Saturday, September 21, 2013

The Frozen Addicts: A Cautionary Tale

MPPP is structurally similar to meperidine, in MPPP the ester is the inverted (red arrow) 
This is a cautionary tale for those who dream of home-baking their own drugs. In 1976 a 23-year old graduate student by the name of Barry Kidston began researching opioid drugs that were not scheduled, nor used precursor chemicals watched by the authorities. He came across MPPP, which at the time was an untested, obscure synthetic opioid related to Demerol (meperidine). Relative to Demerol, the ester in MPPP is inverted (red arrow in figure). MPPP is slightly less potent than morphine, and has a shorter duration of action. 

Unfortunately the synthesis is sensitive to both temperature and acidity, if the conditions are not kept perfect a monsterous impurity is formed,  MPTP. MPTP readily crosses into the brain and in uptaken into neurons by the dopamine transporter. It is then converted to the ion MPP+ by the enzyme mono amide oxidase B. From there MPP+ enters the mitochondria where it wrecks absolute havok, setting off a chain reaction that ultimately ends in cell death. The damage done by MPP+ is localized to a region of the brain known as the substantia nigra. Destruction of this brain region results in symptoms of Parkinson's Disease.
Parkinson's usually progresses slowly, symptoms include tremor while at rest, movements are slow, and muscles rigid. In the latter stages patients have reduced facial expressions, inability to move from fixed postures and aphonia (reduced or absent speech). Senses and the intellect are unaffected. For the victims of MPTP induced Parkinson's this must truly have been a traumatic experience; it is must have been terrifying to wake up one day unable to move or speak and then to experience withdrawal on top of this is almost too terrible to imagine. 
Parkinson's Disease in a 23-year-old was unheard of, and Kidston was originally misdiagnosed with catatonic schizophrenia. Treatment for Parkinson's Disease involves administration of the drug L-Dopa,which is converted to dopamine in the body replacing the dopamine usually produced by the cells. It was only after a neurologist administered the drug L-Dopa that Kidston was able to speak again. After telling the doctors about his recent home chemistry work, scientists at the National Institute of Mental Health recovered some samples of Kidston's synthesis from his glassware and discovered the MPTP impurity. 

Drug manufacture should not be attempted without less than a BS degree in chemistry or a related field. A master's degree in organic chemistry is even better. For example I was reading a forum where the synthesis of fentanyl was being discussed. Someone posted a comment asking, what is an SN2 reaction? If you do not know that SN2 refers to a 2nd order nucleophilic substitution, something that is covered in the first semester of a college level organic chemistry course, you have no business trying to synthesize fentanyl. Even Barry Kidston was a graduate student and he made a serious error (if he had access to GC-MS equipment he might have detected the impurity, but since such machines run into the tens of thousands of dollars few clandestine labs are such equipped). 

Unless you are an experienced chemist with a well-equipped laboratory, you should not attempt to synthesize opioids. Instead buy the book Opium for the Masses by Jim Hogshire and try growing your own poppies. Poppy cultivation and opium harvesting is comparatively easy, and not likely to result in devastating errors. 

I wish that I could say that the damage from MPTP was limited to Barry Kidston, unfortunately it has reared its ugly head again in 1982 in San Jose, California. Apparently these chemists' technique was no better than Kidston's and samples confiscated by authorities were found to be contaminated by MPTP.  


Advice for Opiate Users (Harm Reduction)

If you are buying dope that the dealers claims to be "synthetic heroin" it is possible that the drug is MPPP. MPPP does not have as long a duration as heroin, nor will it appear on a standard drug screen. Moreover mixtures of MPPP-MPTP causes a severe burning at the site of injection, blurred vision, tremors, a metallic taste in the mouth, jerking of the arms and legs followed by tightness and stiffness in the muscles. 

If you think that you have been exposed to MPTP, there are things you can do to prevent the onset of Parkinson's symptoms. It takes 3-4 days for MPTP to do its damage, and it is actually the metabolite MPP+ that does the damage. Taking an MAO-B inhibitor may prevent the conversion of MPTP to MPP+, and thus prevent the onset of symptoms. MPTP can remain in the body for over 2-weeks, so administration of the MAO-B inhibitor may need to continue for several weeks.

Afterword

Thanks to prohibition, opiates are far more expensive than they would be in a free marketplace. It is not surprising then to see people attempting to manufacture their own drugs. Some simply want to self-medicate without having to spend a small fortune doing so, others undoubtedly dream of being like Walter White (Breaking Bad) and running a drug empire. If it were not for prohibition, this would not be an issue. Users would have access to drugs produced by pharmaceutical firms with quality control, and make purchases from pharmacies instead of street corners. 

MPTP induced Parkinson's Disease is another unintended consequence of our War On (the people who use certain) Drugs. During the days of alcohol prohibition, tens of thousands of alcohol users were poisoned by contaminated booze. Opiate users who are poisoned by contaminated drugs are more collateral damage in this futile war. Few people today would suggest that alcohol consumers deserve to contract horrible diseases simply because they choose to consume alcohol (and alcohol is certainly a "hard" drug if the hard/soft distinction is to have any meaning whatsoever).

We are not collateral damage, we are people. It is time to admit that drugs have won the drug war, and  well past time to make peace with drugs.

Further Reading:

Restak, Richard M. (1994) Receptors New York, NY. Bantam Books

MPTP, mitochondrial Complex I, and William Gibson's Necromancer

The Frozen Addicts

The Case of the Frozen Addicts [Book - Amazon Link]

Lee, J.; Ziering, A.; Heineman, S. D.; Berger, L. (1947). "Piperidine Derivatives. Part II. 2-Phenyl- and 2-Phenylalkyl-Piperidines". Journal of Organic Chemistry 12 (6): 885–893. doi:10.1021/jo01170a021

6 comments:

  1. This is a wonderful post and it is a shame that the majority do not hold the same sentiment.

    ReplyDelete
  2. Man good thing I read this article that could of been catastrophic! Thanks again always looking for a cheaper way out

    ReplyDelete
  3. The War on Drugs. Never been about drugs, actually.
    It is all about consolidation of power.
    Junkies are easy to demonize. They lie, steal and even kill for their fix.
    That is the image sold by the image makers that makes horrible laws more palatable.
    The reality is that Junkies are people who cannot say no to their most base desires.
    Many felons had trouble controlling base desires, and when that control snaps, they often blame the victim.
    "I just had to get some of that! Too damn fine to pass up! If I hadn't got to that first, someone else would have! It wouldn't be out there is it wasn't available. I saw it, I wanted it, I had to have it, so I took what I wanted. Goddamn Cops, messing up my good thing."
    I will leave it as an exercise for the student to figure out if the above quote is about a pretty woman, a child walking home from school, a purse left on a table, cash in a register, oily-rags in a ware-house, drugs in your dealers home.

    ReplyDelete
    Replies
    1. Your stereotypes about junkies is completely inaccurate. There are plenty of junkies out there who hold down jobs, raise families and lead otherwise ordinary lives. They are invisible, for obvious reasons. Unless they get caught up in the drug war and the government turns their lives upside down.

      Do some junkies lie, cheat, steal and even murder? Sure, but so do non-junkies. Most of the antisocial behavior exhibited by opioid addicts is the result of prohibition, which forces addicts into dire poverty. Given a safe and reliable source of drugs, opioid addicts are pretty much indistinguishable from anyone else.

      Delete
  4. Ins't better to work harder for a high pay job and then pay someone qualified to do the work?

    ReplyDelete
    Replies
    1. I have no idea what your comment is in reference to.

      Delete