Parallel to the boom of cocaine as a local anesthetic in the world of surgery, the cocaine molecule entered in another scenario where it started as a hero and ended up as the villain or the culpable of all the evils of modern society: cocaine, and its modern derivatives also happened to be powerful stimulants of the central nervous system.
“In man, the small doses of cocaine also act on the cerebral cortex, causing psychic stimulation with an increase of work capacity, possibly due to the absence of a feeling of fatigue (central analgesic action and reduction of the transmission of nerve impulses), then the production of excitement, even of a sexual nature, euphoria, loquacity, restlessness” states Manuel Litter in his Pharmacology Treatise.
On local anesthetics, he states: “Local anesthetics, once absorbed, produce stimulation, tremor, etc. Then (at highly toxic concentrations, most likely,) the stimulation phenomena is followed by central depression by exhaustion of the nerve centers.”
In reference to intoxication, Litter recommends: “…the best way to prevent and treat intoxication by local anesthetics is the dispensation of depressors. The same author, when dealing with opium and its derivatives qualifies them as selective depressors of the central nervous system. In other words, opium and cocaine, or local anesthetics are so contradictory that one of them is the antidote of the other.
Later on we will examine why the 1961 United Nations Convention classified these substances as homologues. Concerning the autonomic nervous system, the same author states: “Cocaine enhances the response of the innervated structures of the sympathetic system, as well as adrenaline and norepinephrine (sympathetic chemical transmitters). In this way, they provoke vessel constriction, mydriasis and tachycardia (sympatho-mimetic action.)”
For this reason, medium cocaine doses produce tachycardia and an increase of blood pressure on the heart. And, as in every excess, high doses revert their action and blood pressure can decrease intensely. The action mechanism of cocaine as a stimulant is based on the blocking of the recapture of norepinephrine in the inter-synaptic gap.
Remember that the transmission of nerve pulses takes place both chemically and electrically. The electric pulse “transforms” upon reaching the end of the nerve cell in a sort of chemical spark. The neuro-transmitter is norepinephrine which is in charge of carrying the message to the other cell and so on until the objective is reached. This neuro-transmitter is norepinephrine, which once its mission has been accomplished, is degraded by special enzymes or recaptured by the emitting cell (saving mechanism). The cocaine molecule blocks the recapturing of the neuro-transmitter, forcing it to remain more time in the synaptic gap and repeat its stimulating action. It is as if the original impulse is repeating itself time and time again.
The final effect is a sympathetic energy many times higher, due to the summatory effect. For didactic purposes we could say that the adrenergic system undergoes a sort of “voltage increase.” On the other hand, the fact that the neuro-transmitter remains more time in the synaptic gap, allows for the enzymes in charge of their downgrading to act more steadily on them and produce, in the end, a depletion of its precursors.
This would explain the post-cocaine depressive backlash in chronic intoxication. It is probable that the increase in sympathetic energy, which by itself would suffice it to explain to explain the stimulating effect of cocaine, also receives the assistance emanating from the systemic analgesic action.
The blocking of unpleasant sensations coming from a tired or exhausted body can cushion the sensation of fatigue reaching the brain during work, thereby increasing the well known extra work tolerance mentioned by almost every author.
On the chapter referring to pharmaco-dependence, we will examine, in more detail, how the adrenergic stimulating factor, upon acting on the pleasure centers of the brain during massive dispensation, produce the compulsive drug-search behavior in search of the “chemical orgasm.”