Psychology of addiction Inhalants and GHB - the date rape drug.

Psychology of addiction

Inhalants and GHB - the date rape drug

Inhalants

dichlorotetrafluoroethane

carbon tetrachloride

C

Cl

Cl

Cl

Cl

chloroform

C

Cl

Cl

H

Cldichlorodifluoromethane

bromochloro-difluoromethane

methyl chloroform

trichloroethylene

C

Cl

F

F

Cl

F FC C

Cl

H

Cl

Cl

C

dichlorotetrafluoroethane

Alcohol (Ethanol)

trichloroethylene

C

Cl

F

F

Cl

F FC C

Cl

H

Cl

Cl

C

C

H

H

OH

H

H HC

AND nitrous oxide

toluene

xylene

N ON

What do these various chemicals all have in common?

volatile liquids/gases

can be sniffed/inhaled/sprayed into mouth

aren't anything else!

Categories

volatile solvents

(liquid at room temperature, give off fumes)

aerosols (contain solvents/propellants)

gases

the above are all euphoriants (get you high)

Behavioural effects

Acute: euphoria, disinhibition, stimulation

then lightheadedness, drowsiness (like alcohol)

Heavy exposure: slurred speech, ataxia, lethargy, hallucinations, sometimes delusions

Very high doses: anaesthaesia, coma

Talk to Frank...

- Users say it's like being drunk with dizziness, dreaminess and fits of the giggles. And it can be difficult to think straight.

- Depending on what's being inhaled, you can hallucinate. This can last for up to 45 minutes.

- The hit is quite short so users tend to keep repeating the dose to keep the feeling going.

- It can give people a 'hangover' afterwards, giving them severe headaches and leaving them tired.

- Depending on the substance, it can leave a red rash around the mouth.

i knew this dude who died of the shit, he tried to do a whole can in one hit and had a fucken anurism in his brain or some shit..

i OD like 20 times in total of all the OD's..and i had one last OD...where i was in a dream..the dream was about my time running out..and i was melting..this voice said "come here again,and u will die" i almost did again..and my friend told me "HEY HEY..LOOK AT ME...U ARENT OVERDOSING..ITS ALL IN UR MIND" and i jus snapped outa it..im glad i quit something tells me that dream was real

Risks

tolerance; withdrawal syndrome?

sudden sniffing death syndromefrom cardia arrhythmia

repeated use damages lungs, kidneys, liver

also brain -- subcortical abnormalities

damage to myelin sheaths around axons (MRI scans)

Talk to Frank...

People can experience vomiting and blackouts

There’s a risk of fatal heart problems which have been known to kill users the very first time they sniff.

Squirting gas products down the throat is a particularly dangerous way of taking the drug. It can make your throat swell so you can't breathe and slows down your heart.

You risk suffocation if you inhale from a plastic bag over your head.

Sniffing can seriously affect your judgment and when you're high there's a real danger you'll try something reckless.

Talk to Frank...

Long-term abuse of solvents has been shown to damage the brain, liver and kidneys.

It can be hard to get the amount right. Just enough will give the desired high – a little too much can result in coma.

Solvent abuse killed 64 people in 2000. A quarter of these were people under 18.

Using solvents in combination with alcohol can lead to an increased risk of death.

Subcortical structural abnormalities in inhalant abusers compared to other abusers

in US about 6% of children have tried inhalants by 4th grade, and usage peaks between 7th and 9th grades - for 12 year olds more popular than marijuana!

(especially in Alaska!)

Solvent misuse isn't illegal. Although, it’s illegal in England and Wales for shopkeepers to sell you intoxicating substances if they think you’re likely to be inhaling them.

In Scotland the law is different but the effect is similar. Under Scottish law you can be prosecuted for 'recklessly' selling substances to any age group if you suspect they're going to inhale them.

Since October 1999, the law makes it an offence to supply gas lighter refills to anyone under the age of 18. This law applies to the whole of the UK.

Why?

not much known, because appearance quite recent, and also chemically diverse... but:

Reinforcing. Funada et al., 1992

Mice in place conditioning task

two chambers, one paired with toluene

Prefer toluene side

How?

rapidly absorbed – fat soluble

distributed widely around the brain

especially striatum, thalamus, deep cerebellar nuclei

  PET images of brain uptake and distribution of radiolabeled toluene in a baboon

Striatum Deep cerebellarnuclei

Why? Neural effects

enhance GABA & glycine inhibitory receptors

inhibit excitatory NMDA glutamate receptors

similar to alcohol - reduce CNS excitability

why reinforcing?

Toluene activates dopamine neurons in ventrotegmental area… dopamine to do with reinforcement

GHB - the date rape drug

gamma hydroxybutyrate

Uses

"club drug" -- used like E's and ketamine

notoriety for use as "date rape" drug

used clinically to treat cataplexy (sudden loss of muscle control experienced by narcoleptics)

Several drugs are used in date rape, not only GHB:

e.g. ketamine (see hallucinogen lecture)and rohypnol (a benzodiazepine)

In the US special beermats can detect GHB and ketamine

Behavioural effects and risks

Low doses: mild euphoria, disinhibition, relaxation

Higher doses: slurred speech, ataxia, lethargy, dizziness, nausea, vomiting

Overdosing: respiratory depression, lack of consciousness, seizures

Risks

Tolerance: Evidence

Informal reports from users suggest that they may increase dose – sometimes every 2-4 hours all day and night

Withdrawal symptoms reported as insomnia, anxiety and tremors,

and at high doses even hallucinations, delirium, extreme agitation and psychosis

Tolerance to the locomotor-suppressant effects of GHB in mice

History

closely related to GABA; were looking for a GABA analogue to use as a CNS depressant

initially sold commercially in US health food shops as nutritional supplement for body builders – supposed to reduce fat and increase muscle

"cherry meth", "Georgia home boy", "liquid X”

then reported adverse effects resulted in a ban

still can be bought, or made at home with a kit from 1,4-butanediol and -butyrolactone (GBL)

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15.4  Chemical structures of GABA, GHB, 1,4-butanediol, and GBL

15.4  Chemical structures of GABA, GHB, 1,4-butanediol, and GBL

Behavioural effects in lab animals

lower doses: sedation, reduced locomotor activity, decreased anxiety in e.g. elevated plus maze

higher doses: catalepsy and paradoxical CNS excitation - maybe like petit mal seizures in humans?

in humans who overdose sometimes have mild seizures - i.e. lose consciousness and cease activity, but no convulsions

Why?

Reinforcing?? Funada et al., 1992

place conditioning task in rats and mice -- yes

intravenous self-administration in monkeys -- not really:

although some sedated themselves

sedation unpleasant? if too drowsy can't get more??

How? Neural effects

Hypothesis 1

GHB acts on GABAB receptors

maybe GHB has weak affinity for pre/post synaptic GABAB receptors

maybe GHB is metabolised into GABA

(except that GHB has only poor affinity for GABAA receptors, so not equivalent to GABA in its effects..)

How? Neural effects

Evidence

Effects of GHB counteracted by GABAB antagonists

rats had to press lever A when they had GHB, lever B when they had saline

then give dose of GABAB antagonist on top

15.6  Dose-dependent blockade of discriminative stimulus properties of GHB by CGP 35348

How? Neural effects

Hypothesis 2

there is a specific GHB receptor

Evidence

- there are selective GHB binding sites in the brain nonuniformly distributed (e.g. in hippocampus and cerebral cortex)

GHB analogue called NCS-382 binds to GHB sites and is selective antagonist at this receptor

How? Neural effects

Evidence

- GHB synthesised in the brain from GABA

- has own uptake mechanisms

- released in Ca2+ dependent manner

- own receptor system

How? Neural effects

Hypothesis 2

BUT

endogenous levels of GHB not behaviourally effectiveso taking it acts via a different mechanism?

not all effects of GHB blocked by GHB receptor antagonist NCS-382

but at high doses NCS-382 acts like agonist - so who knows!!

Next time ... anabolic steroids

Psychopharmacology: Drugs, the brain and behaviour Meyer & Quenzer

Chapter 15

Lectures may be found here:

http://www.psychology.nottingham.ac.uk/staff/lch/C81ADD/