Wednesday, October 16, 2013


I recently presented a group meeting on Hallucinogens and Phil wanted me to do a little write-up to promote it.  As a brief overview, I cover different classes of hallucinogenic natural products and synthetic compounds.  It starts with a historical overview of the hallucinogenic natural and synthetic compounds.  Then I cover pharmacology and synthesis of a variety of structurally unique hallucinogens.  You can read the group meeting for all of the details on that, but what I wanted to cover here is some of the interesting legal and social issues surrounding research with hallucinogenic compounds.

In the interest of clarity I have to state this from the beginning: Don't do drugs.  They are illegal and the penalties are astronomical.  It's also completely insane to take something in an uncontrolled environment without knowing anything about what it actually contains.

I have to point out an excellent review by David Nichols that covers extensively the pharmacological side of classical hallucinogens and some of the social and political aspects.

Lophophora williamsii (peyote), has been used by Native Americans in religious practices for almost 6000 years.

Hallucinogens have an extremely old relationship with mankind dating back thousands of years.  They played a significant role in the development of ancient religious traditions.  In modern times, however, they are associated with a serious stigma and have been illegal in most western countries since the early 1970's.  The motivations for criminalization are complex but David Nichols pins them on ignorance and fear:
It should be apparent ... that hallucinogens have a unique and powerful ability to affect the human psyche. They may alter one’s concepts of reality, may change one’s views on life and death, and can provoke and challenge one’s most cherished beliefs. Therein... lay the roots of much of the fear and hysteria that these substances have fostered in our society.
While from comedian Bill Hicks:
I'm glad mushrooms are against the law, because I took them one time, and you know what happened to me? I laid in a field of green grass for four hours going, "My God! I love everything!" Yeah, now if that isn't a hazard to our country … how are we gonna justify arms dealing when we realize that we're all one?
Whatever the reasons for criminalization, it is clear that severe regulation and public stigma, especially in the United States, has had a serious chilling effect on research for potential medical uses of hallucinogens.  Research in the 1960's and 70's focused on the use of hallucinogens in terminal cancer patients, for the treatment of alcoholism, and in treating obsessive compulsive disorder.  While the studies showed some promise, the new criminalization and overwhelming media exposure of hallucinogens all but ended this work.  After a nearly 20 year hiatus, research in human beings began again in 1991, following a nearly two year regulatory process.  Current ongoing research focuses on using hallucinogenic molecules as a tool for exploring cognitive neuroscience.
The failure of much of modern science to envision hallucinogens as key ingredients in our efforts to understand the nature of consciousness and the human mind is what has allowed society to view these molecules for so long only as dangerous drugs of abuse. It is quite unfortunate that legal restrictions have kept these extremely interesting substances from receiving more extensive clinical study, but there are hopeful recent signs that this situation may be changing.
          -David Nichols

The group meeting hasn't made it to the website yet but I've uploaded a version here.


  1. Thank you very much for the post! I am a fan of the work of Nichols, Shulgin, Strassman, and Hofmann. It's great to see other chemists acknowledging the importance of these substances.
    Nice compilation of organic perspectives on the powerpoint by the way. Just a point of interest, on slide 6, I was under the impression that psilocybin and psilocin were N,N-dimethyls...
    Anyway great stuff.

    1. Good catch, it's wrong on the first slide as well. I've put up an corrected version with one other mistake fixed as well. Thanks!

  2. There is one more typo: it should be serotonin, not seratonin (it is repeated through out the presentation).

    Two additional deeply worrisome problems seen with long-term users: 1) Changes in personality - namely a social withdrawal: shunning any competitive interactions like sports and games, and activities seen as "materialistic" and "aggressive" 2) Hallucinogen persisting perception disorder - a "static" in the field of vision that is more than just annoying, it can prevent you from driving a car, and it is an indication of lasting CNS impairment

    Then there are extremely long-acting hallucinogens (infamous DOB and Bromo-DragonFly) that can produce nightmarish trips lasting 2-3 days (before you die or kill yourself). And the super-active "N-bomb" NBOMe phenethylamine analogs are know to produce life-threatening complications even when used in "correct" dose. So it appears that LSD and psylocibin low acute toxicity is rather an anomaly than a rule. Very close analogue like LSA or other substituted tryptamines aren't so benign.

    Also, diethylamide in LSD can be replaced with 2,4-trans-diMe-azetidine without any loss of potency. N-allyl instead of N-methyl on the dihydropyridine ring of LSD improves the potency about 2-3 times.

  3. Thanks for the interesting post, it's always pleasing to see reputable sources and academics report on this rather difficult subject. I think it's a great shame that the doors were so stubbornly closed on the research of these compounds, as it stands to reason that a plethora of possible medicinal uses could be explored, particularly in the realm of psychiatry. Of course the fear is that development of pharmaceuticals like these will also prompt their abuse... but to be frank, I don't believe the abuse potential of psychedelics comes slightly close to currently marketed pharmaceuticals which also have their place as valid treatments (Oxycontin, Klonopin, Adderall)... I don't quite understand the double standards, there.

    I think one of the most remarkably efficacious pharmaceuticals is sumatriptan, a 5-sulfonamido dimethyltriptamine - it is a beast against chronic migraines, which I know to be a crippling disorder. Although its side effects can be rather unpleasant. I have also heard that psilocybin was potentially useful against migraines? It makes me wonder if the silver bullet for migraines is chained up in this unexplored treasure chest of psychedelics...

  4. yes PIKAL and TIKAL have to be on your reading list

  5. Thanks very much David, for the post and the slides. It is a very interesting topic, this one. I have also been collecting literature.