Lecture 10

Question 1

Prolonged exposure to some of drugs may then lead to…

Answer 1

• Physical dependence (physiological/psychological need to continue taking the drug)
• Tolerance (require greater doses to obtain the desired effect – reduced response to the normal dose)
• Withdrawal (discomfort or distress that follows discontinuation of drug – effects are usually the opposite of the drug taken)

Question 2

A novel psychoactive substance is…

Answer 2

a new term used to describe a large group of drugs that are meant to mimic the effects of more commonly known drugs such as amphtemaines, cocaine, opiates, or delta-9-tetrahydrocannabinol (THC). With many new
identifications appearing monthly, the number of these drugs has grown significantly in recent years. Therapeutic, toxic, and/or lethal concentrations overlap, and drug interactions are not well known. Caution should be used when interpreting their potential role in deaths, taking into account the circumstances surrounding death. Novel psychoactive substances can be sedating, stimulating, or hallucinogenic compounds. The main classes of these drugs can be separated into synthetiannabing. synthetic stimulants and hallucinogens, and syntheopioids.

Question 3

During the 1970s-1980s the recreational drugs…

Answer 3

now considered the traditional drugs - were drugs such as heroin and magic mushrooms. Over the years different drugs appeared on the market as people started to look for alternatives to the traditional drugs in an attempt to avoid prosecution.

Question 4

The NPS market

Answer 4

The NPS market started in 2001. The initial NPS were BZP and methylone, soon followed by mephedrone.
These NPS were produced in clandestine (secret) labs and sold on the black market as a replacement for MDMA – commonly referred to as ‘ecstasy’, or cocaine, or heroin. These NPS could be sold on the streets
without any legal implications, or over the internet – “legal highs”.

Question 5

What are stimulants

Answer 5

Stimulants are drugs which speed up the bodys functions and central nervous system.

Question 6

Effects of stimulants

Answer 6

*Increased heart rate
*Elevated blood pressure
*Feeling more alert and awake
*Acting out of character
*Seizures
*Anxiety or panic
*Headaches
*Nausea or vomiting
*Aggression and paranoia

Question 7

Examples of stimulants

Answer 7

*Amphetamines (indlcuing crystal methamphetamine)
*Caffeine
*Cocaine
*Ecstasy
*Nicotine

Question 8

What are depressants

Answer 8

Depressants are drugs which slow down the body’s functions and central nervous system

Question 9

Effects of depressants

Answer 9

*Feeling tired, fatigued, relaxed or lethargic
*Acting out of character
*Unconsciousness
*Vomiting
*Death

Question 10

Examples of depressants

Answer 10

*Alcohol
*Benzodiazepines
*Cannabis
*Heroin
*Kava
*Opioids
*Sedatives

Question 11

What are hallucinogens

Answer 11

Hallucinogenic drugs alter a persons perception of reality. They can make the user see, hear, feel or experience things that are not really there.

Question 12

Effects of hallucinogens

Answer 12

*Mood changes
*Elevated heart rate
*Aggression/ paranoia
*Loss of contact with reality
*Irrational and bizarre behaviour
*Anxiety
*Acting out of character
*Depression

Question 13

The facial effects of stimulant
drugs

Answer 13

*Dilated pupils of eyes
*Wide-open eyelids, jerky eyes
*Flushed/hot-looking skin
*Clenched jaw, teeth-grinding
*Muscle-rippling, lip-chewing

Question 14

The facial effects of depressant
drugs

Answer 14

*Pinned (constricted) pupils
*Sagging/droopy eyelids
*Paler complexion
*Relaxed facial muscles
*Nodding head (gouching)

Question 15

Opioids

Answer 15

Opioids is an umbrella term. Opioids cover any substance that acts upon opioid receptors within our bodies.

There are naturally derived opioids, these are called opiates. Opiates include drugs such as morphine, codeine, thebaine. The opiates are found in the opium poppy

These opiates can be isolated and undergo a slight chemical alteration, e.g. heroin. Heroin is an example of a semi-synthetic opioid. It is created by adding two acetyl groups to the opiate, morphine.
These exogenous (external) opioids act on the same receptors in our bodies that our endogenous (internal) opioids do.

Question 16

Our endogenous opioids are the neurotransmitters…

Answer 16

enkephalins, dynorphins, endorphins, endomorphins.

These neurotransmitters fall under the neuropeptide classification, which means they can only be made in the cell body of the nerve cell, not anywhere like the other neurotransmitters.
These endogenous opioids cannot be as quickly replenished if they are effected by toxins that cause neuronopathy or axonopathy. The endogenous opioids are our bodies pain control mechanism, and is involved in reward pathways.

Question 17

Synthetic opioids

Answer 17

fentanyls –are the most problematic synthetic opioids being sold. Users do not realise that these fentanyls are far more potent that heroin and are taking the same doses resulting in death by respiratory failure. In some cases, users are unaware that they are consuming the fentanyls.

Fake Xanax tablets (should contain benzodiazepines – another central nervous system depressant) actually contain potent fentanyls (pictured) and were a cause of over 80 deaths last year.

Question 18

How much drug is required to get the desired effect?

Answer 18

• Codeine- 120 mg
• Methadone- 10 mg
• Heroin- 3 mg
• Fentanyl- 0.125 mg
• Sufentanil- 0.010 mg
• Etorphine- 0.005 mg
• Carfentanil- 0.0001 mg

Question 19

Effects of opioids

Answer 19

Effects:
* Analgesia – pain relief
* Miosis – pin prick pupils
* Bradycardia – slow heart rate
* Hypothermia – lowered body temperature, controlled by the hypothalamus – blood vessels dilate
* Constipation – caused by opioids binding to
receptors in the gastrointestinal tract – inhibits peristalsis (involuntary bowel movements that occur in the intestines that propels digested products)
* Changes in mood – opioids cause euphoria.
(this is the reason that opioids may be misused)
* Physical dependence
* Respiratory depression (Dose-dependent)

Overall opioid effect: reduction of cell membrane excitability, slowing of cell firing, inhibition of neurotransmitter release.

Question 20

Naloxone

Answer 20

Naloxone is a drug that can reverse the
effects of opioids, such as heroin, methadone, opium, codeine, morphine, and buprenorphine. A naloxone dose can even save someone’s life if it’s used quickly after they’ve overdosed on opioids and before emergency help arrives.

Question 21

Three important subspecies of cannabis
plant

Answer 21

Cannabis sativa (has the greatest THC content)
Cannabis indica
Cannabis ruderalis

Question 22

Cannabinoids are substances that act on…

Answer 22

cannabis receptors within our bodies, and cause depressant effects.

Δ9-Tetrahydrocannabinol (THC)
(THC is the psychoactive element)

Cannabidiol (CBD)
(CBD has antipsychotic properties)

Question 23

Endogenous and exogenous
cannabinoids

Answer 23

While THC is an example of an
exogenous cannabinoid, we have
endogenous cannabinoids, namely 2-AG
and anandamide.
These endogenous and exogenous
cannabinoids bind to cannabinoid receptors in our bodies. These receptors are called CB1, and CB2 receptors

Question 24

Effects of cannabis

Answer 24

*Feeling of well being
*Euphoria
*Relaxation
*Distortion in the perception of
space and time
*Deterioration in co-ordination
*Disturbance of judgement
*Loss of concentration
*Drowsiness, sleepiness, lethargy,
*Slowed reactions
*Decrease sperm count
*Delay or prevent ovulation
*Possible infertility
*Anxiety
*Tachycardi

Question 25

Cannabinoids

Answer 25

Cannabinoids are actually retrograde messengers.

Typically a neurotransmitter will be released from a presynaptic nerve and interact with a postsynaptic nerve. This is not the case of endogenous cannabinoids, they are the opposite. The endogenous cannabinoids move from the postsynaptic nerve and cause changes to the presynaptic nerve.

Why? Because cannabinoids are extremely lipid soluble, it means they cannot be stored inside vesicles, instead, when cannabinoids are needed our bodies take components from the postsynaptic cell membrane as and when required.

Once the endogenous cannabinoids have been produced they interact with CB receptors on the presynaptic nerve and close Ca2+ channel ( vesicles don’t bind – NT not released); K+ channels opened (nerve made negative [hyperpolarised] – signal transmission inhibited)

THC acts on the same receptors, but has a greater affinity for the receptors than our endogenous cannabinoids; and the synthetic versions that have been created are full agonists of the endocannabinoid systems which results in psychosis.

Question 26

Serotonin

Answer 26

mood regulation, greater concentrations of this neurotransmitter results in better mood (drugs that increase serotonin are prescribed to treat anxiety and depression)

Question 27

Dopamine

Answer 27

coordination of movement, reward,
attention, pleasure, emotional stability

Question 28

Norepinephrine/Epinephrine

Answer 28

stimulates the body, stress responses, fight/flight

Question 29

Mephedrone

Answer 29

One of the synthetic cathinones that
was most widely used in the UK.

Question 30

3,4-Methylenedioxypyrovalerone (MDPV)

Answer 30

MDPV is a powerful norepinephrine and dopamine reuptake inhibitor, but does not stimulate the release of neurotransmitters, which is why it is likened to cocaine.
It is a much more potent effector, 10x more potent than cocaine and the effects last longer. A good example of a synthetic cathinone that has increased potency and also has a higher addiction potential.

Question 31

3,4-Methylenedioxypyrovalerone (MDPV) effects

Answer 31

Stimulant effects: Headache, Nausea, palpitation, increased sex drive, excessive
sweating, cold blue fingers

Adverse effects: Teeth grinding, paranoia, sore nasal passage, sore throat, nose
bleeding, appetite suppression, blurred vision, burns & cold extremities

Psychological Effects: Paranoia, Insomnia, Hallucination, dependence/ addiction

Question 32

Benzo- stimulants
(Benzofurans and Benzodifurans)

Answer 32

These drugs have prominent effects on the serotonin receptors –causing hallucinogenic properties. In addition DragonFLY is a potent
vasoconstrictor that has resulted in limb amputations following its consumption.
DragonFLY is also considered “too powerful” by the psychonaut community because of its duration and potency, therefore it appeared quickly on the market and then disappeared again quickly. What was particularly problematic with this drug, was that it took
about 6 hours for the drug to kick in. The user would think that it wasn’t working so would take more. These are examples of longer acting drugs that last for days and have led to cases of exhaustion.

The benzofurans are more intense than the amphetamines, acting directly on the serotonin receptors, not just increasing
the concentration of neurotransmitters within the synaptic cleft, and deaths have been attributed to these drugs.

Question 33

Tryptamines

Answer 33

Tryptamines are a group of monoamine alkaloids – they are found in plants, fungi, animals, microbes and amphibia.

The tryptamines are also a crossover between
stimulants and hallucinogens, but they have a
classification closer to being hallucinogens.
Whereas the cathinones are stimulants with
hallucinogenic properties, tryptamines are
hallucinogens with stimulant properties.

These drugs have a dramatic impact on mood stability, appetite, sleep control, sexual activity, aggression, and self esteem

Question 34

These NPS have cause toxicologist many problems, including

Answer 34

• Rapidly manufactured and distributed
• Unknown constituents
• Variable potency
• Polydrug use
• Unknown safety profiles
• Analytical challenges