Archive for the ‘neurotransmitters’ Category

Epinephrine (also known as adrenaline) is a hormone and a neurotransmitter.[1] It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system.[2] In chemical terms, adrenaline is one of a group of monoamines called the catecholamines. It is produced in some neurons of the central nervous system, and in the chromaffin cells of the adrenal medulla from the amino acids phenylalanine and tyrosine.[3]

Extracts of the adrenal gland were first obtained by Polish physiologist Napoleon Cybulski in 1895. These extracts, which he called nadnerczyna, contained adrenaline and other catecholamines.[4] Japanese chemist Jokichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900.[5][6] In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen.[7] Adrenaline was first synthesized in the laboratory by Friedrich Stolz and Henry Drysdale Dakin, independently, in 1904.[6]

Adrenaline is used to treat a number of conditions including: cardiac arrest, anaphylaxis, and superficial bleeding.[8] It has been used historically for bronchospasm and hypoglycemia, but newer treatments for these, such as salbutamol, a synthetic epinephrine derivative, and dextrose, respectively, are currently preferred.[8]


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 The feeling of doing DMT is as though one had been struck by noetic lightning. The ordinary world is almost instantaneously replaced, not only with a hallucination, but a hallucination whose alien character is its utter alienness. Nothing in this world can prepare one for the impressions that fill your mind when you enter the DMT sensorium.

Terence McKenna

N,N-dimethyltryptamine(DMT) is a psychoactive chemical in the tryptamine family, which causes intense visuals and strong psychedelic mental affects when smoked, injected, snorted, or when swallowed orally (with an MAOI such as haramaline). DMT was first synthesized in 1931, and demonstrated to be hallucinogenic in 1956. It has been shown to be present in many plant genera (Acacia, Anadenanthera, Mimosa, Piptadenia, Virola) and is a major component of several hallucinogenic snuffs (cohoba, parica, yopo). It is also present in the intoxicating beverage ayahuasca made from banisteriopsis caapi. This drink inspired much rock art and paintings drawn on the walls of native shelters in tribal Africa- what would be called ‘psychedelic’ art today (Bindal, 1983). The mechanism of action of DMT and related compounds is still a scientific mystery, however DMT has been identified as an endogenous psychadelic- it is a neurotransmitter found naturally in the human body and takes part in normal brain metabolism. Twenty-five years ago, Japanese scientists discovered that the brain actively transports DMT across the blood-brain barrier into its tissues. “I know of no other psychedelic drug that the brain treats with such eagerness,” said one of the scientists. What intrigued me were the questions, how and why does DMT alter our perception so drastically if it is already present in our bodies?

DMT is known as the “spirit molecule” because it elicits with reasonable reliability, certain psychological states that are considered ‘spiritual.’ These are feelings of extraordinary joy, timelessness, and a certainty that what we are experiencing is more real than present day reality. DMT leads us to an acceptance of the coexistence of opposites, such as life and death, good and evil; a knowledge that consciousness continues after death; a deep understanding of the basic unity of all phenomena; and a sense of wisdom or love pervading all existence. The smoked DMT experience is short, but generally incredibly intense. Onset is fast and furious, and thus the term “mind-blowing” was used to describe the effect. It is a fully engaging and enveloping experience of visions and visuals, which vary greatly from one individual to the next. Users report visiting other worlds, talking with alien entities, profound changes in ontological perspective, fanciful dreamscapes, frightening and overwhelming forces, complete shifts in perception and identity followed by an abrupt return to baseline. “The effect can be like instant transportation to another universe for a timeless sojourn” (Alan Watts).

The physical and psychological effects of DMT include a powerful rushing sensation, intense open eye visuals, radical perspective shifting, stomach discomfort, overwhelming fear, color changes and auditory hallucination (buzzing sounds). One of the primary physical problems encountered with smoked DMT is the harsh nature of the smoke which can cause throat and lung irritation. Surprisingly however, DMT is neither physically addictive nor likely to cause psychological dependence (Szara, 1967).

Most subjects were reported to have had memorable positive experiences, however the possibility of unpleasant experiences is not ruled out. William Borroughs, a psychologist in London tried it and reported of it in most negative terms. Burroughs was working at the time on a theory of neurological geography and after trying DMT, he described certain cortical areas as ‘heavenly’, while others were ‘diabolical’. In Burroughs’ pharmacological cartography, DMT propelled the voyager into strange and decidedly unfriendly territory. The lesson however, was clear. DMT, like the other psychedelic keys, could open an infinity of possibilities. Set, setting, suggestibility and temperamental background were always present as filters through which the ecstatic experience could be distorted (Jacobs, 1987).

The brain however, is where DMT exerts its most interesting effects. The brain is a highly sensitive organ, especially susceptible to toxins and metabolic imbalances. In the brain, sites rich in DMT-sensitive serotonin receptors are involved in mood, perception, and thought. Although the brain denies access to most drugs and chemicals, it takes a particular and remarkable fancy to DMT. According to one scientist, “it is not stretching the truth to suggest that the brain hungers for it.” A nearly impenetrable shield, the blood-brain barrier, prevents unwelcome agents from leaving the blood and crossing the capillary walls into the brain tissue. This defense extends to keep out the complex carbohydrates and fats that other tissues use for energy, as the brain only uses glucose or simple sugars as its energy sources. Amino acids are among the few molecules that are transported across the blood brain barrier and thus to find that brain actively transported DMT into its tissues was astounding. DMT is part of a high turnover system and is rapidly broken down once it enters the brain, giving it the ability to exert its effects in a short period of time. Researchers labeled DMT as ‘brain food,’ as it was treated in a manner similar to how the brain handles glucose. In the early nineties, DMT was thought to be required by the brain in small quantities to maintain normal functioning and only when DMT levels crossed a threshold did a person undergo ‘unusual experiences.’ These unusual experiences involved a separation of consciousness from the body and when psychedelic effects completely replaced the mind’s normal thought processes. This hypothesis led scientists to believe that as an endogenous psychedelic, DMT may be involved in naturally occurring psychedelic states that have nothing to do with taking drugs, but whose similarities to drug-induced conditions are striking. DMT was considered to be a possible ‘schizotoxin’ which could be linked to states such as psychosis and schizophrenia. “It may be upon endogenous DMT’s wings that we experience other life-changing states of mind associated with birth, death and near-death, entity or alien contact experiences, and mystical/spiritual consciousness” (Strassman, 2001).

Hallucinogenic drugs have multiple effects on central neurotransmission. In 1997, it was found that like LSD and Psilocybin, DMT has the property of increasing the metabolic turnover of serotonin in the body. Serotonin is found in specific neurons in the brain that mediate chemical neurotransmission. Axons of serotonergic neurons project to almost every part of the brain, affecting overall communication within the brain. Early in the research on hallucinogens, it was determined that hallucinogenic drugs structurally resemble serotonin (5-HT) and thus researchers thought that DMT bound itself to serotonin receptors in the cerebral cortex (Strassman, 1990).

Further, an increase in 5-hydroxy-IAA excretion suggests the involvement of serotonin in DMT action and elevated blood levels of indoleacetic acid (IAA) are seen during the time of peak effects, implying its role as a metabolite. The relationship between DMT and serotonin led researchers to become interested in the pineal gland. The pineal gland in humans regulates homeostasis of the body and body rhythms. A dysfunction could be associated with mental disorders presenting themselves as disturbances of normal sleep patterns, seasonal affective disorders, bipolar disorder, and chronic schizophrenia. Strassman proposed that the pineal gland, besides producing melatonin, is associated with ‘unusual states of consciousness.’ For example, it possesses the highest levels of serotonin in the body and contains the necessary building blocks to make DMT. The pineal gland also has the ability to convert serotonin to tryptamine, a critical step in DMT formation. In addition, 5-methoxy-tryptamine, which is a precursor of several hallucinogens, has been found in pineal tissue [Bosin and Beck, 1979; Pevet, 1983] and in the cerebrospinal fluid [Koslow, 1976; Prozialeck et al., 1978].

Every night Pinoline (made by the pineal gland), DMT and 5meoDMT are produced in the brain and are the causal agents of vivid dreams. The interior dialogue produced on a DMT trip leads scientists to believe that the language centers are also affected. Of late, various experiments have been conducted that show that DMT allows awareness of processes at a cellular or even atomic level. Could DMT smokers be tapping into the network of cells in the brain or into communication among molecules themselves?

According to Groff, the major psychedelics do not produce specific pharmacologic states (i.e-toxic psychosis) but are unspecific amplifiers of mental processes (Groff, 1980). At the same time, the identification of 5HT2 receptors as possibly being involved in the action of hallucinogens has provided a focal point for new studies. Is there a prototypic classical hallucinogen? Until we have the answers to such questions, we continue to seek out the complex relationship between humans and psychoactives.


Szara, S. Hallucinogenic Drugs- Curse or Blessing? Am J Psychiatry 123: 1513-1518, 1967.

Strassman, R. Human Hallucinogenic Drug Research: Regulatory, Clinical and Scientific Issues. Brain Res. 162. 1990.

B.L. Jacobs. 1987. How Hallucinogenic Drugs Work. “American Scientist”. 75:385-92.

M.C. Bindal, S.P. Gupta, and P. Singh. 1983. QSAR Studies on Hallucinogens. ‘Chemical Reviews’. 83:633-49.

Groff, S. Realms of the Human Unconcious: Observations from LSD Research. Jeremy Tarcher Inc., LA. 1980, pp 87-99.



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A recent focus of the Heffter Zürich Research Center has been an examination of serotonin 5-HT2A neuroreceptor dynamics in the human brain following psilocybin, and its potential relevance for the treatment of obsessive-compulsive spectrum disorders (OCSDs), including OCD and eating disorders. The study is being carried out by Dr. Felix Hasler, Ph.D. and Boris B. Quednow, under the direction of Heffter board member Franz X. Vollenweider.

Initial studies involved synthesizing the positron-emitting tracer molecule [18F]-altanserin, which binds to brain serotonin 5-HT2A receptors. Using positron-emission tomography (PET), the location and density of these receptors can then be visualized in the living human brain. The picture on the left is a side view showing the 5-HT2A brain receptors where psilocybin acts. The receptor density is correlated with color, where red/yellow are the highest receptor concentrations.

Administration of psilocybin can completely prevent the binding of the radioactive tracer to this area. Preliminary analysis reveals a strong and consistent decrease (30%) of [18F]-altanserin binding in the psilocybin condition as compared to placebo.

When the actual clinical study of psilocybin in OCSD patients begins, the Zürich group will have the baseline data to show the normal levels of 5-HT2A receptors in the brain and how psilocybin affects them. Those data will be essential to compare with OCSD patients to gain an understanding of how psilocybin could be an effective treatment. These are the first steps toward demonstrating a mechanism for how psilocybin might help patients with OCD, following up on the pilot study we supported at the University of Arizona, above. We now plan to move toward the biologically-related but difficult to treat problem of eating disorders.

In the other major Zürich study, comparing subjects in a meditation state with subjects under the influence of psilocybin, 3-D EEGs showed striking similarities between the two states of consciousness. This result may further explain how psilocybin “awakens” the brain patterns that occur during meditative and spiritual states of consciousness.

More info at webpage of The Clinic of Affective Disorders and General Psychiatry is part of the University Hospital of Psychiatry Zurich.

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The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems.[1][2] They mediate both excitatory and inhibitoryneurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

The serotonin receptors modulate the release of many neurotransmitters, including glutamate,GABAdopamineepinephrine / norepinephrine, and acetylcholine, as well as many hormones, including oxytocinprolactinvasopressincortisolcorticotropin, and substance P, among others. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, andthermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and illicit drugs, including many antidepressantsantipsychoticsanorecticsantiemeticsgastroprokinetic agentsantimigraine agentshallucinogens, and entactogens.

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Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to receptors in the membrane on the postsynaptic side of the synapse. Release of neurotransmitters usually follows arrival of an action potential at the synapse, but may also follow graded electrical potentials. Low level “baseline” release also occurs without electrical stimulation. Neurotransmitters are synthesized from plentiful and simple precursors, such as amino acids, which are readily available from the diet and which require only a small number of biosynthetic steps to convert.

The chemical identity of neurotransmitters is often difficult to determine experimentally. For example, it is easy using an electron microscope to recognize vesicles on the presynaptic side of a synapse, but it may not be easy to determine directly what chemical is packed into them. The difficulties led to many historical controversies over whether a given chemical was or was not clearly established as a transmitter. In an effort to give some structure to the arguments, neurochemists worked out a set of experimentally tractable rules. According to the prevailing beliefs of the 1960s, a chemical can be classified as a neurotransmitter if it meets the following conditions:

  • There are precursors and/or synthesis enzymes located in the presynaptic side of the synapse.
  • The chemical is present in the presynaptic element.
  • It is available in sufficient quantity in the presynaptic neuron to affect the postsynaptic neuron.
  • There are postsynaptic receptors and the chemical is able to bind to them.
  • A biochemical mechanism for inactivation is present.

Modern advances in pharmacology, genetics, and chemical neuroanatomy have greatly reduced the importance of these rules. A series of experiments that may have taken several years in the 1960s can now be done, with much better precision, in a few months. Thus, it is unusual nowadays for the identification of a chemical as a neurotransmitter to remain controversial for very long periods of time.

Types of neurotransmitters

There are many different ways to classify neurotransmitters. Dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes.

Major neurotransmitters:

In addition, over 50 neuroactive peptides have been found, and new ones are discovered regularly. Many of these are “co-released” along with a small-molecule transmitter, but in some cases a peptide is the primary transmitter at a synapse. β-endorphin is a relatively well known example of a peptide neurotransmitter; it engages in highly specific interactions with opioid receptors in the central nervous system.

Single ions, such as synaptically released zinc, are also considered neurotransmitters by some[5], as are some gaseous molecules such as nitric oxide (NO) and carbon monoxide (CO). These are not classical neurotransmitters by the strictest definition, however, because although they have all been shown experimentally to be released by presynaptic terminals in an activity-dependent way, they are not packaged into vesicles.

By far the most prevalent transmitter is glutamate, which is excitatory at well over 90% of the synapses in the human brain.[2] The next most prevalent is GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Even though other transmitters are used in far fewer synapses, they may be very important functionally—the great majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, often acting through transmitters other than glutamate or GABA. Addictive drugs such as cocaine and amphetamine exert their effects primarily on the dopamine system. The addictive opiate drugs exert their effects primarily as functional analogs of opioid peptides, which, in turn, regulate dopamine levels.

Excitatory and inhibitory

Some neurotransmitters are commonly described as “excitatory” or “inhibitory”. The only direct effect of a neurotransmitter is to activate one or more types of receptors. The effect on the postsynaptic cell depends, therefore, entirely on the properties of those receptors. It happens that for some neurotransmitters (for example, glutamate), the most important receptors all have excitatory effects: that is, they increase the probability that the target cell will fire an action potential. For other neurotransmitters, such as GABA, the most important receptors all have inhibitory effects (although there is evidence that GABA is excitatory during early brain development). There are, however, other neurotransmitters, such as acetylcholine, for which both excitatory and inhibitory receptors exist; and there are some types of receptors that activate complex metabolic pathways in the postsynaptic cell to produce effects that cannot appropriately be called either excitatory or inhibitory. Thus, it is an oversimplification to call a neurotransmitter excitatory or inhibitory—nevertheless it is so convenient to call glutamate excitatory and GABA inhibitory that this usage is seen very frequently.

Here are a few examples of important neurotransmitter actions:

  • Glutamate is used at the great majority of fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are “modifiable”, i.e. capable of increasing or decreasing in strength. Modifiable synapses are thought to be the main memory-storage elements in the brain. Excessive glutamate release can lead to excitotoxicity causing cell death.
  • GABA is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of GABA. Correspondingly glycine is the inhibitory transmitter in the spinal cord.
  • Acetylcholine is distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles. The paralytic arrow-poison curare acts by blocking transmission at these synapses. Acetylcholine also operates in many regions of the brain, but using different types of receptors.
  • Dopamine has a number of important functions in the brain. It plays a critical role in the reward system, but dysfunction of the dopamine system is also implicated in Parkinson’s disease and schizophrenia.
  • Serotonin is a monoamine neurotransmitter. Most is produced by and found in the intestine (approximately 90%), and the remainder in central nervous system neurons. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behaviour, muscle contraction, and function of the cardiovascular system and endocrine system. It is speculated to have a role in depression, as some depressed patients are seen to have lower concentrations of metabolites of serotonin in their cerebrospinal fluid and brain tissue.
  • Substance P is an undecapeptide responsible for transmission of pain from certain sensory neurons to the central nervous system.

Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system affects large volumes of the brain, called volume transmission. Major neurotransmitter systems include the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system.

Drugs targeting the neurotransmitter of such systems affect the whole system; this fact explains the complexity of action of some drugs. Cocaine, for example, blocks the reuptake of dopamine back into the presynaptic neuron, leaving the neurotransmitter molecules in the synaptic gap longer. Since the dopamine remains in the synapse longer, the neurotransmitter continues to bind to the receptors on the postsynaptic neuron, eliciting a pleasurable emotional response. Physical addiction to cocaine may result from prolonged exposure to excess dopamine in the synapses, which leads to the downregulation of some postsynaptic receptors. After the effects of the drug wear off, one might feel depressed because of the decreased probability of the neurotransmitter binding to a receptor. Prozac is a selective serotonin reuptake inhibitor (SSRI), which blocks re-uptake of serotonin by the presynaptic cell. This increases the amount of serotonin present at the synapse and allows it to remain there longer, hence potentiating the effect of naturally released serotonin. AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.

Diseases may affect specific neurotransmitter systems. For example, Parkinson’s disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for example the substantia nigra. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.

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