Recreational drugs

Opiates

Can derive morphine, codeine and thebaine

Naturally occuring alkaloids
- morphine, codeine

Heroin

Diacetylmorphine

- diacetyl derivative of morphine

- in body --> deacetylated to morphine

- replace OH with acetyl group on morphine --> heroin

Morphine metabolites

- M3G, M6G

Heroin metabolite

- 6-monoacetylmorphine

- penetrates brain more = lipophilic

- marker for heroin use in forensics

Pharmacological effects of opioids

Analgesia
- major use

Euphoria
- contributes to addiction

Impaired cough reflex
- anti-tussive

Constipation
- anti-diarrhoeal

N&V

Tolerance and dependence

Respiratory depression

Heroin MOA

Converted to morphine in the body

Acts on mu receptors

Needle syringe program

Provides sterile equipment to prevent blood-borne viruses

Injecting drug users major mode of HIV transmission

Fentanyl

80-100x more potent as morphine

IV drug users remove fentanyl from patches to inject

Major killer in US

Methamphetamine

Synthetic homologue of amphetamine

- highly addictive

MOA

- release of DA

- blocks monoamine transporters

- can last several hours (long t1/2)

Pharmacological effects

- euphoria, increased alertness

- increased energy, libido

- appetite suppressant

ADRs

- increased HR, breathing

- hypertension

- irregular body temperature

- cognitive and emotional changes

Meth long term ADRs

Meth mouth

- dry mouth

- tooth decay

- teeth grinding

Addiction

Overdose risk even at low doses from cardiac failure

Neurotoxicity

- long-term emotional and cognitive impairments

- due to damage to DA and 5HT neurons and transporters

- loss of gray matter

- altered BBB

History of cocaine use

Derived from coca plant where its leaves were chewed

Initially used a local anaesthetic, in Coca-Cola

Increasing lifetime use

Cocaine

Often used in binges, followed by severe crash with intense depression, lethargy and hunger

MOA

- inhibits NA and 5HT transporters

- blocks DA reuptake transporter --> more DA in synapse

Pharmacological effects

- euphoria, appetite suppressant

- increased alertness

- confidence

- increased HR, BP

- local anaesthesia

ADRs of repeated use

- eating and sleeping disorders

- sexual dysfunction

- kidney failure

- convulsions

Cocaine side effects

Low purity --> unknown potentially toxic fillers

Damage to nasal membranes if snorted

Tissue damage due to vasoconstriction when injected

Chronic use can lead to

- psychotic episodes

- heart failure

Excessive dosages

- tremors, convulsions

- respiratory depression

- cardiac arrhythmias

History of MDMA

First used as appetite suppressant and aid psychotherapy

Increasing lifetime use

MDMA

MOA

- binds to 5HT transporter, blocks reuptake of 5HT

--> increases 5HT release

- inhibits VMAT, MAO

- increase oxytocin

ADRs

- acute psychosis

- panic attacks

- insomnia

- involuntary teeth clenching

- seizures

Role of 5HT

Roles
- hallucination, mood
- aggression, impulsivity
- eating, sleeping
- arousal, sensory and pain transmission

Does MDMA cause brain damage?

Long term 5HT neurotoxicity

- in animals, causes reduction in 5HT receptors and transporters

- axonal damage

Elevated body temperature accelerate neuronal damage

5HT depletion with heavy use

--> impulsivity, depression, memory loss

Cannabis use

Use has increased among older people

Top indications

- pain

- anxiety

- depression

- sleep disorder

- PTSD

Main way accessing cannabis

- least with prescription

- greatest with dealer

WHO recommendations of cannabis

Cannabis and cannabis resin to be deleted from prohibition schedule

Pure CBD is unscheduled

THC

Main intoxicant
- CB1/CB2 receptor partial agonist
- moderate affinity

CBD

Non-intoxicant
- anticonvulsant, anxiolytic
- antipsychotic
- anti-inflammatory, wakefulness

Cannabis effects

The good
- euphoria
- appetite stimulation
- analgesia

The bad
- anxiety
- memory impairment
- sedation

The ugly
- schizophrenia
- addiction

Cannabis MOA

CB1

- found in CNS and periphery

CB2

- found in periphery (immune cells)

THC binds to CB1 receptors

--> psychotropic effects

Endocannabinoids

Naturally occurring cannabis found in body

- anandamide

- 2AG

Act as messengers in CNS