Ketamine Flashcards
When was ketamine invented, and what was the initial purpose of the drug?
Ketamine was derived from PCP, in order to create an anaesthetic drug without the psychomimetic side effects. This was in the 1960’s and in 1970 it was approved as an anaesthetic by the FDA.
Effects of ketamine intake:
Sedation
Immobility
Marked Analgesia (pain reduction)
Feeling of dissociation from the environment
Ketamine can cross the blood/brain barrier
True or false?
True, ketamine is a lipophilic molecule that rapidly crosses the bbb.
Ketamine’s mode of action
Ketamine acts as an antagonist to NMDA-receptors.
When cells are depolarized, NMDA-receptors release a Mg+ that usually blocks the channel, which leads to an influx of Ca+ and Na+ and efflux of K+. When ketamine is taken, it enters the NMDA-receptor and blocks the channel.
This essentially blocks the neuronal activation, which is why it can induce unconsciousness in large quantities.
Ketamine also binds to other receptors, but mainly NMDA-r
What is the mechanism of SSRIs?
As depression was hypothesised to be mainly caused by a decrease in serotonin, selective serotonin reuptake inhibitors (SSRI) were developed to treat depression by increasing extracellular serotonin levels, by preventing reuptake by neurons.
However, depression is more complex than decreased serotonin, and 1/3 patients don’t respond to SSRIs.
Ketamine as an antidepressant
Ketamine was discovered to have an antidepressant effect already in the 1990s. However, it was only in 2019 it was approved by the FDA and EMA as an antidepressive. It is given intra-nasally to people with treatment resistant depression.
The antidepressant effects can be seen within hours after taking the drug and can last for weeks. SSRIs on the other hand can take months to reach full effect and their effects vanish quickly when patients stop taking them.
The antidepressant effects have been linked to 5 main brain areas: Prefrontal cortex Amygdala Nucleus accumbens Hippocampus Lateral Habenula
fMRI studies have shown both increased and decrease activity in the PFC following ketamine treatment
True or false?
True!
However this is dose dependent, and most likely the positive antidepressant effects are caused by a decreased activity in the PFC.
Magnetic resonance imaging shows that ketamine treatment enlarges Nucleus Accumbens volume in MDD patients
True or false?
True!
Ketamine seems to have a restoring effect on the areas in the brain affected by MDD. Similarly, ketamine treatment can alleviate stress-induced changes in neuroplasticity in the nucleus accumbens.
Lateral Habenula
Can be thought of as the “anti-reward center” as it inhibits reward signaling.
Neurons in the lateral habenula are ‘reward-negative’ as they are activated by stimuli associated with unpleasant events, the absence of the reward or the presence of punishment especially when this is unpredictable.
How does ketamine affect the lateral habenula?
A recent study shows that ketamine’s inhibition of the NMDA receptor and subsequent block of the glutamatergic input to the Lateral habenula caused disinhibition of the ventral tegmental area dopamine neurons, resulting in increased dopamine neurotransmission
Side effects of ketamine treatment
- Potential for addiction
- Psychomimetic effects at high doses
- Cognitive impairment and urinary tract toxicity
- A strange, weird, or loopy feeling.
However, for nasal spray antidepressant, the side effects were:
- Dissociation
- Nausea
- Vertigo
- Dysgeusi (Dysgeusia is a taste disorder. People with the condition feel that all foods taste sour, sweet, bitter or metallic)
- Dizziness
Ketamine-assisted psychotherapy
A type of therapy where the dissociative effects of ketamine become the vehicle for treatment, assisted by psychotherapy. It has shown very promising results, but it is costly, and like with other treatments that include psychomimetic effects, it is subject to political resistance.
