New Drugs: Diarylethylamines

[AS OF 3/20/2023, THIS ARTICLE IS MORE OR LESS RENDERED OBSOLETE WITH THE PUBLICATION OF MICHAEL DYBEK PH.D'S DOCTORAL DISSERTATION, "STRUCTURE ACTIVITY RELATIONSHIP (SAR) STUDIES OF 1,2-DIARYLETHYLAMINES AS N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS"; THIS PUBLICATION DEFINITIVELY MAPS OUT THE EFFECT THAT VARIOUS SUBSTITUTIONS HAS ON DIARYLETHYLAMINES IN TERMS OF NMDA RECEPTOR AFFINITY. IT IS COMPREHESIVE AND I DON'T FEEL LIKE REWRITING THIS ARTICLE. I SUMMARIZED THE FINDINGS OF THAT DISSERTATION HERE. IT IS INCREDIBLY EXCITING TO HAVE THESE HYPOTHESIS AND SEE THEM TESTED THROUGH THE WORK THAT DR. DYBEK HAS DONE OVER THE PAST FEW YEARS!]

[EDITED 1/2/21 to include information the diarylethylamine stimulant A-D2PV]

The Diarylethylamines are a class of chemical best known for producing a series of fascinating dissociative hallucinogenic compounds. 3 of these compounds-Ephenidine, Diphenidine, and Methoxphenidine, were widely produced and were widely available for a time. (Some others, such as Fluorolintane and Isopropylphenidine were known to exist too, though they saw limited availability and little data exists for them). There exist some other compounds with the basic Diarylethylamine backbone that appear to have activity at other receptors, such as µ-opioid agonism or stimulant activity. 

The basic structure of the Diarylethylamine is an aromatic ring, with an ethylamine side chain and another aromatic ring at the α-position of the side chain. Almost all known examples of diarylethylamines see two phenyl rings as the aromatic rings, though psychoactive activity can still possibly be retained with other aromatic rings. With a phenyl ring, a diarlethylamine is in fact a type of phenethylamine!

Diarylethylamines respond to modifications in a fairly predictable pattern, similar to the arylcyclohexylamines (which I have written about at length before), though a lot is yet to be understood and as such, all sorts of SAR surprises pop up.

Generalized structure of a diarylethylamine, with phenyl rings as the aromatic rings. Some amine is placed at the blue line

The first diarylethylamines to be tested for their pharmacological properties were a series of diphenyl compounds with either a primary amine, various alkane chains as secondary amines (including Ephenidine and Isopropylphenidine), and 4-MeO-Substituted versions of the primary amine along with Ephenidine. They were evaluated for their stimulant properties, as at the time (1943), dissociative NMDA antagonists had not been formally identified or described yet [11]. Most compounds in this development series would likely be active as dissociatives nonetheless.

Diarylethylamine development was dominated for the rest of the century by lefetamine, which saw abuse in Japan and Europe briefly. The action of lefetamine was never fully defined, though it is suggested to be a partial opioid agonist, and in some manner a stimulant [4]. It is possible it may also be an NMDA antagonist (more on that later). As the defining structure for the series, other diarylethylamines were for a while referenced in literature as analogues of lefetamine. Dissociative compounds were revisited in the 80’s and 90’s for the same reason many dissociative NMDA antagonists were investigated in medicine- as anticonvulsants, antparkinsonians, anti-ischeimics, or as neuroprotectives [2]. This is likely the same literature that would guide the development of the first diarylethylamines to hit the streets. Diarylethylamines as recreational drugs were first identified in 2008 in a seizure by German police, where Ephenidine and Isopropylphenidine were discovered. Interest in these compounds would explode in 2013 however, following a UK ban on arylcyclohexylamines that was put in place to stamp out MXE [12]. Ephenidine, Diphenidine, and Methoxphenidine would inundate the online markets, see widespread use and abuse, and eventually, as of 2020, fall out of favor and become scarce. Fluorolintane, and Isopropylphenidine were available at some point, though they did not see widespread sale or use and very little information exists about them in internet drug communities [18]. A Methylethylphenidine, billed as N-methylephenidine or “Ephenidine 2” also supposedly existed at some point, though a single report states that it didn’t have NMDA antagonist effects. [20].

A selection of existing Diarylethylamines that have shown NMDA antagonist activity

So what exactly are the Diarylethylamines like? Why did they wane in popularity? There were several distinct properties they had that set them apart from many of the diarylethylamines- First was bioavailability, particularly that they were not active intranasally, a preferred method for many dissociative users. They had to be taken orally or rectally, or possibly by IV. Second is their potency- most of these compounds saw active doses upwards of 100 mg- not the most cost effective for the producer or the consumer. (This is odd because many have a higher in vitro affinity for the NMDAr receptor than PCP! Are pharmacokinetics to blame? It is not fully understood yet) [14]. Lastly, they had an effect similar to psychedelics where they would instill a cross tolerance against other NMDA receptors for about a week, which was a turnoff for frequent users. However, they also saw acclaim for their euphoric, hallucinogenic, and stimulant properties. Many remarked on the powerful compulsive redosing instilled by vaporizing Diphenidine. Ephenidine received the best reviews of them all, praised for its sociability, euphoria, visuals and general sensation. The dissocation of the diarylethylamines was characterized as “smooth” and “sinking”, without as much of a stimulant edge as the Arycyclohexylamines for most users. This author personally found value and interesting properties in all 3 of those compounds. Nonetheless, all of this information comes from the sample size of the 3 compounds that were actually produced for market though. Perhaps other unique properties are hiding out there with other compounds.

 

Generalized Diarylethylamine structure with 2 phenyl rings and positions labeled

So where to go for developing these? Well, they have remarkably similar properties to the arylcyclohexylamines in terms of how you can modify them yet retain activity. The nitrogen appears to accept all variety of amine substitutions, primary, secondary and tertiary, potentially the same variety of amines that could possibly be used for arylcyclohexylamines [1]. It should be noted that there appear to be pitfalls in this regard and there may be a wide range of unexpected patterns. For example, a non-cyclic tertiary amine seems to reduce NMDA antagonist activity and present partial opioid activity, as seen in Lefetamine [5]. A single report of a tertiary Methylethylamine suggested the compound was a stimulant and had no NMDA antagonist activity [20].

Then there’s the aromatic rings- most commonly presented as phenyl rings. It is possible however that other rings could conserve activity in that position [6]. Speaking strictly of phenyl rings however, similar to the arylcyclohexylamines, they can potentially see substitutions- at their 2, 3, and 4 positions. It would appear that activity is best conserved via substitutions at the 2 position of ring 1 and the 3’ position of ring 2 (At least in the unique compound fluorolintane, which has a pyrollidine as the amine) [13]. Substitutions at other positions on these rings may be inactive, at least with a pyrollidine. It is also alleged that 2’ position substitutions on ring 2 are active, though the evidence for this is conflicting and dubious [12][18]. These are not hard, fast rules though and there are already exceptions that may render these not even rules in the first place- or perhaps different sets of rules apply depending on what the amine is- for example a 3-Methoxy substituted version of Diphenidine retained appreciable activity and potency [14]. Oddly enough, a 2-Cl Diphenidine showed to be even more potent than its parent compound, and one of the higher in vitro affinity compounds out there [14]. So it really is hard to predict, and as mentioned before, with diarylethylamines, in vitro affinity does not translate directly to in vivo potency.

As for which substitutions work? Hypothetically any that have been seen to retain or potentially retain activity in arylcyclohexylamines, though only halogens and methoxy groups have been attempted so far. It would be exciting to see others! Perhaps simple alkane chains and hydroxy groups would also show promise.

 

So a quick summary if you want to design a new diarylethylamine:

1. The amine has proven to be active with an N-ethyl, N-isopropyl, piperidine, and pyrollidine. Thus it can be presumed that longer secondary amine chains and other tertiary amine rings will work. Noncyclic tertiary amines appear to have less receptor selectivity. A primary amine is also likely accepted [1].

 

2. The aromatic rings will definitely provide the most predictable results when both are phenyl rings. Other aromatic rings may work too, though this requires further study. Information on modifying the aromatic rings can be found in Mealing et al. 2001 [6] and Massa et al. 1989 [5].

 

3. Substitutions seem to work best on the 2 and 3’ positions of phenyl rings, (or on the 3 position if you have a piperidine instead of a pyrollidine for the amine- tons more exceptions like this may exist!). Substitutions such as halogens and methoxy groups have proven active- it is possible that other substitutions like alkane chains, hydroxy groups, amino groups, and others may conserve activity too! It is also alleged that substitutions on the 2’ position may be active, though the evidence for this is conflicting. [13][18]

 

4. It appears possible to add addition moieties on the α and β positions of the ethylamine side chain. In vitro, it has so far been demonstrated that an α-methyl and a β-amino group have an appreciable affinity for the NMDA receptor [1]. OH- substitutions were demonstrated to be inactive so it’s hard to say what else may or may not work in those positions. It seems a  β-ketone produces a pure stimulant, as it builds a structure resembling a cathinone. This is seen in the compound A-D2PV. 

5. As far as stereochemistry is concerned, it would appear that the (S)-enantiomer of any diarylethylamine will have a higher affinity for the NMDA receptor than the (R)-enantiomer. [1] [9]

This is a lot of words- perhaps seeing it mapped out again will help visualize the door to all of the possibilities!

 

But first of course, a word of warning: As with any new class of drugs, extreme caution is warranted when developing and testing Diarylethylamines. Known risks specific to this class of chemical include overdose [22], Carcinogenic properties [23], and nonselective receptor activity such as opioid agonism, which could lead to other forms of overdose [4].

NMDA antagonists in general will also present a set of risks. For ease, I am simply going to copy the warning given in my post on arylcyclohexylamines. The cited sources in the following block of text can be found on the page for that article.

“There are also a number of ways chronic toxicity is reported to present with NMDA antagonists, mainly neurotoxicity and cytotoxicity. In terms of neurotoxicity, there are the infamous Olney’s lesions, a form of brain damage, that has been observed in other animals, though they have still not officially been observed in humans yet [43]. However, a recent study reportedly observed some form of damage in the brain of extremely frequent users of ketamine [44]. The other main reported symptom that indicates toxicity is urinary toxicity [45, 46], supposedly a result of damage to the epithelial cells lining the bladder caused by direct toxicity from ketamine metabolites. This has so far only been officially reported with ketamine, though there are anecdotal reports of it occurring in frequent users of other dissociatives. There is also a potential for cognitive dysfunction from extreme repeated use of dissociatives, mostly in the form of “brain fog” and memory loss, though there is some literature on the matter [47].

These substances also carry the risk of generating dangerous behaviors that can be damaging to one’s life circumstances and relationships, both through the dangerous interplay of prohibition and substance, and in properties inherent to the chemicals themselves. One key risk is addiction- while physical dependence to dissociatives is significantly more rare than with other classes of substance, it is entirely possible and psychological dependence is commonly reported. Frequent usage significantly increases the chance of toxic effects or cognitive dysfunction presenting. Other substances, such as PCP, are notorious for causing intense mania that can push into psychosis, which can lead to violence, damaging relationships, and legal trouble. All of these risks are real and it is up to the user to determine what methods personally work best for mitigating them, including total abstinence if necessary.

I would suggest, in a perfect world (keep in mind this is all very handwaved, this actual process can be expensive, difficult, and extremely time consuming)- First, doing a virtual docking simulation of the compound. This of course is not a surefire way to determine activity, but can perhaps give warning of possible unexpected activity or help to rule out certain options as being less viable. The compound can be synthesized from there, at which point it must be properly characterized via NMR and GC/MS analysis. From there, an in-vitro receptor affinity study can be done to confirm or deny certain targeted activities in nerve cells in comparison to familiar reference compounds, like PCP, Ketamine, MK-801 or Morphine. The safest step from there would be in-vivo studies in animals, also compared to a control group of reference compounds. Behavioral tests can be done for comparison to any references, and drug substitution tests can help indicate similarity to the references. There is a huge variety of animal tests that can be done in combination with each other and with various controls to really narrow down possible mechanism of action depending on what a researcher has at their disposal. In-vivo tests also help to determine an mg/kg dosage range and possible acute or chronic toxicity, or even an LD-50. Only after it has been presumed nontoxic and its likely activities have been characterized should one even consider human testing. This must also be done in the context of extremely precise doses, titrated upwards from a microgram range, with the subject physically monitored by a healthcare professional. If you want to get really fancy, this can be performed in a double blind test with a placebo.

Of course not all those processes or resources are available to every researcher. Those are all long, difficult, expensive processes that may require specialty equipment, facilities, and faculty. Many researchers of psychoactive compounds have opted to skip some or most or all of those steps, and prohibition absolutely makes obtaining any of those resources extremely difficult. I would recommend approaching with maximum caution, but I’m also not the boss of anyone and can’t make anyone do anything, and understand how the spirit of curiosity can sometimes overcome a lack of available resources. Ideally a team of researchers could easily have infrastructure to efficiently run multiple compounds through that gauntlet of safety determinations. But this world is less than ideal. Please just for the love of god, be safe, be smart, be responsible.”

For a larger image: https://i.imgur.com/v7rVSoR.png

To download a pdf: https://gofile.io/d/tYPnG1

 

Some things that you may have noticed in this chart- First is the exclusion of many of the amines that I used in my arylcyclohexylamine chart- this is simply due to how little knowledge currently exists for the diarylethylamines. I cut it down to which ones seem to have a higher likelihood of being selective NMDA antagonists, while leaving out many of the more experimental variations that have hardly even been tested on the better understood arylcyclohexylamines. I also only left the option for substitutions for the 2,3, and 3’ positions on the phenyl rings (As well as some 2,3-cyclic substitutions), as substitutions at other positions, as far as we understand, render the compound inactive. Speaking of aromatics, I leave the option to exchange the default phenyl rings in the structure for aromatics known to conserve activity in the arylcyclohexylamines. Not enough data exists to even conjecture on then adding substitutions to those, though one study suggests other aromatics will accept a methyl substitution at times [6]

Moieties that have demonstrated some sort of activity in vivo or in vitro are cited on the chart.

As for nomenclature? To copy the blurb included in the chart-

There are no hard fast rules for naming diarylethylamines, just like with any class of drug. Lefetamine, Lanicemine, Remacemide, Fluorolintane, are all names of compounds in this class that don’t seem to follow any convention. The advent of commercially available dissociative diarylethylamines brought about the -phenidine naming scheme, which for now stands as the most recognizable way to name possible dissociative compounds. If you are using the chart, the amines are labeled with prefixes that can be appended to the “-phenidine” suffix. Denoting the presence of substitutions is as easy as simply appending the positional number and an abbreviation of the moiety, as seen in the arylcyclohexylamines. For example, a compound could be named 2-F-Morpholidophenidine, or 3’-EtO-EtHydroxyphenidine. Of course in popular usage, exceptions crop up everywhere. 2-MeO-Diphenidine was sold on the market as simply Methoxphenidine, abbreviated MXP (likely to market it as being similar to the recently banned and immensely popular MXE). As for instances where one of the standard phenyl rings is replaced with a different aromatic name, the -phenidine suffix will not suffice. I suggest just amending that suffix depending on the ring. If there are 2 thiophene rings for example, -dithiophenidine would be a usable name. If there is say, a thiophene + a phenyl, then thiophenidine could be a valid name. I am still unsure of how to denote which ring is which in this naming scheme however- perhaps the first name listed could represent ring 1, with the second ring as ring 2. So “Thiophenidine” would denote that ring 1 was a thiophene, while “Phenithiophenidine” would denote that ring 2 was the thiophene. Thus, if you were to name lanicemine with this scheme, it would be Apheni-2-pyridine. This produces structures whose names can be a mouthful, but I fail to think of a better solution. Nevertheless, this nomenclatural scheme should make it relatively easy for the name of novel compounds to reflect their structure.

 

 

 

Some other Diarylethylamines:

So far, the diarylethylamines that have been shown to have dissociative hallucinogenic effects in humans are, as mentioned before, Ephenidine, Diphenidine, Methoxphenidine, Fluorolintane, and Isopropylphenidine.

Opioid Compounds

To illustrate how complicated designing diarylethylamines can be, how rife with pitfalls and exceptions it is, let’s look at some other compounds that technically fall within the diarylethylamine family but have quite different activity. Compounds with a piperazine as the amine have proven to be opioids (namely MT-45, AD-1211, and Diphenpipenol) though this may also be virtue of the various structures then appended to the other nitrogen in the ring, rendering it tertiary, or it may also be a function of variously placed hydroxy substitutions. It’s hard to pin down what exactly dictates that activity but something keeps them from being more selective regular NMDA antagonists. Perhaps a piperazine as the amine in an arylcyclohexylamine would also generate an opioid?

Lefetamine

Lefetamine was mentioned before as the representative diarylethylamine in medical literature for much of the 20^th century. It was commercially available in postwar Japan where it was marketed a painkiller, then later saw abuse in Europe, but seems to have disappeared entirely since then [4]. It was sold under the trade name Santonel. Users reported a combination of opioid-like and stimulant effects. One study confirmed that it was at least in part, a µ-opioid agonist [4]. It is not yet known what activity it derives it stimulant properties from. It has not yet been explicitly tested for NMDA antagonist activity, though it’s entirely possible that it possesses this property.

One possibility lies in the fact that only the (R)-enantiomer of lefetamine has been produced and tested in vivo, yielding measurable opioid effects. When we look at dissociative diarylethylamines, such as diphenidine, it is the (S)-enantiomer that possesses NMDA antagonist properties, as opposed to the (R)-enantiomer, which shows lower affinity [1]. With this in mind, it is entirely possible that a racemic mixture of lefetamine or simply a sample of the pure (S)-enantiomer may have different selectivity, and could perhaps even have a high affinity for the NMDA receptor! This also raises the questions of how a tertiary amine on a diarylethylamine behaves- it appears for now that non-cyclic tertiary amines see reduced NMDA antagonist activity- perhaps affinity increases with bulkier alkanes? Or perhaps some sort of ring structure is necessary, as seen in Diphenidine. But for now, this is pure conjecture, and lefetamine remains an interesting footnote in the history of this family of chemicals.

"Ephenidine-2"

Also worth mentioning is the compound Methylethylphenidine, aka N-methylephenidine, aka “Ephenidine-2”. As the name implies, it is a tertiary amine very similar in structure to lefetamine with a methylethyl tertiary amine. A single report exists for this substance, citing no dissociative effects, but rather unremarkable stimulant effects with a series of oral and intranasal doses ranging from 20-100 mg [20]. This supports the hypothesis that a noncyclic tertiary amine is likely to be show affinity for other receptors either alongside the NMDA receptor, or entirely instead of it.

 

Lanicemine and Remacemide

The structures of Lanicemine and Remacemide

These are two other Diarylethylamines that were produced and studied for possible medical uses. Though fairly different in structure, they both share the property of being weak NMDA antagonists.

Lanicemine,also called AR-R15896, consists of a primary ethylamine, where ring 1 is replaced with a 2-pyridine. It was developed to be an antidepressant- possibly due to having a similar action to ketamine but less ketamine-like dissociative effects [17]. Like many NMDA antagonists, it was also studied as an anti-ischemic [8]. This is owed to a phenomenon called trapping, where it is conjectured that certain molecules such as PCP or MK-801 become “trapped” in the channel of the NMDA receptor, amplifying their hallucinogenic effects (to put it extremely simply) [6]. This is an example of what may happen when one of the typical phenyl rings is substituted for another aromatic ring. Mealing et al. in the study “Structural modifications to an N-methyl-D-aspartate receptor antagonist result in large differences in trapping block” touches upon a number of diarylethylamines with other aromatic rings replacing a phenyl [6]. Many of these compounds show higher trapping than lanicemine, which hypothetically may suggest that they will display certain familiar hallucinatory NMDA antagonist effects. The correlation between trapping and activity as a dissociative isn’t direct, confirmed, or fully understood however, and this is just conjecture.

Remacemide meanwhile, sports a methyl group sharing the α-carbon with the phenyl, and an acetamide as the amine (on a secondary amine). Remacemide has also been demonstrated to be a weak NMDA antagonist and has been investigated thoroughly for the suite of possible medical applications of NMDA antagonists (Anticonvulsants, antiparkinsonians, anti-ischemics etc.) [9] [10]. While it is an NMDA antagonist it is noted for not producing familiar NMDA antagonist “side effects”. Whether this is a result of the α-methyl group or the acetamide is unknown, though it has been demonstrated that diarylethylamines with α-methyl groups on a quaternary carbon shared with one of the aromatic rings can retain affinity for the NMDA receptor (at least in vitro) [1].

A-D2PV

Chemical Structure of A-D2PV (or α-d2PV)

A-D2PV is a diarylethylamine with a beta-ketone, giving it a remarkable similarity to the subclass of cathinone stimulants called pyrovalerones, which include drugs like MDPV, α-PVP (aka Flakka), α-PHP, α-PCYP etc. It also bears resemblance to fluorolintane, or one could say that fluorolintane bears resemblance to the pyrovalerones. Ultimately, they are both phenethylamines with a pyrrolidine as an amine. The pyrovalerones are powerful stimulants that typically have some sort of alkane chain on the α-carbon of the ethylamine. This drug first appeared on the market in 2020. It seems that stimulant activity is moderated by the combination of the beta-ketone and some sort of hydrocarbon on the α-position. It seems that NMDA antagonist activity is not solely modulated by having two phenyl rings- but rather that the presence of a beta-ketone overrides that and makes it primarily a pyrovalerone-like stimulant. Scant reports mention some distinct similarities to other pyrovalerones- most notably a semen-like odor when vaporized [24]. Most found it to be overly short in duration and ultimately subtle, lackluster, and impotent as a stimulant [24] [25] [26]. Like any drug however, some people out there found its qualities agreeable [27]. Everything has its fans. This compound is nonetheless important and noteworthy because it demonstrates what adding a beta-ketone will do to a diarylethylamine. 

So its apparent that some relatively tame and expectable modifications of the diarylethylamine backbone can yield an unpredictable variety of receptor activities, some could possibly be nonselective NMDA antagonists in addition to hitting other targets while others may be selective for different receptor systems entirely! Only by developing and testing more of them can we try and figure out what would yield a possible interesting, nontoxic, and active substance that is sufficiently potent. There’s a whole world to explore! Unlike the last essay, I am not including a section of what I think should be investigated next- simply put, we only have 3 dissociative compounds with enough data to provide a reference for their effects in vivo, it's hard to discern any clear patterns or development leads on that, beyond extending a secondary alkane chain and strapping substitutions to amines that are known to be active. Really any potential pathway within this family is worth investigating in my opinion. This is out of my hands now, I don't know anything about synth or orgo reactions. I hope this infomation will be valuable to an intrepid explorer.

 

Sources and Further Reading:

[1]- Berger ML, Schweifer A, Rebernik P, Hammerschmidt F (2009) NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds. Bioorg Med Chem 17:3456–3462

[2]- Gray NM, Cheng BK (1989) 1,2-Diarylethylamines for treatment of neurotoxic injury. Patent No. EP346791A1. G.D. Searle and Co., Chicago

[3]- Kang H, Park P, Bortolotto ZA, Brandt SD, Colestock T, Wallach J, Collingridge GL, Lodge D (2017) Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties. Neuropharmacology. 112(Pt A):144-149

[4]- Mannelli P, Janiri L, De Marinis M, Tempesta E (1989) Lefetamine: new abuse of an old drug--clinical evaluation of opioid activity. Drug Alcohol Depend 24(2):95-101

[5]- Massa S, Stefancich G, Artico M, Corelli F, Silvestri R, Pantaleoni GC, Fanini D, Palumbo G, Giorgi R (1989) Synthesis, neuropsychopharmacological effects and analgesic-antiinflammatory activities of pyrrole analogues of lefetamine. Farmaco 44(9):763-77

[6]- Mealing GA, Lanthorn TH, Small DL, Murray RJ, Mattes KC, Comas TM, Morley P (2001) Structural modifications to an N-methyl-D-aspartate receptor antagonist result in large differences in trapping block. J Pharmacol Exp Ther. 297(3):906-14

[7]- Morris H, Wallach J. From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. (2014) Drug Test Anal. 6(7-8):614-632.

[8]- Palmer GC, Cregan EF, Bialobok P, Sydserff SG, Hudzik TJ, McCarthy DJ .(1999) The low-affinity, use-dependent NMDA receptor antagonist AR-R 15896AR. An update of progress in stroke. Ann N Y Acad Sci 890:406-20

[9]- Palmer GC, Murray RJ, Wilson TC, Eisman MS, Ray RK, Griffith RC, Napier JJ, Fedorchuk M, Stagnitto ML, Garske GE (1992) Biological profile of the metabolites and potential metabolites of the anticonvulsant remacemide. Epilepsy Res. 12(1):9-20

[10]- Santangeli S, Sills GJ, Thompson GG, Brodie MJ (2002) Na(+) channel effects of remacemide and desglycinyl-remacemide in rat cortical synaptosomes. Eur J Pharmacol. 438(1-2):63-8

[11]- Tainter ML, Luduena FP, Lackey RW, Neuru EN (1943) Actions of a series of Diphenyl-ethylamines. Journal of Pharmacology and Experimental Therapeutics 77(4):317-323

[12]- Wallach J, Brandt SD (2018) 1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances. Handb Exp Pharmacol. 252:305-352

[13]- Wallach J, Colestock T, Agramunt J, Claydon MDB, Dybek M, Filemban N, Chatha M, Halberstadt AL, Brandt SD, Lodge D, Bortolotto ZA, Adejare A (2019) Pharmacological characterizations of the 'legal high' fluorolintane and isomers. European Journal of Pharmacology 857:172427

[14]- Wallach J, Kang H, Colestock T, Morris H, Bortolotto ZA, Collingridge GL, Lodge D, Halberstadt AL, Brandt SD, Adejare A (2016) Pharmacological Investigations of the Dissociative 'Legal Highs' Diphenidine, Methoxphenidine and Analogues. PLoS One. 11(6):e0157021

[15]-Wallach J, Kavanagh PV, McLaughlin G, Morris N, Power JD, Elliott SP, Mercier MS, Lodge D, Morris H, Dempster NM, Brandt SD (2015) Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers. Drug Test Anal 7(5):358-67

[16]- Wink CS, Meyer GM, Wissenbach DK, Jacobsen-Bauer A, Meyer MR, Maurer HH (2014) Lefetamine-derived designer drugs N-ethyl-1,2-diphenylethylamine (NEDPA) and N-iso-propyl-1,2-diphenylethylamine (NPDPA): metabolism and detectability in rat urine using GC-MS, LC-MSn and LC-HR-MS/MS. Drug Test Anal. (10):1038-48

[17]- Zarate CA Jr, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I, Jolkovsky L, Brutsche NE, Smith MA, Luckenbaugh DA (2013) A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression. Biol Psychiatry 74(4):257-64

 [18]- https://www.bluelight.org/xf/threads/new-dissociative-rcs-ephenidine-2-chloro-ephenidine-and-2-meo-ephenidine.744515/

[19]- https://www.bluelight.org/xf/threads/lefetamine.275135/

[20]- https://www.bluelight.org/xf/threads/the-small-handy-n-methyl-ephenidine-ephenidine-2-thread.781268/

[21]- https://journals.plos.org/plosone/article/file?type=supplementary&id=info:doi/10.1371/journal.pone.0157021.s019

[22]- Elliott SP, Brandt SD, Wallach J, Morris H, Kavanagh PV (2015). First reported fatalities associated with the 'research chemical' 2-methoxydiphenidine. J Anal Toxicol. 39(4):287-93

[23]- https://psychonautwiki.org/wiki/Diphenidine

[24]- https://www.reddit.com/r/researchchemicals/comments/jl6ygj/ad2pv_report_including_bonus_pre084_information/

[25]- https://www.reddit.com/r/researchchemicals/comments/jah4cn/ad2pv_any_new_user_reports/

[26]- https://www.reddit.com/r/researchchemicals/comments/ibebx5/ad2pv_12diphenyl2pyrrolidin1ylethan1one/

[27]- https://www.reddit.com/r/researchchemicals/comments/iq4i1a/ad2pv_is_anyone_into_it/

 

 

 

2019 in Review

Typically I post a "year in review post" at the end of the year. 2019 was conspicuously absent from this. I am just getting around to writing it. I'm a bit late. "2020 is almost over" you might say, and to that I say shut up, shut the fuck up

But really the reason I never wrote this was because 2019 was a fairly unremarkable year in drug use, I did't do as much and I didn't do as much that was new or interesting. I abused dissociatives, particularly 3-MeO-PCP, 3-MeO-PCE, and 3-HO-PCP fairly regularly. They were immensely recreational, and could still be exploratory at the same time. I began using etizolam, and then flualprazolam, with concerning regularity. I generally used psychedelics less because of their increasingly painful body load. I kept cocaine handy for when I needed a brief little boost, virtue of living within a community where it was easily accessible. I smoked it freebase too. My predominant hallucinogen use was through dissociatives, which I mixed and matched in various permutations, yielding certain extreme and alarmingly intense experiences, sometimes delightful, sometimes terrifying. I had some fulfilling and enlightening experiences with combining n,n-DiPT which I never ended up writing about. I also had a series of extremely powerful and exciting experiences combining 3-MeO-PCE and MXPr, which yielded vivid closed eyed visuals that responded to my command. Not much in the way of new substances however. The most important discovery perhaps was the immense therapeutic value of  3-MeO-PCE. I made another abortive attempt to seek formal treatment for my mental illnesses, therapy that ended up going in circles and producing nothing. My depression transitioned from a constant state of despair to being more episodic (I'm sure that finally losing a major stressor in my life helped too). I've found that a single 25 mg intranasal dose of 3-MeO-PCE could often stop these episodes in their tracks before they had an opportunity to spiral and cause lasting damage. This was not so much a psychiatric pharmacological action as it was a cognitive aid. The little boost of mania and extra confidence perhaps helped me think my way out of self destructive positive feedback loops. I discovered this through trial and error- I cannot state strongly enough how much I recommend against pursuing mental health treatment in a similar way. Don't do it. I got lucky. I hope you can find some fortune too if you're struggling, but not in this way. It works for me though, and I found that to be very interesting.

But mainly, I took the longest abstention from drugs since I began- a whole 3 months using nothing except cannabis. This presented no issues and brought about no cravings, dependence, or withdrawal symptoms. This maybe gave me too much of a confidence boost and I fell hard back into the sauce when that period was over. Drugs hard largely become purely recreational and I also had found there were few new substances left that I had interest in exploring. I tried the fewest new drugs this year than since I began documenting all of this.

There's not really much else to say about 2019. I don't think I lost much data in taking this long to write this. 2020 is going to be a very long post though. As I do in every one of these posts, I will rank the new drugs I tried this year. There weren't that many.

1. MXPr- I'm ranking this as #1 because it's the only dissociative an I love dissociatives. But as far as dissociatives go, this one is pretty lackluster. It's short, has an interesting peak, and then a drawn out boring comedown. It's also pretty boring at lower doses. It's ultimately quite shallow and offers little- on its own. It makes an excellent mixer drug- it adds visual flair and extra dissociation to other dissociatives, so long as they are stimulating enough to power through MXPr's boring comedown. It mixes particularly well with 3-MeO-PCE, 3-MeO-PCP, and 3-HO-PCP (also DMXE, which, if I had written this post on time, would not have existed yet. Shhhh)

2. Flualprazolam- Good and bad. Bad. Idk. This has proven to be an immensely useful and immensely problematic drug at the same time (once again if I was writing this on time, I would not yet be aware of that fact...) It is the ultimate sleep aid for me. Nothing knocks me out quite as well. I could take it at the peak of a stim binge and be out like a lightbulb. It will smother all. It's a bit too good at putting me to sleep. Easy for dependence to form. hm. 

3. 4-PrO-DMT- It had interesting auditory hallucinations. It was intense, a bit uncomfortable, but fun and interesting. Suspected to be a prodrug to 4-HO-DMT but I found it to be quite unique. My batch degraded quickly, at least visually, going from off-white to a dark brown in a few months (stored in a zipoc bag sealed in an amber bag with a dessicant and kept at room temperature). I only revisited it once so no idea if this has affected the potency of the one or two doses I have left.

4. Isobutyl Nitrite- Poppers were unavoidable in the community I found myself living in for a chunk of 2019, just like cocaine. It's fun, that's really all I can say about it. Fun alone, fun with friends. Not that deep or interesting or exciting.

5. 4-AcO-EPT- Short and boring and fairly standard for tryptamine, the most remarkable thing I can say about it is that it's more stimulating than most and has kind of a manic "push" to do things and motivate me into activity.

6. Cocaine (freebase)- literally crack, I didn't get the moreishness or the compulsive redosing that others claim to get from this. I hit what I wanted and was fine. I would, like the ironically named punk band, have leftover crack. It's a fun little stim boost, a good way to get a little kick before doing something else. Not that deep. Mostly, the actual action of smoking it from a glass pipe and preparing all that was really fun and interesting. I wish there were less stigmatized drugs I could smoke in the same way and have a similar low-key experience. (Don't tell me about other stims- another tip that wouldn't have existed if I had written this on time is that most other stims feel a lot shittier to me when vaped)

3-Cl-PCP

 Age: 25

Weight: 130 lbs

Dosage: 150 mg sublingual

Setting: Not my house

 

Preface: Per usual, there’s a tl;dr at the end.

This was one of a suite of new arylcyclohexylamines to debut this year. It was the second attempt at a 3-halogenation with PCP as the base structure – for those not chemically inclined, a halogen atom (Fluorine, Chlorine, Bromine etc.) is attached to a certain place on the familiar PCP molecule. That first attempt saw a Fluorine- 3-F-PCP, a compound that was received with initial interest but ultimately dismissed as being lackluster. I personally found it to be short, intense, and quite neutral and boring with little useful to offer. Just a dumb smack upside the head with dissociation. It also dosed higher than many users found economical. 3-Cl-PCP appeared a few months later, but met little fanfare, perhaps due to the lukewarm reception of its fluorinated counterpart. In the months that have passed, very little information has trickled in about this compound, beyond noting similarities to 3-F-PCP and an even lower potency. The reviews didn’t have me enthralled as those for MXiPr, which was released concurrently and likely helped to overshadow humble 3-Cl-PCP, and I was in no rush to obtain and test this compound. However, I got around to it eventually and was pleasantly surprised by some if its unique qualities! I found it to be interesting and enjoyable and I believe it is worthwhile to investigate and has something to offer to psychonauts of any experience level. This leads me to believe that further development of 3-halogenated arylcyclohexylamines is warranted and will produce worthwhile compounds.

My initial experiences with this compound were with intranasal doses, starting at 50 mg and stepping upwards in what were initially 10 mg increments every ½ hour, but I eventually lost track of the doses and timing and found myself in a pleasant and unique dissociated state after several hours and an unknown cumulative dose >100 mg. Later trials with intranasal and sublingual administration in the range of 80-120  mg showed promise but were still lacking, so I settled on a 150 mg sublingual dose to fully feel out the character of this compound.

A note on the different routes of administration: It seems to be the same potency no matter how you take it, though I have only tried intranasal, oral and sublingual. I imagine rectal dosing would be a similar dose. Intranasal dosing is simply not worth it- it’s a large volume of powder with a strong unpleasant odor and a lingering irritating burn that I could feel into the next day-not quite the sharp instant sting some compounds will impart but something drawn out and torturous. Intranasal doses also appeared to have a shorter duration than other methods. Details on sublingual dosing are in the body of the report.

The setting of this experience was not my usual house, but rather a luxurious apartment in the upscale downtown of the city where I live, where me and my partner were briefly staying. It was an architectural wonder on a quiet block, towering over most of the surrounding houses, affording spectacular views of the skyline and the surrounding cityscape. All of the floors were accessed by a spiral staircase and there were grand windows looking out onto the city in all directions. My partner and I had to vacate our home for a week but were fortunately allowed to stay here during that time- a little vacation in an opulent and luxurious space.

 

T0:00- Dose poured under my tongue. It tastes bitter, not as much the bitter and familiar arylcyclohexylamine petroleum flavor, but fairly rancid and a little sickeningly sweet. Despite the fact that it's in my mouth I feel like I am smelling it more than tasting it.

It's definitely bitter and unpleasant but not like some drugs that reflexively induce retching from the flavor. Unpalatable but entirely manageable. Interestingly, I notice when drinking a lightly flavored seltzer as a chaser, the sweetness seems significantly magnified- a mild and subtle drink suddenly becomes something delicious and tantalizing.

There is a slight tingling sensation directly on the mucous membrane, and just a bit of localized anesthesia. There is some slight corrosion of the mucous membrane but it was fully healed by the next day, unlike compounds like 3-MeO-PCP which can wear a spot on a user’s gums If they’re not careful.

 

T0:30- Onset- feeling a bit warm, heavy, lightheaded.

 

T0:45- It’s hitting more and more, I am feeling faint and distant, like the volume has been turned down on all of my senses. It is a lightheaded and dizzy sinking sort of dissociation, like a pebble spiraling down as it sinks into a river. There is a soothing and calming numbness gently running down my extremities in light blue pulses, it’s cold but pleasantly so, like a cool shower on a hot day. I am bathing in this pleasant dissociative mist, getting thicker and thicker by the second to form into banks of luminous fog.

There is no rush or stimulation, but there isn’t any particular sedation or couchlock either. Getting up and walking around is fun and interesting, I am fairly functional and able to move without issue, just a bit of looseness and excess momentum in my limbs. Lying down on a big soft bed is heavenly too- neither state is necessarily motivated or preferred, it all just feels tranquil and sublime. No matter where I am or what I’m doing there’s this sense of a lukewarm dissociative bath filling up around me, the water a miraculous icy turquoise in color.

I can communicate with my partner without issue for right now, I feel mentally lucid though it feels as though that is starting to wane. I am for the most part in awe of the physically euphoric sensations washing over me like ocean waves and just desire to communicate it effectively with them.

 

T0:50- Feeling it stronger and stronger now, it seems to be building momentum without showing any sign of stopping. I wonder how intense this is going to get- intensity perhaps not being the correct word to describe this experience, it’s an intensifying of a state of bliss and relaxation, sinking into comforts of an increasingly newfound magnitude. Open eyed visuals begin to present- the typical fleeting visuals from dissociatives that just fade into the background. There are gridlike quadrilateral patterns, offset like bricks, ringed in glowing mortar of teal and pink and purple. There is a persistent flashing and strobing in white spaces, like on my computer screen or the white walls of the house.

 

T1:00- It’s building and building, there are dams blocking my flows of thought now as conversation becomes more and more difficult. These dams are big shiny white blocks, wedging themselves into my thought processes, getting in the way. But I am content with this.

While I still feel very relaxed and tranquil, there are paradoxically stimulant side effects I am observing- a shortness and shallowness of breath, constant finger stimming. In contrast to most of my experience with stimulants, I feel quite comfortable and at ease, and despite these little side effects, my heart rate feels normal and I am entirely at peace with lying perfectly still, fingers tapping away at each other. I declare to my partner that I want to hang out in the penthouse/office on the top floor of the house, that I want to play with my pet millipedes (we brought them along on this little vacation because they need to be misted every other day), that I want to go out onto the roof and look out over the skyline, then hang out in the big soft bed downstairs, and then maybe lounge around in the living room. All of these are sensible and attainable goals, easily within my grasp.

 

T1:09- This is delightful! Too much even! It feels like more than I should be feeling, like an absolutely aggressive blockade of my NMDA receptors, like a furious divorce from reality- yet at the same time, it is still so calm, so gentle, so utterly blissful. I find myself mostly in a joyous shock at this contradiction- that I can feel so intensely tranquil. My notes become sparse beyond this point, the timestamps become jumbled as my cognitive function loses its sense of sequence and continuity. I need to close one eye to read letters, and even then, they are an assortment of symbols that I have a hard time parsing meaning from. I am a being of pure senses now, and all of my senses have been dulled and replaced with an alien dissociated euphoria. I feel like I am levitating, constantly rising higher and higher into ascendancy. When I sit still I lose myself to the power of this drug, I lose my sense of body, I feel like I go entirely numb. I can stand up and walk around still, but it feels automatic and aimless. Ascending and descending the spiral stairs is challenging and in the dim light they are taken with flashes of magenta and teal patterns on the walls, swirls and spirals constructed from right angles, washing their way down into the earth. So intense, but what a delight, I feel so happy about this. Whereas 3-F-PCP was cold, grey, absent of color or emotion, this is a subdued festival of the neurons, not necessarily warm, but pleasantly cool, intense but without a rush, visual and colorful and awash with pleasant emotions.

 

T1:18- I have made it up to the top floor somehow, I have opted to just curl up in the corner on the wood floor. I am wearing several soft warm layers and I am quite cozy here in my little space. My body feels like it has absorbed into itself, that my entirety is just as small as I am while curled up like this, and it is as large as I will ever be. My proprioception has become more and more vague and scrambled. The short and shallow breathing from before had now given way to slow, soft, deep and gentle breaths. Every part of me was at peace. My memory gets hazier past this point. My partner brings up my pet millipedes to play with, I don’t recall taking them out at any point though I’m sure the tactile sensation of them crawling on my skin would’ve been lovely.

My notes at this point are hard to decipher- they are laden with typos and seemingly keyboard smashing gibberish, a testament to my rapidly declining motor skills. My physical form feels like it’s drooping and dripping and literally physically melting at points, like a candle. At some point my phone ran out of battery and I couldn’t piece together the process of finding a charger for it, which further unanchored me and particularly made it hard to readily keep time. It’s hard to type, hard to think, hard to move, all I can do is just melt in the corner, and frankly it’s still a joyous carnival of total inhibition, I am still feeling calm and tranquil and awash in euphoria, I am still having a great time. At points my eyes drift shut, I allow myself to sink into the hole of this dissociation and there is a sensation of my body melting into a puddle that seeps into the floor, it’s weight stretching the surface like a bowling ball dropped onto a trampoline. I am greeted by endless spirals and blossoms of tangled forms in silhouette, backlit by a shifting cool light. Everything is spinning and swirling and drifting, slowly and deliberately, everything gentle and just as it needs to be.

At some point my partner brings up a book that is a collection of plates done by the legendary artist-naturalist Ernst Haeckel- opulent and intricate depictions of the diversity of life in this world, embellished with symmetry and sublime composition. His style can render even familiar species as unrecognizable, while a certain alien quality is also inherent in many of the obscure invertebrates and odd microbes that he illustrated. I feel like I am gazing upon a bestiary of another world- even the species I recognize, my memory falters and I fail to remember their names. I decide to take joy in resigning to the separation from the familiar, to simply revel in not knowing, in just assuming that yes, these are indeed novel life forms the likes of which mankind has yet to encounter or describe. Even cognitively, this drug seems to force me to settle for the least stressful option, to always assume the best. Anxiolysis is certainly a trait that can be explicitly and uniquely ascribed to this dissociative.

 

T1:40- At some point I manage to go down the stairs to go pee. I sit in the dark and distinctly recall marveling at how vivid the visuals are in this setting- Everything is tinted in deep violets and vivid electric blues- everything is in a constant downward motion, like the visuals are a liquid cascading down every surface in the room. They swirl like the clouds of Jupiter, they are fringed with tendrils and fractals like a tangle of vines, always in flux, always in motion. I am nothing at this point, I am hardly even aware of what I’m doing or why I’m in this room right now, beyond a vague suggestion from my body. Never before have I quite reckoned with the simple biological fact that every animal, save for some highly evolved parasites, is ultimately nothing more than a glorified tube, sometimes branching at points, but nonetheless the body of each creature is constructed around a basic in and out dynamic. My appendages, my organs, my senses, all suddenly seem superfluous in the face of this fact- what is a tube to do other than sit completely still? I couldn’t keep exact track of time due to my phone still being dead, but I was presumably in there for quite a while after I was done what I needed to, just reckoning with my facts of my biology and staring in awe at the vivid drifting visuals, like a constant shower of branches, a garden of translucent vines, or perhaps a bed of seaweed undulating in the waves. I eventually manage to stand up, wash my hands, and navigate myself back upstairs, with a distinct memory of crawling up the spiral stairs on all fours. I believe my next objective was to go out on the roof deck and gaze at the scenery, though my memory is especially foggy around this point. I recall fiddling around with bundling up and gathering what supplies I may need. I recall grappling with various technological challenges- my laptop’s touchpad failing (as it will occasionally do), it failing to connect to a speaker, my phone still being bafflingly dead (I seemed to have kept forgetting this and checking its blank black surface time and time again)- after struggling with what would have otherwise been quite simple tasks for some amount of time, I managed to settle in successfully- laptop still there for notes, hooked up to a nice bassy speaker, my external mouse somehow successfully established, water and cannabis at the ready, and warm soft layers to shield me from the cold. Perhaps being on a rooftop 5 stories up sounds ill-advised in this state, and perhaps it is, though I was confident it wouldn’t be an issue for me.

 

T2:20- I feel a sudden sense of clarity now that I have settled down and worked through the confusion of technology and small objects while heavily dissociated. It’s hard to grasp what I need to do and why when my short term memory is faltering and my sense of cause and effect has been stunted. I take a few hits of cannabis from my one hitter as I usually do, though this seems to have little effect on the experience beyond perhaps adding a bit more definition to the visuals. I lie on my back first and gaze into the night sky, rows upon rows of violet-blue clouds illuminated from below by the city lights. Great pulses of waves and ripples pass through the clouds in regular patterns, their fronts not curved but constructed from a series of right angles. These jagged step-by-step undulations leave washes of color in their wake, little flashes of iridescent lightning. I truly get a sense of the sky being a great dome above, it feels like it seals me in where it meets the horizon, I am not truly outdoors but simply enclosed in yet another vast space. Lying here in all of my soft layers is heavenly, I don’t even notice the bite of the December air or the cold tarmac of the roof- my eyelids grow heavy and drift shut from the weight of my bliss under this great hemisphere. I hug my speaker against my body as a nice bassy pop pulses into my body, the vibrations massaging my abdomen.

I wish I could lay like this forever, in the darkness of the back of my eyelids, a shimmering gossamer spiral of blue cellophane rippling and pulsing to the vibrations of the music, extending into the infinite walls of the great sphere that encloses me. I feel my body sink straight downwards, melting and drooping into the abyss until it is conjoined with the pulsing membrane, and suddenly without a body I am a being of pure vibration and vitreous blue energy. Changes in the music elicit slight changes in the visuals like flashes of color and light in the distance, taking various patterns and aligning to various synesthetic themes and emotions. Ultimately, the hallucinatory space remains abstract, predominantly dark with small flashes of cool colored lights, and mostly unchanging, in steady and gentle motion like ocean waves lapping up on a beach at night, laden with bioluminescent plankton.

It’s quiet here- my mind is blank and I am not really delving into coherent thoughts-ruminations on memories or emotions or the self, it’s just a quiet tranquility, the sensory pleasure of such a vivid yet ultimately cryptic and subdued forms in the endless dark. I could be here forever, but eventually, as time passes, the drug’s effects begin to wane, thoughts of the world beyond this space begin to invade, I begin to feel bored and impatient, I want to open my eyes.

I sit up and begin to really take in my surroundings- skyscrapers tower over me in one direction, their peaks lit up by an array of prismatically colored lights, their bodies a constellation of pockmarked windows lit windows. It is around 1 AM and very quiet. In another direction, the distant twinkling of vast industrial fields and refineries, smokestacks and plumes of steam illuminated by the lights bellow, to one side, a single massive building with a grand art deco topper towered particularly close. As I took in the scene, they would blur, split into double images or mirror themselves, be accompanied by shadow forms that would shoot up infinitely into the sky as beams of light and shadow. What was once the familiar skyline was soon becoming a dense jungle of phantoms, pillars of light and glass piercing into the dark, cloudy heavens. I sighed, the same slow and heavy breaths as had taken the peak of this experience, and felt so at peace. This city was beautiful, all of this, all of the glass and light intentionally constructed to be deliciously consumed by my hungry eyes, it was a wall of pure rippling sensation that tore through me. I was taken yet again with cresting waves of euphoria.

 

T3:00- I come back inside- I can walk a little easier now, I am a bit more lucid and aware of what I am doing and how time proceeds and the nature of cause and effect. I stumble around looking for my partner, finding it odd and lonely that the room is empty when I come back in, before finding them in the living room downstairs. The stairs are a bit more navigable by this point. There are still strong visuals in place, abstracted patterns in gently lit relief settling into various surfaces, still usually along the lines of a simple gridwork. In the dark coming down the stairs I was still greeted by the same drifting and flowing curtains of vines and tangles of tendrils that I was treated to before, flowing down the walls like the light cast through a window during a heavy rainstorm at night. My head is still spinning and I find myself tending to sink into wherever I come to rest- not fully disintegrating into a hole but becoming still and immersed in what sensations come through.

 

T3:30- What a soft and comfortable dissociation- at this point what remains of it feels like a gentle plush pressing in on all sides of me, a steady pressure that pulses and beats with my heart. I am so cozy, at no point has this drug made me feel any semblance of physical discomfort, no matter what my body is doing or what position it’s in or what surface it’s resting on. After a point we go up and hang out in the bedroom. Lying on the bed is as heavenly as it was when I was coming up. I am steadily coming down now, my thoughts are becoming steadily more lucid and coherent and I can hold conversation better as time passes. I notice there is still a loss of proprioception around my lips and tongue, causing me to stumble over words as I speak and mispronounce things. I realize now how important the feedback of being able to feel one’s mouth is to the ability to speak clearly and articulately.

 

T4:20- Mostly down- there is a lingering numbness in my limbs but my brain feels like it has mostly returned to normal, with maybe a slight persisting short term memory loss.

 

T6:00- The effects of the drug are no longer discernible. I try to sleep but find myself lying awake well into the morning, despite lacking any marked stimulation. Perhaps it was just the setting and my overall health that kept me up all night, as I felt in a state of sober anxiety the entire time. It would appear those distinct anxiolytic effects do not last. I eventually fall asleep around 9 am.

 

Conclusion: 3-F-PCP was received by many (including this author) as lackluster and just a surge of pure neutral dissociation. Thus, expectations were fairly low for 3-Cl-PCP, which initial reports indicated was similar in character. For me personally however, my expectations were far exceeded. So much pleasantly surprised me about this drug, but chiefly, it was how novel and unique it felt. It was really incomparable to any other dissociative I’ve taken, due to several factors. The first is simply how soft and soothing and supremely anxiolytic it is- it is a gentle plush dissociation, pleasant and euphoric the whole way through abound with delightful physical sensations. It feels like lying on a king size bed made of clouds. Yet it was absent of any noticeable sedation or stimulation. There was no mania, no rush, no intense motivation to do things- but there was also no couchlock, no mental inhibition that just left me drooling in a daze for hours. It was simple and matter-of-fact- if I wanted to get up and move, I could, and it felt good and soft and melty- if I wanted to sit still, I had no issue with doing so for long periods of time, and that too was soft and good and melty. A dose of 150 mg was sufficient for a deeper out of body experience for me, other users may find such a dose a bit intense. A dose from 100-120 mg orally or sublingually should still present some degree of the soft and pleasurable dissociative anxiolytic effects. A dose this high was, for the peak of it, largely non-functional and cognitively inhibiting, though still greatly enjoyable. The comeup and comedown were sociable and warm. Add to that a distinct character for the visuals and sensory aspect of the trip and it yields a uniquely pleasant experience, ideal for a night at home alone with soft surfaces and some music or with a loved one. Perhaps not an ideal drug for going out for a walk during the daytime. If I had to compare it with anything, it would in fact be Ephenidine, or another diarylethylamine- they share a similar still, sinking dissociation, as opposed to any kind of rushing sensation. But it is ultimately something unique and worthwhile of its own. My only complaint is the fairly high dose required for desired effects.