndrome risksupported
Serotonin syndrome typically occurs within hours of addition of new serotonergic agent or abuse of stimulants such as MDMA or methamphetamine. pmid:16227063
Pregnancy: Prenatal exposure associated with adverse neonatal outcomessupported
102 neonates from mothers with antenatal METH consumption admitted to University Hospital Leipzig 2004-2015. Documents neonatal outcomes from prenatal METH exposure. s-0043-121991
neuroscience14 · 12 ok
Microglial activation: Sustained neuroinflammatory response amplifies ongoing neurodegenerative processessupported
Methamphetamine neurotoxicity includes... activated astroglial and microglial cells. Mechanisms:... microglial activation. s0074-7742(09)88005-7
Haloperidol (3 mg/day) prevented provocation in experimental challenge studies, implicating dopaminergic supersensitivity as the mechanism.supported
Haloperidol (3 mg/day) prevented acute provocation. Suggests dopaminergic supersensitivity mechanism. pmid:6860719
Rothman et al. proposed a dual-deficit model in which methamphetamine withdrawal involves simultaneous depletion of both dopaminergic and serotonergic neurotransmissionsupported
Dual-deficit model of stimulant withdrawal: DA dysfunction underlies anhedonia and psychomotor disturbances; 5-HT dysfunction leads to depressed mood and lack of impulse control. pmid:12105089
Claim in neuroscience — inconclusiveinconclusiveworking →
Low doses enhance executive function — particularly attention and working memory — selectively in individuals with depressed baseline performance, consistent with an inverted-U dose-response relationship between prefrontal dopamine levels and cognitive performance.supported
30 mg IV METH improved attention/information processing speed and working memory (choice reaction time, 1-back, 2-back) in METH-dependent individuals displaying poorer cognitive performance at baseline. Those with high baseline performance showed similar or decreased performance. j.pnpbp.2010.11.034
Oxidative stress: Excess cytosolic dopamine undergoes auto-oxidation generating reactive oxygen species (ROS), compounded by mitochondrial dysfunctionsupported
Oxidative stress, excitotoxicity and mitochondrial dysfunction play major roles in METH neurotoxicity, producing monoaminergic depletions. pmid:16796384
Oxidative stress: Excess cytosolic dopamine undergoes auto-oxidation generating reactive oxygen species (ROS), compounded by mitochondrial dysfunctionsupported
Mechanisms: oxidative stress, transcription factor activation, DNA damage, excitotoxicity, blood-brain barrier breakdown, microglial activation. s0074-7742(09)88005-7
McCann et al. used PET with [¹¹C]WIN-35,428 to demonstrate DAT density reductions of 23–25% in the caudate nucleus and putamen of abstinent methamphetamine users, persisting after approximately 3 years of abstinencesupported
PET showed DAT density reductions of 23-25% in caudate/putamen of abstinent METH users after ~3 years abstinence vs controls. pmid:9763484
Thompson et al. reported MRI-based structural findings in 22 chronic methamphetamine users versus matched controls: 11.3% gray-matter deficit in cingulate, limbic, and paralimbic cortex; 7.8% smaller hippocampal volumes (significantly correlated with memory task performance); and 7.0% white-matter hypertrophy, the latter possibly reflecting adaptive gliosis.supported
MRI showed 11.3% gray-matter deficit in cingulate/limbic/paralimbic cortex, 7.8% smaller hippocampal volumes, 7.0% white-matter hypertrophy in chronic MA users vs controls. Hippocampal deficits correlated with memory performance. pmid:15229250
Claim in neuroscience — inconclusiveinconclusiveworking →
Even after years of abstinence, administration of small methamphetamine doses — or exposure to non-drug stressors — reliably triggered acute psychotic episodes identical to the initial drug-induced psychosissupported
Chronic MAP abuse produces a lasting vulnerability to paranoid delusional psychosis with hallucinations similar to schizophrenia. Reuse of MAP, alcohol, and nonspecific stressors can trigger acute recurrence. pmid:1632581
TAAR1 therapeutic potential: Selective TAAR1 agonists may reduce methamphetamine self-administration without the adverse effects of dopamine antagonists. The structural basis for TAAR1-methamphetamine recognition is now characterized, but clinical translation to human addiction treatment remains untested.supported
TAAR1 is an established METH target relevant to drug addiction and neurological disorders. Cryo-EM structures of human TAAR1 bound to methamphetamine. s41586-023-06775-1
β2AR-TAAR1 interaction: Wang et al. identified β2AR as mechanistically distinct from TAAR1 in mediating methamphetamine's effects on NAc circuitry. Whether combined TAAR1 agonism and β2AR antagonism offers synergistic therapeutic benefit is unknown.supported
Cryo-EM study demonstrating β2-adrenergic receptor as a novel METH target via Gs-mediated cAMP signaling, structurally distinct from TAAR1. Beta2AR inhibition via zenidolol elevates GluA1-Ser831 phosphorylation in NAc D2-MSNs. j.celrep.2025.116337
Reversibility of DAT loss: McCann et al. showed 23–25% DAT reductions persisting after 3 years of abstinence. Whether further recovery occurs over decades, and whether this deficit translates to clinically increased Parkinson's disease risk, remains unresolved.supported
PET showed DAT density reductions of 23-25% in caudate/putamen of abstinent METH users after ~3 years abstinence vs controls. Raises possibility of increased risk for parkinsonism. pmid:9763484
pharmacology12 · 12 ok
As a lipophilic amine, it enters presynaptic terminals via DAT, NET, and SERT and drives non-exocytotic efflux of dopamine, norepinephrine, and serotonin through transporter reversalsupported
Methamphetamine caused efflux at concentrations similar to those inhibiting transport (substrate-type releaser). Cocaine, mazindol, citalopram, nisoxetine failed to stimulate efflux despite inhibiting uptake. pmid:7700252
As a lipophilic amine, it enters presynaptic terminals via DAT, NET, and SERT and drives non-exocytotic efflux of dopamine, norepinephrine, and serotonin through transporter reversalsupported
Amphetamine acts at the vesicular level where it redistributes dopamine to the cytosol, promoting reverse transport and dopamine release from synaptic vesicles. pmid:7751968
The selectivity profile — NET (Ki ≈ 110 nM) > DAT (Ki ≈ 460 nM) >> SERT (Ki ≈ 31,740 nM) — produces a predominantly dopaminergic and noradrenergic pharmacological signature, distinguishing methamphetamine from serotonin-preferring releasers such as mdma.supported
Methamphetamine Ki values: human DAT 0.46 ± 0.06 μM (460 nM); human NET 0.11 ± 0.01 μM (110 nM); human SERT 31.74 ± 2.40 μM (31,740 nM). Methamphetamine and amphetamine are most potent at NET and much less potent at SERT. pmid:16515684
This cytosolic pool becomes available for DAT-mediated reverse transport, amplifying extracellular dopamine concentrations beyond what DAT reversal alone would producesupported
Amphetamine acts at the vesicular level where it redistributes dopamine to the cytosol, promoting reverse transport and dopamine release from synaptic vesicles. pmid:7751968
This cytosolic pool becomes available for DAT-mediated reverse transport, amplifying extracellular dopamine concentrations beyond what DAT reversal alone would producesupported
METH-induced efflux 50-60% in DAT+VMAT2 vs 20% when VMAT2 blocked during loading. pmid:15102929
Wilhelm et al. demonstrated that the EC₅₀ for [³H]dopamine release from DAT/VMAT2 co-expressing HEK-293 cells is 33.8 μM with intact VMAT2 function and 3.2 μM when VMAT2 is independently blocked, illustrating the quantitative contribution of VMAT2-mediated vesicular redistribution.supported
Methamphetamine EC50 for DAT-mediated [3H]DA release: 33.8 μM (hDAT+hVMAT2 cotransfected cells without VMAT2 blockade) or 3.2 μM with VMAT2 blocked by DHTB. pmid:15102929
Additional molecular targets include trace amine-associated receptor 1 (TAAR1), a Gs-coupled GPCR where methamphetamine acts as an agonist, and β2-adrenergic receptors, activated through Gs-mediated cAMP signaling with a structural binding mode distinct from TAAR1supported
TAAR1 is an established METH target relevant to drug addiction and neurological disorders. Cryo-EM structures of human TAAR1 bound to methamphetamine and β-PEA. s41586-023-06775-1
Additional molecular targets include trace amine-associated receptor 1 (TAAR1), a Gs-coupled GPCR where methamphetamine acts as an agonist, and β2-adrenergic receptors, activated through Gs-mediated cAMP signaling with a structural binding mode distinct from TAAR1supported
Cryo-EM study demonstrating β2-adrenergic receptor as a novel METH target via Gs-mediated cAMP signaling, structurally distinct from TAAR1. j.celrep.2025.116337
Methamphetamine also weakly inhibits monoamine oxidase A (Ki = 17.2 μM) — approximately 3-fold weaker than amphetamine (Ki = 5.3 μM) and orders of magnitude weaker than clinical MAO inhibitorssupported
Methamphetamine Ki for MAO-A inhibition = 17.2 μM. Ranking: amphetamine (5.3 μM) > methamphetamine (17.2 μM) >> phentermine (196 μM). Weak MAO-A inhibition confirmed. pmid:25455893
Methamphetamine demonstrates high bioavailability across routes: 90.3 ± 10.4% smoked and 67.2 ± 3.1% oralsupported
Bioavailability of smoked methamphetamine was 90.3 +/- 10.4%. Oral bioavailability calculated as 67.2 +/- 3.1%. pmid:8104133
The elimination half-life is 11.1 hours (smoked, geometric mean) to 12.2 hours (intravenous), supporting the prolonged duration of subjective effectssupported
Plasma half-life 11.1 hr smoked, 12.2 hr IV. pmid:8104133
Approximately 37–45% of a dose is excreted unchanged in urine, with 62% of an oral dose eliminated renally within 24 hourspartially supported
37-45% excreted in urine as methamphetamine, 7% as amphetamine. pmid:8104133
clinical-evidence7 · 6 ok
The evidence base for methamphetamine withdrawal treatment remains poorsupported
Insufficient knowledge regarding the withdrawal syndrome of methamphetamine and appropriate management may contribute to low treatment attendance. j.1465-3362.2010.00240.x
Li and Shoptaw reviewed available evidence across acute and protracted withdrawal phases, identifying potential efficacy signals for mirtazapine, naltrexone, bupropion, and repetitive transcranial magnetic stimulation (rTMS).supported
Potential efficacy for MA withdrawal noted for mirtazapine, naltrexone, bupropion and repetitive transcranial magnetic stimulation during acute, early protracted and late protracted withdrawal phases. add.16093
An active randomized controlled trial (NCT01309470) is evaluating lisdexamfetamine — an agonist substitution approach — for acute methamphetamine withdrawal in inpatient settingssupported
Protocol for RCT of lisdexamfetamine (LDX) as agonist therapy for acute METH withdrawal. bmjopen-2025-107242
The British Association for Psychopharmacology (BAP) 2026 consensus guidelines include methamphetamine/amphetamine dependence in their pharmacological management recommendations, confirming the absence of established pharmacotherapy while providing current clinical guidance for management.supported
BAP consensus guidelines covering pharmacological management of dependence on multiple substances including amphetamine and methamphetamine. International expert panel. 02698811251399593
Systematic reviews confirm this therapeutic gap despite decades of clinical investigation.supported
No established pharmacotherapy for AMPH/MA dependence. Comprehensive assessment of research literature on pharmacotherapy. s40263-020-00711-x
Systematic reviews confirm this therapeutic gap despite decades of clinical investigation.supported
No established pharmacotherapy for METH dependence. dar.12048
Claim in clinical-evidence — inconclusiveinconclusiveworking →
summary6 · 5 ok
Methamphetamine ((2S)-N-methyl-1-phenylpropan-2-amine) is a potent substituted amphetamine and monoamine releasing agent with an oral bioavailability of 67.2% and an elimination half-life of 10–12 hourssupported
Oral bioavailability calculated as 67.2 +/- 3.1%. Plasma half-life 11.1 hr smoked, 12.2 hr IV. pmid:8104133
Claim in summary — inconclusiveinconclusiveworking →
Methamphetamine enters presynaptic terminals as a substrate at DAT (Ki ≈ 460 nM), NET (Ki ≈ 110 nM), and SERT (Ki ≈ 31,740 nM), driving non-exocytotic monoamine efflux through reverse transportsupported
Methamphetamine Ki values: human DAT 0.46 ± 0.06 μM (460 nM); human NET 0.11 ± 0.01 μM (110 nM); human SERT 31.74 ± 2.40 μM (31,740 nM). pmid:16515684
It simultaneously disrupts vesicular dopamine storage via VMAT2, redistributing cytosolic dopamine for DAT-mediated effluxsupported
Amphetamine acts at the vesicular level where it redistributes dopamine to the cytosol, promoting reverse transport and dopamine release from synaptic vesicles. pmid:7751968
Cardiovascular toxicity — hypertension, cardiomyopathy, pulmonary arterial hypertension, stroke — constitutes the primary organ-system risksupported
Cardiovascular complications are the second leading cause of death in methamphetamine abusers. Includes hypertension, aortic dissection, acute coronary syndromes, pulmonary arterial hypertension and cardiomyopathy. j.hlc.2015.10.019
Neurotoxicity produces persistent dopamine transporter reductions of 23–25% in the striatum after years of abstinencesupported
PET showed DAT density reductions of 23-25% in caudate/putamen of abstinent METH users after ~3 years abstinence vs controls. pmid:9763484
receptor-pharmacology5 · 4 ok
Ligand binding assays at human recombinant transporters established the following selectivity profile for d-methamphetamine:supported
Methamphetamine Ki values: human DAT 0.46 ± 0.06 μM (460 nM); human NET 0.11 ± 0.01 μM (110 nM); human SERT 31.74 ± 2.40 μM (31,740 nM). pmid:16515684
Wilhelm et al. characterized methamphetamine's dual action at DAT and VMAT2 in HEK-293 cells co-expressing both transporterssupported
Methamphetamine EC50 for DAT-mediated [3H]DA release: 33.8 μM (hDAT+hVMAT2 cotransfected cells without VMAT2 blockade) or 3.2 μM with VMAT2 blocked by DHTB. pmid:15102929
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
TAAR1 activation opposes dopaminergic reward signaling: functional TAAR1 mediates aversive effects of methamphetamine and suppresses voluntary intake, while mice lacking functional TAAR1 exhibit binge-level methamphetamine consumption and increased excitability of dorsal raphe serotonin neuronssupported
TAAR1 function suppresses MA reward sensitivity and binge-level intake. Mice lacking functional TAAR1 show binge-level MA consumption. s41386-025-02063-w
Wang et al. demonstrated via cryo-EM and mutagenesis that methamphetamine activates β2-adrenergic receptors (β2AR) through Gs-mediated cAMP signaling, with a structural binding mode distinct from TAAR1supported
Cryo-EM study demonstrating β2-adrenergic receptor as a novel METH target via Gs-mediated cAMP signaling, structurally distinct from TAAR1. j.celrep.2025.116337
chemistry3 · 2 ok
Claim in chemistry — inconclusiveinconclusiveworking →
L-methamphetamine achieves complete (approximately 100%) oral bioavailability without producing significant psychoactive effects and is used in some over-the-counter nasal decongestants (e.g., Vicks VapoInhaler).supported
R-methamphetamine: complete bioavailability and pharmacologic inactivity for all oral doses 1-10 mg. Linear pharmacokinetics observed. ftd.0b013e3181db82f2
The compound is highly lipophilic, reflected in a large volume of distribution (3.2–3.7 L/kg), which enables rapid passage across the blood-brain barrier.supported
Volume of distribution 3.24 L/kg smoked, 3.73 L/kg IV. pmid:8104133
comparative-pharmacology3 · 2 ok
Amphetamine is the more potent MAO-A inhibitor (Ki = 5.3 μM vs 17.2 μM), though both are weak inhibitors relative to clinical MAOIs.supported
Methamphetamine Ki for MAO-A inhibition = 17.2 μM. Ranking: amphetamine (5.3 μM) > methamphetamine (17.2 μM) >> phentermine (196 μM). Weak MAO-A inhibition confirmed. pmid:25455893
Methamphetamine is 200–500-fold less potent at SERT relative to NET, whereas MDMA's SERT/DAT selectivity ratio is inverted.supported
Methamphetamine Ki values: human NET 0.11 ± 0.01 μM (110 nM); human SERT 31.74 ± 2.40 μM (31,740 nM). Methamphetamine and amphetamine are most potent at NET and much less potent at SERT. pmid:16515684
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
pharmacokinetic-detail3 · 2 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Data: Cook et al. 1993; urinary excretion: StatPearls.supported
37-45% excreted in urine as methamphetamine, 7% as amphetamine. pmid:8104133
Carboxylesterase 1 (CES1) participates in methamphetamine metabolism; loss-of-function CES1 variants may increase the risk of methamphetamine-associated pulmonary arterial hypertension through impaired metabolism and endothelial oxidative stresssupported
CYP2D6 and carboxylesterase 1 (CES1) involved in METH metabolism. 94.4% of METH-PAH patients had CES1 variant (rs115629050). Reduced CES1 promotes endothelial apoptosis. ajplung.00453.2016
history1 · 0 ok
Claim in history — inconclusiveinconclusiveworking →