HaCKeRz KrOnIcKLeZ 3/HaCKeRz_KrOnIcKLeZ.iso/drugs/opiate.info

Text File | 1996-05-06 | 35KB | 689 lines

Newsgroups: alt.drugs
From: [e-mail] (Scott Grigsby)
Subject: Why opium causes constipation
Message-ID: <[e-mail]>
Date: Fri, 11 Feb 1994 02:23:24 GMT

Well, I bugged all of you to tell me why opium causes constipation.
I hadn't received a reply, so while on my way to class today
I stopped at the library (and never quite made it to class.  The
library has that effect...).  When I got home, I found that someone
had sent me a reply, confirming what the library told me.  So here's
what I found out (you're dying to know, aren't you?):

The gastrointestinal tract contains many opioid receptors (gamma,
kappa, and sigma, I think), to which the opiods bond (duh).
The rest I'll copy from this book (I forgot the title, but the
authors (of this chapter) are T.H. Bewley and A.H. Ghodse):

"There is a decrease of motility with increase in tone of the central
part of the stomach.  There is an increase tone in the first part
of the duodenum...  Digestion of food in the small intestine is
delayed where propulsive contractions are markedly decreased.  The
action on the small intestine is thought to cause about a quarter
of the total constipating effect.  In the large intestine,
propulsive peristaltic waves in the colon are diminished or
abolished after morphine.  Delay in passage of contents causes
dessication of feces.  Anal sphincter tone is augmented."

So that's it.

Scott
--
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~\__________/~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
               Scott Grigsby   ///-///-///  The cut worm forgives the plow.
                               \\\-\\\-\\\                       -Blake
    [e-mail]   ///-///-///

=============================================================================

Date: Thu, 17 Mar 1994 11:56:17 +1300
From: Brandon Hutchison <[e-mail]>
Subject: Re: natural history of opiate addiction
Sender: "Academic & Scholarly discussion of addiction related topics."
 <[e-mail]>
Message-id: <[e-mail]>

On Tue, 15 Mar 1994, ROB ANDERSON wrote:
> > If those causes consisted of gunshot or stab wounds,accidental
> > overdose,hepatitis,HIV, etc then I would suggest you are
> > looking at the "unnatural" history of opiate addiction as these deaths are
> > generally a consequence of prohibition
> >
>
> I think that this is an oversimplification.  BTW, could you please
> explain to me why you think that "accidental overdose" is generally a
> consequence of prohibition?

I don't think this is oversimple.  Was it the CATO institute that
estimated that 80% of the deaths associated with opiates would not have
occurred under a legal regime?

Accidental overdoses can occur when the dose taken is greater than what
one is used to. (excuse me for stating the obvious)
How much heroin is in a given illicit sample is usually quite variable.
Depends on how often its been cut, where it came from etc.
 (excuse me again for stating the obvious)

If a batch of stronger stuff gets out onto the street then there is likely to
be an increase of ODs. This happened last year in the New York area and
eastern Canada, so I read in our papers.

It seems paradoxic to some people, but the greater the purity the safer
the stuff is, though consistency is obviously the critical factor. Under a
legal regime, such problems would be solved. Overdoses, while not eliminated
would be substantially reduced.

Here 's a little article I picked up which discusses these issues...

Copied from p.56 (Box 5-1) of 'Drugs and Behavior' by William A. McKim.

One of the greatest risks of being a heroin addict is death from heroin
overdose. Each year about one percent of all heroin addicts in the United
States die from an overdose of heroin despite having developed a fantastic
tolerance to the effects of the dr ug. In a nontolerant person the
estimated lethal dose of heroin may range from 200 to 500 mg, but addicts
have tolerated doses as high as 1800 mg without even being sick[1]. No
doubt, some overdoses are a result of mixing heroin with other drugs, but
appear to result from a sudden loss of tolerance. Addicts have been killed
one day by a dose that was readily tolerated the day before. An
explanation for this sudden loss of tolerance has been suggested by
Shepard Siegel of McMaster University, and his a ssociated, Riley Hinson,
Marvin Krank, and Jane McCully.

Siegel reasoned that the tolerance to heroin was partially conditioned to
the environment where the drug was normally administered. If the drug is
consumed in a new setting, much of the conditioned tolerance will
disappear and the addict will be more like ly to overdose. To test this
theory Siegel and associates ran the following experiment[2].

Rats were given daily intravenous injections for 30 days. The injections
were either a dextrose placebo or heroin and they were given in either the
animal colony or a different room where there was a constant white noise.
The drug and the placebo were giv en on alternate days and the drug
condition always corresponded with a particular environment so that for
some rats, the heroin was always administered in the white noise room and
the placebo was always given in the colony. For other rats the heroin ways
given in the colony and the placebo was always given in the white noise
room. Another group of rats served as a control: these were injected in
different rooms on alternate dates, but were only injected with the
dextrose and had no experience with th e heroin at all.

All rats were then injected with a large dose of heroin: 15.0 mg/kg. The
rats in one group were given the heroin in the same room where they had
previously been given heroin. (This was labeled the ST group.) The other
rats, the DT group, were given the he roin in the room where they had
previously been given the placebo.

Siegel found that 96 percent of the control group died, showing the lethal
effect of the heroin in nontolerant animals. Rats in the DT group who
receieved heroin were partially tolerant, and only 64 percent died. Only
32 percent of ST rats died, showing t hat the tolerance was even greter
when the overdose test was done in the same environment where the drug
previously had been administered.

Siegel suggested that one reason addicts suddenly lose their tolerance
could be because they take the drug in a different or unusual environment
like the rats in the DT group. Surveys of heroin addicts admitted to
hospitals suffering from heroin overdose tend to support this conclusion.
Many addicts report that they had taken the near-fatal dose in an unusual
circumstance or that their normal pattern was different on that day[2].

[1] Brecher, E. M., & the editors of Consumer Reports (1972). _Licit and
illicit drugs_ Mount Vernon, New York: Consumers Union.

[2] Siegel, S. (1982). Drug dissociation in the nineteenth century. In F.
C. Colpart & J. L. Slangen (Eds.), _Drug discrimination: Applications in
CNS pharmacology (pp. 257-262). Amsterdam: Elsevier Biomedical Press.

Brandon Hutchison,University of Canterbury, Christchurch
                  New Zealand
(Long 172deg35min00sec,Lat43deg31min13sec south)

=============================================================================

Subject: Re: death sentence for drug users
From: [e-mail] (funky chicken)
Date: 13 May 91 02:50:05 GMT

In article <[e-mail]> [e-mail] responds
to my claim that heroin "IS reasonably safe and a lot of fun" by writing:

>    Considering that my only source of information on heroin
>    is the Voice of Daddy Knows Best, and his little brothers
>    in propaganda, I can safely say I know fuck all about it.
>    I will not necessarily assume that their lie means heroin
>    is safe and fun.  Since you said this, can you please tell
>    us more, and document it please?

Sure, Old Man.  I assume that the provocative part of my statement concerns
its safety and I will therefore not discuss the issue of whether heroin
is fun.

Let me first qualify my provocative statement by saying that heroin use
CAN BE reasonably safe, if used in a smart manner.  Heroin in itself seems
to pose no real health problems, even when it is used for long periods of
time.  G. Dimijian in "Contemporary Drug Abuse" (in _Medical Pharmacology:
Principles and Concepts_ ed A. Goth, p. 299) describes an 84-yr old
physician who had been a morphine addict for 60 years and seemed to have
no mental or physical problems from the addiction.  In general, it seems
that middle-class heroin/morphine addicts are no less healthy than the
general population (see D. Musto and M. Ramos (1981) "Follow-up Study of the
New England Morphine Maintenance CLinic of 1920," _New Eng J Med_ 308(30):
p. 1075-76; J. Ball and J. Urbaitis (1970) "Absence of Major Medical
Complications among Chronic Opiate Addicts" in _The Epidemiology of Opiate
Addiction in the United States (eds J. Ball and C. Chambers), p. 301-6.)
There may be some problems associated with long-term controlled use of H,
but they aren't well documented and they are certainly not comparable to
those associated with either tobacco or alcohol.

So where do the health problems of heroin come from?  Primarily from the use
of needles, the presence of adulterants in the drug, the poor nutrition and
health care associated with the hard core addict liife-style; and the
violence associated with said life-style.  Before I discuss these, we should
note that all of these factors except adulterants are controllable by the
user.  The many "chippers" (that being the term for non-addicts who use
addictive drugs in a controlled fashion; see, for example N. Zinberg and
R. Jacobson's (1976) "The Natural History of 'Chipping,'" _Amer J Psych_
133(1): p. 37-40.) who avoid injections (usually by "chasing the dragon"
ie smoking it) have few problems.

Let's start with needles.  There are two reasons to use needles: it gives
a bigger rush, and it makes more effective use of the drug.  This second
reason is, of course, only a consideration because the drug is expensive
and difficult to get.  The problems with needles are that you inject a
lot of crap into your body (adulterants and dilutants), you run the risk
of infecting yourself with something (HIV or a Hepatitis virus), and
you wreck your veins and skin.  Most IV Heroin users are constantly
plagued by irritated, infected skin.  Hey, you inject talc into your skin,
that's what you get.  Even the quinine (which is believed to have originated
in heroin during an outbreak of malaria among addicts) can cause
numerous health problems (there's a large literature on the problems of
adulterants and dilutants in heroin and cocaine).

The life-style that an addict leads is generally pretty unhealthy as well.
Often, addicts don't get an adequate diet.  Vitamin deficiencies are not
uncommon.  Constipation caused by a combination of poor eating that the
effects of the drug on the bowels can lead to haemorrhoids.  Chest
infections seem pretty common too, especially among cigarette smokers.
Then you've got the problems of trafficking in the (potentially) violent
underworld.  Joe and Leishman (et al (1982), "Addict Death Rates During
a Four-Year Post-Treatment Follow-up," _Amer J of Public Health_ 72:
p. 703-9.) found that 28% of deaths among addicts were from violence (17%
were from natural causes, and 44% were drug related).

So, it would seem that if one had clean heroin from a reliable source
and avoided the IV route, there'd be few health problems.  Potential
problems would arise from becoming addicted and becoming unproductive
or from accidentally ODing.  It seems that "Chippers" avoid addiction
by setting strict limits on their use ("I'll only do it on weekends"
being a common limit).  In the lab, it takes a couple weeks of 3 shots
a day before one gets withdrawl symptoms.  So, if you avoid hanging
around hardcore addicts, it is not that hard to avoid an addiction.
The existence of non-addict users shouldn't be surprising.  It is only
because of silly people like Anslinger and Henry Giordano (head of the
FB of Narc, who testified that anyone who used H more than six times
would become an addict).  Admittedly, controlled heroin use is
difficult to locate, since the users stay out of trouble to the best of
their abilities.  However, if we look at who has used heroin daily
(a nice substitute for the vague notion of 'addict'), we find substantial
numbers of regular users who have never taken H on a daily basis (see,
for example, J. O'Donnell's (1976) "Young Men and Drugs," _NIDA Res Mon_ 5,
p. 13, where only a third of the users taken from a cross-section of
American males had ever used H daily).  In fact, considering the small
amount of H in street samples, it is a wonder that users can even
become true addicts.  (As a side note, many of the people who present
themselves or are presented by the Feds to clinics are not physicially
dependent on cocaine, heroin, etc.) D. Waldorf's _Careers in Dope_
provides examples of H addicts who have held employment for long periods
of time.  So, even addicts can hold down jobs.  Dr. William Halsted,
a great surgeon and one of the founders of Johns Hopkins was a
morphine addict.  Surprise surprise, they aren't all the domestic version
of Viet Cong, despite what the Man tells us.

Overdose is a probably largely due to people not knowing the purity
of their H, the presence of adulterants which act in conjunction
with the H, and addicts misjudging their tolerance.  Using non-IV
routes probably reduces the chances of ODing.  R. Gardner (1970) in
"Deaths in UK Opioid Users 1965-69" _Lancet_ 2: p. 650-3 found that
26 of the 42 accidental ODs recorded happened after a period of
abstinence, so maybe 60% of ODs are from misjudging tolerance.
Since abstinence is often forced, I can only imagine that most ODs
could be avoided entirely by proper measures.

Oddly enough, British addicts, who get clean heroin, have about as high a
mortality rate as Americans who shoot street shit (see T. Bewley et al (1968)
"Morbidity and Mortality from Heroin Dependence, 1: Survey of Heroin
Addicts Known to the Home Office," _Brit Med J_ 23 March: p 725-26).

Tolerance is a funny thing.  Addicts have been known to die from their
second shot of the day after dividing their daily amount into three
piles.  It would therefore seem that their tolerance had been reduced since
the first shot.  Someone conjectured that tolerance was partially a matter
of place-conditioning and that addicts who shoot in a particular gallery
get conditioned so that their body begins to gear up for a shot when
they go their and that therefore they have higher tolerance there.  When
they shoot up someplace else, their body isn't ready and they OD.

Before I quit typing, I'll say something about the myth of "pushers."
John Kaplan (1983), in his excellent book _The Hardest Drug_, points
out the numerous holes in this myth.  The idea of the "pusher" is that
a dealer tries to get people hooked through free samples so that
he can have a helpless and reliable market for high-priced drugs.
This model works pretty well for cigarette companies.  However, it
is totally off the mark with respect to H sellers.  To begin with, as
Big Bill Burroughs has documented, the model is empirically wrong
since there is no clear distinction between users and sellers.  Most
users sell to their friends, making a little profit.  In the social
network of users, some will sell on a large scale, but typically not
for a long period of time, as it is a hassle.  The only real organization
in drug dealing is at the higher levels where the drugs are purified,
smuggled, and cut.  Furthermore, ignoring empirical facts, the image
of the pusher is pretty unsound.  It only makes sense to spend time
hooking people if you plan on selling to them for a long time and they
will not be able to go elsewhere.  Neither condition tends to be true.
Addicts are notoriously unreliable customers.  Furthermore, as I have
already mentioned, it is difficult to get hooked on H.  Addiction is
rare within the first 6 months of H use. (See Kaplan, p. 27).  So,
you'd have to be giving out samples for a while before you had an
addict customer.  Finally, associating with non-addicts is the surest
way to get busted.  Dealers stick to themselves; they don't hang out
on play grounds.

Anything I left out that should be discussed?

>William "Alain" Simon
>                                                   UUCP: [e-mail]

--Matt Funkchick

=============================================================================

According to a Cato Institute Policy Analysis (May 25, 1989, no. 121),
80 percent of the deaths attributed to cocaine and heroin are actually
caused by black market factors.  For example, many heroin deaths are
caused by an allergic reaction to the street mixture of the drug, while
30 percent are caused by infections.

Decriminalization and proper regulation would lower these deaths markedly.

Of course, LAPD Chief Darryl Gates has said that casual drug users should
be executed for "aiding the enemy in time of war."

=============================================================================

Newsgroups: alt.drugs
From: [e-mail] (Jerry Stratton)
Subject: Heroin and Alcohol
Message-ID: <[e-mail]>
Date: Fri, 12 Nov 93 23:36:08 GMT

Thanks to Lamont for providing the pointer to this study. Here are some
highlights from it:

                  THE ROLE OF ETHANOL ABUSE
          IN THE ETIOLOGY OF HEROIN-RELATED DEATHS
                                Ruttenber, A. J., Kalter, H.
                                        D., and Santinga, P.
                               Journal of Forensic Sciences,
                                Vol 35, No. 4, July 1990, pp
                                                     891-900

p. 891
"Our data suggest that ethanol enhances the acute toxicity
of heroin, and that ethanol use indirectly influences fatal
overdose through its association with infrequent
(nonaddictive) heroin use and thus with reduced tolerance to
the acute toxic effects of heroin."

[Ruttenber, A. J. and Luke, J. L., "Heroin-Related Deaths:
New Epidemiologic Insights," Science, Vol 226, Oct 5, 1984,
pp 14-20] "found that blood ethanol concentrations in excess
of 1000 mg/L raised by a factor of 22 the odds of a heroin
user experiencing a fatal overdose."

"The concomitant use of heroin and ethanol is well
recognized and considered dangerous..."

"The phenomenon of combining ethanol and opiate use and the
resultant toxic effects were noted as early as 1881
[Hubbard, F. H., The Opium Habit and Alcoholism, Barnes, New
York, 1881, pp 3-14]."

Possibilities examined:
     1. Ethanol and heroin act additively or
        synergistically on the central nervous and
        respiratory systems, producing cardiopulmonary
        arrest that is more often fatal than that
        produced by heroin alone.
     2. Ethanol interferes with the metabolism of
        heroin, prolonging toxic effects.
     3. Ethanol consumption is commonly associated
        with infrequent (nonaddictive) use of heroin,
        [Greene, M. H., Luke, J. L., and Dupont, R.
        L., "Opiate 'Overdose' Deaths in the District
        of Columbia," Medical Annals of the District
        of Columbia, Vol 43, #4, April 1974, pp 175-
        181] which results in reduced tolerance to
        acute toxicity of heroin.

Decedents with toxicological evidence of drugs other than
heroin/ethanol were excluded from the study.

p. 895
"We determined that HE [High Ethanol] decedents had
significantly lower blood morphine concentrations than LE
[Low Ethanol] decedents and identified a significant inverse
correlation between concentrations of ethanol and morphine
in the blood. These findings suggest that there is a dose-
response relationship between consumption of ethanol and the
acute toxicity of heroin. However, blood ethanol
concentrations explained only 11% of the variation in blood
morphine concentrations, indicating that additional factors
are probably involved in the etiology of fatal overdose by
users of heroin and ethanol."

"There is no evidence from our study that ethanol interferes
with the metabolism of heroin." (This is in response to possibility
3.)

p. 897
"Our data suggest that decedents who consumed large
quantities of ethanol before death also had used heroin
infrequently in the days before death."

"Data presented here and in other studies [Ruttenber, A. J.
and Luke, J. L., "Heroin-Related Deaths: New Epidemiologic
Insights," Science, Vol 226, Oct 5, 1984, pp 14-20; and
Kalter, H. D., Ruttenber, A. J., and Zack, M. M., "Temporal
clustering of Heroin Overdoses in Washington, DC," Journal
of Forensic Sciences, Vol. 34, No. 1, Jan. 1989, pp. 156-
163.] indicate that fatal heroin overdose can be influenced
by the toxic effects of other drugs and by other risk
factors and is not merely the consequence of injecting
unusually high doses of heroin. Our results suggest that
simply discouraging the practice of drinking and injecting
heroin may not be effective in preventing fatal overdose.
Combining chronic ethanol abuse with infrequent
(nonaddictive) heroin use should also be discouraged. Since
fatal overdoses are commonly associated with ethanol use,
public health measures directed towards those who use both
drugs may help reduce the incidence of these deaths."

"Address requests for reprints or additional information to
A. James Ruttenber, Ph.D., M.D.
Center for Environmental Health and Injury Control
Centers for Disease Control
Mail Stop F-28
Atlanta, GA 30333"


Jerry Stratton
[e-mail] (Finger/Reply for PGP Public Key)
------
"You need only reflect that one of the best ways to get yourself a
 reputation as a dangerous citizen these days is to go about repeating
 the very phrases which our founding fathers used in their struggle
 for independence."
                   -- C. A. Beard

=============================================================================

From: [e-mail] (Lamont Granquist)
Newsgroups: alt.drugs
Subject: chemistry: levorphanol
Date: 30 May 1994 06:41:38 GMT
Message-ID: <2sc1r2$[e-mail]>

More copyright violations of Loompanics Books.  I'll be getting that catalog
of theirs up on my WWW site shortly to assuade my guilty conscience...

I have *zero* comments on the process involved, indeed i've yet to read
through it all...

A small section out of _Recreational Drugs_ by Professor Buzz:


Dromoran (Sometimes called Methorphinan or 3-Hydroxy-N-Methyl-Morphinan)

    This drug is quite easily synthesized, yet it contains the same
numbering system as morphine, which is considerably harder to synthesize.
Although Dromoran lacks the oxygen bridge, the Alicyclic double bond, and
the alcoholic hydroxyl of morphine it is still 4-5 times more powerful, as
well as longer acting.  The average dose is 1-3 mg intramuscularly
injected.  Dromoran has less than one half the addiction liability of
morphine and is, therefore, used almost exclusively for severe injuries,
amputations , etc.  The incredible feeling of well-being it produces is
accompanied by addiction, so it cannot be used regularly.  It also has no
marked hypnotic effect, so it may be taken and enjoyed without drowsiness
or reduced clarity of thought.  The drug is wel l tolerated and does not
depress blood pressure or cause other circulatory disturbances.  The
effects begin after ten minutes and continue for nine to thirteen hours
with a minimal dose.

    This first formula is a street method, but I am sure it was taken
from the Swiss patents 252,755 and/or 254,106.  You should always look up
all references, even though I know that this method does work and I have
double checked all the figures.

    Prepare a Grignard reagent from 325 parts (as usual all parts
refer to parts by weight) of p-methoxy-benzyl bromide in 800 parts of
absolute ether with 40 parts thin clean magnesium (unlike THCs, different
Grignard reagents cannot be substituted here) an d cool to 0-3 C.  275
parts of (5,6,7,8) tetrahydroisoquinoline methiodide are added in small
portions.  This mixture is allowed to stand for one hour at 0 C and
saturate with ammonium chloride after pouring onto cracked ice, then
basify with ammonia by a dding in small portions and checking pH often.
Separate the ether solution and extract the base with hydrochloric acid.
The acid solution is basified with ammonia and extracted with ether, the
ethereal solution is dried in the usual manner.  Remove the ether by
evaporation in vacuo with gentle heating, or distill it out at a low
temperature in the next step.  Distill with 0.2 mmHg of vacuo, collecting
the fraction at 149 to 154 C to get the desired base.

    The above base is catalytically hydrogenated (platinum oxide seems
to work the best) to 1-(p-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-
octahydro-isoquinoline.  This is separated from the catalyst and purified
by distilling under 0.2 mmHg of vacuum, collect ing the fraction at
138-142 C.  Heat at 150 C for three days with ten times its weight of
phosphoric acid (specific gravity 1.75).  The resulting brown solution is
cooled with ice (in water and externally) and made alkaline to the
indicator phenolphthalei n, by carefully adding ammonia.  The free base is
then shaken out with ether (this is an extraction) and the ether is
removed by evaporation in vacuo.  Purify the Dromoran by sublimation on an
oil bath, at 180-199 C with 0.3 mmHg of vacuo and recrystalliz e once with
anisole, or recrystallize twice with anisole after evaporating the ether.
Yield: about 30-35%.  To get the hydrochloride form, or the sulphate,
etc., use any of the above methods for isomethorphinan, amidone, etc.

Dromoran  JOC, 24, 2043 (1950)

    This method is more modern than the last and it gives details for
making a lower starting material, eliminating the need for purchasing
(5,6,7,8) tetrahydroisoquinoline methiodide.

    6.2 g of 2-(1,4-cyclohexadienyl)ethylamine in 80 ml of benzene is
treated with p-methoxyphenylacetyl chloride (9.4 g in benzene) in the
presence of sodium bicarbonate (200 ml of a 5% solution) with stirring and
external cooling.  An oily amide results, w hich solidifies (crystallizes)
upon scratching the flask with a glass rod (see crystallization in the
equipment chapter).  Recrystallize from a mixture of n-hexane and benzene
to get colorless scales that melt at 86-86.5 C.  Yield of this
N-2(1,4-cyclohex adienyl)ethyl-p-methoxyphenylacetamide is 12.5 grams or
92%.

    A mixture of the above amide (3 g), phosphoryl chloride (3 g) and
50 ml of benzene is refluxed for 30 minutes creating a reddish-yellow
solution and evolution of hydrogen chloride.  Cool, add enough petroleum
ether to give a reddish precipitate, which is separated by filtration,
after allowing to stand long enough to make sure no more precipitation
will occur.  Dissolve the precipitate in dilute hydrochloric acid, then
shake with benzene and filter through a benzene wetted filter paper.  Make
the filtrat e alkaline by carefully adding a strong caustic soda solution
with external cooling and stirring.  Separate the benzene layer and dry,
evaporate the solvent (benzene) under vacuo in a hydrogen atmosphere.
Dissolve the red residue in 50 ml of methanol and reduce over 1.5 g of
Raney nickel (see reductions chapter for complete information, then work
in 1.5 g of catalyst).  The catalyst is removed by filtration and the
solvent by evaporation in vacuo.  The residue is dissolved in benzene and
purified by runn ing through an alumina filled chromatography column.
Evaporate the benzene in vacuo and dissolve the resulting yellow, oily
base in methanol (50 ml), neutralize with hydrobromic acid, and evaporate
in vacuo.  The residue crystallizes on scratching with a glass rod.  Use a
minimum amount of water to dissolve, upon boiling, add decolorizing carbon
and filter off hot to get 1.5 g of the hydrobromide salt of
1-p-methoxybenzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline as colorless
prisms, mp: 197-198 C.

    The above quinoline can be converted in several ways to Dromoran.
The process given below methylates it at the same time as the reduction
takes place and is a superior operation.

    Reduce the quinoline catalytically in the presence of
formaldehyde.  Most any of the general methods of catalytic reductions
found in the reductions chapter will work fine, as long as you remember to
use formaldehyde.

    Another method is to proceed after the Raney Nickel reduction like
this: filter the catalyst off and purify as above.  React the product with
CH2O and hydrogen or HCO2H to get the 2-Me derivative, which is heated
with H3PO4 at 140-150 C for 70 hours.  Note: HCO2H is a strange way to
say formic acid.

[From _The Merck Index_ Eleventh Edition] slighty abbreviated

Levorphanol.  17-methylmorphinan-3-ol; (-)-3-hydroxy-N-methylmorphinan;
levorphan; lemoran; Ro 1-5341.  C17H23NO; mol wt. 257.38.  Orally active
synthetic morphine analog.  Preparation of racemate from 2-methyl-1-
benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline:  Grewe, Naturwiss. 33, 333
(1946); Angew. Chem. A59, 198 (1947); Grewe, Mondon, Ber. 81, 279 (1948);
Swiss pat. 280,674 (1952 to Hoffman-LaRoche), C.A. 47, 7554 (1953).
Preparation of isomers:  Schnider, Grussner, Helv. Chim. Acta. 34, 2211
(1951); Vogler, U.S. patent 2,744,112 (1956 to Hoffman-LaRoche).  Absolute
configuration:  Corrodi, et al., Helv. Chim. Acta. 42, 212 (1959).
Analgesic activity and toxicity data:  L.O. Randall, G. Lehmann, J.
Pharmacol. Exp. Ther. 99, 163, (1950).  HPLC determination in plasma: R.
Lucek, R. Dixon, J. Chromatog. 341, 239 (1985).  Clinical pharmokinetics:
R. Dixon et al., Res. Commun. Chem. Pathol. Pharmacol. 41, 3 (1983).
    Crystals, mp 198-199 C.
    Tartrate dihydrate, C21H29NO72H2O, Ro 1-5341/7, Dromoran,
Levo-Dromoran.  Crystals, mp. 113-115 C (when anhydrous, mp 206-208 C).
pH of a 0.2% aq solution 3.4 to 4.0.  One gram dissolves in 45 ml water,
in 110 g alcohol, in 50 g ether.
    dl-Form, racemorphan, methorphinan.  Crystals from anisole and dil
alcohol, mp. 251-253 C.
    dl-Form Hydrobromide, C17H24BrNO, NU-2206.  Crystals, mp 193-195.
Sol in water; sparingly sol in alcohol.  Practically insoluble in ether.
LD50 i.v. in mice: 41 mg/kg (Randall, Lehmann).
    d-Form, Ro 1-6794, dextrorphan.  Crystals, mp 198-199 C.


[From 48th edition Physicians Desk Reference]

                                         Equianalgesic Dose (mg)
Name                                    IM                     PO
-------------------------------------------------------------------------
morphine                                10                     60
hydromorphone (Dilaudid)                 1.5                    7.5
methadone (Dolophine)                   10                     20
oxycodone (Percocet)                    15                     30
levorphanol (Dromoran)                   2                      4
oxymorphone (Numorphan)                  1                     10 (PR)
heroin                                   5                     60
meperidine (Demerol)                    75                     --
codeine                                130                    200
-------------------------------------------------------------------------
Note: All IM and PO doses in this chart are considered equivalent to 10 mg
of IM morphine in analgesic effect.  IM denotes intramuscular, PO oral,
and PR rectal.

--
Lamont Granquist ([e-mail])
"And then the alien anthropologists - Admitted they were still perplexed - But
on eliminating every other reason - For our sad demise - They logged the only
explanation left - This species has amused itself to death" -- Roger Waters

=============================================================================

Message-ID: <[e-mail]>
Newsgroups: alt.psychoactives
From: [e-mail] (Holden Caulfield)
Date: Wed,  9 Mar 1994 10:27:13 UTC
Subject: Re: How to oxidize codeine to hydrocodone

[quoted text deleted -cak]

The Merck Index has this to say about oxycodone:

    Prepn by catalytic reduction of hydroxycodeinone, its oxime,
    or its bromination products, or by reduction of hydroxycodeinone
    with sodium hydrosulfite.  Bibliography: Small, Lutz, "Chemistry
    of the Opium Alkaloids," Suppl. No. 103 to Public Health Reports,
    Washington (1932); K.W. Bentley, _The Chemistry of the Morphine
    Alkaloids_ (Oxford, 1954).

So, this leaves the question "How do you prepare hydroxycodeinone?"  Back
to the Merck it says, about hydroxycodeinone:

    From codeine: Merck, Ger. pat. 411,530; _Frdl._ 15, 1516; K.W.
    Bentley, _The Chemistry of the Morphine Alkaloids_ (Oxford, 1954).
    Improved synthesis [from ??]: F.M. Hauser et al., _J. Med. Chem._
    17, 1117 (1974).

About hydrocodone:

    Prepn by hydrogenation of codeinone: Mannich, Lowenheim, _Arch Pharm_
    258, 295 (1920); by oxidation of dihydrocodeine, Ger. pat. 415,097
    (1925 to E. Merck), _Frdl._ 15, 1518 (1925-1927); by catalytic
    rearrangement of codeine: Ger. pat. 623,821.  Industrial prepn from
    dihydrocodeine: Pfister, Tishler, U.S. pat. 2,715,626 (1955 to Merck
    & Co.).  [...]  Review: Small, Lutz, "Chemistry of the Opium
    Alkaloids," Suppl. No. 103, Public Health Reports, Washington (1932).

I wonder if all those methods for reduction of the double bond in hydroxycodeine
to get oxycodone are applicable to reduction of codeine or codeinone.
The one about "reduction of the bromination products" sounds like they add
bromine across the double bond and then reduce the halide,  I believe hydrides
(LAH, NaBH4) can be used for this, and maybe H2 + catalyst, but I'm really not
too sure.

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Newsgroups: talk.politics.drugs,alt.drugs
From: [e-mail] (Jerry Stratton)
Subject: Re: Heroin OTC pre-1914 ?
Message-ID: <[e-mail]>
Date: Thu, 18 Nov 93 18:02:40 GMT

[e-mail] writes:
>I am looking for references or quotes that indicate that heroin, or
>preparations using it were available over-the-counter in the pre-Harrison
>Act days.

Opium and Morphine were certainly available OTC. I don't know if heroin
was available OTC, but the Harrison Act folks seemed to think it was:

From Brecher, Licit & Illicit Drugs, Ch. 8, p. 49:

The patent-medicine manufacturers were exempted even from the licensing
and tax provisions, provided that they limited themselves to "preparations
and remedies which do not contain more than two grains of opium, or
more than one-fourth of a grain of morphine, or more than one-eighth of
a grain of heroin... in one avoirdupois ounce." (5)
(5) Public Law No. 223, 63rd Cong., approved December 17, 1914

Jerry Stratton
[e-mail] (Finger/Reply for PGP Public Key)
------
"They play Paranoia seriously. What more can I say?"
                        -- T. Kelly