Heroin

Very addictive and illegal!

Belongs to the opioid family

- Derived from the opium poppy (Papaver somniferium)

- Semi-synthesized from morphine providing a stronger and more immediate effect.

Pain reliever and cough suppressant

http://upload.wikimedia.org/wikipedia/commons/8/87/Opium_poppy.jpg

Street Names: - Black Tar, Mud, Smack, Junk, China White, Mexican Brown,

Horse, H, Skag, Dope=

Diacetylmorphine: the International Nonproprietary Name

Diamorphiane: the British Approved Name; legally prescribed drug

The -OH group of morphine is replaced by –OCH3 producing codeine

Both –OH groups of morphine replaced by –OCOCH3 produces heroin

Morphine

Codeine

Heroin

N

O

O

O

CH3

CH3

O

CH3

O

O

O

OH

CH3

N

CH3

N

O

HO

OH

CH3

Morphine: - used for medicinal reasons- prescribed pain killer

Heroin: - illegal to manufacture, possess, or sell- used as a pain-killer as well as a recreational drug- highly addictive!

Pure Heroin White powder Has a bitter taste

http://www.pbs.org/wnet/wideangle/shows/centralasia/images/heroin5.jpg

- The opium gum is converted to morphine in labs near the fields and to heroine in labs near the producing countries.

- The dealers then dilute it with sugars, starch, or powder milk prior to selling

- Sometimes quinine is also added to imitate the bitter taste so the user is unable to tell the quantity of heroin in the sample. http://www.spiegel.de/img/0,1020,817155,00.jpg

Can be mixed with other narcotics for various effects

Sniffed, snorted or smoked for high purity

Powder form can be heated to melt and then injecting the liquid form into veins using a syringe- 3-5 times more potent than the powder form.

Easily overdosed and can lead to death

Possible transmission of HIV and other diseases due to the sharing of needles [1-3]

http://i.current.com/images/asset/889/022/26/PN7mpv.jpg

http://www.russianspy.org/wp-content/uploads/2006/11/heroin.jpg

Varies in color from white to dark brown due to additives or impurities left from the synthesis process

Comes in granule, powder, solution, or pill forms

The dealers then dilute it with sugars, starch, or powder milk prior to sellingso the user is unable to tell the quantity of heroin in the sample

Sometimes quinine is also added to imitate the bitter taste.

http://upload.wikimedia.org/wikipedia/commons/archive/5/5b/20070725121556!Heroin_asian.jpg

After intake, heroin crosses the blood-brain barrier:- Converts into morphine by removal of the acetyl groups

Binds quickly to µ,κ, or δ opioid receptors- µ: results in analgesia, euphoria, CNS depression, respiratory depression, and miosis- Κ and δ: also analgesia but kappa receptors are mostly found in the spine.

Feeling of a quick surge of pleasure targeted in the gut

“High” or a “rush”

Pain relief [2,3]

The intensity dependant on dose of heroin is taken in and therefore how quickly the heroin enters the brain and binds to the µ-opioid receptors

Warm flushing of the skin

Dry mouth

Extremities feel heavy

Nausea and Vomiting

Several hours of drowsiness

Clouded mental function by effect on the CNS

Slows the heart as well as breathing

http://www.vlib.us/medical/HMSO/skin1.jpg

Flushing of the skin

Alters the Paleomammalian brain Manipulates emotions with increased feelings of pleasure and

euphoria

Blocks pain signals transmitted by the spinal cord

Changes the brain stem Controls reflexes Slows down breathing [2,3]

Addiction Increased tolerance Physical dependence Euphoric reward decreases Need higher doses for the same effect Increased repetition

Severe shortening of breath or suffocation

Increase in intensity and occur more often Restlessness Insomnia Muscle and bone damage Can cause death to the fetus of a pregnant user [2-4] Major affect on gastric movements Cold sweats Quivers Nail biting Yellowing and darkening of the nails

Endogenous Substance: The natural neurotransmitters are endorphins Used to combat pain

Endorphins production reduced when present

Difference- Endorphins: naturally produced by the body and are quickly broken down after they are released;

- Heroin: more addictive; stays in the body for a longer period of time

Reduced endorphin production creates strong dependence on heroin [5]

Mimicry of Endorphins:

Heroin is first converted into morphine then mimics endorphins, creating a sense of well-being

Direct agonist that directly binds to the µ-opioid receptor and activates it

Mimics and substitutes for endorphins

Leads to increases in dopamine release in the limbic system

Increased dopamine concentration produces the “high” [6]

Pleasurable sensation from heroin occurs due to the reward centre being stimulated

Dopamine: Key neurotransmitter in the reward system

Three types of neurons are involved in the reward process: Endorphin neurons GABA neurons Dopamine neurons [4,5,7]

Dopamine Neuron

GABA Receptors

Dopamine

GABA Neuron

GABA

Electric Signal

Incentive

1. Normally, Dopamine is released continuously

2. Neurotransmitter GABA inhibits the release of dopamine

µ-OpioidReceptors

Dopamine intercepted No reward

µ-Opioid Receptors

Inhibitory Signal

(Normal Conditions)

Dopamine Neuron

GABA Receptors

Dopamine

GABA Neuron

GABA

Electric Signal

µ-Opioid Receptors

Endorphin Neuron

Endorphin

Incentive

1. Electrical signal is applied on an endorphin neuron, the vesicles are exocytosed and are able to bind to the µ-opioid receptors on the GABA neuron [5]

2. When bound, the opioid receptors prevent electric signals from releasing GABA [5,7]

GABA not released

Dopamine free to proceed to target

3. Inhibition of GABA allows the dopamine neuron to release dopamine, resulting in the feeling of pleasure and well-being [5,7].

Inhibitory Signal

µ-Opioid Receptors

Endorphins immediately begin dissociating and break down after being bound to opioid receptors

Endorphin Neuron

Dopamine Neuron

Dopamine

Electric Signal

Endorphin

Inhibitory Signal

The dopamine neuron possesses µ-opioid receptors.

Binding inhibits dopamine from reaching its target.

Endorphins can therefore produce stimulatory and inhibitory effects [5].

µ-Opioid Receptors

Dopamine Neuron

GABA Receptors

Dopamine GABA Neuron

GABA

Electric SignalEndorphin Neuron

Endorphin

Reward

Dopamine free to proceed to target

Inhibitory Signal

GABA not released

(Heroin Conditions)

Morphine

Heroin converts into morphine and mimics the endorphins by binding tightly to the µ-opioid receptors. As the GABA supply decreases, dopamine is more free to proceed to its target and stimulate pleasurable reward [5,7].

µ-Opioid Receptors

µ-Opioid Receptors

Morphine also binds to µ-opioid receptors of the dopamine neuron, decreasing inhibition of dopamine activity

However, the release of dopamine is independent as it is not being inhibited or intercepted by the inhibitory signals due to the binding of morphine to the GABA neuron µ-opioid receptors [7]

Endorphin

Morphine

Endorphin Neuron

P Neuron

Adjacent Neuron

µ-opioid Receptors

Adjacent Neuron Receptors

Morphine: competitive agonist as it binds to receptors on the P neuron, blocking the release of more P substance (pain signals) [5,7]

Morphine also acts as a competitive antagonist as it will also block the receptors on the adjacent neuron from receiving P substance [5,7]

P SubstancePrevention of P Substance release

Morphine eventually dissociates from receptors and slowly breaks down

Difference:- Endorphin: short term effect; dissociate almost immediately; quick break down

- Heroin: longer lasting; stays bound for a longer period of time

Heroin can easily lead to overdose and can most dangerously cause suffocation

Can severely affects breathing rhythm- neurons regulating breathing patterns also possess µ-opioid- morphine acts like an antagonist, inhibiting signal transmission to the breathing muscles and slowing down the breathing

An overdose can cause lungs to collapse and therefore prevent all breathing causing suffocation [2-5]

Heroin contracts the pupils to as small as less than one millimete Many areas in the gastro-intestinal tract contain many opioid receptors

Heroin inhibits bowel activity leading to constipation

The vomiting centre is stimulated by heroin

The cough centre is suppressed by heroin

After continuous use, ability to feel pleasure is reduced or terminated if heroin is not taken often

Body has reduced or complete inability to release dopamine in a natural way [2-5]

OPIOID AGONISTS Methadone: standard drug treatment for heroin addicts

Mimics morphine Binds to and activates the same µ-opioid receptors as

heroin/morphine, and produces the same cellular effects as heroin/morphine

PRO: more sterile, no crime or violence involved, reduces relapse CON: still harmful!

Levomethadyl Acetate Hydrochloride (LAAM) produces effects similar to methadone in the brain and to reduce relapse

Longer duration of action than methadone [8]

OPIOID ANTAGONISTS Naloxone

Reduces heroin craving post-withdrawal Induces rapid detoxification in heroin addicts

Naltrexone similar to naloxone, but is longer-acting

Nalmefene Most effective since block more µ-opioid receptors

Buprenorphine mimics the brain’s natural neurotransmitters, resulting in gradual reduced withdrawal

Partial agonist Acts as both an opioid agonist and antagonist [8]

[1] Clatts MC, Giang LM, Goldsamt LA, Yi H. 2007. Novel Heroin Injection Practices: Implications for Transmission of HIV and other Bloodborne Pathogens. American Journal of Preventive Medicine; 32(6): 226-233.

[2] Michels II, Stöver H, Gerlach R. 2007. Substitution treatment for opioid addicts in Germany. Harm Reduction Journal; 4: 5.

[3] Jaffe JA and Kimmel PL. 2006. Chronic Nephropathies of Cocaine and Heroin Abuse: A Critical Review. Clinical Journal of the American Society of Nephrology; 1: 655-667.

[4] Lenoir M and Keiflin R. 2006. Heroin Addiction: Anticipating the Reward of Heroin or the Agony of Withdrawal. The Journal of Neuroscience; 26(36): 9080-9081

[5] Belgraver M, Erkamp B, Dragutinovic, Kerssemakers R. 2007. Heroin and the Brain. Jellinek Preventie Amsterdam:

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[6] Terenius L. 1997. Opioid Peptides and Receptors in Drug Abuse. Department of Clinical Neuroscience; 11: 171-176.

[7] Yao L, McFarland K, Fan, Peidong, Jiang Z, Inoue Y, Diamond I. 2005. Activator of G protein signaling 3 regulates opiate activation of protein kinase A signaling and relapse of heroin-seeking behavior. Proceedings of the National Academy of Sciences of the United States of America; 102(24): 8746-8751.

[8] Wasilow-Mueller S and Erickson CK. 2001. Drug Abuse and Dependency: Understanding Gender Differences in Etiology and Management. Journal of the American Pharmaceutical Association; 41(1): 78-90.