David E. Nichols
Encyclopedia
David E. Nichols is an American
pharmacologist and medicinal chemist.
Presently the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University
, Nichols has worked in the field of psychoactive drugs since 1969. While still a graduate student, he patented the method that is used to make the optical isomers of hallucinogenic
amphetamines. His contributions include the synthesis and reporting of escaline
and the coining of the term "entactogen".
He is the founding president of the Heffter Research Institute
, named after German
chemist and pharmacologist Arthur Heffter
, who first discovered that mescaline
was the active component in the peyote
cactus. In 2004 he was named the Irwin H. Page Lecturer by the International Serotonin
Club, and delivered an address in Portugal titled, "35 years studying psychedelics: what a long strange trip it's been." Among pharmacologists, he is considered to be one of the world's top experts on psychedelics. Nichols's other professional activities include teaching medicinal chemistry and molecular pharmacology at Purdue University in West Lafayette, IN, and teaching medical students at the Indiana University School of Medicine
.
, or SAR). Although his research mostly uses rats, a number of compounds included in Shulgin's PIHKAL
were actually first synthesized in Nichols's lab. His lab also first developed [125I
]-(R)-DOI
as a radioligand
. Nichols is one of the few people who has published legitimate research on the chemistry and pharmacology
of LSD
in the last 20 years, and first reported that several LSD analogues, including ETH-LAD
, PRO-LAD
, and AL-LAD
, were more potent than LSD itself. Their human effects are described in TiHKAL
. He also improved the synthesis of psilocybin
so that it would be accessible for several recent clinical studies.
Other notable research he helped carry out includes extensive studies of the structure-activity relationships and mechanisms of action of MDA
and MDMA, during which he helped to discover many novel analogues including such compounds as 5-methyl-MDA
, 4-MTA
and MDAI. Nichols has said that "he believes gray-market chemists used information from papers he published on 4-methylthioamphetamine (MTA) in the 1990s to synthesize the drug, which they sold in tablets nicknamed "flatliners" as a substitute for MDMA (Ecstasy)."
More recently, Nichols has become one of the world leaders in research on dopamine
, and his team has developed several notable dopamine receptor ligands, including the selective D1
full agonist compounds dihydrexidine
and dinapsoline
which have been researched for the treatment of Parkinson's disease
, and a number of other subtype-selective dopamine agonists derived from dinoxyline
. He co-founded DarPharma, Inc. to commercialize his dopamine compounds; several of his team's compounds are now being studied in clinical trials for the treatment of Parkinson's disease and the cognitive and memory deficits of schizophrenia
.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
pharmacologist and medicinal chemist.
Presently the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University
Purdue University
Purdue University, located in West Lafayette, Indiana, U.S., is the flagship university of the six-campus Purdue University system. Purdue was founded on May 6, 1869, as a land-grant university when the Indiana General Assembly, taking advantage of the Morrill Act, accepted a donation of land and...
, Nichols has worked in the field of psychoactive drugs since 1969. While still a graduate student, he patented the method that is used to make the optical isomers of hallucinogenic
Psychedelics, dissociatives and deliriants
This general group of pharmacological agents can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness...
amphetamines. His contributions include the synthesis and reporting of escaline
Escaline
Escaline is a psychedelic drug and entheogen of the phenethylamine class of compounds. Escaline was first synthesized and reported in the scientific literature by Benington, et al., in 1954, but was later re-examined in the laboratory of David E. Nichols, who prepared a series of mescaline...
and the coining of the term "entactogen".
He is the founding president of the Heffter Research Institute
Heffter Research Institute
The Heffter Research Institute was incorporated in New Mexico in 1993 as a non-profit organization to support and promote investigation into the medical uses of psychedelic hallucinogens...
, named after German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
chemist and pharmacologist Arthur Heffter
Arthur Heffter
Arthur Carl Wilhelm Heffter was a German pharmacologist and chemist. He was the first chairman of the German Society of Pharmacologists, and was largely responsible for the first Handbook of Experimental Pharmacology...
, who first discovered that mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....
was the active component in the peyote
Peyote
Lophophora williamsii , better known by its common name Peyote , is a small, spineless cactus with psychoactive alkaloids, particularly mescaline.It is native to southwestern Texas and Mexico...
cactus. In 2004 he was named the Irwin H. Page Lecturer by the International Serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
Club, and delivered an address in Portugal titled, "35 years studying psychedelics: what a long strange trip it's been." Among pharmacologists, he is considered to be one of the world's top experts on psychedelics. Nichols's other professional activities include teaching medicinal chemistry and molecular pharmacology at Purdue University in West Lafayette, IN, and teaching medical students at the Indiana University School of Medicine
Indiana University School of Medicine
The Indiana University School of Medicine is a leading medical school and medical research powerhouse connected to Indiana University. With several teaching campuses in the state, the School of Medicine has its predominant research and medical center at the Indiana University – Purdue University...
.
Education
- B.S. - 1969 - University of CincinnatiUniversity of CincinnatiThe University of Cincinnati is a comprehensive public research university in Cincinnati, Ohio, and a part of the University System of Ohio....
- Ph.D.Ph.D.A Ph.D. is a Doctor of Philosophy, an academic degree.Ph.D. may also refer to:* Ph.D. , a 1980s British group*Piled Higher and Deeper, a web comic strip*PhD: Phantasy Degree, a Korean comic series* PhD Docbook renderer, an XML renderer...
- 1973 - University of IowaUniversity of IowaThe University of Iowa is a public state-supported research university located in Iowa City, Iowa, United States. It is the oldest public university in the state. The university is organized into eleven colleges granting undergraduate, graduate, and professional degrees... - Postdoc Work - 1973-74 - University of Iowa
Research areas
Nichols is still carrying out legitimate research on the chemistry of psychedelics. He has published approximately 250 scientific reports and book chapters, all describing the relationship between the structure of a molecule and its biological effects (often referred to as a Structure-activity relationshipStructure-activity relationship
The structure–activity relationship is the relationship between the chemical or 3D structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism...
, or SAR). Although his research mostly uses rats, a number of compounds included in Shulgin's PIHKAL
PiHKAL
PiHKAL: A Chemical Love Story is a book by Dr. Alexander Shulgin and Ann Shulgin which was published in 1991. The subject of the work is psychoactive phenethylamine chemical derivatives, notably those that act as psychedelics and/or empathogen-entactogens...
were actually first synthesized in Nichols's lab. His lab also first developed [125I
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
]-(R)-DOI
2,5-Dimethoxy-4-iodoamphetamine
2,5-dimethoxy-4-iodoamphetamine is a psychedelic drug and a substituted amphetamine of the phenethylamine family. It is also a powerful anti-inflammatory that is effective at doses on the order of 100 micrograms in humans, far below its effective dose as a psychedelic. Despite being a substituted...
as a radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....
. Nichols is one of the few people who has published legitimate research on the chemistry and pharmacology
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
of LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
in the last 20 years, and first reported that several LSD analogues, including ETH-LAD
ETH-LAD
ETH-LAD, 6-ethyl-6-nor-lysergic acid diethylamide is an analogue of LSD. It is described by Alexander Shulgin in the book TiHKAL. ETH-LAD is a hallucinogenic drug similar to LSD, and is slightly more potent than LSD itself, with an active dose reported at between 40 and 150 micrograms...
, PRO-LAD
PRO-LAD
PRO-LAD is an analogue of LSD. It is described by Alexander Shulgin in the book TiHKAL. PRO-LAD is a hallucinogenic drug similar to LSD, and is around as potent as LSD itself with an active dose reported at between 100 and 200 micrograms....
, and AL-LAD
AL-LAD
AL-LAD, also known as 6-allyl-6-nor-lysergic acid diethylamide, is a hallucinogenic drug and an analogue of LSD. It is described by Alexander Shulgin in the book TiHKAL ...
, were more potent than LSD itself. Their human effects are described in TiHKAL
TiHKAL
TiHKAL: The Continuation is a 1997 book written by Alexander Shulgin and Ann Shulgin about a family of psychoactive drugs known as tryptamines. A sequel to PiHKAL: A Chemical Love Story, TiHKAL is an acronym that stands for Tryptamines I Have Known and Loved.-Content:TiHKAL, much like its...
. He also improved the synthesis of psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...
so that it would be accessible for several recent clinical studies.
Other notable research he helped carry out includes extensive studies of the structure-activity relationships and mechanisms of action of MDA
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...
and MDMA, during which he helped to discover many novel analogues including such compounds as 5-methyl-MDA
3-Methyl-4,5-methylenedioxyamphetamine
5-Methyl-3,4-methylenedioxyamphetamine is an entactogen and psychedelic drug of the amphetamine class. It is a ring-methylated derivative of MDA and a structural isomer of MDMA...
, 4-MTA
4-MTA
4-Methylthioamphetamine is an illicit drug and research chemical developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic highly selective serotonin releasing agent in animals...
and MDAI. Nichols has said that "he believes gray-market chemists used information from papers he published on 4-methylthioamphetamine (MTA) in the 1990s to synthesize the drug, which they sold in tablets nicknamed "flatliners" as a substitute for MDMA (Ecstasy)."
More recently, Nichols has become one of the world leaders in research on dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, and his team has developed several notable dopamine receptor ligands, including the selective D1
Dopamine receptor D1
Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.- Function :This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein-coupled receptor stimulates...
full agonist compounds dihydrexidine
Dihydrexidine
Dihydrexidine is a moderately selective full agonist at the dopamine D1 and D5 receptors. It has approximately 10-fold selectivity for D1 and D5 over the D2 receptor. Although dihydrexidine has some affinity for the D2 receptor, it has functionally selective D2 signaling, thereby explaining...
and dinapsoline
Dinapsoline
Dinapsoline is a drug developed for the treatment of Parkinson's disease, that acts as a selective full agonist at the dopamine D1 receptor....
which have been researched for the treatment of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, and a number of other subtype-selective dopamine agonists derived from dinoxyline
Dinoxyline
Dinoxyline is a synthetic compound developed for scientific research, which acts as a potent full agonist at all five dopamine receptor subtypes....
. He co-founded DarPharma, Inc. to commercialize his dopamine compounds; several of his team's compounds are now being studied in clinical trials for the treatment of Parkinson's disease and the cognitive and memory deficits of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.