1P-LSD

1-Propionyl-lysergic acid diethylamide (commonly known as 1P-LSD or 1P-LAD) is a novel semi-synthetic psychedelic substance of the lysergamide chemical class that produces "classical psychedelic" effects reported to be near-identical with those of LSD when administered. Like ALD-52, it is principally theorized to act as a prodrug for LSD, not exerting any activity until it has been converted into LSD after entering the body, although there is ongoing speculation that it might possess some intrinsic activity in its own right.[citation needed]

The structural resemblance 1P-LSD shares with LSD suggests an extremely similar effect profile, with perhaps the only significant differences stemming from variations in the rate of absorption, duration, metabolism, and excretion of the compound (i.e. its pharmacokinetic factors). Due to the lack of research relating to this substance, all following discussion relating to its pharmacology is purely based on its structural and subjective effect similarities to LSD and other designer lysergamides.

Very little data exists about the pharmacological properties, metabolism, and toxicity of 1P-LSD, and it has a very brief history of human usage. Over the first few months of 2015, 1P-LSD began to be marketed as a legal alternative to LSD alongside research lysergamides like ETH-LAD and AL-LAD and commercially distributed through a network of online research chemical vendors.

As with LSD itself, 1P-LSD does not meet the criteria to be considered addictive or toxic by the scientific community.[1][2] Nevertheless, unpredictable adverse reactions such as anxiety, paranoia, delusions and psychotic breaks are always liable to occur, particularly among those who are predisposed to psychiatric disorders.[3] While these negative reactions or "bad trips" can often be attributed to factors like the user's inexperience or improper preparation of their set and setting, they are known to happen spontaneously among even the most experienced of users as well.

For this reason, it is highly advised to approach this very potent, unpredictable, long-lasting, hallucinogenic substance with the proper amount of precaution, preparation, and harm reduction practices if choosing to use it.
History and culture
1P-LSD first appeared as a research chemical sold by grey market vendors in January 2015.[4] 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.[5] Interestingly, the future usage of 1-akylated 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. ”
— Donald A. Cooper, Future Synthetic Drugs of Abuse, 1988[6]

Chemistry

1P-LSD is a molecule 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
Further information: Serotonergic psychedelic
As with LSD, 1P-LSD likely acts as a 5-HT2A partial agonist. The psychedelic effects are thought to primarily come from 1P-LSD's efficacy at the 5-HT2A receptors distributed throughout the brain, although it also likely displays binding activity at a wide-range of monoamine receptors such as those for dopamine and norepinephrine (due to the structural similarity it shares with LSD). However, the precise role of these interactions and how they result in the psychedelic experience continues to remain an object of scientific elucidation.

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.[7] Otherwise, it is possible that 1P-LSD may be capable of exerting its own psychedelic activity.

Prior to the publishing of the above-cited research, medicinal chemist and psychedelics researcher David E. Nichols reportedly commented with his thoughts on potential 1P-LSD serotonin receptor binding dynamics:[8]

“ 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
Subjective effects
Anecdotal reports from many users suggest that the subjective effects of 1P-LSD are essentially the same to that of its close structural relative LSD so as to be virtually indistinguishable from one another. In comparison to other psychedelics such as psilocin, LSA and ayahuasca, 1P-LSD is significantly more stimulating and fast-paced regarding the specific style of its physical and cognitive effects.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.

Physical effects Child.svg
Stimulation - In terms of its effects on the physical energy levels of the user, 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.
Perception of decreased weight
Spontaneous physical 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 pleasure.
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 trips. 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
Increased heart rate
Increased perspiration
Muscle contractions
Muscle spasms
Pupil dilation
Salivation
Seizure - This is an effect whose likelihood is largely extrapolated from the seizures that have been reported from the use of LSD. They are 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.
Visual effects Eye.svg
Enhancements
Colour enhancement - In comparison to other psychedelics, this effect is often reported to be brighter but not as varied in its character.
Pattern recognition enhancement
Visual acuity enhancement
Distortions
Drifting (melting, breathing, morphing and flowing) - In comparison to other psychedelics, this effect can be described as highly detailed yet cartoon-like in its appearance. The distortions are slow and smooth in motion and fleeting in their appearance.
Colour shifting
Colour tinting
Tracers
After images
Depth perception distortions
Perspective distortions
Recursion
Symmetrical texture repetition
Scenery slicing
Geometry
The visual geometry that is present throughout this trip can be described as more similar in appearance to that of 2C-B or 2C-I than psilocin, LSA or DMT. It can be comprehensively described through its variations as primarily intricate in complexity, algorithmic in form, unstructured in organization, brightly lit, colourful in scheme, synthetic in feel, multicoloured in scheme, flat in shading, sharp in edges, large in size, fast in speed, smooth in motion, angular in its corners, non-immersive in-depth and consistent in intensity.

In the case of higher-level geometry, this substance is level 8A dominant but is also capable of inducing 8B Geometry under the right circumstances.

Hallucinatory states
1P-LSD is capable of producing a full range of low and high level hallucinatory states in a fashion that is significantly less consistent and reproducible than that of many other commonly used psychedelics, specifically tryptamines like DMT or psilocybin mushrooms. These effects include:

Transformations
Machinescapes - This component is a rare effect that typically only occurs at very strong to heavy doses, and not as consistently as with notably visual psychedelics like DMT, ETH-LAD, and 2C-P, and atypical psychedelics like salvia.
Internal hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots) - Although 1P-LSD is technically capable of producing hallucinatory states in a fashion that is on par with psilocin or DMT in its vividness and intensity, these effects are incredibly rare and inconsistent in comparison. While traditional psychedelics such as LSA, ayahuasca and mescaline will induce internal hallucinations near consistently at level 5 geometry and above, 1P-LSD will for most simply go straight into Level 8A visual geometry. This lack of consistently induced hallucinatory breakthroughs means that for most, LSD is simply not as deep of an experience as certain other psychedelics. On the rare occasion that they are induced, however, they can be comprehensively described in terms of their variations as lucid in believability, interactive in style, new experiences in content, autonomous in controllability and geometry-based in appearance.
External hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots)
Cognitive effects User.svg
The cognitive effects of 1P-LSD can be broken down into several components which progressively intensify proportional to dosage. In comparison to other psychedelics such as psilocybin, LSA and ayahuasca, 1P-LSD is significantly more stimulating and fast-paced in terms of the specific style of thought streams produced and contains a large number of potential effects that is attributed to its binding activity at a wide range of monoamine receptors other than serotonin, specifically receptors for dopamine and norepinephrine. The most prominent of these cognitive effects generally include:
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".
Conceptual thinking
Creativity enhancement
Emotion enhancement
Simultaneous emotions
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.
Delusions
Déjà vu
Ego replacement
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
Multiple thought streams
Personality regression
Thought acceleration
Thought disorganization
Thought loops
Time distortion
Wakefulness
Auditory effects Volume-up.svg
Enhancements
Distortions
Hallucinations
Multi-sensory effects Gears.svg
Synaesthesia - In its fullest manifestation, this is a very rare and non-reproducible effect. Increasing the dosage can increase the likelihood of this occurring, but seems to only be a prominent part of the experience among those who are already predisposed to synaesthetic states.
Transpersonal effects Infinity4.svg
Spirituality enhancement
Existential self-realization
Perception of interdependent opposites
Unity and interconnectedness
Experience reports
Anecdotal reports which describe the effects of this compound within our experience index include:

Experience:1P-LSD: 100ug, A Fear and loathing into Bliss
Experience:300μg 1P-LSD + 40mg diphenidine - My first psychotic break
Experience:Finding myself within the forest
Additional experience reports can be found here:

Erowid Experience Vaults: 1P-LSD
Combinations
Cannabis - When used in combination with cannabis, both the visual and cognitive effects of 1P-LSD can be intensified and extended with extreme efficiency. This should be used with extreme caution if one is not experienced with psychedelics, however, as this can also amplify the anxiety, confusion and psychosis producing aspects of cannabis significantly. If using this combination, users are advised to start off consuming only a fraction of their usual amount, spacing out hits, and waiting until the offset of the trip to avoid potentially being overwhelmed.
Dissociatives - When used in combination with dissociatives, the geometry, euphoria, dissociation and hallucinatory effects are often greatly enhanced. Dissociative-induced holes, spaces, and voids while under the influence of 1P-LSD have significantly more vivid visuals than dissociatives alone present, and more intense internal hallucinations, and corresponding confusion which can spontaneously manifest as delusions and psychosis.
MDMA - When used in conjunction with MDMA, the physical and cognitive effects of MDMA are amplified. The visual, physical and cognitive effects of 1P-LSD are also intensified to great euphoric heights manifested through uniquely pleasurable body highs and headspaces, and amazingly colorful and awe-inspiring visuals. The synergy between these substances is unpredictable, and it is best to start with markedly lower dosages than one would take for both substances individually. Additionally, users should be aware that there are reasons to believe that this combination may result in unforeseen neurotoxic effects, so a strong sense of caution and independent research are highly advised if one decides to experiment with this combination.[citation needed]
Alcohol - This interaction is not typically recommended due to alcohol’s ability to cause dehydration and nausea which can negatively affect a trip if taken in moderate to high dosages. This combination is, however, reasonably safe in low doses and can often "take the edge off" a trip as well as dull its psychedelic effects in a fashion somewhat similar to benzodiazepines, albeit in a more physically stressful way.
Benzodiazepines - When used in combination with benzodiazepines, benzodiazepines can, depending on the dosage, slightly to completely reduce the intensity of the cognitive, physical and visual effects of an LSD trip. They are very efficient at stopping "bad trips" at the cost of amnesia and reduced trip intensity. Caution is advised when acquiring them for this purpose due to the very high addiction potential that benzodiazepines possess.
Psychedelics - When used in combination with other psychedelics, each substance's physical, cognitive and visual effects intensify and synergize strongly. The synergy between those substances is unpredictable, and for this reason generally not advised. If choosing to combine psychedelics, it is recommended to start with significantly lower dosages than one would take for either substance individually.
Toxicity and harm potential
Further information: Research chemicals § Toxicity and harm potential, and Responsible use § Hallucinogens
The toxicity and long-term health effects of recreational 1P-LSD use do not appear to have been studied in any scientific context and the exact toxic dose is unknown. This is because 1P-LSD is a research chemical with a very limited history of human use.

Anecdotal evidence from people within the community who have tried 1P-LSD suggests that there are no negative health effects attributed to simply trying the drug by itself at low to moderate doses and using it very sparingly (although nothing can be completely guaranteed). Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

Although no formal studies have been conducted, it is considered reasonable to assume that like LSD itself, 1P-LSD is likely to end up being considered non-addictive, incapable of causing brain damage, with an extremely low toxicity relative to dose.[9] It is also likely that as with LSD, there are little to no negative physical, cognitive, psychiatric or other toxic consequences associated with acute 1P-LSD exposure.

However, as with LSD and psychedelics in general, it is possible that 1P-LSD can act as a potential trigger for those with underlying psychiatric conditions, so those with a personal or family history of mental illness are generally advised not to use this substance.

It is strongly recommended that one uses harm reduction practices when using this substance.

Tolerance and addiction potential
Although no formal studies have been conducted, it is not unreasonable to assume that like LSD itself, 1P-LSD is not habit-forming and that the desire to use it can actually decrease with use. As with most psychedelics, it is generally considered to have a built-in, self-regulating aspect to it, though cases of dependence and addiction to psychedelics, albeit uncommon, have been documented in the medical literature.[citation needed]

Tolerance to the effects of 1P-LSD are 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 presents cross-tolerance with all psychedelics, meaning that after the use of 1P-LSD all psychedelics will have a reduced effect.

Dangerous interactions
Although many substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be relatively harmless in low doses of each but can still increase the risk of unpredictable injury or death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Note that the following substances are included on the assumption that 1P-LSD possesses a similar if not the same dangerous interactions profile as LSD, and may include more due to its status as an unstudied research chemical

Tramadol - Tramadol lowers seizure threshold[10] and psychedelics may cause occasional seizures.[11][12][13]
Stimulants - Stimulants may provoke anxiety or thought loops.[14]
Lithium - Individuals who take lithium for bipolar disorder or other psychiatric conditions should not take LSD. There are numerous anecdotal reports of seizures and or unsafe psychosis from this combination.[15][16][17][18]
Legal status
International - 1P-LSD is currently a gray area compound within many parts of the world. This means that it is not known to be specifically illegal within most countries, but people may still be charged for its possession under certain circumstances such as under analog laws and with the intent to sell or consume.
United Kingdom - It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.[19]
United States - Since 1P-LSD is theorized to be a prodrug of LSD, it would likely be illegal in the United States under the Federal Analogue Act.
Virginia - 1P-LSD is currently illegal as a Schedule I substance until May 10, 2018 [20]
Switzerland - 1P-LSD is illegal in Switzerland as of December 2015.[21]
Latvia - 1P-LSD is illegal in Latvia. Although it is not officially scheduled, it is controlled as an LSD structural analog due to an amendment made on June 1st, 2015.[22]
Sweden - Following its sale as a designer drug, 1P-LSD was made illegal in Sweden on 26 January 2016.[23]
Germany - 1P-LSD is not listed under their controlled substance act.
See also
Responsible use
Research chemical
Psychedelic
Lysergamide
LSD
ALD-52
AL-LAD
ETH-LAD
LSZ
External links
1P-LSD (Wikipedia)
1P-LSD (Tripsit)
1P-LSD (Bluelight)
Literature
Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). The Pharmacology of Lysergic Acid Diethylamide: A Review, 14, 295–314. https://doi.org/10.1111/j.1755-5949.2008.00059.x
Nichols, D. E. (2016). Psychedelics, (April), 264–355. https://doi.org/10.1124/pr.115.011478.
Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., … Nutt, D. J. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1518377113
Halberstadt, A. L. (2015). Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behavioral Brain Research, 277, 99–120. https://doi.org/10.1016/j.bbr.2014.07.016
Nichols, C. D., Garcia, E. E., & Sanders-bush, E. (2003). Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration, 111, 182–188. PMID: 12654518
Vollenweider, F. X., & Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Publishing Group, 11(9), 642–651. https://doi.org/10.1038/nrn2884
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Jump up 1P-LSD (Google Trends) | https://trends.google.com/trends/explore?q=1p-lsd
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Jump up Cooper, D. A. (1988, March). Future synthetic drugs of abuse. In Proceedings of the international symposium on the forensic aspects of controlled substances: March (Vol. 28, p. 79). https://www.erowid.org/library/books_online/future_synthetic/future_synthetic.shtml
Jump up Brandt, S. D., Kavanagh, P. V., Westphal, F., Stratford, A., Elliott, S. P., Hoang, K., ... & Halberstadt, A. L. (2015). Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD). Drug Testing and Analysis. https://doi.org/10.1002/dta.1884
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Jump up Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). The Pharmacology of Lysergic Acid Diethylamide: A Review, 14, 295–314. https://doi.org/10.1111/j.1755-5949.2008.00059.x
Jump up Talaie, H., Panahandeh, R., Fayaznouri, M. R., Asadi, Z., & Abdollahi, M. (2009). Dose-independent occurrence of seizure with tramadol. Journal of medical toxicology, 5(2), 63-67. doi:10.1007/BF03161089
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