Over the past 20 years, ketamine has demonstrated powerful antidepressant effects and benefits for other mental health chronic pain conditions. Initially an effective sedative on the battlefield with a wide safety margin, ketamine has become an invaluable resource for various physical and mental issues, known for its transformative power and speedy results.
Ketamine interacts with multiple aspects of our psychology and physiology. Traditional medications like antidepressants can take months to start working. Ketamine therapy, on the other hand, offers patients relief quickly, with some individuals reporting relief within a few hours of their first infusion session.
How Ketamine Works
Recent evidence points to ketamine’s inhibitory effects on the NMDA receptor in the lateral habenula. The lateral habenula is a brain region primarily responsible for encoding negative rewards or anti-reward cause-and-effect relationships. Those with depression and anxiety show an overactivity of burst firing in the lateral habenula. As a non-competitive NMDA antagonist, ketamine prevents glutamate from activating the NMDA receptor.
The inhibition of the NMDA receptor may cause a build-up of free glutamate, which then activates the AMPA receptors. When surplus glutamate activates the AMPA receptor, it releases a brain-derived neurotrophic factor (BDNF) chemical. BDNF, in interaction with the mammalian target of rapamycin (mTOR), promotes new neural growth. This new growth may reroute the brain from hyperactive areas associated with negative reward signals, thereby providing long-term relief from mental health and chronic pain conditions.
If you want a deep dive into the neuroscience behind ketamine as a treatment for mental health and pain, click below to hear from Dr. Andrew Huberman, Professor of Neurobiology and Ophthalmology at Stanford School of Medicine.
Brain Regions and Chemicals to Know
A picture of a neuron. The neuron below shows new dendritic formations, or new neural growth, within just 2 hours of receiving ketamine.
A prominent neurotransmitter in the brain. Glutamate is now strongly associated with mood disorders. It is partly responsible for memory, learning, and mood regulation.
While this glutamate receptor and ion channel has many different roles, researchers have implicated it in mental health issues. Overactive NMDArs are associated with heightened depression and general distress.
This receptor is suspected to be primarily responsible for instigating neural plasticity in excitatory transmission. It is a key region of stimulation regarding ketamine’s healing properties.
Brain-derived neurotrophic factor signals new neural growth in the brain and is released when glutamate stimulates the AMPA receptor.
The mammalian target of rapamycin complex 1 (mTOR) is a signaling pathway that regulates new neural growth. Its stimulation is associated with the effects of BDNF.
The lateral habenula is a brain region largely responsible for our interpreting and predicting negative consequences. Those with depression and anxiety show an overactivity of burst firing in the lateral habenula.
IV vs IM Ketamine Treatments
- IV ketamine has a faster onset of action and more precise dosing than IM ketamine. This can be beneficial in situations where rapid symptom relief is needed.
- IM ketamine may be preferred when IV access is impossible or if a slower onset of action is desired.
- IM ketamine may also be easier to administer in certain settings where IV access is not readily available.