Psychedelic Medicine Resources & FAQs

Electric impulses, (Action Potentials) are transmitted from the axon of one neuron to the dendrites of another neuron. The junction where the neurons communicate is called the synapse. Neurotransmitters are brain chemicals, like serotonin, Nor-epinephrine, Dopamine and others. To transmit the nerve impulse neurotransmitters travel across the gap or synpatic cleft between neurons as chemical messengers to allow the impulse or signal to be propagated.

Neurotransmitters are made in the neurons and stored in tiny sacs, vesicles, at the ends of axons. The cell membrane or outer covering of the neurons are covered with receptors, which channel the neurotransmitters through to the next neuron. There receptors are specific for each type of neurotransmitter. The neurotransmitter fit like a key on the receptor which then opens the channel into the cell.

The nerve impulse at the end of the tip, also affect the opening of Calcium channels. Thes Calcium-charged elements then cause the vesicles to attach to the neuron cell membrane, which then allows for the pouring of Neurotransmitters to be secreted into the synapse. Neurotransmitters diffuse across the synapse gap and bind to their matching and specific receptors in the membrane of the postsynaptic neuron (the target neuron). The binding opens the channels leading into the cell interior and calcium, sodium, magnesium, and other ions flow in.

The flow of incoming ions such as calcium and sodium depolarizes( or changes the charge) the cell membrane, which gives the inside of the cell to be more negatively charges. When the depolarization threshold is reached the neuron fires an electrical signal. This impulse is then transmitted through the cell, down its axon, and on to the next neuron in the chain.

After the neurotransmitter has done its jobs in the synapse, it is taken back up or (reuptake) into the pre-synaptic cell membrane. From there the neurotransmitter is taken back into the cell and stored once again in the tiny sacs, vesicles. Neurotransmitters now repackaged await the signal of another cycle of impulses to repeat the actions as the messenger between neurons once again.

When the neurotransmitters are re-absorbed, the synapse turns off. The entire process of impulse and neurotransmitter communication back to reuptake into the cell occurs in milliseconds and happens billions of time a day, 24 hours a day!

In the brain, the neurotransmitters glutamate and dopamine are excitatory. The inhibitory neurotransmitters are GABA (gamma-aminobutyric acid), serotonin, and dopamine.

The release, removal, and reuptake of neurotransmitters is tightly regulated. If there is an effect on the reuptake of neurotransmitters, the concentration neurotransmitter or the sensitivity of neuron’s impulse, there can be a disruption in the brain’s communication, connectivity, and balance. This can lead to a dysregulated state of either too much excitation or inhibition in specific parts of the brain.

Glutamate is the most common excitatory neurotransmitter in the brain. It plays a particularly important role in neuroplasticity (the brain’s ability to form new synapses and neural connections over a lifetime), learning, and forming memories. When there’s too much glutamate in the brain, the postsynaptic neurons can become hyperexcited; when there’s way too much glutamate in the brain, it can damage neurons or even cause neuron death.

Toxic level and persistent stress affects the neurons of the cortex. Toxic stress puts the brain in an inflammatory and increases cortisol concentrations in the brain. Cortisol can cause neurons atrophy or early death and shrinkage of neurons. Dendrites also decrease in their ability to branch and spread, which leads to fewer connections between neurons. The axons are thinner and smaller. Glutamate signaling is also less effective and responsive.

It has been shown that in chronically depressed people, the size of the prefrontal cortex is smaller and connections to other key components of the brain, are restricted and become dysfunctional in the emotional (limbic) and memory centers (hippocampus) of the brain.

The toxic and inflammatory state of the brain, in trauma, depression, anxiety limits effectiveness of the glutamate neuronal pathways.

Ketamine, which is an anesthetic works by activating glutamate release into the synapse. Researchers studying depression discovered that glutamate receptors can be “dysfunctional” in people with depression. -this is focus of ketamines effect on the glutamate system in treating depression.

Ketamine when used as an anesthetic, was also found to lift symptoms of depression. Since the 1990’s more research has shown that small doses of ketamine when given to severely depressed patients, who did not respond to standard antidepressants like SSRI’s had remarkable results.

We know that ketamine does affect other receptors but it most important receptor it activates are glutamate receptors.

Neurons have many binding sites for glutamate, but when it comes to ketamine, two are of particular interest: the NMDA (N-methyl-D-aspartate) receptor and the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor.

Glutamate activates the ion channels in both NMDA (N-methyl-D-aspartate) and AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors.

At the very low dose, Ketamine increases release of glutamate from presynaptic cleft into the synapse, which has an antidepressant effect. However, Ketamine then preferentially blocks glutamate at the NMDA receptors of the postsynaptic cell but not at the adjacent AMPA receptors. This causes a net effect to increase AMPA activation. In addition, Ketamine triggers the neuron to make more AMPA receptors, moving them into the membrane of the synapse area.

Further research has uncovered the effect of Ketamine on other receptors, NMDA and parvalumin interneurons. Ketamine blocks one part of the NMDA receptors, and in these parvalbumin interneurons, the effect is and increase activity of brain circuitry which awakens the brain. Ketamine can trigger increased release of the neuromodulators dopamine and noradrenaline; it also binds weakly to nicotinic and opioid receptors. More actions of Ketamine are also known to effect on organelles (structures) in the neuron that are involved in signaling, protein and lipid synthesis, and transport proteins.

Toxic level stress impacts the brain at both micro -cellular and macro structural level on the brain. Chronic depression, anxiety, and PTSD leads to decreased size, response, and connectivity in the key parts of the brain. The prefrontal cortex is where a significant portion of executive functioning ocurs, planning, organizing, self regulation, problem solving. Ketamine enhances global connectivity within the prefrontal cortex and the pathways in other sub-regions of the brain.