Drugs Of Abuse 1 (Lecture 19) Flashcards by Louisa Mukherjee

Why is there a high risk of dependence for cocaine (particularly crack)?

Because it is a potent but short-acting stimulant

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Who first produced MDMA?

Merck in 1912

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What was MDMA initially used for?

An adjunct for psychotherapy in the 1970s
Used recreationally from 1980s - emerged / popularised by the rave scene

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Stimulants affect the transmission of which NTs?

Serotonin
Noradrenaline
Dopamine

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What is the mechanism of action of stimulants?

Stimulants increase serotonergic, noradrenergic & dopaminergic transmission through 2 mechanisms:

Major mechanism - inhibit transmitter removal
- block SERT, NAT & DAT re-uptake transporters
Minor mechanism - reverse transportation
- drug molecule itself is taken up by the transporter, substituting for K+ ions
- extra transmitter released via reverse transport through the transporter

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What is MDMA as a class of drug?

A synthetic amphetamine derivative

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What is cocaine hydrochloride isolated from?

(It is the active ingredient) isolated from coca leaves (erythroxylaceae)

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What is an example of a clinically used amphetamine?

Adderall for ADHD

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What are the medical uses of cocaine?

Highly effective LA - used for nose, mouth & throat surgeries
(Lidocaine is a derivative of cocaine)

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What is the meaning of substance abuse?

Compulsive & continuous use despite adverse effects

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What is the meaning of addiction?

State of psychological / physical dependence (or both) on the use of alcohol or drugs

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What are the functional / subjective effects of inhalants?

Euphoria / lightheadedness (brief)

Increase HR & body temp

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What are the functional / subjective effects of hallucinogens?

Altered perspective

Introspection

Panic / paranoia

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What are the functional / subjective effects of dissociative anaesthetics? (E.g. ketamine, PCP)

Sedation
Hallucinations
Dissociation from reality
Slowed breathing & increased BP

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What are (5) functional / subjective effects of CNS depressants (e.g. benzodiazepines, barbiturates) ?

Euphoria
Drowsiness
Confusion / memory loss
Slowed breathing
Lowered BP

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What are the functional / subjective effects of cannabinoids?

Euphoria
Relaxation / sedation
Increased HR & appetite

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What are the 5 environmental factors of drug abuse?

Chaotic home & abuse
Parental use & attitudes
Peer influences
Community attitudes
Low academic achievement

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What are the biological / genetic factors of drug abuse?

Genetics
Gender
Mental disorders

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What are the 7 drug categories?

CNS depressants
CNS stimulants
Hallucinogens
Dissociative anaesthetics
Narcotic analgesics
Cannabinoids
Inhalants

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What are the 5 categories in the spectrum of drug use?

Non-use

Beneficial use - use that can have positive health, social / spiritual effects (eg. Taking prescribed medication / ceremonial or religious use of tobacco)

Lower-risk use - has minimal impact to an individual, their close ones & others (eg. Drinking according to guidelines)

Higher-risk use - has harmful impact to an individual, their close ones & others (eg. Using illegal drugs, binge drinking)

Addiction - substance use disorder - medical condition affecting the brain involving compulsive & continuous use despite negative impacts

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What are the 4 stages of drug use?

Experimental - early stages, peers, choice
Recreational - non-addictive,
Dependent - addicts, disrupted lifestyle
Abstinent (post-use)

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What are 3 common CNS stimulants?

Cocaine (hydrochloride)
Amphetamines (speed)
MDMA (3,4-methylenedioxymethamphetamine)

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What are CNS stimulants structurally very similar to?

Monoamine molecules

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MDMA is currently in clinical trials with which conditions?

PTSD
Alcoholism

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What are the functional / subjective effects of narcotic analgesics?

Euphoria Pain relief Sedation Slowed breathing & HR

What are the functional / subjective effects of CNS stimulants?

Stimulation / hyperactivity Euphoria Agitation / paranoia Increased HR & BP

Give 4 examples of narcotic analgesics

Opium Heroin Fentanyl OxyContin

What are 3 examples of inhalants?

Nitrous oxide Amyl nitrite Lighter gas / household aerosols

What are 5 examples of hallucinogenic drugs?

LSD Mescaline (from peyote & San Pedro cacti) DMT (from ayahuasca, synthetic) Psilocybin MDMA

What are examples of dissociative anaesthetics?

ketamine PCP

What are examples of CNS stimulants?

Cocaine Amphetamine / methamphetamine Nicotine MDMA

What are examples of CNS depressants? (5)

Alcohol Barbiturates (e.g. phenobarbital) Anxiolytics (e.g. Diazepram, fluoxetine) GHB Rohypnol

What are 2 examples of cannabinoids?

Cannabis sativa Synthetic cannabinoids

What are amphetamines a class of?

Naturally occurring (ephedrine & cathinone) and synthetic alkaloid stimulants

How is cocaine typically consumed?

Snorted Smoked (crack / freebase forms)

What are examples of narcotic analgesics? (4)

1. Opium 2. Heroin 3. Fentanyl 4. OxyContin

What are 3 examples of CNS stimulants?

1. Cocaine 2. Amphetamines 3. MDMA

What are 2 examples of CNS depressants?

1. Benzodiazepines - e.g. Diazepam (Valium) 2. Barbiturates - e.g. Phenobarbital

Give 2 examples of dissociative anaesthetics

1. Ketamine 2. PCP

Give examples of inhalants (3)

1. Nitrous oxide 2. Lighter gas / household aerosols 3. Amyl nitrite

What are 3 examples of hallucinogens?

1. LSD 2. Psilocybin (magic mushrooms) 3. Ayahuasca

The Cannabis sativa plant contains >100 unique compounds called…

Phytocannabinoids (pCBs)

What are the psychoactive / medicinal effects of Cannabis thought to result from?

The combined effects of multiple pCBs on multiple targets (CNS and the body)

What are the majority of effects of Cannabis due to?

THC & CBD

What do differences in potency of different cannabis strains / methods of preparation result from?

THC and CBD concentrations and their ratio

How do THC & CBD (from cannabis) affect the endocannabinoid system?

They work predominantly by modulating endocannabinoid (eCB signalling) via the CB1 receptor Endocannabinoids AEA (anandamide) & 2-AG act as retrograde neuromodulators and are endogenous ligands for CB1R (type of pre-synaptic heteroceptor / GPCR, widely expressed in the CNS & elsewhere)

What is the CB2R receptor?

The main endocannabinoid receptor in the periphery (Less relevant for psychoactive effects of cannabis)

How does THC affect the endocannabinoid system?

- THC is a partial agonist of CB1 (and CB2) receptors - disrupts endogenous retrograde signalling process by interfere in with anandamide & 2-AG (endogenous ligands for CB1R) - this alters glutamatergic & GABAergic signalling throughout the brain and modulates release of neuromodulatory transmitters (particularly dopamine) - this causes wide-ranging effects - combination of excitation & inhibition

Why is THC not a particularly good therapeutic drug?

THC > CB1R not functionally selective - implications for dose / side effects

What can be said about commercial CBD products?

(Mainly) the doses are far too low to have an effect - effectively an expensive & fashionable placebo

What effect can CBD have on THC and what is this implication of this?

CBD thought to reduce some of the psychotomimetic effects of THC Inc THC & dec CBD in modern cannabis is driving increased incidence of psychosis (causes hallucinations & delusions)

What is CBD’s effect on CB1R (receptors)?

Negative allosteric modulator at CB1R —> reduces binding & activity of AEA, 2-AG and / or THC

How does CBD potentiate AEA (anandamide) signalling?

Inhibits FAAH-mediated breakdown of anandamide

CBD and targets

There are many targets for CBD, but it has low affinity / potency for most of them

When was LSD synthesised?

1938 - by Alex Hoffman

When was LSD discovered to be a highly potent hallucinogen?

1943

When was LSD marketed as a clinical medication for psychiatric indications?

1947

When was LSD extensively used in psychotherapy research?

1950s / early 1960s

When was the recreational use of LSD popularised?

Early - mid 1960s

When was LSD made illegal in the USA?

1966

What happens to psilocybin when orally ingested by mammals?

It’s converted to the hallucinogen psilocin

What has psilocybin recently been in clinical trials for?

Depression Anxiety (Drug) dependence

What is ayahuasca ?

A hallucinogen used by the indigenous peoples of Amazonian jungle

What is ayahuasca ‘tea’ made from?

1. Bark of Banisteriopsis caapi 2. Leaves of Psychotria viridis - contains potent & rapid hallucinogen DMT (N,N-dimethyltryptamine)

Why is ayahuasca made with both (DMT-containing) leaves of P. viridis and B. caapi?

Orally consumed DMT is broken down by MAO-A (monoamine oxidase - A) in the periphery - so little / no effect will occur if taken alone B.caapi contains harmala alkaloids which inhibit MAO-A and allow DMT to reach the brain

All hallucinogens are agonists of which receptor?

5-HT2A (crucial for psychoactive effects)

What are the perceptual abnormalities (caused by hallucinogens) due to?

Impairment of sensory (sensorimotor) gating - the filtering of irrelevant auditory / visual / olfactory stimuli to prevent overload of cortical processing (This is thought to break down in schizophrenia)

What is sensorimotor gating controlled by?

The interaction of serotonin and dopamine signalling, particularly in the thalamus & cortex Serotonin signalling via 5-HT2A (and 5-HT1A / 2C to a lesser extent) is crucial for gating process

Impaired sensorimotor gating is thought to be a part of the pathophysiology of which condition?

Schizophrenia

What are hallucinogens sometimes called?

Psychotomimetics (Sometimes thought to, temporarily, mimic the process of psychosis)

What 5 drugs are approved and in regular medical use?

1. Cocaine hydrochloride 2. Morphine 3. Amphetamine 4. Cannabis 5. Ketamine

What is the approved and medical use of COCAINE HYDROCHLORIDE ?

Local anaesthesia during surgery

What is the approved and medical use of MORPHINE

Emergency analgesia and acute / chronic pain

What is the approved and medical use of AMPHETAMINE

ADHD (Adderall component)

What is the approved and medical use of CANNABIS

Childhood epilepsy, multiple sclerosis

What is the approved and medical use of KETAMINE

Surgical anaesthesia

What 3 drugs are under clinical investigation? And for what?

Psilocybin MDMA Ketamine Depression, anxiety, PTSD

What 2 drugs have no known medical use?

Alcohol Nicotine

Give examples of cannabinoids (2)

1. Cannabis sativa 2. Synthetic cannabinoids