I’m on a plane with cocaine,
And yes I’m all lit up again.


The mystery of cocaine.

When not applying his exacting mind to the mysteries of tenuous circumstances, the fine detective of Baker Street would dispel the tedium that surrounded him with cocaine injections. Solving crimes and cruising coke channels describe an enviable lifestyle! Both activities would be expected to have sent Holmes into a dopaminergic ecstasy. But whereas the first required sleepless nights of deductions, inductions, and refuted hypotheses, the latter merely involved a short cut of the brain's reward circuitry and hence a much faster effect. But how fast?

Cocaine therapy.

When not peeling away at the subconscious, the brave Austrian psychoanalyst would sometimes take a stroll down cocaine alley. As soon as ten second after injection, dopamine could be seen accumulating in the Freudian nucleus accumbens. The nucleus accumbens sits along the mesolimbic pathway in the brain, where it rewards the Id, Ego, and Superego for their good behaviour, making them all feel great and assuring them to continue doing whatever it is that they're doing.

The time taken for this effect is dependent on the cocaine crossing the blood brain barrier, getting to the right parts of the brain, and then acting on dopamine transport. Cocaine blocks the uptake of dopamine back into neurons, leaving the feel-good neurotransmitter to build up in the synaptic clefts. More dopamine in the synapses means more dopaminergic signalling, means more activation of the reward pathway, means more Freud bouncing off the walls.

Annexing cocaine.

Sometime in between dropping out of art school and locking himself in a bunker, fascism's infamous poster boy took to perking himself up with a fistful of stimulants, including cocaine. Once Hitler learned just how good a coke hit felt, his brain developed a Pavlovian expectation to the drug, so that signalling would begin even before the cocaine had penetrated into the Nazi grey matter. This anticipatory euphoria takes less than five seconds, and involves another part of the reward pathway. The ventral tegmental area lights up upon administration, sending dopamine packages to the nucleus accumbens, activating the neurons there.

The speed of coke.

Cocaine euphoria travels by two pathways.

The first is an anticipatory activation of the ventral tegmental area, based on learned expectations. This occurs in less than five seconds, and the neurons there signal down to the nucleus accumbens where dopamine is released and reward experienced.

The second pathway involves the cocaine itself reaching the nucleus accumbens, and by ten seconds or more blocking the uptake of dopamine. Dopamine immediately accumulates in the nucleus accumbens, where the build up induces continued reward experience.

Which is to say, whether you're cornering London's criminals, analyzing Vienna's sexually repressed, or even committing war crimes across Europe, coke gets you there fast. Where there is, is another question altogether. 


Driving that train, high on cocaine,
Casey Jones is ready, watch your speed.


References: Wikipedia, Wise et al. Differentiating the rapid actions of cocaine (2011) Nat Rev Neuro.

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