r/anhedonia

1P-LSD

• 
• Also known as 1-propanoyl-lysergic acid diethylamide (1-propionyl-LSD).
• Psychoactive substance related to LSD.
• Thought to work by turning into LSD in the body, leading to similar effects.
• 1P-LSD is quickly changed into LSD after you take it, whether by mouth or injection. Studies show it’s almost fully converted, with LSD detectable in blood and urine soon after.
• 1P-LSD’s effects are mainly due to LSD.
• Mainly affects serotonin receptors, especially the 5-HT2A type, which is key for the mind-altering effects like hallucinations and altered perception.
• Interacts with other serotonin and dopamine receptors, but these are less understood for 1P-LSD specifically.
• Can boost brain plasticity, potentially helping with memory and neural growth, similar to LSD.
• It seems likely that 1P-LSD is not addictive, with no signs of compulsive use or withdrawal.
• Tolerance builds quickly, meaning repeated use within a short time reduces its effects, resetting after a few days without use.
• Theoretical risk of heart issues due to effects on 5-HT2B receptors.
• Effects last around 7–12 hours, similar to LSD.
• Blood half-life of about 6.4 hours for 1P-LSD.
• Almost fully absorbed when taken by mouth, and LSD can be detected in urine for up to 80 hours.
• A study published in Drug Testing and Analysis in 2020 found that after oral or intravenous administration of 100 μg 1P-LSD hemitartrate (equivalent to 71.2 μg LSD base), 1P-LSD was detectable in serum for up to 4.16 hours, after which it was completely converted to LSD. This conversion was confirmed by detecting LSD in all serum samples, with the last sampling after approximately 24 hours, and in urine for up to 80 hours. The bioavailability of LSD after oral ingestion of 1P-LSD was close to 100%, indicating efficient conversion.
• LSD (and thus 1P-LSD) binds with high affinity to most serotonin receptors except 5-HT3 and 5-HT4, affecting 5-HT1A, 5-HT2B, 5-HT2C, 5-HT5A, and 5-HT6 at recreational doses. Specific affinity values include:
• 5-HT1A: 0.64 – 7.3 nM
• 5-HT2A: 0.47 – 21 nM
• 5-HT2B: 0.98 – 30 nM
• 5-HT2C: 1.1 – 48 nM
• It also shows significant affinity for dopamine receptors, with Ki values such as D1: 155–340 nM and D2: 61–126 nM, though these are lower than for serotonin receptors.
• The conversion of 1P-LSD to LSD leads to increased glutamate release in the cerebral cortex, specifically in layer V, enhancing excitation.
• 1P-LSD, like LSD, exhibits significant tachyphylaxis, with tolerance developing almost immediately after ingestion, as noted in PsychonautWiki. Tolerance is reduced to half after 5–7 days and returns to baseline after 14 days without further consumption. There is cross-tolerance with other psychedelics, such as mescaline and psilocybin.
• While 1P-LSD itself shows 38% the potency of LSD in mice, as per PsychonautWiki, its effects are primarily due to conversion to LSD.
• The elimination half-life for 1P-LSD is approximately 6.4 hours, while for LSD, it is about 5.7 hours, as per the PubMed entry.
• 1P-LSD is metabolized in the liver by CYP450 enzymes, with the major metabolite being LSD.
• Given its prodrug nature, 1P-LSD’s pharmacological actions mirror those of LSD, with differences primarily in pharmacokinetics, such as rate of absorption and duration.

• Table: Summary of Pharmacological Actions

• Aspect	Details for 1P-LSD (via LSD Conversion)
  Primary Mechanism	Serotonin 5-HT2A receptor agonist, psychedelic effects mediated by this.
  Receptor Affinity	High affinity for 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C; moderate for dopamine.
  Neurotransmitter Effects	Increases glutamate release, enhances D2–5-HT2A signaling.
  Psychoplastogenic Effects	Promotes neural plasticity, binds to TrkB receptor.
  Tolerance	Rapid tolerance, resets after 3–4 days; cross-tolerance with psychedelics.
  Addiction Liability	Non-addictive, no withdrawal, low abuse potential.
  Potency	Effects at low doses (via LSD), 200x psilocybin, 5,000x mescaline potency.
  Duration	7–12 hours, onset 0.4–1.0 hours.
  Metabolism	Converted to LSD, liver metabolism by CYP450, 13% urine elimination in 24h.
  Potential Risks	Theoretical cardiac risk due to 5-HT2B agonism, needs more research.

• Condition	Bioavailability	Onset of Effects	Duration	Notes
  Empty Stomach	Likely close to 100%	Faster, more intense	Potentially shorter	Based on user reports and inferred from light meal study.
  Light Meal (Study)	Close to 100% (92-100%)	Not specified, likely slow	Not specified	Grumann et al. (2020), experiments started 2 hours after light breakfast.
  Full Stomach	Possibly high, data limited	Slower, less intense	Potentially longer	Inferred from LSD studies and user reports, no direct data for 1P-LSD.