i would worry more about cardio toxicity than neurological. Cocaine isnt much worse than ritalin for the brain IMO
D-methlyphenidate is technically, on paper, mg to mg, more "potent" than cocaine as a DNRI (understand the relationship or in some cases lack thereof between Ki values, IC50 and other metrics, etc......they do not always correlate, in fact they can differ in statistical significance levels well beyond that of even wide confidence intervals).
While IV d-MPH seems to sufficiently "substitute" for cocaine in cocaine depend individuals, the subjective "liking" is different. Sure it "hits the spot" and generally satisfies the dopaminergic craving, it is not nearly as "euphoric" or enjoyable.
Self-administration studies will show methylphenidate or even some of the very potent and specific DRI's to be somewhat similar to cocaine (in terns of replacement). However, the "subjective liking" of these drugs effects varies in humans, and the DSNRI's appear to be qualitatively "more euphoric" . In otherwords, MPH is technically almost as "addictive" as cocaine, and will lead to self-administration in humans. However, qualitatively, cocaine is hands down, more "euphoric" and has a short-lived but fast acting "anti-depressant" effect. By this logic, I an can infer that (albeit, overly-simplified) cocaine's affinity for the SERT and its rather unique pharmacokinetics makes it subjectively far more euphoric than d-MPH.
While a bit controversial, the "general" consensus is that D-methylphenidate lacks, in vivo, any apparently "significant" or direct serotonergic activity, having a comparatively low affinity (and nearly irrelevant) for the SERT (in the micromolar range, while its affinities for the DAT and NET are much higher, in the nanomolar range). Thus, D-MPH, while highly addictive and can (for the most part) substitute for cocaine when administered intravenously, lacks cocaine's appreciable affinity for the SERT, and cocaine binding ratios are far more "balanced" (impressively so). Comparatively, D-MPH is rather "unbalanced".
Again cocaine is a powerful SNDRI, and cocaine's impressively rapid serotonin reuptake-inhibition differentiates it from primarily DNRI's such as D-MPH, which does not share cocaines pronounced anti-depressant/euphoric properties. Thus, again my assumption is that cocaine's pronounced serotonergic properties directly mediate (at least in part, perhaps in large part) the subjective "liking" of cocaine over D-MPH.
Unfortunately, along with this "balance" comes some issues related to potential serotonergic neurotoxicity, something that has not been studied sufficiently and (at least to me), appears to far more complicated than the heavily studied dopaminergic mediated neurotoxicity (I am by no means an expert on this, I am just recalling what I have read). Though different in mechanism, we know methamphetamine is a rather potent serotonergic neurotoxin, and while the action is different, cocaine's serotonergic properties may have 5-HT toxicity implications (again my understanding beyond this is only mediocre, and accordingly, I will not draw any conclusions; I am not in a position to make any specific conclusions about cocaine's potential 5-HT mediated toxicity). But I certainly acknowledge the possibility of such toxicity, I just don't know the mechanism or nature through which it actually occurs. I can guess, but I won't here, there are others whose understanding greatly exceeds my superficial viewpoint, I am merely a physician (please demystify your view of physicians, I am doctor of medicine, my knowledge is far more clinical than theoretical). I am not a PhD medical chemist, MCB etc..........
Interestingly, although again a very controversial subject, in the treatment of ADHD cocaine appears to function rather poorly, and from personal experience, this appears to be
not simply be a function of its pharmacokinetics. Its usage for treatment of ADHD is questionable, particularly when used through the more "direct" routes of administration. However, a large dose of oral cocaine (large enough to compensate for its low oral bioavailability) does seem to have some "potential" as a medicine, perhaps not for ADHD, but as a palliative/analgesic for treatment resistant chronic pain, acute major depression and cognitive and mood altering effects for the terminally ill. In most parts of the world, good quality cocaine is often to expensive to use orally, however due to my state's close proximity to mexico, cocaine of very high quality can be bought for a fraction of the lower grade cocaine found in europe, australia etc (with good connections, an ounce of extremely high quality cocaine can be here bought for a mere $800; i've seen it come straight from brick in which it was packaged and "branded"). despite its poor bioavailability
Cocaine, though well studied, is still misunderstood, and depending on what you read, you will see a wide spectrum of viewpoints. Cocaine is not an
especially "potent" neurotoxin (it does however possess a rather high acute toxicity, i.e. overdose) however, sustained use appears to have either direct neurotoxicity (decreased DAT density etc, and perhaps some cytotoxic DA-associated reactive species) or more commonly, indirect toxicity. These indirect toxicities relate to the commonly found comorbid issues associated with long term cocaine abuse; malnutrition, extended sleep deprivation, immunosuppression/general disregard for health, polydrug abuse and interactions, and some of the unique issues surrounding the routes of administration -namely vaporized base and IV. Ir is rather sad, but I have witnessed patients who have measurable (PET scans with some glaring abnormalities) neuropsychiatric/cognitive damage resulting from either acute overdose or less commonly extended high dose abuse. When the damage can be seen clearly via PET scan, the patient often has severe cognitive impairments, which are generally irreversible (at least for the time being).
The issue when assessing the long term neurotoxic properties of cocaine is that much of the study has put far too great emphasis on its dopaminergic properties. In my opinion, these studies fail to pay sufficient attention to cocaine's powerful and
extremely fast-acting reuptake of serotonin, which is something that is in great need of further study and elucidation.
Ok, sorry for the verbose reply, I am dictating this message and have likely repeated myself.
BOTTOM LINE: cocaine is a neurotoxin. Does this mean that you should never take cocaine; no, its up to you. Putting acute toxicity aside, it is my interpretation that cocaine's neurotoxic/cytotoxic properties are highly dose and time dependent. Unless you have the rare allergy, a few lines of a known quantity of cocaine of known or estimated potency is something that the human body can easily withstand. Binge or everyday usage for years on end will, in one way or another, take its toll, and is something I have to highly recommend against.
The smoked base is particularly insidious, I recalling making some of the base, and I spent two days straight smoking it and making more and more of the base. The toxic body load after this binge was severe, body aches, sort muscles, and a general feeling of being "poisoned". While I am not advocating it, I once went through 8 grams of highly pure cocaine (was already of excellent quality, but I cleaned it up to a point where, according to my MPA-100 melting point apparatus, was somewhere in the low 90% purity range). I used all the 8 grams of this very pure cocaine intravenously over the course of 3 days, and much unlike the base binge, I felt very little post-binge body load. This is NOT endorsement to do the same. Do as I say, not as I do.
Summary: cocaine poses various types of toxicities, but sporadic use of purified, measured doses will likely not produce measurable damage. Unfortunately, the phrase "sporadic use" doesn't even belong in the same sentence as vaporized base/IV cocaine. Extended use of the plant itself without extraction or concentration is rather safe to consume with greater regularity; I would feel more comfortable chewing on coca leaves than Khat, but that is largely a person preference.
Back to work...........
Dictated, not proof-read
