rational exploration of the underground

There are common visual concepts which cut across boundaries of culture and time and reflect what it truly means to be human. Near death experiences are often associated with seeing a “light at the end of a tunnel”. In the Bible, God appeared to Ezekiel as a “wheel within a wheel”. Spirals and concentric circles are commonly found in petrogylphs carved by cultures long dead. Similar visual effects are reported during extreme psychological stress, fever delirium, psychotic episodes, sensory deprivation, and are reliably induced by psychedelic drugs.

In 1926, Heinrich Klüver undertook a groundbreaking series of experiments where he categorized the visual effects produced by mescaline. Various volunteers were recruited, peyote administered, reports taken, and results classified into categories. There were general perceptual effects, variations in color and distortions of shape. But the most interesting reports were consistent visual concepts he dubbed “form constants”. Across many volunteers and many sessions, all reported seeing visual patterns with similar structure.

They were classified into four main types: I) tunnels, II) spirals, III) lattices, and IV) cobwebs. For almost fifty years, these form constants were regarded as a strange mystery of visual perception, a seemingly unexplainable common human experience.

In 1979 Jack Cowan and G. Bard Ermentrout put forward a very interesting explanation, supported by a rigorous mathematical treatment. These visual effects are the result of specific noise patterns in the visual cortex, which are then transformed by the wiring between the brain and the eye to produce these unique shapes. They generated simple biologically allowable noise patterns, transformed them, and produced graphs of these form constants.

Let’s dive a bit deeper into how this was done, by first having a look at the structure of the visual cortex. We’ll look specifically at V1, the first layer of visual processing where information from the retina is fed to. We can think of it as a sheet of hypercolumns, cells sensitive to lines oriented in any direction. This surface is crinkled up like a ball of paper in your brain, but we can unfold it in a theoretical sense. These hypercolumns are linked together in a specific manner, which allows noise patterns of only certain types to form. Just like a tarp in the wind will only flap in certain predictable ways assuming it does not tear, so too will noise only travel across the visual cortex in specific ways. Four types of noise were found.

These stable planforms can be thought of as excited noisy states in contrast to the normal low-activity state of the visual cortex. We can refer to them as I) the non-contoured roll, II) the non-contoured hexagon, III) the even contoured hexagon, and IV) the even contoured square.

So now that we have our noise patterns, how are they mapped from the visual cortex to what we actually see? Biology provides a clue here. Experiments have been done which allow mapping of how the visual cortex represents input from the retina. By stimulating a certain point or region of the retina, the corresponding cells which light up in V1 can be measured. The easiest mapping you might think of would be for the input of the retina to be represented as a flat sheet, which is then passed to the visual cortex like a photocopy. Instead, it turns out that the circular retina’s image is twisted and mapped in a slightly more complex manner to the flat surface of V1.

Visual Cortex (V1)	Retina

We can see that straight lines in our visual cortex are mapped to curved lines in the retina, and vice versa. We can represent this relationship mathematically using the complex logarithm, so let’s apply this complex log transform to our four types of visual cortex noise.

And beautifully, Klüver’s four form constants are produced, visual cortex noise twisted by the wiring between mind and eye. This hypothesis fits the fact that these high energy states may be caused by a variety of stimuli affecting excitability of the brain but most reliably by psychedelic drugs which bind to serotonin receptors richly expressed in the visual cortex.

It is compelling to think that these powerful symbols rely on no religion, no culture, and no time. They are a product of the fact that we are all human and share the same biology. A true tragedy that these visions have been used as an excuse to kill others when we all see the same wheels within wheels.

Ermentrout, G.B. and Cowan, J.D., “A mathematical theory of visual hallucination patterns.” Biol. Cybernet. 34 (1979), no. 3, 137-150.

Bressloff, Paul C.; Cowan, Jack D.; Golubitsky, Martin; Thomas, Peter J.; Weiner, Matthew C. (March 2002). “What Geometric Visual Hallucinations Tell Us About the Visual Cortex“. Neural Computation (The MIT Press) 14 (3): 473–491.

In an age where individual privacy is dead yet corporate structure easily dilutes personal responsibility to nothing, a strange cadre has emerged. With no central organization, no stated goal, and no membership list, they have earned the name “Anonymous”.

Why Anonymous? Why not a catchy counterculture label of choice? It has stuck for the same reason that the words “peace activist” are spit from the lips of news anchors with incredulity that anyone would actually bother. War makes quite a bit of money after all, and those who benefit decide what is news.

Any label, any characteristic, any identifying mark can be used to stereotype, to appeal to dark tribal instincts and create the fear of the “other” and external attack. Someone working toward something as abstract and universally desirable as peace would seem inoffensive, but there is certainly something a speaker can latch onto to create fear. There are the tribal basics that have worked for millennia - a different sex, different culture or religion, or different appearance. Perhaps you consider yourself above such base instincts - you will then be manipulated based on the fact that the “other” holds different political beliefs than you on unrelated issues. There will be something different, something to set them apart, something that makes them a member of a foreign tribe. Despite a desirable common goal for nearly all of society, all that is needed is a single difference that will be publicized and our ancient tribal fears take over. We fall for it again and again.

The popular social movements of the past failed for one common reason. They assumed that we are all part of the same tribe, that we will come together and unite. This is the root of the failure. One cannot overcome tribal instincts by making the tribe large, especially when a very powerful segment of society refuses to join.

The way forward is the first post-tribal movement Anonymous, legion who do not belong to anything.

Göring: Why, of course, the people don’t want war. Why would some poor slob on a farm want to risk his life in a war when the best that he can get out of it is to come back to his farm in one piece? Naturally, the common people don’t want war; neither in Russia nor in England nor in America, nor for that matter in Germany. That is understood. But, after all, it is the leaders of the country who determine the policy and it is always a simple matter to drag the people along, whether it is a democracy or a fascist dictatorship or a Parliament or a Communist dictatorship.

Gilbert: There is one difference. In a democracy, the people have some say in the matter through their elected representatives, and in the United States only Congress can declare wars.

Göring: Oh, that is all well and good, but, voice or no voice, the people can always be brought to the bidding of the leaders. That is easy. All you have to do is tell them they are being attacked and denounce the pacifists for lack of patriotism and exposing the country to danger. It works the same way in any country.

From Gustave Gilbert‘s interview with Hermann Göring in his jail cell, Nuremberg War Crimes Trials, 18 April 1946.

The alkylated napthoylindoles were the first synthetic cannabinoids cheap and potent enough to make real noise on the recreational drug market. Concern was initially raised about metabolism of the naphthalene ring and resulting carcinogenic risk, which turned out to be validated (abstract O43) although perhaps initially overstated as it lies within a similar risk envelope as cigarettes. Compounds have now been produced that replace the naphthalene ring with a phenylacetyl group. These represent a new and unique class of synthetic cannabinoids, with applications as both replacements for banned cannabinoids and use as a possibly healthier alternative for informed users. Without substitution the structure is much less potent than JWH-018, but various substitutions at the 2, 3, and 4-position have been attempted. The 2-position substitutions demonstrate the highest potency as a class, and are outlined here.

JWH-167 (CB1 K_i = 90 ± 17 nM, CB2 K_i = 159 ± 14 nM) is shown here with JWH-018 and its naphthalene group in a light grey underlay for reference. Without any substitutions this base phenylacetylindole is not potent enough for sale on the recreational drug market, as it is roughly a tenth as potent as JWH-018 as measured by binding affinity.

JWH-251 (CB1 K_i = 29 ± 3 nM, CB2 K_i = 146 ± 36 nM). A methyl group at the 2-position increases potency, but binding affinities seem to be too weak for practical sale. This is contrasted with the facts that JWH-251 was found to be a component of certain Japanese “herbal smoke” blends and limited reports indicate this to be of somewhat similar qualitative potency to JWH-250. Time will tell if this compound will remain on the edge of the market or gain popularity.

JWH-250 (CB1 K_i = 11 ± 2 nM, CB2 K_i = 33 ± 2 nM). Currently the most popular phenylacetylindole. The 2-methoxy substitution produces a compound that is qualitatively slightly less potent than JWH-018, but produces a much more pleasant effect in higher dose ranges. As such, this compound has found favor with those who prefer a stronger cannabinoid experience without the near-certainty of anxiety in higher doses that JWH-018 was known to cause.

JWH-311 (CB1 K_i = 23 ± 2 nM, CB2 K_i = 39 ± 3 nM). Fluorine substitution provides the least potent outcome of the three halogens Huffman explored. Not widely available or tested.

JWH-203 (CB1 K_i = 8.0 ± 0.9 nM, CB2 K_i = 7.0 ± 1.3 nM). The most potent halogen substitution, and one of the most potent phenylacetylindoles along with JWH-250. Currently available for sale, but not widely explored.

JWH-249 (CB1 K_i = 8.4 ± 1.8 nM, CB2 K_i = 20 ± 2 nM). Slightly less potent than JWH-203, with a lower CB2 affinity that may be associated with reduced anxiety effects. Not widely available for sale, but could be waiting in the wings if JWH-203 takes off and is scheduled.

John W. Huffman, P. V. Szklennik, A. Almond, K. Bushell, D. E. Selley, H. He, M. P. Cassidy, J. L. Wiley, B. R. Martin, 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles, Bioorganic & Medicinal Chemistry Letters, Volume 15, Issue 18, 15 September 2005, Pages 4110-4113, ISSN 0960-894X, DOI: 10.1016/j.bmcl.2005.06.008.

Burn it up, Thoughts on JWH-18 carcinogenicity, 01-05-2010, 02:22, Bluelight > Drug Discussion > Advanced Drug Discussion.

The 2C class of psychedelic compounds first researched by Alexander Shulgin encompasses a wide range of mental experiences, but one substitution in particular seemed to resonate with the magic seen in legendary compounds like mescaline. Thioalkylation at the 4-position produced the famed 2C-T-2 and 2C-T-7, compounds noted for an almost overwhelming visual character with echos of the cosmic choir, and a dismantling of the ego more prominent relative to the perceptually focused halogenated and alkylated 2Cs. This unique experience caused Shulgin to focus his substantial talents on sulfur based substitutions at the 4-position for a period of time, producing a large number compounds named in the format 2C-T-x. The first twelve are outlined in this post.

One attribute of these compounds must be emphasized at the outset. Unlike the halogenated or alkylated 2Cs, sulfur substitutions appear to be correlated with varying degrees of MAO inhibition, which can cause significant health issues up to and including death in extreme doses or in combination with other recreational drugs, particularly stimulants. These compounds were used safely in reasonable oral doses for twenty years among a qualified group of explorers, but the research chemical surge of the early 2000s introduced these compounds to an untrained audience in pure bulk forms. With resellers actively encouraged not to disseminate information on safer consumption due to legal pressures to maintain an appearance of “not for human consumption”, reckless dosing and routes of administration led to tragedy.

2C-T-2 has been sold widely, and has not been involved in any fatalities to my knowledge presumably due to less significant MAOI effect as judged by euphoric “push” relative to the other sulfur substitutions. 2C-T-7 can be considered the most popular of the group, and has nonetheless been involved in at least three deaths involving either excessive insufflated doses over 30mg, use in combination with stimulants such as MDMA or ephedrine, or both. The less popular 2C-T-21 has produced one death after an extreme oral dose (sticking tongue in full vial of pure compound).

The desire to experience the mental state produced by these compounds should be weighed with the intentions, ability, and risk tolerance of the end user. A society which allows the purchase of firearms with the assumption of responsibility should allow the same for self-exploration, but this is often not the case. If you are unfamiliar with the mechanism of risk of these compounds (ie MAO inhibition), if you are unable to weigh these compounds accurately, and if you are unwilling to respect the impact of route of administration, then an alternative should be selected.

2C-T (2C-T-1, 2,5-dimethoxy-4-methylthiophenethylamine) Active in doses of 50-150mg, this compound produces a euphoric psychedelic experience for 5-6 hours that nonetheless was described as “generic” by Shulgin. Lack of potency relative to other closely related compounds and the somewhat shallow mental state make this a rare find on the research chemical market.

2C-T-2 (2,5-dimethoxy-4-ethylthiophenethylamine) Active in doses of 10-30mg, this compound produces a 6-8 hour experience most notable for its intellectual introspection, mescaline styled visuals, and unholy ability at higher doses to cause physical distress including nausea during the first hour of the experience. Like mescaline, after the purge a sense of contentment develops and the experience then progresses naturally. 2C-T-2 first rose to wide fame after the banning of 2C-B, and was first sold by Dutch smartshops as a substitute in 1997. As it produced a much richer and deeper psychedelic experience than 2C-B, it did not have as wide an appeal on the club circuit, but still sold widely enough that it was eventually banned by Dutch authorities.

2C-T-3 (2C-T-20, 2,5-dimethoxy-4-(beta-methallyl)thiophenethylamine) Also known as 2C-T-20. Before working on the 2C-T series Shulgin investigated a similar series of promising compounds dubbed the Alephs, of which Aleph-3 was the beta-methallyl homologue. The synthesis of Aleph-3 was attempted, abandoned, and eventually forgotten. Years later the idea came to Shulgin again, and the beta-methallyl Aleph was begun anew along with the corresponding beta-methallyl 2C-T compound (2C-T-20). This led to the rediscovery of notes referencing the initial Aleph-3 synthesis attempt, and 2C-T-20 was renamed 2C-T-3 in order to maintain consistency with the Aleph project.

It is unclear if there was ever an “original” 2C-T-3 whose place was overwritten or shifted by insertion of the beta-methallyl. It is certainly an odd man out in the progression, as it would seem reasonable to place the n-propyl 2C-T-7 here after the ethyl 2C-T-2 and before the isopropyl 2C-T-4. A numbering system based on the previous Alephs appears to explain the gap, as perhaps the initial synthesis of the 2C-T-3 was simply left for later due to the increased difficulty relative to the alkyls surrounding it. The synthesis of 2C-T-3/2C-T-20 has never been completed according to public knowledge.

2C-T-4 (2,5-dimethoxy-4-isopropylthiophenethylamine) The isopropyl companion to the propyl substituted 2C-T-7. Active in doses between 8-20mg, it produces a long lasting change in mental state for 12 to 18 hours with a slight dissociative character. Human testing showed huge variance in responses, particularly in the subcategories of visual distortion and euphoric response. The inability to predict whether a 12+ hour long psychedelic experience would be euphoric and illuminating or dysphoric and anxiety ridden has contributed to a lack of recreational usage of this drug.

2C-T-5 (2,5-dimethoxy-4-cyclohexylthiophenethylamine) Has never been synthesized according to public knowledge, and was presumably based the similarly structured Aleph-5.

2C-T-6 (2,5-dimethoxy-4-phenylthiophenethylamine) Has never been synthesized according to public knowledge, and was presumably based the similarly structured and successfully synthesized Aleph-6.

2C-T-7 (2,5-dimethoxy-4-(n)-propylthiophenethylamine) Active in doses of 10-40mg with a duration of 8-16 hours, 2C-T-7 is perhaps the most popular of Shulgin’s sulfur substitutions likely due to a more consistent euphoric effect. A powerful psychedelic character lies underneath however, and initial hype about a easy to handle “candyflip” experience may have resulted in some overwhelming experiences. With nausea reported less frequently as a side effect in comparison to 2C-T-2, many cast 2C-T-2 aside as a shorter less euphoric 2C-T-7. This is not necessarily a valid critique, as the more euphoric mental state of 2C-T-7 often results in “sloppier” emotional analysis relative to the slightly more difficult and intellectual 2C-T-2. 2C-T-7 began its rise to fame in the summer of 1999 as Dutch smartshops began selling it in 7.5mg tablets dubbed “Blue Mystic” due to the success (and resulting ban) of 2C-T-2. Unsurprisingly, 2C-T-7 was quickly banned as well.

2C-T-8 (2,5-dimethoxy-4-cyclopropylmethylthiophenethylamine) Active in doses of 30-50mg and producing a 10-15 hour experience, this compound produces a mental state that many did not wish to repeat. Shulgin said in PiHKAL, “there are as many negatives as there are positives, and the particular substitution pattern is not one to set the world on fire.”

2C-T-9 (2,5-dimethoxy-4-(t)-butylthiophenethylamine) Active in doses of 60-100mg, it produces a 12-18 hour experience with significant peripheral body load and little psychedelic reward for the effort. Note that Wikipedia currently incorrectly refers to this as the n-butylthio substitution rather than the tert-butylthio referenced in PiHKAL, as the n-butylthio substitution should be referred to as 2C-T-19.

2C-T-10 (2,5-dimethoxy-4-(2-pyridylthio)phenethylamine) Synthesis was abandoned before completion, and has not been completed by others according to public knowledge.

2C-T-11 (2,5-dimethoxy-4-(4-bromophenylthio)phenethylamine) Synthesis was abandoned before completion, and has not been completed by others according to public knowledge.

2C-T-12 (2,5-dimethoxy-4-(1-morpholinothio)phenethylamine) Synthesis was abandoned before completion, and has not been completed by others according to public knowledge.

Sulfurous Samadhi, An Investigation of 2C-T-2 & 2C-T-7 by Murple, Feb 6, 2001.

Nichols, D. E. and Shulgin, A. T. (1976), Sulfur analogs of psychotomimetic amines. Journal of Pharmaceutical Sciences, 65: 1554–1556. doi: 10.1002/jps.2600651040

With the recent legal issues surrounding certain synthetic cannabinoids in the United States, the market has changed. Instead of economic pressures selecting certain cheap to produce cannabinoids with desirable effects, legal pressures have now created a situation where the inelastic demand of recreational drug users causes overseas manufacturers to seek the highest potency compounds in order to minimize risk of seizure. People still want to buy it, but they want to minimize the number of transactions, so send the tiniest package with the largest value.

Previously in the market we saw various simple substitutions of the cheap, easy to synthesize, and potent original, JWH-018. But halogenated analogs, previously cast to the side due to more involved synthesis routes, are now becoming more popular due to the trend of increasing potency and duration. The difficulty in handling these very powerful compounds has caused them to be most prevalent in the commercial “smoke blends” market, where a fraction of these halogenated analogs can replace a far larger volume of the earlier generation cannabinoids. With these new legal pressures on end users however, we are seeing an increasing tendency toward the retail sale of these pure compounds.

The first of the halogenated AM series cannabinoids to reach the market was AM-694, discussed in Synthetic Cannabinoids: JWH-018 Replacements. This shares a fluoropentyl chain with AM-2201, and initially health concerns were raised about possible metabolism to toxic fluoroacetate. Luckily it appears that the odd-numbered (pentyl) chain means that the less toxic 3-fluoropropanoic acid will likely be produced instead, but this raises questions - if an even numbered fluoroalkylated chain was found to obscenely potent, would these health concerns prevent it from being brought to market? Or would the economic incentives of this crudely regulated market result in a product being sold with the excuse that only chronic long-term exposure is likely to result in apparent health risks? One would hope that manufacturers would not be so greedy, but history is not reassuring.

The effects of AM-2201 also appear to differ from natural cannabis and the first generation synthetic cannabinoids, both to start and as tolerance builds. Initially the effects are quite similar, although doses for AM-2201 are approximately a third of JWH-018. This has resulted in many reports of self-reported “seasoned” synthetic cannabinoid users having anxiety reactions as a result of apparent overdose due to increased sensitivity to inaccurate measurement. Tolerance builds quickly, and frequent users have reported psychedelic-style effects typically previously only associated with high-dose oral consumption of marijuana. The major difficulty with these high potency compounds is finding the “window” - that range of dosage where effects are strong enough to be considered enjoyable, but not so strong that peripheral effects such as anxiety or or dissociation affect the recreational potential. Measurement noise appears to translate to a rather inconsistently enjoyable experience.

It is frustrating that regulators appear to not consider the consequences of the time-tested inelastic demand of recreational drug users. Natural cannabis has been used for thousands of years with little ill effect, and its prohibition resulted in the birth of the synthetic cannabinoid market, compounds that have been known to science for at most a few decades. Now unthinking attempts to stamp out the first generation synthetic cannabinoid market have resulted in the promotion of hyperpotent substitutes patented in the mid-2000s. It is the very definition of unintended consequence to consider that regulatory promotion of these relatively unknown compounds could result in more public health concerns rather than less.