Neurotransmitters are chemicals that relay signals from one neurone to another at the synapse.

More than 100 known

Ramon y cajal discovered the synaptic cleft and this suggested it s not electrical transmission between neurones, as previously
thought. Otto Leowi first proved chemical communication through experiments with vagus nerves (10 th cranial nerve extending from brainstem to abdomen via heat, oesophagus and lungs) of frogs and is credited with discovering acetylcholine.
Most common NT is Glutamate (excitatory) present in more than 90% of brains synapses
Most addictive/psychoactive drugs act by altering the concentrations of certain NTs and changing the functioning of certain NT
systems
They are released by pre-synaptic neurone when the synaptic vesicle fuses with membrane and dumps them into the synaptic
cleft. They then bind to specific receptors on post-synaptic neurone and trigger/inhibit action potentials. After a short while, the
neurotransmitter is broken down by enzymes and reabsorbed into the pre-synaptic neurone.
Most neurotrasmitters are monoamines (similar to size of amino acids). Sme neurotransmitters are larger polypeptides/proteins
Neurotransmitters are classified as:
Amino acids Glutamate is the main fast excitatory NT in synapses of brain and spinal cord. It is used a lot in modifiable
synapses which seem to be involved in memory storing. Excessive glutamate can cause excitotoxicity leading to seizures and
strokes. It might be invoved in Alzheimers disease, ALS, Ischemic stroke
GABA is the main fast inhibitory NT in synapses of brain and glycine does that job in spinal cord synapses. Tranquilizing drugs
act by increasing effect of GABA
Peptides
Monoamines Dopamine regulates pleasure, motivation, emotional arousal and voluntary motor behaviour. It is critical for
the reward system of the brain. Parkinsons disease patients seem to have low levels of dopamine while high levels are
associated with schzophrenia
Serotonin 90% found in intestine and 10% in CNS. It has vast functions ranging from regulating appetite and causing feelings
of satiation, regulating mood, sleep, learning and memory and functioning of endocrine system. Low levels of it are associated
with depression and most common depression medications are SSRI (selective serotonin reuptake inhibitors allow serotonin to
be retained in the synaptic cleft for longer)
Others Acetylcholine stimulates skeletal muscles in the voluntary (somatic) nervous system and can excite or inhibit organs as
part of involuntary (autonomic) nervous system. It is normally released in the neuromuscular junction (motor neurones
connected to muscles). Drugs/poisons that cause paralysis act by blocking the acetylcholine receptors or its release.
Single ions and gaseous molecules (Carbon monoxide, hydrogen sulphide) are also considered as neurotransmitters by some.

Drugs
Psychoactive drugs are chemical substances that affect the nervous system, alter perception, consciousness or mood.
Recreational drugs are drugs that are used for pleasure and not medical cause.
Drugs considered to have religious usage are called etheogens and those that claim to improve human cognitive abilities are
called nootropics.
MDMA
3,4 methylenedioxy-methamphetamine Consists of methylenedioxy group bonded to benzene ring through 3, 4 carbon
position. The rest of the molecule is methamphetamine. It causes feelings of euphoria and empathy, feeling of oneness, sense of
inner peace, enhanced sensation and sexuality and mild hallucinations. It blocks the reuptake of neurotransmitters Serotonin,
Dophamine and norepinephrine by the neurone that released them into the synapse and also causes them to release more of it,
thereby increasing concentration of these NT in the synapse which cause continuous action potentials to be fired in the
neurones. It is a monoamine transporter substrate and so it is able to enter monoamine neurones. At the sypapse, it competes
with the endogenous monoamines for reuptake.
MDMA reaches maximum concentrations in the blood between 1.5 to 3 hours after ingestion. Users report effects within 0.5 1
hour of consumption, hitting a peak at about 1.25 2 hours.
Neurotoxicity and addiction harmful effects of use
Currently no accepted medical uses
Short term health risks:
Hyperthermia
Dehydration
Fatal Hyponatremia excessively low Na+ conc. In blood): happens when MDMA users try to prevent dehydration by drinking
excessive water but not enough electrolytes so blood is diluted.
Diarrhea, Nausea and volmiting
Increased heart rate and blood pressure
After effects that can last upto a week:
Trismus (lockjaw)
Insomnia
Anxiety and paranoia
Depression
Irritability, impulsiveness and restlessness
Anhedonia inability to experience pleasure from usually enjoyable activities
Long term effects:
Brain lesions/damage in serotonergic neural pathways of humans
Neurotoxicity in serotonergic axon terminals that persist for more than two years

Inflammatory effects in brain and spinal cord

Cognitive impairments leading to significant derogatory effect on memory, visual processing and sleep etc.