What level of Academic degree is required (if any) to do resrch on psychoactive drugs

[daddysgone]

Hi
I have some basic questions about the possible requirements (in terms of academic degree), that may be required in order to be granted permission to conduct research on certain psychoactive drugs.
Brief history: I attained my undergraduate degree back in 2001, in a non-science related field. I have recently decided to embark on the path to becoming a MD. I am well underway in completing my basic science pre-recs, required of medical school (2 semesters each of BIO, Gen Chem, Orgo, and Physics).

However, I am increasingly becoming interested in chemistry, particularly, and have been considering putting my aspirations of med school on hold temporarily, so that I might pursue some research into certain classes of psychoactive drugs.

Specifically, I am interested in conducting research on several alkaloids derived from the kratom plant, and ideally hope that I would be permitted to pursue the myriad of potential analogs of these alkaloids, which, with some tweaking, might result in analgesic compounds which induce a both greater analgesia, and longer duration of action.

This direction of research is appealing to me for a number of reasons. I would argue that kratom and its related alkaloids, represent the greatest promise in terms of a completely new analgesic, unrelated to poppy based alkaloids and their semi-synthetics. I am unaware of any other plant and its related alkaloids, which offer more in terms of leading to a totally new class of analgesic compounds.
Adding to this novelty, I feel that kratom and its alkaloids, offer inherent advantages, unrivaled by any of the current, "traditional" narcotic analgesics.
The alkaloids of kratom are quite abundant, and prove incredibly simple to extract. Additionally, there seems to be a VERY large therapeutic margin of dosages when compared to that of the current class of analgesics (kratom alkaloids seem far more unlikely to induce a fatal overdose then do the traditional analgesics). Lastly, there seems to be some minor alkaloids of kratom which, while not contributing to analgesia, have been shown to greatly delay the development of tolerance.

Unfortunately, the kratom alkaloids (especially mitragynine) are lacking in that they are not very potent, and have a short analgesic duration. From briefly discussing this problem with some members here, it seems that there likely are several "tweakings" of mitragynine, which would likely lead to increased potency and duration (mitragynine has already been oxidized to form the far-more-potent, 7-hydroxymitragynine).

All of these facts suggest to me, that given proper funding and experimentation, kratom and its alkaloids offer a great opportunity to lead to analogs which could become a great weapon in the arsenal of analgesic drugs.

This brings me to the original question of this thread. Would it be even possible for someone in my position (someone with an undergraduate degree who is now back in school pursuing another degree in chemistry), to be given the opportunity to conduct research into the analgesic potential of the alkaloids from this plant? I would tend to think that work of this sort is usually (or always) reserved for those seeking the Phd in chem, or their masters at least.

However, when considering that kratom and its alkaloids are as legal and unregulated as St. John's Wart, perhaps there is no technical reason why I would not be allowed to pursue this line of research. If I were asking to work with morphine, Im sure that would pose some problems, but given the unscheduled/unregulated nature of this plant, might I be able to convince my university to go along with this. All input welcome. Thanks-DG

 

[fastandbulbous]

Generally postgraduate research, but you'd need backing from a lecturer with a doctorate to get the project up & running

 

[seep]

Generally postgraduate research, but you'd need backing from a lecturer with a doctorate to get the project up & running

Another route is to have an MD oversee the project. It also helps to catch the interest of a pharmaceutical corp (for funding, etc). Around here, a firm that markets an antipsychotic is funding research into the effects of ergoloid mesylates on schizophrenics with early-onset AD (whether or not the ergs worsen their perceptual disturbances, etc).

 

[Quanta]

I would agree that post-graduate studies is the best route. If you are going to attain the alkaloids through extraction and then tedious separation then biochem/molecular biology might be your best choice of majors but if you intend to synth compounds for SAR in search of more potent analogs and such then probably chemistry. This type of research is always collaborative in nature and universities are a great place for that. Good Luck!

 

[daddysgone]

Thanks for the replies.

Regarding the suggestion that I would have better luck getting up and running if I was able to get a pharmaceutical company invovled.
I totally agree on this point, but I very much doubt this would be possible.

From my understanding, pharmaceutical companies are not able to patent (and thus profit from), plants and the medicinal chemicals they contain, which have already been in use by certain (often indiginous) people, in a certain part of the world. I can't recall what the name of this law/clause is, but it was basically put in place so that a giant pharaceutical company cant just walk into a rain forest, see that a tribe has been medicinally using a particular plant or extract for thousands of years, and then simply patent this plant/extract for their own exclusive use and profit.
My guess is that since kratom has been traditionally used in places like Thailand for so long, it would fall into this category of "plants whose traditional use in medicine within a certain group of people, prevent it from being patented by pharmaceutical companies".
Am I incorrect about this?-DG

 

[Sturnam]

^ Maybe that's true, but didn't you say you'd want to do research into derivates anyway? That would completely get around the issue. I mean, think of oxycodone. Derived from thebaine, which has been used for many thousands of years, and it's still on patent!

 

[daddysgone]

^ Maybe that's true, but didn't you say you'd want to do research into derivates anyway? That would completely get around the issue. I mean, think of oxycodone. Derived from thebaine, which has been used for many thousands of years, and it's still on patent!

Hmm, I hadn't considered this. I assumed that any direct derivatives of a plant or its chemicals, which would be protected by this law, would also enjoy similar projection.
So you are suggesting that while kratom and mitragynine etc, might be precluded from being patented by pharmaceutical companines, analogs and derivatives of these kratom based alkaloids, would indeed be patentable? Thanks-DG

 

[vecktor]

Hmm, I hadn't considered this. I assumed that any direct derivatives of a plant or its chemicals, which would be protected by this law, would also enjoy similar projection.
So you are suggesting that while kratom and mitragynine etc, might be precluded from being patented by pharmaceutical companines, analogs and derivatives of these kratom based alkaloids, would indeed be patentable? Thanks-DG

There are various ways where kratom its extracts or its active ingredients could be patented by the pharmaceutical industry if needed, i rather suspect that there is not enough medicinal or financial value for pharma to explore around kratom, however it is perfect for academic NIH or NIDA funded research

 

[phsycho]

@daddysgone: priceless ... god i wish english would be my 2nd native language

 

[Smyth]

I have not even tried kratom.

Clearly the first step was to identify the chemical structure of the alkaloids contained within the plant extract. Fortunately this has been done already and mighht possibly even be taken forgranted.

Next, it needs to be elucidated as far as possible the pharmacology of these alkaloids. Does anybody know anything more about this?

Using SAR and other methods it needs then to be found is there an analog that can be made or is there some way of getting the price of kratom down to les expesive prices that are more reasonable.

Take morphine, making analogs was facile after the structure was elucidated and the foundations had been laid. Interestingly many of the analogs are not considered superior to the parent structure from which they are derived. In some cases they are just "tacky" mimics that cost less to produce.

Discusing whether man-made analogs are better or worse than compounds made by mother-nature is ofcourse entirely opinion based. Artificial sweetners for example are no better than real sugar, but they do still have their advantages. That is sort of an analogous though.

 

[daddysgone]

@daddysgone: priceless ... god i wish english would be my 2nd native language

??????????
What does that mean? I honestly have no clue if you are insulting me, complimenting me, or neither. Care to explain?

 

[daddysgone]

I have not even tried kratom.

Clearly the first step was to identify the chemical structure of the alkaloids contained within the plant extract. Fortunately this has been done already and mighht possibly even be taken forgranted.

Next, it needs to be elucidated as far as possible the pharmacology of these alkaloids. Does anybody know anything more about this?

Using SAR and other methods it needs then to be found is there an analog that can be made or is there some way of getting the price of kratom down to les expesive prices that are more reasonable.

Take morphine, making analogs was facile after the structure was elucidated and the foundations had been laid. Interestingly many of the analogs are not considered superior to the parent structure from which they are derived. In some cases they are just "tacky" mimics that cost less to produce.

Discusing whether man-made analogs are better or worse than compounds made by mother-nature is ofcourse entirely opinion based. Artificial sweetners for example are no better than real sugar, but they do still have their advantages. That is sort of an analogous though.

I know that the pharmacology of kratom and its alkaloids, have been studied.
Mitragynine for example has been demonstrated to be adrenergic at lower doses, and at higher doses it acts as both a mu and delta agonist. This is consistent with anecdotal reports of users who state that low doses of kratom are stimulatory, while higher doses closely resemble the effects of standard opioids.
More interestingly, oxidation of mitragynine yields 7-hydroxymitragynine, which is a very selective mu agonist, and depending on which study you read, it is anywhere from from 5 to 17X more potent then morphine (I suspect it is actually on the lower end of this spectrum).

So, there certainly has been research done into the pharmacology of this plant and its alkaloids, though I am unsure whether or not SAR or other methods have been employed to examine the possibility of more potent or selective analogs. Thanks-DG

 

[Quanta]

The intellectual property arena for the use of kratom alkaloids as pharmaceutical analgesics is pretty crowded already. You will need to identify a new molecular entity from the plant extract that is free of intellectual property to receive any pharma/biotech involvement. Also, FDA is currently of the mindset there are enough opiates on the market unless you can make a strong arguement that the compound offers some type of advantage. None of this invalidates your project through.

 

[daddysgone]

The intellectual property arena for the use of kratom alkaloids as pharmaceutical analgesics is pretty crowded already. You will need to identify a new molecular entity from the plant extract that is free of intellectual property to receive any pharma/biotech involvement. Also, FDA is currently of the mindset there are enough opiates on the market unless you can make a strong arguement that the compound offers some type of advantage. None of this invalidates your project through.

Thanks for the response. Let me address the several issues you raised.
1-Im actually completely unaware of anyone or any company having a legitimate, legal "claim" to the kratom alkaloids. While there certainly are many out there who are creating extracts/blends derived from kratom (mostly those who are in the ethnobotanical business), I do not think that anyone has procured the actual exclusive, legal ownership or rights to kratom and its alkaloids. Do you have information to the contrary?

As per your second comment that the FDA is of the mindset that there are already enough opioids on the market:
First off, I dont believe the FDA would be the entity who would make this sort of decision. Perhaps you meant to say that the pharmaceutical industry feels that there are sufficient opioid medications in production, and that there would be no advantage in researching and developing a new one.
In either case, I would have to strongly disagree with this statement.

First, you must remember that pharmaceutical companies are CONSTANTLY trying to develop new drugs which very often, offer no real advantage over the existing drugs. The reason being that a pharmaceutical company only retains the exclusive rights for a drug which they develop, for a certain number of years. During this time, they can charge whatever they like because there is no competition. After this "exclusive period" other pharma companies develop generics, and thus the price of this drug plumments.
I know Im not blowing anyone's mind with this info, as it is common knowledge, but the fact is, pharma companies are ALWAYS trying to develop a new drug that does the same old thing, so that they can be granted exclusive rights to it, spend tens of millions in convincing the medical community and patients that this new drug is "state of the art", and should be prescribed above the "old class" of drugs.
So as you can see, even if kratom alkaloids dont offer any "real" advantage over traditional analgesics, if pharma companies could retain the exclusive rights, and convince the medical community that this new class of drugs were a better option, this could lead to huge profits for this company.

Secondly, I actually do think that the kratom alkaloids might have inherent qualities which could lead to an improved class of analgesics. I mentioned some of these in my first post. Briefly, I am almost certain that kratom alkaloids have a FAR broader therapeutic range. Even at very high doses, I believe the chance of a fatal overdose is a fraction of that of traditional opioids. Thanks-DG

 

[Smyth]

When the FDA recently decided to put tapentadol into the same group as morphine this massively dented sales of the said drug. Ofcourse the FDA is going to have an impetus on research where money is involved. That is the primary reason why "Bromadol" was never developed further was because fentanyl already had the rights to the market of exceedingly potent synthetic opioids.

For kratom the best thing that should be done is to somehow get more plantations or what not, but the cost of production needs to drop because at the moment people just regard it as vastly overpriced. I dont see why it should be so expensive.

Could one not just make the 6-methoxy positional isomer of this compound: http://en.wikipedia.org/wiki/Pinoline

Then they could think of a suitable N-group to alkylate it with?

Im not even sure why im bothering to write this though, because until I have actualy tried kratom im not even really certain of what the point is.

 

[daddysgone]

When the FDA recently decided to put tapentadol into the same group as morphine this massively dented sales of the said drug. Ofcourse the FDA is going to have an impetus on research where money is involved. That is the primary reason why "Bromadol" was never developed further was because fentanyl already had the rights to the market of exceedingly potent synthetic opioids.

For kratom the best thing that should be done is to somehow get more plantations or what not, but the cost of production needs to drop because at the moment people just regard it as vastly overpriced.

Agreed, which is why I have started a thread over at blacklight where I am trying to ascertain who realistic and "do-able" it would be, to perfrom a complete synth of mitragynine on a large scale. I know for a fact that a total synthesis of mitragynine has been successfully executed- I believe they used 4-methoxy-D-tryptophan as a pre-cursor. Im not sure how difficult of synth this is, but if there is any sort of decent yield, I would have to imagine that it is more economical to produce mitragynine via the total synth route, then it is to do an extraction from the raw leaves (due to the current high prices you mentioned).

I also agree that there really needs to be more plantations/sources of kratom. I got into a debate recently with a member at a kratom forum where I was making that point that there must be extreme price-gouging in the kratom business. He felt that the prices were fair, and an accurate representation of the value of the leaf (whatever that means)- I just kept emphasizing how absolutely ABSURD it is that the dried foliage of a TREE, costs upwards of $150 per kg. I really dont see how the foliage from a tree that is so ubiquitous (in south east asia, at least) should cost anywhere near that much.-DG

 

[seep]

From my understanding, pharmaceutical companies are not able to patent (and thus profit from), plants and the medicinal chemicals they contain, which have already been in use by certain (often indiginous) people, in a certain part of the world. I can't recall what the name of this law/clause is, but it was basically put in place so that a giant pharaceutical company cant just walk into a rain forest, see that a tribe has been medicinally using a particular plant or extract for thousands of years, and then simply patent this plant/extract for their own exclusive use and profit.
My guess is that since kratom has been traditionally used in places like Thailand for so long, it would fall into this category of "plants whose traditional use in medicine within a certain group of people, prevent it from being patented by pharmaceutical companies".
Am I incorrect about this?-DG

If anyone knows about such a law, I'd also be interested in reading about it. Anyways the MD/pharm route involves a lot of networking (read asslicking), but I mentioned it because it can be pulled off with no formal education whatsoever. Start a clinic, hire a doc who's recently been acquitted (so he's desperate for action), get licensing and go to pharm parties (laws may vary from region to region; sexual favors may be required).

 

[Quanta]

Thanks for the response. Let me address the several issues you raised.
1-Im actually completely unaware of anyone or any company having a legitimate, legal "claim" to the kratom alkaloids. While there certainly are many out there who are creating extracts/blends derived from kratom (mostly those who are in the ethnobotanical business), I do not think that anyone has procured the actual exclusive, legal ownership or rights to kratom and its alkaloids. Do you have information to the contrary?

As per your second comment that the FDA is of the mindset that there are already enough opioids on the market:
First off, I dont believe the FDA would be the entity who would make this sort of decision. Perhaps you meant to say that the pharmaceutical industry feels that there are sufficient opioid medications in production, and that there would be no advantage in researching and developing a new one.
In either case, I would have to strongly disagree with this statement.

First, you must remember that pharmaceutical companies are CONSTANTLY trying to develop new drugs which very often, offer no real advantage over the existing drugs. The reason being that a pharmaceutical company only retains the exclusive rights for a drug which they develop, for a certain number of years. During this time, they can charge whatever they like because there is no competition. After this "exclusive period" other pharma companies develop generics, and thus the price of this drug plumments.
I know Im not blowing anyone's mind with this info, as it is common knowledge, but the fact is, pharma companies are ALWAYS trying to develop a new drug that does the same old thing, so that they can be granted exclusive rights to it, spend tens of millions in convincing the medical community and patients that this new drug is "state of the art", and should be prescribed above the "old class" of drugs.
So as you can see, even if kratom alkaloids dont offer any "real" advantage over traditional analgesics, if pharma companies could retain the exclusive rights, and convince the medical community that this new class of drugs were a better option, this could lead to huge profits for this company.

Secondly, I actually do think that the kratom alkaloids might have inherent qualities which could lead to an improved class of analgesics. I mentioned some of these in my first post. Briefly, I am almost certain that kratom alkaloids have a FAR broader therapeutic range. Even at very high doses, I believe the chance of a fatal overdose is a fraction of that of traditional opioids. Thanks-DG

Respectfully, I disagree with most of the above post.

You CAN patent pure natural products with known molecular structures for a certain use. If you are the first to discover it, you may patent it. The patent may also contain structural analogs that you have not even made as long as the core structure remains intact. Patent for Mitragynine and related: US20090221623 (I tried to attach it but the pdf was too large but you can get it online at the US patent office)

I'm glad that you are making a case for the advantages of kratom alkaloids over existing opiates. The FDA does not approve a drug just for the sake of approving a drug, it must meet an unmet medical need or improve upon existing therapies.

I work for large pharma and I can guarantee you that strategically we would not touch a project unless it offers significant market advantage and therefore potential sales and profit to recover development costs which are large. Cheers!

 

[shibireru]

Imagine if someone were getting a degree in mathematics and his highest aspirations were devising a slightly different way of formulating an inveterate and widely known mathematical equation... Okay. Done? Why? Because that's you, but change mathematics for pharmacology and mathematical equation for chemical structure.

Booooring. Why are you aiming so low? You could do anything and all you're aiming for at the moment is to create mitragynine derivatives? Excuse me?

The main reason why kratom doesn't cause respiratory depression is that one or more molecules within it is a sympathomimetic, being related to Yohimbine; the other reason is that 7-hydroxymitragynine is probably a mixed mu-delta-opioid receptor agonist. So.... if that's what you like, I dun' know.... take tramadol with some hydrocodone (or whatever opioid is your pleasure) or a DOR agonist with a MOR or synthesize one of the dozens of already known mixed Delta-Mu agonists.

Wow. It just seems like such a freaking waste to me. There are hundreds if not thousands of known opioids already. You're hardly doing the world or even the recreational drug community any favours by pursuing this path.

I feel like there's a pink elephant in the room and I'm the only one making any explicit mention of it. Someone want to back me up here so this guy doesn't waste his life?


Edit: This seems to be a problem with drug designers in general, actually. "Hey! Let's make something that does the exact same things as certain existing drugs, but does it having a slightly different chemical structure! Wheeeeeeeeee!" It's not as if there were absolutely no value in that whatsoever, since there are hardly any two drugs that are precisely identical pharmacokinetically and phamacodynamically, but when that's what everyone's up to... Jesus. Case in point: the thread "Stimulants of the Future" Am I really the only one who bored to death by that thread? There are enough stimulants already; if you're not satisfied with any of those currently available you probably won't be satisfied with any devised in the future. And if you're holding out for one that much more strongly released dopamine and serotonin than epinephrine/norepinephrine... well... don't. I don't see what the problem with sympatholytics is.

 

[Quanta]

Wow. It just seems like such a freaking waste to me. There are hundreds if not thousands of known opioids already. You're hardly doing the world or even the recreational drug community any favours by pursuing this path.

I feel like there's a pink elephant in the room and I'm the only one making any explicit mention of it. Someone want to back me up here so this guy doesn't waste his life?

I think that you are being a little harsh here. What I see here is a young person looking for academic direction. If he wants to go to med school that is great and if he wants to do post-grad studies in a pharmacology related subject that is great too, I don't think he will regret either. I had to make the same choice a number of years ago and have not looked back.

As for kratom alkaloids ever becoming actual pharmaceutical drugs, I agree there is little chance of that happening. However, this is potentially a great academic project in which he would learn countless methodologies, skills and philospohy that will last a lifetime and be applicable in his career which he has an obvious passion for and that should not be supressed. Cheers.