Lecture 14 - Amphetamines Flashcards
What are amphetamines?
- Amphetamines are a synthetic psychostimulant that in terms of its chemical structure is similar in nature to the neurotransmitter dopamine
- You may be aware of various amphetamines by more common names, such as MDMA, meth, speed, Ecstasy, Molly etc. (can be used as a party drug)
- Increases concentration and wakefulness (e.g. adoral used as a study drug)
- Also has hallucinogenic properties (may be taken in a home environment)
Where can you get amphetamines?
- Originated in Romania
- Amphetamines for medicinal purposes are regularly prescribed by doctors for a range of medical conditions
- Similar chemical compounds that are naturally occurring (Ephedra) have been consumed for more than 5,000 years across north America, southern Europe, northern Africa, southwest and central Asia, northern China, and western South America
- 1920s = Japanese chemist isolated medicinal compounds from plant (used as a treatment for asthma because it dilates bronchioles in the lungs, or hay fever, or the common cold)
What are the origins of consumption of amphetamines?
- Ephedra now banned appetite suppressant (for those who watch Brooklyn 99 you remember Sully was taking “diet pills” in the 70’s)
- In 1920s, ephedrine used for asthma
- Led to search for synthetic substitute: amphetamine inhaler
- Later marketed for narcolepsy
- Pseudoephedrine still used as bronchodilator
- Obetrol was a popular diet pill in America in the 1950s and 1960s
- Also used in WW2 by soldiers (more alert and lower appetite so needed feeding less)
- Resurgence after the war for e.g. shift workers
What are some methods of ingestion of amphetamines?
- Originally inhaled (e.g. in asthma inhalers)
- Recreational drugs such as meth/speed are taken orally and takes up to 30 minutes for effects to occur
- Due to the half-life of the drug (7-30 hours) users typically experiences a longer high than users of drugs such as cocaine
- Typically taken orally as a tablet, however, it can be crushed and then snorted or dissolved in water and injected (injection generally more for medical use)
- Injection rapid increase in bloodstream, nasal/inhaled less peak getting into bloodstream but longer lasting effects, orally slower increase but longer effect
What are some behavioural effects of amphetamines?
Euphoria, heightened energy and alertness
- Has many medicinal properties and is used to treat a range of psychological conditions
- As a recreational drug it is taken to give a sense of euphoria, alertness, and to increase energy
(More in notes)
Amphetamines in the news
- “You can’t sleep or even close your eyes, forget about it.. And whatever you take to stop it, nothing can stop it. There was no fear anymore after I took Captagon.”
- Captagon: The tiny amphetamine pill fuelling the Syrian civil war and turning fighters into superhuman soldiers
- Influences many humanitarian crises (war)
Which neurotransmitters are involved in amphetamine action?
- Mesolimbic pathway
- Amphetamines inhibits transporter to increase synaptic levels, but also stimulates DA release
- DA, NA, 5-HT (serotonin)
- Unlike cocaine which just blocks catecholamine reuptake (dopamine), amphetamines also actively release these neurotransmitters from nerve terminals (increase production in presynaptic neural)
- They also prevent reuptake of Noradrenalin (hyper focus effect)
- AMPH taken up by DAT, Inside terminal provokes DA release. Plus DAT functions in reverse to further release DA
- Dopamine reuptake transporters are blocked by cocaine, this results in increased dopamine in the synaptic cleft, leading to behavioural symptoms of cocaine use
What are the mechanisms of ampthetamine action in animals?
- Nucleus accumbens = locomotor effect
- Amphetamine injection into nucleus accumbens is reinforcing to the animal, but cocaine injection into the nucleus accumbens is not
Describe amphetamine psychosis
- Griffith et al. (1972)
- Participants (n = 7) users but no prior history of psychosis
- Given 10 mg dextroamphetamine every hour for up to 5 days
- All became psychotic within 2-5 days
- Delusions mostly auditory, also included poisoning by experimenters and electric dynamo thought control (mirror schizophrenia)
What are some behavioural effects of taking amphetamines?
Addiction and Dependence: Long-term use often leads to physical and psychological dependence. Users may feel unable to function without the drug and experience intense cravings
Aggressive Behaviour: Users may exhibit increased aggression and hostility, which can strain relationships and lead to social isolation
Cognitive Impairment: Chronic use can impair cognitive functions, including memory, attention, and decision-making abilities. This can affect daily activities and overall quality of life
Sleep Disturbances: Long-term use disrupts normal sleep patterns, leading to insomnia and other sleep-related issues
Mood Disorders: Amphetamine abuse is associated with mood swings, irritability, anxiety, and depression. These mood disturbances can become more severe over time
Physical Health Decline: Chronic use can result in weight loss, malnutrition, and cardiovascular problems, further affecting mental health and behaviour
Psychosis: Extended use can lead to amphetamine-induced psychosis, characterized by paranoia, hallucinations, and delusions. This condition can be similar to schizophrenia and requires medical intervention
What are some neurological effects of taking amphetamines?
- Neurotransmitter Imbalance: Chronic use disrupts the regulation of dopamine, norepinephrine, and serotonin, leading to significant chemical imbalances and withdrawal symptoms (if you abstain for over a year, neural activity can return to healthy controls)
- Cognitive Impairment: Long-term use can impair memory, attention, and decision-making abilities, affecting daily life and mental health
- Amphetamine-Induced Psychosis: Prolonged use can result in paranoia, hallucinations, and delusions, resembling symptoms of schizophrenia
- Neurotoxicity: Extended use can cause nerve cell damage, increasing the risk of seizures and strokes
- Structural Brain Changes: Chronic use affects neural plasticity, leading to changes in brain structure and function, impacting overall brain health
Describe the Inada et al. (1992) tolerance study
- Inada et al. (1992)
- 11 days continuous iv infusion (to total 60 mg/kg/day)
- 20 mg/kg amphetamine challenge
- Schedule produces tolerance
What is sensitisation?
- O’Daly (2014)
- Need less of the substance to have the same reaction (second exposure gives increased reaction)
- Initial sensitization period followed by tolerance
- Enhanced Neural Responses: Sensitization leads to increased activity in reward-related brain regions, such as the ventromedial caudate, during reward anticipation. This was measured using blood oxygen level dependent (BOLD) signal during functional MRI scans
- Heightened Subjective Effects: Participants reported stronger subjective experiences of amphetamines after repeated exposure, correlating with changes in brain activity. The study involved a sensitizing dosage regime followed by acute amphetamine administration
- Implications for Psychiatric Conditions: Sensitization provides insights into the neurobiological mechanisms underlying addiction and psychiatric disorders like schizophrenia, highlighting altered dopamine signalling
How may amphetamines be applied clinically to ADHD?
- Amphetamines such as Ritalin are commonly used to treat symptoms of ADHD to increase focus and decrease inattention, hyperactivity, and impulsivity
- Low doses of amphetamines can reduce locomotor activity (hyperactivity) in both humans and in rats (Cortese et al., 2018; Kuczenski & Segal, 2002)
- However, evidence becomes unclear on long term benefits to these substances for treating symptoms, alongside potential health consequences of long term substance use
- Works better in lower doses (and less side effects)
- Interestingly there is a high rate of ADHD associated with various compulsive behaviours such as compulsive sexual behaviours, such as pornography addictions, excessive masturbation etc.
- This may be a result of impulsivity associated with ADHD, or dopamine release associated with such behaviours (Niazof et al., 2019)
How may amphetamines be applied clinically to narcolepsy?
- Individuals with narcolepsy often struggle with daytime sleepiness.
- Amphetamines can stimulate wakefulness during the day allowing individuals to function more adequately (Morgenthaler et al., 2007)
- Narcolepsy is a condition where your brain can’t control your ability to sleep or stay awake
- Interestingly individuals with narcolepsy seem to have a loss of orexinergic signalling
- Administration of an orexin receptor antagonist to an individual addicted to alcohol or cocaine completely or substantially extinguishes the reward response and therefore the craving for the drug (Baimel et al., 2015; Brown et al., 2013) – don’t get addicted due to disruption in signalling
- Why this is interesting is that individuals with narcolepsy can be treat with amphetamines… but they are unlikely to become addicted to these substances as they do not receive the rewards response or cravings for the drug
How may amphetamines be applied clinically to binge eating disorder?
- The neural underpinning of this condition are relatively unknown; however, it is believed that amphetamines help with this condition by increased dopamine and norepinephrine in the synaptic cleft
- Amphetamines increase dopamine, so there are higher dopamine levels in general, binge eating episodes don’t give as much of a rush (like a dopamine antagonist)
- In preclinical studies of binge eating in rats, lisdexamfetamine was shown to reduce chocolate binge eating and reverse binge-eating impulsiveness (Vickers et al., 2015; 2017)
- Binge Eating Disorder is where a person feels compelled to overeat on a regular basis
- People may find it difficult to stop during a binge even if they want to
- Diagnosis of binge eating disorder is not limited to overweight individuals
What are some pharmacological treatment strategies?
- Desipramine, DA antagonists (work on postsynaptic terminals, block postsynaptic dopamine receptors, so don’t get high when dopamine is in the synaptic cleft), maybe D3, even vaccines
What are some behavioural treatment strategies?
- Avoid triggers for relapse
What are some psychosocial treatment strategies?
- Counselling and support
- CBT
- Sometimes used in conjunction with medications
