4-Hydroxy Tryptamines

The indole ring of tryptamine provides a number of possible locations for functional groups to be substituted. Addition of a hydroxy group at the 4-position produces a large number of active psychedelic compounds including some true classics.

4-hydroxylation of alpha substituted tryptamines such as AMT has been conducted but further exploration has been limited due to potential toxic effects.

The 4-hydroxy analogue of α-MT has been looked at in human subjects. It is reported to be markedly visual in its effects, with some subjects reporting dizziness and a depressed feeling. There were, however, several toxic signs at doses of 15 to 20 milligrams orally, including abdominal pain, tachycardia, increased blood pressure and, with several people, headache and diarrhea.

-Alexander Shulgin

4-hydroxylation of the n-alkylated tryptamines is more fruitful. For instance, 4-hydroxylation of DMT (dimethyltryptamine) produces the classic psilocin (4-HO-DMT, 4-hydroxy-dimethyltryptamine). These 4-hydroxy n-alkyl tryptamines are similar in general psychedelic character, moderately potent (active at 10-25 mg) and of medium duration (2-6 hours).

Other functional groups can be substituted at the 4-position which are converted to 4-HO tryptamines in the human body. Psilocybin (4-PO-DMT, 4-phosphoryloxy-dimethyltryptamine) contained in psychedelic mushrooms is water soluble and too polar to cross the blood-brain barrier. After consumption phosphatase enzymes rapidly break apart the phosphoryloxy group producing the active psilocin (4-HO-DMT, 4-hydroxy-dimethyltryptamine).

The phosphoryl group in psilocybin that is cleaved off by enzymes is known as an ester, and other esters can be substituted that react in similar ways once consumed by man.

O-acetylpsilocin (4-AcO-DMT, 4-acetoxy-dimethyltryptamine) can be thought of as psilocybin with an acetoxy group instead of a phosphoryloxy group. Like psilocybin, it is rapidly converted to 4-HO-DMT in the body. This produces a compound with a similar subjective experience to that of psilocybin.

4-HO tryptamines can therefore have a 4-AcO pair with very similar effects. The 4-AcO partner tends to be slightly less potent, have a longer duration, and be subjectively “smoother” than the 4-HO counterpart. It is a matter of debate whether this is simply the result of varying rates of administration due to metabolic conversion, or if 4-AcO tryptamines are active in their own right.

Shulgin, A. #48 AMT. Tryptamines I Have Known and Loved. Transform Press, 1997.

Vito Cozzi, Nicholas. MAPS: Re: Psilocybin and the blood brain barrier. MAPS Forum, April 29 2003.

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).

N-Alkylated Tryptamines

The amine group of tryptamine possesses a nitrogen with two hydrogens where functional groups can be substituted. Let’s start with the simple case where both of these substitutions are identical. The best known example is dimethyltryptamine, abbreviated as DMT (D for di meaning two, M for the methyl alkyl substitions, and T for the tryptamine backbone). There are other tryptamines like DMT with longer symmetrical alkyl chains which have similar effects and are named in a similar manner.

Some dialkylated tryptamines: dimethyltryptamine (DMT), diethyltryptamine (DET), dipropyltryptamine (DPT), dibutyltryptamine (DBT).

DMT is typically smoked as other consumption routes are ineffective due to MAO degradation, but the longer alkyl chains do not have this issue and are all orally active. There is no theoretical limit to the alkyl chain length, but potency decreases as chain length increases. DBT is the longest simple chain dialkylated tryptamine commonly bioassayed in man.

We can also consider asymmetrical cases where the two substitutions are different. The possible combinations quickly increase in number as the following table up to alkyl chains of three carbons in size illustrates. Asymmetric compounds are referred to by giving initials to both of their substitutions (shortest chain first) and ending with a T to signify the tryptamine backbone.

methyl ethyl propyl isopropyl
ethyl DET EPT EiPT
propyl DPT PiPT
isopropyl DiPT

Linked compounds have a full entry in TiHKAL.

These two rulesets for symmetric and asymmetric substitutions allow us to refer to a huge variety of n-alkylated tryptamines using abbreviations in a simple and consistent manner.

Shulgin, A. #2 DBT. Tryptamines I Have Known and Loved. Transform Press, 1997.

Alpha Substituted Tryptamines

The tryptamine backbone provides a building block for a large number of research chemicals. One such class is the alpha-substituted tryptamines. There are two carbons between the amine group (NH2) and the indole ring of tryptamine, referred to as alpha and beta.

Short alkyl chains have successfully been substituted at the alpha position nearest the amine group. These include compounds such as AMT and AET, which are releasing agents of serotonin, norepinephrine, and dopamine resulting in stimulating and euphoric effects. At higher doses their psychedelic character becomes more prominent. Potency decreases as alkyl chain length increases, and alpha-propyltryptamine has not been widely explored.

What about substitution on the beta carbon instead? It doesn’t seem hopeful. Substitution at the alpha carbon acts to protect the compound against enzymatic degradation but the beta position does not have this advantage. Little actual data regarding synthesis or effects are available however, and this remains an unexplored possibility.

Biosynthesis of 4-Substituted Tryptamine Derivatives

Biological organisms are wondrous little molecular factories, their enzyme catalyzed reactions often accomplishing in a single step what would confound a chemist in a well-stocked laboratory. Researchers have attempted to harness these biosynthetic pathways to create complex molecules not easily synthesized by conventional methods.

Psilocybin is produced via a biosynthetic grid where enzymes act on various closely related intermediate compounds in turn. The enzymes do not appear to be particularly picky about the compounds they modify. For instance, dimethyltryptamine (DMT) is hydroxylated to 4-HO-DMT naturally in psilocybin mushrooms. Other precursor compounds like tryptamine and methyltryptamine are also hydroxlyated to 4-hydroxy-tryptamine and 4-hydroxy-methyltryptamine respectively.

If an entirely new synthetic tryptamine of similar structure was introduced to these mushrooms, would the same enzymes act on it? This could produce a new and unique psychedelic compound where some of the heavy lifting of synthesis is accomplished by the biological expertise of the mushroom itself and not by conventional laboratory chemistry.

Jochen Gartz decided to attempt this by adding diethyltryptamine (DET, a close relative of DMT) to the fruiting body of psilocybe cubensis. He hoped that it would be hydroxylated to 4-HO-DET, or possibly phosphorylated even further to 4-PO-DET. He first colonized a mixture of cow dung and rice grain with psilocybe cubensis, and then injected it with a solution of DET. Within four weeks mushrooms were produced, and five total flushes of mushrooms were obtained.

First Second Third Fourth Fifth
4-HO-DET 2.5% 0.2% 3.1% 3.3% 2.1%
4-PO-DET - 0.8% 0.01% - 0.02%

all values % by weight of dry mushroom

The project was a success, with significant amounts of 4-HO-DET produced. No DET was found in the dried mushrooms. A mass balance was not conducted to determine the efficiency of the conversion and possible losses in the fruiting body itself. The demonstrated non-selectivity of the enzymes in psilocybe cubensis toward other tryptamine derivatives opened to the door to the possibility of producing truly exotic and difficult to synthesize compounds such as 4-HO-5-MeO-DMT.

Despite this little additional data is available on the tryptamine derivatives that are able to be substituted in the fruiting body and the repeatability of the experiment. Some have found little success, noting only a decrease in the size of the mushrooms produced. Other attempts have discovered perhaps a qualitative difference in potency and character of the psychedelic experience, but this has not been substantiated by quantitative measurement.

Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe
. Gartz, J. Journal of Basic Microbiology, Volume 29, Issue 6, Pages 347-352 (1989).

Why Does Cannabis Potentiate Psychedelics?

It’s an effect that many psychedelic users are familiar with – at the tail end of trip, with the experience waning, smoking cannabis will tend to increase the psychedelic effects and “bring the trip back”. Similar effects occur on the comedown of drugs like MDMA. Why does this happen?

It appears that this may be a result of the interrelationship between the brain’s natural cannabinoid receptors and the GABA system.

Nerve cells are designed to fire repetitively, and are subject to a barrage of stimuli. The brain prevents itself from spiraling out of control into hyperexcitable states by inhibition, a way of “turning down the volume” in the brain. The major workhorse for this is gamma animobutyric acid, or GABA. In a strange parallel, the brain synthesizes GABA in one step from glutamate, the brain’s major excitatory neurotransmitter.

We know that cannabis gets us “high”, that it produces a general excitatory effect across many areas of the brain. First this was thought to be a result of cannabinoid (specifically CB1) receptors being expressed on glutamate receptors. This was not the case. Instead, they appear to be almost exclusively expressed on GABAergic neurons where they have an inhibitory effect.

So it seems that cannabis inhibits the inhibitor, and ends up having a general excitatory effect. In the same manner that a benzodiazepine or alcohol may dull a trip via direct GABA agonism, cannabis may increase the effects of a waning psychedelic due to GABA inhibition.

Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations. N. Hajos et. al. European Journal of Neuroscience, Vol. 12, pp. 3239-3249, 2000.

Grid Biosynthesis of Psilocybin

The biosynthesis of psilocybin in psychedelic mushrooms is a multi-step process, and the precise mechanism is debated by many authors. The essential amino acid l-tryptophan undergoes several modifying reactions (decarboxylation, N-methylation, 4-hydroxylation, and O-phosphorylation) but the specific order is unclear. A series of steps similar to the following is generally accepted.

Experiments with radiolabled precursors have shown that this is likely the primary path to psilocybin, however, labelled 4-hydroxytryptamine was also shown to be incorporated into the produced psilocybin indicating the possibility of an additional biosynthetic pathway. Other alkaloids present in psilocybin mushrooms such as baeocystin or norbaeocystin are not explained by this single pathway as well.

An elegant alternative has been proposed. What if instead of a single path and a set order of modifying reactions, there were multiple paths to psilocybin – with branching edges that led to baeocystin and norbaeocystin? The enzymes would compete and feed back among each other in a biosynthetic grid that preferred to produce psilocybin and psilocin but also produced small amounts of baeocystin and norbaeocystin as typically seen in nature.

There is no longer a preferred order to the modifying reactions, except for the obvious that 4-hydroxylation must precede O-phosphorylation. There are three paths to psilocin and psilocybin (the predominant alkaloids in psychedelic mushrooms), two paths to baeocystin (found in lesser concentrations than the two signature alkaloids), and one path to norbaeocystin (found in the lowest concentrations, if it is detectable at all). The number of paths does not indicate the absolute likelihood of producing a certain alkaloid, but it can be seen as a measure of resiliency. The precise weighting of each connection in the network is not clear at this point, or even if a steady state model would be an appropriate approximation.

Biosynthesis of Psilocybin. Part II: Introduction of Labelled Tryptamine Derivatives. S. Agurell and J. Lars G. Nilsson. Acta Chemica Scandinavica 22 (1968), 1210-1218.

Baeocystin and Norbaeocystin: New Analogs of Psilocybin from Psilocybe baeocystis. A.Y. Leung and A.G. Paul. Journal of Pharmaceutical Sciences, Vol. 57, No. 10, October 1968, 1667-1671.

Tryptamines as Ligands and Modulators of the Serotonin 5-HT2A Receptor and the
Isolation of Aeruginascin from the Hallucinogenic Mushroom Inocybe aeruginascens
. Niels Jensen, Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultäten der Georg-August-Universität zu Göttingen, 2004.

Non-LSD Ergoloids

The research chemical market is based on the philosophy of tweaking existing recreational molecular backbones, yet compounds based on LSD appear to be few and far between. There is nothing at all preventing the existence of exotic research chemicals based on the ergoloid backbone, and in fact several are known that have significant recreational potential based on academic studies. The interesting fact is that none of them appear to have hit the market in significant volume. Perhaps this is simply the result of watched precursors and more elaborate synthesis routes than established products, but experimentation by the research chemical market seems rather lackluster based on the reputation of the parent drug and possible potential.

There are some who argue that experimentation of this nature has been ongoing, but has been executed through entirely different distribution channels – namely the LSD black market. Certain blotter prints have been distributed with something that could pass for LSD but seems different to experienced tastes. This particular variant has been described as a sort of neo-LSD that appears more euphoric, more visual, shorter acting, and less “spiritual” with the accompanying decrease in potential for anxiety.

One suspected blotter print is the 1906-2008 Hoffman Oms. This is not a esoteric print with limited circulation. It celebrates the life of Albert Hofmann, who lived from 1906 to 2008 and was the first to synthesize and consume LSD. It is part of a larger recurring blotter art series that is consistently widely distributed and well received, and as such appears to originate from the depths of the notoriously secretive LSD black market.

Sufficient suspicions were raised about the contents of this blotter to instigate a GC/MS test.

Initial evaluation seemed to bear out the hypothesis that these results reflected a novel and interesting compound closely related to LSD, perhaps lysergic acid 2-butyl amide (LSB) or lysergic acid 3-pentyl amide (LSP). These early interpretations of the GC/MS results were challenged however.

sec-LSB gives an almost indistinguishable MS to actual LSD, so I doubt it’s that. It’s not the N-(3-Pentyl) derivative [..] as well[.]

I personally have not a clue what this is — the fragment for d-Lysergic acid diethylamide, LAMPA or sec-LSB is always at 324, yet here we have 326 (the only one that comes to mind is deuterated-LSD which is usually 327). The huge peak at 72 is suspicious and the initial peaks at 44/58 as well (small substituted amines?).

296-208 is usual fragment for N-Et-LSD and a peak adjacent to 209 is present
310-209 characteristic of nor-LSD/nor-iso-LSD

So, you’re missing quite a bunch of the normal peaks but you have what might be degradation products or side impure product present, but it seems pretty inconclusive.


Unfortunately it appears that no clear conclusions can be drawn. The blotter cannot be positively identified as LSD, but it also cannot be identified as a closely related compound or even as a completely different psychedelic compound. These blotters were clearly active in man, and displayed a psychedelic character very close to LSD. The major issue is lack of comprehensive test results, as GC/MS analysis is not easily available. Even if these tests are conducted, the data is not typically shared widely. It seems likely that these problems will become more manageable as technology progresses.

It is very likely that closely related compounds to LSD have been synthesized and tested in man. The precursors are available, the skills are out there, and the desire exists. Whether these exotic relatives of the world’s most famous psychedelic remain limited to a select few or have been surreptitiously released on a wider scale to a mostly unaware public remains to be seen.

Bluelight Forum > Focus Forums > Psychedelic Drugs > The Big & Dandy Non-LSD Ergoloids Blotter Thread.

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.