HEROIN: AN OPIATE DRUG OF ABUSE

Joanna Rocco

	Heroin is a drug that is produced from morphine, which is 
isolated from opium.  Opium, in turn, comes from the opium poppy.  
Opium use has a long and rich history.  Use of opium may date back 
as far as 6,000 years.  It is likely that opium was used by 
ancient Egyptians, Greeks, and Romans.  Opium was imported to 
China around 800 A.D. and eventually use of opium became 
widespread there and all through Europe.  
	For many years opium, or morphine, was used medically to 
treat a variety of ailments.  It was primarily used as a cough 
suppressant and a pain reliever.  Opium was first brought to the 
medical community in 1680 by a physician named Thomas Syndenham.  
In 1803 morphine was isolated from opium by Frederick Serturner.  
In 1874 heroin (diacetylmorphine) was first produced from 
morphine.  In 1898 the Bayer Company packaged and marketed heroin 
as a substitute for morphine.  In 1914 the Harrison narcotic act 
added a tax on opiate distribution, and in 1924 the Heroin Act was 
passed, which made manufacture and possession of heroin illegal. 
The use and abuse of opioids is still on the rise. It is estimated 
that as many as 8 million people around the world are currently 
abusing these substances (Brink & Ree, 2003).
In the early 1970s researchers at New York University and 
Johns Hopkins found that the brain had its own natural and 
specific opiate receptor sites (Palfai & Jankiewicz, 2001).  The 
goal was to find out why.  These receptors were found in high 
concentrations in the limbic system and in pathways for chronic 
pain.  It was discovered that even a vertebrate as ancient as the 
hagfish had opiate receptors.  Eventually it was discovered that 
the body manufactured its own opiates known as endorphins which 
are made when the body experiences pain or stress.
	The pain killing effect of endorphins occurs when they flood 
the space between nerve cells and inhibit neurons from firing.  
Endorphins, like opiates, can create feelings of euphoria and 
relief from pain.  Heroin is metabolized to morphine, and as it 
reaches the brain the morphine molecule attaches to endorphin 
receptors creating feelings of warmth, euphoria, relaxation, 
drowsiness, and satisfaction (Young, 1999).
	Addictive drugs activate processes of reward and mimic or 
copy natural transmitters which then change brain circuits which 
are involved in learning.  What is, in part, so dangerous about 
addictive drugs is this ability to affect brain chemistry in such 
a profound way.  What opiates do primarily is to inhibit GABA 
neurons that usually in turn inhibit dopaminergic neurons in the 
ventral tegmental area of the brain.  This leads to a rush of 
dopamine in the nucleus accumbens as well as other mesolimbic and 
mesocortical brain regions (Kreek, Laforge, & Butelman, 2002).
Addictive drugs such as heroin are able to block or short-
circuit the brain's natural reward pathways.  Normally these 
pathways help us to survive, but the drug has such a strong effect 
on memory and learning that getting the effect produced by the 
drug becomes more important (Young, 1999).  The mesolimbic 
dopamine system is a very important part of the brain's reward 
system.  Nerve cells originating in the ventral tegmental area 
near the base of the brain send messages to the nucleus accumbens 
deep beneath the frontal cortex.  The VTA neurons send out 
dopamine from the terminal boutons to the receptors on nucleus 
accumbens neurons.  This dopamine pathway plays a crucial part in 
the role of addiction (Nestler & Malenka, 2004).  Animals with 
lesions or tumors in these parts of the brain don't show interest 
in addictive drugs, while healthy animals quickly learn to self 
administer drugs such as heroin by pressing a lever.
Continued use of heroin will cause tolerance, dependence, and 
eventually addiction and withdrawal.  Tolerance occurs when more 
and more heroin is needed to produce the euphoria and other 
desirable effects of the drug. Addiction is the physical and 
psychological need for heroin.  The user begins to crave the drug 
and will go to greater and greater lengths to obtain it.  
Withdrawal occurs when the heroin user experiences negative or 
adverse affects if he doesn't use heroin for a certain amount of 
time.  Once a user reaches this stage the habit often begins to 
harm his health, finances and personal relationships (Nestler & 
Malenka, 2004).
When heroin is used initially, endorphins and the 
neurotransmitter dopamine (DA) play important roles in reinforcing 
the effects of the drug.  The primary brain areas associated with 
this initial effect are the ventral tegmental area (VTA) and the 
nucleus accumbens (NcA). When drug use is continued and cravings 
for the drug begin to develop, many neurotransmitters become 
involved.  In addition to dopamine there is also corticotrophin 
releasing hormone in the amygdale and glutamate in the frontal 
cingulated circuit. In detoxification and withdrawal, 
norepinephrine and glutamate are pronounced and the locus 
coeruleus is the brain region most affected.  In relapse, y amino 
butyric acid or GABA and glutamate are involved in the 
compulsivity of heroin addiction while norepinephribe (NE) seems 
to play a role in the brain's stress system (Brink & Ree, 2003).
	 Addiction refers to compulsive use of a drug in spite of 
harmful and unpleasant consequences. Heroin use changes chemistry 
and brain function for a long time after the last use.  In mice 
studies it was found that certain stable proteins rise in the 
brain during drug use and remain active for months.  Long term 
exposure to heroin may even cause the neurons of the nucleus 
accumbens to sprout extra terminal spines, thereby supporting 
these cell's connections to other neurons throughout the brain and 
further reinforcing use of the drug (Nestler & Malenka, 2004).  
Treatment of heroin addiction is tricky, and relapse rates are 
high.  Even with all this discouraging evidence however, there are 
options for treatment of opiate addiction, unlike cocaine 
addiction, which has few means of treatment. There are a variety 
of ways to interrupt the addictive process, both pharmacologically 
and socially. 
	Before treatment can begin, the user must go through what is 
known as detoxification.  Some people just stop taking the drug 
abruptly, a method known as going "cold turkey."  More often the 
heroin is replaced by another opiate or an opiod-agonist such as 
methadone, which is then tapered down.  Often heroin addicts are 
maintained for long periods on the drug methadone, a synthetic 
analgesic and morphine like agonist.  Other opiate agonists are 
also used.  These drugs block the effects of opiates and the 
purpose of the treatment is to break the reward cycle of heroin 
use (Palfai & Jankiewicz, 2001).  There are studies being done on 
the effects of drugs such as naltrexone and buprenorphine to see 
if they may be more affective than methadone in long term 
abstinence of heroin use (Lange, Fudala, Dax, & Johnson, 1990).  
Lastly there is heroin maintenance or heroin assisted treatment.  
This was introduced in Switzerland in 1994 and keeps addicts on a 
low level of the drug.  This treatment method is very 
controversial.  Heroin maintenance may reduce crime associated 
with the use of the drug, but does little in terms of actually 
getting the addict off of heroin altogether (Kilias & Rabasa, 
1998).
	Drug related cues or "triggers" play an important role in 
relapse.  Studies with rats show that those animals with a higher 
degree of use before detoxification were more likely to seek out 
heroin when cues were introduced, even after a significant amount 
of time without the drug (Shaham, Highfield, Delfs, Leung, & 
Stewart, 2000).  This emphasizes the importance of avoiding 
people, places and things an addict associates with past drug use 
in the prevention of relapse.  
	Stress is another important factor in relapse.  It has been 
shown that norepinephrine (NE) neurons in the pons and medulla of 
the brain contribute to relapse.  In rats stress is induced by 
using foot shock, and does increase a reinstatement of heroin use 
after a time of abstinence (Zhang, Zhou, Tang, Lai, Liu, & Yang, 
2003).  It is therefore important for a recovering addict to 
engage in some activity, be it counseling or involvement in a 12 
step group that helps him deal with life stressors.  The use of 
adrenergic receptor agonists such as clonidine in heroin treatment 
and relapse prevention is still being investigated (Shaham et al., 
2000).
	Addiction to heroin is a condition that is chronic and 
lifelong.  The "how" of addiction is becoming more and more 
understood, while the "why" of addiction is still not fully 
understood.  Why do some people seem to be so much more vulnerable 
to addiction than others?  It is a complex process that most 
likely involves a genetic component and environmental factors 
(Brink & Ree, 2003).  It is also important to note that the reason 
for the use of the drug may also play a factor.  Young (1999) 
suggests that voluntary use of a drug might activate different 
chemical systems in the brain than when the drug is administered 
by a doctor in a hospital, for example. Addiction involves 
interaction between one's brain chemistry, particular genetic 
vulnerability, and a person's own life experiences.
Studies continue to move forward toward the search for a 
neurobilogical cause.  It is theorized that permanent dysfunctions 
of the dopaminergic system may be responsible.  It is even 
possible that someday a specific marker may be discovered that can 
identify people at risk for addiction and perhaps predict the risk 
of relapse (Czermak et al., 2004).  Drug addiction costs the 
United States almost $300 billion a year which makes it one of the 
most serious problems facing society today (Nestler & Malenka, 
2004).



References

Brink, W., & Ree, J.M. (2003). Pharmacological treatments for 
heroin and cocaine addiction. European Neuropsychopharmacology, 
13, 476-487.

Czermak, C., Lehofer, M., Wagner, E., Prietl, B., Lemonis, L., 
Rohrhofer, A., Schauenstein, K., & Liebmann, P.M. (2004).  Reduced 
dopamine D4 receptor mRNA expression in lymphocytes of long term 
abstinent alcohol and heroin addicts. Addiction, 99, 251-257.

Kilias, M., & Rabasa, J. (1998). Does heroin prescription reduce 
crime? Results from the evaluation of the Swiss Heroin 
Prescription projects. Studies on Crime Prevention, 7, 127-133.

Kreek, M.J., LaForge, K.S., & Butelman, E. (2002). Pharmacotherapy 
of addictions. National Review, 1, 710-726.

Lange, W.R., Fudala, P.J., Dax, E.M., & Johnson, R.E. (1990). 
Safety and side effects of buprenorphine in the clinical 
management of heroin addiction. Drug and Alcohol Dependence, 26, 
19-28.

Nestler, E.J., & Malenka, R.C. (2004). The addicted brain. 
Scientific American, 290(3).

Palfai, T., & Jankiewicz, H. (2001). Drugs and human behavior (2nd 
ed.). New York: McGraw Hill.

Shaham, Y., Highfield, D., Delfs, J., & Sterwart, J. (2000). 
Clonidine blocks stress induced reinstatement of heroin seeking in 
rats: an effect independent of locus coeruleus noradrenergic 
neurons. European Journal of Neuroscience, 12, 292-302.

Young, A.M. (1999). Addictive drugs and the brain. National Forum, 
79, 15-23.

Zhang, F., Zhou, W., Tang, S., Lai, M., Liu, H., & Yang, G. 
(2004). Motivation of heroin seeking elicited by drug associated 
cues is related to total amount of heroin exposure during self 
administration in rats. Pharmacology, Biochemistry and Behavior, 
79, 291-298. 

THE CHEMISTRY AND PHARMACOLOGY OF HEROIN 

Heather French

Neurons, synaptic transmitters, and inhibitory and excitatory 
potential changes: Heroin's affect on the brain

Heroin, or diacetylmorphine, is an opiate derivative and an opioid 
agonist (Smith, 2003.)  Opiate derivatives bind to pain receptors 
in the surface membrane of cells in the brain known as opiate 
receptors, therefore preventing pain or causing a sense of 
euphoria for users who are not experiencing pain (Doweiko, 2002.)  
Most opiates bind fairly selectively to one of three types of 
receptors (mu, delta, and kappa) known as mu receptors (North, 
1993.)  Potassium channels on these neurons are opened by opioids, 
which then results in hyperpolarization and a reduction in firing.  
This then causes less GABA to be released onto the dopamine cells, 
and consequently the dopamine cells fire more rapidly (North, 
1993.)  However, some researchers have found that heroin does not 
bind to these known receptors.  

Heroin seems to be more of a prodrug, or a compound that is 
biotransformed by the liver into a compound that is biologically 
active.  This compound is technically a metabolite of the parent 
drug and has a stronger biological action than the parent compound 
(Doweiko, 2002.)  This phenomenon occurs when heroin is deacylated 
by pseudocholinestarase and nonspecific liver carboxylesterases 
hCE1 and hCE2 to active metabolites 6monoacetylmorphine and 
morphine (Smith, 2003).  Essentially, heroin is active through its 
biotransformation into morphine.  Heroin molecules are hydrolyzed 
into morphine molecules in the brain (Palfai & Jankiewicz, 2001.)

The chemistry of heroin

The chemical structures of heroin and morphine are quite similar 
(see figure 1.)  The heroin molecule is essentially a morphine 
molecule with two acetyl groups added to it between the identical 
alcohol and phenylhydroxyl groups (Palfai & Jankiewicz, 2001.)   



The routes of access for heroin

There are several routes of access for heroin.  When taken 
intranasally, or snorted, about 25% of the available heroin in the 
heroin powder is absorbed into the body through the nasal 
membranes (Doweiko, 2002; Brick & Erickson, 1998.)  When heroin is 
smoked, it is well absorbed through the lungs.  However, the 
process of smoking destroys approximately 80% of the heroin, so 
the user needs a very potent and plentiful supply in order to 
achieve the same affects (Doweiko, 2002.)  Heroin is most 
affective when taken by injection.  It can be injected 
intravenously, intramuscularly, and subcutaneously.  When 
administered intravenously 100% of the drug is absorbed (Doweiko, 
2002; Brick & Erickson, 1998.)  The high success rate of using 
heroin by this method of administration is illustrated in the 
figure below (see figure 2.)



The pharmacology of heroin

The pharmacological characteristics of heroin produce a more 
potent analgesic than morphine.  "A standard conversion formula is 
that 4 milligrams (mg) of heroin is as powerful as 10 mg of 
morphine (Doweiko, p. 173.)"  Additionally, because it is much 
more lipid soluble than morphine, heroin is able to cross the 
blood brain barrier 100 times faster than morphine (Doweiko, 
2002.)  The typical onset of heroin is approximately 15 minutes, 
as compared to 20 minutes for morphine (Brick & Erickson, 1998.)  
Peak effects of both heroin and morphine are commonly experienced 
within 60 minutes, with the typical duration lasting between 4 to 
5 hours for heroin and approximately 7 hours for morphine (Brick & 
Erickson, 1998.)  Heroin has a half life of only 3 minutes, 
although one of its primary metabolites has an analgesic potential 
and its half life is approximately 30 minutes (Doweiko, 2002.)  

References

Brick, J., & Erickson, C. (1998).  Drugs, the Brain, and Behavior.  
Binghamton, NY: The Haworth Medical Press, Inc. 

Doweiko, H. (Ed.) (2002).  Concepts of chemical dependency (5th 
ed).  Pacific Grove, CA:  BROOKS/COLE.

North, R. Cellular basis of opioid action.  In Korenman, S., & 
Barchas, J. (Eds).  Biological Basis of Substance Abuse.  (1993). 
Oxford:  Oxford University Press.

Palfai, T., & Jankiewicz, H. (2001).  Drugs and Human Behavior (2nd 
ed).  New York: McGraw-Hill Primis Custom Publishing.

Smith, H. (2003).  Drugs for Pain.  Philadelphia, PA: Hanley & 
Belfus, Inc.

  

Physiological and Primary Behavior Changes Related to Heroin Use

Erin C. Villa

PHYSIOLOGICAL CHANGES:

Heroin or diacetylmorphine also known on the street as horse, 
smack, jive, junk, golden brown, black tar, etcetera, is one of a 
group of drugs called 'opiates', which are derived from the opium 
plant.  Compounds like heroin, which come from alterations of the 
morphine molecule, along with other synthetic painkillers 
unrelated to morphine or heroin by structure or potency, are 
called opioids (Palfai, & Jankiewicz, 2001). Heroin being a 
derivative of morphine and morphine being opium's most potent 
active ingredient, once introduced to the body whether through 
inhalation, injection, or ingestion can have serious health 
consequences.  However, injected IM or IV, heroin is about three 
times as potent (Palfai & Jankiewicz, 2001).  Heroin, the most 
fast-acting of all the opiates when injected, it reaches the brain 
in around 15-30 seconds and within one minute the surge of 
pleasure seems to start in the abdomen; a delicious warmth then 
spreads throughout the body (HYPERLINK ' 
http://www.heroin.org/heroin.html '). Heroin and other opiates are 
sedative drugs that depress the central nervous system by slowing 
down body functioning and are able to combat both physical and 
emotional pain (HYPERLINK ' http://www.drugscope.org.uk ').  It 
does this by mimicking the action of natural chemicals in our 
body, endorphins and these endorphins are involved in respiration, 
nausea, vomiting, pain modulation, hormonal regulations and  
itching (HYPERLINK ' http://www.heroin.org/heroin.html ').  
Although the CNS is affected with the introduction of heroin in 
the body, there are also peripheral affects (HYPERLINK ' 
http://www.emedicine.com/med/topic1003.htm ').  In the article 
Toxicity, Heroin (2004), Dr. Laurie Grier explains these effects 
as follows:

CNS:
Mild to moderate heroin toxicity manifests as analgesia, 
drowsiness, reduced physical activity, and difficulty in 
mentation.

Respiratory:
Respiratory depression is also a trademark of heroin and is the 
result of CNS depression.

Heroin reduces the brain's responsiveness to changes in PCO2. With 
high doses, heroin can also depress the brain's response to 
hypoxia.  This results in severe respiratory depression 
progressing to apnea.

Tachypea may result from concomitant sympathomimetic intoxication, 
hypoxia, and hypoglycemia.  

Wheezing due to bronchospasm may be evident.  Wheezing may also 
indicate bronchospasm secondary to histamine release.

Eyes:
The presence of miosis in the setting of opioid toxicity, 
including heroin.  Miosis results when the mu and kappa receptors 
of the parasympathetic nerve innervating the pupil are stimulated 
by the heroin.

With mixed toxicities, mydriasis may also be noted.

Cardiovascular:
Mild bradycardia and mild hypotension.

Mild peripheral vasodilation occurs with reduced peripheral 
resistance and inhibition of baroreceptor reflexes.

Blood pressure is usually well maintained unless the body is 
stressed by hypoxia, hypovolemia, or acidosis.

Hypotension due to heroin is generally attributable to histamine 
release and is observed in a number of opioid, including heroin.

Heroin my cause ventricular arrhythmias.

Gastrointestinal:
Decreased gastric motility, thereby prolonging gastric emptying 
time by as much as 12 hours.

Heroin can also inhibit acetylcholine's effect on the small 
intestine and diminish the colonic propulsive waves, thereby 
delaying colonic emptying and resulting in constipation.

Skin:
Heroin causes vasodilatation of the cutaneous blood vessels, 
resulting in flushing. 

The vasodilatory effect may be enhanced by histamine release, 
which also results in pruritus.


Stated succinctly, heroin/morphine reaches all body tissues.  The 
liver rapidly metabolizes opiates, biotransforming a significant 
amount on the first pass, although this tends to vary widely among 
people (Palfai & Jankiewicz, 2001).  Due to this rapid 
metabolizing, the high only ranges between 3-5 hours, depending on 
the individual.  This is a matter of great importance to the drug 
dependent, who must seek another "fix" three or four times a day 
to avoid withdrawal symptoms (Palfai & Jankiewicz, 2001).  
	
Ninety percent of a dose of morphine is excreted in 24 hours 
through the kidneys, with most of it metabolized.  Traces may be 
found in the urine, however, well after 2 days.  Another 7 to 10 
percent of the dose enters the bile and passes out through the 
gastrointestinal tract. (Palfai & Jankiewicz, 2001).

PRIMARY BEHAVIOR CHANGES:
Although heroin's creator, Heinrich Dreser, pronounced heroin as 
an effective treatment for a variety of respiratory ailments, such 
as bronchitis, asthma and tuberculosis, it's use is illegal.  Even 
though the medical and psychological fields can not use heroin, 
specifically, there are other forms that can be used.

Medicinally, several forms of opioids are used such as opium, 
morphine, codeine, and other opium derivatives such as 
hydromorphine (Dilaudid), meperidine (Demerol), oxycodone 
(Percodan, Percocet), and hydrocodone (Vicodin, Lortab, Lorcet), 
and Fentanyl (HYPERLINK ' http://www.acde.org/common/Heroin.htm 
').

All of these are used for pain control and have been used for 
calming and sedation.  Fentanyl is the most powerful synthetic 
used for severe pain and as a surgical anesthetic (HYPERLINK ' 
http://www.acde.org/common/Heroin.htm ').

In the psychological arena, the one most used would be Methadone.  
Methadone is most known for its aid in the treatment of heroin 
addiction.  Methadone, a mu-opioid agonist often used to 
substitute for heroin in treatment of heroin addiction is well 
absorbed orally and has a much longer duration of action.  Thus 
methadone maintenance avoids the rapid cycling between 
intoxication and withdrawal associated with heroin addiction.  
Also, by keeping the addict physically tolerant to opioids, 
methadone effectively blocks the euphoric effects of heroin.  In 
this way, methadone has shown some success as a 'less harmful 
substitute'; it is in fact the single most effective treatment 
known for opioid addiction, and is recommended for those who have 
repeatedly complete detoxification. (HYPERLINK ' 
http://en.wikipedia.org/wiki/Heroin ').
	
The theory behind the methadone use is the user will not be 
inclined to venture out and seek heroin on the street.  Methadone 
does not produce the same high as heroin, but it does help the 
addict with withdrawals and the cravings that opioids produce.

Methadone paired with several other tools is the most effective.  
Patients in methadone maintenance programs also receive 
counseling, vocational training, and education to help them reach 
the ultimate goal of a drug-free normal life (HYPERLINK ' 
http://www.well.com/user/woa/fsheroin.htm 
').

Refernces

Basic facts about drugs: heroin, (n.d.).  Retrieved March 21, 2005 
fromhttp://www.acde.org/common/Heroin.htm.

Deadly short cuts, (n.d.). Retrieved March 21, 2005 from 
http://heroin.org/heroin.html.

Heroin, (n.d.). Retrieved March 21, 2005 from 
http://en.wikipedia.org/wiki/Heroin.

Heroin (and other opiates), (n.d.). Retreived March 21, 2005 from 
http://www.drugscope.org.uk/druginfo/drugsearch/ds...

Heroin and other opiates, (n.d.). Retrieved March 21, 2005 from 
http:/www.well.com/user/woa/fsheroin.htm.

Palfai, T., Jankiewicz, H. (2001). Drugs and human behavior. 
McGraw Hill Primis: New York.

Toxicity, Heroin, (2004). Retrieved March 21, 2005 from 
http://emedicine.com/med/topic1003.htm.

Copyright © 2005, Dr. John M. Morgan, All rights reserved - This page last edited 04-23, 2004
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