PRO-LAD

PRO-LAD, or 6-propyl-6-nor-lysergic acid diethylamide, is a semisynthetic alkaloid of the lysergamide family. PRO-LAD is a chiral compound with two stereocenters at R₅ and R₈. PRO-LAD, also called (+)-D-PRO-LAD, has an absolute configuration of (5R, 8R).^{[citation needed]} It is a structural analog of lysergic acid, with an N,N-diethylamide functional group bound to R_N of the chemical structure. This core polycyclic structure is an ergoline derivative, and has overlapping tryptamine and phenethylamine groups embedded within it (although it is principally classed as a tryptamine). It differs from LSD by the addition of two carbons to the methyl group at R₆ of the structure to form a propyl chain. PRO-LAD is also homologous to ETH-LAD, which contains an ethyl substitution at R₆ instead of a propyl chain.

PRO-LAD's structure contains a bicyclic hexahydroindole fused to a bicyclic quinoline group (nor-lysergic acid). Unlike LSD, PRO-LAD does not contain a methyl group substituted at R₆ of its nor-lysergic acid skeleton, this is represented by the nor- prefix. Instead, PRO-LAD is substituted at R₆ with a propyl group. At carbon 8 of the quinoline a N,N-diethyl carboxamide is bound. At carbon 8 of the quinoline a N,N-diethyl carboxamide is bound. PRO-LAD is a derivative of LSD, differing by the addition of two carbons to the methyl group at R6 of the structure to form a propyl chain.

PRO-LAD is also homologous to ETH-LAD, which contains an ethyl substitution at R6 instead of a propyl chain. PRO-LAD is a chiral compound with two stereocenters at R5 and R8. It is also sometimes called (+)-D-PRO-LAD, as an absolute configuration of (5R, 8R).

PRO-LAD likely acts as a 5-HT_2A partial agonist. The psychedelic effects are believed to come from PRO-LAD's efficacy at the 5-HT_2A receptors. However, the role of these interactions and how they result in the psychedelic experience continues to remain an object of scientific elucidation.

As a derivative of LSD, the pharmacodynamic and pharmacokinetic properties of PRO-LAD are similar to those of LSD. However, they are not exactly the same. The addition of two carbons to the methyl group at R6, and the resulting propyl chain may lead to PRO-LAD being absorbed at a slower rate and therefore a differing initial onset and a peak effect. This could be the reason for the higher threshold and common dosages.^[4]

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Combination effects

• Cannabis - When used in conjunction with cannabis, both the visual and cognitive effects of PRO-LAD can be intensified and extended with extreme efficiency. This should be used with caution if one is not experienced with psychedelics. Many users sometimes report a dramatically more intense visual trip when combining it with THC concentrates such as hashish as opposed to cannabis flower. However, this can also amplify the anxiety, confusion and psychosis producing aspects of both substances significantly, so extreme caution with this combination is advised.
• 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 PRO-LAD have significantly more vivid visuals than dissociatives alone present, and more intense internal hallucinations and confusion.
• MDMA - When used in conjunction with MDMA, the physical and cognitive effects of MDMA are amplified. The visual, physical and cognitive effects of PRO-LAD are also intensified with an overwhelming euphoric pleasure manifested through uniquely pleasurable body highs and headspaces, and uniquely colorful and awe-inspiring visuals. It is often recommended to wait at least three to four hours after ingesting PRO-LAD to take MDMA so as to avoid coming down from the latter while peaking on the former, but positive experiences have been reported with all possible timings. The synergy between these substances is unpredictable (and likely neurotoxic)^{[citation needed]}, and it is best to start with lower dosages than one would take for both substances individually.
• Alcohol - This interaction is not typically recommended due to alcohol’s ability to cause dehydration, depression and thought disorganization which can negatively affect a trip if taken in high dosages. This combination is however reasonably safe in low doses and when used responsibly, this can often take the edge off a trip as well as dull its psychedelic effects in a fashion somewhat similar to benzodiazepines, albeit more stressful on the body.
• 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 a PRO-LAD 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 drug'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 lower dosages than one would take for either substance individually.

The toxicity and long-term health effects of recreational PRO-LAD do not seem to have been studied in any scientific context and the exact toxic dose is unknown. This is because PRO-LAD is a research chemical with very little history of human usage. Anecdotal evidence from people within the psychonaut community who have tried PRO-LAD 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 (but nothing can be completely guaranteed). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

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

Dependence and abuse potential

While no formal studies have been conducted, PRO-LAD is likely not habit-forming and it is reasonable to speculate that the desire to use it can actually decrease with repeated administratino. As with most psychedelics, it likely possesses what is considered an intrinsic, self-regulating aspect to it.

Tolerance to the effects of PRO-LAD 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). PRO-LAD presents cross-tolerance with all psychedelics, meaning that after the consumption of PRO-LAD all psychedelics will have a reduced effect.

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

• Lithium - Lithium is commonly prescribed for the treatment of bipolar disorder. There is a large body of anecdotal evidence that suggests taking it with psychedelics significantly increases the risk of psychosis and seizures. As a result, this combination is strictly discouraged.
• Cannabis - Cannabis may have an unexpectedly strong and unpredictable synergy with the effects of PRO-LAD. Caution is advised with this combination as it can significantly increase the risk of adverse psychological reactions like anxiety, paranoia, panic attacks, and psychosis. Users are advised to start off with only a fraction of their normal cannabis dose and take long breaks between hits to avoid unintentional overdose.
• Stimulants - Stimulants like amphetamine, cocaine or methylphenidate affect many parts of the brain and alter dopaminergic function. This combination can increase the risk of anxiety, paranoia, panic attacks, and thought loops. This interaction may also result in an elevated risk of mania and psychosis.^{[citation needed]}
• Tramadol - Tramadol is well-documented to lower the seizure threshold^[5] and psychedelics may act to trigger seizures in susceptible individuals.^{[citation needed]}

• Austria: PRO-LAD is technically not illegal but it may fall in the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich) as an analogue of LSD.^{[citation needed]}
• Germany: PRO-LAD is controlled under the NpSG (New Psychoactive Substances Act)^[6] as of July 18, 2019.^[4] Production and import with the aim to place it on the market, administration to another person and trading is punishable. Possession is illegal but not penalized.^[7]
• Latvia: PRO-LAD is illegal in Latvia. Although it isn't officially scheduled, it is controlled as an LSD structural analog due to an amendment made on June 1, 2015.^[8]
• Switzerland: On December 1, 2015, Switzerland added PRO-LAD to the list of controlled substances. It is a controlled substance specifically named under Verzeichnis E.^[9]
• United Kingdom: As of January 7, 2015, PRO-LAD is specifically named in the U.K. Misuse of Drugs Act as a Class A drug.^[10]

• Responsible use (Hallucinogens)
• Research chemical
• Hallucinogens
• Psychedelic
• Lysergamide
• AL-LAD
• ETH-LAD
• LSD

• PRO-LAD (Wikipedia)
• PRO-LAD (TiHKAL / Isomer Design)

• Hoffman, A. J., & Nichols, D. E. (1985). Synthesis and LSD-like discriminative stimulus properties in a series of N (6)-alkyl norlysergic acid N, N-diethylamide derivatives. Journal of Medicinal Chemistry, 28(9), 1252-1255. https://doi.org/10.1021/jm00147a022.
• Watts, V. J., Mailman, R. B., Lawler, C. P., Neve, K. A., & Nichols, D. E. (1995). LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors. Psychopharmacology, 118(4), 401-409. https://doi.org/10.1007/BF02245940.
• Niwaguchi, T., Nakahara, Y., & Ishii, H. (1976). Studies on lysergic acid diethylamide and related compounds. IV. Syntheses of various amide derivatives of norlysergic acid and related compounds. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan, 96(5), 673-678. PMID 987200.
• Pfaff, R. C., Huang, X., Marona-Lewicka, D., Oberlender, R., & Nichols, D. E. (1994). Lysergamides Revisited. NIDA Research Monograph, 146, 52-73. PMID: 8742794.