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Opioid Substances Overview

October 2016

Opioids

Four classes of opioids

1. Naturally produced in the body (such as

endorphins)

2. Opiates derived from opium poppy (morphine,

codeine)

3. Semi-synthetic compounds (Heroin, OxyContin,

Dilaudid, and Percocet)

4. Fully synthetic opioids (Methadone, Demerol)

• Historically opiates were derived from the poppy plant;

opioids were synthetically derived

• Opioids often refers to both these days

• Both affect the same receptors in the brain

Opiates vs. Opioids?Opiates in nature

• Opiates occur naturally in

poppy plant

• Poppies are native to

Europe and East Asia

• They also grow in Mexico,

Columbia, and the Middle

East

Opiate based substances

• Substances made

using natural opiates

include

• Heroin

• Morphine

• Codeine

• Made from the milky

substance inside the

poppy plant pod

Heroin CodeineMorphine

• 30 mg Codeine, 15 mg of

caffeine and 300 mg of

acetaminophen, sold without a

prescription (T3s)

• A similar tablet called an AC&C

which contains 325 mg of

acetylsalicylic acid (Aspirin)

instead of acetaminophen

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Heroin

• Mainly administered IV; also snorted and smoked

• Dose depends greatly on the purity of the heroin and level

of tolerance• Common IV doses generally fall between 5 and 10 mg; smoked

heroin doses may range from 15 to 25 mg.

• Use small quantities of new supply to determine potency and

reduce the risk of overdose

• ± $50 a point (1/10 of a gram)

• Intense feelings of euphoria and well-being (for some)

• Sedation, analgesia, nausea are common, especially with

higher doses

• Tolerance builds and ceasing use may result in

withdrawal symptoms

• https://erowid.org/chemicals/heroin/heroin.shtml

Cough medicine

Synthetic Opioids

• Synthetically manufactured to

mimic natural opiates

• Most often prescribed for pain

relief

• Synthetic:

• Fentanyl

• Demerol

• Methadone

• Buprenorphine

• Semi-synthetic:

• Oxycodone

• Percocet

• Hydromorphone

Opioid substances*not all inclusive

• Pharmaceutical• Codeine (e.g., Tylenol 3)

• Oxycodone (e.g., Percocet)

• Oxycontin (time release oxycodone)

• Morphine

• Hydromorphone (e.g., Dilaudid)

• Hydrocodone (e.g., Hycodan)

• Meperidine (e.g., Demerol)

• Fentanyl (and analogues)• Transdermal patch;

• Illicit powder; analogues

• Substitutes • Methadone

• Bubrenorphine

• Suboxone (Bup + naloxone)

Image: cbc.ca

Image: theinfluence.org

Common generic, trade and street

names for opioids

Source: CCSA

• Oxycodone was developed in 1917

• OxyContin contains Oxycodone in

a timed-release tablet• Introduced in 1996 by Purdue

Pharma

• Designed for 12-hour pain relief

• Reduces pill-burden

• In 2012, Oxycontin was discontinued and

replaced by OxyNEO

• OxyNEO is still Oxycodone but in a

supposedly harder to tamper with pill

OxyContin / Oxycodone

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• When used illicitly could be

taken in pill form, or crushed

and then ingested, snorted, or

injected• Delivering the whole time released

dose at once

• Many users tend to trust pills

because they assume they are

of pharmaceutical quality, but

there are many counterfeit

“Oxy’s”

OxyContin

The top image is a

real 80mg OxyContin.

The bottom image is

a counterfeit 80mg

OxyContin. The

shade of green is

clearly wrong.

Counterfeit 80mg OxyContin.

The outer casing colour (green)

is extremely close, however, the

inside should be white.

Source: www.studiolonline.net

Prescription Opioids and their

Ingredients

Tylenol #2, #3 and #4

Codeine with acetaminophen

Percocet Oxycodone with acetaminophen

Oxy Neo

OxyContinOxycodone in a time-released formula

Dilaudid Hydromorphone

Prescription Opioids and their

ingredients

MS Contin, M-Eslon Morphine

Duragesic patch Fentanyl

Talwin Pentazocine

Demerol Meperidine

Fentanyl

• Medically used for pain relief

• Typically as a patch, dispensing drug for several

hours (2-3 days)

• Micrograms vs milligrams!

• Now in many opioid street drugs and

occasionally some stimulant drugs

• Illicit powder > patch diversion

• “Bootleg fentanyl” and analogues

• 0.4mg naloxone should reverse overdose

• May not be enough for some analogues

• Extremely potent pain medication

• Usually prescribed as a trans-dermal, time

release patch.• 5 strengths with 1.25, 2.5, 5.0, 7.5, 10 mg

• Delivers 12, 25, 50, 75, 100 mcg/hr for 72 hours

• When used off prescription, people may

suck, or scrape the patch and smoke or

inject the fentanyl• Uneven distribution on patch

• One patch can give about 10 injections

• People can easily inject too much and overdose

• Testing strips?

Fentanyl patch Novel Synthetic Opioids

• Counterfeit pharmaceuticals manufactured illegally

• Designed to look like legitimate pharmaceuticals

• In the US and Canada there are counterfeit pills

including OxyContin and Percocet

– Often contain a synthetic opioid different from the active

substance users believe is present

• Novel synthetic opioids that have been used include

“bootleg fentanyl” and fentanyl analogues

• Other substances that have been used, or might be

used, include W-18 (not actually an opioid), U-47700,

AH-7921 and MT-45.

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Source:

https://www.googl

e.com/patents/W

O2012062439A1?

cl=en

Carfentanil

• Carfentanil (4-carbomethoxyfentanyl) is an analog of the

synthetic opioid analgesic fentanyl

• Four orders of magnitude or 10,000 times more potent

than morphine; 100 times more potent than Fentanyl

• One of the most potent known and the most potent commercially used

opioids

• First synthesized in 1974

• Marketed under the trade name Wildnil as a general

anaesthetic agent for large animals

• As little as 20 micrograms could be fatal to the average person (one

microgram is smaller than a grain of salt)

• Canadian seizures include powders, pills and blotter tabs

• Would need more than one dose of naloxone (US report of 18mg

needed; standard dose is 0.4mg)

• W-18 is a compound in a series of 32 substances (named W-1 to W-32)

• First synthesized in research on analgesic drugs in the 1980s

• Started appearing illicit/recreationally in the 2010s

• W-18 was commonly reported to be an opioid but new understanding

shows this is not true

• W-18 was found to obtain weak activity at both sigma receptors and

the translocator protein (peripheral benzodiazepine receptor)

• http://www.forbes.com/sites/davidkroll/2016/07/28/w-18-is-not-a-

super-potent-designer-opioid-as-originally-believed

• May not respond to naloxone

• In Canada, W-18 and its analogues were made Schedule I controlled

substances effective November 2016

W-series of compounds Novel Synthetic Opioids

• CCSA bulletin:

Novel Synthetic Opioids in Counterfeit Pharmaceuticals

and Other Illicit Street Drugs

http://www.ccsa.ca/Resource%20Library/CCSA-

CCENDU-Novel-Synthetic-Opioids-Bulletin-2016-en.pdf

Concerns

• The use of many and diverse active substances

in counterfeit pharmaceuticals and other illicitly

produced powders means that people using

these products have little information about what

or how much of the substance or substances

they are taking, or their potency and toxicity

• This places them at great risk of overdose

• Information should be provided to people who

use drugs (PWUDs) about what might be

included in the tablets and powders they are

consuming

Concerns

• In their pure form substances such as fentanyl and other synthetic

opioids can be orders of magnitude more potent, and therefore

possibly more toxic, than morphine. However, rarely do those

purchasing these substances in the illicit market encounter them in

their pure form. Instead, they purchase products mixed with bulking

agents or diluents designed to increase the volume of the product

without increasing the amount of active ingredient. However,

clandestine labs or illicit pill pressing operations have difficulty

distributing the active substance evenly across an entire batch of

tablets or powders, particularly when the active dose is very small,

as when using such potent substances as fentanyl. The result is an

uneven distribution of active substance, which means that some

tablets or powders might contain a small quantity of the active

substance, while other tablets or powders might contain a lethal

dose.

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Communicating drug alerts among

people who use drugs

• Flyers, posters or other advisories should avoid

terms that might attract users, such as “potent”,

“strong”, or “more powerful”, which could

inadvertently result in an increase in people

seeking out the drug

• Better alternatives are “toxic”, “dangerous”, or

“lethal” - terms that imply harm

• Date information materials so that people know

when something is a recent concern, not an

ongoing issue

Communicating drug alerts among

people who use drugs

• Include specific calls to action. If individuals

decide to use substances regardless of the

danger, advise them to:

• Make a plan in case of overdose

• Make sure that someone with them is sober enough

to call 911 if an overdose is suspected

• Use a small amount to start

• If an overdose is suspected, perform rescue

breathing, administer naloxone and call 911

Communicating drug alerts among

people who use drugs

• Consider mentioning some of the signs of an

overdose, so people know what to look out for:

• Early signs of opioid overdose include severe

sleepiness; trouble breathing (can sound like

laboured snoring); slow, shallow breathing; cold,

clammy skin; and unresponsiveness to pain.

• Ontario Harm Reduction Distribution Program

poster

– http://www.ohrdp.ca/wp-

content/uploads/pdf/SignsSymptoms.pdf

• All are “downers”

• Primary risks are slowed breathing and heart rate

• High potential for tolerance and dependence with many

• Heroin use has become an increasingly marginal form of

drug use among illicit opioid users in Canada, particularly

outside of Vancouver and Montréal

• Most of the pharmaceuticals are prescribed for pain

management but have increasingly become the predominant

form of illicit opioid use

• “Opioid-rich" environment:

• Canada is a world per capita consumer of

pharmaceutical opioids

Opioids

Ontario, Canada - Student Data Bioavailability and half-life

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Percocet 5 mg tabs $5

Oxycocet 5 mg tabs $3

Morphine 30 mg tabs $4

Morphine 100 mg tabs $8

Oxycontin 10 mg tabs $7-8

Oxycontin 40 mg tabs $20-30 ($20 Renfrew Cty)

Oxycontin 80 mg tabs $45-60 ($40 Renfrew Cty)

Fentanyl 50 mcg patch $30

“Underground Economy”

South East LHIN – North Hastings

From presentation: “Below the Radar: Exploring Substance Use In Rural Ontario”. Kathy Hardill and Sean Lee-Popham

(North Hastings Harm Reduction Network), Canada Harm Reduction 2011 Conference , Ottawa

*In Northern Ontario, in some First Nation’s communities, 80mg pills can be sold for $200-$500.

What’s most cost effective for dealers?

Source: European Monitoring Centre for Drugs and Drug Addiction

Opioid deaths in Ontario

Depressant intoxication: What are the signs?

• Breathing is very slow, erratic or not there at all

• Finger nails & lips turn blue or purple

• Body is very limp

• Deep snoring or gurgling sounds

• Vomiting

• Loss of consciousness

• Unresponsive to stimuli

• Pinpoint pupils

• *Not all symptoms have to be present*

• A short clip explaining what an opioid overdose is and how the

emergency medicine naloxone (Peterborough Drug Strategy)

– https://youtu.be/g-9KyxMtGXg www.ohrdp.ca

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Opioid Overdose vs ‘The Nods’

Check for:• Breathing

• A good way to check someone’s breathing is by using the

back of your hand (very sensitive) or your cell phone to

see if there is ‘fog’

• Alertness

• Pulse

• Other signs?

• It’s important to not let too much time pass

before deciding whether or not to administer

naloxone and call EMS

Depressant overdose response myths

Do Not Implications

Put the person in a bath/cold waterCould drown or put

person into shock

Induce vomiting Could choke

Inject them with anything (saltwater, cocaine, milk) other than naloxone

Will not help and

could cause more

harm

Slap too hard, kick them in the testicles, burn

the bottom of their feet

Could cause serious

harm

Let them sleep it off!Could stop breathing

and die

*Toronto Public Health

Opioid overdose – calling 911

When calling 911, keep it simple: Ask for an ambulance

Let them know that a person is not

breathing/unresponsive/turning blue/unconscious

Let them know the exact location where the person is

Keep the loud noise in the background to a minimum, so that

the safety of the paramedics is not in question

When EMS/paramedics arrive: Let them know what drugs the person may have been using so

they can administer naloxone (if they have it) in a timely

manner

If naloxone has already been administered, let EMS know,

along with the outcome Toronto – Take home naloxone and training through The Works:

http://www1.toronto.ca/wps/portal/contentonly?vgnextoid=aeb94e2c82f1d410Vg

nVCM10000071d60f89RCRD

Naloxone

• Naloxone is an opioid antagonist that reverses

opioid-related respiratory depression

• Currently in Canada, naloxone is available in a

form that is to be injected intra-muscularly

• In Ontario, naloxone is used by many EMS and

emergency departments

• As of summer 2016, available for free at many

pharmacies across the province

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Opioid Overdose Prevention Resources

• There are many opioid overdose

prevention and response programs

in Ontario

• Overdose prevention and

response programs do not need to

distribute naloxone in order to

successfully work with clients to

prevent opioid overdose

• Each existing program is unique

and meets the needs of the local

community

• For resources on how to

implement a program and how to

respond to an overdose check out:

www.ohrdp.ca/opioid-overdose-prevention/

Withdrawal

• Opioid drugs can produce withdrawal symptoms just

hours after the last dose

• Symptoms can last for a week or more

• Unassisted withdrawal may not be life-threatening, but it

can lead to relapse

• Medications and therapy, accessed in medical detox,

may make relapse less likely

Withdrawal

Source: American Addiction Centers

Source: discoveryplace.info

Opiate Risk Reduction and Treatment

• Basic risk reduction strategies, particularly using new equipment when

injecting.

• Be cautious when using after periods of abstinence, as tolerance may

have dropped and risk of overdose is increased.

• naloxone may be used in cases of overdose to provide temporary

relief but person should still be taken to hospital.

• Snorting and injecting opioid painkillers can result in a quicker and

stronger effect.

• These methods can be dangerous as they release several hours

worth of opioid painkillers into your body at once.

• Mixing with other substances, particularly depressants such as alcohol

and narcotics, can be dangerous.

• Some opioid painkillers (such as codeine and hydrocodone) also

contain acetaminophen, which can cause liver toxicity with regular use

and high doses.

• Medications (Methadone; Buprenorphine) can assist with detoxification,

in combination with other therapeutic interventions.

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Some people struggling with opioid dependence are unable to

maintain a state of abstinence. Prolonged methadone

treatment can lead to:

• A decrease and often the cessation of opioid use.

• A decrease in the use of other substances.

• A substantial decrease in crime and prostitution.

• Improved health.

• An improvement in living conditions.

• Better conditions for the continuation of pregnancy.

Methadone Maintenance Programs

What is methadone?

Methadone is an effective and legal substitute for opioid drugs such as

heroin, codeine, morphine, Dilaudid® and Percodan®. Methadone is a long-

acting opioid drug. This means it acts more slowly in the body, for a longer

period of time, than most other opioids. By acting slowly it can prevent

withdrawal and eliminate or reduce drug cravings, without causing a person

to get high. People who are dependent on opioid drugs can take methadone

to help stabilize their lives and to reduce the harms related to their drug use.

It has been used in treatment programs since the early 1960s. Methadone is

available through specialized drug treatment clinics or it may be prescribed

by family physicians and dispensed by community pharmacists, in

accordance with Canadian regulations. Only physicians who have received

an exemption under Section 56 of the Controlled Drugs and Substances Act

are allowed to prescribe methadone.

Methadone Maintenance Programs

How does it work?

Methadone can be used to replace the opioid drug that a

person is dependent on. It prevents withdrawal symptoms and

cuts down on the person’s drug cravings. It does not alter

someone’s ability to work, go to school or care for their family.

Users usually need one dose every 24 hours. When

methadone is diluted in juice, it does not have a euphoric effect

or interfere with a person’s thinking, however, it does block the

euphoric effect of heroin and other opioid drugs, so it makes

the idea of using those drugs much less attractive. Methadone

works best when it is combined with drug counseling.

Methadone Maintenance Programs

Is methadone safe?

When taken as prescribed, methadone is very safe and will not cause damage to the body or

mind, even if it is taken daily for many years. On the other hand, methadone is a powerful drug

and can be extremely dangerous if not taken properly.

How is methadone taken?

Your doctor will give the pharmacy a prescription for your methadone. This prescription must be

renewed regularly by your doctor. He or she will determine how often you come for

appointments, depending on your needs and progress. Your dose of methadone is usually

mixed with orange juice. When you first start on methadone, you will be asked to go to your

pharmacy each day to drink the medication. After two months you may be able to begin to take

home some doses. These are called “carries.”

How long do people stay on methadone?

People stay on methadone as long as they need to. Some health care providers promote short-

term methadone detoxification, where the dependent person is stabilized on methadone and

then tapers off using it over the next one to six months. Others may stay on it for up to twenty

years. Whether short-term or long-term, research has shown that methadone maintenance is

the most effective treatment for opioid dependence.

Methadone Maintenance Programs

Given the costs of untreated opioid dependence, methadone maintenance treatment

offers significant benefits to society, which far outweigh the costs of providing

treatment. American researchers have found:

• The annual costs of methadone maintenance treatment are much lower than the

annual costs of either untreated heroin use, incarceration or drug-free treatment

programs;

• Criminal activities related to heroin use resulted in social costs that were four times

higher than the cost of methadone maintenance treatment;

• For every dollar spent on methadone maintenance treatment there is a savings to

the community of between US$4-$13.

Similar cost benefits are being identified in Canada. In Toronto, the average social

cost of an untreated person who is dependent on illicit opioids has recently been

estimated to be $44,600 per year. According to an estimate from the Centre for

Addiction and Mental Health in Toronto, methadone maintenance treatment can be

provided for approximately $6,000 per year. (2000)

In Canada, methadone maintenance has increased five-fold since the mid-1990s.

Methadone Maintenance Programs

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Methadone and HIV

• Some HIV meds decrease the strength of

methadone, which means you could go

into methadone withdrawal.

• Not a lot is known about how HIV meds

interact with substances - it’s a good idea

to talk with your doctor, nurse or

pharmacist about what is known so you

can stay as healthy as possible.

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Methadone Interactions

• Viramune: methadone up to 60%

• Sustiva: methadone up to 60%

• Rescriptor: Not studied

Methadone Interactions

• Crixivan: None

• Norvir: Decreases methadone levels

• Invirase/ Fortovase: Minimal effects on

methadone

• Agenerase: Decreases methadone by 13%

• Viracept: methadone 35-45%

– ( NFV 50%)

• Kaletra: methadone up to 50%

Buprenorphine/Suboxone

• Buprenorphine hydrochloride is one of the first new treatment options

for opioid dependence since methadone was introduced in Canada

over 40 years ago.

• Physicians do not have to obtain a section 56 methadone exemption1

from Health Canada in order to prescribe buprenorphine.

• While international clinical evidence indicates that buprenorphine is a

much safer drug than methadone, it is important to keep in mind that

the opioid-dependent patient population presents special risks and

challenges.

• Two formulations of buprenorphine – Subutex® and Suboxone® –

have been approved by Health Canada for use in treating opioid

dependence.

Buprenorphine

• Is efficacious as substitution therapy in the treatment of opioid dependence.

• Is an alternative to, but not a substitute for, methadone maintenance treatment.

• Is considered safer in overdose than methadone, although if combined with other CNS depressant drugs (e.g., benzodiazepines) respiratory depression can occur. If clinical symptoms of overdose occur it may require higher doses of naloxone or other measures for treatment.

• May have a lower potential for abuse and dependence than pure agonists such as morphine, although abuse does occur.

• Can be titrated to an effective dose within days, in contrast to methadone which typically may take weeks to achieve.

• May induce withdrawal in patients dependent on opioids if administered too soon after last use of full opioid agonists.

• May be easier to taper from than methadone.

• May be associated with less stigma than methadone.

• Suboxone (Buprenorphione plus naloxone) is a sub-lingual tablet, available in two different doses. The naloxone is intended to deter injection.

• Coverage for Suboxone is currently not universal in Ontario.

Source: (CAMH 2008)