Archive for the ‘ History ’ Category

Leminger’s Scalines

Otakar Leminger was a little-known Czechoslovakian chemist who worked for years in industry and lived on the banks of the Elbe River in Ústí north of Prague. When he retired in the early 1970s he published a paper entitled “A Contribution to the Chemistry of Alkoxylated Phenethylamines” in which he describes the synthesis of several novel phenethylamines which he tested on himself to determine activity.

(1) allylescaline, 3,5-dimethoxy-4-allyloxy-phenethylamine (2) proscaline, 3,5-dimethoxy-4-n-propoxy-phenethylamine (3) escaline, 3,5-dimethoxy-4-ethoxy-phenethylamine (4) MAPEA, 3-methoxy-4-allyloxy-phenethylamine (5) MEPEA, 3-methoxy-4-ethoxy-phenethylamine

We can classify the compounds he discussed into two groups depending on the number of ring substitutions. Allylescaline, proscaline, and escaline have three while MAPEA and MEPEA have two. Generally phenethylamines with two ring substitutions are not active, but Leminger had found some exceptions. This knowledge might have been lost to time if not for the fact that Stanislov Wistupkin brought the paper to the attention of Alexander Shulgin.

[MAPEA and MEPEA are some] of the few phenethylamines with only two substituents that show even a hint of central activity. And there is an interesting story attached. I got a call out of absolutely nowhere, from a Stanislov Wistupkin, that he had discovered a number of new psychedelic drugs which he would like to share with me. They were simple phenethylamines, one with an ethoxy group at the 4-position, and one with an allyloxy group there. Both, he said, were mood elevators active between 100 and 300 milligrams. One of them was a material called MEPEA, and the other one was 3-methoxy-4-allyloxyphenethylamine, or MAPEA. When I did meet him in person, he gave me a most remarkable publication which had been authored some ten years earlier, by a person named Leminger, now dead. It was all in Czech, but quite unmistakably, right there on the third page, were the structures of MEPEA and MAPEA, and the statement that they were active at between 100 and 300 milligrams.

– Alexander Shulgin

MAPEA and MEPEA are only mildly active and interesting mostly in the sense that they appear to be the exception to the rule that phenethylamines with two ring substitutions are inactive. Leminger also created several mescaline variants with three ring substitutions by modifying the methoxy group at the 4 position and replacing it with an allyloxy, propoxy, or ethoxy group. The resulting compounds allylescaline, proscaline, and escaline were then tested on himself and found to be much more potent and intriguing.

Physiological effects of the compounds were examined only approximately on my body. The sulphate salts of MEPEA and MAPEA in doses 0.1-0.3 g were mild mood-elevators and were also cough calming agents. Allylescaline, proscaline, and escaline were much more active. Qualitatively there wasn’t a big difference among them and quantitatively their effect decreased: allylescaline was more potent than proscaline, and proscaline more potent than escaline. As an example the allylescaline experience is described:

“One hour after a 20 mg dose of allylescaline: perhaps slight vertigo, light drunkeness and pleasant excitation with locomotion need was observed. Eye perceptions were pricked up, colours seemed to be more warm and objects more plastic. Surroundings were much more interesting than usual. Colourful hallucinations were observed in the dark. Moreover, a calming effect to the breathing system and some kind of constriction of the digestive system was observed. Sleep at night was restless with megalomaniacal fantasies. Even 12 h after administration the effects were present. More serious studies of physiological activity are in contemplation.”

– Otakar Leminger

Leminger was the first to synthesize and consume allylescaline, the most potent of the mescaline derivatives explored. He was able to identify active phenethyamines with only two ring substitutions, a notoriously unproductive class of compounds. Did he conduct additional experimentation and screening beyond that detailed in this paper? No other publications by Leminger relating to psychedelic compounds are known.

Might there be other treasures that he had discovered, and never published? Was young Wistupkin a student of his? Are there unrecognized notes of Otakar Leminger sitting in some farm house attic in Northern Czechoslovakia? I extend my heartfelt salute to an almost unknown explorer in the psychedelic drug area.

– Alexander Shulgin

Otakar Leminger, A Contribution to the Chemistry of Alkoxylated Phenethylamines – Part 2. Chemicky Prumysl 22, 553 (1972).

Alexander Shulgin, #2 Allylescaline. Phenethylamines I Have Known and Loved, Transform Press (1991).

Alexander Shulgin, #123 MEPEA. Phenethylamines I Have Known and Loved, Transform Press (1991).

Dr. Atomic’s Marijuana Multiplier

First published in the early 1970s, Dr. Atomic’s Marijuana Multiplier provides an illustrated walkthrough to produce high quality hash oil based on the methods described in Gold’s Cannabis Alchemy.

from Dr. Atomic’s Marijuana Multiplier. Larry S. Todd, 1974.

Clarifying the Confusion Regarding LSD-25

The following article was published in the mid-1960s as an attempt to provide an educated response to the increasing hysteria about LSD use in the popular media of the time. It proposes a model of responsible psychedelic use through an understanding of the experience itself, factors affecting the experience, and typical routes of misuse.

An edited version follows, and a link to the original paper may be found at the end of the post.

In recent months, both the lay and medical press have been filled with warnings about the dangers and harmful effects of the hallucinogenic agents such as LSD-25, mescaline and psilocybin. These warnings have risen in response to flagrant misuse of the substances by illicit operators using black-market materials for parties and “kicks,” and by irresponsible investigators who, enthralled with the remarkable possibilities of these chemicals, have sponsored and encouraged their widespread use under improperly controlled conditions without medical supervision.

In view of the substantial promise which even a cursory study of the work of the leading investigators in this field reveals, it is puzzling that there should be so little acceptance of the usefulness of the hallucinogens. Following are probably the outstanding reasons:

1) Lack of understanding of the drug experience: The hallucinogens (more properly called psychedelic agents when used to explore new understanding of the mind) open up dimensions of consciousness with which few therapists are familiar. The heightened sensitivity and enhancement of sensory modalities, the reliving of events in time and other dimensionless phenomena, and the oft-reported profound philosophic and universal experiences, tend to lie outside the therapists’ conceptual frame of reference. By denying these experiences, or attempting to restrict the experience to his own theoretical framework, the therapist can produce great conflict in the subject, and cause him to reject important parts of the experience or force him into delusional solutions.

2) Lack of knowledge of factors affecting the experience: Contrary to the belief of many investigators, the hallucinogens do not produce experiences but inhibit repressive mechanisms that ordinarily operate and simply allow subjects to explore the contents of their own minds. The nature of his exploration will depend on a) the mental content, the subject’s individual personality, conditioning, attitudes, values and beliefs; b) his preparation for the experience, which determines in part how he will use the opportunity; and c) his environment during the experience, which very appreciably affects how he will deal with the material he touches on and the opportunities afforded. Most investigators now agree that preparation and setting profoundly affect the subject’s experience, and the presence of supportive, understanding, accepting companions is essential to a comfortable and rewarding session.

3) Misuse of the hallucinogens: Unfortunately, the dramatic appeal of the psychedelic experience has attracted many elements of the community–the “beatnik” crowd seeking new experiences or escape from the established and the humdrum, the unsavory elements sensing an opportunity to expand narcotic traffic, and persons genuinely seeking greater knowledge. There are included many unstable persons seeking a ready solution to their difficulties, which has led to flourishing black-market trade in the psychedelics, as well as widespread, uncontrolled clandestine usage, in settings that afford little in the way of safeguards. It is from precisely such illicit usage that has come the bulk of the reports of harmful outcomes.

Even professional investigators have sometimes used these substances improperly, which undoubtedly accounts for the absence of support for research in these fields. Such misuse includes:

Inadequate preparation: If the nature of the experience and the factors affecting it are not properly understood (as mentioned above), then the subject is unlikely to be in a frame of mind to take full advantage of the exploration the experience affords.

Improper support to subject: A clinical or judgmental attitude or too ready a desire to analyze or interpret the patient’s experience will inhibit the experience seriously and may cause grave discomfort. The impact of the therapist holding conceptual views that do not encompass what the patient is experiencing has already been discussed.

Too frequent use of LSD: Regardless of the content of the experience and whether or not it is interpretable, every exposure of the deep layers of the mind produces material which must then be assimilated and integrated by him into his personality structure. This takes time, and can only be done in the process of facing life experiences. To have LSD experiences one on top of another can so swamp the psyche with data that dissociation is the inevitable result. The object of any educational experience is to produce data for more successful living, and to adulterate one with additional data before it has been properly assimilated not only distorts all the data, but can result in great confusion.

Improper handling of patients: By not understanding the powerful subjective states experienced under LSD, uninformed therapists or companions can wreak considerable havoc. Subjects left alone can sometimes become quite frightened, or can escape and commit harmful acts. Those permitted to drive while still experiencing imagery are dangerous to themselves and others. Insensitive companions who do not detect the extremely hostile or destructive feelings of the subject may not be ready with restraints when necessary.

Improper dosage: Subjects vary appreciably in their sensitivity to LSD, and in the rigidity of the intellectual defenses to be penetrated. Consequently, the dosage must be adjusted to the individual patient. Under-dosage leads to an unsatisfactory experience, where the patient is unable to break through to a satisfactory resolution of his problems. Far more dangerous is pronounced overdosage, where subjects may be driven into ranges of experience for which they are not prepared or willing to accept, so that they may become considerably unbalanced as a result of the experience.

Overenthusiastic response: Just as damaging as the ignorant and inept administrators of these drugs are those who have become so enthusiastic about them that they have lost their sense of rational judgment. It is not unnatural for those who have had the privilege of experiencing profound philosophic, perhaps even spiritual, truths to be elated about them. But by the same token, it would appear that the more one has learned about the nature of things, the greater is one’s responsibility to society. And it seems only natural that the greater one penetrates beyond the habitual frames of reference, the more time and work and effort is required to assimilate such profound truths into one’s daily life. Apparently there are those who having discovered a fairly simple way to stand on those great pinnacles of knowledge, choose to return to them frequently and enjoy them rather than to go to the effort of readjusting their personalities to be in line with the new truths discovered. The consequences of these repeated high dosages seems to be the twofold result of deteriorated judgment and impaired perception and communication on the usual level of operation. The ability to work creatively within the structures of society seems lost, and inflation and feelings of omnipotence, followed by revolution or withdrawal from society are likely.

By far the greatest damage has been caused by the illicit use of the hallucinogens. Lay interest has been great, both through fascination with the exploration of new experience and knowledge, and as a means of fulfilling special self-interests. Black market usage of LSD is widespread, and becoming an ever greater problem. The most effective counter-measure to improper and uninformed use of these agents is forward and aggressive medical leadership. Should the intense public interest in these substances as new avenues to increased self-understanding and general knowledge prove justified, then the medical profession has an obligation to see that all factors concerning the use of these substances are well known, and that the proper circumstances for their use be well defined and provided.

In summary, there is substantial evidence that many avenues may be opened up by research with the psychedelics, both in developing new treatment methods and improving the understanding of the human mind. Hazards can be reduced to negligible considerations through informed use. In addition, proper medical knowledge is urgently needed to curtail widespread illicit use. In view of these factors, it is hoped that more intensive investigation of these powerful new tools will take place.

Savage, C., and Stolaroff, M.J. Clarifying the confusion regarding LSD-25. The Journal of Nervous and Mental Disease, Vol. 140, No. 3. 1965.

Bicycle Day

While researching lysergic acid derivatives, Dr. Albert Hofmann first synthesized LSD on November 16, 1938. The main intention of the synthesis was to obtain a respiratory and circulatory stimulant. It was set aside for five years, until April 16, 1943, when Hofmann decided to take a second look at it. While re-synthesizing LSD, he accidentally absorbed a small quantity through his fingertips and serendipitously discovered its powerful effects. He described what he felt as being:

… affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away.”

Three days later, April 19, 1943, Hofmann performed a self-experiment to determine the true effects of LSD, intentionally ingesting 0.25 miligrams (250 micrograms) of the substance, an amount he predicted to be a threshold dose (an actual threshold dose is 20 micrograms). Less than an hour later, Hofmann experienced sudden and intense changes in perception. He asked his laboratory assistant to escort him home and, as use of motor vehicles was prohibited because of wartime restrictions, they had to make the journey on a bicycle. On the way, Hofmann’s condition rapidly deteriorated as he struggled with feelings of anxiety, alternating in his beliefs that the next-door neighbor was a malevolent witch, that he was going insane, and that the LSD had poisoned him. When the house doctor arrived, however, he could detect no physical abnormalities, save for a pair of incredibly dilated pupils. Hofmann was reassured, and soon his terror began to give way to a sense of good fortune and enjoyment, as he later wrote.

“… little by little I could begin to enjoy the unprecedented colors and plays of shapes that persisted behind my closed eyes. Kaleidoscopic, fantastic images surged in on me, alternating, variegated, opening and then closing themselves in circles and spirals, exploding in colored fountains, rearranging and hybridizing themselves in constant flux …”

The events of the first LSD trip, now known as “Bicycle Day”, after the bicycle ride home, proved to Hofmann that he had indeed made a significant discovery. A psychoactive substance with extraordinary potency, capable of causing significant shifts of consciousness in incredibly low doses, Hofmann foresaw the drug as a powerful psychiatric tool; because of its intense and introspective nature, he couldn’t imagine anyone using it recreationally.

Timothy Leary’s Escape From Prison

Timothy Leary’s escape from prison seems to be torn straight from the script of a bad movie, but the best part is that it actually happened.

On January 21, 1970, Leary received a ten-year sentence for [possession of two marijuana roaches], with a further ten added later while in custody, for a previous [marijuana possession] arrest in 1965, twenty years in total to be served consecutively. When Leary arrived in prison, he was given psychological tests that were used to assign inmates to appropriate work details. Having designed some of the tests himself (including the “Leary Interpersonal Behavior Test”), Leary answered them in such a way that he seemed to be a very conforming, conventional person with a great interest in forestry and gardening. As a result, Leary was assigned to work as a gardener in a lower security prison, and in September 1970 he escaped. Leary claimed his non-violent escape was a humorous prank, and left a challenging note for the authorities to find after he was gone. For a fee, paid by The Brotherhood of Eternal Love, the Weathermen smuggled Leary and his wife, Rosemary Woodruff Leary, out of the United States and into Algeria.

The FBI didn’t seem to see the humor in the situation, as seen in part of the Weather Underground file. Their part in the escape was seen as evidence for “continuing foreign influence” of the movement.

The Weathermen couldn’t resist needling the government with a letter stating their involvement (Communique #4 referenced above).

After hopping from country to country, he was arrested on a plane in Kabul, Afghanistan, and returned to the United States.

He was then held on five million dollars bail. President Richard Nixon had earlier labeled him “the most dangerous man in America.” The judge at his remand hearing remarked, “If he is allowed to travel freely, he will speak publicly and spread his ideas.” Facing a total of 95 years in prison, Leary hired criminal defense attorney Bruce Margolin and was put into solitary confinement in Folsom Prison, California.

Leary made somewhat of a pretense of cooperating with the FBI’s investigation of the Weathermen and radical attorneys, by giving them information that they already had or that was of little consequence; in response, the FBI gave him the code name “Charlie Thrush”. Leary would later claim, and members of the Weathermen would later support, that no one was ever prosecuted based on any information he gave to the FBI.

Leary was released from prison on April 21, 1976, by Governor Jerry Brown. After briefly relocating to San Diego, Leary established residence in Laurel Canyon and continued to write books and appear as a lecturer and (by his own terminology) “stand-up philosopher.”

LSD in the FBI Vault

The FBI Vault provides an interesting view of previously confidential documents.

They include a heavily redacted collection of documents regarding the Grateful Dead.

The Frank Sinatra file includes a newspaper clipping where Roger Corman discusses his LSD experience.

DMT and the Pineal Gland

One of the most popular “drug geek” myths is that the powerful psychedelic compound DMT is produced naturally within your body, specifically the pineal gland. Not only this, but this natural DMT is apparently involved in a wide variety of previously unexplained processes – it is the mechanism of dreaming, it causes religious feelings, and DMT production spikes near death to “carry away the soul”. This appears to stem primarily from Dr. Richard Strassman’s book The Spirit Molecule, which advanced many of these hypotheses which were then passed on and extrapolated telephone-game style to the point where fluoridated water is apparently an Illuminati plot to suppress natural DMT production.

There’s just one problem – there doesn’t appear to be any concrete evidence whatsoever for this. Dr. Strassman himself explains:

I did my best in the DMT book to differentiate between what is known, and what I was conjecturing about (based upon what is known), regarding certain aspects of DMT dynamics. However, it’s amazing how ineffective my efforts seem to have been. So many people write me, or write elsewhere, about DMT, and the pineal, assuming that the things I conjecture about are true. When I was writing the book, I thought I was clear enough, and repeating myself would have gotten tedious.

We don’t know whether DMT is made in the pineal. I muster a lot of circumstantial evidence supporting a reason to look long and hard at the pineal, but we do not yet know. There are data suggesting urinary DMT rises in psychotic patients when their psychosis is worse. However, we don’t know whether DMT rises during dreams, meditation, near-death, death, birth or any other endogenous altered state. To the extent those states resemble those brought on by giving DMT, it certainly makes one wonder if endogenous DMT might be involved, and if it were, it would explain a lot. But we don’t know yet. Even if the pineal weren’t involved, that would have little overall effect on my theories regarding a role for DMT in endogenous altered states, because we do know that the gene involved in DMT synthesis is present in many organs, particularly lung. If the pineal made DMT, it would tie up a lot of loose ends regarding this enigmatic little organ. But people seem to live pretty normals lives without a pineal gland; for example, when it has had to be removed because of a tumor.

In both these regards–the pineal-DMT connection, and endogenous DMT dynamics–we ought to know a lot more within the next several years due to the efforts of a research group being led by Steven Barker at Louisiana State University. He, with his grad student Ethan McIlhenny, are developing a new super-assay for DMT, 5-MeO-DMT, bufotenine, and metabolites. This assay will be capable of detecting those compounds much more sensitively than previous generations of assays. They’re looking at endogenous levels in awake sober normals, to assess baseline values of these compounds. We should have some data from those samples within a year. They also will be looking at pineal tissue. Once we have some baseline data in normal humans in normal waking consciousness, comparisons can be made between those levels and levels in endogenous altered states, like dreams, near-death, and so on.

It appears that myths about drugs can cut both ways, and this is an important illustration of the requirement for critical thinking, no matter how appealing the initial conjecture. Steven Barker and Ethan McIlhenny’s work to determine baseline DMT levels continues, with their latest paper involving detection of metabolites produced by ayahuasca consumption.

Hanna J. “DMT and the Pineal: Fact or Fiction?” www.erowid.org/chemicals/dmt/dmt_article2.shtml. Jun 3 2010.

Psychedelics in the Public Consciousness

Google Ngram is a very interesting project which measures the frequency of the occurrence of words in a large body of books published over the last several hundred years. This can be considered somewhat as a measure of public awareness of a certain term, so let’s use it to see how various prominent psychedelic compounds (mescaline, LSD, psilocybin, and MDMA) have risen and fallen in the public consciousness from 1900 to 2000.

The first thing we see is that psychedelic compounds as a whole are a very new concept, entering popular usage only in the middle of the 20th century with knowledge becoming more widespread in the 1960s. The word LSD has an almost overwhelming frequency of use, reflecting the intimate association of the drug with the popular concept of the psychedelic experience. Switching this out for “lysergic acid diethylamide” should allow us to compare relative trends with other psychedelic compounds due to decreased frequency while still maintaining a sensible relation to the original term.

This normalizes the dataset somewhat.

Mescaline had been used for thousands of years until it was first isolated and identified in 1897. It slowly grew in the public consciousness until Aldous Huxley’s 1954 work The Doors of Perception thrust the compound into the mainstream.  
LSD (lysergic acid diethylamide) was first consumed by Albert Hofmann in 1943, initially introduced to the market as a psychiatic drug in 1947, and its potential became more clear with corporate and government experiments during the 1950s including the infamous Project MKULTRA. High potency and its positive character led to efficient distribution and widespread use in the 1960s.  
Psilocybin is another ancient compound with sacramental use spanning thousands of years. Vice President of J.P. Morgan and amateur mycologist R. Gordon Wasson travelled to a remote village of Mexico on a rumor that their religion included ingestion of mushrooms. In 1957, he published an article in Life magazine entitled Seeking the Magic Mushroom that did for psilocybin what Huxley did for mescaline.  
MDMA was first synthesized in 1912, but it languished in obscurity until the mid-1970s when Alexander Shulgin, then at University of California, heard from his students about unusual effects of the amphetamine derivative. In 1978 he and David Nichols published the first report on the drug’s psychotropic effect in humans and its use spread among the psychiatric community as an adjunct to therapy. MDMA used in a recreational context was first reported in gay nightclubs in the Dallas area in the early 1980s with usage peaking during the 1990s rave scene.  

Other trends become apparent when we separate our observations geographically. While the opportunity to do this is necessarily limited due to language restrictions, we can compare American English usage with British English usage quite easily from 1950 to 2000.

We can see that MDMA citations peaked in the mid 1990s in American English as the British rave scene made noise in North America, but the trend faded in the US while use continued to climb in British English.

Effects of LSD on Troops Marching

Rich Remsburg works as an archival image researcher on documentaries for PBS, National Geographic, the History Channel, museum exhibits and independent films. While working on a documentary on the history of biological warfare he came across a clip detailing US Army research in LSD and its effect on troops marching. Transcript:

US Army Chemical Corps
Edgewood Arsenal, Maryland
1958

These film records do not necessarily denote official Army doctrine. They cannot be obtained from the US Signal Corps.

A typical drill seargeant orders his men to fall in. The squad, composed of volunteers for the test, responded like well trained soldiers, immediately and without question. On the drill field the men obeyed his commands accurately and with precision. A second drill seargant assumed command. He put the squad through its paces capably. This man also proved to be an able drill seargant, giving precise commands.

Two hours later, the squad all except the [first] drill seargant are drugged with LSD and again were ordered to fall in. The response was not the same. The squad leader thought it was not necessary for him to dress right. There was much laughter as the group attempted to give expression to inner emotions. This elation was group supported, and an individual who was seperated from the group would show severe disturbance. Notice the volunteer who salutes several times. Five minutes later a severe depression [of the saluting volunteer] convince the medical officers to end his participation in this test.

Response and reaction to the [first] drill seargant who did not receive LSD were as before. But in marching, the drugged squad, although starting fairly well, gave a sluggish and ragged performance. After a few minutes, the men found it difficult to obey orders, and soon, the results were chaotic.

The second drill seargant, who had performed effectively earlier in the day, was now given command of the squad. He too had received LSD and he no longer was an effective leader. When an officer ordered the leader to drill the squad, he responded with “You want a drill? You drill ’em!”. Ordered to leave the field, he refused to go. In answer to a direct question, he said he was capable of drilling the men and was instructed to do so. Minutes later, it was evident that he was unable to carry out his orders, and he was escorted from the field.

We have seen some of the effects of LSD. What effect would it have on a vital operation? Further research is required to give us that answer.

[cut to a Nike Ajax missile battery readying for launch, typically placed around population centers and strategic locations such as long-range bomber bases, nuclear plants, and ICBM sites in the late 1950s]

A far better explanation for why LSD is currently Schedule I under the UN Convention on Psychotropic Substances than I have heard to date.