1p-LSD:Everything You Need To Know and What No One Tells You

What is 1p-LSD?

1P-LSD stands for 1-propionyl-lysergic acid diethylamide. It’s a derivative of LSD — which essentially means it’s a modified version of the classic LSD-25 that Albert Hofmann discovered in 1943.

This molecule is differentiated from LSD by a propionyl group attached to the nitrogen molecule in the indole portion of LSD. The central indole molecule of LSD is the characterizing element of the molecule that’s shared with all other tryptamine-based psychedelics (such as DMT or psilocybin).

1P-LSD itself is only mildly psychedelic. It has a 67-fold less binding affinity for the 5-HT1A receptors, 13-fold less activity at the 5-HT2A receptors, and a 3.5-fold increase at h5-HT2C receptors than LSD-25 [1].

However, 1P-LSD is a prodrug for LSD, which means it’s converted to LSD by the liver, which then goes on to produce psychoactive effects [2]. The bioavailability of LSD from 1P-LSD is nearly 100%.

History and Culture

1P-LSD first appeared on the online research chemical market in January 2015.[1] Although it was likely discovered in an academic setting, it is unknown who first synthesized 1P-LSD, as the substance does not appear in any academic literature pre-dating its arrival on the research chemical market.[3]

Interestingly, the future usage of 1-alkylated lysergamide derivatives as a means to bypass controlled substance laws banning LSD as a precursor was foreseen in a DEA report from 1988:

“ …a reduction in hallucinogenic activity may become acceptable to the U.S. clandestine chemist when he notes that lysergic acid amide is listed as a Schedule III substance in the CFR; therefore, structurally similar substances of this compound are exempted from the CsA amendment.
A lucid argument can then be made that lysergic acid N,N-dimethylamide is derived from lysergic acid amide rather than LSD. Carrying this theme to the next logical step one would then assume that the 1-alkyl and 1-acyl derivatives of the N,N-dimethyl isomer would also not be controlled by the CsA amendment.

Chemistry

1P-LSD is a semisynthetic compound of the lysergamide family. It is similar to LSD and is named for the propionyl group bound to the nitrogen of the polycyclic indole group of LSD. Propionyl consists of the carbonyl chain CH₃CH₂CO- bound to an amino group.

1P-LSD is homologous to ALD-52, which holds an acetyl group bound to the nitrogen instead of the propionyl group bound at the same location. The structure of 1P-LSD contains a polycyclic group featuring a bicyclic hexahydro indole bound to a bicyclic quinoline group. At carbon 8 of the quinoline, an N,N-diethyl carboxamide is bound.

Pharmacology

Based on its structural similarity to LSD, 1P-LSD likely acts as a partial agonist at the 5-HT2A receptor. The psychedelic effects are thought to primarily come from its efficacy at the 5-HT2A receptors distributed throughout the brain.

1P-LSD also likely displays binding activity at a wide range of monoamine receptors, such as those for dopamine and norepinephrine. However, there is currently no experimental data to support these claims.

It has been theorized that 1P-LSD may act as a prodrug for LSD. While 1P-LSD shows only 38% the potency of LSD in mice, LSD is detected via LC-MS when 1P-LSD is incubated in human serum. Follow-up studies are currently being conducted to compare the affinity and selectivity of LSD and 1P-LSD at 5-HT receptors, and to determine whether 1P-LSD is hydrolyzed to LSD in vivo.[3] Otherwise, it is possible that 1P-LSD possesses intrinsic activity.

Prior to the publishing of the above-cited research, medicinal chemist and psychedelics researcher David E. Nichols reportedly commented on the potential 1P-LSD serotonin receptor binding dynamics in private correspondence:

“ I am sure that the 1-propionyl would also hydrolyze off of an indole, but I don’t know whether in vivo conditions would work. In a chemistry lab, you can get off an N-benzoyl, so an N-propionyl will probably come off too. But in the body? I don’t know the answer to that. The compound would not be active as the N-propionyl however. The way that LSD docks into the 5-HT2A receptor, the indole NH hydrogen bonds to serine 5.46. With the propionyl, it won’t fit into the receptor. ”
— David E. Nichols.[5]
A 2020 study on two human male volunteers found that the levels of 1P-LSD in the serum after administration quickly diminished within the first hour while LSD has been found consistently during the experiment, which further supports the prodrug theory.[6] The study also found that LSD’s bioavailability after oral ingestion of 1P-LSD was close to 100%.

Additionally, it has been theorized that 1P-LSD may act as a prodrug of LSD. This is further concluded via a LC-MS where LSD is detected when 1P-LSD is incubated in human serum. Thus far it remains unclear if 1P-LSD is hydrolyzed to LSD in vivo.

Effects of 1p-LSD

The effects profile of 1P-LSD is not well defined in the scientific literature. It is generally thought to be comparable to that of LSD. A study in 2020 found that intravenous administration of 1P-LSD has a somewhat shorter duration than LSD in humans. 1P-LSD is present for a very short time (4 hours) prior to being completed metabolized to LSD. The 2020 study found that it is not possible to reliably distinguish between the oral uptake of LSD and 1P-LSD until unique metabolites are detected by sensitive analytical methods.

Qualitative effects were similar when comparing intravenous and oral delivery between the two drugs. The slow onset after intravenous application for 1P-LSD appears to be due to the slowed passage of LSD into the central nervous system compared to other serotonergic hallucinogens. Some users in the study reported an absence of “bad drug effects”, but this is likely due to the setting than as a characteristic of 1P-LSD.

Physical Effects

• Stimulation – 1P-LSD is usually regarded as very energetic and stimulating without being forced. For example, when taken in any environment it will usually encourage physical activities such as running, walking, climbing or dancing. In comparison, other more commonly used psychedelics such as psilocybin which are generally sedating and relaxed.
• Spontaneous bodily sensations – The “body high” of 1P-LSD can be characterized as proportionally very intense in comparison to its accompanying visual and cognitive effects. It behaves as a euphoric, fast-moving, sharp and location-specific tingling sensation. For some, it is manifested spontaneously at different, unpredictable points throughout the trip, but for most, it maintains a steady presence that rises with the onset and hits its limit once the peak has been reached. At moderate to high doses of 1P-LSD, this sensation often approaches its highest level and can become so overwhelming that people may find themselves debilitated with pleasurable sensations.
  • Physical euphoria – It should be noted that this effect is not as reliably induceable as it is with substances like stimulants or entactogens, and can just as easily manifest as extreme physical discomfort without any apparent reason.
• Tactile enhancement – Feelings of enhanced tactile sensations are consistently present at moderate levels throughout most 1P-LSD experiences. If level 8A geometry is reached, an intense sensation of suddenly becoming aware of and being able to feel every single nerve ending across a person’s entire body all at once is consistently present.
• Stamina enhancement – This is generally mild in comparison to the stamina enhancement produced by traditional stimulants.
• Appetite suppression
• Bodily control enhancement
• Difficulty urinating
• Excessive yawning – This effect is significantly less pronounced than it is with psilocybin and its related compounds, the four-position substituted tryptamines.
• Nausea – Mild nausea is occasionally reported when consumed in moderate to high dosages and either passes instantly soon after the user has vomited or gradually fades by itself as the peak sets in.
• Increased blood pressure^{[citation needed]}
• Increased heart rate^{[citation needed]}
• Increased perspiration
• Muscle contractions
• Muscle spasms
• Pupil dilation
• Increased salivation
• Vasoconstriction – Vasoconstriction may lead to users feeling cold, especially in the extremities.
• Seizure – The likelihood is largely extrapolated from the seizures that have been reported from the use of LSD. It is thought to mainly be a risk in those who are genetically predisposed to them, particularly while accompanied by physically taxing conditions such as states of dehydration, fatigue, undernourishment or overheating.

Cognitive Effects

• Analysis enhancement – This effect is consistent in its manifestation and introspection dominant.
• Anxiety & Paranoia – This effect is not as common at low to moderate doses and is less likely to occur when the basic rules of set and setting are taken into account. It should be noted that this inconsistently induced effect is seemingly more likely to manifest when used with cannabis. This combination should be used with extreme caution if one is not experienced with psychedelics, meaning that the user should adequately pace themselves with a fraction of their usual amount. It is commonly reported that psychedelics can to a certain extent counteract some of the perceived mental cloudiness or intoxicating effects of THC causing the user to in turn use more cannabis than is needed which can often lead to an overwhelmingly anxious headspace or a “bad trip”.
• Catharsis
• Conceptual thinking
• Creativity enhancement
• Emotion enhancement
• Novelty enhancement
• Personal bias suppression
• Personal meaning enhancement
• Focus enhancement – This effect is experienced exclusively on low or threshold dosages and feels less forced than it does with stimulants.
• Immersion enhancement
• Suggestibility enhancement
• Cognitive euphoria – This component is, generally speaking less consistent and pronounced than it is with substances like psilocybin and MDMA. The mental euphoria experienced on LSD is usually simply due to an enhancement of the user’s current psychological and emotional state coupled with its more regularly occurring effect, physical euphoria.
• Delusion
• Déjà vu
• Increased libido
• Increased music appreciation
• Increased sense of humor
  • Laughter fits – This can manifest prominently during a 1P-LSD experience, particularly during the come up phase, often resulting in bouts of uncontrollable giggles and laughter that can form a feedback loop if around others who are also under the influence.
• Memory suppression
  • Ego death
• Thought acceleration
• Thought disorganization
• Thought loops
• Time distortion
• Wakefulness

Overdose

1P-LSD has no known toxic dose. However, higher doses increase the risk of adverse psychological reactions. These reactions include anxiety, delusions, panic attacks and, more rarely, seizures. Medical attention is usually not needed except in the case of severe psychotic episodes or the ingestion of fake acid (such as 25i-NBOMe or DOB). Administration of benzodiazepines or antipsychotics can help to relieve the acute negative cognitive effects of 1P-LSD.

Dependence and abuse potential

Although no formal studies have been conducted, it is assumed that like LSD itself, 1P-LSD is non-addictive with a low abuse potential. There are no literature reports of successful attempts to train animals to self-administer LSD — an animal model predictive of abuse liability — indicating that it does not have the necessary pharmacology to either initiate or maintain dependence.^[10] Likewise, there is virtually no withdrawal syndrome when chronic use of LSD is stopped.^{[citation needed]} It is assumed that 1P-LSD shares these properties with LSD.

Tolerance to the effects of 1P-LSD is built almost immediately after ingestion. After that, it takes about 5-7 days for the tolerance to be reduced to half and 14 days to be back at baseline (in the absence of further consumption). 1P-LSD produces cross-tolerance with all psychedelics, meaning that after the use of 1P-LSD they will have a reduced effect.